FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Canugovi, C
Misiak, M
Ferrarelli, LK
Croteau, DL
Bohr, VA
AF Canugovi, Chandrika
Misiak, Magdalena
Ferrarelli, Leslie K.
Croteau, Deborah L.
Bohr, Vilhelm A.
TI The role of DNA repair in brain related disease pathology
SO DNA REPAIR
LA English
DT Article
ID BASE-EXCISION-REPAIR; PURINE NUCLEOSIDE TRIPHOSPHATASE; FOCAL
CEREBRAL-ISCHEMIA; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; OXIDATIVE
DAMAGE; ENDOPLASMIC-RETICULUM; NUCLEIC-ACIDS;
NEURODEGENERATIVE-DISEASES; MEMORY RETENTION
AB Oxidative DNA damage is implicated in brain aging, neurodegeneration and neurological diseases. Damage can be created by normal cellular metabolism, which accumulates with age, or by acute cellular stress conditions which create bursts of oxidative damage. Brain cells have a particularly high basal level of metabolic activity and use distinct oxidative damage repair mechanisms to remove oxidative damage from DNA and dNTP pools. Accumulation of this damage in the background of a functional DNA repair response is associated with normal aging, but defective repair in brain cells can contribute to neurological dysfunction. Emerging research strongly associates three common neurodegenerative conditions, Alzheimer's, Parkinson's and stroke, with defects in the ability to repair chronic or acute oxidative damage in neurons. This review explores the current knowledge of the role of oxidative damage repair in preserving brain function and highlights the emerging models and methods being used to advance our knowledge of the pathology of neurodegenerative disease. Published by Elsevier B.V.
C1 [Canugovi, Chandrika; Misiak, Magdalena; Ferrarelli, Leslie K.; Croteau, Deborah L.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, Intramural Res Program, Baltimore, MD 21224 USA.
[Misiak, Magdalena] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, Intramural Res Program, Baltimore, MD 21224 USA.
EM BohrV@grc.nia.nih.gov
FU Intramural NIH HHS [Z01 AG000723-01]
NR 82
TC 41
Z9 42
U1 1
U2 13
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD AUG
PY 2013
VL 12
IS 8
SI SI
BP 578
EP 587
DI 10.1016/j.dnarep.2013.04.010
PG 10
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 200QS
UT WOS:000323084600005
PM 23721970
ER
PT J
AU Iyama, T
Wilson, DM
AF Iyama, Teruaki
Wilson, David M., III
TI DNA repair mechanisms in dividing and non-dividing cells
SO DNA REPAIR
LA English
DT Article
DE DNA repair; Neural cells; Neurological disorder; Dividing and
non-dividing; Endogenous DNA damage
ID STRAND-BREAK REPAIR; NUCLEOTIDE EXCISION-REPAIR; SYNDROME GROUP-B;
RNA-POLYMERASE-II; NONPOLYPOSIS COLORECTAL-CANCER; HOLLIDAY JUNCTION
RESOLVASE; HUMAN POLYNUCLEOTIDE KINASE; REPLICATION PROTEIN-A;
END-JOINING PATHWAY; HAMSTER OVARY CELLS
AB DNA damage created by endogenous or exogenous genotoxic agents can exist in multiple forms, and if allowed to persist, can promote genome instability and directly lead to various human diseases, particularly cancer, neurological abnormalities, immunodeficiency and premature aging. To avoid such deleterious outcomes, cells have evolved an array of DNA repair pathways, which carry out what is typically a multiple-step process to resolve specific DNA lesions and maintain genome integrity. To fully appreciate the biological contributions of the different DNA repair systems, one must keep in mind the cellular context within which they operate. For example, the human body is composed of non-dividing and dividing cell types, including, in the brain, neurons and glial cells. We describe herein the molecular mechanisms of the different DNA repair pathways, and review their roles in non-dividing and dividing cells, with an eye toward how these pathways may regulate the development of neurological disease. Published by Elsevier B.V.
C1 [Iyama, Teruaki; Wilson, David M., III] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
RP Wilson, DM (reprint author), NIA, Lab Mol Gerontol, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM wilsonda@mail.nih.gov
FU Intramural Research Program at the NIH, National Institute on Aging
FX We thank Drs. Peter Sykora and Magdalena Misiak for their critical
reading of the manuscript. This effort was supported entirely by the
Intramural Research Program at the NIH, National Institute on Aging.
NR 269
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Z9 133
U1 9
U2 75
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 AUG
PY 2013
VL 12
IS 8
SI SI
BP 620
EP 636
DI 10.1016/j.dnarep.2013.04.015
PG 17
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 200QS
UT WOS:000323084600010
PM 23684800
ER
PT J
AU Brooks, PJ
AF Brooks, P. J.
TI Blinded by the UV light: How the focus on transcription-coupled NER has
distracted from understanding the mechanisms of Cockayne syndrome
neurologic disease
SO DNA REPAIR
LA English
DT Article
DE Leukodystrophy; Rare disease; Demyelination; Developmental disorders;
Aging; Calcification; Vasculopathy; Neurodegeration
ID NUCLEOTIDE-EXCISION-REPAIR; RNA-POLYMERASE-II; GROUP-B PROTEIN;
OXIDATIVE DNA-DAMAGE; UBIQUITIN LIGASE ACTIVITY; CROSS-LINK LESION;
ONE-HIT MODEL; XERODERMA-PIGMENTOSUM; SENSITIVE SYNDROME; RIBOSOMAL-RNA
AB Cockayne syndrome (CS) is a devastating neurodevelopmental disorder, with growth abnormalities, progeriod features, and sun sensitivity. CS is typically considered to be a DNA repair disorder, since cells from CS patients have a defect in transcription-coupled nucleotide excision repair (TC-NER). However, cells from UV-sensitive syndrome patients also lack TC-NER, but these patients do not suffer from the neurologic and other abnormalities that CS patients do. Also, the neurologic abnormalities that affect CS patients (CS neurologic disease) are qualitatively different from those seen in NER-deficient XP patients. Therefore, the TC-NER defect explains the sun sensitive phenotype common to both CS and UVsS, but cannot explain CS neurologic disease. However, as CS neurologic disease is of much greater clinical significance than the sun sensitivity, there is a pressing need to understand its molecular basis. While there is evidence for defective repair of oxidative DNA damage and mitochondrial abnormalities in CS cells, here I propose that the defects in transcription by both RNA polymerases I and II that have been documented in CS cells provide a better explanation for many of the severe growth and neurodevelopmental defects in CS patients than defective DNA repair. The implications of these ideas for interpreting results from mouse models of CS, and for the development of treatments and therapies for CS patients are discussed. (C) 2013 Published by Elsevier B.V.
C1 [Brooks, P. J.] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Brooks, P. J.] NIH, Off Rare Dis Res, Natl Ctr Advancing Translat Sci, Bethesda, MD 20892 USA.
RP Brooks, PJ (reprint author), NIAAA, Div Metab & Hlth Effects, NIH, 5635 Fishers Lane Room 2117, Bethesda, MD 20892 USA.
EM pjbrooks@mail.nih.gov
FU NICHD Brain and Tissue Bank for Developmental Disorders at the
University of Maryland, Baltimore, MD (NICHD) [HHSN275200900011C,
NO1-HD-9-0011]
FX The human tissue used in Fig. 1 was obtained from the NICHD Brain and
Tissue Bank for Developmental Disorders at the University of Maryland,
Baltimore, MD (NICHD contract #HHSN275200900011C, Ref. No.
NO1-HD-9-0011).
NR 166
TC 21
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U1 0
U2 16
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD AUG
PY 2013
VL 12
IS 8
SI SI
BP 656
EP 671
DI 10.1016/j.dnarep.2013.04.018
PG 16
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 200QS
UT WOS:000323084600013
PM 23683874
ER
PT J
AU Attene-Ramos, MS
Miller, N
Huang, RL
Michael, S
Itkin, M
Kavlock, RJ
Austin, CP
Shinn, P
Simeonov, A
Tice, RR
Xia, MH
AF Attene-Ramos, Matias S.
Miller, Nicole
Huang, Ruili
Michael, Sam
Itkin, Misha
Kavlock, Robert J.
Austin, Christopher P.
Shinn, Paul
Simeonov, Anton
Tice, Raymond R.
Xia, Menghang
TI The Tox21 robotic platform for the assessment of environmental chemicals
- from vision to reality
SO DRUG DISCOVERY TODAY
LA English
DT Review
ID TOXICITY; 21ST-CENTURY; VALIDATION; ASSAYS; MODEL
AB Since its establishment in 2008, the US Tox21 inter-agency collaboration has made great progress in developing and evaluating cellular models for the evaluation of environmental chemicals as a proof of principle. Currently, the program has entered its production phase (Tox21 Phase II) focusing initially on the areas of modulation of nuclear receptors and stress response pathways. During Tox21 Phase II, the set of chemicals to be tested has been expanded to nearly 10,000 (10K) compounds and a fully automated screening platform has been implemented. The Tox21 robotic system combined with informatics efforts is capable of screening and profiling the collection of 10K environmental chemicals in triplicate in a week. In this article, we describe the Tox21 screening process, compound library preparation, data processing, and robotic system validation.
C1 [Attene-Ramos, Matias S.; Miller, Nicole; Huang, Ruili; Michael, Sam; Itkin, Misha; Austin, Christopher P.; Shinn, Paul; Simeonov, Anton; Xia, Menghang] NIH, Natl Ctr Adv Translat Sci, Chem Genom Ctr, Rockville, MD 20850 USA.
[Kavlock, Robert J.] US EPA, Natl Ctr Computat Toxicol, Off Res & Dev, Res Triangle Pk, NC 27711 USA.
[Tice, Raymond R.] NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
RP Xia, MH (reprint author), NIH, Natl Ctr Adv Translat Sci, Chem Genom Ctr, Rockville, MD 20850 USA.
EM mxia@mail.nih.gov
FU Intramural Research Programs of the National Toxicology Program
[Y2-ES-7020-01]; National Institute of Environmental Health Sciences;
U.S. Environmental Protection Agency
FX We gratefully acknowledge Danielle VanLeer and Tongan Zhao for
developing the compound plate tracking system. This work was supported
by the Intramural Research Programs of the National Toxicology Program
(Interagency agreement #Y2-ES-7020-01), the National Institute of
Environmental Health Sciences, and the U.S. Environmental Protection
Agency.
NR 25
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U1 2
U2 14
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1359-6446
J9 DRUG DISCOV TODAY
JI Drug Discov. Today
PD AUG
PY 2013
VL 18
IS 15-16
BP 716
EP 723
DI 10.1016/j.drudis.2013.05.015
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 204YP
UT WOS:000323407500005
PM 23732176
ER
PT J
AU Guerra-Giraldez, C
Marzal, M
Cangalaya, C
Balboa, D
Orrego, MA
Paredes, A
Gonzales-Gustavson, E
Arroyo, G
Garcia, HH
Gonzalez, AE
Mahanty, S
Nash, TE
AF Guerra-Giraldez, Cristina
Marzal, Miguel
Cangalaya, Carla
Balboa, Diana
Angel Orrego, Miguel
Paredes, Adriana
Gonzales-Gustavson, Eloy
Arroyo, Gianfranco
Garcia, Hector H.
Gonzalez, Armando E.
Mahanty, Siddhartha
Nash, Theodore E.
CA Cysticercosis Working Grp Peru
TI Disruption of the blood-brain barrier in pigs naturally infected with
Taenia solium, untreated and after anthelmintic treatment
SO EXPERIMENTAL PARASITOLOGY
LA English
DT Article
DE Blood-brain barrier; Neurocysticercosis; Taenia solium; Praziquantel
ID CELL BIOLOGY; EVANS BLUE; NEUROCYSTICERCOSIS; PERMEABILITY;
CYSTICERCOSIS; ASTROCYTES; DIAGNOSIS; ALBUMIN
AB Neurocysticercosis is a widely prevalent disease in the tropics that causes seizures and a variety into of neurological symptoms in most of the world. Experimental models are limited and do not allow assessment of the degree of inflammation around brain cysts. The vital dye Evans Blue (EB) was injected to 11 pigs naturally infected with Taenia solium cysts to visually identify the extent of disruption of the blood-brain barrier. A total of 369 cysts were recovered from the 11 brains and classified according to the staining of their capsules as blue or unstained. The proportion of cysts with blue capsules was significantly higher in brains from pigs that had received anthelmintic treatment 48 and 120 h before the EB infusion, indicating a greater compromise of the blood-brain barrier due to treatment. The model could be useful for understanding the pathology of treatment-induced inflammation in neurocysticercosis. Published by Elsevier Inc.
C1 [Guerra-Giraldez, Cristina; Marzal, Miguel; Cangalaya, Carla; Balboa, Diana; Angel Orrego, Miguel; Paredes, Adriana; Garcia, Hector H.; Mahanty, Siddhartha; Nash, Theodore E.] Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Lab Inmunopatol Neurocisticercosis, Lima, Peru.
[Guerra-Giraldez, Cristina; Garcia, Hector H.] Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Dept Ciencias Celulares & Mol, Lima, Peru.
[Gonzales-Gustavson, Eloy; Arroyo, Gianfranco; Gonzalez, Armando E.] Univ Nacl Mayor San Marcos, Fac Med Vet, Lima 14, Peru.
[Garcia, Hector H.] Inst Nacl Ciencias Neurol, Unidad Cisticercosis, Lima, Peru.
[Mahanty, Siddhartha; Nash, Theodore E.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Nash, TE (reprint author), 9000 Rockville Pike,Bldg 4 Rm 424, Bethesda, MD 20892 USA.
EM cristina.guerra@upch.pe; miguel.marzal.m@upch.pe;
carla.cangalaya.l@upch.pe; dsbalboa@gmail.com; miguel.orrego.s@upch.pe;
adriana.paredes.a@upch.pe; gonzaleseloy@yahoo.com;
arroyogianfranco@gmail.-com; hgarcia@jhsph.edu; agonzale@jhsph.edu;
smahanty@niaid.nih.gov; tnash@niaid.nih.gov
OI Guerra-Giraldez, Cristina/0000-0002-9287-9838; Cangalaya,
Carla/0000-0002-3525-8445; Gonzales-Gustavson, Eloy/0000-0001-7328-2983;
Mahanty, Siddhartha/0000-0003-1068-0524
FU National Institutes of Allergy and Infectious Diseases
FX We thank Valentina Salas for valuable assistance at the preliminary
stage, also Teresa Lopez and Linda Gallegos for help at the veterinary
facilities. This work was supported in part by an intramural Research
Program of the National Institutes of Allergy and Infectious Diseases.
NR 34
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U1 0
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4894
J9 EXP PARASITOL
JI Exp. Parasitol.
PD AUG
PY 2013
VL 134
IS 4
BP 443
EP 446
DI 10.1016/j.exppara.2013.05.005
PG 4
WC Parasitology
SC Parasitology
GA 198SJ
UT WOS:000322942300007
PM 23684909
ER
PT J
AU Lu, MJ
Zhao, SH
Jiang, SL
Yin, G
Wang, C
Zhang, Y
Liu, Q
Cheng, HB
Ma, N
Zhao, T
Chen, XY
Huang, JH
Zou, YB
Song, L
He, ZX
An, J
Renate, J
Xue, H
Shah, S
AF Lu, Minjie
Zhao, Shihua
Jiang, Shiliang
Yin, Gang
Wang, Cheng
Zhang, Yan
Liu, Qiong
Cheng, Huaibing
Ma, Ning
Zhao, Tao
Chen, Xiuyu
Huang, Jinghan
Zou, Yubao
Song, Lei
He, Zuoxiang
An, Jing
Renate, Jerecic
Xue, Hui
Shah, Saurabh
TI Fat Deposition in Dilated Cardiomyopathy Assessed by CMR
SO JACC-CARDIOVASCULAR IMAGING
LA English
DT Article
DE dilated cardiomyopathy; fat deposition; late gadolinium enhancement;
MRI; water-fat separation imaging
ID CARDIOVASCULAR MAGNETIC-RESONANCE; MYOCARDIAL-INFARCTION; LIPOMATOUS
METAPLASIA; SEPARATION; QUANTIFICATION; MRI; ENHANCEMENT; FIBROSIS;
HEART
AB OBJECTIVES The aim of this study was to prospectively investigate the prevalence of fat deposition in idiopathic dilated cardiomyopathy (DCM) by fat-water separation imaging. An auxiliary aim was to determine the relationship between left ventricular (LV) fat deposition and characteristic myocardial fibrosis, as well as cardiac functional parameters.
BACKGROUND Idiopathic DCM remains the most common cause of heart failure in young people referred for cardiac-transplantation; little is known about the clinical value of fat deposition in DCM.
METHODS A total of 124 patients with DCM were studied after written informed consent was obtained. The magnetic resonance imaging scan protocols included a series of short-axis LV cine imaging for functional analysis, fat-water separation imaging, and late gadolinium enhancement (LGE) imaging. Fat deposition and fibrosis location were compared to the scar regions on LGE images using a 17-segment model. Statistical comparisons of LV global functional parameters, fibrosis volumes, and fat deposition were carried out using the Pearson correlation, Student t test, and multiple regressions.
RESULTS The patients had a 41.9% (52 of 124) prevalence of positive LGE, and 12.9% (16 of 124) fat deposition prevalence was found in this DCM cohort. The patients with fat deposition had larger LV end-diastolic volume (LVEDV) index (140.8 +/- 20.2 ml/m(2) vs. 123.4 +/- 15.8 ml/m(2); p < 0.01), larger LV end-systolic volume (LVESV) index (111.3 +/- 19.2 ml/m(2) vs. 87.0 +/- 20.3 ml/m(2); p < 0.01), and decreased LV ejection fraction (LVEF) (21.1 +/- 7.1% vs. 30.0 +/- 10.7%; p < 0.01). Higher volumes of LGE were found in the group with myocardial fat deposition (18.39 +/- 9.0 ml vs. 13.40 +/- 6.54 ml; p = 0.001), as well as a higher percentage of LGE/LV mass (19.11 +/- 7.78% vs. 13.60 +/- 4.58%; p = 0.000). The volume of fat deposition was correlated with scar volume, LVEF, LVEDV index, and LVESV index.
CONCLUSIONS Fat deposition is a common phenomenon in DCM, and it is associated with DCM characteristics such as fibrosis volume and LV function. (J Am Coll Cardiol Img 2013;6:889-98) (C) 2013 by the American College of Cardiology Foundation
C1 [Lu, Minjie; Zhao, Shihua; Jiang, Shiliang; Yin, Gang; Zhang, Yan; Liu, Qiong; Ma, Ning; Zhao, Tao; Chen, Xiuyu] Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, State Key Lab Cardiovasc Dis, Dept Radiol,Fuwai Hosp, Beijing 100037, Peoples R China.
[Lu, Minjie; Zhao, Shihua; Jiang, Shiliang; Yin, Gang; Zhang, Yan; Liu, Qiong; Ma, Ning; Zhao, Tao; Chen, Xiuyu; Huang, Jinghan; Zou, Yubao; Song, Lei; He, Zuoxiang] Peking Union Med Coll, Beijing 100037, Peoples R China.
[Wang, Cheng] Xuzhou Med Coll, Affiliated Hosp, Dept Cardiol, Xuzhou, Jiangsu, Peoples R China.
[Cheng, Huaibing] Anhui Med Univ, Affiliated Hosp 1, Dept Cardiol, Hefei, Anhui, Peoples R China.
[Huang, Jinghan] Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, State Key Lab Cardiovasc Dis, Dept Electrocardiogram,Fuwai Hosp, Beijing 100037, Peoples R China.
[Zou, Yubao; Song, Lei] Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, State Key Lab Cardiovasc Dis, Dept Cardiol,Fuwai Hosp, Beijing 100037, Peoples R China.
[He, Zuoxiang] Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, State Key Lab Cardiovasc Dis, Dept Nucl Med,Fuwai Hosp, Beijing 100037, Peoples R China.
[An, Jing] Siemens Shenzhen Magnet Resonance Ltd, Siemens MRI Ctr, Shenzhen, Guangdong, Peoples R China.
[Renate, Jerecic] Siemens AG, Healthcare Sect, Erlangen, Germany.
[Xue, Hui] NHLBI, NIH, Bethesda, MD 20892 USA.
[Shah, Saurabh] Siemens Med Solut USA Inc, Chicago, IL USA.
Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, State Key Lab Cardiovasc Dis, Fuwai Hosp, Beijing 100037, Peoples R China.
RP Zhao, SH (reprint author), Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, State Key Lab Cardiovasc Dis, Dept Radiol,Fuwai Hosp, Beijing 100037, Peoples R China.
EM coolkan@163.com
FU National Natural Science Foundation of China [81000604, 81130029]; PUMC
Youth Fund; Fundamental Research Funds for the Central Universities
[3332013105]; Talent Research Star of Fuwai Hospital [2012-FWXX01]
FX This study was supported in part by research grants from the National
Natural Science Foundation of China (81000604 and 81130029), PUMC Youth
Fund, the Fundamental Research Funds for the Central Universities
(3332013105), and Talent Research Star of Fuwai Hospital (2012-FWXX01).
NR 30
TC 7
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U1 1
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-878X
EI 1876-7591
J9 JACC-CARDIOVASC IMAG
JI JACC-Cardiovasc. Imag.
PD AUG
PY 2013
VL 6
IS 8
BP 889
EP 898
DI 10.1016/j.jcmg.2013.04.010
PG 10
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 202QT
UT WOS:000323235400008
PM 23850250
ER
PT J
AU Fiuzat, M
O'Connor, CM
Gueyffier, F
Mascette, AM
Geller, NL
Mebazaa, A
Voors, AA
Adams, KF
Pina, IL
Neyses, L
Muntendam, P
Felker, GM
Pitt, B
Zannad, F
Bristow, MR
AF Fiuzat, Mona
O'Connor, Christopher M.
Gueyffier, Francois
Mascette, Alice M.
Geller, Nancy L.
Mebazaa, Alexandre
Voors, Adriaan A.
Adams, Kirkwood F.
Pina, Ileana L.
Neyses, Ludwig
Muntendam, Pieter
Felker, G. Michael
Pitt, Bertram
Zannad, Faiez
Bristow, Michael R.
TI Biomarker-Guided Therapies in Heart Failure: A Forum for Unified
Strategies
SO JOURNAL OF CARDIAC FAILURE
LA English
DT Review
DE Pharmacogenetics; biologic markers; clinical trials; cardiovascular
diseases
ID BRAIN-NATRIURETIC PEPTIDE; ROSUVASTATIN MULTINATIONAL TRIAL;
ADRENERGIC-RECEPTOR GENOTYPES; CARDIOVASCULAR-DISEASE;
BETA(1)-ADRENERGIC RECEPTOR; DIAGNOSTIC BIOMARKERS; GENE POLYMORPHISM;
RANDOMIZED-TRIAL; ACUTE DYSPNEA; ASSOCIATION
AB The complexity of standard medical treatment for heart failure is growing, and such therapy typically involves 5 or more different medications. Given these pressures, there is increasing interest in harnessing cardiovascular biomarkers for clinical application to more effectively guide diagnosis, risk stratification, and therapy. It may be possible to realize an era of personalized medicine for heart failure treatment in which therapy is optimized and costs are controlled. The direct mechanistic coupling of biologic processes and therapies achieved in cancer treatment remains elusive in heart failure. Recent clinical trials and meta-analyses of biomarkers in heart failure have produced conflicting evidence. In this article, which comprises a summary of discussions from the Global Cardiovascular Clinical Trialists Forum held in Paris, France, we offer a brief overview of the background and rationale for biomarker testing in heart failure, describe opportunities and challenges from a regulatory perspective, and summarize current positions from government agencies in the United States and European Union.
C1 [Fiuzat, Mona; O'Connor, Christopher M.; Felker, G. Michael] Duke Univ Med Ctr, Durham, NC USA.
[Gueyffier, Francois] Hosp Civils Lyon, Lyon, France.
[Gueyffier, Francois] Univ Lyon 1, UMR5558, CNRS, F-69365 Lyon, France.
[Mascette, Alice M.; Geller, Nancy L.] NHLBI, Bethesda, MD 20892 USA.
[Mebazaa, Alexandre] Lariboisiere Hosp, Paris, France.
[Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands.
[Adams, Kirkwood F.] Univ N Carolina, Chapel Hill, NC USA.
[Pina, Ileana L.] Montefiore Einstein Med Ctr, New York, NY USA.
[Neyses, Ludwig] Univ Manchester, Manchester, Lancs, England.
[Muntendam, Pieter] BG Med, Waltham, MA USA.
[Pitt, Bertram] Univ Michigan, Ann Arbor, MI 48109 USA.
[Zannad, Faiez] Nancy Univ, Nancy, France.
[Bristow, Michael R.] Univ Colorado Hlth Sci Ctr, Denver, CO USA.
[Bristow, Michael R.] ARCA Biopharma, Denver, CO USA.
RP Fiuzat, M (reprint author), Duke Clin Res Inst, 2400 Pratt St,Room 8011, Durham, NC 27705 USA.
EM mona.fiuzat@duke.edu
RI Gueyffier, Francois/B-8545-2008
OI Gueyffier, Francois/0000-0002-9921-0977
NR 75
TC 9
Z9 10
U1 4
U2 16
PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS
PI PHILADELPHIA
PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA
SN 1071-9164
J9 J CARD FAIL
JI J. Card. Fail.
PD AUG
PY 2013
VL 19
IS 8
BP 592
EP 599
DI 10.1016/j.cardfail.2013.05.012
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 201LF
UT WOS:000323142400011
PM 23910590
ER
PT J
AU Sim, BTT
Browne, SK
Vigliani, M
Zachary, D
Rosen, L
Holland, SM
Opal, SM
AF Sim, Bich-Thuy T.
Browne, Sarah K.
Vigliani, Marguerite
Zachary, Dalila
Rosen, Lindsey
Holland, Steven M.
Opal, Steven M.
TI Recurrent Burkholderia gladioli Suppurative Lymphadenitis associated
with Neutralizing Anti-IL-12p70 Autoantibodies
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Article
ID NONTUBERCULOUS MYCOBACTERIAL INFECTIONS; ANTI-CYTOKINE AUTOANTIBODIES;
IFN-GAMMA AUTOANTIBODIES; INTERFERON-GAMMA; ACQUIRED-IMMUNODEFICIENCY;
CYSTIC-FIBROSIS; AVIUM COMPLEX; INTERLEUKIN-12; DISEASE; DEFICIENCY
C1 [Sim, Bich-Thuy T.; Zachary, Dalila; Opal, Steven M.] Brown Univ, Div Infect Dis, Alpert Med Sch, Providence, RI 02912 USA.
[Sim, Bich-Thuy T.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Sim, Bich-Thuy T.] Harvard Univ, Sch Med, Boston, MA USA.
[Browne, Sarah K.; Rosen, Lindsey; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Vigliani, Marguerite] Brown Univ, Dept Obstet & Gynecol, Alpert Med Sch, Providence, RI 02912 USA.
RP Sim, BTT (reprint author), 51-53 Vo Van Tan St,8th Floor,Dist 3, Ho Chi Minh City, Vietnam.
EM bsim1@bidmc.harvard.edu
NR 30
TC 7
Z9 7
U1 0
U2 4
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 AUG
PY 2013
VL 33
IS 6
BP 1057
EP 1061
DI 10.1007/s10875-013-9908-z
PG 5
WC Immunology
SC Immunology
GA 201GD
UT WOS:000323127800004
PM 23708995
ER
PT J
AU Bax, HI
Freeman, AF
Anderson, VL
Vesterhus, P
Laerum, D
Pittaluga, S
Wilson, WH
Holland, SM
AF Bax, Hannelore I.
Freeman, Alexandra F.
Anderson, Victoria L.
Vesterhus, Per
Laerum, Dan
Pittaluga, Stefania
Wilson, Wyndham H.
Holland, Steven M.
TI B-Cell Lymphoma in a Patient with Complete Interferon Gamma Receptor 1
Deficiency
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Article
DE B-cell lymphoma; interferon gamma receptor deficiency
ID IFN-GAMMA; IFN-GAMMA-R1 DEFICIENCY; MYCOBACTERIAL DISEASE;
CLINICAL-FEATURES; CANCER; IMMUNODEFICIENCY; SURVEILLANCE; MUTATIONS;
MALIGNANCIES; INFECTIONS
AB Immunosuppression-associated lymphoproliferative disorders can be related to primary as well as acquired immune disorders. Interferon gamma receptor (IFN-gamma R) deficiency is a rare primary immune disorder, characterized by increased susceptibility to mycobacterial infections. Here we report the first case of an Epstein Barr Virus (EBV) related B-cell lymphoma in a patient with complete IFN-gamma R1 deficiency. The patient was a 20-year-old man with homozygous 22Cdel in IFNGR1 resulting in complete absence of IFN-gamma R1 surface expression and complete lack of responsiveness to IFN-gamma in vitro. He had disseminated refractory Mycobacterium avium complex and Mycobacterium abscessus infections. At age 18 he presented with new spiking fever and weight loss that was due to an EBV-positive B-cell non-Hodgkin lymphoma. Two years later he died of progressive lymphoma. IFN-gamma plays an important role in tumor protection and rejection. Patients with IFN-gamma R deficiencies and other immune deficits predisposing to mycobacterial disease seem to have an increased risk of malignancies, especially those related to viral infections. As more of these patients survive their early infections, cancer awareness and tumor surveillance may need to become a more routine part of management.
C1 [Bax, Hannelore I.; Freeman, Alexandra F.; Anderson, Victoria L.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Bax, Hannelore I.] Erasmus MC, Dept Internal Med, Div Infect Dis, Rotterdam, Netherlands.
[Vesterhus, Per] Sorlandet Hosp Kristiansand, Dept Paediat, Kristiansand, Norway.
[Laerum, Dan] Sorlandet Hosp Kristiansand, Div Pulmonol, Kristiansand, Norway.
[Pittaluga, Stefania] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Wilson, Wyndham H.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
RP Bax, HI (reprint author), Erasmus MC, Dept Internal Med, Div Infect Dis, Rotterdam, Netherlands.
EM h.bax@erasmusmc.nl
FU Intramural NIH HHS [Z01 AI000647-16]
NR 35
TC 10
Z9 13
U1 0
U2 6
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD AUG
PY 2013
VL 33
IS 6
BP 1062
EP 1066
DI 10.1007/s10875-013-9907-0
PG 5
WC Immunology
SC Immunology
GA 201GD
UT WOS:000323127800005
PM 23800860
ER
PT J
AU Ward, MM
AF Ward, Michael M.
TI Estimating Disease Prevalence and Incidence Using Administrative Data:
Some Assembly Required
SO JOURNAL OF RHEUMATOLOGY
LA English
DT Editorial Material
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; POPULATION; EPIDEMIOLOGY
C1 [Ward, Michael M.] NIH, Natl Inst Arthrit & Musculoskeletal & Skin Dis, Intramural Res Program, Bethesda, MD 20892 USA.
RP Ward, MM (reprint author), Bldg 10 CRC,Room 4-1339,10 Ctr Dr, Bethesda, MD 20892 USA.
EM wardm1@mail.nih.gov
FU Intramural NIH HHS [ZIA AR041153-09]
NR 15
TC 7
Z9 7
U1 2
U2 2
PU J RHEUMATOL PUBL CO
PI TORONTO
PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA
SN 0315-162X
EI 1499-2752
J9 J RHEUMATOL
JI J. Rheumatol.
PD AUG
PY 2013
VL 40
IS 8
BP 1241
EP 1243
DI 10.3899/jrheum.130675
PG 3
WC Rheumatology
SC Rheumatology
GA 202CY
UT WOS:000323192300001
PM 23908527
ER
PT J
AU Lerman, MA
Burnham, JM
Chang, PY
Daniel, E
Foster, CS
Hennessy, S
Jabs, DA
Joffe, MM
Kacmaz, RO
Levy-Clarke, GA
Mills, MD
Nussenblatt, RB
Rosenbaum, JT
Suhler, EB
Thorne, JE
Kempen, JH
AF Lerman, Melissa A.
Burnham, Jon M.
Chang, Peter Y.
Daniel, Ebenezer
Foster, C. Stephen
Hennessy, Sean
Jabs, Douglas A.
Joffe, Marshall M.
Kacmaz, R. Oktay
Levy-Clarke, Grace A.
Mills, Monte D.
Nussenblatt, Robert B.
Rosenbaum, James T.
Suhler, Eric B.
Thorne, Jennifer E.
Kempen, John H.
TI Response of Pediatric Uveitis to Tumor Necrosis Factor-alpha Inhibitors
SO JOURNAL OF RHEUMATOLOGY
LA English
DT Article
DE UVEITIS; TUMOR NECROSIS FACTOR ANTAGONIST; JUVENILE IDIOPATHIC ARTHRITIS
ID JUVENILE IDIOPATHIC ARTHRITIS; CHRONIC NONINFECTIOUS UVEITIS; REFRACTORY
CHILDHOOD UVEITIS; OCULAR INFLAMMATORY DISEASES; TERM-FOLLOW-UP;
RHEUMATOID-ARTHRITIS; INFLIXIMAB THERAPY; RISK-FACTORS; CASE SERIES;
CHILDREN
AB Objective. To evaluate the outcome of tumor necrosis factor-alpha inhibition (anti-TNF) for pediatric uveitis.
Methods. We retrospectively assessed children (age <= 18 yrs) with noninfectious uveitis receiving anti-TNF at 5 uveitis centers and 1 pediatric rheumatology center. Incident treatment success was defined as minimal or no uveitis activity at >= 2 consecutive ophthalmological examinations L 28 days apart while taking no oral and <= 2 eyedrops/day of corticosteroids. Eligible children had active uveitis and/or were taking higher corticosteroid doses.
Results. Among 56 eligible children followed over 33.73 person-years, 52% had juvenile idiopathic arthritis (JIA) and 75% had anterior uveitis (AU). The Kaplan-Meier estimated proportion achieving treatment success within 12 months was 75% (95% CI 62%-87%). Complete absence of inflammatory signs with discontinuation of all corticosteroids was observed in an estimated 64% by 12 months (95% CI 51%-76%). Diagnoses of JIA or AU were associated with greater likelihood of success, as was the oligoarticular subtype among JIA cases. In a multivariable model, compared to those with JIA-associated AU, those with neither or with JIA or AU alone had a 75%-80% lower rate of achieving quiescence under anti-TNF, independent of the number of immunomodulators previously or concomitantly prescribed. Uveitis reactivated within 12 months of achieving quiescence in 14% of those continuing anti-TNF (95% CI 6%-31%). The incidence of discontinuation for adverse effects was 8%/year (95% CI 1%-43%).
Conclusion. Treatment with anti-TNF was successful and sustained in a majority of children with noninfectious uveitis, and treatment-limiting toxicity was infrequent. JIA-associated AU may be especially responsive to anti-TNF.
C1 Childrens Hosp Philadelphia, Div Rheumatol, Philadelphia, PA 19104 USA.
Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Ctr Clin Epidemiol & Biostat,Dept Epidemiol & Bio, Philadelphia, PA 19104 USA.
Univ Penn, Perelman Sch Med SOM, Philadelphia, PA 19104 USA.
Ocular Immunol & Uveitis Fdn, Massachusetts Eye Res & Surg Inst, Cambridge, MA USA.
[Chang, Peter Y.] New York Eye & Ear Infirm, New York, NY 10003 USA.
[Foster, C. Stephen] Harvard Univ, Sch Med, Boston, MA USA.
Mt Sinai Sch Med, Dept Med, New York, NY USA.
Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA.
Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21218 USA.
[Kacmaz, R. Oktay] Allergan Pharmaceut Inc, Irvine, CA 92715 USA.
[Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD 20892 USA.
[Levy-Clarke, Grace A.] Johnson & Johnson Vis Care, Jacksonville, FL USA.
Childrens Hosp Philadelphia, Div Ophthalmol, Philadelphia, PA 19104 USA.
Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR USA.
Oregon Hlth & Sci Univ, Div Rheumatol, Dept Internal Med, Portland, OR USA.
Portland VA Med Ctr, Dept Ophthalmol, Portland, OR USA.
RP Lerman, MA (reprint author), Childrens Hosp Philadelphia, Div Rheumatol, Abramson Res Ctr, Suite 1102,3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM lermanm@email.chop.edu
FU Rheumatology Research Foundation Scientist Development Award;
Autoimmunity Centers of Excellence, National Institute of Allergy and
Infectious Diseases; National Eye Institute (NEI), US National
Institutes of Health (NIH) [R01 EY014943]; National Institute on Aging
[AG025152, AG035751]; NEI [U10 EY08052]; NIH [U10 EY08052]; Johns
Hopkins University Bloomberg School of Public Health [U10 EY08057];
University of Wisconsin [U10 EY08067]; US Department of Veterans
Affairs; Abbott; LuxBio Genentech; Bristol Myers Squibb; Novartis;
EyeGate; RPB Sybil B. Harrington Special Scholars Award; Research to
Prevent Blindness; Paul and Evanina Mackall Foundation
FX Supported by a Rheumatology Research Foundation Scientist Development
Award (Dr. Lerman); Autoimmunity Centers of Excellence, National
Institute of Allergy and Infectious Diseases (Dr. Burnham); R01 EY014943
National Eye Institute (NEI), US National Institutes of Health (NIH;
Drs. Daniel, Rosenbaum, Suhler, Thorne, and Kempen); grants AG025152 and
AG035751 from the National Institute on Aging (Dr. Hennessy);
cooperative agreements from the NEI and the NIH to the Mount Sinai
School of Medicine (U10 EY08052), the Johns Hopkins University Bloomberg
School of Public Health, (U10 EY08057), and the University of Wisconsin
(U10 EY08067; Dr. Jabs); intramural funding from the NEI (Dr.
Levy-Clarke, and previously, Dr. Nussenblatt); The US Department of
Veterans Affairs (Dr. Suhler); research grants from Abbott, LuxBio
Genentech, Bristol Myers Squibb, Novartis, EyeGate, and the RPB Sybil B.
Harrington Special Scholars Award (Dr. Thorne); and Research to Prevent
Blindness, and the Paul and Evanina Mackall Foundation (Dr. Kempen).
NR 50
TC 17
Z9 17
U1 0
U2 1
PU J RHEUMATOL PUBL CO
PI TORONTO
PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA
SN 0315-162X
J9 J RHEUMATOL
JI J. Rheumatol.
PD AUG
PY 2013
VL 40
IS 8
BP 1394
EP 1403
DI 10.3899/jrheum.121180
PG 10
WC Rheumatology
SC Rheumatology
GA 202CY
UT WOS:000323192300025
PM 23818712
ER
PT J
AU White, CL
Szychowski, JM
Roldan, A
Benavente, MF
Pretell, EJ
Del Brutto, OH
Kase, CS
Arauz, A
Meyer, BC
Meissner, I
Demaerschalk, BM
McClure, LA
Coffey, CS
Pearce, LA
Conwit, R
Irby, LH
Peri, K
Pergola, PE
Hart, RG
Benavente, OR
AF White, Carole L.
Szychowski, Jeff M.
Roldan, Ana
Benavente, Marie-France
Pretell, Edwin J.
Del Brutto, Oscar H.
Kase, Carlos S.
Arauz, Antonio
Meyer, Brett C.
Meissner, Irene
Demaerschalk, Bart M.
McClure, Leslie A.
Coffey, Christopher S.
Pearce, Lesly A.
Conwit, Robin
Irby, Lisa H.
Peri, Kalyani
Pergola, Pablo E.
Hart, Robert G.
Benavente, Oscar R.
CA SPS3 Investigators
TI Clinical Features and Racial/Ethnic Differences Among the 3020
Participants in the Secondary Prevention of Small Subcortical Strokes
(SPS3) Trial
SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
LA English
DT Article
DE Lacunar; clinical trial; prevention; blood pressure; antiplatelet;
cognition; small vessel disease
ID LONG-TERM PROGNOSIS; NORTHERN MANHATTAN STROKE; NON-HISPANIC WHITES;
RISK-FACTORS; ISCHEMIC-STROKE; LACUNAR STROKE; CEREBRAL INFARCTION;
ETHNIC DISPARITIES; MEXICAN-AMERICANS; SUBTYPES
AB This study examined the baseline characteristics, racial/ethnic differences, and geographic differences among participants in the Secondary Prevention of Small Subcortical Strokes (SPS3) study. The SPS3 trial enrolled patients who experienced a symptomatic small subcortical stroke (lacunar stroke) within the previous 6 months and an eligible lesion on detected on magnetic resonance imaging. The patients were randomized, in a factorial design, to antiplatelet therapy (aspirin 325 mg daily plus clopidogrel 75 mg daily vs aspirin 325 mg daily plus placebo) and to one of two levels of systolic blood pressure targets ("intensive" [<130 mmHg] or "usual" [130-149 mmHg]). A total of 3020 participants were recruited from 81 clinical sites in 8 countries. In this cohort, the mean age was 63 years, 63% were men, 75% had a history of hypertension, and 37% had diabetes. The racial distribution was 51% white, 30% Hispanic, and 16% black. Compared with white subjects, black subjects were younger (mean age, 58 years vs 64 years; P <.001) and had a higher prevalence of hypertension (87% vs 70%; P <.001). The prevalence of diabetes was higher in the Hispanic and black subjects compared with the white subjects (42% and 40% vs 32%; both P <.001). Tobacco smoking at the time of qualifying stroke was much more frequent in the Spanish participants than in subjects from North America and from Latin America (32%, 22%, and 9%, respectively; P <.001). Mean systolic blood pressure at study entry was 4 mmHg lower in the Spanish subjects compared with the North American subjects (P <.01). The SPS3 cohort is the largest magnetic resonance imaging-defined series of patients with S3. Among the racially/ethnically diverse SPS3 participants, important differences in patient features and vascular risk factors could influence prognosis for recurrent stroke and response to interventions.
C1 [White, Carole L.] Univ Texas Hlth Sci Ctr San Antonio, Sch Nursing, San Antonio, TX 78229 USA.
[Szychowski, Jeff M.; McClure, Leslie A.; Irby, Lisa H.; Peri, Kalyani] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA.
[Roldan, Ana; Benavente, Marie-France; Benavente, Oscar R.] Univ British Columbia, Dept Med, Div Neurol, Brain Res Ctr, Vancouver, BC V6T 1W5, Canada.
[Pretell, Edwin J.] Hosp Alberto Sabogal, Lima, Peru.
[Del Brutto, Oscar H.] Hosp Clin Kennedy, Dept Neurol Sci, Guayaquil, Ecuador.
[Kase, Carlos S.] Boston Med Ctr, Dept Neurol, Boston, MA USA.
[Arauz, Antonio] Inst Nacl Neurol & Neurocirugia Manuel Velasco, Stroke Clin, Suarez, Mexico.
[Meyer, Brett C.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA.
[Meissner, Irene] Mayo Clin, Dept Neurol, Rochester, MN USA.
[Demaerschalk, Bart M.] Mayo Clin, Dept Neurol, Div Cerebrovasc Dis, Phoenix, AZ USA.
[Coffey, Christopher S.] Univ Iowa, Dept Biostat, Iowa City, IA USA.
[Pearce, Lesly A.] Bel Air Court, Minot, ND USA.
[Conwit, Robin] Natl Inst Neurol Disorders & Stroke, Off Clin Res, Bethesda, MD USA.
[Pergola, Pablo E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurol, San Antonio, TX 78229 USA.
[Hart, Robert G.] McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
RP Benavente, OR (reprint author), Univ British Columbia, Dept Med, Div Neurol, Brain Res Ctr, Vancouver, BC V6T 1W5, Canada.
EM oscar.benavente@ubc.ca
RI McClure, Leslie/P-2929-2015
FU National Institute of Neurological Disorders and Stroke [2U01
NS38529-04A1]
FX Supported by the National Institute of Neurological Disorders and Stroke
(grant 2U01 NS38529-04A1). Clopidogrel and matching placebo were donated
by Sanofi US and Bristol-Myers Squibb.
NR 44
TC 14
Z9 14
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1052-3057
J9 J STROKE CEREBROVASC
JI J. Stroke Cerebrovasc. Dis.
PD AUG
PY 2013
VL 22
IS 6
BP 764
EP 774
DI 10.1016/j.jstrokecerebrovasdis.2012.03.002
PG 11
WC Neurosciences; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 206DM
UT WOS:000323497700011
PM 22516427
ER
PT J
AU Camp, KM
Lloyd-Puryear, MA
Yao, L
Groft, SC
Parisi, MA
Mulberg, A
Gopal-Srivastava, R
Cederbaum, S
Enns, GM
Ershow, AG
Frazier, DM
Gohagan, J
Harding, C
Howell, RR
Regan, K
Stacpoole, PW
Venditti, C
Vockley, J
Watson, M
Coates, PM
AF Camp, Kathryn M.
Lloyd-Puryear, Michele A.
Yao, Lynne
Groft, Stephen C.
Parisi, Melissa A.
Mulberg, Andrew
Gopal-Srivastava, Rashmi
Cederbaum, Stephen
Enns, Gregory M.
Ershow, Abby G.
Frazier, Dianne M.
Gohagan, John
Harding, Cary
Howell, R. Rodney
Regan, Karen
Stacpoole, Peter W.
Venditti, Charles
Vockley, Jerry
Watson, Michael
Coates, Paul M.
TI Expanding research to provide an evidence base for nutritional
interventions for the management of inborn errors of metabolism
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Inborn errors of metabolism; Newborn screening; Genetic; Rare diseases;
Dietary supplements; Medical foods
AB A trans-National Institutes of Health initiative, Nutrition and Dietary Supplement Interventions for Inborn Errors of Metabolism (NDSI-IEM), was launched in 2010 to identify gaps in knowledge regarding the safety and utility of nutritional interventions for the management of inborn errors of metabolism (IEM) that need to be filled with evidence-based research. IEM include inherited biochemical disorders in which specific enzyme defects interfere with the normal metabolism of exogenous (dietary) or endogenous protein, carbohydrate, or fat. For some of these IEM, effective management depends primarily on nutritional interventions. Further research is needed to demonstrate the impact of nutritional interventions on individual health outcomes and on the psychosocial issues identified by patients and their families. A series of meetings and discussions were convened to explore the current United States' funding and regulatory infrastructure and the challenges to the conduct of research for nutritional interventions for the management of IEM. Although the research and regulatory infrastructure are well-established, a collaborative pathway that includes the professional and advocacy rare disease community and federal regulatory and research agencies will be needed to overcome current barriers.
C1 [Camp, Kathryn M.; Lloyd-Puryear, Michele A.; Regan, Karen; Coates, Paul M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Yao, Lynne; Mulberg, Andrew] US FDA, Silver Spring, MD 20993 USA.
[Groft, Stephen C.; Gopal-Srivastava, Rashmi] NIH, Off Rare Dis Res, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Parisi, Melissa A.] NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
[Cederbaum, Stephen] Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
[Enns, Gregory M.] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA.
[Ershow, Abby G.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Frazier, Dianne M.] Univ N Carolina, Chapel Hill, NC 27599 USA.
[Gohagan, John] NIH, Off Dis Prevent, Bethesda, MD 20892 USA.
[Harding, Cary] Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
[Howell, R. Rodney] Univ Miami, Miami, FL 33136 USA.
[Regan, Karen] NIH, Div Nutr Res Coordinat, Bethesda, MD 20892 USA.
[Stacpoole, Peter W.] Univ Florida, Gainesville, FL 32610 USA.
[Venditti, Charles] NHGRI, NIH, Bethesda, MD 20892 USA.
[Vockley, Jerry] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15224 USA.
[Watson, Michael] Amer Coll Med Genet & Genom, Bethesda, MD 20814 USA.
RP Camp, KM (reprint author), NIH, Off Dietary Supplements, Bldg 10, Bethesda, MD 20892 USA.
EM campkm@od.nih.gov; lloydpuryearma@od.nih.gov; Lynne.Yao@fda.hhs.gov;
Stephen.Groft@nih.gov; parisima@mail.nih.gov;
Andrew.Mulberg@fda.hhs.gov; gopalr@mail.nih.gov;
scederbaum@mednet.ucla.edu; genns@stanford.edu; ershowa@nhlbi.nih.gov;
dianne_frazier@med.unc.edu; gohaganj@mail.nih.gov; hardingc@ohsu.edu;
RHowell@med.miami.edu; regank@mail.nih.gov; pws@ufl.edu;
venditti@mail.nih.gov; vockleyg@upmc.edu; mwatson@acmg.net;
CoatesP@od.nih.gov
OI Vockley, Jerry/0000-0002-8180-6457
FU Intramural NIH HHS [Z99 OD999999]
NR 42
TC 6
Z9 7
U1 0
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD AUG
PY 2013
VL 109
IS 4
BP 319
EP 328
DI 10.1016/j.ymgme.2013.05.008
PG 10
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 200QU
UT WOS:000323084800001
PM 23806236
ER
PT J
AU Bauer, PJ
Dikmen, SS
Heaton, RK
Mungas, D
Slotkin, J
Beaumont, JL
AF Bauer, Patricia J.
Dikmen, Sureyya S.
Heaton, Robert K.
Mungas, Dan
Slotkin, Jerry
Beaumont, Jennifer L.
TI III. NIH TOOLBOX COGNITION BATTERY (CB): MEASURING EPISODIC MEMORY
SO MONOGRAPHS OF THE SOCIETY FOR RESEARCH IN CHILD DEVELOPMENT
LA English
DT Article
ID FRONTAL-LOBE; NEURODEVELOPMENTAL ACCOUNT; DEVELOPMENTAL AMNESIA;
DECLARATIVE MEMORY; ACTION SEQUENCES; TEMPORAL-LOBE; HUMAN BRAIN;
MATURATION; CHILDHOOD; CORTEX
AB One of the most significant domains of cognition is episodic memory, which allows for rapid acquisition and long-term storage of new information. For purposes of the NIH Toolbox, we devised a new test of episodic memory. The nonverbal NIH Toolbox Picture Sequence Memory Test (TPSMT) requires participants to reproduce the order of an arbitrarily ordered sequence of pictures presented on a computer. To adjust for ability, sequence length varies from 6 to 15 pictures. Multiple trials are administered to increase reliability. Pediatric data from the validation study revealed the TPSMT to be sensitive to age-related changes. The task also has high test-retest reliability and promising construct validity. Steps to further increase the sensitivity of the instrument to individual and age-related variability are described.
C1 [Bauer, Patricia J.] Emory Univ, Coll Arts & Sci, Atlanta, GA 30322 USA.
[Dikmen, Sureyya S.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA.
[Dikmen, Sureyya S.] Univ Washington, Dept Neurosurg, Seattle, WA 98195 USA.
[Dikmen, Sureyya S.] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA.
[Dikmen, Sureyya S.] Univ Washington, Dept Behav Sci, Seattle, WA 98195 USA.
[Dikmen, Sureyya S.] NINDS, Bethesda, MD 20892 USA.
[Dikmen, Sureyya S.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Heaton, Robert K.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Mungas, Dan] Univ Calif Davis, Davis, CA 95616 USA.
[Slotkin, Jerry; Beaumont, Jennifer L.] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Evanston, IL 60208 USA.
RP Bauer, PJ (reprint author), Emory Univ, Dept Psychol, 36 Eagle Row, Atlanta, GA 30322 USA.
EM patricia.bauer@emory.edu
FU NIA NIH HHS [P30 AG010129, R01 AG010220]; NIMH NIH HHS [P30 MH062512]
NR 46
TC 7
Z9 7
U1 3
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0037-976X
J9 MONOGR SOC RES CHILD
JI Monogr. Soc. Res. Child Dev.
PD AUG
PY 2013
VL 78
IS 4
BP 34
EP 48
DI 10.1111/mono.12033
PG 15
WC Psychology, Developmental
SC Psychology
GA 201YE
UT WOS:000323178200003
PM 23952201
ER
PT J
AU Akshoomoff, N
Beaumont, JL
Bauer, PJ
Dikmen, SS
Gershon, RC
Mungas, D
Slotkin, J
Tulsky, D
Weintraub, S
Zelazo, PD
Heaton, RK
AF Akshoomoff, Natacha
Beaumont, Jennifer L.
Bauer, Patricia J.
Dikmen, Sureyya S.
Gershon, Richard C.
Mungas, Dan
Slotkin, Jerry
Tulsky, David
Weintraub, Sandra
Zelazo, Philip David
Heaton, Robert K.
TI VIII. NIH TOOLBOX COGNITION BATTERY (CB): COMPOSITE SCORES OF
CRYSTALLIZED, FLUID, AND OVERALL COGNITION
SO MONOGRAPHS OF THE SOCIETY FOR RESEARCH IN CHILD DEVELOPMENT
LA English
DT Article
ID INTELLIGENCE; ABILITIES
AB The NIH Toolbox Cognition Battery (CB) includes 7 tests covering 6 cognitive abilities. This chapter describes the psychometric characteristics in children ages 3-15 years of a total summary score and composite scores reflecting two major types of cognition: crystallized (more dependent upon past learning experiences) and fluid (capacity for new learning and information processing in novel situations). Both types of cognition are considered important in everyday functioning, but are thought to be differently affected by brain health status throughout life, from early childhood through older adulthood. All three Toolbox composite scores showed excellent test-retest reliability, robust developmental effects across the childhood age range considered here, and strong correlations with established measures of similar abilities. Additional preliminary evidence of validity includes significant associations between all three Toolbox composite scores and maternal reports of children's health status and school performance.
C1 [Akshoomoff, Natacha] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Beaumont, Jennifer L.; Gershon, Richard C.; Slotkin, Jerry] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Evanston, IL 60208 USA.
[Bauer, Patricia J.] Emory Univ, Emory Coll Arts & Sci, Atlanta, GA 30322 USA.
[Dikmen, Sureyya S.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA.
[Dikmen, Sureyya S.] Univ Washington, Dept Neurosurg, Seattle, WA 98195 USA.
[Dikmen, Sureyya S.] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA.
[Dikmen, Sureyya S.] Univ Washington, Dept Behav Sci, Seattle, WA 98195 USA.
[Dikmen, Sureyya S.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA.
[Dikmen, Sureyya S.] NINDS, NIDRR, DoD, Bethesda, MD 20892 USA.
[Mungas, Dan] Univ Calif Davis, Davis, CA 95616 USA.
[Tulsky, David] Univ Michigan, Sch Med, Dept Phys Med & Rehabil, Ann Arbor, MI 48109 USA.
[Tulsky, David] Univ Michigan, Sch Med, Ctr Rehabil Outcomes & Assessment Res, Ann Arbor, MI 48109 USA.
[Weintraub, Sandra] Northwestern Univ, Feinberg Sch Med, Cognit Neurol & Alzheimers Dis Ctr, Evanston, IL 60208 USA.
[Zelazo, Philip David] Univ Minnesota, Inst Child Dev, Minneapolis, MN 55455 USA.
[Heaton, Robert K.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Heaton, Robert K.] Amer Psychol Assoc, Washington, DC USA.
[Heaton, Robert K.] Amer Psychol Assoc, Int Neuropsychol Soc, Washington, DC USA.
[Heaton, Robert K.] Amer Psychol Assoc, Clin Neuropsychol Div, Washington, DC USA.
RP Heaton, RK (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM rheaton@ucsd.edu
FU NIA NIH HHS [P30 AG010129, R01 AG010220]; NIMH NIH HHS [P30 MH062512]
NR 22
TC 8
Z9 8
U1 2
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0037-976X
J9 MONOGR SOC RES CHILD
JI Monogr. Soc. Res. Child Dev.
PD AUG
PY 2013
VL 78
IS 4
BP 119
EP 132
DI 10.1111/mono.12038
PG 14
WC Psychology, Developmental
SC Psychology
GA 201YE
UT WOS:000323178200008
PM 23952206
ER
PT J
AU Manolio, TA
AF Manolio, Teri A.
TI Bringing genome-wide association findings into clinical use
SO NATURE REVIEWS GENETICS
LA English
DT Review
ID C-REACTIVE PROTEIN; GENETIC RISK PREDICTION; MISSING HERITABILITY;
MACULAR DEGENERATION; COMPLEX DISEASES; COMMON VARIANTS; YOUNG MODY;
LOCI; MEDICINE; RARE
AB Genome-wide association studies (GWASs) have been heralded as a major advance in biomedical discovery, having identified similar to 2,000 robust associations with complex diseases since 2005. Despite this success, they have met considerable scepticism regarding their clinical applicability; this scepticism arises from such aspects as the modest effect sizes of associated variants and their unclear functional consequences. There are, however, promising examples of GWAS findings that will or that may soon be translated into clinical care. These examples include variants identified through GWASs that provide strongly predictive or prognostic information or that have important pharmacological implications; these examples may illustrate promising approaches to wider clinical application.
C1 NHGRI, Div Genom Med, Rockville, MD 20892 USA.
RP Manolio, TA (reprint author), NHGRI, Div Genom Med, 5635 Fishers Lane,Room 4113,MSC 9305, Rockville, MD 20892 USA.
EM manolio@nih.gov
NR 94
TC 132
Z9 134
U1 4
U2 58
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-0056
EI 1471-0064
J9 NAT REV GENET
JI Nat. Rev. Genet.
PD AUG
PY 2013
VL 14
IS 8
BP 549
EP 558
DI 10.1038/nrg3523
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 185HB
UT WOS:000321956900010
PM 23835440
ER
PT J
AU Coulon, A
Chow, CC
Singer, RH
Larson, DR
AF Coulon, Antoine
Chow, Carson C.
Singer, Robert H.
Larson, Daniel R.
TI Eukaryotic transcriptional dynamics: from single molecules to cell
populations
SO NATURE REVIEWS GENETICS
LA English
DT Review
ID RNA-POLYMERASE-II; STOCHASTIC GENE-EXPRESSION; CHROMATIN-REMODELING
COMPLEXES; ESTROGEN-RECEPTOR-ALPHA; PROTEIN-DNA INTERACTIONS; IN-VIVO;
LIVING CELLS; GLUCOCORTICOID-RECEPTOR; NUCLEOSOME ORGANIZATION;
MESSENGER-RNA
AB Transcriptional regulation is achieved through combinatorial interactions between regulatory elements in the human genome and a vast range of factors that modulate the recruitment and activity of RNA polymerase. Experimental approaches for studying transcription in vivo now extend from single-molecule techniques to genome-wide measurements. Parallel to these developments is the need for testable quantitative and predictive models for understanding gene regulation. These conceptual models must also provide insight into the dynamics of transcription and the variability that is observed at the single-cell level. In this Review, we discuss recent results on transcriptional regulation and also the models those results engender. We show how a non-equilibrium description informs our view of transcription by explicitly considering time-and energy-dependence at the molecular level.
C1 [Coulon, Antoine; Chow, Carson C.] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
[Singer, Robert H.] Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10461 USA.
[Singer, Robert H.] HHMI, Ashburn, VA 20147 USA.
[Larson, Daniel R.] NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Larson, DR (reprint author), NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM dan.larson@nih.gov
RI Larson, Daniel/B-9829-2008; Coulon, Antoine/A-9006-2012
OI Larson, Daniel/0000-0001-9253-3055;
FU US National Institutes of Health (NIH) [GM57071, 84364, 86217]; NIH,
National Cancer Institute, Center for Cancer Research
FX We would like to thank the members of the Transcription Imaging
Consortium at the Janelia Farm Research Campus for their important
contributions to the theories proposed here. We also thank B. Lewis for
critical reading of the manuscript. This work is supported in part by
funding from the US National Institutes of Health (NIH) grants GM57071,
84364 and 86217 to R. H. S. D. R. L. is supported by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research.
NR 154
TC 82
Z9 82
U1 3
U2 79
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-0056
J9 NAT REV GENET
JI Nat. Rev. Genet.
PD AUG
PY 2013
VL 14
IS 8
BP 572
EP 584
DI 10.1038/nrg3484
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 185HB
UT WOS:000321956900012
PM 23835438
ER
PT J
AU Turanov, AA
Lobanov, AV
Hatfield, DL
Gladyshev, VN
AF Turanov, Anton A.
Lobanov, Alexei V.
Hatfield, Dolph L.
Gladyshev, Vadim N.
TI UGA codon position-dependent incorporation of selenocysteine into
mammalian selenoproteins
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID THIOREDOXIN REDUCTASE; CELLULAR TARGETS; SECIS ELEMENTS; MESSENGER-RNAS;
EXPRESSION; EFFICIENCY; INSERTION; IDENTIFICATION; EUKARYOTES; SIGNATURE
AB It is thought that the SelenoCysteine Insertion Sequence (SECIS) element and UGA codon are sufficient for selenocysteine (Sec) insertion. However, we found that UGA supported Sec insertion only at its natural position or in its close proximity in mammalian thioredoxin reductase 1 (TR1). In contrast, Sec could be inserted at any tested position in mammalian TR3. Replacement of the 3'-UTR of TR3 with the corresponding segment of a Euplotes crassus TR restricted Sec insertion into the C-terminal region, whereas the 3'-UTR of TR3 conferred unrestricted Sec insertion into E. crassus TR, in which Sec insertion is normally limited to the C-terminal region. Exchanges of 3'-UTRs between mammalian TR1 and E. crassus TR had no effect, as both proteins restricted Sec insertion. We further found that these effects could be explained by the use of selenoprotein-specific SECIS elements. Examination of Sec insertion into other selenoproteins was consistent with this model. The data indicate that mammals evolved the ability to limit Sec insertion into natural positions within selenoproteins, but do so in a selenoprotein-specific manner, and that this process is controlled by the SECIS element in the 3'-UTR.
C1 [Turanov, Anton A.; Lobanov, Alexei V.; Gladyshev, Vadim N.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
[Turanov, Anton A.; Lobanov, Alexei V.; Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Gladyshev, VN (reprint author), Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA.
EM vgladyshev@rics.bwh.harvard.edu
FU National Institutes of Health (NIH) [GM065204, GM061603]; Intramural
Research Program at the Center for Cancer Research, NCI, NIH
FX National Institutes of Health (NIH) grants [GM065204 and GM061603 to
V.N.G.] and the Intramural Research Program at the Center for Cancer
Research, NCI, NIH (to D.LH.). Funding for open access charge: NIH
[GM065204 and GM061603].
NR 28
TC 7
Z9 8
U1 1
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD AUG
PY 2013
VL 41
IS 14
BP 6952
EP 6959
DI 10.1093/nar/gkt409
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 200EN
UT WOS:000323050700024
PM 23716634
ER
PT J
AU Takeda, Y
Jetten, AM
AF Takeda, Yukimasa
Jetten, Anton M.
TI Prospero-related homeobox 1 (Prox1) functions as a novel modulator of
retinoic acid-related orphan receptors alpha- and gamma-mediated
transactivation
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID ROR-ALPHA; NUCLEAR RECEPTOR; GENE-EXPRESSION; REV-ERB; TRANSCRIPTIONAL
ACTIVATION; CIRCADIAN TRANSCRIPTION; INSULIN SENSITIVITY; PROFILING
REVEALS; LIPID HOMEOSTASIS; MAMMALIAN CLOCK
AB In this study, we identify Prospero-related homeobox 1 (Prox1) as a novel co-repressor of the retinoic acid-related orphan receptors, ROR alpha and ROR gamma. Prox1 interacts directly with ROR gamma and ROR alpha and negatively regulates their transcriptional activity. The AF2 domain of RORs is essential for the interaction, whereas Prox1 interacts with RORs through either its 28 amino acids N-terminal region or its C-terminal prospero-like domain. ROR gamma antagonists stabilize the interaction between ROR gamma and Prox1. The homeodomain and the interaction through the prospero-like domain of Prox1 are critical for its repression of ROR transcriptional activity. Chromatin immunoprecipitation analysis demonstrated that in liver, Prox1 is recruited to the ROR response element sites of the clock genes, brain and muscle Arnt-like protein 1 (Bmal1), neuronal PAS domain protein 2 (Npas2) and cryptochrome 1 (Cry1), as part of the same complex as RORs. Knockdown of Prox1 by siRNAs in human hepatoma Huh-7 cells increased the expression of ROR gamma and several ROR-target genes, along with increased histone acetylation at these ROR response element sites. Chromatin immunoprecipitation sequencing analysis suggests that Prox1 is a potential ROR target gene in liver, which is supported by the regulation of the rhythmic expression of Prox1 by ROR gamma. Our data suggest that Prox1 is part of a feedback loop that negatively regulates the transcriptional control of clock and metabolic networks by RORs.
C1 [Takeda, Yukimasa; Jetten, Anton M.] NIEHS, Div Intramural Res, Cell Biol Sect, NIH, Res Triangle Pk, NC 27709 USA.
RP Jetten, AM (reprint author), NIEHS, Div Intramural Res, Cell Biol Sect, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM jetten@niehs.nih.gov
OI Jetten, Anton/0000-0003-0954-4445
FU National Institute of Environmental Health Sciences, the National
Institutes of Health (NIH) [Z01-ES-101586]; Japanese Society for the
Promotion of Science (JSPS); NIH
FX Intramural Research Program of the National Institute of Environmental
Health Sciences, the National Institutes of Health (NIH) [Z01-ES-101586]
and the Japanese Society for the Promotion of Science (JSPS). Funding
for open access charge: NIH.
NR 67
TC 10
Z9 14
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD AUG
PY 2013
VL 41
IS 14
BP 6992
EP 7008
DI 10.1093/nar/gkt447
PG 17
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 200EN
UT WOS:000323050700027
PM 23723244
ER
PT J
AU Albrecht, SS
Roux, AVD
Kandula, NR
Osypuk, TL
Ni, HY
Shrager, S
AF Albrecht, Sandra S.
Roux, Ana V. Diez
Kandula, Namratha R.
Osypuk, Theresa L.
Ni, Hanyu
Shrager, Sandi
TI Immigrant Assimilation and BMI and Waist Size: A Longitudinal
Examination Among Hispanic and Chinese Participants in the Multi-ethnic
Study of Atherosclerosis
SO OBESITY
LA English
DT Article
ID BODY-MASS INDEX; NEW-YORK-CITY; UNITED-STATES; SOCIOECONOMIC-STATUS;
NATIONAL SAMPLE; OBESITY; RESIDENCE; ACCULTURATION; US; AMERICANS
AB Objective: US birth and longer length of US residence among the foreign-born have been linked to higher anthropometric measures. However, previous studies have been cross sectional and few have examined heterogeneity by ethnic group. Cross-sectional findings that show immigrant weight converging to US-born levels with longer time in the United States imply that immigrants' weight is increasing at a faster rate relative to US-born individuals. Prospective studies are necessary to confirm this pattern.
Design and Methods: Using longitudinal data from 1,486 Hispanic and 802 Chinese adults aged 45-84 years in the Multi-ethnic Study of Atherosclerosis, we examined whether foreign-born participants experienced greater increases in BMI and waist circumference (WC) than the US-born over a median follow-up of 5 years. We also investigated heterogeneity in these associations by Hispanic subgroup.
Results: Among Hispanics and Chinese, the foreign-born had a lower adjusted mean BMI and WC at baseline than the US-born, but there were no significant differences in BMI or WC change over time. There was heterogeneity by Hispanic subgroup: despite small baseline nativity differences in WC, foreign-born Mexican Hispanics had a greater annual mean increase in WC over time compared to US-born Mexican Hispanics (mean difference in annual change = 0.28 cm, P = 0.03). There were no nativity differences in the rate of WC increase over time among non-Mexican Hispanics. Foreign-born Mexican Hispanics also experienced a faster rate of WC increase compared to foreign-born non-Mexican Hispanics (mean difference in annual change = 0.24 cm, P = 0.01).
Conclusions: Longer time in the United States, examined prospectively, may only be linked to adverse anthropometric changes in some immigrant groups.
C1 [Albrecht, Sandra S.; Roux, Ana V. Diez] Univ Michigan, Dept Epidemiol, Ctr Social Epidemiol & Populat Hlth, Ann Arbor, MI 48109 USA.
[Kandula, Namratha R.] Northwestern Univ, Feinberg Sch Med, Div Gen Internal Med, Chicago, IL 60611 USA.
[Osypuk, Theresa L.] Northeastern Univ, Bouve Coll Hlth Sci, Boston, MA 02115 USA.
[Ni, Hanyu] NHLBI, NIH, Bethesda, MD 20892 USA.
[Shrager, Sandi] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA.
RP Albrecht, SS (reprint author), Univ Michigan, Dept Epidemiol, Ctr Social Epidemiol & Populat Hlth, Ann Arbor, MI 48109 USA.
EM ssalb@unc.edu
FU National Heart, Lung, and Blood Institute [R01 HL071759, N01-HC-95159,
N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164,
N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169,
PA-08-190, R01 HL071759 05A1]; Michigan Center for Integrative
Approaches to Health Disparities [P60 MD002249]; National Institute on
Minority Health and Health Disparities
FX This work was supported by the National Heart, Lung, and Blood Institute
grant R01 HL071759 (Diez Roux); the Research Supplement to Promote
Diversity in Health-Related Research (PA-08-190)-supplement to grant R01
HL071759 05A1 (Diez Roux); and by the Michigan Center for Integrative
Approaches to Health Disparities (P60 MD002249) funded by the National
Institute on Minority Health and Health Disparities. The Multi-Ethnic
Study of Atherosclerosis is supported by contracts N01-HC-95159 through
N01-HC-95169 from the National Heart, Lung, and Blood Institute. The
authors thank the other investigators, staff, and participants of the
MESA study for their valuable contributions. A full list of
participating MESA investigators and institutions can be found at:
http://www.mesa-nhlbi.org.
NR 43
TC 14
Z9 15
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD AUG
PY 2013
VL 21
IS 8
BP 1695
EP 1703
DI 10.1002/oby.20104
PG 9
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 206LE
UT WOS:000323521500029
PM 23716458
ER
PT J
AU Murabito, JM
Massaro, JM
Clifford, B
Hoffmann, U
Fox, CS
AF Murabito, Joanne M.
Massaro, Joseph M.
Clifford, Brian
Hoffmann, Udo
Fox, Caroline S.
TI Depressive Symptoms Are Associated with Visceral Adiposity in a
Community-Based Sample of Middle-Aged Women and Men
SO OBESITY
LA English
DT Article
ID CORONARY HEART-DISEASE; MAJOR DEPRESSION; ABDOMINAL OBESITY; TISSUE
VOLUMES; OLDER PERSONS; FAT; MARKERS; HEALTH; OVERWEIGHT; DISORDERS
AB Objective: To examine the relation between measures of adiposity and depressive symptoms in a large well characterized community-based sample, we examined the relations of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) to depressive symptoms in 1,581 women (mean age 52.2 years) and 1,718 men (mean age 49.8 years) in the Framingham Heart Study.
Design and Methods: Depressive symptoms were measured using the Center for Epidemiologic Studies Depression (CES-D) scale. Regression models were created to examine the association between each fat depot (exposure) and depressive symptoms (outcome). Sex-specific models were adjusted for age, body mass index, smoking, alcohol consumption, diabetes, hypertension, total and HDL cholesterol, lipid lowering treatment, CVD, menopause, C-reactive protein, and physical activity.
Results: Mean CES-D scores were 6.8 and 5.6 in women and men. High levels of depressive symptoms were present in 22.5% of women and 12.3% of men. In women, one standard deviation increase in VAT was associated with a 1.3 point higher CES-D score after adjusting for age and BMI (P < 0.01) and remained significant in the fully adjusted model (P = 0.03). The odds ratio of depressive symptoms per 1 standard deviation increase in VAT in women was 1.33 (P = 0.015); results were attenuated in fully adjusted models (OR 1.29, P = 0.055). In men, the association between VAT and CES-D score and depressive symptoms was not significant. SAT was not associated with CES-D score or depressive symptoms.
Conclusions: This study supports an association between VAT and depressive symptoms in women. Further work is needed to uncover the complex biologic mechanisms mediating the association.
C1 [Murabito, Joanne M.; Clifford, Brian] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA.
[Murabito, Joanne M.; Fox, Caroline S.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
[Massaro, Joseph M.] Boston Univ, Dept Math, Boston, MA 02215 USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Dept Cardiac MR PET CT, Boston, MA 02114 USA.
[Hoffmann, Udo; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA.
RP Murabito, JM (reprint author), Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA.
EM murabito@bu.edu
OI Murabito, Joanne/0000-0002-0192-7516; Massaro,
Joseph/0000-0002-2682-4812
FU National Heart Blood and Lung Institute [N01-HC-25195]
FX The Framingham Heart Study is funded by National Heart Blood and Lung
Institute (contract N01-HC-25195).
NR 33
TC 9
Z9 9
U1 2
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD AUG
PY 2013
VL 21
IS 8
BP 1713
EP 1719
DI 10.1002/oby.20130
PG 7
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 206LE
UT WOS:000323521500031
PM 23666906
ER
PT J
AU Xie, XF
Colberg-Poley, AM
Das, JR
Li, JL
Zhang, AP
Tang, PA
Jerebtsova, M
Gukind, SJ
Ray, PE
AF Xie, Xuefang
Colberg-Poley, Anamaris M.
Das, Jharna R.
Li, Jinliang
Zhang, Aiping
Tang, Pingato
Jerebtsova, Marina
Gukind, Silvio J.
Ray, Patricio E.
TI The Basic Domain is Essential for Targeting HIV-Tat to Lipid Rafts and
Regulating Fibroblast Growth Factor-2 (FGF-2) Signaling in Human
Podocytes
SO PEDIATRIC NEPHROLOGY
LA English
DT Meeting Abstract
C1 [Xie, Xuefang; Colberg-Poley, Anamaris M.; Das, Jharna R.; Li, Jinliang; Zhang, Aiping; Tang, Pingato; Jerebtsova, Marina; Ray, Patricio E.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Gukind, Silvio J.] Natl Inst Dent & Craneofacial Res, NIH, Bethesda, MD USA.
[Colberg-Poley, Anamaris M.; Tang, Pingato; Jerebtsova, Marina; Ray, Patricio E.] George Washington Univ, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0931-041X
J9 PEDIATR NEPHROL
JI Pediatr. Nephrol.
PD AUG
PY 2013
VL 28
IS 8
BP 1365
EP 1365
PG 1
WC Pediatrics; Urology & Nephrology
SC Pediatrics; Urology & Nephrology
GA 177PJ
UT WOS:000321387201055
ER
PT J
AU Das, JR
Hui, XX
Perazzo, S
Gutkind, JS
Ray, PE
AF Das, Jharna R.
Hui Xie-Xukauskas
Perazzo, Sofia
Gutkind, J. Silvio
Ray, Patricio E.
TI Novel mechanisms by which Heparin can regulate the vascular activity of
Angiotensin II (Ang-II) and Fibroblast Growth Factor-2 (FGF-2) and
affect the outcome of acute kidney injury (AKI)
SO PEDIATRIC NEPHROLOGY
LA English
DT Meeting Abstract
C1 [Das, Jharna R.; Hui Xie-Xukauskas; Perazzo, Sofia; Ray, Patricio E.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Gutkind, J. Silvio] Natl Inst Dent & Craneofacial Res, NIH, Bethesda, MD USA.
[Ray, Patricio E.] George Washington Univ, Dept Pediat, Washington, DC 20052 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0931-041X
J9 PEDIATR NEPHROL
JI Pediatr. Nephrol.
PD AUG
PY 2013
VL 28
IS 8
BP 1475
EP 1475
PG 1
WC Pediatrics; Urology & Nephrology
SC Pediatrics; Urology & Nephrology
GA 177PJ
UT WOS:000321387202197
ER
PT J
AU Warady, B
Schwartz, G
Wong, C
Mitsnefes, M
Kaskel, F
Greenbaum, L
Mak, R
Flynn, J
Moxey-Mims, M
AF Warady, Bradley
Schwartz, George
Wong, Craig
Mitsnefes, Mark
Kaskel, Frederick
Greenbaum, Larry
Mak, Robert
Flynn, Joseph
Moxey-Mims, Marva
CA Susan Furth CKiD Study
TI Disease Progression in Children with Chronic Kidney Disease
SO PEDIATRIC NEPHROLOGY
LA English
DT Meeting Abstract
C1 [Warady, Bradley] Childrens Mercy Hosp & Clin, Kansas City, MO USA.
[Schwartz, George] Golisano Childrens Hosp Strong, Rochester, NY USA.
[Wong, Craig] Univ New Mexico, Childrens Hosp, Albuquerque, NM 87131 USA.
[Mitsnefes, Mark] Cincinnati Childrens Hosp, Cincinnati, OH USA.
[Kaskel, Frederick] Childrens Hosp Montefiore, Bronx, NY USA.
[Greenbaum, Larry] Emory Univ, Sch Med, Atlanta, GA USA.
[Mak, Robert] Univ Calif San Diego, San Diego, CA 92103 USA.
[Flynn, Joseph] Seattle Childrens Hosp, Seattle, WA USA.
[Moxey-Mims, Marva] NIDDK, NIH, DKUH, Bethesda, MD 20892 USA.
[Susan Furth CKiD Study] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0931-041X
J9 PEDIATR NEPHROL
JI Pediatr. Nephrol.
PD AUG
PY 2013
VL 28
IS 8
BP 1493
EP 1494
PG 2
WC Pediatrics; Urology & Nephrology
SC Pediatrics; Urology & Nephrology
GA 177PJ
UT WOS:000321387202250
ER
PT J
AU Akchurin, OM
Skversky, AL
Schneider, MF
Malquin, L
Langman, CB
Greenbaum, LA
Furth, SL
Moxey-Mims, M
Warady, BA
Kaskel, FJ
AF Akchurin, Oleh M.
Skversky, Amy L.
Schneider, Michael F.
Malquin, Lucy
Langman, Craig B.
Greenbaum, Laurence A.
Furth, Susan L.
Moxey-Mims, Marva
Warady, Bradley A.
Kaskel, Frederick J.
TI Medication Adherence and Growth in the Chronic Kidney Disease in
Children (CKiD) study
SO PEDIATRIC NEPHROLOGY
LA English
DT Meeting Abstract
C1 [Akchurin, Oleh M.; Skversky, Amy L.; Kaskel, Frederick J.] Childrens Hosp Montefiore, Albert Einstein Coll Med, Bronx, NY USA.
[Schneider, Michael F.; Malquin, Lucy] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Langman, Craig B.] Feinberg Sch Med, Chicago, IL USA.
[Greenbaum, Laurence A.] Emory Univ, Sch Med, Emory Childrens Ctr, Atlanta, GA USA.
[Furth, Susan L.] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Moxey-Mims, Marva] NIDDK, Bethesda, MD USA.
[Warady, Bradley A.] Univ Missouri Kansas City, Sch Med, Childrens Mercy Hosp & Clin, Kansas City, MO USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0931-041X
J9 PEDIATR NEPHROL
JI Pediatr. Nephrol.
PD AUG
PY 2013
VL 28
IS 8
BP 1652
EP 1652
PG 1
WC Pediatrics; Urology & Nephrology
SC Pediatrics; Urology & Nephrology
GA 177PJ
UT WOS:000321387204016
ER
PT J
AU Tsai, CJ
Nussinov, R
AF Tsai, Chung-Jung
Nussinov, Ruth
TI The molecular basis of targeting protein kinases in cancer therapeutics
SO SEMINARS IN CANCER BIOLOGY
LA English
DT Review
DE Kinases; Cancer; Oncogenic mutations; Inhibitors; Drug discovery;
Therapeutics; Oncogene addiction; Bow-tie model; EGFR
ID GROWTH-FACTOR RECEPTOR; ONCOGENE ADDICTION; EGF RECEPTOR; DRUG
DISCOVERY; STRUCTURAL BASIS; TYROSINE KINASE; LUNG-CANCER;
SIGNAL-TRANSDUCTION; ANTICANCER THERAPY; 20-1ST CENTURY
AB In this paper, we provide an overview of targeted anticancer therapies with small molecule kinase inhibitors. First, we discuss why a single constitutively active kinase emanating from a variety of aberrant genetic alterations is capable of transforming a normal cell, leading it to acquire the hallmarks of a cancer cell. To draw attention to the fact that kinase inhibition in targeted cancer therapeutics differs from conventional cytotoxic chemotherapy, we exploit a conceptual framework explaining why suppressed kinase activity will selectively kill only the so-called oncogene 'addicted' cancer cell, while sparing the healthy cell. Second, we introduce the protein kinase superfamily in light of its common active conformation with precisely positioned structural elements, and the diversified auto-inhibitory conformations among the kinase families. Understanding the detailed activation mechanism of individual kinases is essential to relate the observed oncogenic alterations to the elevated constitutively active state, to identify the mechanism of consequent drug resistance, and to guide the development of the next-generation inhibitors. To clarify the vital importance of structural guidelines in studies of oncogenesis, we explain how somatic mutations in EGFR result in kinase constitutive activation. Third, in addition to the common theme of secondary (acquired) mutations that prevent drug binding from blocking a signaling pathway which is hijacked by the aberrant activated kinase, we discuss scenarios of drug resistance and relapse by compensating lesions that bypass the inactivated pathway in a vertical or horizontal fashion. Collectively, these suggest that the future challenge of cancer therapy with small molecule kinase inhibitors will rely on the discovery of distinct combinations of optimized drugs to target individual subtypes of different cancers. (c) 2013 Elsevier Ltd. All rights reserved.
C1 [Tsai, Chung-Jung; Nussinov, Ruth] NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program,Frederick Natl Lab, 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, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program,Frederick Natl Lab, Frederick, MD 21702 USA.
EM nussinor@helix.nih.gov
FU Federal funds from the National Cancer Institute, National Institutes of
Health [HHSN261200800001E]; Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research
FX This project has been funded in whole or in part with Federal funds from
the National Cancer Institute, National Institutes of Health, under
contract number HHSN261200800001E. The content of this publication does
not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
This research was supported (in part) by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research.
NR 74
TC 30
Z9 30
U1 2
U2 57
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1044-579X
J9 SEMIN CANCER BIOL
JI Semin. Cancer Biol.
PD AUG
PY 2013
VL 23
IS 4
BP 235
EP 242
DI 10.1016/j.semcancer.2013.04.001
PG 8
WC Oncology
SC Oncology
GA 205PF
UT WOS:000323455900005
PM 23651790
ER
PT J
AU Maiorov, EG
Keskin, O
Gursoy, A
Nussinov, R
AF Maiorov, Emine Guven
Keskin, Ozlem
Gursoy, Attila
Nussinov, Ruth
TI The structural network of inflammation and cancer: Merits and challenges
SO SEMINARS IN CANCER BIOLOGY
LA English
DT Review
DE TLR; NF-kappa B; Inflammation; Cancer; Inflammation and cancer link;
Structural pathway; MyD88; Structural data
ID TOLL-LIKE RECEPTORS; PROTEIN-PROTEIN INTERACTIONS; DRUG DISCOVERY;
SIGNAL-TRANSDUCTION; TUMOR-GROWTH; INTERFERON-BETA; OVARIAN-CANCER;
INTERFACES; PATHWAYS; SCALE
AB Inflammation, the first line of defense against pathogens can contribute to all phases of tumorigenesis, including tumor initiation, promotion and metastasis. Within this framework, the Toll-like receptor (TLR) pathway plays a central role in inflammation and cancer. Although extremely useful, the classical representation of this, and other pathways in the cellular network in terms of nodes (proteins) and edges (interactions) is incomplete. Structural pathways can help complete missing parts of such diagrams: they demonstrate in detail how signals coming from different upstream pathways merge and propagate downstream, how parallel pathways compensate each other in drug resistant mutants, how multi-subunit signaling complexes form and in particular why they are needed and how they work, how allosteric events can control these proteins and their pathways, and intricate details of feedback loops and how kick in. They can also explain the mechanisms of some oncogenic SNP mutations. Constructing structural pathways is a challenging task. Here, our goal is to provide an overview of inflammation and cancer from the structural standpoint, focusing on the TLR pathway. We use the powerful PRISM (PRotein Interactions by Structural Matching) tool to reveal important structural information of interactions in and within key orchestrators of the TLR pathway, such as MyD88. (c) 2013 Elsevier Ltd. All rights reserved.
C1 [Maiorov, Emine Guven; Keskin, Ozlem; Gursoy, Attila] Koc Univ, Coll Engn, Ctr Computat Biol & Bioinformat, Istanbul, Turkey.
[Nussinov, Ruth] Natl Canc Inst, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
RP Nussinov, R (reprint author), Natl Canc Inst, Frederick, MD USA.
EM eguven@ku.edu.tr; okeskin@ku.edu.tr; agursoy@ku.edu.tr;
NussinoR@helix.nih.gov
RI Gursoy, Attila/E-9565-2015;
OI Gursoy, Attila/0000-0002-2297-2113; Guven Maiorov,
Emine/0000-0002-7388-9811
FU Federal funds from the National Cancer Institute, National Institutes of
Health [HHSN261200800001E]; Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research; Science Academy
(of Turkey)
FX This project has been funded in whole or in part with Federal funds from
the National Cancer Institute, National Institutes of Health, under
contract number HHSN261200800001E. The content of this publication does
not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government. This
research was supported (in part) by the Intramural Research Program of
the NIH, National Cancer Institute, Center for Cancer Research. O.K.
acknowledges the support of Science Academy (of Turkey).
NR 68
TC 19
Z9 19
U1 1
U2 24
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1044-579X
J9 SEMIN CANCER BIOL
JI Semin. Cancer Biol.
PD AUG
PY 2013
VL 23
IS 4
BP 243
EP 251
DI 10.1016/j.semcancer.2013.05.003
PG 9
WC Oncology
SC Oncology
GA 205PF
UT WOS:000323455900006
ER
PT J
AU Dal Monte, O
Krueger, F
Solomon, JM
Schintu, S
Knutson, KM
Strenziok, M
Pardini, M
Leopold, A
Raymont, V
Grafman, J
AF Dal Monte, Olga
Krueger, Frank
Solomon, Jeffrey M.
Schintu, Selene
Knutson, Kristine M.
Strenziok, Maren
Pardini, Matteo
Leopold, Anne
Raymont, Vanessa
Grafman, Jordan
TI A voxel-based lesion study on facial emotion recognition after
penetrating brain injury
SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE
LA English
DT Article
DE facial emotion recognition; voxel-based lesion symptom mapping; labeling
task; basic emotions; traumatic brain injury
ID ANTERIOR TEMPORAL INVOLVEMENT; FRONTAL-LOBE DAMAGE; HUMAN AMYGDALA;
IMPAIRED RECOGNITION; PREFRONTAL CORTEX; COGNITIVE-ABILITIES;
RIGHT-HEMISPHERE; BASIC EMOTIONS; NEURAL BASES; HEAD-INJURY
AB The ability to read emotions in the face of another person is an important social skill that can be impaired in subjects with traumatic brain injury (TBI). To determine the brain regions that modulate facial emotion recognition, we conducted a whole-brain analysis using a well-validated facial emotion recognition task and voxel-based lesion symptom mapping (VLSM) in a large sample of patients with focal penetrating TBIs (pTBIs). Our results revealed that individuals with pTBI performed significantly worse than normal controls in recognizing unpleasant emotions. VLSM mapping results showed that impairment in facial emotion recognition was due to damage in a bilateral fronto-temporo-limbic network, including medial prefrontal cortex (PFC), anterior cingulate cortex, left insula and temporal areas. Beside those common areas, damage to the bilateral and anterior regions of PFC led to impairment in recognizing unpleasant emotions, whereas bilateral posterior PFC and left temporal areas led to impairment in recognizing pleasant emotions. Our findings add empirical evidence that the ability to read pleasant and unpleasant emotions in other people's faces is a complex process involving not only a common network that includes bilateral fronto-temporo-limbic lobes, but also other regions depending on emotional valence.
C1 [Dal Monte, Olga; Schintu, Selene; Knutson, Kristine M.; Raymont, Vanessa; Grafman, Jordan] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA.
[Dal Monte, Olga] Univ Turin, Dept Neuropsychol, I-10123 Turin, Italy.
[Dal Monte, Olga; Schintu, Selene] Henry M Jackson Fdn, Rockville, MD 20852 USA.
[Krueger, Frank; Strenziok, Maren] George Mason Univ, Dept Mol Neurosci, Fairfax, VA 22030 USA.
[Krueger, Frank] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA.
[Solomon, Jeffrey M.] Expert Image Anal LLC, Potomac, MD 20859 USA.
[Pardini, Matteo] Univ Genoa, Dept Neurosci Ophthalmol & Genet, I-16132 Genoa, Italy.
[Leopold, Anne] Univ Utrecht, Social & Hlth Psychol Dept, NL-3508 Utrecht, Netherlands.
[Raymont, Vanessa] Johns Hopkins Univ, Dept Radiol, Baltimore, MD 21287 USA.
[Raymont, Vanessa] Univ London Imperial Coll Sci Technol & Med, Dept Med, London SW72WY, England.
[Grafman, Jordan] Kessler Fdn Res Ctr, Traumat Brain Injury Res Lab, W Orange, NJ 07052 USA.
RP Krueger, F (reprint author), George Mason Univ, Dept Mol Neurosci, 4400 Univ Dr,Mail Stop 2A1, Fairfax, VA 22030 USA.
EM fkrueger@gmu.edu
RI Pardini, Matteo/F-8414-2010;
OI Pardini, Matteo/0000-0002-4740-1982; Grafman, Jordan
H./0000-0001-8645-4457; dal monte, olga/0000-0002-7823-4769; Knutson,
Kristine/0000-0003-4626-4514
FU National Naval Medical Center
FX The authors are grateful to all the Vietnam veterans who participated in
this study. Without their long-term commitment to improving the health
care of veterans, this study could not have been completed. We thank the
National Naval Medical Center for their support and provision of their
facilities as well as S. Bonifant, B. Cheon, C. Ngo, A. Greathouse, K.
Reding and G. Tasick for their invaluable help with the testing of
participants and organization of this study. For further information
about the Vietnam Head Injury Study, please contact Dr. Grafman at:
jgrafman@kesslerfoundation.org
NR 107
TC 15
Z9 15
U1 5
U2 28
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1749-5016
J9 SOC COGN AFFECT NEUR
JI Soc. Cogn. Affect. Neurosci.
PD AUG
PY 2013
VL 8
IS 6
BP 632
EP 639
DI 10.1093/scan/nss041
PG 8
WC Neurosciences; Psychology; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 205OU
UT WOS:000323454700004
PM 22496440
ER
PT J
AU Helfinstein, SM
Kirwan, ML
Benson, BE
Hardin, MG
Pine, DS
Ernst, M
Fox, NA
AF Helfinstein, Sarah M.
Kirwan, Michael L.
Benson, Brenda E.
Hardin, Michael G.
Pine, Daniel S.
Ernst, Monique
Fox, Nathan A.
TI Validation of a child-friendly version of the monetary incentive delay
task
SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE
LA English
DT Article
DE Reward; childhood; fMRI
ID EVENT-RELATED FMRI; REWARD ANTICIPATION; ADOLESCENTS; ADULTS;
VISUALIZATION; PREDICTION; ACCUMBENS; DISORDER; CHOICE; SYSTEM
AB The monetary incentive delay (MID) task (Knutson, 2000) is an imaging paradigm used to measure neural activity of incentive receipt anticipation. The task reliably elicits striatal activation and is commonly used with both adult and adolescent populations, but is not designed for use with children. In the current article, we present data on the newly designed 'pinata task' a child-friendly analog of the MID task. We demonstrate the task can be used successfully in children to study the neural correlates of anticipatory incentive processing. Results from a behavioral study and a neuroimaging study are reported. In Study #1, a sample of 8- to 14-year-old children demonstrates expected behavioral effects: subjects responded most quickly and most accurately on trials with greater potential rewards; older children displayed faster reaction times than younger. In Study #2, 8- to 12-year-old children showed neural activation patterns consistent with those seen in adults in the MID task: activation was modulated by cue incentive value in reward-processing regions, including the striatum, thalamus, mesial prefrontal cortex and insula. Study results suggest that the pinata task is a valid analog of the MID task, and can be used to assess neural correlates of reward processing in children as young as 8-9 years of age.
C1 [Helfinstein, Sarah M.] Univ Texas Austin, Dept Psychol, Imaging Res Ctr, Austin, TX 78712 USA.
[Helfinstein, Sarah M.] Univ Texas Austin, Dept Neurobiol, Austin, TX 78712 USA.
[Kirwan, Michael L.] Harvard Univ, Ctr Developing Child, Cambridge, MA 02138 USA.
[Benson, Brenda E.; Pine, Daniel S.; Ernst, Monique] NIMH, Bethesda, MD 20814 USA.
[Hardin, Michael G.] Stanford Univ, Dept Psychol, Palo Alto, CA 94304 USA.
[Fox, Nathan A.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA.
RP Helfinstein, SM (reprint author), 3925-B W Braker Ln, Austin, TX 78759 USA.
EM shelfins@gmail.com
FU National Institute of Mental Health-Intramural Research Program;
National Institutes of Health [MH078105]
FX This work was supported by the National Institute of Mental
Health-Intramural Research Program, and by a grant from the National
Institutes of Health to NAF [MH078105].
NR 28
TC 6
Z9 6
U1 2
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1749-5016
J9 SOC COGN AFFECT NEUR
JI Soc. Cogn. Affect. Neurosci.
PD AUG
PY 2013
VL 8
IS 6
BP 720
EP 726
DI 10.1093/scan/nss057
PG 7
WC Neurosciences; Psychology; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 205OU
UT WOS:000323454700015
PM 22569186
ER
PT J
AU Sun, L
Mathews, LA
Cabarcas, SM
Zhang, XH
Yang, AC
Zhang, Y
Young, MR
Klarmann, KD
Keller, JR
Farrar, WL
AF Sun, Lei
Mathews, Lesley A.
Cabarcas, Stephanie M.
Zhang, Xiaohu
Yang, Acong
Zhang, Ying
Young, Matthew R.
Klarmann, Kimberly D.
Keller, Jonathan R.
Farrar, William L.
TI Epigenetic Regulation of SOX9 by the NF-kappa B Signaling Pathway in
Pancreatic Cancer Stem Cells
SO STEM CELLS
LA English
DT Article
DE Pancreatic cancer; Cancer stem cells; Invasion; Epigenetic regulation;
NF-B signaling; SOX9
ID EPITHELIAL-MESENCHYMAL TRANSITION; TUMOR INITIATING CELLS; TRANSCRIPTION
FACTOR; DNA METHYLATION; GROWTH-FACTOR; DRUG-RESISTANCE;
DOWN-REGULATION; UP-REGULATION; PHASE-I; C-MET
AB Pancreatic cancer is the fourth leading cause of cancer-related mortality in the world. Pancreatic cancer can be localized, locally advanced, or metastatic. The median 1- and 5-year survival rates are 25% and 6%, respectively. Epigenetic modifications such as DNA methylation play a significant role during both normal human development and cancer progression. To investigate epigenetic regulation of genes in the tumor-initiating population of pancreatic cancer cells, which are also termed cancer stem cells (CSCs), we conducted epigenetic arrays in PANC1 and HPAC pancreatic cancer cell lines and compared the global DNA methylation status of CpG promoters in invasive cells, demonstrated to be CSCs, to their noninvasive counterparts, or non-CSCs. Our results suggested that the NF-B pathway is one of the most activated pathways in pancreatic CSCs. In agreement with this, we determined that upon treatment with NF-B pathway inhibitors, the stem cell-like properties of cells are significantly disrupted. Moreover, SOX9, demethylated in CSCs, is shown to play a crucial role in the invasion process. Additionally, we found a potential NF-B binding site located in the SOX9 promoter and determined that the NF-B subunit p65 positively regulates SOX9 expression by binding to its promoter directly. This interaction can be efficiently blocked by NF-B inhibitors. Thus, our work establishes a link between the classic NF-B signaling transduction pathway and the invasiveness of pancreatic CSCs, which may result in the identification of novel signals and molecules that function at an epigenetic level, and could potentially be targeted for pharmaceutical investigations and clinical trials.
C1 [Sun, Lei; Mathews, Lesley A.; Cabarcas, Stephanie M.; Farrar, William L.] NIH, Natl Ctr Adv Translat Sci, Canc Stem Cell Sect, Lab Canc Prevent, Rockville, MD USA.
[Mathews, Lesley A.; Zhang, Xiaohu] NIH, Natl Ctr Adv Translat Sci, Div Preclin Innovat, Rockville, MD USA.
[Cabarcas, Stephanie M.] Gannon Univ, Dept Biol, Erie, PA USA.
[Zhang, Xiaohu; Klarmann, Kimberly D.; Keller, Jonathan R.] Frederick Natl Lab Canc Res, SAIC Frederick Inc, Basic Res Program, Frederick, MD USA.
[Yang, Acong] China Acad Chinese Med Sci, Lab Prot Dynam & Signaling, Beijing, Peoples R China.
[Zhang, Ying] China Acad Chinese Med Sci, Guang An Men Hosp, Beijing, Peoples R China.
[Young, Matthew R.] NCI, Gene Regulat Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
RP Sun, L (reprint author), NCI, NIH, 1050 Boyles St,Bldg 560,Room 12-03, Frederick, MD 21702 USA.
EM lei.sun@nih.gov
RI Sun, Lei/J-9943-2015
FU National Cancer Institute, National Institute of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research
FX We thank Dr. Nancy H. Colburn for her critical reading and suggestions
in preparation of this manuscript. This project has been funded in whole
or in part with federal funds from the National Cancer Institute,
National Institute of Health, under Contract No. HHSN261200800001E. This
research was supported in part by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. The content
of this publication does not necessarily reflect the views of 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 71
TC 40
Z9 42
U1 0
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1066-5099
J9 STEM CELLS
JI Stem Cells
PD AUG
PY 2013
VL 31
IS 8
BP 1454
EP 1466
DI 10.1002/stem.1394
PG 13
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 205CM
UT WOS:000323418700002
PM 23592398
ER
PT J
AU Dahle, O
Kuehn, MR
AF Dahle, Oyvind
Kuehn, Michael R.
TI Polycomb Determines Responses to Smad2/3 Signaling in Embryonic Stem
Cell Differentiation and in Reprogramming
SO STEM CELLS
LA English
DT Article
DE Oct4 Pluripotency; Polycomb; Reprogramming; Smad2; 3
ID FACTOR-BETA SUPERFAMILY; GROUND-STATE; TARGET GENES; SELF-RENEWAL;
PLURIPOTENCY; MESENDODERM; TRANSITIONS; PROGENITORS; MECHANISMS;
INDUCTION
AB Integration of extrinsic signals, epigenetic regulators, and intrinsic transcription factors establishes pluripotent stem cell identity. Interplay between these components also underlies the capacity of stem cells to undergo differentiation, and of differentiated cells to re-establish the pluripotent state in direct reprogramming. Polycomb repressive complexes are epigenetic regulators that play key roles in stem cell identity and in differentiated cell fates. Smad2 and Smad3 (Smad2/3), the intracellular mediators of the Nodal/Activin/transforming growth factor (TGF) cell-cell signaling pathway also are implicated in stem cell pluripotency and in differentiation. Here, we show that Polycomb imposes responses to Smad2/3-mediated signaling to selectively regulate expression of the master pluripotency factor Oct4 during initiation of differentiation, but not in the self-renewing pluripotent ground state. During reprogramming back to the ground state, we find that the enhancement of reprogramming efficiency stemming from blocking Nodal/Activin/TGF signaling also depends on Polycomb. These context-dependent responses to Smad2/3 imposed by Polycomb action provide a mechanism for selective gene regulation that can reconcile the apparently conflicting roles of this signaling pathway in pluripotency, differentiation, and reprogramming. STEM Cells2013;31:1488-1497
C1 [Dahle, Oyvind; Kuehn, Michael R.] NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
RP Kuehn, MR (reprint author), NCI, LPDS, Bldg 560 Rm 12-90, Frederick, MD 21702 USA.
EM mkuehn@mail.nih.gov
RI Kuehn, Michael/A-4573-2014
OI Kuehn, Michael/0000-0002-7703-9160
FU National Cancer Institute, National Institutes of Health
FX We thank Dr. Lionel Feigenbaum and the Transgenic Mouse Model Laboratory
for generation of NanogNeo chimeric embryos; and Drs. Philipp
Oberdoerffer, David Salomon, and Kathrin Muegge for comments on the
manuscript. This work was supported by the Intramural Research Program
of the National Cancer Institute, National Institutes of Health. The
content of this publication does not necessarily reflect the views or
policies of the Department of Health and Human Services and nor does
mention of trade names, commercial products, or organizations imply
endorsement by the U.S. Government.
NR 49
TC 3
Z9 3
U1 2
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1066-5099
J9 STEM CELLS
JI Stem Cells
PD AUG
PY 2013
VL 31
IS 8
BP 1488
EP 1497
DI 10.1002/stem.1417
PG 10
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 205CM
UT WOS:000323418700005
PM 23666711
ER
PT J
AU Salcedo, R
Cataisson, C
Hasan, U
Yuspa, SH
Trinchieri, G
AF Salcedo, Rosalba
Cataisson, Christophe
Hasan, Uzma
Yuspa, Stuart H.
Trinchieri, Giorgio
TI MyD88 and its divergent toll in carcinogenesis
SO TRENDS IN IMMUNOLOGY
LA English
DT Review
DE skin carcinogenesis; colon carcinogenesis; cancer and inflammation;
oncogene-induced inflammation; Toll-like receptors; interleukin-1 family
receptors
ID NF-KAPPA-B; INFLAMMATORY CYTOKINE SECRETION; COLORECTAL-CANCER; SKIN
CARCINOGENESIS; FACTOR RECEPTOR; EXPRESSION PROFILE; MICROBIAL PRODUCTS;
BOUND IL-1-ALPHA; LUNG-CANCER; MOUSE MODEL
AB Toll-like and interleukin-1 (IL-1) family receptors recognize microbial or endogenous ligands and inflammatory mediators, respectively, and with the exception of Toll-like receptor 3 (TLR3), signal via the adaptor molecule myeloid differentiation factor 88 (MyD88). MyD88 is involved in oncogene-induced cell intrinsic inflammation and in cancer-associated extrinsic inflammation, and as such MyD88 contributes to skin, liver, pancreatic, and colon carcinogenesis, as well as sarcomagenesis. MyD88 is also protective, for example in oncogenic virus carcinogenesis or, acting downstream of IL-18R to strengthen mucosal repair, in azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colon carcinogenesis. Here, we discuss the mechanisms of the divergent effects of MyD88 and the balance of its protumor role in cancer-enhancing inflammation and immunity and its antitumor role in tissue homeostasis, repair, and immunity against the tumor or oncogenic pathogens.
C1 [Salcedo, Rosalba; Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Frederick, MD USA.
[Cataisson, Christophe; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
[Hasan, Uzma] Univ Lyon, Hosp Civils Lyon, Ecole Normale Super, Ctr Int Rech Infectiol,INSERM,U1111,CNRS,UMR5308, Lyon, France.
RP Trinchieri, G (reprint author), NCI, Canc & Inflammat Program, Frederick, MD USA.
EM trinchig@mail.nih.gov
RI hasan, uzma/G-3247-2013
FU Intramural Research Program of the National Cancer Institute, National
Institutes of Health (NCI/NIH)
FX This work was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health (NCI/NIH).
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PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4906
J9 TRENDS IMMUNOL
JI Trends Immunol.
PD AUG
PY 2013
VL 34
IS 8
BP 379
EP 389
DI 10.1016/j.it.2013.03.008
PG 11
WC Immunology
SC Immunology
GA 207JJ
UT WOS:000323594400003
PM 23660392
ER
PT J
AU Earl, LA
Lifson, JD
Subramaniam, S
AF Earl, Lesley A.
Lifson, Jeffrey D.
Subramaniam, Sriram
TI Catching HIV 'in the act' with 3D electron microscopy
SO TRENDS IN MICROBIOLOGY
LA English
DT Review
DE cryo-electron tomography; focused ion beam scanning electron microscopy
(FIB-SEM); ion abrasion scanning electron microscopy (IA-SEM); vaccine
design; virus-cell interaction
ID HUMAN-IMMUNODEFICIENCY-VIRUS; TO-CELL TRANSMISSION; HUMAN
MONOCLONAL-ANTIBODIES; HIV-1/SIV CHIMERIC VIRUS; DENDRITIC CELLS;
NEUTRALIZING ANTIBODIES; ENVELOPE GLYCOPROTEIN; POTENT NEUTRALIZATION;
VIROLOGICAL SYNAPSE; TYPE-1 INFECTION
AB The development of a safe, effective vaccine to prevent HIV infection is a key step for controlling the disease on a global scale. However, many aspects of HIV biology make vaccine design problematic, including the sequence diversity and structural variability of the surface envelope glycoproteins and the poor accessibility of neutralization-sensitive epitopes on the virus. In this review, we discuss recent progress in understanding HIV in a structural context using emerging tools in 3D electron microscopy, and outline how some of these advances could be important for a better understanding of mechanisms of viral entry and for vaccine design.
C1 [Earl, Lesley A.; Subramaniam, Sriram] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Lifson, Jeffrey D.] SAIC Frederick Inc, Frederick Natl Lab, AIDS & Canc Virus Program, Frederick, MD 21702 USA.
RP Subramaniam, S (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM ss1@nih.gov
FU National Institutes of Health (NIH) Intramural AIDS Targeted Antiviral
Program; Center for Cancer Research at the National Cancer Institute;
National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX We thank Donald Bliss for assistance with illustrations. This work was
supported by funds from the National Institutes of Health (NIH)
Intramural AIDS Targeted Antiviral Program and the Center for Cancer
Research at the National Cancer Institute (to S.S.) and National Cancer
Institute, National Institutes of Health Contract HHSN261200800001E (to
J.D.L.).
NR 72
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U2 48
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0966-842X
J9 TRENDS MICROBIOL
JI Trends Microbiol.
PD AUG
PY 2013
VL 21
IS 8
BP 397
EP 404
DI 10.1016/j.tim.2013.06.004
PG 8
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 205QR
UT WOS:000323460100007
PM 23850373
ER
PT J
AU Xue, WQ
Qin, HD
Ruan, HL
Shugart, YY
Jia, WH
AF Xue, Wen-Qiong
Qin, Hai-De
Ruan, Hong-Lian
Shugart, Yin Yao
Jia, Wei-Hua
TI Quantitative Association of Tobacco Smoking With the Risk of
Nasopharyngeal Carcinoma: A Comprehensive Meta-Analysis of Studies
Conducted Between 1979 and 2011
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Review
DE case-control studies; cohort studies; meta-analysis; nasopharyngeal
carcinoma; odds ratio; tobacco smoking
ID CIGARETTE-SMOKING; FORMALDEHYDE EXPOSURE; ALCOHOL-CONSUMPTION;
UNITED-STATES; EPIDEMIOLOGIC EVIDENCE; MALAYSIAN CHINESE;
FAMILY-HISTORY; LUNG-CANCER; POPULATION; THAILAND
AB Over the years, many studies have attempted to establish a link between tobacco smoking and an increased risk of nasopharyngeal carcinoma (NPC), but their results have been inconsistent. To clarify this link, we first conducted a comprehensive meta-analysis to integrate the findings of epidemiologic studies from the last half-century. The methodology used for this study followed the checklist proposed by the Meta-analysis of Observational Studies in Epidemiology (MOOSE) Group. Pooled risk estimates were generated using a random-effects model. Twenty-eight case-control studies and 4 cohort studies involving a total of 10,274 NPC cases and 415,266 comparison subjects were included. A substantial effect of smoking on the risk of NPC was identified in this study. The results showed that ever smokers had a 60 greater risk of developing the disease than never smokers (95 confidence interval: 1.38, 1.87); this was a robust dose-dependent association. More importantly, stronger associations were observed in low-risk populations and among persons with the predominant histological type of differentiated NPC than in high-risk populations and persons with an undifferentiated type; the odds ratios were 1.76 and 2.20, respectively, versus 1.29 and 1.27. In this comprehensive meta-analysis, well-established statistical evidence was provided about the role of tobacco smoking in the etiology of NPC.
C1 [Xue, Wen-Qiong; Ruan, Hong-Lian; Jia, Wei-Hua] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Dept Expt Res, Guangzhou 510060, Guangdong, Peoples R China.
[Qin, Hai-De; Shugart, Yin Yao] NIMH, Unit Stat Genom, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA.
RP Jia, WH (reprint author), Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol Southern China, Dept Expt Res, Guangzhou 510060, Guangdong, Peoples R China.
EM jiaweih@mail.sysu.edu.cn
FU National Natural Science Foundation of China [81220108022]; Chinese
National High Technology Research and Development Program (grant 863)
[2012AA02A206, 2012AA02A501]; National Basic Research Program of China
(grant 973) [2011CB504303]
FX This work was supported by the National Natural Science Foundation of
China (grant 81220108022), the Chinese National High Technology Research
and Development Program (grant 863, programs 2012AA02A206 and
2012AA02A501), and the National Basic Research Program of China (grant
973, program 2011CB504303).
NR 57
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PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 1
PY 2013
VL 178
IS 3
BP 325
EP 338
DI 10.1093/aje/kws479
PG 14
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 195WO
UT WOS:000322734500001
PM 23785114
ER
PT J
AU Cho, H
Mariotto, AB
Mann, BS
Klabunde, CN
Feuer, EJ
AF Cho, Hyunsoon
Mariotto, Angela B.
Mann, Bhupinder S.
Klabunde, Carrie N.
Feuer, Eric J.
TI Assessing NonCancer-Related Health Status of US Cancer Patients:
Other-Cause Survival and Comorbidity Prevalence
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE cancer survival; cancer survivorship; comorbidity; health status;
left-truncated survival; non-cancer-related survival; other-cause
mortality; SEER
ID COLON-CANCER; PHYSICAL-ACTIVITY; COMPETING CAUSES; UNITED-STATES;
INSURANCE STATUS; BREAST-CANCER; TIME-SCALE; RISK; POPULATION; DEATH
AB With advances in prevention, screening, and treatment, cancer patients are living longer; hence, noncancer-related health status will likely play a larger role in determining their life expectancy. In this study, we present a novel method for characterizing noncancer-related health status of cancer patients using population-based cancer registry data. We assessed noncancer-related health status in the context of survival from other causes of death and prevalence of comorbidities. Data from the Surveillance, Epidemiology, and End Results program (20002006) were used to analyze cancer patients survival probabilities by cause of death. Other-cause survival was estimated using a left-truncated survival method with the hazard of death due to other causes characterized as a function of age. Surveillance, Epidemiology, and End Results data linked to Medicare claims (19922005) were used to quantify comorbidity prevalence. Relative to the US population, survival from a noncancer-related death was higher for patients diagnosed with early stage breast and prostate cancer but lower for lung cancer patients at all stages. Lung cancer patients had worse comorbidity status than did other cancer patients. The present study represents the first attempt to evaluate the noncancer-related health status of US cancer patients by cancer site (breast, prostate, colorectal, and lung) and stage. The findings provide insight into noncancer-related health issues among cancer patients and their risk of dying from other causes.
C1 [Cho, Hyunsoon; Mariotto, Angela B.] NCI, Data Modeling Branch, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Mann, Bhupinder S.] NCI, Clin Invest Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Klabunde, Carrie N.] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Feuer, Eric J.] NCI, Stat Methodol & Applicat Branch, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Cho, H (reprint author), NCI, Data Modeling Branch, Surveillance Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 4E568, Bethesda, MD 20892 USA.
EM choh3@mail.nih.gov
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PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 1
PY 2013
VL 178
IS 3
BP 339
EP 349
DI 10.1093/aje/kws580
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 195WO
UT WOS:000322734500002
PM 23825168
ER
PT J
AU Nyante, SJ
Dallal, CM
Gierach, GL
Park, Y
Hollenbeck, AR
Brinton, LA
AF Nyante, Sarah J.
Dallal, Cher M.
Gierach, Gretchen L.
Park, Yikyung
Hollenbeck, Albert R.
Brinton, Louise A.
TI Risk Factors for Specific Histopathological Types of Postmenopausal
Breast Cancer in the NIH-AARP Diet and Health Study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE breast neoplasms; cohort studies; histology; risk factors
ID INVASIVE DUCTAL CARCINOMAS; DIFFERENT HISTOLOGIC TYPES; NO SPECIAL TYPE;
TERM-FOLLOW-UP; HORMONE-THERAPY; RECEPTOR STATUS; REPRODUCTIVE FACTORS;
MOLECULAR PORTRAITS; MUCINOUS CARCINOMA; UNITED-STATES
AB Risk factor associations for rare breast cancer variants are often imprecise, obscuring differences between tumor types. To clarify differences, we examined risk factors for 5 histological types of breast cancer in the National Institutes of Health-AARP Diet and Health Study. Risk factor information was self-reported. We followed 192,076 postmenopausal women aged 5071 years from 19951996 through 2006. During that time period, 5,334 ductal, 836 lobular, 639 mixed ductal-lobular, 216 mucinous, and 132 tubular breast cancers were diagnosed. Hazard ratios and 95 confidence intervals were estimated using Cox proportional hazards regression. Heterogeneity was evaluated using case-only logistic regression. The strongest differences were for menopausal hormone therapy (P-heterogeneity 0.01) and age at first birth (P-heterogeneity 0.01). Risk of tubular cancer in relation to current menopausal hormone therapy (for current use vs. never use, hazard ratio (HR) 4.39, 95 confidence interval (CI): 2.77, 6.96) was several times stronger than risk of other histological types (range of HRs, 1.391.75). Older age at first birth was unassociated with risk of mucinous (for 30 years vs. 2024 years, HR 0.62, 95 CI: 0.27, 1.42) or tubular (HR 1.08, 95 CI: 0.51, 2.29) tumors, in contrast to clear positive associations with lobular (HR 1.82, 95 CI: 1.39, 2.37) and mixed ductal-lobular (HR 1.87, 95 CI: 1.39, 2.51) tumors. Differing associations for hormonal factors and mucinous and tubular cancers suggest etiologies distinct from those of common breast cancers.
C1 [Nyante, Sarah J.; Dallal, Cher M.; Gierach, Gretchen L.; Park, Yikyung; Brinton, Louise A.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Hollenbeck, Albert R.] AARP, Org & Tracking Res Dept, Washington, DC USA.
RP Nyante, SJ (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 7-E236,MSC 9774, Bethesda, MD 20892 USA.
EM sarah.nyante@nih.gov
RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016;
OI Brinton, Louise/0000-0003-3853-8562; Gierach,
Gretchen/0000-0002-0165-5522; Park, Yikyung/0000-0002-6281-489X
FU National Cancer Institute, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health.
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PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 1
PY 2013
VL 178
IS 3
BP 359
EP 371
DI 10.1093/aje/kws471
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 195WO
UT WOS:000322734500004
PM 23899816
ER
PT J
AU Edwards, DRV
Baird, DD
Hartmann, KE
AF Edwards, Digna R. Velez
Baird, Donna D.
Hartmann, Katherine E.
TI Association of Age at Menarche With Increasing Number of Fibroids in a
Cohort of Women Who Underwent Standardized Ultrasound Assessment
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE age at menarche; epidemiology; fibroids; uterine leiomyoma
ID MENSTRUAL-CYCLE CHARACTERISTICS; POLYCYSTIC-OVARY-SYNDROME; UTERINE
LEIOMYOMATA; PREMENOPAUSAL WOMEN; RISK-FACTORS; REPRODUCTIVE HISTORY;
BREAST-CANCER; PREECLAMPSIA; PREGNANCY; OBESITY
AB Age at menarche has been associated with several reproductive conditions, and frequencies differ by race. Racial disparities also impact fibroid risk. We comprehensively examined the relationship between age at menarche, fibroid characteristics, and race. Women were enrolled in Right From the Start (20012010), a multistate study that systematically screened for fibroids during very early pregnancy. Endovaginal ultrasounds were conducted, and fibroid presence, number, type, volume, and diameter were recorded according to standardized definitions. Generalized estimating equations adjusted for correlations within study site were used to estimate associations between age at menarche and fibroid status and to test for interactions with race. Of 5,023 participants, 11 had a fibroid. Seven percent underwent menarche before 11 years of age and 11 at 15 years or later. We did not observe interactions between age at menarche and race. A 1-year increase in age at menarche was inversely associated with fibroids (adjusted risk ratio 0.87, 95 confidence interval: 0.82, 0.91). Early age at menarche had a similar positive association in individual analyses with fibroid size, type, and location but was stronger for multiple fibroids (adjusted risk ratio 0.75, 95 confidence interval: 0.68, 0.83). Our findings confirm other reports of an association between age at menarche and fibroid development (regardless of characteristics), demonstrate no effect modification by race, and suggest a stronger association for women with multiple fibroids, possibly reflecting a stronger association for early-onset disease.
C1 [Edwards, Digna R. Velez; Hartmann, Katherine E.] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Dept Obstet & Gynecol, Inst Med & Publ Hlth, Nashville, TN 37235 USA.
[Edwards, Digna R. Velez] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37235 USA.
[Baird, Donna D.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
RP Edwards, DRV (reprint author), Vanderbilt Epidemiol Ctr, 2525 West End Ave,Suite 600,6th Floor, Nashville, TN 37203 USA.
EM digna.r.velez.edwards@vanderbilt.edu
RI Baird, Donna/D-5214-2017
OI Baird, Donna/0000-0002-5544-2653
FU National Institute of Child and Human Development [R01HD043883,
R01HD049675]; American Water Works Association Research Foundation
[2579]; Building Interdisciplinary Research Careers in Women's Health
career development program [2K12HD043483-11]; Vanderbilt Clinical and
Translational Science Award (CTSA) grant from the National Center for
Advancing Translational Sciences/National Institutes of Health
[ULTR000445]; Intramural Research Program of the National Institutes of
Health, National Institute of Environmental Health Sciences
FX The field research was supported by grants from the National Institute
of Child and Human Development (R01HD043883 and R01HD049675) and the
American Water Works Association Research Foundation (2579). Additional
funds were provided by the Building Interdisciplinary Research Careers
in Women's Health career development program (2K12HD043483-11), and the
study was supported in part by the Vanderbilt Clinical and Translational
Science Award (CTSA) grant ULTR000445 from the National Center for
Advancing Translational Sciences/National Institutes of Health. This
research was also supported in part by the Intramural Research Program
of the National Institutes of Health, National Institute of
Environmental Health Sciences (support for coauthor Donna D. Baird).
NR 47
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PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 1
PY 2013
VL 178
IS 3
BP 426
EP 433
DI 10.1093/aje/kws585
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 195WO
UT WOS:000322734500011
ER
PT J
AU Murray, ET
Ben-Shlomo, Y
Tilling, K
Southall, H
Aucott, P
Kuh, D
Hardy, R
AF Murray, Emily T.
Ben-Shlomo, Yoav
Tilling, Kate
Southall, Humphrey
Aucott, Paula
Kuh, Diana
Hardy, Rebecca
TI Area Deprivation Across the Life Course and Physical Capability in
Midlife: Findings From the 1946 British Birth Cohort
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE geography; Great Britain; health status disparities; longitudinal
studies; multilevel analysis; physical endurance; residence
characteristics; socioeconomic factors
ID RISK-FACTORS; NEIGHBORHOOD DEPRIVATION; SOCIOECONOMIC DEPRIVATION;
DEVELOPMENTAL ORIGINS; CARDIOVASCULAR RISK; MULTILEVEL ANALYSIS;
OLDER-ADULTS; HEALTH; CHILDHOOD; DISABILITY
AB Physical capability in later life is influenced by factors occurring across the life course, yet exposures to area conditions have only been examined cross-sectionally. Data from the National Survey of Health and Development, a longitudinal study of a 1946 British birth cohort, were used to estimate associations of area deprivation (defined as percentage of employed people working in partly skilled or unskilled occupations) at ages 4, 26, and 53 years (residential addresses linked to census data in 1950, 1972, and 1999) with 3 measures of physical capability at age 53 years: grip strength, standing balance, and chair-rise time. Cross-classified multilevel models with individuals nested within areas at the 3 ages showed that models assessing a single time point underestimate total area contributions to physical capability. For balance and chair-rise performance, associations with area deprivation in midlife were robust to adjustment for individual socioeconomic position and prior area deprivation (mean change for a 1-standard-deviation increase: balance, 7.4 (95 confidence interval (CI): 12.8, 2.8); chair rise, 2.1 (95 CI: 0.1, 4.3)). In addition, area deprivation in childhood was related to balance after adjustment for childhood socioeconomic position (5.1, 95 CI: 8.7, 1.6). Interventions aimed at reducing midlife disparities in physical capability should target the socioeconomic environment of individualsufor standing balance, as early as childhood.
C1 [Murray, Emily T.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Ben-Shlomo, Yoav; Tilling, Kate] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England.
[Southall, Humphrey; Aucott, Paula] Univ Portsmouth, Dept Geog, Great Britain Hist GIS Project, Portsmouth, Hants, England.
[Kuh, Diana; Hardy, Rebecca] UCL, MRC Unit Lifelong Hlth & Ageing, London WC1B 5JU, England.
[Kuh, Diana; Hardy, Rebecca] Royal Free Med Sch, London WC1B 5JU, England.
RP Murray, ET (reprint author), UCL, MRC Unit Lifelong Hlth & Ageing, 33 Bedford Pl, London WC1B 5JU, England.
EM Emily.taylor.murray@gmail.com
OI Tilling, Kate/0000-0002-1010-8926
FU Intramural Research Program of the US National Institute on Aging; New
Dynamics of Ageing Programme [RES-353-25-0001]; National Institutes of
Health
FX This research was supported in part by the Intramural Research Program
of the US National Institute on Aging, National Institutes of Health,
and the New Dynamics of Ageing Programme (grant RES-353-25-0001).
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PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 1
PY 2013
VL 178
IS 3
BP 441
EP 450
DI 10.1093/aje/kwt003
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 195WO
UT WOS:000322734500013
PM 23788665
ER
PT J
AU Fernandez-Rhodes, L
Demerath, EW
Cousminer, DL
Tao, R
Dreyfus, JG
Esko, T
Smith, AV
Gudnason, V
Harris, TB
Launer, L
McArdle, PF
Yerges-Armstrong, LM
Elks, CE
Strachan, DP
Kutalik, Z
Vollenweider, P
Feenstra, B
Boyd, HA
Metspalu, A
Mihailov, E
Broer, L
Zillikens, MC
Oostra, B
van Duijn, CM
Lunetta, KL
Perry, JRB
Murray, A
Koller, DL
Lai, D
Corre, T
Toniolo, D
Albrecht, E
Stockl, D
Grallert, H
Gieger, C
Hayward, C
Polasek, O
Rudan, I
Wilson, JF
He, C
Kraft, P
Hu, FB
Hunter, DJ
Hottenga, JJ
Willemsen, G
Boomsma, DI
Byrne, EM
Martin, NG
Montgomery, GW
Warrington, NM
Pennell, CE
Stolk, L
Visser, JA
Hofman, A
Uitterlinden, AG
Rivadeneira, F
Lin, P
Fisher, SL
Bierut, LJ
Crisponi, L
Porcu, E
Mangino, M
Zhai, G
Spector, TD
Buring, JE
Rose, LM
Ridker, PM
Poole, C
Hirschhorn, JN
Murabito, JM
Chasman, DI
Widen, E
North, KE
Ong, KK
Franceschini, N
AF Fernandez-Rhodes, Lindsay
Demerath, Ellen W.
Cousminer, Diana L.
Tao, Ran
Dreyfus, Jill G.
Esko, Tonu
Smith, Albert V.
Gudnason, Vilmundur
Harris, Tamara B.
Launer, Lenore
McArdle, Patrick F.
Yerges-Armstrong, Laura M.
Elks, Cathy E.
Strachan, David P.
Kutalik, Zoltan
Vollenweider, Peter
Feenstra, Bjarke
Boyd, Heather A.
Metspalu, Andres
Mihailov, Evelin
Broer, Linda
Zillikens, M. Carola
Oostra, Ben
van Duijn, Cornelia M.
Lunetta, Kathryn L.
Perry, John R. B.
Murray, Anna
Koller, Daniel L.
Lai, Dongbing
Corre, Tanguy
Toniolo, Daniela
Albrecht, Eva
Stoeckl, Doris
Grallert, Harald
Gieger, Christian
Hayward, Caroline
Polasek, Ozren
Rudan, Igor
Wilson, James F.
He, Chunyan
Kraft, Peter
Hu, Frank B.
Hunter, David J.
Hottenga, Jouke-Jan
Willemsen, Gonneke
Boomsma, Dorret I.
Byrne, Enda M.
Martin, Nicholas G.
Montgomery, Grant W.
Warrington, Nicole M.
Pennell, Craig E.
Stolk, Lisette
Visser, Jenny A.
Hofman, Albert
Uitterlinden, Andre G.
Rivadeneira, Fernando
Lin, Peng
Fisher, Sherri L.
Bierut, Laura J.
Crisponi, Laura
Porcu, Eleonora
Mangino, Massimo
Zhai, Guangju
Spector, Tim D.
Buring, Julie E.
Rose, Lynda M.
Ridker, Paul M.
Poole, Charles
Hirschhorn, Joel N.
Murabito, Joanne M.
Chasman, Daniel I.
Widen, Elisabeth
North, Kari E.
Ong, Ken K.
Franceschini, Nora
TI Association of Adiposity Genetic Variants With Menarche Timing in 92,105
Women of European Descent
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE adiposity; body mass index; genetic association studies; menarche;
obesity; waist circumference; waist:hip ratio; womens health
ID GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; WAIST CIRCUMFERENCE; SEQUENCE
VARIANTS; AGE; OBESITY; LOCI; METAANALYSIS; RISK; WEIGHT
AB Obesity is of global health concern. There are well-described inverse relationships between female pubertal timing and obesity. Recent genome-wide association studies of age at menarche identified several obesity-related variants. Using data from the ReproGen Consortium, we employed meta-analytical techniques to estimate the associations of 95 a priori and recently identified obesity-related (body mass index (weight (kg)/height (m)(2)), waist circumference, and waist:hip ratio) single-nucleotide polymorphisms (SNPs) with age at menarche in 92,116 women of European descent from 38 studies (19702010), in order to estimate associations between genetic variants associated with central or overall adiposity and pubertal timing in girls. Investigators in each study performed a separate analysis of associations between the selected SNPs and age at menarche (ages 917 years) using linear regression models and adjusting for birth year, site (as appropriate), and population stratification. Heterogeneity of effect-measure estimates was investigated using meta-regression. Six novel associations of body mass index loci with age at menarche were identified, and 11 adiposity loci previously reported to be associated with age at menarche were confirmed, but none of the central adiposity variants individually showed significant associations. These findings suggest complex genetic relationships between menarche and overall obesity, and to a lesser extent central obesity, in normal processes of growth and development.
C1 [North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA.
[Perry, John R. B.] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Rudan, Igor; Wilson, James F.] Univ Edinburgh, Coll Med & Vet Med, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Polasek, Ozren] Univ Split, Sch Med, Dept Publ Hlth, Split, Croatia.
[Hottenga, Jouke-Jan; Willemsen, Gonneke; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, Fac Psychol & Educ, Amsterdam, Netherlands.
[Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Tao, Ran] Univ N Carolina, Dept Biostat, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Esko, Tonu; Metspalu, Andres; Mihailov, Evelin] Univ Tartu, Inst Mol & Cell Biol, Dept Biotechnol, EE-50090 Tartu, Estonia.
[Oostra, Ben] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands.
[Feenstra, Bjarke; Boyd, Heather A.] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark.
[Broer, Linda; van Duijn, Cornelia M.; Hofman, Albert; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Fernandez-Rhodes, Lindsay; Poole, Charles; North, Kari E.; Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[North, Kari E.] Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC USA.
[Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Zillikens, M. Carola; Stolk, Lisette; Visser, Jenny A.; Uitterlinden, Andre G.; Rivadeneira, Fernando] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Koller, Daniel L.; Lai, Dongbing] Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN USA.
[Kutalik, Zoltan] Univ Lausanne, Fac Biol & Med, Dept Med Genet, Lausanne, Switzerland.
[McArdle, Patrick F.; Yerges-Armstrong, Laura M.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Vollenweider, Peter] Univ Vaudois, Ctr Hosp, Internal Med Unit, Dept Med, Lausanne, Switzerland.
[Kraft, Peter; Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA USA.
[Stoeckl, Doris] Univ Munich, Dept Obstet & Gynaecol, Munich, Germany.
[Lin, Peng; Fisher, Sherri L.; Bierut, Laura J.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[He, Chunyan] Indiana Univ, Sch Med, Dept Publ Hlth, Indianapolis, IN 46202 USA.
[Perry, John R. B.; Mangino, Massimo; Zhai, Guangju; Spector, Tim D.] Kings Coll London, Sch Med, Dept Twin Res & Genet Epidemiol, Div Genet & Mol Med, London, England.
[Porcu, Eleonora] Univ Sassari, Fac Med & Surg, Dept Biomed Sci, I-07100 Sassari, Italy.
[Zhai, Guangju] Mem Univ Newfoundland, Fac Med, Discipline Genet, St John, NF, Canada.
[Corre, Tanguy; Toniolo, Daniela] Ist Sci San Raffaele, Div Cell Biol, I-20132 Milan, Italy.
[Demerath, Ellen W.; Dreyfus, Jill G.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Corre, Tanguy; Toniolo, Daniela] Ist Sci San Raffaele, Div Genet, I-20132 Milan, Italy.
[Strachan, David P.] Univ London, Sch Med, St Georges Hosp, Div Populat Hlth Sci & Educ, London, England.
[Buring, Julie E.; Rose, Lynda M.; Ridker, Paul M.; Chasman, Daniel I.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Esko, Tonu; Metspalu, Andres; Mihailov, Evelin] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Polasek, Ozren] Gen Info Ltd, Zagreb, Croatia.
[Byrne, Enda M.; Martin, Nicholas G.; Montgomery, Grant W.] Queensland Inst Med Res, Genet Epidemiol Mol Epidemiol & Neurogenet Labs, Brisbane, Qld 4006, Australia.
[Perry, John R. B.; Murray, Anna] Univ Exeter, Peninsula Med Sch, Genet Complex Traits Res Grp, Exeter, Devon, England.
[Buring, Julie E.; Ridker, Paul M.; Chasman, Daniel I.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Smith, Albert V.; Gudnason, Vilmundur] Iceland Heart Assoc, Reykjavik, Iceland.
[Stoeckl, Doris] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
[Albrecht, Eva; Gieger, Christian] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.
[Cousminer, Diana L.; Widen, Elisabeth] Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.
[Crisponi, Laura; Porcu, Eleonora] CNR, Ist Ric Genet & Biomed, Cagliari, Italy.
[Harris, Tamara B.; Launer, Lenore] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Elks, Cathy E.; Ong, Ken K.] Univ Cambridge, MRC Epidemiol Unit, Cambridge, England.
[Hayward, Caroline] Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland.
[Broer, Linda; Zillikens, M. Carola; van Duijn, Cornelia M.; Stolk, Lisette; Uitterlinden, Andre G.; Rivadeneira, Fernando] Netherlands Genom Initiat, Netherlands Consortium Hlth Aging, Leiden, Netherlands.
[Hottenga, Jouke-Jan; Willemsen, Gonneke; Boomsma, Dorret I.] Netherlands Twin Register, Amsterdam, Netherlands.
[McArdle, Patrick F.; Yerges-Armstrong, Laura M.] Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA.
[Grallert, Harald] German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Warrington, Nicole M.; Pennell, Craig E.] Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA 6009, Australia.
[Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA.
[Kutalik, Zoltan] Swiss Inst Bioinformat, Lausanne, Switzerland.
[Byrne, Enda M.] Univ Queensland, Queensland Brain Inst, Complex Traits Genom Grp, Brisbane, Qld, Australia.
[Perry, John R. B.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
RP Fernandez-Rhodes, L (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, 137 East Franklin St,Suite 306,Campus Box 8050, Chapel Hill, NC 27514 USA.
EM fernandez-rhodes@unc.edu
RI mangino, massimo/F-5134-2011; Hayward, Caroline/M-8818-2016; Byrne,
Enda/J-6068-2014; Warrington, Nicole/P-4868-2014; Visser, Jenny
/F-8156-2011; Grallert, Harald/B-3424-2013; Gudnason,
Vilmundur/K-6885-2015; Wilson, James F/A-5704-2009; Polasek,
Ozren/B-6002-2011; Montgomery, Grant/B-7148-2008; Rivadeneira,
Fernando/O-5385-2015; Rudan, Igor/I-1467-2012; Smith,
Albert/K-5150-2015; Colaus, PsyColaus/K-6607-2013; Stockl,
Doris/B-5352-2014; Lin, P/G-7702-2014
OI mangino, massimo/0000-0002-2167-7470; Hayward,
Caroline/0000-0002-9405-9550; Byrne, Enda/0000-0002-9491-7797; Murabito,
Joanne/0000-0002-0192-7516; Lunetta, Kathryn/0000-0002-9268-810X;
Murray, Anna/0000-0002-2351-2522; Esko, Tonu/0000-0003-1982-6569;
Gieger, Christian/0000-0001-6986-9554; Martin,
Nicholas/0000-0003-4069-8020; Warrington, Nicole/0000-0003-4195-775X;
Gudnason, Vilmundur/0000-0001-5696-0084; Wilson, James
F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862; Montgomery,
Grant/0000-0002-4140-8139; Rivadeneira, Fernando/0000-0001-9435-9441;
Rudan, Igor/0000-0001-6993-6884; Smith, Albert/0000-0003-1942-5845;
FU US National Heart, Lung, and Blood Institute [5T32HL007055, T32HL007779,
K02 DA021237]; Wellcome Trust [092447/Z/10/Z]; GlaxoSmithKline
FX This work was supported by the US National Heart, Lung, and Blood
Institute (grants 5T32HL007055 to L. F. R., T32HL007779 to J.G.D., and
K02 DA021237 to L.J.B.) and the Wellcome Trust (Sir Henry Wellcome
Fellowship 092447/Z/10/Z to J.R.B.P.).; P.V. received an unrestricted
grant from GlaxoSmithKline to build the CoLaus Study, and L.J.B. is
listed as an inventor on Issued United States Patent 8,080,371, "Markers
for Addiction," covering the use of certain SNPs in determining the
diagnosis, prognosis, and treatment of addiction.
NR 53
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U1 1
U2 17
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 1
PY 2013
VL 178
IS 3
BP 451
EP 460
DI 10.1093/aje/kws473
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 195WO
UT WOS:000322734500014
PM 23558354
ER
PT J
AU Chang, A
Van Horn, L
Jacobs, DR
Liu, K
Muntner, P
Newsome, B
Shoham, DA
Durazo-Arvizu, R
Bibbins-Domingo, K
Reis, J
Kramer, H
AF Chang, Alex
Van Horn, Linda
Jacobs, David R., Jr.
Liu, Kiang
Muntner, Paul
Newsome, Britt
Shoham, David A.
Durazo-Arvizu, Ramon
Bibbins-Domingo, Kirsten
Reis, Jared
Kramer, Holly
TI Lifestyle-Related Factors, Obesity, and Incident Microalbuminuria: The
CARDIA (Coronary Artery Risk Development in Young Adults) Study
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE DASH diet; kidney disease; lifestyle factors; microalbuminuria; obesity
ID CHRONIC KIDNEY-DISEASE; URINARY ALBUMIN EXCRETION;
GLOMERULAR-FILTRATION-RATE; COMMUNITY-BASED POPULATION;
CARDIOVASCULAR-DISEASE; PHYSICAL-ACTIVITY; FOLLOW-UP; NONDIABETIC
INDIVIDUALS; DIABETIC-PATIENTS; DIETARY PATTERNS
AB Background: Modifiable lifestyle-related factors are associated with risk of coronary heart disease and may also influence kidney disease risk.
Study Design: Community-based prospective cohort study.
Setting & Participants: 2,354 African American and white participants aged 28-40 years without baseline microalbuminuria or estimated glomerular filtration rate <60 mL/min/1.73 m(2) recruited from 4 US centers: Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA.
Factors: Current smoking, physical activity, fast food habits, obesity, and diet quality, which was based on 8 fundamental components of the Dietary Approaches to Stop Hypertension (DASH) diet, including increased intake of fruits, vegetables, low-fat dairy products, whole grains, and nuts and legumes and reduced intake of sodium, sugar-sweetened beverages, and red and processed meats.
Outcomes & Measurements: Spot urine albumin-creatinine ratios were obtained at baseline (1995-1996) and three 5-year follow-up examinations (5, 10, and 15 years' follow-up). Incident microalbuminuria was defined as the presence of age- and sex-adjusted albumin-creatinine ratio >= 25 mg/g at 2 or more of the successive follow-up examinations.
Results: During the 15-year follow-up, 77 (3.3%) individuals developed incident microalbuminuria. After multivariable adjustment, poor diet quality (OR, 2.0; 95% CI, 1.1-3.4) and obesity (OR, 1.9; 95% CI, 1.1-3.3) were associated significantly with microalbuminuria; current smoking (OR, 1.6; 95% CI, 0.9-2.8) was associated with microalbuminuria, although the CI crossed 1.0. Neither low physical activity (OR, 1.0; 95% CI, 0.5-1.8) nor fast food consumption (OR, 1.2; 95% CI, 0.7-2.3) was associated with microalbuminuria. Compared with individuals with no unhealthy lifestyle-related factors (poor diet quality, current smoking, and obesity), adjusted odds of incident microalbuminuria were 131%, 273%, and 634% higher for the presence of 1 (OR, 2.3; 95% CI, 1.3-4.3), 2 (OR, 3.7; 95% CI, 1.8-7.7), and 3 (OR, 7.3; 95% CI, 2.1-26.1) unhealthy lifestyle-related factors.
Limitations: Self-reported dietary history and physical activity, low number of outcomes.
Conclusions: Consuming an unhealthy diet and obesity are associated with incident microalbuminuria. (c) 2013 by the National Kidney Foundation, Inc.
C1 [Chang, Alex] Johns Hopkins Univ, Div Nephrol, Baltimore, MD 21205 USA.
[Van Horn, Linda; Liu, Kiang] Northwestern Univ, Dept Prevent Med, Evanston, IL 60208 USA.
[Jacobs, David R., Jr.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Jacobs, David R., Jr.] Univ Oslo, Sch Med, Dept Nutr, Oslo, Norway.
[Muntner, Paul] Univ Alabama Birmingham, Div Nephrol & Prevent Med, Birmingham, AL USA.
[Newsome, Britt] Denver Nephrol, Denver, CO USA.
[Shoham, David A.; Durazo-Arvizu, Ramon; Kramer, Holly] Loyola Univ, Med Ctr, Dept Prevent Med & Epidemiol, New Orleans, LA 70118 USA.
[Bibbins-Domingo, Kirsten] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA.
[Reis, Jared] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Kramer, Holly] Loyola Univ, Med Ctr, Dept Nephrol, New Orleans, LA 70118 USA.
RP Chang, A (reprint author), Johns Hopkins Univ, Div Nephrol, 1830 Monument St,Ste 416, Baltimore, MD 21205 USA.
EM achang43@jhmi.edu
OI Kramer, Holly/0000-0002-6374-837X
FU National Institute of Diabetes and Digestive and Kidney Diseases
[T32DK007732]
FX Dr Chang was supported by National Institute of Diabetes and Digestive
and Kidney Diseases grant T32DK007732.
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PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD AUG
PY 2013
VL 62
IS 2
BP 267
EP 275
DI 10.1053/j.ajkd.2013.02.363
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 196OK
UT WOS:000322784700013
PM 23601954
ER
PT J
AU Klempner, MS
Baker, PJ
Shapiro, ED
Marques, A
Dattwyler, RJ
Halperin, JJ
Wormser, GP
AF Klempner, Mark S.
Baker, Phillip J.
Shapiro, Eugene D.
Marques, Adriana
Dattwyler, Raymond J.
Halperin, John J.
Wormser, Gary P.
TI Treatment Trials for Post-Lyme Disease Symptoms Revisited
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Review
DE Borrelia burgdorferi; Clinical trials; Lyme disease; Post-Lyme disease
syndrome
ID PSYCHIATRIC COMORBIDITY; ANTIBIOTIC-TREATMENT; PERSISTENT SYMPTOMS; ORAL
DOXYCYCLINE; DOUBLE-BLIND; PLACEBO; NEUROBORRELIOSIS; THERAPY
AB The authors of 4 National Institutes of Health-sponsored antibiotic treatment trials of patients with persistent unexplained symptoms despite previous antibiotic treatment of Lyme disease determined that retreatment provides little if any benefit and carries significant risk. Two groups recently provided an independent reassessment of these trials and concluded that prolonged courses of antibiotics are likely to be helpful. We have carefully considered the points raised by these groups, along with our own critical review of the treatment trials. On the basis of this analysis, the conclusion that there is a meaningful clinical benefit to be gained from retreatment of such patients with parenteral antibiotic therapy cannot be justified. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Klempner, Mark S.] Univ Massachusetts, Sch Med, Boston, MA 02125 USA.
[Baker, Phillip J.] Amer Lyme Dis Fdn, Lyme, CT USA.
[Shapiro, Eugene D.] Yale Univ, Dept Pediat, New Haven, CT 06520 USA.
[Shapiro, Eugene D.] Yale Univ, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA.
[Shapiro, Eugene D.] Yale Univ, Dept Invest Med, New Haven, CT 06520 USA.
[Marques, Adriana] NIAID, NIH, Bethesda, MD USA.
[Dattwyler, Raymond J.] New York Med Coll, Dept Med, Div Allergy Immunol & Rheumatol, Valhalla, NY 10595 USA.
[Halperin, John J.] Overlook Med Ctr, Dept Neurosci, Summit, NJ USA.
[Halperin, John J.] Overlook Med Ctr, Atlantic Neurosci Inst, Summit, NJ USA.
[Wormser, Gary P.] New York Med Coll, Dept Med, Div Infect Dis, Valhalla, NY 10595 USA.
RP Klempner, MS (reprint author), Univ Massachusetts, Sch Med, Harbor Campus, Boston, MA 02125 USA.
OI Dattwyler, Raymond/0000-0002-1983-1301
FU CTSA from NCATS [KL2 TR000140, UL1 TR000142]
FX The authors thank Lisa Giarratano and Shantale Williams, of the office
support staff of NY Medical College, for expert assistance in editing
and preparing the text of this article. EDS receives support from CTSA
Grant Numbers KL2 TR000140 and UL1 TR000142 from NCATS. The contents of
this paper are solely the responsibility of the authors and do not
necessarily represent the official view of NCATS or the NIH.
NR 20
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
J9 AM J MED
JI Am. J. Med.
PD AUG
PY 2013
VL 126
IS 8
BP 665
EP 669
DI 10.1016/j.amjmed.2013.02.014
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 197CS
UT WOS:000322827200017
PM 23764268
ER
PT J
AU Bourge, RC
Fleg, JL
Fonarow, GC
Cleland, JGF
McMurray, JJV
van Veldhuisen, DJ
Gheorghiade, M
Patel, K
Aban, IB
Allman, RM
White-Williams, C
White, M
Filippatos, GS
Anker, SD
Ahmed, A
AF Bourge, Robert C.
Fleg, Jerome L.
Fonarow, Gregg C.
Cleland, John G. F.
McMurray, John J. V.
van Veldhuisen, Dirk J.
Gheorghiade, Mihai
Patel, Kanan
Aban, Inmaculada B.
Allman, Richard M.
White-Williams, Connie
White, Michel
Filippatos, Gerasimos S.
Anker, Stefan D.
Ahmed, Ali
TI Digoxin Reduces 30-day All-cause Hospital Admission in Older Patients
with Chronic Systolic Heart Failure
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
DE Digoxin; Heart failure; 30-day all-cause hospital admission
ID CONVERTING-ENZYME-INHIBITORS; INVESTIGATION GROUP TRIAL; DIG TRIAL;
MORTALITY; MORBIDITY; DIGITALIS; MANAGEMENT; WITHDRAWAL; OUTCOMES
AB BACKGROUND: Heart failure is a leading cause of hospital admission and readmission in older adults. The new United States healthcare reform law has created provisions for financial penalties for hospitals with higher than expected 30-day all-cause readmission rates for hospitalized Medicare beneficiaries aged >= 65 years with heart failure. We examined the effect of digoxin on 30-day all-cause hospital admission in older patients with heart failure and reduced ejection fraction.
METHODS: In the main Digitalis Investigation Group trial, 6800 ambulatory patients with chronic heart failure (ejection fraction <= 45%) were randomly assigned to digoxin or placebo. Of these, 3405 were aged >= 65 years (mean age, 72 years; 25% were women; 11% were nonwhite). The main outcome in the current analysis was 30-day all-cause hospital admission.
RESULTS: In the first 30 days after randomization, all-cause hospitalization occurred in 5.4% (92/1693) and 8.1% (139/1712) of patients in the digoxin and placebo groups, respectively, (hazard ratio {HR} when digoxin was compared with placebo, 0.66; 95% confidence interval {CI}, 0.51-0.86; P = .002). Digoxin also reduced both 30-day cardiovascular (3.5% vs 6.5%; HR, 0.53; 95% CI, 0.38-0.72; P < .001) and heart failure (1.7 vs 4.2%; HR, 0.40; 95% CI, 0.26-0.62; P = .001) hospitalizations, with similar trends for 30-day all-cause mortality (0.7% vs 1.3%; HR, 0.55; 95% CI, 0.27-1.11; P = .096). Younger patients were at lower risk of events but obtained similar benefits from digoxin.
CONCLUSIONS: Digoxin reduces 30-day all-cause hospital admission in ambulatory older patients with chronic systolic heart failure. Future studies need to examine its effect on 30-day all-cause hospital readmission in hospitalized patients with acute heart failure. Published by Elsevier Inc.
C1 [Bourge, Robert C.; Patel, Kanan; Aban, Inmaculada B.; Allman, Richard M.; White-Williams, Connie; Ahmed, Ali] Univ Alabama Birmingham, Birmingham, AL USA.
[Fleg, Jerome L.] NHLBI, Bethesda, MD 20892 USA.
[Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Cleland, John G. F.] Hull York Med Sch, Kingston Upon Hull, Yorks, England.
[McMurray, John J. V.] Univ Glasgow, Glasgow, Lanark, Scotland.
[van Veldhuisen, Dirk J.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands.
[Gheorghiade, Mihai] Northwestern Univ, Chicago, IL USA.
[Allman, Richard M.; Ahmed, Ali] Vet Affairs Med Ctr, Birmingham, AL USA.
[White, Michel] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.
[Filippatos, Gerasimos S.] Attikon Univ Hosp, Athens, Greece.
[Anker, Stefan D.] IRCCS San Raffaele, Ctr Clin & Basic Res, Rome, Italy.
RP Ahmed, A (reprint author), UAB Ctr Aging, 1720 2nd Ave South,CH19-219, Birmingham, AL 35294 USA.
EM aahmed@uab.edu
RI van Veldhuisen, Dirk Jan/E-8967-2014; Lainscak, Mitja/F-3237-2015;
OI Cleland, John/0000-0002-1471-7016; mcmurray, john/0000-0002-6317-3975
FU National Heart, Lung, and Blood Institute (NHLBI); Department of
Veterans Affairs Cooperative Studies Program; National Institutes of
Health from the National Heart, Lung, and Blood Institute [R01-HL085561,
R01-HL085561-S, R01-HL097047]
FX The Digitalis Investigation Group (DIG) study was conducted and
supported by the National Heart, Lung, and Blood Institute (NHLBI) and
the Department of Veterans Affairs Cooperative Studies Program, in
collaboration with the DIG Investigators. This article was prepared
using a limited access dataset obtained from the NHLBI and does not
necessarily reflect the opinions or views of the DIG Study or the NHLBI.
Dr Ahmed was in part supported by the National Institutes of Health
through grants (R01-HL085561, R01-HL085561-S and R01-HL097047) from the
National Heart, Lung, and Blood Institute.
NR 29
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U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
J9 AM J MED
JI Am. J. Med.
PD AUG
PY 2013
VL 126
IS 8
BP 701
EP 708
DI 10.1016/j.amjmed.2013.02.001
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 197CS
UT WOS:000322827200024
PM 23490060
ER
PT J
AU Zhang, RH
Li, Q
Chuang, PY
Lu, GM
Liu, RJ
Yang, JJ
Peng, L
Dai, Y
Zheng, ZH
Qi, CF
He, JCJ
Xiong, HB
AF Zhang, Ruihua
Li, Qin
Chuang, Peter Y.
Lu, Geming
Liu, Ruijie
Yang, Jianjun
Peng, Liang
Dai, Yan
Zheng, Zihan
Qi, Chen-Feng
He, John Cijiang
Xiong, Huabao
TI Regulation of Pathogenic Th17 Cell Differentiation by IL-10 in the
Development of Glomerulonephritis
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID T-HELPER-CELLS; EXPERIMENTAL CRESCENTIC GLOMERULONEPHRITIS; T(H)17
CELLS; TGF-BETA; IN-VIVO; INFLAMMATION; INTERLEUKIN-10; CYTOKINE;
RECEPTOR; IL-23
AB Although it is clear that T helper (Th)17 cells play a pathologic role in the pathogenesis of several inflammatory diseases, the contribution and regulation of pathogenic Th17 cells in the development of glomerulonephritis are still not fully understood. Herein, we show that IL-10-deficient mice exhibit exacerbation of glomerulonephritis after induction with anti-glomerular basement membrane globulin, with enhanced pathogenic Th17 immune responses. We further demonstrate that Rag1(-/-) mice reconstituted with IL-10(-/-) CD4(+) T-cells develop more severe glomerulonephritis after induction of anti-glomerular basement membrane disease, with more infiltration of inflammatory cells into the kidneys. Finally, IL-17 and interferon gamma double-positive cells were significantly increased in IL-10(-/-) CD4(+) T-cell cultures under pathogenic Th17 conditions compared with wild-type cell cultures. These findings suggest that T-cell-derived IL-10 plays a critical suppressive role in the control of pathogenic Th17 cell differentiation and highlights the importance of IL-10 as protection against glomerulonephritis development.
C1 [Zhang, Ruihua; Li, Qin; Lu, Geming; Yang, Jianjun; Peng, Liang; Zheng, Zihan; Xiong, Huabao] Icahn Sch Med Mt Sinai, Inst Immunol, Dept Med, New York, NY 10029 USA.
[Dai, Yan; He, John Cijiang] Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY USA.
[Li, Qin; Chuang, Peter Y.] Shanghai Blood Ctr, Shanghai, Peoples R China.
[Qi, Chen-Feng] NIAID, Natl Inst Hlth, Immunogenet Lab, Bethesda, MD 20892 USA.
RP Xiong, HB (reprint author), Icahn Sch Med Mt Sinai, Inst Immunol, Box 1630,1 Gustave L Levy Pl, New York, NY 10029 USA.
EM huabao.xiong@mssm.edu
FU NIH [P01 DK072201, R56AI091871]; Broad Medical Research Program of The
Broad Foundation
FX Supported by NIH grants P01 DK072201 and R56AI091871 and by the Broad
Medical Research Program of The Broad Foundation (H.X.).
NR 39
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U2 2
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PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD AUG
PY 2013
VL 183
IS 2
BP 402
EP 412
DI 10.1016/j.ajpath.2013.05.001
PG 11
WC Pathology
SC Pathology
GA 194DR
UT WOS:000322611700009
PM 23747510
ER
PT J
AU Zhou, XM
Wang, H
Burg, MB
Ferraris, JD
AF Zhou, Xiaoming
Wang, Hong
Burg, Maurice B.
Ferraris, Joan D.
TI High NaCl-induced inhibition of PTG contributes to activation of NFAT5
through attenuation of the negative effect of SHP-1
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE protein targeting to glycogen; TonEBP; PP1 gamma; PPP1R3C;
hypertonicity; protein phosphatase 1
ID TRANSCRIPTION FACTOR TONEBP/OREBP; TYROSINE-PHOSPHATASE; PHOSPHOLIPASE
C-GAMMA-1; GENE-EXPRESSION; GLYCOGEN PTG; PROTEIN; PHOSPHORYLATION;
CELLS; KINASE; TRANSACTIVATION
AB Activation of the transcription factor NFAT5 by high NaCl involves changes in phosphorylation. By siRNA screening, we previously found that protein targeting to glycogen (PTG), a regulatory subunit of protein phosphatase1 (PP1), contributes to regulation of high NaCl-induced NFAT5 transcriptional activity. The present study addresses the mechanism involved. We find that high NaCl-induced inhibition of PTG elevates NFAT5 activity by increasing NFAT5 transactivating activity, protein abundance, and nuclear localization. PTG acts via a catalytic subunit PP1 gamma. PTG associates physically with PP1 gamma, and NaCl reduces both this association and remaining PTG-associated PP1 gamma activity. High NaCl-induced phosphorylation of p38, ERK, and SHP-1 contributes to activation of NFAT5. Knockdown of PTG does not affect phosphorylation of p38 or ERK. However, PTG and PP1 gamma bind to SHP-1, and knockdown of either PTG or PP1 gamma increases high NaCl-induced phosphorylation of SHP-1-S591, which inhibits SHP-1. Mutation of SHP-1-S591 to alanine, which cannot be phosphorylated, increases inhibition of NFAT5 by SHP-1. Thus high NaCl reduces the stimulatory effect of PTG and PP1 gamma on SHP-1, which in turn reduces the inhibitory effect of SHP-1 on NFAT5. Our findings add to the known functions of PTG, which was previously recognized only for its glycogenic activity.
C1 [Zhou, Xiaoming; Wang, Hong] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA.
[Burg, Maurice B.; Ferraris, Joan D.] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
RP Zhou, XM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM xiaoming.zhou@usuhs.edu
FU National Heart, Lung, and Blood Institute, Department of Health and
Human Services; National Kidney Foundation/National Capital Area
FX This study was supported by the Intramural Research Program of the
National Heart, Lung, and Blood Institute, Department of Health and
Human Services, and by a grant-in-aid from the National Kidney
Foundation/National Capital Area.
NR 43
TC 6
Z9 6
U1 1
U2 2
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD AUG
PY 2013
VL 305
IS 3
BP F362
EP F369
DI 10.1152/ajprenal.00218.2013
PG 8
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 195JU
UT WOS:000322699000016
PM 23720348
ER
PT J
AU Dehdashti, SJ
Abbott, J
Nguyen, DT
McKew, JC
Williamson, PR
Zheng, W
AF Dehdashti, Seameen J.
Abbott, Jennifer
Dac-Trung Nguyen
McKew, John C.
Williamson, Peter R.
Zheng, Wei
TI A high-throughput screening assay for assessing the viability of
Cryptococcus neoformans under nutrient starvation conditions
SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY
LA English
DT Article
DE Cryptococcus neoformans; Cryptococcal infections; Cryptococcal
meningitis; High-throughput screening; ATP content assay
ID AMPHOTERICIN-B; MENINGITIS; FLUCONAZOLE; INHIBITOR; BURDEN
AB Cryptococcus neoformans causes an estimated 600,000 AIDS-related deaths annually that occur primarily in resource-limited countries. Fluconazole and amphotericin B are currently available for the treatment of cryptococcal-related infections. However, fluconazole has limited clinical efficacy and amphotericin B requires intravenous infusion and is associated with high renal toxicity. Therefore, there is an unmet need for a new orally administrable anti-cryptococcal drug. We have developed a high-throughput screening assay for the measurement of C. neoformans viability in 1,536-well plate format. The signal-to-basal ratio of the ATP content assay was 21.9 fold with a coefficient of variation and Z' factor of 7.1 % and 0.76, respectively. A pilot screen of 1,280 known compounds against the wild-type C. neoformans (strain H99) led to the identification of four active compounds including niclosamide, malonoben, 6-bromoindirubin-3'-oxime, and 5-[(4-ethylphenyl)methylene]-2-thioxo-4-thiazolidinone. These compounds were further tested against nine clinical isolates of C. neoformans, and their fungicidal activities were confirmed. The results demonstrate that this miniaturized C. neoformans assay is advantageous for the high-throughput screening of large compound collections to identify lead compounds for new anti-cryptococcal drug development.
C1 [Dehdashti, Seameen J.; Dac-Trung Nguyen; McKew, John C.; Zheng, Wei] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Abbott, Jennifer; Williamson, Peter R.] NIAID, Translat Mycol Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Williamson, Peter R.] Univ Illinois, Dept Med, Infect Dis Sect, Chicago, IL 60612 USA.
RP Zheng, W (reprint author), NIH, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr,MSC 3370, Bethesda, MD 20892 USA.
EM williamsonpr@mail.nih.gov; wzheng@mail.nih.gov
RI Zheng, Wei/J-8889-2014
OI Zheng, Wei/0000-0003-1034-0757
FU Therapeutics for Rare and Neglected Diseases, National Center for
Advancing Translational Sciences (NCATS); National Institute of Allergy
and Infectious Diseases, National Institutes of Health (NIH)
FX This work was supported by the Intramural Research Programs of the
Therapeutics for Rare and Neglected Diseases, National Center for
Advancing Translational Sciences (NCATS), and National Institute of
Allergy and Infectious Diseases, National Institutes of Health (NIH).
The authors thank Paul Shinn and compound management team at NCATS for
their assistance.
NR 20
TC 5
Z9 5
U1 0
U2 4
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1618-2642
J9 ANAL BIOANAL CHEM
JI Anal. Bioanal. Chem.
PD AUG
PY 2013
VL 405
IS 21
BP 6823
EP 6829
DI 10.1007/s00216-013-7134-4
PG 7
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 195MC
UT WOS:000322705600022
PM 23812880
ER
PT J
AU Rahma, OE
Duffy, A
Liewehr, DJ
Steinberg, SM
Greten, TF
AF Rahma, O. E.
Duffy, A.
Liewehr, D. J.
Steinberg, S. M.
Greten, T. F.
TI Second-line treatment in advanced pancreatic cancer: a comprehensive
analysis of published clinical trials
SO ANNALS OF ONCOLOGY
LA English
DT Review
DE analysis; cancer; pancreatic; review; second-line; treatment
ID PHASE-III TRIAL; GEMCITABINE-PRETREATED PATIENTS; SUPPORTIVE CARE;
RANDOMIZED-TRIAL; FOLINIC ACID; CHEMOTHERAPY; OXALIPLATIN;
5-FLUOROURACIL; THERAPY; IRINOTECAN
AB There is currently no standard of care for the second-line treatment of advanced pancreatic cancer. The aim of this analysis was to compare the different therapeutic approaches in this setting.
We carried out a systematic analysis of second-line studies in advanced pancreatic cancer that have progressed on or following gemcitabine and published or presented from 2000 to 2012.
Forty-four clinical trials (t) were identified; of which 34 met the inclusion criteria treating an aggregate total of 1503 patients (n). Patients who received treatments (t: 33; n: 1269) had a median overall survival (OS) of 6 months compared with 2.8 months for patients who received best supportive care only (t: 2; n: 234) (P = 0.013). The gemcitabine and platinum-based combination (t: 5; n: 154) provided a median progression-free survival and OS of 4 and 6 months compared with 1.6 and 5.3 for the rest of the regimens (t: 29; n: 1349) (P = 0.059 and 0.10, respectively) and 2.9 and 5.7 for the combination of 5-fluorouracil and platinum agents (t: 12; n: 450) (P = 0.60 and 0.22, respectively).
Although not conclusive, these data showed that the advantage of second-line chemotherapy in pancreatic cancer is very limited and there is a need for more studies.
C1 [Rahma, O. E.; Duffy, A.; Greten, T. F.] NCI, Gastrointestinal Malignancy Sect, Med Oncol Branch, Bethesda, MD 20892 USA.
[Liewehr, D. J.; Steinberg, S. M.] NCI, Biostat & Data Management Sect, Rockville, MD USA.
RP Greten, TF (reprint author), NCI, Gastrointestinal Malignancy Sect, Med Oncol Branch, 9000 Rockville Pike,10-12N224, Bethesda, MD 20892 USA.
EM tim.greten@nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX This work was supported by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research. 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.
NR 65
TC 42
Z9 43
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD AUG
PY 2013
VL 24
IS 8
BP 1972
EP 1979
DI 10.1093/annonc/mdt166
PG 8
WC Oncology
SC Oncology
GA 190KR
UT WOS:000322339300005
PM 23670093
ER
PT J
AU Bodelon, C
Polley, MY
Kemp, TJ
Pesatori, AC
McShane, LM
Caporaso, NE
Hildesheim, A
Pinto, LA
Landi, MT
AF Bodelon, C.
Polley, M. Y.
Kemp, T. J.
Pesatori, A. C.
McShane, L. M.
Caporaso, N. E.
Hildesheim, A.
Pinto, L. A.
Landi, M. T.
TI Circulating levels of immune and inflammatory markers and long versus
short survival in early-stage lung cancer
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE CCL15; inflammatory markers; lung cancer; survival
ID SMOKING STATUS; GROWTH-FACTOR; CHEMOKINE; EXPRESSION; GENE;
POLYMORPHISMS; ADENOCARCINOMA; ASSOCIATION; RECURRENCE; PROGNOSIS
AB Some patients diagnosed with early-stage lung cancer and treated according to standard care survive for only a short period of time, while others survive for years for reasons that are not well understood. Associations between markers of inflammation and survival from lung cancer have been observed.
Here, we investigate whether circulating levels of 77 inflammatory markers are associated with long versus short survival in stage I and II lung cancer. Patients who had survived either < 79 weeks (similar to 1.5 years) (short survivors, SS) or > 156 weeks (3 years) (long survivors, LS) were selected from a retrospective population-based study. Logistic regression was used to calculate adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs). The false discovery rate was calculated to adjust for multiple testing.
A total of 157 LS and 84 SS were included in this analysis. Thirteen markers had adjusted OR on the order of 2- to 5-fold when comparing the upper and lower quartiles with regard to the odds of short survival versus long. Chemokine CCL15 [chemokine (C-C motif) ligand 15] was the most significant marker associated with increased odds of short survival (ORs = 4.93; 95% CI 1.90-12.8; q-value: 0.042). Smoking and chronic obstructive pulmonary disease were not associated with marker levels.
Our results provide some evidence that deregulation of inflammatory responses may play a role in the survival of early-stage lung cancer. These findings will require confirmation in future studies.
C1 [Bodelon, C.; Caporaso, N. E.; Hildesheim, A.; Landi, M. T.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Polley, M. Y.; McShane, L. M.] NCI, Div Canc Treatment & Diag, Rockville, MD 20852 USA.
[Kemp, T. J.; Pinto, L. A.] NCI, HPV Immunol Lab, SAIC, Frederick, MD 21701 USA.
[Pesatori, A. C.] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy.
[Pesatori, A. C.] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy.
RP Bodelon, C (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 5100, Rockville, MD 20852 USA.
EM clara.bodelon@nih.gov
RI Hildesheim, Allan/B-9760-2015;
OI Hildesheim, Allan/0000-0003-0257-2363; pesatori,
angela/0000-0002-0261-3252
FU National Cancer Institute, Division of Cancer Epidemiology and Genetics,
National Institutes of Health
FX This study was supported by the Intramural Research Program of the
National Cancer Institute, Division of Cancer Epidemiology and Genetics,
National Institutes of Health.
NR 36
TC 17
Z9 17
U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD AUG
PY 2013
VL 24
IS 8
BP 2073
EP 2079
DI 10.1093/annonc/mdt175
PG 7
WC Oncology
SC Oncology
GA 190KR
UT WOS:000322339300021
PM 23680692
ER
PT J
AU Alfahad, T
Nath, A
AF Alfahad, Tariq
Nath, Avindra
TI Retroviruses and amyotrophic lateral sclerosis
SO ANTIVIRAL RESEARCH
LA English
DT Review
DE Human endogenous retrovirus; Transposons; Amyotropic lateral sclerosis;
Reverse transcriptase; Human immunodeficiency virus
ID MOTOR-NEURON DISEASE; IMMUNODEFICIENCY-VIRUS-INFECTION;
REVERSE-TRANSCRIPTASE ACTIVITY; HUMAN ENDOGENOUS RETROVIRUSES;
I-ASSOCIATED MYELOPATHY; ACTIVE ANTIRETROVIRAL THERAPY; ALS-LIKE
DISORDER; HIV-INFECTION; HEXANUCLEOTIDE REPEAT; DNA-POLYMERASE
AB Amyotrophic lateral sclerosis (ALS) is a progressive, invariably fatal neurologic disorder resulting from upper and lower motor neuron degeneration, which typically develops during the sixth or seventh decade of life, and is diagnosed based on standard clinical criteria. Its underlying cause remains undetermined. The disease may occur with increased frequency within certain families, often in association with specific genomic mutations, while some sporadic cases have been linked to environmental toxins or trauma. Another possibility, first proposed in the 1970s, is that retroviruses play a role in pathogenesis. In this paper, we review the published literature for evidence that ALS is associated either with infection by an exogenous retrovirus or with the expression of human endogenous retroviral (HERV) sequences in cells of the central nervous system. A small percentage of persons infected with the human immunodeficiency virus-1 (HIV-1) or human T cell leukemia virus-1 (HTLV-1) develop ALS-like syndromes. While HTLV-1 associated ALS-like syndrome has several features that may distinguish it from classical ALS, HIV-infected patients may develop neurological manifestations that resemble classical ALS although it occurs at a younger age and they may show a dramatic improvement following the initiation of antiretroviral therapy. However, most patients with probable or definite ALS show no evidence of HIV-1 or HTLV-1 infection. In contrast, recent reports have shown a stronger association with HERV, as analysis of serum samples, and postmortem brain tissue from a number of patients with a classical ALS has revealed significantly increased expression of HERV-K, compared to controls. These findings suggest that endogenous retroviral elements are involved in the pathophysiology of ALS, but there is no evidence that they are the primary cause of the syndrome. Published by Elsevier B.V.
C1 [Alfahad, Tariq; Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA.
RP Nath, A (reprint author), Bldg 10-7C-103,10 Ctr Dr, Bethesda, MD 20892 USA.
EM natha@ninds.nih.gov
FU Intramural NIH HHS [ZIA NS003130-02]
NR 68
TC 21
Z9 21
U1 0
U2 18
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-3542
J9 ANTIVIR RES
JI Antiviral Res.
PD AUG
PY 2013
VL 99
IS 2
BP 180
EP 187
DI 10.1016/j.antiviral.2013.05.006
PG 8
WC Pharmacology & Pharmacy; Virology
SC Pharmacology & Pharmacy; Virology
GA 200QZ
UT WOS:000323085300014
PM 23707220
ER
PT J
AU Blouin, AM
Stern, AL
Han, SH
Theberge, FR
Wang, CS
During, MJ
Baraban, JM
Reti, IM
AF Blouin, Ashley M.
Stern, Anna L.
Han, Sungho
Theberge, Florence R.
Wang, Chuansong
During, Matthew J.
Baraban, Jay M.
Reti, Irving M.
TI Neuronal activity-regulated pentraxin expressed in medial prefrontal
cortex neurons is not necessary for extinction of heroin
self-administration
SO BEHAVIOURAL PHARMACOLOGY
LA English
DT Article
DE addiction; extinction; heroin; neuronal activity-regulated pentraxin;
prefrontal cortex; self-administration
ID CONDITIONED PLACE PREFERENCE; COCAINE-ASSOCIATED STIMULUS;
NUCLEUS-ACCUMBENS; AMPA RECEPTORS; NARP; INCUBATION; SEEKING;
ASSOCIATION; DRUGS; RATS
AB The medial prefrontal cortex (mPFC) plays a key role in extinction learning. Previously, we found that expression of a neuronal activity-regulated pentraxin (Narp) dominant-negative construct in the mPFC of mice blocked extinction of morphine-conditioned place preference. To further investigate the role of mPFC Narp in the extinction of drug seeking, we tested whether mPFC Narp is necessary for the extinction of heroin self-administration in rats. Specifically, we injected an adeno-associated viral vector expressing a dominant-negative form of Narp (NarpN) into the infralimbic region of the mPFC of rats and compared lever presses during extinction to those of rats injected with a control virus. In contrast to our previous study, we found that injection of NarpN did not affect extinction of heroin self-administration. Our findings suggest that mPFC Narp is necessary for extinction of opiate seeking in the Pavlovian-conditioned place preference paradigm but not in the operant paradigm of drug self-administration.
C1 [Blouin, Ashley M.; Han, Sungho; Baraban, Jay M.; Reti, Irving M.] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Baraban, Jay M.; Reti, Irving M.] Johns Hopkins Sch Med, Solomon Snyder Dept Neurosci, Baltimore, MD 21205 USA.
[Stern, Anna L.; Theberge, Florence R.] NIDA, NIH, IRP, Baltimore, MD USA.
[Wang, Chuansong; During, Matthew J.] Ohio State Univ, Dept Mol Virol Immunol & Mol Genet, Columbus, OH 43210 USA.
RP Blouin, AM (reprint author), Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Ross Res Bldg Rm 618,720 Rutland Ave, Baltimore, MD 21205 USA.
EM ablouin1@jhmi.edu
OI Baraban, Jay/0000-0002-8165-2638
FU NIDA [R25DA21630-3]; [RO1 DA016303]
FX The behavioral part of this paper was carried out at the IRP-NIDA in the
laboratory of Dr Yavin Shaham. The authors thank Dr Yavin Shaham for his
assistance in the design and analysis of this study, Dr Peter Holland
for helpful comments on the manuscript, and Drs Alexander Johnson and
Gregory Michealson for statistical advice. The Narp antibody was
provided by Dr Paul Worley. This work was funded by RO1 DA016303, NIDA
R25DA21630-3, and funds to the intramural research program of NIDA.
NR 22
TC 3
Z9 3
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0955-8810
J9 BEHAV PHARMACOL
JI Behav. Pharmacol.
PD AUG
PY 2013
VL 24
IS 4
BP 332
EP 336
DI 10.1097/FBP.0b013e328363367b
PG 5
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 202OK
UT WOS:000323227100012
PM 23751516
ER
PT J
AU Aka, P
Vila, MC
Jariwala, A
Nkrumah, F
Emmanuel, B
Yagi, M
Palacpac, NMQ
Periago, MV
Neequaye, J
Kiruthu, C
Tougan, T
Levine, PH
Biggar, RJ
Pfeiffer, RM
Bhatia, K
Horii, T
Bethony, JM
Mbulaiteye, SM
AF Aka, Peter
Vila, Maria Candida
Jariwala, Amar
Nkrumah, Francis
Emmanuel, Benjamin
Yagi, Masanori
Palacpac, Nirianne Marie Q.
Periago, Maria V.
Neequaye, Janet
Kiruthu, Christine
Tougan, Takahiro
Levine, Paul H.
Biggar, Robert J.
Pfeiffer, Ruth M.
Bhatia, Kishor
Horii, Toshihiro
Bethony, Jeffrey M.
Mbulaiteye, Sam M.
TI Endemic Burkitt lymphoma is associated with strength and diversity of
Plasmodium falciparum malaria stage-specific antigen antibody response
SO BLOOD
LA English
DT Article
ID SERINE REPEAT ANTIGEN; EPSTEIN-BARR-VIRUS; VACCINE; CHILDREN; SERUM;
TRANSMISSION; IMMUNITY; UGANDA; GHANA
AB Endemic Burkitt lymphoma (eBL) is linked to Plasmodium falciparum (Pf) infection geographically, but evidence from individual-level studies is limited. We investigated this issue among 354 childhood eBL cases and 384 age-, sex-, and location-matched controls enrolled in Ghana from 1965 to 1994. Immunoglobulin G1 (IgG1) and immunoglobulin G3 (IgG3) antibodies to antigens diagnostic of recent infection Pf histidine-rich protein-II (HRP-II) and 6NANP, Pf-vaccine candidates SE36 and 42-kDa region of the 3D7 Pf merozoite surface protein-1 (MSP-1), and tetanus toxoid were measured by indirect enzyme-linked immunoassay. Odds ratios (ORs) and 95% confidence intervals (CIs) for association with eBL were estimated using unconditional logistic regression. After adjustments, eBL was positively associated with HRP-IIIgG3 seropositivity (adjusted OR: 1.60; 95% CI 1.08-2.36) and inversely associated with SE36(IgG1) seropositivity (adjusted OR: 0.37; 95% CI 0.21-0.64) and with tetanus toxoid(IgG3) levels equal or higher than the mean (adjusted OR: 0.46; 95% CI 0.32-0.66). Anti-MSP-1(IgG3) and anti-6NANP(IgG3) were indeterminate. eBL risk was potentially 21 times higher (95% CI 5.8-74) in HRP-IIIgG3-seropositive and SE36(IgG1)-seronegative responders compared with HRP-IIIgG3-seronegative and SE36(IgG1)-seropositive responders. Our results suggest that recent malaria may be associated with risk of eBL but long-term infection may be protective.
C1 [Aka, Peter; Emmanuel, Benjamin; Kiruthu, Christine; Pfeiffer, Ruth M.; Bhatia, Kishor; Mbulaiteye, Sam M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Vila, Maria Candida; Jariwala, Amar; Periago, Maria V.; Levine, Paul H.; Bethony, Jeffrey M.] George Washington Univ, Dept Microbiol Immunol & Trop Med, Washington, DC USA.
[Nkrumah, Francis] Noguchi Mem Inst, Accra, Ghana.
[Yagi, Masanori; Palacpac, Nirianne Marie Q.; Tougan, Takahiro; Horii, Toshihiro] Osaka Univ, Microbial Dis Res Inst, Dept Mol Protozool, Osaka, Japan.
[Neequaye, Janet] Korle Bu Univ Teaching Hosp, Dept Child Hlth, Accra, Ghana.
[Biggar, Robert J.] Queensland Univ Technol, Inst Hlth & Biotechnol, Brisbane, Qld 4001, Australia.
RP Mbulaiteye, SM (reprint author), NCI, NIH, 9600 Med Ctr Dr,Rm 6E118,MSC 9704, Bethesda, MD 20892 USA.
EM mbulaits@mail.nih.gov
RI Periago, Maria/H-1054-2013;
OI Periago, Maria Victoria/0000-0002-1470-5146
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health, Department of Health and Human Services
[N01-CO-12400]; Ministry of Education, Culture, Sports, Science and
Technology of Japan; George Washington University
FX This work was supported by a grant from the Intramural Research Program
of the Division of Cancer Epidemiology and Genetics, National Cancer
Institute, National Institutes of Health, Department of Health and Human
Services (grant number N01-CO-12400) and by The Biomedical Kansai
project supported by the Regional Innovation Cluster Program of the
Ministry of Education, Culture, Sports, Science and Technology of Japan
and The George Washington University.
NR 38
TC 9
Z9 9
U1 0
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 1
PY 2013
VL 122
IS 5
BP 629
EP 635
DI 10.1182/blood-2012-12-475665
PG 7
WC Hematology
SC Hematology
GA 196RN
UT WOS:000322793400008
PM 23645841
ER
PT J
AU Doyle, AD
Jacobsen, EA
Ochkur, SI
McGarry, MP
Shim, KG
Nguyen, DTC
Protheroe, C
Colbert, D
Kloeber, J
Neely, J
Shim, KP
Dyer, KD
Rosenberg, HF
Lee, JJ
Lee, NA
AF Doyle, Alfred D.
Jacobsen, Elizabeth A.
Ochkur, Sergei I.
McGarry, Michael P.
Shim, Kevin G.
Nguyen, David T. C.
Protheroe, Cheryl
Colbert, Dana
Kloeber, Jake
Neely, Joseph
Shim, Kelly P.
Dyer, Kimberly D.
Rosenberg, Helene F.
Lee, James J.
Lee, Nancy A.
TI Expression of the secondary granule proteins major basic protein 1
(MBP-1) and eosinophil peroxidase (EPX) is required for
eosinophilopoiesis in mice
SO BLOOD
LA English
DT Article
ID SEVERE CONGENITAL NEUTROPENIA; MOLECULAR-CLONING; BONE-MARROW; PULMONARY
INFLAMMATION; RIBONUCLEASE GENES; MOUSE EOSINOPHILS; CATIONIC PROTEIN;
UNIT GRANULES; ASTHMA; IDENTIFICATION
AB Eosinophil activities are often linked with allergic diseases such as asthma and the pathologies accompanying helminth infection. These activities have been hypothesized to be mediated, in part, by the release of cationic proteins stored in the secondary granules of these granulocytes. The majority of the proteins stored in these secondary granules (by mass) are major basic protein 1 (MBP-1) and eosinophil peroxidase (EPX). Unpredictably, a knockout approach targeting the genes encoding these proteins demonstrated that, unlike in mice containing a single deficiency of only MBP-1 or EPX, the absence of both granule proteins resulted in the near complete loss of peripheral blood eosinophils with no apparent impact on any other hematopoietic lineage. Moreover, the absence of MBP-1 and EPX promoted a concomitant loss of eosinophil lineage-committed progenitors in the marrow, identifying a specific blockade in eosinophilopoiesis as the causative event. Significantly, this blockade of eosinophilopoiesis is also observed in ex vivo cultures of marrow progenitors and is not rescued in vivo by adoptive bone marrow engraftment, suggesting a cell-autonomous defect in marrow progenitors. These observations implicate a role for granule protein gene expression as a regulator of eosinophilopoiesis and provide another strain of mice congenitally deficient of eosinophils.
C1 [Doyle, Alfred D.; Jacobsen, Elizabeth A.; Ochkur, Sergei I.; McGarry, Michael P.; Shim, Kevin G.; Protheroe, Cheryl; Kloeber, Jake; Shim, Kelly P.; Lee, James J.] Mayo Clin Arizona, Dept Biochem & Mol Biol, Div Pulm Med, Scottsdale, AZ 85259 USA.
[Nguyen, David T. C.; Colbert, Dana; Neely, Joseph; Lee, Nancy A.] Mayo Clin Arizona, Dept Biochem & Mol Biol, Div Hematol Oncol, Scottsdale, AZ 85259 USA.
[Dyer, Kimberly D.; Rosenberg, Helene F.] NIAID, Inflammat Immunobiol Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Lee, NA (reprint author), Mayo Clin Arizona, Dept Biochem & Mol Biol, Mayo Clin Coll Med, Mayo Clin Collaborat Res Bldg 2-206,13400 E Shea, Scottsdale, AZ 85259 USA.
EM nlee@mayo.edu
FU Mayo Foundation; National Institutes of Health from the National
Institute of Allergy and Infectious Diseases, Division of Intramural
Research [HL058723, HL065228, RR0109709, AI000941]; Mayo Clinic Sidney
Luckman Family Pre-doctoral Fellowship
FX This work was supported by the Mayo Foundation, by National Institutes
of Health grants HL058723 (N.A.L.), HL065228, and RR0109709 (J.J.L.),
and grant AI000941 (H. F. R.) from the National Institute of Allergy and
Infectious Diseases, Division of Intramural Research. Support for A. D.
D. was provided by a Mayo Clinic Sidney Luckman Family Pre-doctoral
Fellowship.
NR 47
TC 25
Z9 25
U1 0
U2 7
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 1
PY 2013
VL 122
IS 5
BP 781
EP 790
DI 10.1182/blood-2013-01-473405
PG 10
WC Hematology
SC Hematology
GA 196RN
UT WOS:000322793400025
PM 23736699
ER
PT J
AU Coghill, JM
Fowler, KA
West, ML
Fulton, LM
van Deventer, H
McKinnon, KP
Vincent, BG
Lin, KF
Panoskaltsis-Mortari, A
Cook, DN
Blazar, BR
Serody, JS
AF Coghill, James M.
Fowler, Kenneth A.
West, Michelle L.
Fulton, LeShara M.
van Deventer, Hendrik
McKinnon, Karen P.
Vincent, Benjamin G.
Lin, Kaifeng
Panoskaltsis-Mortari, Angela
Cook, Donald N.
Blazar, Bruce R.
Serody, Jonathan S.
TI CC chemokine receptor 8 potentiates donor T-reg survival and is critical
for the prevention of murine graft-versus-host disease
SO BLOOD
LA English
DT Article
ID PERIPHERAL-BLOOD; REGULATORY CELLS; DENDRITIC CELLS; IN-VIVO;
OVARIAN-CANCER; BONE-MARROW; MICE; RECRUITMENT; EXPRESSION; LEUKEMIA
AB The infusion of donor regulatory T cells (T-regs) has been used to prevent acute graft-versus-host disease (GVHD) in mice and has shown promise in phase 1 clinical trials. Previous work suggested that early T-reg migration into lymphoid tissue was important for GVHD prevention. However, it is unclear how and where T-regs function longitudinally to affect GVHD. To better understand their mechanism of action, we studied 2 T-reg-associated chemokine receptors in murine stem cell transplant models. CC chemokine receptor (CCR) 4 was dispensable for donor T-reg function in the transplant setting. Donor T-regs lacking CCR8 (CCR8(-/-)), however, were severely impaired in their ability to prevent lethal GVHD because of increased cell death. By itself, CCR8 stimulation was unable to rescue T-regs from apoptosis. Instead, CCR8 potentiated T-reg survival by promoting critical interactions with dendritic cells. In vivo, donor bone marrow-derived CD11c(+) antigen-presenting cells (APCs) were important for promoting donor T-reg maintenance after transplant. In contrast, host CD11c(+) APCs appeared to be dispensable for early activation and expansion of donor T-regs. Collectively, our data indicate that a sustained donor T-reg presence is critical for their beneficial properties, and that their survival depends on CCR8 and donor but not host CD11c(+) APCs.
C1 [Coghill, James M.; Fulton, LeShara M.; van Deventer, Hendrik; Vincent, Benjamin G.; Serody, Jonathan S.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Dept Med, Chapel Hill, NC 27599 USA.
[Coghill, James M.; Fowler, Kenneth A.; West, Michelle L.; Fulton, LeShara M.; van Deventer, Hendrik; McKinnon, Karen P.; Vincent, Benjamin G.; Lin, Kaifeng; Serody, Jonathan S.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Immunotherapy Program, Chapel Hill, NC 27599 USA.
[Panoskaltsis-Mortari, Angela; Blazar, Bruce R.] Univ Minnesota, Ctr Canc, Minneapolis, MN USA.
[Cook, Donald N.] NIEHS, Durham, NC USA.
RP Coghill, JM (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, 450 West Dr, Chapel Hill, NC 27599 USA.
EM jcoghill@e-mail.unc.edu
OI Serody, Jonathan/0000-0003-4568-1092
FU National Institutes of Health, National Cancer Institute
[5K12CA120780-05]; National Heart, Lung, and Blood Institute
[5K08HL111205-02]; National Cancer Institute [RO1CA166794]; National
Institute of Allergy and Infectious Diseases [R56 AI064363]
FX This work was supported by the following National Institutes of Health
grants: National Cancer Institute 5K12CA120780-05 and National Heart,
Lung, and Blood Institute 5K08HL111205-02 (J.M.C.); and National Heart,
Lung, and Blood Institute R01HL115761, National Cancer Institute
RO1CA166794, and National Institute of Allergy and Infectious Diseases
R56 AI064363 (J.S.S.).
NR 43
TC 9
Z9 10
U1 0
U2 5
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 1
PY 2013
VL 122
IS 5
BP 825
EP 836
DI 10.1182/blood-2012-06-435735
PG 12
WC Hematology
SC Hematology
GA 196RN
UT WOS:000322793400030
PM 23798714
ER
PT J
AU Hale, GA
Arora, M
Ahn, KW
He, W
Camitta, B
Bishop, MR
Bitan, M
Cairo, MS
Chan, K
Childs, RW
Copelan, E
Davies, SM
Perez, MAD
Doyle, JJ
Gale, RP
Vicent, MG
Horn, BN
Hussein, AA
Jodele, S
Kamani, NR
Kasow, KA
Kletzel, M
Lazarus, HM
Lewis, VA
Myers, KC
Olsson, R
Pulsipher, M
Qayed, M
Sanders, JE
Shaw, PJ
Soni, S
Stiff, PJ
Stadtmauer, EA
Ueno, NT
Wall, DA
Grupp, SA
AF Hale, G. A.
Arora, M.
Ahn, K. W.
He, W.
Camitta, B.
Bishop, M. R.
Bitan, M.
Cairo, M. S.
Chan, K.
Childs, R. W.
Copelan, E.
Davies, S. M.
Perez, M. A. D.
Doyle, J. J.
Gale, R. P.
Vicent, M. G.
Horn, B. N.
Hussein, A. A.
Jodele, S.
Kamani, N. R.
Kasow, K. A.
Kletzel, M.
Lazarus, H. M.
Lewis, V. A.
Myers, K. C.
Olsson, R.
Pulsipher, M.
Qayed, M.
Sanders, J. E.
Shaw, P. J.
Soni, S.
Stiff, P. J.
Stadtmauer, E. A.
Ueno, N. T.
Wall, D. A.
Grupp, S. A.
TI Allogeneic hematopoietic cell transplantation for neuroblastoma: the
CIBMTR experience
SO BONE MARROW TRANSPLANTATION
LA English
DT Article
DE neuroblastoma; allogeneic HCT; autologous HCT; CIBMTR
ID HIGH-RISK NEUROBLASTOMA; BONE-MARROW-TRANSPLANTATION; INTENSITY
CONDITIONING REGIMEN; HIGH-DOSE THERAPY; UNRELATED CORD BLOOD;
13-CIS-RETINOIC ACID; CHILDREN; SURVIVAL; GRAFT; GENOTYPES
AB Although the role of autologous hematopoietic cell transplantation (auto-HCT) is well established in neuroblastoma (NBL), the role of allogeneic HCT (allo-HCT) is controversial. The Center for International Blood and Marrow Transplant Research conducted a retrospective review of 143 allo-HCT for NBL reported in 1990-2007. Patients were categorized into two different groups: those who had not (Group 1) and had (Group 2) undergone a prior auto-HCT (n = 46 and 97, respectively). One-year and five-year OS were 59% and 29% for Group 1 and 50% and 7% for Group 2, respectively. Among donor types, disease-free survival (DFS) and OS were significantly lower for unrelated transplants at 1 and 3 years but not at 5 years post HCT. Patients in CR or very good partial response (VGPR) at transplant had lower relapse rates and better DFS and OS, compared with those not in CR or VGPR. Our analysis indicates that allo-HCT can cure some neuroblastoma patients, with lower relapse rates and improved survival in patients without a history of prior auto-HCT as compared with those patients who had previously undergone auto-HCT. Although the data do not address why either strategy was chosen for patients, allo-HCT after a prior auto-HCT appears to offer minimal benefit. Disease recurrence remains the most common cause of treatment failure.
C1 [Hale, G. A.] Univ S Florida, All Childrens Hosp, Dept Blood & Marrow Transplant Program, St Petersburg, FL 33701 USA.
[Arora, M.] Univ Minnesota, Med Ctr, Div Hematol Oncol & Transplant, Minneapolis, MN 55455 USA.
[Ahn, K. W.] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA.
[He, W.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Camitta, B.] Med Coll Wisconsin, Midwest Ctr Canc & Blood Disorders, Milwaukee, WI 53226 USA.
[Camitta, B.] Childrens Hosp Wisconsin, Midwest Ctr Canc & Blood Disorders, Milwaukee, WI 53201 USA.
[Bishop, M. R.] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA.
[Bitan, M.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Pediat Hematol Oncol, IL-69978 Tel Aviv, Israel.
[Cairo, M. S.] New York Med Coll, Dept Pediat Hematol Oncol Stem Cell Transplantat, Valhalla, NY 10595 USA.
[Chan, K.] Texas Transplant Inst, Dept Pediat, San Antonio, TX USA.
[Childs, R. W.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Copelan, E.] Cleveland Clin Fdn, Dept Hematol Oncol & Blood Disorders, Cleveland, OH 44195 USA.
[Davies, S. M.; Jodele, S.; Myers, K. C.] Cincinnati Childrens Hosp Med Ctr, Dept Bone Marrow Transplantat & Immune Deficiency, Cincinnati, OH 45229 USA.
[Perez, M. A. D.; Vicent, M. G.] Hosp Infantil Univ Nino Jesus, Serv Oncohematol, Madrid, Spain.
[Doyle, J. J.] Hosp Sick Children, Div Hematol Oncol, Toronto, ON M5G 1X8, Canada.
[Gale, R. P.] Univ London Imperial Coll Sci Technol & Med, Dept Med, Div Expt Med, Sect Hematol, London, England.
[Horn, B. N.] Univ Calif San Francisco, Med Ctr, Dept Pediat, San Francisco, CA USA.
[Hussein, A. A.] King Hussein Canc Ctr, Dept Bone Marrow & Stem Cell Transplantat, Amman, Jordan.
[Kamani, N. R.] Childrens Natl Med Ctr, Ctr Canc & Bloor Disorders, Washington, DC 20010 USA.
[Kasow, K. A.] Univ North Carolina Hosp, Dept Pediat, Chapel Hill, NC USA.
[Kletzel, M.] Ann & Robert H Lurie Childrens Hosp Chicago, Dept Pediat, Chicago, IL USA.
[Lazarus, H. M.] Univ Hosp Case Med Ctr, Dept Pediat Hematol Oncol, Cleveland, OH USA.
[Lewis, V. A.] Alberta Childrens Prov Gen Hosp, Dept Pediat Hematol Oncol, Calgary, AB, Canada.
[Olsson, R.] Karolinska Univ Hosp, Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden.
[Pulsipher, M.] Primary Childrens Med Ctr, Dept Hematol, Salt Lake City, UT 84103 USA.
[Qayed, M.] Childrens Healthcare Atlanta Egleston, Dept Pediat Hematol Oncol, Atlanta, GA USA.
[Sanders, J. E.] Fred Hutchinson Canc Res Ctr, Dept Clin Res Div, Seattle, WA 98104 USA.
[Shaw, P. J.] Childrens Hosp Westmead, Dept BMT Serv, Sydney, NSW, Australia.
[Soni, S.] Nationwide Childrens Hosp, Div Hematol Oncol, Dept Blood & Marrow Transplant Program, Columbus, OH USA.
[Stiff, P. J.] Loyola Univ, Med Ctr, Dept Hematol Oncol, Maywood, IL 60153 USA.
[Stadtmauer, E. A.] Univ Penn, Med Ctr, Abramson Canc Ctr, Dept Hematol Oncol, Philadelphia, PA 19104 USA.
[Ueno, N. T.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA.
[Wall, D. A.] Univ Manitoba, CancerCare Manitoba, Manitoba Blood & Marrow Transplant Program, Winnipeg, MB, Canada.
[Grupp, S. A.] Univ Penn, Childrens Hosp Philadelphia, Dept Pediat, Div Oncol, Philadelphia, PA 19104 USA.
[Grupp, S. A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Arora, M (reprint author), Univ Minnesota, Med Ctr, Div Hematol Oncol & Transplant, MMC 480,420 Delaware St SE, Minneapolis, MN 55455 USA.
EM arora005@umn.edu
OI Olsson, Richard/0000-0001-5970-2128
FU National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung and
Blood Institute (NHLBI); National Institute of Allergy and Infectious
Diseases (NIAID); NHLBI [5U01HL069294]; NCI; Health Resources and
Services Administration (HRSA/DHHS) [HHSH234200637015C]; Office of Naval
Research [N00014-06-1-0704, N00014-08-1-0058]; Allos, Inc.; Amgen, Inc.;
Angioblast; Ariad; Be the Match Foundation; Blue Cross and Blue Shield
Association; Buchanan Family Foundation; CaridianBCT; Celgene
Corporation; CellGenix, GmbH; Children's Leukemia Research Association;
Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture
Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline;
HistoGenetics, Inc.; Kiadis Pharma; The Leukemia and Lymphoma Society;
The Medical College of Wisconsin; Merck Co, Inc.; Millennium: The Takeda
Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow
Donor Program; Optum Healthcare Solutions, Inc.; Osiris Therapeutics,
Inc.; Otsuka America Pharmaceutical, Inc.; RemedyMD; Sanofi; Seattle
Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global
Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan
Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.; THERAKOS,
Inc.; Wellpoint, Inc
FX The CIBMTR is supported by Public Health Service Grant/Cooperative
Agreement U24-CA76518 from the National Cancer Institute (NCI), the
National Heart, Lung and Blood Institute (NHLBI) and the National
Institute of Allergy and Infectious Diseases (NIAID); a
Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; a contract
HHSH234200637015C with Health Resources and Services Administration
(HRSA/DHHS); two Grants N00014-06-1-0704 and N00014-08-1-0058 from the
Office of Naval Research; and grants from Allos, Inc.; Amgen, Inc.;
Angioblast; Anonymous donation to the Medical College of Wisconsin;
Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association;
Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix,
GmbH; Children's Leukemia Research Association; Fresenius-Biotech North
America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.;
Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis
Pharma; The Leukemia and Lymphoma Society; The Medical College of
Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.;
Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor
Program; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.;
Otsuka America Pharmaceutical, Inc.; RemedyMD; Sanofi; Seattle Genetics;
Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord
Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan
Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.; THERAKOS,
Inc.; and Wellpoint, Inc. The views expressed in this article do not
reflect the official policy or position of the National Institute of
Health, the Department of the Navy, the Department of Defense, or any
other agency of the US Government.
NR 30
TC 3
Z9 4
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD AUG
PY 2013
VL 48
IS 8
BP 1056
EP 1064
DI 10.1038/bmt.2012.284
PG 9
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 197AR
UT WOS:000322819900008
PM 23419433
ER
PT J
AU Treister, N
Chai, X
Kurland, B
Pavletic, S
Weisdorf, D
Pidala, J
Palmer, J
Martin, P
Inamoto, Y
Arora, M
Flowers, M
Jacobsohn, D
Jagasia, M
Arai, S
Lee, SJ
Cutler, C
AF Treister, N.
Chai, X.
Kurland, B.
Pavletic, S.
Weisdorf, D.
Pidala, J.
Palmer, J.
Martin, P.
Inamoto, Y.
Arora, M.
Flowers, M.
Jacobsohn, D.
Jagasia, M.
Arai, S.
Lee, S. J.
Cutler, C.
TI Measurement of oral chronic GVHD: results from the Chronic GVHD
Consortium
SO BONE MARROW TRANSPLANTATION
LA English
DT Article
DE oral cavity; SCT; GVHD; quality of life
ID VERSUS-HOST-DISEASE; CONSENSUS DEVELOPMENT PROJECT; WORKING
GROUP-REPORT; CLINICAL-TRIALS; THERAPEUTIC RESPONSE; CRITERIA;
RELIABILITY; DESIGN
AB Oral chronic GVHD (cGVHD) is a serious complication of alloSCT. Scales and instruments to measure oral cGVHD activity and severity have not been prospectively validated. The objective of this study was to describe the characteristics of oral cGVHD and determine the measures most sensitive to change. Patients enrolled in the cGVHD Consortium with oral involvement were included. Clinicians scored oral changes according to the National Institutes of Health (NIH) criteria, and patients completed symptom and quality-of-life measures at each visit. Both rated change on an eight-point scale. Of the 458 participants, 72% (n = 331) had objective oral involvement at enrollment. Lichenoid change was the most common feature (n = 293; 89%). At visits where oral change could be assessed, 50% of clinicians and 56% of patients reported improvement, with worsening reported in 4-5% for both the groups (weighted kappa = 0.41). Multivariable regression modeling suggested that the measurement changes most predictive of perceived change by clinicians and patients were erythema and lichenoid, NIH severity and symptom scores. Oral cGVHD is common and associated with a range of signs and symptoms. Measurement of erythema and lichenoid changes and symptoms may adequately capture the activity of oral cGVHD in clinical trials but require prospective validation.
C1 [Treister, N.] Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02115 USA.
[Chai, X.; Kurland, B.; Martin, P.; Inamoto, Y.; Flowers, M.; Lee, S. J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Pavletic, S.] NCI, Ctr Canc Res, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
[Weisdorf, D.; Arora, M.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA.
[Pidala, J.] H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL USA.
[Palmer, J.] Med Coll Wisconsin, Dept Hematol & Oncol, Milwaukee, WI 53226 USA.
[Jacobsohn, D.] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Div Blood & Marrow Transplantat, Washington, DC 20010 USA.
[Jagasia, M.] Vanderbilt Ingram Canc Ctr, Div Hematol Stem Cell Transplantat, Nashville, TN USA.
[Arai, S.] Stanford Univ, Ctr Med, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA.
[Cutler, C.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA.
RP Treister, N (reprint author), Brigham & Womens Hosp, Div Oral Med & Dent, 1620 Tremont St,3rd Floor, Boston, MA 02115 USA.
EM ntreister@partners.org
OI Kurland, Brenda/0000-0002-5669-0595
FU [CA118953]; [CA163438]
FX This work was supported by Grants CA118953 and CA163438.
NR 27
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U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD AUG
PY 2013
VL 48
IS 8
BP 1123
EP 1128
DI 10.1038/bmt.2012.285
PG 6
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 197AR
UT WOS:000322819900018
PM 23353804
ER
PT J
AU Pang, YL
Gara, SK
Achyut, BR
Li, ZY
Yan, HH
Day, CP
Weiss, JM
Trinchieri, G
Morris, JC
Yang, L
AF Pang, Yanli
Gara, Sudheer Kumar
Achyut, Bhagelu R.
Li, Zhaoyang
Yan, Hannah H.
Day, Chi-Ping
Weiss, Jonathan M.
Trinchieri, Giorgio
Morris, John C.
Yang, Li
TI TGF-beta Signaling in Myeloid Cells Is Required for Tumor Metastasis
SO CANCER DISCOVERY
LA English
DT Article
ID GROWTH-FACTOR; SUPPRESSOR-CELLS; IMMUNE CELLS; T-CELLS; DENDRITIC CELLS;
MAMMARY-TUMORS; PARACRINE LOOP; BREAST-CANCER; MOUSE MODEL; MACROPHAGES
AB TGF-beta is overexpressed in advanced human cancers. It correlates with metastasis and poor prognosis. However, TGF-beta functions as both a tumor suppressor and a tumor promoter. Here, we report for the first time that genetic deletion of Tgfbr2 specifically in myeloid cells (Tgfbr2(MyeK0)) significantly inhibited tumor metastasis. Reconstitution of tumor-bearing mice with Tgfbr2(MyeK0) bone marrow recapitulated the inhibited metastasis phenotype. This effect is mediated through decreased production of type II cytokines, TGF-beta 1, arginase 1, and inducible nitric oxide synthase, which promoted IFN-gamma production and improved systemic immunity. Depletion of CD8 T cells diminished the metastasis defect in the Tgfbr2(MyeK0) mice. Consistent with animal studies, myeloid cells from patients with advanced-stage cancer showed increased TGF-beta receptor II expression. Our studies show that myeloid-specific TGF-beta signaling is an essential component of the metastasis-promoting puzzle of TGF-beta. This is in contrast to the previously reported tumor-suppressing phenotypes in fibroblasts, epithelial cells, and T cells.
C1 [Pang, Yanli; Gara, Sudheer Kumar; Achyut, Bhagelu R.; Li, Zhaoyang; Yan, Hannah H.; Day, Chi-Ping; Yang, Li] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
[Weiss, Jonathan M.; Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA.
[Morris, John C.] Univ Cincinnati, Dept Med, Div Hematol Oncol, Cincinnati, OH 45221 USA.
RP Yang, L (reprint author), NCI, Ctr Canc Res, Bldg 37,Room 3134C,37 Convent Dr,MSC 4258, Bethesda, MD 20892 USA.
EM yangl3@mail.nih.gov
RI Gara, Sudheer Kumar/E-8084-2016
FU NCI
FX This work was supported by NCI intramural funding (to L. Yang).
NR 59
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U1 0
U2 10
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
J9 CANCER DISCOV
JI Cancer Discov.
PD AUG
PY 2013
VL 3
IS 8
BP 936
EP 951
DI 10.1158/2159-8290.CD-12-0527
PG 16
WC Oncology
SC Oncology
GA 198XQ
UT WOS:000322957600026
PM 23661553
ER
PT J
AU Perlmutter, J
Bell, SK
Darien, G
AF Perlmutter, Jane
Bell, Shannon K.
Darien, Gwen
TI Cancer Research Advocacy: Past, Present, and Future
SO CANCER RESEARCH
LA English
DT Article
ID UNITED-STATES
AB In this article, we present a brief history of cancer advocacy and discuss the variety of ways advocates have become involved in cancer research and subsequently present principles that establish a framework for successful research advocacy based on a review of many early initiatives coupled with our knowledge as long-time cancer advocates. Challenges to effective advocacy are described, and recommendations for increasing meaningful contributions by research advocates are proposed. The purpose of this article is to discuss the exciting field of research advocacy and to help shape a more productive future for advocates and their scientific collaborators. (C)2013 AACR.
C1 [Perlmutter, Jane] Gemini Grp, Ann Arbor, MI 48104 USA.
[Bell, Shannon K.] NCI, Bethesda, MD 20892 USA.
[Darien, Gwen] Pathways Project, Montclair, NJ USA.
RP Perlmutter, J (reprint author), Gemini Grp, 507 N 5th Ave, Ann Arbor, MI 48104 USA.
EM janep@gemini-grp.com
NR 13
TC 3
Z9 3
U1 1
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD AUG 1
PY 2013
VL 73
IS 15
BP 4611
EP 4615
DI 10.1158/0008-5472.CAN-12-4553-T
PG 5
WC Oncology
SC Oncology
GA 194HC
UT WOS:000322620800004
PM 23720053
ER
PT J
AU Solier, S
Ryan, MC
Martin, SE
Varma, S
Kohn, KW
Liu, HF
Zeeberg, BR
Pommier, Y
AF Solier, Stephanie
Ryan, Michael C.
Martin, Scott E.
Varma, Sudhir
Kohn, Kurt W.
Liu, Hongfang
Zeeberg, Barry R.
Pommier, Yves
TI Transcription Poisoning by Topoisomerase I Is Controlled by Gene Length,
Splice Sites, and miR-142-3p
SO CANCER RESEARCH
LA English
DT Article
ID RNA-POLYMERASE-II; DNA-DAMAGE; HUMAN-CELLS; CLEAVABLE COMPLEXES;
REGULATORY NETWORK; MESSENGER-RNA; CAMPTOTHECIN; REPLICATION; MICRORNAS;
P53
AB Topoisomerase I (Top1) relaxes DNA supercoiling by forming transient cleavage complexes (Top1cc) up- and downstream of transcription complexes. Top1cc can be trapped by carcinogenic and endogenous DNA lesions and by camptothecin, resulting in transcription blocks. Here, we undertook genome-wide analysis of camptothecin-treated cells at exon resolution. RNA samples from HCT116 and MCF7 cells were analyzed with the Affy Exon Array platform, allowing high-resolution mapping along 18,537 genes. Long genes that are highly expressed were the most susceptible to downregulation, whereas short genes were preferentially upregulated. Along the body of genes, downregulation was most important toward the 3'-end and increased with the number of exon-intron junctions. Ubiquitin and RNA degradation-related pathway genes were selectively downregulated. Parallel analysis of microRNA with the Agilent miRNA microarray platform revealed that miR-142-3p was highly induced by camptothecin. More than 10% of the downregulated genes were targets of this p53-dependent microRNA. Our study shows the profound impact of Top1cc on transcription elongation, especially at intron-exon junctions and on transcript stability by microRNA miR-142-3p upregulation. (C)2013 AACR.
C1 [Solier, Stephanie; Ryan, Michael C.; Varma, Sudhir; Kohn, Kurt W.; Liu, Hongfang; Zeeberg, Barry R.; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Martin, Scott E.] NIH, Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Ryan, Michael C.] In Silico Solut, Fairfax, VA USA.
RP Pommier, Y (reprint author), NIH, Mol Pharmacol Lab, Ctr Canc Res, Bldg 37,Rm 5068, Bethesda, MD 20892 USA.
EM pommier@nih.gov
RI Varma, Sudhir/N-8763-2014
OI Varma, Sudhir/0000-0002-4096-4782
FU Center for Cancer Research, the Intramural program of the National
Cancer Institute, NIH
FX This study was supported by the Center for Cancer Research, the
Intramural program of the National Cancer Institute, NIH.
NR 50
TC 18
Z9 19
U1 0
U2 14
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 AUG 1
PY 2013
VL 73
IS 15
BP 4830
EP 4839
DI 10.1158/0008-5472.CAN-12-3504
PG 10
WC Oncology
SC Oncology
GA 194HC
UT WOS:000322620800024
PM 23786772
ER
PT J
AU Xu, SW
Ogura, S
Chen, JW
Little, PJ
Moss, J
Liu, PQ
AF Xu, Suowen
Ogura, Sayoko
Chen, Jiawei
Little, Peter J.
Moss, Joel
Liu, Peiqing
TI LOX-1 in atherosclerosis: biological functions and pharmacological
modifiers
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Review
DE Atherosclerosis; Oxidized LDL; LOX-1; Soluble LOX-1; Review
ID LOW-DENSITY-LIPOPROTEIN; ARTERY ENDOTHELIAL-CELLS; SMOOTH-MUSCLE-CELLS;
OXIDIZED LDL RECEPTOR-1; HIGH-CHOLESTEROL DIET; ACUTE CORONARY SYNDROME;
NF-KAPPA-B; LECTIN-LIKE; OX-LDL; KNOCKOUT MICE
AB Lectin-like oxidized LDL (oxLDL) receptor-1 (LOX-1, also known as OLR-1), is a class E scavenger receptor that mediates the uptake of oxLDL by vascular cells. LOX-1 is involved in endothelial dysfunction, monocyte adhesion, the proliferation, migration, and apoptosis of smooth muscle cells, foam cell formation, platelet activation, as well as plaque instability; all of these events are critical in the pathogenesis of atherosclerosis. These LOX-1-dependent biological processes contribute to plaque instability and the ultimate clinical sequelae of plaque rupture and life-threatening tissue ischemia. Administration of anti-LOX-1 antibodies inhibits atherosclerosis by decreasing these cellular events. Over the past decade, multiple drugs including naturally occurring antioxidants, statins, antiinflammatory agents, antihypertensive and antihyperglycemic drugs have been demonstrated to inhibit vascular LOX-1 expression and activity. Therefore, LOX-1 represents an attractive therapeutic target for the treatment of human atherosclerotic diseases. This review aims to integrate the current understanding of LOX-1 signaling, regulation of LOX-1 by vasculoprotective drugs, and the importance of LOX-1 in the pathogenesis of atherosclerosis.
C1 [Xu, Suowen; Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Xu, Suowen; Liu, Peiqing] Sun Yat Sen Univ, Sch Pharmaceut Sci, Dept Pharmacol & Toxicol, Guangzhou 510006, Guangdong, Peoples R China.
[Ogura, Sayoko] Nihon Univ, Fac Med, Surugadai Hosp, Chiyoda Ku, Tokyo 1018309, Japan.
[Chen, Jiawei] Fudan Univ, Dept Anesthesiol, Shanghai Canc Ctr, Shanghai 200032, Peoples R China.
[Little, Peter J.] RMIT Univ, Hlth Innovat Res Inst, Sch Med Sci, Discipline Pharm, Melbourne, Vic 3083, Australia.
[Little, Peter J.] RMIT Univ, Hlth Innovat Res Inst, Diabet Complicat Grp, Melbourne, Vic 3083, Australia.
RP Xu, SW (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM suo-wen.xu@nih.gov; liupq@mail.sysu.edu.cn
RI Little, Peter/F-9865-2015
OI Little, Peter/0000-0002-0335-3835
FU National Natural Science Foundation of China [81072641]; NSFC-CIHR
CHINA-CANADA Joint Health Research Initiative Proposal [30811120434];
National Science and Technology Major Project of China "Key New Drug
Creation and Manufacturing Program'' [2009ZX09102-152, 2011ZX09401-307];
Natural Science Foundation of Guangdong Province [S2011030003190]; Major
Project of Guangdong Province [2008A030201013, 2012A080201007]; Major
Project of Department of Education of Guangdong Province [CXZD1006];
National Health and Medical Research Council of Australia; National
Heart Foundation of Australia; Diabetes Australia Research Trust;
Ministry of Education of China
FX This work was supported by grants from the National Natural Science
Foundation of China (No. 81072641); NSFC-CIHR CHINA-CANADA Joint Health
Research Initiative Proposal (No. 30811120434); National Science and
Technology Major Project of China "Key New Drug Creation and
Manufacturing Program'' (No. 2009ZX09102-152, 2011ZX09401-307); Team
Item of Natural Science Foundation of Guangdong Province (No.
S2011030003190); Major Project of Guangdong Province (No.
2008A030201013, No. 2012A080201007); Major Project of Department of
Education of Guangdong Province (No. CXZD1006). General work in this
area has also been supported by grants from the National Health and
Medical Research Council of Australia, National Heart Foundation of
Australia and Diabetes Australia Research Trust. Suowen Xu received the
"New Investigator Award'' from Ministry of Education of China. We
gratefully acknowledge the contributions of investigators dedicated to
the LOX-1 field, and apologize to those investigators whose work we
could not cite owing to space limitations.
NR 114
TC 47
Z9 50
U1 0
U2 32
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD AUG
PY 2013
VL 70
IS 16
BP 2859
EP 2872
DI 10.1007/s00018-012-1194-z
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 189GN
UT WOS:000322255500004
PM 23124189
ER
PT J
AU Matharu, K
Zarember, KA
Marciano, BE
Kuhns, DB
Spalding, C
Garofalo, M
Dimaggio, T
Estwick, T
Huang, CY
Fink, D
Priel, DL
Fleisher, TA
Holland, SM
Malech, HL
Gallin, JI
AF Matharu, Kabir
Zarember, Kol A.
Marciano, Beatriz E.
Kuhns, Douglas B.
Spalding, Christine
Garofalo, Mary
Dimaggio, Thomas
Estwick, Tyra
Huang, Chiung-Yu
Fink, Danielle
Priel, Debra L.
Fleisher, Thomas A.
Holland, Steven M.
Malech, Harry L.
Gallin, John I.
TI B-cell activating factor (BAFF) is elevated in Chronic Granulomatous
Disease
SO CLINICAL IMMUNOLOGY
LA English
DT Article
DE Chronic Granulomatous Disease; B-cell activating factor; Inflammation
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; HUMAN POLYMORPHONUCLEAR LEUKOCYTES;
LYMPHOCYTE STIMULATOR; SJOGRENS-SYNDROME; MYELOMA CELLS; SERUM; APRIL;
EXPRESSION; MEMORY; BLYS
AB Chronic Granulomatous Disease (CGD) is an inherited defect in superoxide production Leading to life-threatening infections, granulomas, and, possibly, abnormal immunoglobulin concentrations. We investigated whether factors controlling antibody production, such as B-cell activating factor (BAFF), were altered in CGD. CGD subjects had significantly increased mean (2.3-fold, p < 0.0001) plasma concentrations of BAFF compared to healthy donors. Patients on IFN-gamma treatment had significantly higher BAFF concentrations compared with CGD patients not taking IFN-gamma (1.6-fold, p < 0.005). Leukocytes from CGD subjects produced normal amounts of BAFF in response to IFN-gamma or G-CSF in vitro. Expression of BAFF-R and TACI was significantly reduced on CGD B cells. Elevated BAFF in CGD correlated with CRP (R = 0.44), ESR (R = 0.49), and IgM(R = 0.47) and increased rapidly in healthy subjects following intravenous endotoxin administration. These findings suggest that elevated BAFF in CGD subjects and healthy donors is a consequence of acute and chronic inflammation. Published by Elsevier Inc.
C1 [Matharu, Kabir; Zarember, Kol A.; Garofalo, Mary; Dimaggio, Thomas; Estwick, Tyra; Malech, Harry L.; Gallin, John I.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
[Matharu, Kabir] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Marciano, Beatriz E.; Spalding, Christine; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Kuhns, Douglas B.; Fink, Danielle; Priel, Debra L.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Clin Serv Program, Appl Dev Res Directorate, Frederick, MD USA.
[Huang, Chiung-Yu] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Fleisher, Thomas A.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Gallin, JI (reprint author), 10 Ctr Dr,RM 6-2551,MSC 1504, Bethesda, MD 20892 USA.
EM jgallin@cc.nih.gov
OI Malech, Harry/0000-0001-5874-5775
FU NIH; National Institute of Allergy and Infectious Diseases; Howard
Hughes Medical Institute
FX This research was supported by the Intramural Research Program of the
NIH and National Institute of Allergy and Infectious Diseases and the
Howard Hughes Medical Institute.
NR 45
TC 5
Z9 5
U1 1
U2 11
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1521-6616
J9 CLIN IMMUNOL
JI Clin. Immunol.
PD AUG
PY 2013
VL 148
IS 2
BP 258
EP 264
DI 10.1016/j.clim.2013.05.007
PG 7
WC Immunology
SC Immunology
GA 187FC
UT WOS:000322101300013
PM 23773925
ER
PT J
AU Degiuseppe, JI
Beltramino, JC
Millan, A
Stupka, JA
Parra, GI
AF Degiuseppe, J. I.
Beltramino, J. C.
Millan, A.
Stupka, J. A.
Parra, G. I.
TI Complete genome analyses of G4P[6] rotavirus detected in Argentinean
children with diarrhoea provides evidence of interspecies transmission
from swine
SO CLINICAL MICROBIOLOGY AND INFECTION
LA English
DT Article
DE Argentina; G4P[6]; interspecies transmission; porcine-like strains;
rotavirus
ID PORCINE ROTAVIRUS; PHYLOGENETIC ANALYSIS; STRAINS; CLASSIFICATION; GENES
AB Rotaviruses are dynamic pathogens that have been shown to infect multiple species. In 2006, two G4P[6] rotavirus strains with porcine characteristics were detected in Santa Fe, Argentina. To further characterize and determine the origin of these strains, nearly the full length of their genome was sequenced. While most of the genome segments were from porcine origin, the two strains grouped in different phylogenetic clusters in five out of the 11 genes, suggesting two independent interspecies transmission events. This study expands our knowledge of G4 rotavirus and reinforces the use of complete genome analyses as a key tool for diversity and evolution mechanicisms.
C1 [Degiuseppe, J. I.; Stupka, J. A.] ANLIS Dr Carlos G Malbran, Inst Nacl Enfermedades Infecciosas, RA-1281 Buenos Aires, DF, Argentina.
[Parra, G. I.] Univ Nacl Asuncion, Inst Invest Ciencias Salud, Asuncion, Paraguay.
[Parra, G. I.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Degiuseppe, JI (reprint author), ANLIS Dr Carlos G Malbran, Inst Nacl Enfermedades Infecciosas, 563 Velez Sarsfield Ave, RA-1281 Buenos Aires, DF, Argentina.
EM jdegiuseppe@anlis.gov.ar
OI Parra, Gabriel/0000-0002-1102-4740
NR 15
TC 14
Z9 14
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1198-743X
J9 CLIN MICROBIOL INFEC
JI Clin. Microbiol. Infect.
PD AUG
PY 2013
VL 19
IS 8
BP E367
EP E371
DI 10.1111/1469-0691.12216
PG 5
WC Infectious Diseases; Microbiology
SC Infectious Diseases; Microbiology
GA 182RP
UT WOS:000321761900006
PM 23586655
ER
PT J
AU Turkbey, B
Mena, E
Aras, O
Garvey, B
Grant, K
Choyke, PL
AF Turkbey, B.
Mena, E.
Aras, O.
Garvey, B.
Grant, K.
Choyke, P. L.
TI Functional and Molecular Imaging: Applications for Diagnosis and Staging
of Localised Prostate Cancer
SO CLINICAL ONCOLOGY
LA English
DT Article
DE Localization; MET; PET/CT; prostate cancer; staging
ID DIFFUSION-WEIGHTED MRI; POSITRON-EMISSION-TOMOGRAPHY; CONTRAST-ENHANCED
MRI; MULTIPARAMETRIC MAGNETIC-RESONANCE; IN-VIVO ASSESSMENT; ENDORECTAL
MR; 3 T; RADICAL PROSTATECTOMY; EXTRACAPSULAR EXTENSION; C-11-CHOLINE
PET/CT
AB Prostate cancer is currently the most common solid organ cancer type among men in the Western world. Currently, all decision-making algorithms and nomograms rely on demographics, clinicopathological data and symptoms. Such an approach can easily miss significant cancers while detecting many insignificant cancers. In this review, novel functional and molecular imaging techniques used in the diagnosis and staging of localised prostate cancer and their effect on treatment decisions are discussed. Published by Elsevier Ltd on behalf of The Royal College of Radiologists.
C1 [Turkbey, B.; Mena, E.; Garvey, B.; Grant, K.; Choyke, P. L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Aras, O.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA.
RP Turkbey, B (reprint author), NCI, Mol Imaging Program, 10 Ctr Dr,MSC 1182 Bldg 10,Room B3B69, Bethesda, MD 20892 USA.
EM turkbeyi@mail.nih.gov
FU Peter Michael Foundation
FX This publication was made possible in part by a Pelican Fellowship grant
to Dr Omer Aras, supported by The Peter Michael Foundation.
NR 93
TC 9
Z9 9
U1 0
U2 10
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0936-6555
EI 1433-2981
J9 CLIN ONCOL-UK
JI Clin. Oncol.
PD AUG
PY 2013
VL 25
IS 8
SI SI
BP 451
EP 460
DI 10.1016/j.clon.2013.05.001
PG 10
WC Oncology
SC Oncology
GA 201ZV
UT WOS:000323182600002
PM 23722008
ER
PT J
AU Passamani, E
AF Passamani, E.
TI Educational Challenges in Implementing Genomic Medicine
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Editorial Material
ID CODEINE
AB Clinical medicine is about to embark on an exciting, although harrowing, period of innovation, the result of astonishing advances in genomic science. The current workforce-physicians, nurses, pharmacists, and others-will soon need to adapt to substantial change, driven by genomics, in diagnostic and therapeutic strategies. If errors of omission and commission are to be prevented, sustained efforts in workforce education will be needed on the part of medical schools, training programs, and professional societies.
C1 NHGRI, Div Policy Commun & Educ, Bethesda, MD 20892 USA.
RP Passamani, E (reprint author), NHGRI, Div Policy Commun & Educ, Bethesda, MD 20892 USA.
EM eugene.passamani@nih.gov
NR 10
TC 10
Z9 10
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD AUG
PY 2013
VL 94
IS 2
BP 192
EP 195
DI 10.1038/clpt.2013.38
PG 5
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 186SG
UT WOS:000322064400012
PM 23872834
ER
PT J
AU Hoffman, AF
Lupica, CR
AF Hoffman, Alexander F.
Lupica, Carl R.
TI Synaptic Targets of Delta(9)-Tetrahydrocannabinol in the Central Nervous
System
SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
LA English
DT Article
ID LONG-TERM POTENTIATION; VENTRAL TEGMENTAL AREA; CB1 CANNABINOID
RECEPTOR; MIDBRAIN DOPAMINE NEURONS; NUCLEUS-ACCUMBENS; CHRONIC
DELTA-9-TETRAHYDROCANNABINOL; HIPPOCAMPAL-NEURONS; RAT-BRAIN;
ENDOCANNABINOID RELEASE; GLUTAMATERGIC SYNAPSES
AB The availability of potent synthetic agonists for cannabinoid receptors has facilitated our understanding of cannabinoid actions on synaptic transmission in the central nervous system. Moreover, the ability of these compounds to inhibit neurotransmitter release at many central synapses is thought to underlie most of the behavioral effects of cannabinoid agonists. However, despite the widespread use and misuse of marijuana, and recognition of its potential adverse psychological effects in humans, comparatively few studies have examined the actions of its primary psychoactive constituent, Delta(9)-tetrahydrocannabinol (THC), at well-defined synaptic pathways. Here we examine the recent literature describing the effects of acute and repeated THC exposure on synaptic function in several brain regions and explore the importance of these neurobiological actions of THC in drug addiction.
C1 [Hoffman, Alexander F.; Lupica, Carl R.] NIDA, US Dept HHS, NIH, Intramural Res Program,Electrophysiol Res Sect, Baltimore, MD 21224 USA.
RP Lupica, CR (reprint author), NIDA, US Dept HHS, NIH, Intramural Res Program,Electrophysiol Res Sect, Baltimore, MD 21224 USA.
EM clupica@intra.nida.nih.gov
FU U.S. Department of Health and Human Services; National Institutes of
Health; National Institute on Drug Abuse Intramural Research Program;
National Institute on Drug Abuse [DA14263]
FX This work is supported by the U.S. Department of Health and Human
Services, The National Institutes of Health, and the National Institute
on Drug Abuse Intramural Research Program, and earlier studies were
supported by a grant from the National Institute on Drug Abuse (DA14263
to C.R.L.).
NR 109
TC 0
Z9 0
U1 0
U2 18
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1943-0264
J9 CSH PERSPECT BIOL
JI Cold Spring Harbor Perspect. Biol.
PD AUG
PY 2013
VL 5
IS 8
AR a012203
DI 10.1101/cshperspect.a012237
PG 14
WC Cell Biology
SC Cell Biology
GA 200EY
UT WOS:000323051800014
ER
PT J
AU Kiriakis, J
Gaich, N
Johnston, SC
Kitterman, D
Rosenblum, D
Salberg, L
Rifkind, A
AF Kiriakis, James
Gaich, Nicholas
Johnston, S. Claiborne
Kitterman, Darlene
Rosenblum, Daniel
Salberg, Libby
Rifkind, Adam
TI Observational Study of Contracts Processing at 29 CTSA Sites
SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE
LA English
DT Article
DE contracts; clinical research management; clinical trials; public private
partnerships; CTSA Consortium; virtual national laboratory
ID CLINICAL-TRIALS
AB We measured contracts final negotiation (FN) and full execution (FE) times using shared definitions in a prospective observational study of management of contracts for clinical trials at 29 CTSA institutions. Median FN and FE times were reached in 39 and 91 days, respectively; mean times for FN and FE were 55 and 103 days, respectively. Individual site medians ranged from 3 to 116 days for FN and 34 to 197 days for FE. The use of master agreements (MAs) and previously negotiated terms (PNTs) was associated with significant reduction of FN times by a mean of 33 days (p < 0) and 22 days (p < 0.001), respectively. PNTs, but not MAs, were associated with significantly reduced FE time (22 days, p < 0.007). Gap analysis revealed a gap of 22 days between contracts negotiation and Institutional Review Board (IRB) review and intervals of 33 days (contracts) and 48 days (IRB review) during which the process steps were being conducted alone, suggesting a potential benefit with parallel processing. These baseline data support a plan to investigate root causes of prolonged study start-up time by examining causes of variation and outliers.
C1 [Kiriakis, James] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Gaich, Nicholas] Stanford Univ, Stanford, CA 94305 USA.
[Johnston, S. Claiborne] Univ Calif San Francisco, Clin & Translat Sci Inst, San Francisco, CA 94143 USA.
[Kitterman, Darlene] Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Inst, Portland, OR 97201 USA.
[Rosenblum, Daniel] NIH, Div Clin Innovat, NCATS, Bethesda, MD 20892 USA.
[Salberg, Libby] Vanderbilt Univ, Off Contracts Management, Nashville, TN 37235 USA.
[Rifkind, Adam] Univ Penn, Off Res Serv, Philadelphia, PA 19104 USA.
RP Rosenblum, D (reprint author), NIH, Div Clin Innovat, NCATS, Bldg 10, Bethesda, MD 20892 USA.
EM rosenblumd@mail.nih.gov
FU Federal funds from the National Center for Research Resources; National
Center for Advancing Translational Sciences (NCATS), National Institutes
of Health, through the Clinical and Translational Science Awards Program
(CTSA); NIH [U54TR000123-02, UL1-TR000003, UL1-TR000445, UL-1-TR000128,
UL1-TR000093, UL1-TR-000004, UL1-TR000086, UL1-TR000170, UL1-TR000439,
UL1-TR000430, UL1-TR000077, UL1-TR000457, UL1-TR000436, UL1-TR000064,
UL1-TR000006, UL1-TR000442, UL1-TR000424]; National Institutes of Health
[UL1-TR000135, UL1-TR000067, UL1-TR000083, UL1-TR000150, UL1-TR000090,
UL1-TR000042, UL1-TR000109, UL1-TR000002, UL1-TR000105, UL1-TR000371,
UL1-TR000448, UL1-TR000427, UL1-TR000142]
FX In addition to the authors, support for the study was provided by staff
at 29 CTSA sites whose institutions are listed in the supplemental
materials. This project has been funded in whole or in part with Federal
funds from the National Center for Research Resources and National
Center for Advancing Translational Sciences (NCATS), National Institutes
of Health, through the Clinical and Translational Science Awards Program
(CTSA). NIH grants: U54TR000123-02, UL1-TR000003, UL1-TR000445,
UL-1-TR000128, UL1-TR000093, UL1-TR-000004, UL1-TR000086, UL1-TR000170,
UL1-TR000439, UL1-TR000430, UL1-TR000077, UL1-TR000457, UL1-TR000436,
UL1-TR000064, UL1-TR000006, UL1-TR000442, UL1-TR000424, UL1-TR000135,
UL1-TR000067, UL1-TR000083, UL1-TR000150, UL1-TR000090, UL1-TR000042,
UL1-TR000109, UL1-TR000002, UL1-TR000105, UL1-TR000371, UL1-TR000448,
UL1-TR000427, UL1-TR000142. The manuscript was approved by the CTSA
Consortium Publications Committee.
NR 8
TC 2
Z9 2
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1752-8054
J9 CTS-CLIN TRANSL SCI
JI CTS-Clin. Transl. Sci.
PD AUG
PY 2013
VL 6
IS 4
BP 279
EP 285
DI 10.1111/cts.12073
PG 7
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 196GR
UT WOS:000322762300007
PM 23919362
ER
PT J
AU Glasgow, RE
Brownson, RC
Kessler, RS
AF Glasgow, Russell E.
Brownson, Ross C.
Kessler, Rodger S.
TI Thinking about Health-Related Outcomes: What Do We Need Evidence about?
SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE
LA English
DT Article
DE evaluation; outcomes; measures; implementation; biomarkers
ID IMPLEMENTATION FIDELITY; TRIAL; CARE; INTERVENTIONS; SUSTAINABILITY;
INDIVIDUALS; TRANSLATION; PREVENTION; PRIORITIES; FRAMEWORK
AB Background There is an urgent need for efficient, equitable interventions across the disease spectrum from prevention to palliative care. To identify and prioritize such interventions, evidence of effectiveness important to potential constituents is needed on outcomes relevant to them.
Methods To inform practice and policy, evidence is needed on actionable, harmonized outcomes which are feasible to collect in most settings and relevant to citizens, practitioners, and decision makers. We propose that increased priority should be given to certain outcomes that are infrequently collected across multiple domains.
Results A modification of a logic model of health outcomes by Proctor et al. is used to propose key domains and measures of implementation, service delivery, biomarkers, and health and functioning outcomes. Recommendations are made to give increased priority to implementation (especially reach, resource requirements/costs; and fidelity/adaptation); Institute of Medicine service delivery categories of equity and safety; and patient reported health and functioning outcomes.
Conclusions Implications of this outcomes framework include that biomarkers are not always the most important or relevant outcomes; that harmonized, pragmatic, and actionable measures are needed for each of these types of outcomes, and that significant changes in training and review of grants and publications are needed.
C1 [Glasgow, Russell E.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Brownson, Ross C.] Washington Univ, Brown Sch, Prevent Res Ctr St Louis, St Louis, MO USA.
[Brownson, Ross C.] Washington Univ, Sch Med, Div Publ Hlth Sci, St Louis, MO USA.
[Brownson, Ross C.] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO USA.
[Kessler, Rodger S.] Univ Vermont, Dept Family Med, Burlington, VT USA.
RP Glasgow, RE (reprint author), NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
EM glasgowre@mail.nih.gov
FU Centers for Disease Control and Prevention (the Prevention Research
Centers Program) [U48/DP001903]
FX We express our gratitude to Dr. Enola Proctor for her seminal work on
this measurement model and to Dr. Borsika Rabin for her work on the
definitions of many of the implementation constructs discussed. This
work was supported in part by Cooperative Agreement Number U48/DP001903
from the Centers for Disease Control and Prevention (the Prevention
Research Centers Program). The opinions expressed are those of the
authors and not necessarily those of the National Cancer Institute or
any funder.
NR 44
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PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1752-8054
J9 CTS-CLIN TRANSL SCI
JI CTS-Clin. Transl. Sci.
PD AUG
PY 2013
VL 6
IS 4
BP 286
EP 291
DI 10.1111/cts.12080
PG 6
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 196GR
UT WOS:000322762300008
PM 23919363
ER
PT J
AU Strasser, JE
Cola, PA
Rosenblum, D
AF Strasser, Jane E.
Cola, Philip A.
Rosenblum, Daniel
TI Evaluating Various Areas of Process Improvement in an Effort to Improve
Clinical Research: Discussions from the 2012 Clinical Translational
Science Award (CTSA) Clinical Research Management Workshop
SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE
LA English
DT Article
DE clinical trials; translational research; trials
AB Emphasis has been placed on assessing the efficiency of clinical and translational research as part of the National Institutes of Health (NIH) goal to improve human health. Improvements identified and implemented by individual organizations cannot address the research infrastructure needs of all clinical and translational research conducted. NIH's National Center for Advancing Translational Sciences (NCATS) has brought together 61 Clinical and Translational Science Award (CTSA) sites creating a virtual national laboratory that reflects the diversity and breadth of academic medical centers to collectively improve clinical and translational science. The annual Clinical Research Management workshop is organized by the CTSA consortium with participation from CTSA awardees, NIH, and others with an interest in clinical research management. The primary objective of the workshop is to disseminate information that improves clinical research management although the specific objectives of each workshop evolve within the consortium. The fifth annual workshop entitled Learning by doing; applying evidence-based tools to re-engineer clinical research management took place in June 2012. The primary objective of the 2012 workshop was to utilize data to evaluate, modify, and improve clinical research management. This report provides a brief summary of the workshop proceedings and the major themes discussed among the participants.
C1 [Strasser, Jane E.] Univ Cincinnati, Ctr Clin & Translat Sci & Training, Cincinnati, OH 45221 USA.
[Cola, Philip A.] Univ Hosp Case Med Ctr, Clin & Translat Sci Collaborat, Cleveland, OH USA.
[Rosenblum, Daniel] Natl Ctr Adv Translat Sci, Bethesda, MD USA.
RP Strasser, JE (reprint author), Univ Cincinnati, Ctr Clin & Translat Sci & Training, Cincinnati, OH 45221 USA.
EM Jane.strasser@uc.edu
FU NCATS [U13TR000059-04]; NCATS award
FX Yale University served as the host institution with support from NCATS
U13TR000059-04. Efforts of the authors were supported by UL1 TR000077
and UL1TR000439; efforts of the presenters are delineated on their
presentations. All of the presentations described were underwritten by
that institution's CTSA and supported by an NCATS award except for those
by Patrick Hagan and Jonathan Kagan. The contents of this publication
are solely the responsibility of the authors and do not necessarily
represent the official views of the NIH.
NR 6
TC 2
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U1 4
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1752-8054
J9 CTS-CLIN TRANSL SCI
JI CTS-Clin. Transl. Sci.
PD AUG
PY 2013
VL 6
IS 4
BP 317
EP 320
DI 10.1111/cts.12051
PG 4
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 196GR
UT WOS:000322762300014
PM 23919369
ER
PT J
AU Glen, DR
Murakami, P
Nunez, JS
AF Glen, D. R.
Murakami, P.
Nunez, J. S.
TI Symptom index P-value and symptom sensitivity index P-value to determine
symptom association between apnea and reflux in premature infants at
term
SO DISEASES OF THE ESOPHAGUS
LA English
DT Article
DE gastroesophageal reflux; multichannel intraluminal impedance-pH probe;
obstructive apnea; permutation; premature infant; simulation; temporal
association
ID CHEST-PAIN; ESOPHAGEAL; PROBABILITY; ACTIVATION; PARAMETER; REFLEXES;
AIRWAY
AB The current method to determine temporal association (TA) between reflux and symptoms is the symptom association probability (SAP), but this method has limitations due to the constraints of binning and the violation of statistical principles of the Fisher's exact test that lead to an invalid estimation of TA. The aim of this study is to develop improved methods of computing the TA between apneic and reflux events using simulation and permutation methods and to compare these to the SAP. TA was analyzed between polysomnographic obstructive apneas and multichannel intraluminal impedance (MII) reflux events. Three new numerical methods were compared to the SAP in four former premature infants with persistent apneas at term. The experimentally found association was compared to the association observed in simulated or permuted data consistent with the lack of association beyond what is expected by chance alone. Temporal association was computed based on symptom and symptom sensitivity indices, SI and SSI, with varying window of association (WA) times from 15 to 300s. The three new methods estimated P-values at varying WA that generally followed the same pattern of the SAP which had a more erratic pattern. The WA that gave the lowest P-value was approximately 120s. Each of the novel methods produced P-value results consistent with each other and the SAP yet not subject to its limitations. The variation of WA gave a temporal profile of TA providing clues to its etiology. These new metrics are called Symptom Index (SIP) and Symptom Sensitivity Index (SSIP) P-values.
C1 [Nunez, J. S.] Johns Hopkins Univ, Dept Pediat, Johns Hopkins Bayview Med Ctr, Div Neonatol,Johns Hopkins Hosp, Baltimore, MD 21218 USA.
[Glen, D. R.] NIH, Sci & Stat Comp Core, NIMH Intramural Res Program, Baltimore, MD USA.
[Murakami, P.] Johns Hopkins Univ, Johns Hopkins Biostat Ctr, Baltimore, MD USA.
RP Nunez, JS (reprint author), Johns Hopkins Bayview Med Ctr, Div Neonatol, 4940 Eastern Ave, Baltimore, MD 21224 USA.
EM jnunez4@jhmi.edu
FU National Center for Research Resources (NCRR), a component of the
National Institutes of Health (NIH) [UL1 RR 025005]; NIH Roadmap for
Medical Research
FX This publication was made possible by Grant Number UL1 RR 025005 from
the National Center for Research Resources (NCRR), a component of the
National Institutes of Health (NIH), and NIH Roadmap for Medical
Research. Its contents are solely the responsibility of the authors and
do not necessarily represent the official view of NCRR or NIH.
NR 22
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U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1120-8694
J9 DIS ESOPHAGUS
JI Dis. Esophagus
PD AUG
PY 2013
VL 26
IS 6
BP 549
EP 556
DI 10.1111/dote.12001
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 197SJ
UT WOS:000322870700001
PM 23163408
ER
PT J
AU Hulvershorn, LA
Finn, P
Hummer, TA
Leibenluft, E
Ball, B
Gichina, V
Anand, A
AF Hulvershorn, Leslie A.
Finn, Peter
Hummer, Tom A.
Leibenluft, Ellen
Ball, Brandon
Gichina, Victoria
Anand, Amit
TI Cortical activation deficits during facial emotion processing in youth
at high risk for the development of substance use disorders
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Addiction risk; Child and adolescent; ADHD; Externalizing; Neuroimaging;
Prefrontal cortex
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; CANNABIS USE DISORDER;
SCHOOL-AGE-CHILDREN; ILLEGAL DRUG-USE; ALCOHOL-USE; NEUROBEHAVIOR
DISINHIBITION; FUNCTIONAL CONNECTIVITY; DIFFICULT TEMPERAMENT; EARLY
ADOLESCENCE; MIDDLE ADULTHOOD
AB Background: Recent longitudinal studies demonstrate that addiction risk may be influenced by a cognitive, affective and behavioral phenotype that emerges during childhood. Relatively little research has focused on the affective or emotional risk components of this high-risk phenotype, including the relevant neurobiology.
Methods: Non-substance abusing youth (N=19; mean age = 12.2) with externalizing psychopathology and paternal history of a substance use disorder and demographically matched healthy comparisons (N=18; mean age = 11.9) were tested on a facial emotion matching task during functional MRI. This task involved matching faces by emotions (angry, anxious) or matching shape orientation.
Results: High-risk youth exhibited increased medial prefrontal, precuneus and occipital cortex activation compared to the healthy comparison group during the face matching condition, relative to the control shape condition. The occipital activation correlated positively with parent-rated emotion regulation impairments in the high-risk group.
Conclusions: These findings suggest a preexisting abnormality in cortical activation in response to facial emotion matching in youth at high risk for the development of problem drug or alcohol use. These cortical deficits may underlie impaired affective processing and regulation, which in turn may contribute to escalating drug use in adolescence. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
C1 [Hulvershorn, Leslie A.; Hummer, Tom A.; Ball, Brandon; Gichina, Victoria] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA.
[Finn, Peter] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA.
[Leibenluft, Ellen] NIMH, Sect Bipolar Spectrum Disorders, Intramural Res Program, Bethesda, MD USA.
[Anand, Amit] Cleveland Clin, Ctr Behav Hlth, Cleveland, OH 44106 USA.
RP Hulvershorn, LA (reprint author), 705 Riley Hosp Dr,Room 4300, Indianapolis, IN 46205 USA.
EM lhulvers@iupui.edu
RI Hulvershorn, Leslie/J-3421-2013; Anand, Amit/D-4232-2013
OI Hulvershorn, Leslie/0000-0001-5827-4889;
FU NIDA [K12 DA000357]
FX Funding for this study was provided by NIDA Grant K12 DA000357 to L.H.
Sponsors had no further role in study design; in the collection,
analysis and interpretation of data; in the writing of the report; or in
the decision to submit the paper for publication.
NR 78
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U2 17
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD AUG 1
PY 2013
VL 131
IS 3
BP 230
EP 237
DI 10.1016/j.drugalcdep.2013.05.015
PG 8
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 197MP
UT WOS:000322855600007
PM 23768841
ER
PT J
AU Sutin, AR
Evans, MK
Zonderman, AB
AF Sutin, Angelina R.
Evans, Michele K.
Zonderman, Alan B.
TI Personality traits and illicit substances: The moderating role of
poverty
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Personality traits; Conscientiousness; Substance use; Poverty; Cocaine;
Heroin
ID 5-FACTOR MODEL; SOCIOECONOMIC-STATUS; DRUG-USE; DISORDERS; ALCOHOL;
NEIGHBORHOODS; DEPENDENCE; HEALTH; METAANALYSIS; NEUROTICISM
AB Background: Illicit substances increase risk of morbidity and mortality and have significant consequences for society. Personality traits are associated with drug use; we test whether these associations vary by socioeconomic status.
Method: Participants (N = 412) from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study completed the Revised NEO Personality Inventory and self-reported use of opiates and cocaine. 50% of participants were living below 125% of the federal poverty line. Mean-level personality differences across never, former, and current opiate/cocaine users were compared. Logistic regressions compared never versus current users and interactions between personality traits and poverty status tested whether these associations varied by socioeconomic status.
Results: High Neuroticism and low Agreeableness increased risk of drug use. The association between low Conscientiousness and drug use was moderated by poverty, such that low Conscientiousness was a stronger risk factor for illicit substance use among those with relatively higher SES. For every standard deviation decrease in Conscientiousness, there was a greater than 2-fold increase in risk of illicit substance use (OR=2.15,95% CI = 1.45-3.17). Conscientiousness was unrelated to drug use among participants living below 125% of the federal poverty line.
Conclusions: Under favorable economic conditions, the tendency to be organized, disciplined, and deliberate is protective against drug use. These tendencies, however, matter less when financial resources are scarce. In contrast, those prone to emotional distress and antagonism are at greater risk for current drug use, regardless of their economic situation. Published by Elsevier Ireland Ltd.
C1 [Sutin, Angelina R.] Florida State Univ, Coll Med, Tallahassee, FL 32306 USA.
[Sutin, Angelina R.; Evans, Michele K.; Zonderman, Alan B.] NIA, Bethesda, MD 20892 USA.
RP Sutin, AR (reprint author), Florida State Univ, Coll Med, 1115 W Call St, Tallahassee, FL 32308 USA.
EM Angelina.sutin@med.fsu.edu
OI Zonderman, Alan B/0000-0002-6523-4778
FU Intramural Research Program at the National Institute on Aging
FX Funding for this study was provided by the Intramural Research Program
at the National Institute on Aging; the NIA had no further role in study
design; in the collection, analysis and interpretation of data; in the
writing of the report; or in the decision to submit the paper for
publication.
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U1 1
U2 15
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD AUG 1
PY 2013
VL 131
IS 3
BP 247
EP 251
DI 10.1016/j.drugalcdep.2012.10.020
PG 5
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 197MP
UT WOS:000322855600009
PM 23265091
ER
PT J
AU Huestis, MA
Cone, EJ
Pirnay, SO
Umbricht, A
Preston, KL
AF Huestis, M. A.
Cone, E. J.
Pirnay, S. O.
Umbricht, A.
Preston, K. L.
TI Intravenous buprenorphine and norbuprenorphine pharmacokinetics in
humans
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Buprenorphine; Norbuprenorphine; Intravenous; Pharmacokinetics
ID ABUSE LIABILITY; NALOXONE; METABOLISM; MISUSE; USERS
AB Background: Prescribed sublingual (SL) buprenorphine is sometimes diverted for intravenous (IV) abuse, but no human pharmacokinetic data are available following high-dose IV buprenorphine.
Methods: Plasma was collected for 72h after administration of placebo or 2, 4, 8, 12, or 16 mg IV buprenorphine in escalating order (single-blind, double-dummy) in 5 healthy male non-dependent opioid users. Buprenorphine and its primary active metabolite, norbuprenorphine, were quantified by liquid chromatography-tandem mass spectrometry with limits of quantitation of 0.1 mu g/L.
Results: Maximum buprenorphine concentrations (mean SE) were detected 10 min after 2, 4, 8, 12, 16 mg IV: 19.3 +/- 1.0, 44.5 +/- 4.8, 85.2 +/- 7.7, 124.6 +/- 16.6, and 137.7 +/- 18.8 mu g/L, respectively. Maximum norbuprenorphine concentrations occurred 10-15 min (3.7 +/- 0.7 mu g/L) after 16 mg IV administration.
Conclusions: Buprenorphine concentrations increased in a significantly linear dose-dependent manner up to 12 mg IV buprenorphine. Thus, previously demonstrated pharmacodynamic ceiling effects (over 2-16 mg) are not due to pharmacokinetic adaptations within this range, although they may play a role at doses higher than 12 mg. Published by Elsevier Ireland Ltd.
C1 [Huestis, M. A.] NIDA, IRP, NIH, Baltimore, MD 21224 USA.
[Cone, E. J.; Umbricht, A.] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD 21224 USA.
[Pirnay, S. O.] Expertox, Toxicol Expertise Agcy & Lab, F-75011 Paris, France.
[Preston, K. L.] NIDA, Clin Pharmacol & Therapeut Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Huestis, MA (reprint author), NIDA, IRP, NIH, 251 Bayview Blvd,Room 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
RI Preston, Kenzie/J-5830-2013
OI Preston, Kenzie/0000-0003-0603-2479
FU Intramural Research Program, NIH, National Institute on Drug Abuse
FX This study was supported by the Intramural Research Program, NIH,
National Institute on Drug Abuse. The funding source played no role in
study design; in the collection, analysis, and interpretation of data;
in the writing of the report; or in the decision to submit the paper for
publication.
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U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD AUG 1
PY 2013
VL 131
IS 3
BP 258
EP 262
DI 10.1016/j.drugalcdep.2012.11.014
PG 5
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 197MP
UT WOS:000322855600011
PM 23246635
ER
PT J
AU Jutkiewicz, EM
Rice, KC
Carroll, FI
Woods, JH
AF Jutkiewicz, Emily M.
Rice, Kenner C.
Carroll, F. Ivy
Woods, James H.
TI Patterns of nicotinic receptor antagonism II: Cardiovascular effects in
rats
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Nicotine; Nicotinic agonists; Cardiovascular effects; Rats
ID DIHYDRO-BETA-ERYTHROIDINE; ACETYLCHOLINE-RECEPTORS; DISCRIMINATIVE
STIMULUS; PHARMACOLOGICAL CHARACTERIZATION; PARTIAL AGONIST;
PARASYMPATHETIC NEURONS; CHOLINERGIC-RECEPTORS; INTRAVENOUS NICOTINE;
SMOKING-CESSATION; CIGARETTE-SMOKING
AB Background: Tobacco cessation pharmacotherapies currently are limited to nicotine itself, the partial nicotine agonists varenicline and cytisine, and the antidepressant bupropion. Compared with agonists, nicotinic antagonists such as the noncompetitive, nonselective compound mecamylamine, and the competitive, alpha 4 beta 2-preferring antagonist dihydro-beta-erythroidine (DH beta E) may be a novel approach to the treatment of tobacco smoking as both are effective antagonists of nicotine's central effects. Considering nicotinic acetylcholine receptors mediate critical peripheral effects of acetylcholine, such as cardiovascular effects, it is important to study how nicotinic antagonists would alter the cardiovascular system and the cardiovascular changes induced by nicotine.
Methods: The effects of several nicotinic agonists and antagonists on blood pressure and heart rate were measured in conscious, unrestrained rats following parenteral administration using a telemetry system.
Results: Nicotine and other nicotinic receptor agonists (epibatidine, varenicline, and cytisine) produced similar increases in blood pressure, whereas their effects on heart rate were biphasic. The cardiovascular changes were attenuated by the nonselective nicotine antagonist, mecamylamine, but the peripherally restricted antagonist hexamethonium blocked only the agonist-induced changes in blood pressure. The alpha 7-preferring antagonist, MLA, and the alpha 4 beta 2-preferring antagonist, DH beta E, were much less effective in blocking the agonist-induced cardiovascular changes, indicating that nicotine's cardiovascular effects, are due to activation at autonomic ganglia involving nicotinic receptor subtypes other than alpha 4, alpha 7, or beta 2.
Conclusions: The data indicate that the cardiovascular effects of nicotine and nicotine-like agents are mediated through receptor mechanisms that are distinct from those that mediate the central effects of nicotine. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
C1 [Jutkiewicz, Emily M.; Woods, James H.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA.
[Woods, James H.] Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA.
[Rice, Kenner C.] NIDA, Chem Biol Res Branch, Bethesda, MD 20892 USA.
[Rice, Kenner C.] NIAAA, DHHS, Bethesda, MD 20892 USA.
[Carroll, F. Ivy] RTI Int, Res Triangle Pk, NC 27709 USA.
RP Woods, JH (reprint author), Univ Michigan, Dept Pharmacol, 1301 Med Sci Res Bldg 3,1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA.
EM jhwoods@umich.edu
FU University of Michigan Tobacco Research Network; National Institutes of
Health National Institute of Drug Abuse [T32 DA007268]; National
Institute on Drug Abuse; National Institute on Alcohol Abuse and
Alcoholism
FX This research and preparation of the manuscript was supported by grants
from the University of Michigan Tobacco Research Network and National
Institutes of Health National Institute of Drug Abuse [T32 DA007268].
NIDA had no further role in study design; in the collection, analysis,
and interpretation of data; in the writing of the report; or in the
decision to submit the paper for publication. Its contents are solely
the responsibility of the authors and do not necessarily represent the
official views of NIDA. A portion of this work was also supported by the
Intramural Research Programs of the National Institute on Drug Abuse and
the National Institute on Alcohol Abuse and Alcoholism.
NR 70
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PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD AUG 1
PY 2013
VL 131
IS 3
BP 284
EP 297
DI 10.1016/j.drugalcdep.2012.12.021
PG 14
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 197MP
UT WOS:000322855600015
PM 23333294
ER
PT J
AU Choi, EY
Rosen, BD
Fernandes, VRS
Yan, RT
Yoneyama, K
Donekal, S
Opdahl, A
Almeida, ALC
Wu, CO
Gomes, AS
Bluemke, DA
Lima, JAC
AF Choi, Eui-Young
Rosen, Boaz D.
Fernandes, Veronica R. S.
Yan, Raymond T.
Yoneyama, Kihei
Donekal, Sirisha
Opdahl, Anders
Almeida, Andre L. C.
Wu, Colin O.
Gomes, Antoinette S.
Bluemke, David A.
Lima, Joao A. C.
TI Prognostic value of myocardial circumferential strain for incident heart
failure and cardiovascular events in asymptomatic individuals: the
Multi-Ethnic Study of Atherosclerosis
SO EUROPEAN HEART JOURNAL
LA English
DT Article
DE Myocardial function; Heart failure; Cardiovascular events
ID VENTRICULAR SYSTOLIC DYSFUNCTION; PRESERVED EJECTION FRACTION;
MAGNETIC-RESONANCE; DISEASE INSIGHTS; PREDICTOR; MECHANICS; MESA; MASS
AB Aims Left ventricular (LV) circumferential strain (Ecc) is a sensitive index of regional myocardial function. Currently, no studies have assessed its prognostic value in general population. We sought to investigate whether Ecc has a prognostic value for predicting incident heart failure (HF) and other major cardiovascular events in asymptomatic individuals without a history of previous cardiovascular diseases.
Methods and results We, prospectively, assessed incident HF and atherosclerotic events during a 5.5 1.3-year period in 1768 asymptomatic individuals aged 4584 (mean age 65 years; 47 female) who underwent tagged magnetic resonance imaging for strain determination. During the follow-up period, 39 (2.2) participants experienced incident HF and 108 (6.1) participants had atherosclerotic cardiovascular events. Average of peak Ecc of 12-LV segments (Ecc-global) and mid-slice (Ecc-mid) was 17.0 2.4 and 17.5 2.7, respectively. Participants with average absolute Ecc-mid lower than 16.9 had a higher cumulative hazard of incident HF (log-rank test, P 0.001). In cox regression analysis, Ecc-mid predicted incident HF independent of age, diabetes status, hypertension, interim myocardial infarction, LV mass index, and LV ejection fraction (hazard ratio 1.15 per 1, 95 CI: 1.011.31, P 0.03). This relationship remained significant after adjustment for LV-end-systolic wall stress into covariates. In addition, by adding Ecc-mid to risk factors, LV ejection fraction, and the LV mass index, both the global (2) value (76.6 vs. 82.4, P 0.04) and category-less net-reclassification index (P 0.01, SE 0.18, z 2.53) were augmented for predicting HF. Circumferential strain was also significantly related to the composite atherosclerotic cardiovascular events, but its relationship was attenuated after introducing the LV mass index.
Conclusion Circumferential shortening provides robust, independent, and incremental predictive value for incident HF in asymptomatic subjects without any history of previous clinical cardiovascular disease.
C1 [Choi, Eui-Young; Yan, Raymond T.; Yoneyama, Kihei; Donekal, Sirisha; Opdahl, Anders; Almeida, Andre L. C.; Lima, Joao A. C.] Johns Hopkins Univ, Baltimore, MD USA.
[Choi, Eui-Young] Yonsei Univ, Coll Med, Seoul, South Korea.
[Rosen, Boaz D.] Univ Utah, Sch Med, Salt Lake City, UT USA.
[Fernandes, Veronica R. S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Wu, Colin O.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Gomes, Antoinette S.] UCLA Sch Med, Los Angeles, CA USA.
[Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Lima, Joao A. C.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
RP Lima, JAC (reprint author), Johns Hopkins Univ, Baltimore, MD USA.
EM jlima@jhmi.edu
RI Opdahl, Anders/I-7580-2015;
OI Opdahl, Anders/0000-0002-0599-592X; Bluemke, David/0000-0002-8323-8086
FU NIH [N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162,
N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167,
N01-HC-95168, N01-HC-95169]; NCRR [UL1-RR-024156, UL1-RR-025005]
FX This research was supported by contracts N01-HC-95159 through
N01-HC-95169 from the NIH and by grants UL1-RR-024156 and UL1-RR-025005
from NCRR.
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U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
J9 EUR HEART J
JI Eur. Heart J.
PD AUG
PY 2013
VL 34
IS 30
BP 2354
EP 2361
DI 10.1093/eurheartj/eht133
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 199KV
UT WOS:000322994300009
PM 23644181
ER
PT J
AU McDannald, MA
Setlow, B
Holland, PC
AF McDannald, Michael A.
Setlow, Barry
Holland, Peter C.
TI Effects of ventral striatal lesions on first- and second-order
appetitive conditioning
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE conditioned reinforcement; incentive learning; nucleus accumbens; rat
ID NUCLEUS-ACCUMBENS CORE; BASOLATERAL AMYGDALA; NEURAL SYSTEMS; RATS;
BEHAVIOR; EXPRESSION; STIMULUS; FOOD; REINFORCEMENT; DETERMINANT
AB Rats with bilateral lesions of the ventral striatal nucleus accumbens failed to acquire Pavlovian second-order conditioning to auditory stimuli paired with visual stimuli that had previously received first-order pairings with food. This deficit in second-order conditioning was specific to learning driven by incentive properties of the first-order cues, and was observed whether the first-order training had occurred prior to or after lesion surgery. Lesions also produced deficits in the display of conditioned responses to the first-order conditioned stimulus, but only when they were made after first-order training. These results suggest a specific role for the ventral striatum in acquiring and expressing incentive properties of conditioned stimuli through second-order conditioning, as well as a more general role in expressing previously acquired Pavlovian conditioned responses.
C1 [McDannald, Michael A.] NIDA, Intramural Res Program, Baltimore, MD USA.
[Setlow, Barry] Univ Florida, Dept Psychiat, Gainesville, FL 32611 USA.
[Holland, Peter C.] Johns Hopkins Univ, Dept Psychol & Brain Sci, Baltimore, MD 21218 USA.
RP Holland, PC (reprint author), Johns Hopkins Univ, Dept Psychol & Brain Sci, Baltimore, MD 21218 USA.
EM pch@jhu.edu
FU US National Institutes of Health [MH53667]
FX This research was supported in part by grant MH53667 from the US
National Institutes of Health. The authors report no conflicts of
interest.
NR 33
TC 5
Z9 5
U1 2
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0953-816X
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD AUG
PY 2013
VL 38
IS 4
BP 2589
EP 2599
DI 10.1111/ejn.12255
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 202EA
UT WOS:000323195100009
PM 23691939
ER
PT J
AU Maroun, M
Ioannides, PJ
Bergman, KL
Kavushansky, A
Holmes, A
Wellman, CL
AF Maroun, Mouna
Ioannides, Pericles J.
Bergman, Krista L.
Kavushansky, Alexandra
Holmes, Andrew
Wellman, Cara L.
TI Fear extinction deficits following acute stress associate with increased
spine density and dendritic retraction in basolateral amygdala neurons
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE amygdala; dendritic spine; emotional learning; rat
ID MEDIAL PREFRONTAL CORTEX; ANTERIOR CINGULATE CORTEX; SINGLE-PROLONGED
STRESS; LONG-TERM; CONTEXTUAL FEAR; UNCONTROLLABLE STRESS; INFRALIMBIC
CORTEX; D-CYCLOSERINE; RAT; HIPPOCAMPAL
AB Stress-sensitive psychopathologies such as post-traumatic stress disorder are characterized by deficits in fear extinction and dysfunction of corticolimbic circuits mediating extinction. Chronic stress facilitates fear conditioning, impairs extinction, and produces dendritic proliferation in the basolateral amygdala (BLA), a critical site of plasticity for extinction. Acute stress impairs extinction, alters plasticity in the medial prefrontal cortex-to-BLA circuit, and causes dendritic retraction in the medial prefrontal cortex. Here, we examined extinction learning and basolateral amygdala pyramidal neuron morphology in adult male rats following a single elevated platform stress. Acute stress impaired extinction acquisition and memory, and produced dendritic retraction and increased mushroom spine density in basolateral amygdala neurons in the right hemisphere. Unexpectedly, irrespective of stress, rats that underwent fear and extinction testing showed basolateral amygdala dendritic retraction and altered spine density relative to non-conditioned rats, particularly in the left hemisphere. Thus, extinction deficits produced by acute stress are associated with increased spine density and dendritic retraction in basolateral amygdala pyramidal neurons. Furthermore, the finding that conditioning and extinction as such was sufficient to alter basolateral amygdala morphology and spine density illustrates the sensitivity of basolateral amygdala morphology to behavioral manipulation. These findings may have implications for elucidating the role of the amygdala in the pathophysiology of stress-related disorders.
C1 [Maroun, Mouna; Kavushansky, Alexandra] Univ Haifa, Fac Nat Sci, Sagol Dept Neurobiol, IL-31999 Haifa, Israel.
[Ioannides, Pericles J.; Wellman, Cara L.] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA.
[Ioannides, Pericles J.; Wellman, Cara L.] Indiana Univ, Ctr Integrat Study Anim Behav, Bloomington, IN USA.
[Bergman, Krista L.] Indiana Univ, Sch Med, Bloomington, IN USA.
[Holmes, Andrew] NIAAA, Lab Behav & Genom Neurosci, NIH, Bethesda, MD USA.
RP Maroun, M (reprint author), Univ Haifa, Fac Nat Sci, Sagol Dept Neurobiol, IL-31999 Haifa, Israel.
EM mouna.maroun@gmail.com; wellmanc@indiana.edu
FU US-Israel Binational Science Foundation [2007096]; Intramural Research
Program of the National Institute on Alcoholism and Alcohol Abuse
[Z01-AA000411]
FX This work was supported by the US-Israel Binational Science Foundation
(grant number 2007096 to A. Holmes, M. Maroun, and C. L. Wellman) and
the Intramural Research Program of the National Institute on Alcoholism
and Alcohol Abuse (Z01-AA000411 to A. Holmes).
NR 67
TC 28
Z9 28
U1 2
U2 21
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0953-816X
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD AUG
PY 2013
VL 38
IS 4
BP 2611
EP 2620
DI 10.1111/ejn.12259
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 202EA
UT WOS:000323195100011
PM 23714419
ER
PT J
AU Kitade, M
Factor, VM
Andersen, JB
Tomokuni, A
Kaji, K
Akita, H
Holczbauer, A
Seo, D
Marquardt, JU
Conner, EA
Lee, SB
Lee, YH
Thorgeirsson, SS
AF Kitade, Mitsuteru
Factor, Valentina M.
Andersen, Jesper B.
Tomokuni, Akira
Kaji, Kosuke
Akita, Hirofumi
Holczbauer, Agnes
Seo, Daekwan
Marquardt, Jens U.
Conner, Elizabeth A.
Lee, Seung-Bum
Lee, Yun-Han
Thorgeirsson, Snorri S.
TI Specific fate decisions in adult hepatic progenitor cells driven by MET
and EGFR signaling
SO GENES & DEVELOPMENT
LA English
DT Article
DE liver progenitor cells; MET; EGFR; lineage commitment
ID HEPATOCYTE GROWTH-FACTOR; EFFICIENT LIVER-REGENERATION; PLURIPOTENT
STEM-CELLS; BILE-DUCT DEVELOPMENT; OVAL CELLS; ALAGILLE-SYNDROME; FACTOR
RECEPTOR; TYROSINE KINASE; HUMAN JAGGED1; FACTOR-ALPHA
AB The relative contribution of hepatocyte growth factor (HGF)/MET and epidermal growth factor (EGF)/EGF receptor (EGFR), two key signal transduction systems in the normal and diseased liver, to fate decisions of adult hepatic progenitor cells (HPCs) has not been resolved. Here, we developed a robust culture system that permitted expansion and genetic manipulation of cells capable of multilineage differentiation in vitro and in vivo to examine the individual roles of HGF/MET and EGF/EGFR in HPC self-renewal and binary cell fate decision. By employing loss-of-function and rescue experiments in vitro, we showed that both receptors collaborate to increase the self-renewal of HPCs through activation of the extracellular signal-regulated kinase (ERK) pathway. MET was a strong inducer of hepatocyte differentiation by activating AKT and signal transducer and activator of transcription (STAT3). Conversely, EGFR selectively induced NOTCH1 to promote cholangiocyte specification and branching morphogenesis while concomitantly suppressing hepatocyte commitment. Furthermore, unlike the deleterious effects of MET deletion, the liver-specific conditional loss of Egfr facilitated rather than suppressed progenitor-mediated liver regeneration by switching progenitor cell differentiation toward hepatocyte lineage. These data provide new insight into the mechanisms regulating the stemness properties of adult HPCs and reveal a previously unrecognized link between EGFR and NOTCH1 in directing cholangiocyte differentiation.
C1 [Kitade, Mitsuteru; Factor, Valentina M.; Andersen, Jesper B.; Tomokuni, Akira; Kaji, Kosuke; Akita, Hirofumi; Holczbauer, Agnes; Seo, Daekwan; Marquardt, Jens U.; Conner, Elizabeth A.; Lee, Seung-Bum; Lee, Yun-Han; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
EM snorri_thorgeirsson@nih.gov
OI Andersen , Jesper B/0000-0003-1760-5244
FU Intramural Research Program of the NIH, National Cancer Institute
FX We are grateful for a kind gift of EpCAM antibody from Dr. Atsushi
Miyajima, Tokyo University. We thank B. Taylor and S. Banerjee for
assistance with flow-cytometry, S. Garfield and P. Mannan for help with
imaging, and T. Hoang and A. Ton for technical assistance. This work was
supported by the Intramural Research Program of the NIH, National Cancer
Institute.
NR 71
TC 18
Z9 18
U1 0
U2 7
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
J9 GENE DEV
JI Genes Dev.
PD AUG 1
PY 2013
VL 27
IS 15
BP 1706
EP 1717
DI 10.1101/gad.214601.113
PG 12
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 195PN
UT WOS:000322716000008
PM 23913923
ER
PT J
AU Lynch, JA
Khoury, MJ
Borzecki, A
Cromwell, J
Hayman, LL
Ponte, PR
Miller, GA
Lathan, CS
AF Lynch, Julie A.
Khoury, Muin J.
Borzecki, Ann
Cromwell, Jerry
Hayman, Laura L.
Ponte, Pat Reid
Miller, Glenn A.
Lathan, Christopher S.
TI Utilization of epidermal growth factor receptor (EGFR) testing in the
United States: a case study of T3 translational research
SO GENETICS IN MEDICINE
LA English
DT Article
DE dissemination and implementation; EGFR assay; equity in access; lung
cancer genomics; T3 translation
ID CELL LUNG-CANCER; AFRICAN-AMERICANS; MUTATIONS; GEFITINIB; GENOMICS;
FREQUENCY; MEDICINE; SURGERY; RISK; CARE
AB Purpose: We examined hospital use of the epidermal growth factor receptor assay in patients with lung cancer in the United States. Our goal was to inform the development of a model to predict phase 3 translation of guideline-directed molecular diagnostic tests.
Methods: This was a retrospective observational study. Using logistic regression, we analyzed the association between hospitals' institutional and regional characteristics and the likelihood that an epidermal growth factor receptor assay would be ordered.
Results: Significant institutional predictors included affiliation with an academic medical center (odds ratio, 1.48; 95% confidence interval, 1.20-1.83), participation in a National Cancer Institute clinical research cooperative group (odds ratio, 2.06, 1.66-2.55), and availability of positron emission tomography scan (odds ratio, 1.44, 1.07-1.94) and cardiothoracic surgery (odds ratio, 1.90, 1.52-2.37) services. Significant regional predictors included metropolitan county (odds ratio, 2.08, 1.48-2.91), population with above-average education (odds ratio, 1.46, 1.09-1.96), and population with above-average income (odds ratio, 1.46, 1.04-2.05). Distance from a National Cancer Institute cancer center was a negative predictor (odds ratio, 0.996, 0.995-0.998), with a 34% decrease in likelihood for every 100 miles.
Conclusion: In 2010, only 12% of US acute-care hospitals ordered the epidermal growth factor receptor assay, suggesting that most patients with lung cancer did not have access to this test. This case study illustrated the need for: (i) increased dissemination and implementation research, and (ii) interventions to improve adoption of guideline-directed molecular diagnostic tests by community hospitals.
C1 [Lynch, Julie A.] Univ Massachusetts, Vet Hlth Adm, Boston, MA 02125 USA.
[Lynch, Julie A.; Ponte, Pat Reid; Lathan, Christopher S.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Khoury, Muin J.] NCI, Off Publ Hlth Genom, CDC, Epidemiol & Genom Res Program, Bethesda, MD 20892 USA.
[Lynch, Julie A.; Borzecki, Ann] Vet Hlth Adm, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA.
[Cromwell, Jerry; Hayman, Laura L.] Univ Massachusetts, Boston, MA 02125 USA.
[Cromwell, Jerry] Res Triangle Inst, Boston, MA USA.
[Miller, Glenn A.] Genzyme Genet, Santa Fe, NM USA.
RP Lynch, JA (reprint author), Univ Massachusetts, Vet Hlth Adm, Harbor Campusol, Boston, MA 02125 USA.
EM Julie.Lynch@va.gov
FU Center for Health Quality, Outcomes and Economic Research, a Veterans
Administration Health Services Research and Development Center of
Excellence; Department of Education GAANN [P200A060243]; National
Institute of Health [DFCI/UMB U54 CA156734-01]; Susan G. Komen
Foundation; Lynch Foundation
FX J.A.L. has received funding from the Center for Health Quality, Outcomes
and Economic Research, a Veterans Administration Health Services
Research and Development Center of Excellence; Department of Education
GAANN #P200A060243; National Institute of Health DFCI/UMB U54
CA156734-01, Susan G. Komen Foundation, and the Lynch Foundation.
Methodology and preliminary results were previously presented as a
poster at the 10th International Congress on Targeted Anticancer
Therapies, Amsterdam, 8-10 March 2012
NR 39
TC 13
Z9 13
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
J9 GENET MED
JI Genet. Med.
PD AUG
PY 2013
VL 15
IS 8
BP 630
EP 638
DI 10.1038/gim.2013.5
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 195NM
UT WOS:000322709800006
PM 23448725
ER
PT J
AU Hurle, B
Citrin, T
Jenkins, JF
Kaphingst, KA
Lamb, N
Roseman, JE
Bonham, VL
AF Hurle, Belen
Citrin, Toby
Jenkins, Jean F.
Kaphingst, Kimberly A.
Lamb, Neil
Roseman, Jo Ellen
Bonham, Vence L.
TI What does it mean to be genomically literate?: National Human Genome
Research Institute Meeting Report
SO GENETICS IN MEDICINE
LA English
DT Article
DE genomic literacy; genomics; National Human Genome Research Institute;
public health genomics
ID FAMILY-HISTORY; HEALTH; GENETICS; UNDERSTANDINGS; PRIORITIES; EDUCATION;
MEDICINE; DISEASE
AB Genomic discoveries will increasingly advance the science of medicine. Limited genomic literacy may adversely impact the public's understanding and use of the power of genetics and genomics in health care and public health. In November 2011, a meeting was held by the National Human Genome Research Institute to examine the challenge of achieving genomic literacy for the general public, from kindergarten to grade 12 to adult education. The role of the media in disseminating scientific messages and in perpetuating or reducing misconceptions was also discussed. Workshop participants agreed that genomic literacy will be achieved only through active engagement between genomics experts and the varied constituencies that comprise the public. This report summarizes the background, content, and outcomes from this meeting, including recommendations for a research agenda to inform decisions about how to advance genomic literacy in our society.
C1 [Hurle, Belen; Bonham, Vence L.] NHGRI, Div Policy Commun & Educ, NIH, Bethesda, MD 20892 USA.
[Citrin, Toby] Univ Michigan, Sch Publ Hlth, Dept Hlth Management & Policy, Ctr Publ Hlth & Community Genom, Ann Arbor, MI 48109 USA.
[Jenkins, Jean F.] NHGRI, Genom Healthcare Branch, NIH, Bethesda, MD 20892 USA.
[Kaphingst, Kimberly A.] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA.
[Lamb, Neil] HudsonAlpha Inst Biotechnol, Huntsville, AL USA.
[Roseman, Jo Ellen] Amer Assoc Advancement Sci, Washington, DC USA.
RP Hurle, B (reprint author), NHGRI, Div Policy Commun & Educ, NIH, Bethesda, MD 20892 USA.
EM bhurle@mail.nih.gov
FU National Center for Research Resources, NIH [R25RR-022703]; National
Cancer Institute [R01 CA168608, 3U54CA153460-03S1]; Agency for
Healthcare Research and Quality [R21 HS020309]; NIH [P50 CA95815, P30
DK092950]; Centers for Disease Control and Prevention [U58 DP0003435];
NIH Science Education Partnership Awards (SEPA) [8R25OD010981]; National
Science Foundation (NSF) [2061]; Atlas of Science Literacy [ESI
0103678]; Office of Public Health Genomics, Centers for Disease Control
and Prevention
FX T.C. is supported by the Office of Public Health Genomics, Centers for
Disease Control and Prevention, and has been funded by R25RR-022703 from
the National Center for Research Resources, NIH. K.A.K. is funded by
grants R01 CA168608 and 3U54CA153460-03S1, National Cancer Institute;
R21 HS020309, Agency for Healthcare Research and Quality; P50 CA95815
and P30 DK092950, NIH; and U58 DP0003435, Centers for Disease Control
and Prevention. N.L. is supported by NIH Science Education Partnership
Awards (SEPA) grant #8R25OD010981. J.E.R. at AAAS Project 2061 is funded
by National Science Foundation (NSF) grants to promote science literacy
since 1997, most recently to continue to support the Atlas of Science
Literacy (ESI 0103678) and to create next-generation science curriculum
materials (ESI 0227557) and science literacy assessment tools (ESI
0352473). The remaining authors declare no conflict of interest.
NR 32
TC 19
Z9 19
U1 1
U2 17
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
J9 GENET MED
JI Genet. Med.
PD AUG
PY 2013
VL 15
IS 8
BP 658
EP 663
DI 10.1038/gim.2013.14
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 195NM
UT WOS:000322709800010
PM 23448722
ER
PT J
AU Graves, KD
Leventhal, KG
Nusbaum, R
Salehizadeh, Y
Hooker, GW
Peshkin, BN
Butrick, M
Tuong, W
Mathew, J
Goerlitz, D
Fishman, MB
Shields, PG
Schwartz, MD
AF Graves, Kristi D.
Leventhal, Kara-Grace
Nusbaum, Rachel
Salehizadeh, Yasmin
Hooker, Gillian W.
Peshkin, Beth N.
Butrick, Morgan
Tuong, William
Mathew, Jeena
Goerlitz, David
Fishman, Mary B.
Shields, Peter G.
Schwartz, Marc D.
TI Behavioral and psychosocial responses to genomic testing for colorectal
cancer risk
SO GENOMICS
LA English
DT Article
DE Translational genomic research; SNP testing; Colorectal cancer risk;
Genomic education; Behavior change
ID SMOKING-CESSATION TREATMENT; BODY-MASS INDEX; GENETIC SUSCEPTIBILITY;
PHYSICAL-ACTIVITY; RANDOMIZED-TRIAL; BREAST-CANCER; SELF-REPORT;
INTERVENTION; ASSOCIATIONS; VARIANTS
AB We conducted a translational genomic pilot study to evaluate the impact of genomic information related to colorectal cancer (CRC) risk on psychosocial, behavioral and communication outcomes. In 47 primary care participants, 96% opted for testing of three single nucleotide polymorphisms (SNPs) related to CRC risk. Participants averaged 2.5 of 6 possible SNP risk alleles (10% lifetime risk). At 3-months, participants did not report significant increases in cancer worry/distress; over half reported physical activity and dietary changes. SNP risk scores were unrelated to behavior change at 3-months. Many participants (64%) shared their SNP results, including 28% who shared results with a physician. In this pilot, genomic risk education, including discussion of other risk factors, appeared to impact patients' health behaviors, regardless of the level of SNP risk. Future work can compare risk education with and without SNP results to evaluate if SNP information adds value to existing approaches. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Graves, Kristi D.; Leventhal, Kara-Grace; Nusbaum, Rachel; Salehizadeh, Yasmin; Peshkin, Beth N.; Butrick, Morgan; Tuong, William; Schwartz, Marc D.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Canc Prevent & Control Program, Washington, DC 20007 USA.
[Graves, Kristi D.; Leventhal, Kara-Grace; Nusbaum, Rachel; Salehizadeh, Yasmin; Peshkin, Beth N.; Butrick, Morgan; Tuong, William; Schwartz, Marc D.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Fisher Ctr Familial Canc Res, Washington, DC 20007 USA.
[Hooker, Gillian W.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
[Mathew, Jeena; Goerlitz, David] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA.
[Fishman, Mary B.] NYU Langone Med Ctr & Sch Med, New York, NY 10016 USA.
[Shields, Peter G.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA.
[Shields, Peter G.] Solove Res Inst, Columbus, OH 43210 USA.
RP Graves, KD (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, Canc Prevent & Control Program, 3300 Whitehaven St NW,Suite 4100, Washington, DC 20007 USA.
EM kdg9@georgetown.edu
FU NCI [K07CA131172-S2, P30CA051008]; Fisher Center for Familial Cancer
Research
FX This project was supported by funding through NCI K07CA131172-S2 (KG),
the Fisher Center for Familial Cancer Research and NCI P30CA051008,
which partially supports the Genomics and Epigenomics Shared Resource at
Lombardi Comprehensive Cancer Center. The content of this manuscript is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Cancer Institute or the
National Institutes of Health.
NR 42
TC 5
Z9 5
U1 2
U2 11
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0888-7543
J9 GENOMICS
JI Genomics
PD AUG
PY 2013
VL 102
IS 2
SI SI
BP 123
EP 130
DI 10.1016/j.ygeno.2013.04.002
PG 8
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 197JW
UT WOS:000322848500007
PM 23583311
ER
PT J
AU Sutin, AR
Terracciano, A
Milaneschi, Y
An, Y
Ferrucci, L
Zonderman, AB
AF Sutin, Angelina R.
Terracciano, Antonio
Milaneschi, Yuri
An, Yang
Ferrucci, Luigi
Zonderman, Alan B.
TI The Trajectory of Depressive Symptoms Across the Adult Life Span
SO JAMA PSYCHIATRY
LA English
DT Article
ID NATIONAL-COMORBIDITY-SURVEY; OLDER-ADULTS; SUBTHRESHOLD DEPRESSION;
UNITED-STATES; SOCIOECONOMIC-STATUS; GENDER-DIFFERENCES; CO-MORBIDITY;
RISK-FACTORS; AGE; HEALTH
AB IMPORTANCE Long-term longitudinal studies are needed to delineate the trajectory of depressive symptoms across adulthood and to individuate factors that may contribute to increases in depressive symptoms in older adulthood.
OBJECTIVES To estimate the trajectory of depressive symptoms across the adult life span; to test whether this trajectory varies by demographic factors (sex, ethnicity, and educational level) and antidepressant medication use; and to test whether disease burden, functional limitations, and proximity to death explain the increase in depressive symptoms in old age.
DESIGN Longitudinal study.
SETTING Community.
PARTICIPANTS The study included 2320 participants (47.0% female; mean [SD] age at baseline, 58.1 [17.0] years; range, 19-95 years) from the Baltimore Longitudinal Study of Aging.
MAIN OUTCOMES AND MEASURES Estimated trajectory of depressive symptoms modeled from 10 982 assessments (mean [SD] assessments per participant, 4.7 [3.6]; range, 1-21) based on the Center for Epidemiologic Studies Depression scale and 3 subscales (depressed affect, somatic complaints, and interpersonal problems).
RESULTS The linear (gamma(10) = 0.52; P < .01) and quadratic (gamma(20) = 0.43; P < .01) terms were significant, which indicated that depressive symptoms were highest in young adulthood, decreased across middle adulthood, and increased again in older adulthood. The subscales followed a similar pattern. Women reported more depressed affect at younger ages, but an interaction with age suggested that this gap disappeared in old age. Accounting for comorbidity, functional limitations, and impending death slightly reduced but did not eliminate the uptick in depressive symptoms in old age.
CONCLUSIONS AND RELEVANCE Symptoms of depression follow a U-shaped pattern across adulthood. Older adults experience an increase in distress that is not due solely to declines in physical health or approaching death.
C1 [Sutin, Angelina R.] Florida State Univ, Coll Med, Dept Med Human & Social Sci, Tallahassee, FL 32306 USA.
[Terracciano, Antonio] Florida State Univ, Coll Med, Dept Geriatr, Tallahassee, FL 32306 USA.
[Sutin, Angelina R.; Terracciano, Antonio; Milaneschi, Yuri; An, Yang; Ferrucci, Luigi; Zonderman, Alan B.] NIA, NIH, Baltimore, MD 21224 USA.
[Milaneschi, Yuri] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands.
RP Sutin, AR (reprint author), Florida State Univ, Coll Med, Dept Med Human & Social Sci, 1115 W Call St, Tallahassee, FL 32306 USA.
EM angelina.sutin@med.fsu.edu
RI terracciano, antonio/B-1884-2008;
OI Zonderman, Alan B/0000-0002-6523-4778
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health
FX This research was supported in part by the Intramural Research Program
of the National Institute on Aging, National Institutes of Health.
NR 57
TC 48
Z9 48
U1 4
U2 29
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-622X
EI 2168-6238
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD AUG
PY 2013
VL 70
IS 8
BP 803
EP 811
DI 10.1001/jamapsychiatry.2013.193
PG 9
WC Psychiatry
SC Psychiatry
GA 197EW
UT WOS:000322833600006
PM 23760442
ER
PT J
AU Konova, AB
Moeller, SJ
Tomasi, D
Volkow, ND
Goldstein, RZ
AF Konova, Anna B.
Moeller, Scott J.
Tomasi, Dardo
Volkow, Nora D.
Goldstein, Rita Z.
TI Effects of Methylphenidate on Resting-State Functional Connectivity of
the Mesocorticolimbic Dopamine Pathways in Cocaine Addiction
SO JAMA PSYCHIATRY
LA English
DT Article
ID ANTERIOR CINGULATE CORTEX; WORKING-MEMORY; HUMAN BRAIN; ORAL
METHYLPHENIDATE; NOREPINEPHRINE TRANSPORTER; SPONTANEOUS FLUCTUATIONS;
DEPENDENT PATIENTS; DORSAL STRIATUM; SEEKING HABITS; ACOUSTIC NOISE
AB IMPORTANCE Cocaine addiction is associated with altered resting-state functional connectivity among regions of the mesocorticolimbic dopamine pathways. Methylphenidate hydrochloride, an indirect dopamine agonist, normalizes task-related regional brain activity and associated behavior in cocaine users; however, the neural systems-level effects of methylphenidate in this population have not yet been described.
OBJECTIVE To use resting-state functional magnetic resonance imaging to examine changes in mesocorticolimbic connectivity with methylphenidate and how connectivity of affected pathways relates to severity of cocaine addiction.
DESIGN Randomized, placebo-controlled, before-after, crossover study.
SETTING Clinical research center.
PARTICIPANTS Eighteen nonabstaining individuals with cocaine use disorders.
INTERVENTIONS Single doses of oralmethylphenidate (20mg) or placebo were administered at each of 2 study sessions. At each session, resting scans were acquired twice: immediately after drug administration (before the onset of effects [baseline]) and 120 minutes later (within the window of peak effects).
MAIN OUTCOMES AND MEASURES Functional connectivity strength was evaluated using a seed voxel correlation approach. Changes in this measure were examined to characterize the neural systems-level effects of methylphenidate; severity of cocaine addiction was assessed by interview and questionnaire.
RESULTS Short-term methylphenidate administration reduced an abnormally strong connectivity of the ventral striatum with the dorsal striatum (putamen/globus pallidus), and lower connectivity between these regions during placebo administration uniquely correlated with less severe addiction. In contrast, methylphenidate strengthened several corticolimbic and corticocortical connections.
CONCLUSIONS AND RELEVANCE These findings help elucidate the neural systems-level effects of methylphenidate and suggest that short-term methylphenidate can, at least transiently, remodel abnormal circuitry relevant to the pathophysiologic characteristics of cocaine addiction. In particular, the effects of methylphenidate within striatal and cortical pathways constitute a potentially viable mechanism by which methylphenidate could facilitate control of behavior in cocaine addiction.
C1 [Konova, Anna B.; Moeller, Scott J.; Goldstein, Rita Z.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY USA.
[Konova, Anna B.; Moeller, Scott J.; Goldstein, Rita Z.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY USA.
[Konova, Anna B.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA.
[Tomasi, Dardo; Volkow, Nora D.] NIAAA, Rockville, MD 20852 USA.
[Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA.
RP Goldstein, RZ (reprint author), Leon & Norma Hess Ctr Sci & Med, Icahn Sch Med Mt Sinai, 1470 Madison Ave, New York, NY 10029 USA.
EM rita.goldstein@mssm.edu
RI Tomasi, Dardo/J-2127-2015; Moeller, Scott/L-5549-2016
OI Moeller, Scott/0000-0002-4449-0844
FU National Institute on Drug Abuse [1R01DA023579, 1F32DA030017-01]
FX This research was conducted with grant support from the National
Institute on Drug Abuse (1R01DA023579 to Dr Goldstein and
1F32DA030017-01 to Dr Moeller).
NR 84
TC 30
Z9 30
U1 0
U2 17
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-622X
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD AUG
PY 2013
VL 70
IS 8
BP 857
EP 868
DI 10.1001/jamapsychiatry.2013.1129
PG 12
WC Psychiatry
SC Psychiatry
GA 197EW
UT WOS:000322833600012
PM 23803700
ER
PT J
AU Liu, LH
Noone, AM
Gomez, SL
Scoppa, S
Gibson, JT
Lichtensztajn, D
Fish, K
Wilkens, LR
Goodman, MT
Morris, C
Kwong, S
Deapen, D
Miller, BA
AF Liu, Lihua
Noone, Anne-Michelle
Gomez, Scarlett Lin
Scoppa, Steve
Gibson, James T.
Lichtensztajn, Daphne
Fish, Kari
Wilkens, Lynne R.
Goodman, Marc T.
Morris, Cyllene
Kwong, Sandy
Deapen, Dennis
Miller, Barry A.
TI Cancer Incidence Trends Among Native Hawaiians and Other Pacific
Islanders in the United States, 1990-2008
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID BREAST-CANCER; MULTIETHNIC COHORT; AMERICAN-SAMOANS; ASIAN SUBGROUPS;
INCIDENCE RATES; CHAMORRO WOMEN; RISK-FACTORS; HEALTH; CALIFORNIA;
POPULATIONS
AB Lack of annual population estimates for disaggregated Native Hawaiian and Other Pacific Islander (NHOPI) populations limits the ability to examine cancer incidence rates and trends to understand the cancer burdens among NHOPIs.
Utilizing 1990 and 2000 population census data, we estimated the annual populations by age and sex for Native Hawaiians, Samoans, and Guamanians/Chamorros for 19902008 in regions covered by 13 of the National Cancer Institutes SEER registries. Cancer diagnoses during 19902008 from these registries were used to calculate the age-adjusted (2000 US Standard) incidence rates by sex, calendar year/period, and cancer type for each population. The annual percentage change (APC) in incidence rates was estimated with the 95% confidence intervals (95% CIs) calculated for both the rate and APC estimates.
Statistically significant declining trends were found in Native Hawaiians, in men for lung and stomach cancers (APC 2.3%; 95% CI 3.3 to 1.3; and APC 3.8%; 95% CI 6.0 to 1.6, respectively), and in women for breast cancer (APC 4.1%; 95% CI 5.7 to 2.5) since 1998 and lung cancer (APC 6.4%; 95% CI 10.7 to 1.8) since 2001. Rising incidence trends were experienced by Samoans, especially by Samoan women for breast (APC 2.7%; 95% CI 0.9 to 4.5) and uterus (APC 7.3%; 95% CI 6.2 to 8.4) cancers. With limited data, Guamanians/Chamorros demonstrated lower, but increasing, incidence rates than other NHOPIs.
Population-based cancer incidence rates for disaggregated NHOPI populations help identify disparities in cancer burden and provide valuable information to improve cancer control efforts among NHOPIs.
C1 [Liu, Lihua; Deapen, Dennis] Univ So Calif, Los Angeles Canc Surveillance Program, Los Angeles, CA 90089 USA.
[Noone, Anne-Michelle; Miller, Barry A.] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Gomez, Scarlett Lin; Lichtensztajn, Daphne] Canc Prevent Inst Calif, Fremont, CA USA.
[Gomez, Scarlett Lin] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Scoppa, Steve; Gibson, James T.] Informat Management Serv Inc, Silver Spring, MD USA.
[Fish, Kari] Canc Registry Greater Calif, Sacramento, CA USA.
[Wilkens, Lynne R.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Goodman, Marc T.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Morris, Cyllene; Kwong, Sandy] Calif Canc Registry, Sacramento, CA USA.
RP Liu, LH (reprint author), Univ So Calif, Los Angeles Canc Surveillance Program, 2001 N Soto St,SSB 305E, Los Angeles, CA 90089 USA.
EM lihualiu@usc.edu
FU National Cancer Institute [HHSN261201000035C, HHSN261201100412P,
HHSN261201000140C, HHSN261201000034C]; Centers for Disease Control and
Prevention's National Program of Cancer Registries [1U58 DP000807-01]
FX This research was supported by the National Cancer Institute's SEER
Program under contract HHSN261201000035C awarded to the University of
Southern California and under contract HHSN261201100412P awarded to one
of the authors (BAM). 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
SEER 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.
NR 54
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Z9 6
U1 1
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD AUG
PY 2013
VL 105
IS 15
BP 1086
EP 1095
DI 10.1093/jnci/djt156
PG 10
WC Oncology
SC Oncology
GA 199DZ
UT WOS:000322976000007
PM 23878354
ER
PT J
AU Gomez, SL
Noone, AM
Lichtensztajn, DY
Scoppa, S
Gibson, JT
Liu, LH
Morris, C
Kwong, S
Fish, K
Wilkens, LR
Goodman, MT
Deapen, D
Miller, BA
AF Gomez, Scarlett Lin
Noone, Anne-Michelle
Lichtensztajn, Daphne Y.
Scoppa, Steve
Gibson, James T.
Liu, Lihua
Morris, Cyllene
Kwong, Sandy
Fish, Kari
Wilkens, Lynne R.
Goodman, Marc T.
Deapen, Dennis
Miller, Barry A.
TI Cancer Incidence Trends Among Asian American Populations in the United
States, 1990-2008
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID HEALTH MAINTENANCE ORGANIZATION; CELL LUNG-CANCER; BREAST-CANCER;
COLORECTAL-CANCER; INCIDENCE RATES; LIVER-CANCER; RISK-FACTORS;
ENDOMETRIAL CANCER; INCIDENCE PATTERNS; ETHNIC-GROUPS
AB National cancer incidence trends are presented for eight Asian American groups: Asian Indians/Pakistanis, Chinese, Filipinos, Japanese, Kampucheans, Koreans, Laotians, and Vietnamese.
Cancer incidence data from 1990 through 2008 were obtained from 13 Surveillance, Epidemiology, End Results (SEER) registries. Incidence rates from 1990 through 2008 and average percentage change were computed using SEER*Stat and Joinpoint software. The annual percentage change (APC) in incidence rates was estimated with 95% confidence intervals (95% CIs) calculated for both the rate and APC estimates. Rates for non-Hispanic whites are presented for comparison.
Prostate cancer was the most common malignancy among most groups, followed by lung, colorectal, liver, and stomach cancers. Breast cancer was generally the most common cancer in women, followed by colorectal and lung cancers; liver, cervix, thyroid, and stomach cancers also ranked highly. Among men, increasing trends were observed for prostate (Asian Indians and Pakistanis: APC 19902003 2.2, 95% CI 0.3 to 4.1; Filipinos: APC 19901994 19.0, 95% CI 4.5 to 35.4; Koreans: APC 19902008 2.9, 95% CI 1.8 to 4.0), colorectal (Koreans: APC 19902008 2.2, 95% CI 0.9 to 3.5), and liver cancers (Filipinos: APC 19902008 1.6, 95% CI 0.4 to 2.7; Koreans: APC 19902006 2.1, 95% CI 0.4 to 3.7; Vietnamese: APC 19902008 1.6, 95% CI 0.3 to 2.8), whereas lung and stomach cancers generally remained stable or decreased. Among women, increases were observed for uterine cancer (Asian Indians: APC 19902008 3.0, 95% CI 0.3 to 5.8; Chinese: APC 20042008 7.0, 95% CI 1.4 to 12.9; Filipina: APC 19902008 3.0, 95% CI 2.4 to 3.7; Japanese: APC 19902008 1.1, 95% CI 0.1 to 2.0), colorectal cancer (Koreans: APC 19902008 2.8, 95% CI 1.7 to 3.9; Laotians: APC: 19902008 5.9, 95% CI 4.0 to 7.7), lung cancer (Filipinas: APC 19902008 2.1, 95% CI 1.4 to 2.8; Koreans: APC 19902008 2.1, 95% CI 0.6 to 3.6), thyroid cancer (Filipinas: APC 19902008 2.5, 95% CI 1.7 to 3.3), and breast cancer in most groups (APC 19902008 from 1.2 among Vietnamese and Chinese to 4.7 among Koreans). Decreases were observed for stomach (Chinese and Japanese), colorectal (Chinese), and cervical cancers (Laotians and Vietnamese).
These data fill a critical knowledge gap concerning the cancer experience of Asian American groups and highlight where increased preventive, screening, and surveillance efforts are neededuin particular, lung cancer among Filipina and Korean women and Asian Indian/Pakistani men, breast cancer among all women, and liver cancer among Vietnamese, Laotian, and Kampuchean women and Filipino, Kampuchean, and Vietnamese men.
C1 [Gomez, Scarlett Lin; Lichtensztajn, Daphne Y.] Canc Prevent Inst Calif, Fremont, CA 94538 USA.
[Gomez, Scarlett Lin] Stanford Univ, Med Ctr, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Noone, Anne-Michelle; Miller, Barry A.] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Scoppa, Steve; Gibson, James T.] Informat Management Serv Inc, Silver Spring, MD USA.
[Liu, Lihua] Univ So Calif, Keck Sch Med, Los Angeles Canc Surveillance Program, Los Angeles, CA 90033 USA.
[Morris, Cyllene; Kwong, Sandy] Calif Canc Registry, Sacramento, CA USA.
[Fish, Kari] Canc Registry Greater Calif, Sacramento, CA USA.
[Wilkens, Lynne R.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
Cedars Sinai Med Ctr, Dept Biomed Sci, Los Angeles, CA 90048 USA.
RP Gomez, SL (reprint author), Canc Prevent Inst Calif, 2201 Walnut Ave,Ste 300, Fremont, CA 94538 USA.
EM scarlett@cpic.org
FU National Cancer Institute [HHSN261201000140C, HHSN261201100412P,
HHSN261201000035C, HHSN261201000034C]; Centers for Disease Control and
Prevention's National Program of Cancer Registries [1U58 DP000807-01]
FX This research was supported by the National Cancer Institute's SEER
Program under contract HHSN261201000140C awarded to the Cancer
Prevention Institute of California and under contract HHSN261201100412P
awarded to BAM. 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
SEER 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.
NR 104
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U1 5
U2 23
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD AUG
PY 2013
VL 105
IS 15
BP 1096
EP 1110
DI 10.1093/jnci/djt157
PG 15
WC Oncology
SC Oncology
GA 199DZ
UT WOS:000322976000008
PM 23878350
ER
PT J
AU Brasky, TM
Darke, AK
Song, XL
Tangen, CM
Goodman, PJ
Thompson, IM
Meyskens, FL
Goodman, GE
Minasian, LM
Parnes, HL
Klein, EA
Kristal, AR
AF Brasky, Theodore M.
Darke, Amy K.
Song, Xiaoling
Tangen, Catherine M.
Goodman, Phyllis J.
Thompson, Ian M.
Meyskens, Frank L., Jr.
Goodman, Gary E.
Minasian, Lori M.
Parnes, Howard L.
Klein, Eric A.
Kristal, Alan R.
TI Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT
Trial
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID PREVENTION TRIAL; VITAMIN-E; CARDIOVASCULAR-DISEASE;
DIETARY/SUPPLEMENTAL OMEGA-3-FATTY-ACIDS; DIETARY-SUPPLEMENTS; GENERAL
HEALTH; SELENIUM; BLOOD; METAANALYSIS; OMEGA-3
AB Studies of dietary ?-3 fatty acid intake and prostate cancer risk are inconsistent; however, recent large prospective studies have found increased risk of prostate cancer among men with high blood concentrations of long-chain ?-3 polyunsaturated fatty acids ([LC?-3PUFA] 20:5?3; 22:5?3; 22:6?3]. This casecohort study examines associations between plasma phospholipid fatty acids and prostate cancer risk among participants in the Selenium and Vitamin E Cancer Prevention Trial.
Case subjects were 834 men diagnosed with prostate cancer, of which 156 had high-grade cancer. The subcohort consisted of 1393 men selected randomly at baseline and from within strata frequency matched to case subjects on age and race. Proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI) for associations between fatty acids and prostate cancer risk overall and by grade. All statistical tests were two-sided.
Compared with men in the lowest quartiles of LC?-3PUFA, men in the highest quartile had increased risks for low-grade (HR 1.44, 95% CI 1.08 to 1.93), high-grade (HR 1.71, 95% CI 1.00 to 2.94), and total prostate cancer (HR 1.43, 95% CI 1.09 to 1.88). Associations were similar for individual long-chain ?-3 fatty acids. Higher linoleic acid (?-6) was associated with reduced risks of low-grade (HR 0.75, 95% CI 0.56 to 0.99) and total prostate cancer (HR 0.77, 95% CI 0.59 to 1.01); however, there was no dose response.
This study confirms previous reports of increased prostate cancer risk among men with high blood concentrations of LC?-3PUFA. The consistency of these findings suggests that these fatty acids are involved in prostate tumorigenesis. Recommendations to increase LC?-3PUFA intake should consider its potential risks.
C1 [Brasky, Theodore M.] Ohio State Univ, Coll Med, Dept Internal Med, Div Canc Prevent & Control, Columbus, OH 43201 USA.
[Brasky, Theodore M.; Song, Xiaoling; Goodman, Gary E.; Kristal, Alan R.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA.
[Darke, Amy K.; Tangen, Catherine M.; Goodman, Phyllis J.] Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, Seattle, WA 98104 USA.
[Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA.
[Meyskens, Frank L., Jr.] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Irvine, CA USA.
[Goodman, Gary E.] Univ Washington, Dept Environm Hlth, Seattle, WA 98195 USA.
[Kristal, Alan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Minasian, Lori M.; Parnes, Howard L.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Klein, Eric A.] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USA.
RP Brasky, TM (reprint author), Ohio State Univ, Ctr Comprehens Canc, 1590 N High St,Ste 525, Columbus, OH 43201 USA.
EM Theodore.Brasky@osumc.edu
OI Kristal, Alan/0000-0002-7329-1617
FU Public Health Service Cooperative Agreement grant [CA37429]; National
Cancer Institute [R25-CA94880]; National Center for Complementary and
Alternative Medicine
FX This work was supported in part by Public Health Service Cooperative
Agreement grant CA37429 awarded by the National Cancer Institute, and in
part by the National Center for Complementary and Alternative Medicine,
and by R25-CA94880 awarded by the National Cancer Institute.
NR 48
TC 103
Z9 104
U1 3
U2 42
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD AUG
PY 2013
VL 105
IS 15
BP 1132
EP 1141
DI 10.1093/jnci/djt174
PG 10
WC Oncology
SC Oncology
GA 199DZ
UT WOS:000322976000011
PM 23843441
ER
PT J
AU Dunlap, ME
Zile, M
Bensimhon, D
Bittner, V
Boineau, R
Kraus, W
Moe, G
O'Connor, C
Stebbins, A
Wertheimer, J
Whellan, D
AF Dunlap, Mark E.
Zile, Michael
Bensimhon, Dan
Bittner, Vera
Boineau, Robin
Kraus, William
Moe, Gordon
O'Connor, Christopher
Stebbins, Amanda
Wertheimer, John
Whellan, David
TI Mode of Death in Contemporary Heart Failure Patients and the Impact of
Structured Exercise: Insights from the HF-ACTION Trial
SO JOURNAL OF CARDIAC FAILURE
LA English
DT Meeting Abstract
CT 17th Annual Scientific Meeting of the Heart-Failure-Society-of-America
(HFSA)
CY SEP 22-25, 2013
CL Orlando, FL
SP Heart Failure Soc Amer (HFSA)
C1 [Dunlap, Mark E.] Metrohlth Med Ctr, Cleveland, OH USA.
[Zile, Michael] RHJ Dept Vet Affairs Med Ctr, Charleston, SC USA.
[Zile, Michael] Med Univ S Carolina, Charleston, SC 29425 USA.
[Bensimhon, Dan; Kraus, William; O'Connor, Christopher; Stebbins, Amanda] Duke Univ, Med Ctr, Durham, NC USA.
[Bittner, Vera] Univ Alabama Birmingham, Birmingham, AL USA.
[Boineau, Robin] NHL&B Inst DECA, NIH, Bethesda, MD USA.
[Moe, Gordon] St Michaels Hosp, Toronto, ON M5B 1W8, Canada.
[Moe, Gordon] Univ Toronto, Inst Med Sci, Toronto, ON, Canada.
[Wertheimer, John] Penn Heart Vasc Grp, Jenkintown, PA USA.
[Whellan, David] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS
PI PHILADELPHIA
PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA
SN 1071-9164
J9 J CARD FAIL
JI J. Card. Fail.
PD AUG
PY 2013
VL 19
IS 8
SU 1
MA 073
BP S27
EP S27
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 201LG
UT WOS:000323142500073
ER
PT J
AU Jacob, RF
Walter, MF
Self-Medlin, Y
Mason, RP
AF Jacob, Robert F.
Walter, Mary F.
Self-Medlin, Yehudi
Mason, R. Preston
TI Atorvastatin Active Metabolite Inhibits Oxidative Modification of Small
Dense Low-Density Lipoprotein
SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
LA English
DT Article
DE atorvastatin metabolite; lipoprotein; sdLDL; cholesterol; oxidation
ID CORONARY-ARTERY-DISEASE; PREDICT CARDIOVASCULAR EVENTS; COA REDUCTASE
INHIBITORS; CARDIAC OUTCOMES TRIAL; LDL-CHOLESTEROL; HEART-DISEASE;
PLASMA; RISK; SUSCEPTIBILITY; STATIN
AB We tested the hypothesis that atorvastatin active metabolite (ATM), on the basis of its distinct structural features and potent antioxidant activity, preferentially inhibits lipid oxidation in human small dense low-density lipoprotein (sdLDL) and other small lipid vesicles. LDL, sdLDL, and various subfractions were isolated from human plasma by sequential ultracentrifugation, treated with ATM, atorvastatin, pravastatin, rosuvastatin, or simvastatin and were subjected to copper-induced oxidation. Lipid oxidation was measured spectrophotometrically as a function of thiobarbituric acid reactive substances formation. Similar analyses were performed in reconstituted lipid vesicles enriched in polyunsaturated fatty acids and prepared at various sizes. ATM was found to inhibit sdLDL oxidation in a dose-dependent manner. The antioxidant effects of ATM in sdLDL were 1.5 and 4.7 times greater (P < 0.001) than those observed in large buoyant LDL and very low-density lipoprotein subfractions, respectively. ATM had similar dose- and size-dependent effects in reconstituted lipid vesicles. None of these effects were reproduced by atorvastatin (parent) or any of the other statins examined in this study. These data suggest that ATM interacts with sdLDL in a specific manner that also confers preferential resistance to oxidative stress. Such interactions may reduce sdLDL atherogenicity and improve clinical outcomes in patients with cardiovascular disease.
C1 [Jacob, Robert F.; Self-Medlin, Yehudi; Mason, R. Preston] Elucida Res LLC, Beverly, MA 01915 USA.
[Walter, Mary F.] NIDDK, Core Clin Lab Serv, NIH, Bethesda, MD USA.
[Mason, R. Preston] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc,Dept Med, Boston, MA 02115 USA.
RP Jacob, RF (reprint author), Elucida Res LLC, Cummings Ctr 100, Suite 135L,POB 7100, Beverly, MA 01915 USA.
EM rjacob@elucidaresearch.com
NR 46
TC 3
Z9 3
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0160-2446
J9 J CARDIOVASC PHARM
JI J. Cardiovasc. Pharmacol.
PD AUG
PY 2013
VL 62
IS 2
BP 160
EP 166
DI 10.1097/FJC.0b013e318294998d
PG 7
WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy
SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy
GA 202JE
UT WOS:000323209800007
PM 23575262
ER
PT J
AU Ito, Y
Knight, M
Finn, TM
AF Ito, Yoichiro
Knight, Martha
Finn, Thomas M.
TI Spiral Countercurrent Chromatography
SO JOURNAL OF CHROMATOGRAPHIC SCIENCE
LA English
DT Review
ID STATIONARY-PHASE RETENTION; LIQUID PARTITION CHROMATOGRAPHY; 2-PHASE
SOLVENT SYSTEMS; HYDRODYNAMIC BEHAVIOR; SOLID SUPPORT; SEPARATION;
PEPTIDES; COLUMNS
AB For many years, high-speed countercurrent chromatography conducted in open tubing coils has been widely used for the separation of natural and synthetic compounds. In this method, the retention of the stationary phase is solely provided by the Archimedean screw effect by rotating the coiled column in the centrifugal force field. However, the system fails to retain enough of the stationary phase for polar solvent systems such as the aqueous-aqueous polymer phase systems. To address this problem, the geometry of the coiled channel was modified to a spiral configuration so that the system could utilize the radially acting centrifugal force. This successfully improved the retention of the stationary phase. Two different types of spiral columns were fabricated: the spiral disk assembly, made by stacking multiple plastic disks with single or four interwoven spiral channels connected in series, and the spiral tube assembly, made by inserting the tetrafluoroethylene tubing into a spiral frame (spiral tube support). The capabilities of these column assemblies were successfully demonstrated by separations of peptides and proteins with polar two-phase solvent systems whose stationary phases had not been well retained in the earlier multilayer coil separation column for high-speed countercurrent chromatography.
C1 [Ito, Yoichiro] NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
[Knight, Martha; Finn, Thomas M.] CC Biotech LLC, Rockville, MD 20850 USA.
RP Ito, Y (reprint author), NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, Bldg 10,Room 8N230,10 Ctr Dr, Bethesda, MD 20892 USA.
EM itoy2@mail.nih.gov
OI Knight, Martha/0000-0003-4863-8858
FU SBIR grant from the National Science Foundation [0638082]; Maryland
Technology Development Corporation (TEDCO)
FX The research was supported in part by a SBIR grant 0638082 to CC Biotech
LLC from the National Science Foundation and a grant from the Maryland
Technology Development Corporation (TEDCO). The company has an exclusive
commercialization license L-144-2007/1 from the National Institutes of
Health for the spiral countercurrent chromatography patents.
NR 38
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U1 2
U2 20
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0021-9665
J9 J CHROMATOGR SCI
JI J. Chromatogr. Sci.
PD AUG
PY 2013
VL 51
IS 7
BP 726
EP 738
DI 10.1093/chromsci/bmt058
PG 13
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 197EE
UT WOS:000322831500014
PM 23833207
ER
PT J
AU Marini, JC
Blissett, AR
AF Marini, Joan C.
Blissett, Angela R.
TI New Genes in Bone Development: What's New in Osteogenesis Imperfecta
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID EPITHELIUM-DERIVED FACTOR; PROLYL 3-HYDROXYLATION COMPLEX;
EXTRACELLULAR-MATRIX; HYPERPLASTIC CALLUS; DANLOS-SYNDROME; BRUCK
SYNDROME; I COLLAGEN; MUTATIONS; DISEASE; FKBP10
AB Osteogenesis imperfecta (OI) is a heritable bone dysplasia characterized by bone fragility and deformity and growth deficiency. Most cases of OI (classical types) have autosomal dominant inheritance and are caused by mutations in the type I collagen genes. During the past several years, a number of noncollagenous genes whose protein products interact with collagen have been identified as the cause(s) of rare forms of OI. This has led to a paradigm shift for OI as a collagen-related condition. The majority of the non-classical OI types have autosomal recessive inheritance and null mutations in their respective genes. The exception is a unique dominant defect in IFITM5, which encodes Bril and leads to hypertrophic callus and interosseous membrane ossification. Three recessive OI types arise from defects in any of the components of the collagen prolyl 3-hydroxylation complex (CRTAP, P3H1, CyPB), which modifies the collagen alpha 1(I)Pro986 residue. Complex dysfunction leads to delayed folding of the procollagen triple helix and increased helical modification. Next, defects in collagen chaperones, HSP47 and FKBP65, lead to improper procollagen folding and deficient collagen cross-linking in matrix, respectively. A form of OI with a mineralization defect is caused by mutations in SERPINF1, whose protein product, PEDF, is a well-known antiangiogenesis factor. Defects in the C-propeptide cleavage enzyme, BMP1, also cause recessive OI. Additional genes, including SP7 and TMEM38B, have been implicated in recessive OI but are as yet unclassified. Elucidating the mechanistic pathways common to dominant and recessive OI may lead to novel therapeutic approaches to improve clinical manifestations.
C1 [Marini, Joan C.; Blissett, Angela R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA.
RP Marini, JC (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bone & Extracellular Matrix Branch, NIH, Bldg 10,Room 10D39,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM oidoc@helix.nih.gov
FU National Institute of Child Health and Human Development
FX This work was supported by National Institute of Child Health and Human
Development intramural funding (to J.C.M.).
NR 47
TC 64
Z9 66
U1 0
U2 32
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD AUG
PY 2013
VL 98
IS 8
BP 3095
EP 3103
DI 10.1210/jc.2013-1505
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 196NC
UT WOS:000322781300021
PM 23771926
ER
PT J
AU Marx, SJ
AF Marx, Stephen J.
TI Multiplicity of Hormone-Secreting Tumors: Common Themes About Cause,
Expression, and Management
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Review
ID ENDOCRINE NEOPLASIA TYPE-1; ZOLLINGER-ELLISON-SYNDROME;
CUSHINGS-SYNDROME; FOLLOW-UP; PRIMARY ALDOSTERONISM; SPARING SURGERY;
MUTATIONS; HYPERPARATHYROIDISM; PHEOCHROMOCYTOMA; CANCER
AB Context: Multiplicity of hormone-secreting tumors occurs in a substantial portion of hormone-excess states. Multiplicity increases the difficulty of management and drives the selection of special strategies.
Evidence Acquisition: This is a synthesis from publications about tumor development and expression, and also about types of clinical strategy for hormone-secreting tumors.
Evidence Synthesis: Comparisons were made between patient groups with solitary tumors vs those with multiple tumors. Major themes with clinical relevance emerged. Usually, tumor multiplicity develops from a genetic susceptibility in all cells of a tissue. This applies to hormone-secreting tumors that begin as either polyclonal (such as in the parathyroids of familial hypocalciuric hypercalcemia) or monoclonal tumors (such as in the parathyroids of multiple endocrine neoplasia type 1 [MEN1]). High penetrance of a hereditary tumor frequently results in bilaterality and in several other types of multiplicity. Managements are better for the hormone excess than for the associated cancers. Management strategies can be categorized broadly as ablation that is total, subtotal, or zero. Examples are discussed for each category, and 1 example of each category is named here: 1) total ablation of the entire tissue with effort to replace ablated functions (for example, in C-cell neoplasia of multiple endocrine neoplasia type 2); 2) subtotal ablation with increased likelihood of persistent disease or recurrent disease (for example, in the parathyroid tumors of MEN1); or 3) no ablation of tissue with or without the use of pharmacotherapy (for example, with blockers for secretion of stomach acid in gastrinomas of MEN1).
Conclusions: Tumor multiplicity usually arises from defects in all cells of the precursor tissue. Even the optimized managements involve compromises. Still, an understanding of pathophysiology and of therapeutic options should guide optimized management.
C1 [Marx, Stephen J.] Natl Inst Diabet & Digest & Kidney Dis, Genet & Endocrinol Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Marx, SJ (reprint author), NIH, Bldg 10,Room 9C-103,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM marxs@mail.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX This work was funded by the intramural program of the National Institute
of Diabetes and Digestive and Kidney Diseases.
NR 58
TC 6
Z9 6
U1 0
U2 2
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD AUG
PY 2013
VL 98
IS 8
BP 3139
EP 3148
DI 10.1210/jc.2013-1511
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 196NC
UT WOS:000322781300029
PM 23771922
ER
PT J
AU Wells, SA
Pacini, F
Robinson, BG
Santoro, M
AF Wells, Samuel A., Jr.
Pacini, Furio
Robinson, Bruce G.
Santoro, Massimo
TI Multiple Endocrine Neoplasia Type 2 and Familial Medullary Thyroid
Carcinoma: An Update
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Review
ID TYROSINE KINASE DOMAIN; CUTANEOUS LICHEN AMYLOIDOSIS; RET PROTOONCOGENE
MUTATIONS; DENDRITIC CELL VACCINATION; OF-THE-LITERATURE; PHASE-II
TRIAL; MEN 2A; SERUM CALCITONIN; PROPHYLACTIC THYROIDECTOMY;
HIRSCHSPRUNGS-DISEASE
AB Context: Over the last decade, our knowledge of the multiple endocrine neoplasia (MEN) type 2 syndromes MEN2A and MEN2B and familial medullary thyroid carcinoma (FMTC) has expanded greatly. In this manuscript, we summarize how recent discoveries have enhanced our understanding of the molecular basis of these diseases and led to improvements in the diagnosis and management of affected patients.
Evidence Acquisition: We reviewed the English literature through PubMed from 2000 to the present, using the search terms medullary thyroid carcinoma, multiple endocrine neoplasia type 2, familial medullary thyroid carcinoma, RET proto-oncogene, and calcitonin.
Evidence Synthesis: Over 70 RET mutations are known to cause MEN2A, MEN2B, or FMTC, and recent findings from studies of large kindreds with these syndromes have clouded the relationship between genotype and phenotype, primarily because of the varied clinical presentation of different families with the same RET mutation. This clinical variability has also confounded decisions about the timing of prophylactic thyroidectomy for MTC, the dominant endocrinopathy associated with these syndromes. A distinct advance has been the demonstration through phase II and phase III clinical trials that molecular targeted therapeutics are effective in the treatment of patients with locally advanced or metastatic MTC.
Conclusions: The effective management of patients with MEN2A, MEN2A, and FMTC depends on an understanding of the variable behavior of disease expression in patients with a specific RET mutation. Information gained from molecular testing, biochemical analysis, and clinical evaluation is important in providing effective management of patients with either early or advanced-stage MTC.
C1 [Wells, Samuel A., Jr.] NCI, Canc Genet Branch, NIH, Bethesda, MD 20814 USA.
[Pacini, Furio] Univ Siena, Dept Internal Med, Sect Endocrinol & Metab, I-53100 Siena, Italy.
[Robinson, Bruce G.] Univ Sydney, Sch Med, Sydney, NSW 2065, Australia.
[Santoro, Massimo] Univ Naples Federico II, Dipartimento Med Mol & Biotecnol Med, I-80131 Naples, Italy.
RP Wells, SA (reprint author), NCI, Canc Genet Branch, NIH, Bldg 37,Room 10106A,37 Convent Dr, Bethesda, MD 20814 USA.
EM wellss@mail.nih.gov
FU AstraZeneca; Roche
FX B.G.R. has served on advisory boards for AstraZeneca, Eisai, and Bayer.
M.S. has received research support from AstraZeneca and Roche and
participated in a collaborative study with Ariad. F.P. and S.A.W. have
nothing to declare.
NR 162
TC 69
Z9 70
U1 2
U2 10
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD AUG
PY 2013
VL 98
IS 8
BP 3149
EP 3164
DI 10.1210/jc.2013-1204
PG 16
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 196NC
UT WOS:000322781300030
PM 23744408
ER
PT J
AU Beydoun, MA
Beydoun, HA
Kitner-Triolo, MH
Kaufman, JS
Evans, MK
Zonderman, AB
AF Beydoun, M. A.
Beydoun, H. A.
Kitner-Triolo, M. H.
Kaufman, J. S.
Evans, M. K.
Zonderman, A. B.
TI Thyroid Hormones Are Associated With Cognitive Function: Moderation by
Sex, Race, and Depressive Symptoms
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID L-THYROXINE TREATMENT; STIMULATING HORMONE; OLD-AGE; SUBCLINICAL
HYPOTHYROIDISM; RANCHO BERNARDO; MOOD; HEALTHY; DEMENTIA; INDIVIDUALS;
REPLACEMENT
AB Context: Recent evidence indicates that thyroid hormones may be closely linked to cognition among adults.
Objective: We investigated associations between thyroid hormones and cognitive performance, while testing effect modification by sex, race, and elevated depressive symptoms (EDS).
Design: This cross-sectional study used extensive data from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study.
Setting: The study was conducted in Baltimore, Maryland, from 2004 to 2009.
Participants: Participants were U.S. adults aged 30 to 64 years. The sample size ranged from 1275 to 1346.
Main Outcome Measures: Outcomes included 13 cognitive test scores spanning domains of learning/memory, language/verbal, attention, visuo-spatial/visuo-construction, psychomotor speed, executive function, and mental status.
Results: Within reference ranges and after Bonferroni correction, elevated free thyroxine (fT(4)) was associated with better performance on tests of visuo-spatial/visuo-construction ability (overall, women, and African Americans) and learning/memory (women and African Americans), whereas a higher total thyroxine (tT(4)) level was associated with better performance in the domain of psychomotor speed (individuals without EDS) and higher levels of both fT(4) and tT(4) were linked to better language/verbal test performance among men. In contrast, higher T3(% uptake) was related to better performance on tests of visuo-spatial/visuo-construction ability and psychomotor speed among whites. When the above reference range was compared within the overall population and after Bonferroni correction, a within reference range fT(4) was linked to better performance on visuo-spatial/visuo-constrution ability and psychomotor speed, whereas a below normal range TSH level (compared with the reference range) was linked to better performance in domains of psychomotor speed and attention.
Conclusions: Thyroid hormones and cognition are closely linked differentially by sex, race, and EDS status.
C1 [Beydoun, M. A.; Kitner-Triolo, M. H.; Evans, M. K.; Zonderman, A. B.] NIA, NIH, Intramural Res Program, Baltimore, MD 21224 USA.
[Beydoun, H. A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23507 USA.
[Kaufman, J. S.] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 1A2, Canada.
RP Beydoun, MA (reprint author), NIA, NIH, Biomed Res Ctr, Intramural Res Program, 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; National Institutes of Health, Intramural
Research Program
FX This work was supported by the National Institute on Aging, National
Institutes of Health, Intramural Research Program.
NR 40
TC 16
Z9 16
U1 0
U2 13
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD AUG
PY 2013
VL 98
IS 8
BP 3470
EP 3481
DI 10.1210/jc.2013-1813
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 196NC
UT WOS:000322781300067
PM 23690311
ER
PT J
AU Azevedo, MF
Horvath, A
Bornstein, ER
Almeida, MQ
Xekouki, P
Faucz, FR
Gourgari, E
Nadella, K
Remmers, EF
Quezado, M
de Alexandre, RB
Kratz, CP
Nesterova, M
Greene, MH
Stratakis, CA
AF Azevedo, Monalisa F.
Horvath, Anelia
Bornstein, Ethan R.
Almeida, Madson Q.
Xekouki, Paraskevi
Faucz, Fabio R.
Gourgari, Evgenia
Nadella, Kiran
Remmers, Elaine F.
Quezado, Martha
de Alexandre, Rodrigo Bertollo
Kratz, Christian P.
Nesterova, Maria
Greene, Mark H.
Stratakis, Constantine A.
TI Cyclic AMP and c-KIT Signaling in Familial Testicular Germ Cell Tumor
Predisposition
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID OF-THE-LITERATURE; PHOSPHODIESTERASE 11A; CANCER; MUTATIONS; SEMINOMA;
VARIANTS; RISK; LINE; SUSCEPTIBILITY; HYPERPLASIA
AB Background: Familial testicular germ cell tumors (FTGCTs) are hypothesized to result from the combined interaction of multiple low-penetrance genes. We reported inactivating germline mutations of the cAMP-binding phosphodiesterase 11A (PDE11A) as modifiers of FTGCT risk. Recent genome-wide association studies have identified single-nucleotide polymorphisms in the KITLG gene, the ligand for the cKIT tyrosine kinase receptor, as strong modifiers of susceptibility to both familial and sporadic testicular germ cell tumors.
Design: We studied 94 patients with FTGCTs and 50 at-risk male relatives from 63 unrelated kindreds, in whom the PDE11A gene had been sequenced by investigating the association between KITLG genome-wide association study single-nucleotide polymorphisms rs3782179 and rs4474514 and FTGCT risk in these patients and in 692 controls. We also examined cAMP and c-KIT signaling in testicular tissues and cell lines and extended the studies to 2 sporadic cases, one with a PDE11A defect and one without, as a comparison.
Results: We found a higher frequency of the KITLG risk alleles in FTGCT patients who also had a PDE11A sequence variant, compared with those with a wild-type PDE11A sequence. In NTERA-2 and Tcam-2 cells transfected with the mutated forms of PDE11A (R52T, F258Y, Y727C, R804H, V820M, R867G, and M878V), cAMP levels were significantly higher, and the relative phosphodiesterase activity was lower than in the wild-type cells. KITLG expression was consistently increased in the presence of PDE11A-inactivating defects, both at the RNA and protein levels, in familial testicular germ cell tumors. The 2 sporadic cases that were studied, one with a PDE11A defect and another without, agreed with the data in FTGTCT and in the cell lines.
Conclusions: Patients with FTGCT and PDE11A defects also carry KITLG risk alleles more frequently. There may be an interaction between cAMP and c-KIT signaling in predisposition to testicular germ cell tumors.
C1 [Azevedo, Monalisa F.; Horvath, Anelia; Bornstein, Ethan R.; Almeida, Madson Q.; Xekouki, Paraskevi; Faucz, Fabio R.; Gourgari, Evgenia; Nadella, Kiran; de Alexandre, Rodrigo Bertollo; Nesterova, Maria; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Remmers, Elaine F.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Quezado, Martha] NCI, Pathol Lab, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Kratz, Christian P.; Greene, Mark H.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH,CRC, Bldg 10,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
RI de Alexandre, Rodrigo/H-9489-2013
OI de Alexandre, Rodrigo/0000-0002-1253-7716
FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico;
University of Brasilia, Brazil; National Institutes of Health Intramural
Research Programs of the Eunice Kennedy Shriver National Institute of
Child Health & Human Development; National Cancer Institute; Westat,
Inc. [N02-CP-11019, N02-CP-65504]
FX This work was supported, in part, by a postdoctoral fellowship grant
from Conselho Nacional de Desenvolvimento Cientifico e Tecnologico and
from the University of Brasilia, Brazil (to M.F.A.) and by the National
Institutes of Health Intramural Research Programs of the Eunice Kennedy
Shriver National Institute of Child Health & Human Development, and the
National Cancer Institute (to M.H.G. and C.P.K.). The Clinical Genetics
Branch Familial Testicular Germ Cell study was supported by Support
Services Contracts N02-CP-11019 and N02-CP-65504 with Westat, Inc.
NR 30
TC 9
Z9 10
U1 0
U2 7
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD AUG
PY 2013
VL 98
IS 8
BP E1393
EP E1400
DI 10.1210/jc.2012-2838
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 196NC
UT WOS:000322781300015
PM 23771924
ER
PT J
AU So, EC
Sallin, MA
Zhang, XY
Chan, SL
Sahni, L
Schulze, DH
Davila, E
Strome, SE
Jain, A
AF So, Edward C.
Sallin, Michelle A.
Zhang, Xiaoyu
Chan, Siaw L.
Sahni, Lepakshi
Schulze, Dan H.
Davila, Eduardo
Strome, Scott E.
Jain, Ajay
TI A high throughput method for enrichment of natural killer cells and
lymphocytes and assessment of in vitro cytotoxicity
SO JOURNAL OF IMMUNOLOGICAL METHODS
LA English
DT Article
DE ADCC; Rapid high-throughput; Tetrameric antibody complexes; Magnetic
cell separation; Chromium release; Calcein
ID COMPLEX CLASS-I; FLOW-CYTOMETRY; CALCEIN-AM; MONOCLONAL-ANTIBODIES;
EFFECTOR-CELLS; ANNEXIN-V; ASSAY; BLOOD; DIFFERENTIATION; EXPRESSION
AB In vitro assessment of lymphocyte and natural killer (NK) cell cytotoxicity typically employs density gradient centrifugation and magnetic cell separation to isolate effector cells, and chromium release to assess cytotoxicity. In order to improve the rapidity and scalability of in vitro cytotoxicity assessment, we evaluated the efficacy of a protocol utilizing tetrameric antibody complexes and SepMate (TM) isolation tubes to negatively select NK cells (TACs/Sep), and calcein-AM release to measure cytotoxicity. We compared the efficiency and accuracy of this protocol to a conventional approach employing density gradient centrifugation and magnetically labeled antibodies (DG/MACS) to isolate NK cells and chromium release to measure cytotoxicity.
The TACs/Sep method significantly decreased the time required for NK cell isolation (1 h vs. 4 h), but resulted in higher red blood cell contamination. NK cell activation marker expression (including CD94, NKG2D, NKp30, NKp46, DNAM-1, 2B4, KIR2DL1/S1, KIR2DL2/L3, intracellular granzyme B, and perforin) was similar when comparing NK cells isolated by the TACs/Sep or DG/MACS methods, but the TACs/Sep method induced higher expression of CD16. In vitro cytotoxicity against HT29 colon cancer and K562 leukemia cells was not affected by the isolation method. Lastly, by combining the TACs/Sep NK cell isolation method with calcein-acetoxymethyl diacetylester (calcein-AM) release, the time required to assess in vitro cytotoxicity was reduced by 33% (4 h) compared to protocols employing DG/MACS and chromium release. Altogether, these results provide the foundation for the development of a rapid, high throughput functional assay, and make it practical for the multiplexing of downstream applications, such as flow cytometric analysis and enzyme-linked immunosorbent assays (ELISAs). Published by Elsevier B.V.
C1 [So, Edward C.; Sahni, Lepakshi; Jain, Ajay] Baltimore Vet Adm Med Ctr, Div Res & Dev & Surg Serv, Baltimore, MD 21201 USA.
[So, Edward C.; Sahni, Lepakshi; Jain, Ajay] Univ Maryland, Sch Med, Div Gen & Oncol Surg, Baltimore, MD 21201 USA.
[So, Edward C.; Sallin, Michelle A.; Zhang, Xiaoyu; Schulze, Dan H.; Davila, Eduardo; Strome, Scott E.; Jain, Ajay] Univ Maryland, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Baltimore, MD 21201 USA.
[Chan, Siaw L.] Gliknik Inc, Baltimore, MD 21201 USA.
[Schulze, Dan H.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
[Davila, Eduardo] Marlene & Stewart Greenebaum NCI Canc Ctr, Baltimore, MD 21201 USA.
RP Jain, A (reprint author), Univ MD Sch Med, Dept Surg, Div Surg Oncol, 22 S Greene St, Baltimore, MD 21201 USA.
EM edward.so@umaryland.edu; msallin001@umaryland.edu;
Xzhang@smail.maryland.edu; achan@gliknik.com; Lsahni@smail.maryland.edu;
dschulze@umaryland.edu; edavila@som.umaryland.edu;
sstrome@smail.umaryland.edu; ajain@smail.umaryland.edu
NR 24
TC 5
Z9 5
U1 1
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-1759
J9 J IMMUNOL METHODS
JI J. Immunol. Methods
PD AUG
PY 2013
VL 394
IS 1-2
BP 40
EP 48
DI 10.1016/j.jim.2013.05.001
PG 9
WC Biochemical Research Methods; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 197NE
UT WOS:000322857100005
PM 23680234
ER
PT J
AU Camberis, M
Prout, M
Tang, SC
Forbes-Blom, E
Robinson, M
Kyle, R
Belkaid, Y
Paul, W
Le Gros, G
AF Camberis, Mali
Prout, Melanie
Tang, Shiau-Choot
Forbes-Blom, Elizabeth
Robinson, Marcus
Kyle, Ryan
Belkaid, Yasmine
Paul, William
Le Gros, Graham
TI Evaluating the in vivo Th2 priming potential among common allergens
SO JOURNAL OF IMMUNOLOGICAL METHODS
LA English
DT Article
DE Allergenicity; In vivo Th2 immunoassay; CD4 T cell; Interleukin-4; House
dust mite; eGFP-reporter
ID HOUSE-DUST MITE; T-CELLS; CROSS-REACTIVITY; RESPONSES; ANTIGEN;
RECEPTOR; MICE; SENSITIZATION; EOSINOPHILIA; INFECTION
AB Exposure to allergens, both man-made and from our environment is increasingly associated with the development of significant human health issues such as allergy and asthma. Allergen induced production of the cytokine interleukin (IL-)4 by Th2 cells is central to the pathogenesis of allergic disease (Gavett et al., 1994). The development of the G4 mouse, that expresses green fluorescent protein (GFP) as a surrogate for IL-4 protein expression has made it possible to directly track the immune cells that produce IL-4. By combining a reliable intradermal immunisation technique with the transgenic G4 mouse we have been able to develop a novel & unique in vivo primary Th2 immune response model (PTh2). When allergens relevant to human disease are evaluated using the PTh2 assay a dose dependent hierarchy of allergenicity is revealed with environmental allergens (cockroach, house dust mite) the most potent and food allergens being the least. In addition, the PTh2 assay is extremely sensitive to the immunoregulatory effects of Mycobacterial extracts and immunosuppressive drugs on primary Th2 cell development. Taken together, this assay provides a standardised method for the identification of the structural and functional properties of proteins relevant to allergenicity, and is a powerful screening tool for novel lead compounds that are effective at inhibiting the primary Th2 response in allergic diseases. (c) 2013 Elsevier B.V. All rights reserved.
C1 [Camberis, Mali; Prout, Melanie; Tang, Shiau-Choot; Forbes-Blom, Elizabeth; Robinson, Marcus; Kyle, Ryan; Le Gros, Graham] Malaghan Inst Med Res, Wellington 6242, New Zealand.
[Belkaid, Yasmine] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Paul, William] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Le Gros, G (reprint author), Malaghan Inst Med Res, POB 7060, Wellington 6242, New Zealand.
EM glegros@malaghan.org.nz
RI Forbes-Blom, Elizabeth/I-3648-2013; Le Gros, Graham/C-6725-2011;
OI Robinson, Marcus/0000-0001-5677-3078
FU Health Research Council of New Zealand; Majorie Barclay Trust
FX This project was supported by the Health Research Council of New Zealand
and the Majorie Barclay Trust.
NR 28
TC 6
Z9 6
U1 0
U2 18
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-1759
J9 J IMMUNOL METHODS
JI J. Immunol. Methods
PD AUG
PY 2013
VL 394
IS 1-2
BP 62
EP 72
DI 10.1016/j.jim.2013.05.004
PG 11
WC Biochemical Research Methods; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 197NE
UT WOS:000322857100008
PM 23688767
ER
PT J
AU Mahadevan, A
Ramalingaiah, AH
Parthasarathy, S
Nath, A
Ranga, U
Krishna, SS
AF Mahadevan, Anita
Ramalingaiah, Arvinda Hanumantapura
Parthasarathy, Satishchandra
Nath, Avindra
Ranga, Udaykumar
Krishna, Shankar Susarla
TI Neuropathological correlate of the "concentric target sign" in MRI of
HIV-associated cerebral toxoplasmosis
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE concentric target sign; MRI; T2 WI; toxoplasmosis; AIDS; neuropathology
ID CENTRAL-NERVOUS-SYSTEM; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PATHOLOGICAL
CORRELATION; AIDS; CT; ENCEPHALITIS; TUBERCULOMA; INFECTIONS; DIAGNOSIS;
HIV/AIDS
AB Cerebral toxoplasmosis is a frequent cause of focal brain lesions in the setting of immunodeficiency states, particularly acquired immune deficiency syndrome (AIDS), and magnetic resonance imaging (MRI) is an important diagnostic modality to differentiate toxoplasmosis from tuberculoma, and primary central nervous system lymphoma with diverse therapeutic implications. Several imaging patterns have been described in cerebral toxoplasmosis. The concentric target sign is a recently described MRI sign on T2-weighted imaging of cerebral toxoplasmosis that has concentric alternating zones of hypo- and hyperintensities. It is believed to be more specific than the well-known eccentric target sign in the diagnosis of cerebral toxoplasmosis and hence more useful in differentiation from other focal brain lesions in the context of AIDS. The concentric target sign, seen in deep parenchymal lesions, is distinct from the surface-based cortical eccentric target sign. The histopathological correlate of the latter has been recently described, but that of the concentric target sign is not known. In this study we describe the neuropathological correlate of this concentric target sign from the postmortem of a 40-year-old man with AIDS-associated cerebral toxoplasmosis. The concentric alternating zones of hypo/hyper/iso/intensities corresponded to zones of hemorrhage/fibrin-rich necrosis with edema/coagulative compact necrosis/inflammation with foamy histiocytes admixed with hemorrhage forming the outermost zone, respectively. The exclusive specificity of this sign in cerebral toxoplasmosis remains to be further elucidated. J. Magn. Reson. Imaging 2013;38:488-495. (c) 2013 Wiley Periodicals, Inc.
C1 [Mahadevan, Anita; Krishna, Shankar Susarla] Natl Inst Mental Hlth & Neurosci, Dept Neuropathol, Bangalore 560029, Karnataka, India.
[Ramalingaiah, Arvinda Hanumantapura] Natl Inst Mental Hlth & Neurosci, Dept Neuroimaging & Intervent Radiol, Bangalore 560029, Karnataka, India.
[Parthasarathy, Satishchandra] Natl Inst Mental Hlth & Neurosci, Dept Neurol, Bangalore 560029, Karnataka, India.
[Nath, Avindra] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA.
[Ranga, Udaykumar] Indian Inst Sci, Jawaharlal Nehru Ctr Adv Sci Res, Mol Biol & Genet Unit, HIV AIDS Lab, Bangalore 560012, Karnataka, India.
RP Mahadevan, A (reprint author), Natl Inst Mental Hlth & Neurosci, Dept Neuropathol, Bangalore 560029, Karnataka, India.
EM anita_mahadevan@yahoo.com
FU Johns Hopkins University; National Institute of Neurological Disorders
and Stroke (NINDS) [1RO1NS055628-01A2]
FX Contract grant sponsor: subaward from Johns Hopkins University; Contract
grant sponsor: National Institute of Neurological Disorders and Stroke
(NINDS); Contract grant number: 1RO1NS055628-01A2. The contents of the
study are solely the responsibility of the authors and do not represent
the official view of NINDS or JHU.
NR 29
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Z9 2
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-1807
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD AUG
PY 2013
VL 38
IS 2
BP 488
EP 495
DI 10.1002/jmri.24036
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 202HS
UT WOS:000323205300029
PM 23440973
ER
PT J
AU Liu, ZJ
Jiang, YH
Hou, YY
Hu, YM
Cao, XW
Tao, Y
Xu, C
Liu, SH
Wang, SL
Wang, LS
Shi, YF
Siebenlist, U
Zhang, XR
AF Liu, Zhanjie
Jiang, Yuhang
Hou, Yinyong
Hu, Yiming
Cao, Xinwei
Tao, Yu
Xu, Chen
Liu, Sanhong
Wang, Shouli
Wang, Lunshan
Shi, Yufang
Siebenlist, Ulrich
Zhang, Xiaoren
TI The I kappa B family member Bcl-3 stabilizes c-Myc in colorectal cancer
SO JOURNAL OF MOLECULAR CELL BIOLOGY
LA English
DT Letter
ID PROTEIN STABILITY
C1 [Liu, Zhanjie; Jiang, Yuhang; Hu, Yiming; Cao, Xinwei; Tao, Yu; Liu, Sanhong; Wang, Shouli; Wang, Lunshan; Shi, Yufang; Zhang, Xiaoren] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai 200031, Peoples R China.
[Liu, Zhanjie; Jiang, Yuhang; Hu, Yiming; Cao, Xinwei; Tao, Yu; Liu, Sanhong; Wang, Shouli; Wang, Lunshan; Shi, Yufang; Zhang, Xiaoren] Shanghai Jiao Tong Univ, Sch Med, Shanghai 200031, Peoples R China.
[Hou, Yinyong; Xu, Chen] Fudan Univ, Zhongshan Hosp, Dept Pathol, Shanghai 200032, Peoples R China.
[Wang, Shouli] Soochow Univ, Sch Med, Dept Pathol, Suzhou 215123, Peoples R China.
[Siebenlist, Ulrich] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Zhang, XR (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Hlth Sci, Key Lab Stem Cell Biol, Shanghai 200031, Peoples R China.
EM xrzhang@sibs.ac.cn
NR 10
TC 12
Z9 12
U1 0
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1674-2788
J9 J MOL CELL BIOL
JI J. Mol. Cell Biol.
PD AUG
PY 2013
VL 5
IS 4
BP 280
EP 282
DI 10.1093/jmcb/mjt020
PG 3
WC Cell Biology
SC Cell Biology
GA 198HT
UT WOS:000322914000008
PM 23794716
ER
PT J
AU Wang, XH
Fang, HQ
Huang, ZL
Shang, W
Hou, TT
Cheng, AW
Cheng, HP
AF Wang, Xianhua
Fang, Huaqiang
Huang, Zhanglong
Shang, Wei
Hou, Tingting
Cheng, Aiwu
Cheng, Heping
TI Imaging ROS signaling in cells and animals
SO JOURNAL OF MOLECULAR MEDICINE-JMM
LA English
DT Review
DE Reactive oxygen species (ROS); Mitochondria; ROS signaling; ROS
indicators; In vivo imaging
ID MITOCHONDRIAL PERMEABILITY TRANSITION; FLUORESCENT PROTEIN INDICATORS;
FREE-RADICAL THEORY; REACTIVE OXYGEN; SUPEROXIDE FLASHES;
HYDROGEN-PEROXIDE; OXIDATIVE-STRESS; CYCLOPHILIN-D; DIHYDRORHODAMINE
123; CARDIAC MYOCYTES
AB Reactive oxygen species (ROS) act as essential cellular messengers, redox regulators, and, when in excess, oxidative stressors that are widely implicated in pathologies of cancer and cardiovascular and neurodegenerative diseases. Understanding such complexity of the ROS signaling is critically hinged on the ability to visualize and quantify local, compartmental, and global ROS dynamics at high selectivity, sensitivity, and spatiotemporal resolution. The past decade has witnessed significant progress in ROS imaging at levels of intact cells, whole organs or tissues, and even live organisms. In particular, major advances include the development of novel synthetic or genetically encoded fluorescent protein-based ROS indicators, the use of protein indicator-expressing animal models, and the advent of in vivo imaging technology. Innovative ROS imaging has led to important discoveries in ROS signaling-for example, mitochondrial superoxide flashes as elemental ROS signaling events and hydrogen peroxide transients for wound healing. This review aims at providing an update of the current status in ROS imaging, while identifying areas of insufficient knowledge and highlighting emerging research directions.
C1 [Wang, Xianhua; Fang, Huaqiang; Huang, Zhanglong; Shang, Wei; Hou, Tingting; Cheng, Heping] Peking Univ, State Key Lab Biomembrane & Membrane Biotechnol, Inst Mol Med, Peking Tsinghua Ctr Life Sci,Beijing Key Lab Card, Beijing 100871, Peoples R China.
[Cheng, Aiwu] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
RP Cheng, HP (reprint author), Peking Univ, State Key Lab Biomembrane & Membrane Biotechnol, Inst Mol Med, Peking Tsinghua Ctr Life Sci,Beijing Key Lab Card, Beijing 100871, Peoples R China.
EM chengp@pku.edu.cn
FU National Key Basic Research Program of China [2013CB531200,
2011CB809100]; National Science Foundation of China [31221002, 31130067,
31123004, 30900264]
FX This work was supported by the National Key Basic Research Program of
China (2013CB531200 and 2011CB809100) and the National Science
Foundation of China (31221002, 31130067, 31123004, and 30900264).
NR 115
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U2 63
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0946-2716
J9 J MOL MED
JI J. Mol. Med.
PD AUG
PY 2013
VL 91
IS 8
BP 917
EP 927
DI 10.1007/s00109-013-1067-4
PG 11
WC Genetics & Heredity; Medicine, Research & Experimental
SC Genetics & Heredity; Research & Experimental Medicine
GA 193SM
UT WOS:000322581800003
PM 23873151
ER
PT J
AU Wynn, JL
Li, L
Cotten, CM
Phelps, DL
Shankaran, S
Goldberg, RN
Carlo, WA
Van Meurs, K
Das, A
Vohr, BR
Higgins, RD
Stoll, BJ
D'Angio, CT
AF Wynn, J. L.
Li, L.
Cotten, C. M.
Phelps, D. L.
Shankaran, S.
Goldberg, R. N.
Carlo, W. A.
Van Meurs, K.
Das, A.
Vohr, B. R.
Higgins, R. D.
Stoll, B. J.
D'Angio, C. T.
CA NICHD NRN
TI Blood stream infection is associated with altered heptavalent
pneumococcal conjugate vaccine immune responses in very low birth weight
infants
SO JOURNAL OF PERINATOLOGY
LA English
DT Article
DE VLBW; immune response; vaccine; sepsis; blood stream infection
ID NEONATAL RESEARCH NETWORK; PRETERM INFANTS; ONSET SEPSIS; AGE;
CHORIOAMNIONITIS; PATHOPHYSIOLOGY; IMMUNOGENICITY; PREMATURE
AB OBJECTIVE: Sepsis in older children and adults modifies immune system function. We compared serotype-specific antibody responses to heptavalent pneumococcal conjugate vaccine (PCV7) in very low birth weight infants (<1500 g, VLBWs) with and without blood stream infection (BSI) during their birth hospitalization.
STUDY DESIGN: Retrospective analysis of prospectively collected data for the Neonatal Research Network study of PCV7 responses among VLBWs. Infants received PCV7 at 2, 4 and 6 months after birth with blood drawn 4 to 6 weeks after third dose. Serotype antibodies were compared between infants with or without a history of BSI. Regression models were constructed with BW groups and other confounding factors identified in the primary study.
RESULT: In all, 244 infants completed the vaccine series and had serum antibody available; 82 had BSI. After adjustment, BSI was not associated with reduced odds of serum antibody >= 0.35 mu g ml(-1).
CONCLUSION: BSI was not associated with reduced odds of World Health Organization-defined protective PCV7 responses in VLBWs.
C1 [Wynn, J. L.; Cotten, C. M.] Vanderbilt Univ, Med Ctr, Dept Pediat, Div Neonatal Perinatal Med, Nashville, TN 37232 USA.
[Li, L.] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
[Cotten, C. M.; Goldberg, R. N.] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
[Phelps, D. L.; D'Angio, C. T.] Univ Rochester, Sch Med & Dent, Dept Pediat, Rochester, NY 14642 USA.
[Shankaran, S.] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
[Carlo, W. A.] Univ Alabama Birmingham, Dept Pediat, Div Neonatol, Birmingham, AL USA.
[Van Meurs, K.] Stanford Univ, Sch Med, Div Neonatal & Dev Med, Dept Pediat, Palo Alto, CA 94304 USA.
[Van Meurs, K.] Lucile Packard Childrens Hosp, Palo Alto, CA USA.
[Das, A.] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
[Vohr, B. R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA.
[Higgins, R. D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Stoll, B. J.] Emory Univ, Sch Med, Dept Pediat, Childrens Healthcare Atlanta, Atlanta, GA USA.
RP Wynn, JL (reprint author), Vanderbilt Univ, Med Ctr, Dept Pediat, Div Neonatal Perinatal Med, 2215 B Garland Ave,1125 MRB4 Light Hall, Nashville, TN 37232 USA.
EM james.wynn@vanderbilt.edu
FU National Institutes of Health; NICHD; National Center for Research
Resources; National Center for Advancing Translational Sciences
FX The National Institutes of Health, the NICHD, the National Center for
Research Resources and the National Center for Advancing Translational
Sciences provided grant support for the Neonatal Research Network's PCV7
and Generic Database Studies. Data collected at participating sites of
the NICHD NRN were transmitted to RTI International, the data
coordinating center (DCC) for the network, which stored, managed and
analyzed the data for this study. One behalf of the NRN, Dr A Das (DCC
Principal Investigator) and Dr L Li (DCC Statistician) had full access
to all of the data in the study, and with the NRN Center Principal
Investigators, take responsibility for the integrity of the data and
accuracy of the data analysis. The content is solely the responsibility
of the authors and does not necessarily represent the official views of
the National Institutes of Health. We are indebted to our medical and
nursing colleagues and the infants and their parents who agreed to take
part in this study.
NR 27
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U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0743-8346
J9 J PERINATOL
JI J. Perinatol.
PD AUG
PY 2013
VL 33
IS 8
BP 613
EP 618
DI 10.1038/jp.2013.5
PG 6
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 191VQ
UT WOS:000322442700008
PM 23370608
ER
PT J
AU Vitiello, B
Grabb, M
AF Vitiello, Benedetto
Grabb, Margaret
TI The Development of Targeted Neurobiological Therapies in Child and
Adolescent Psychiatry
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Editorial Material
ID RANDOMIZED CONTROLLED-TRIAL; COGNITIVE-BEHAVIORAL THERAPY;
FRAGILE-X-SYNDROME; TRANSCRANIAL MAGNETIC STIMULATION; RESISTANT
DEPRESSION; SPECTRUM DISORDERS; CLINICAL-TRIAL; COMBINATION;
METHYLPHENIDATE; SERTRALINE
C1 [Vitiello, Benedetto; Grabb, Margaret] NIMH, Bethesda, MD 20892 USA.
RP Vitiello, B (reprint author), NIMH, Room 7147,6001 Execut Blvd, Bethesda, MD 20892 USA.
EM bvitiell@mail.nih.gov
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U1 2
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD AUG
PY 2013
VL 52
IS 8
BP 775
EP 779
DI 10.1016/j.jaac.2013.06.002
PG 5
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 195HG
UT WOS:000322692300003
PM 23880487
ER
PT J
AU Guthrie, W
Swineford, LB
Wetherby, AM
Lord, C
AF Guthrie, Whitney
Swineford, Lauren B.
Wetherby, Amy M.
Lord, Catherine
TI Comparison of DSM-IV and DSM-5 Factor Structure Models for Toddlers With
Autism Spectrum Disorder
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE autism spectrum disorder (ASD); confirmatory factor analysis (CFA);
DSM-5; factor structure
ID REPETITIVE BEHAVIORS; DIAGNOSTIC INSTRUMENTS; SYMPTOM MODEL; CHILDREN;
CRITERIA; VALIDITY; AGE; INTERESTS; STABILITY; PHENOTYPE
AB Objective: The present study examined the factor structure of autism symptoms in toddlers, to aid understanding of the phenotype during the developmental period that represents the earliest manifestations of autism symptoms. This endeavor is particularly timely, given changes in symptom structure from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) to the recently released Fifth Edition (DSM-5). Method: Factor structure was examined in a sample of toddlers between 12 and 30 months of age (mean = 20.37 months, SD = 3.32 months) diagnosed with autism spectrum disorder (ASD) and recruited from community settings or referred for evaluation (N = 237). Confirmatory factor analyses were conducted comparing the relative fit of 4 distinct, previously proposed and validated models: DSM-5, DSM-IV, 1-factor, and an alternative 3-factor model proposed by van Lang et al. Results: Findings revealed that the 1-factor model provided the poorest fit, followed by the DSM-IV model and the van Lang et al. model. The DSM-5 model provided the best fit to the data relative to other models and good absolute fit. Indicators for the confirmatory factor analyses, drawn from the Autism Diagnostic Observation Schedule Toddler Module (ADOS-T), loaded strongly onto the DSM-5 Social Communication and Social Interaction factor and more variably onto the DSM-5 Restricted/Repetitive Language and Behavior factor. Conclusions: Results indicate that autism symptoms in toddlers, as measured by the ADOS-T, are separable and best deconstructed into the 2-factor DSM-5 structure, supporting the reorganization of symptoms in the DSM-5. Consistency of the present results in toddlers with previous studies in older children and adults suggests that the structure of autism symptoms may be similar throughout development.
C1 [Guthrie, Whitney; Wetherby, Amy M.] Florida State Univ, Tallahassee, FL 32303 USA.
[Swineford, Lauren B.] NIMH, Pediat & Dev Neuroscie Branch, Bethesda, MD USA.
RP Guthrie, W (reprint author), Florida State Univ, Autism Inst, 1940 North Monroe St,Suite 72, Tallahassee, FL 32303 USA.
EM whitney.guthrie@med.fsu.edu
FU National Institute on Deafness and Other Communication Disorders (NIDCD)
[R01DC007462, CDC U01DD000304]; National Institute of Child Health and
Human Development (NICHD) [R01HD065272]; NIMH [R01MH078165/R01MH077730];
Simons Foundation
FX This research was supported in part by the National Institute on
Deafness and Other Communication Disorders (NIDCD) grants R01DC007462
and CDC U01DD000304 (A.M W.), the National Institute of Child Health and
Human Development (NICHD) grants R01HD065272 and NIMH
R01MH078165/R01MH077730 (A.M.W., C.L.), and funding from the Simons
Foundation (C.L.).
NR 51
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U1 2
U2 58
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD AUG
PY 2013
VL 52
IS 8
BP 797
EP 805
DI 10.1016/j.jaac.2013.05.004
PG 9
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 195HG
UT WOS:000322692300006
PM 23880490
ER
PT J
AU Abi-Jaoudeh, N
Duffy, AG
Greten, TF
Kohn, EC
Clark, TWI
Wood, BJ
AF Abi-Jaoudeh, Nadine
Duffy, Austin G.
Greten, Tim F.
Kohn, Elise C.
Clark, Timothy W. I.
Wood, Bradford J.
TI Personalized Oncology in Interventional Radiology
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Review
ID METASTATIC COLORECTAL-CANCER; HER2-POSITIVE BREAST-CANCER; ENDOTHELIAL
GROWTH-FACTOR; CELL LUNG-CANCER; HEPATOCELLULAR-CARCINOMA; 1ST-LINE
TREATMENT; CLINICAL-TRIALS; TARGETED THERAPIES; NEXT-GENERATION; PLUS
IRINOTECAN
AB As personalized medicine-becomes more applicable to oncologic practice, image-guided biopsies will be integral for enabling predictive and pharmacodynamic molecular pathology. Interventional radiology has a key role in defining patient-specific Management. Advances in diagnostic techniques, genomics, and proteomics enable a window into subcellular mechanisms driving hyperproliferation, metastatic capabilities, and tumor angiogenesis. A new era of personalized medicine has evolved whereby clinical decisions are adjusted according to a patient's molecular profile. Several mutations and key markets already have been introduced into standard oncologic practice. A broader understanding of personalized oncology will help interventionalists play a greater role in therapy selection and discovery.
C1 [Abi-Jaoudeh, Nadine; Wood, Bradford J.] NIH, Bethesda, MD 20892 USA.
[Duffy, Austin G.; Greten, Tim F.; Kohn, Elise C.] NIH, Med Oncol Branch, Bethesda, MD 20892 USA.
[Clark, Timothy W. I.] Penn Presbyterian Med Ctr, Sect Intervent Radiol, Philadelphia, PA USA.
RP Abi-Jaoudeh, N (reprint author), NIH, Rm 1C365,Bldg 10,MSC 1182,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM naj@mail.nih.gov
RI Greten, Tim/B-3127-2015
OI Greten, Tim/0000-0002-0806-2535
FU National Institutes of Health Center for Interventional Oncology;
Intramural Research Program of the National Institutes of Health
[1Z01CL046011-01]
FX This work is supported in part by the National Institutes of Health
Center for Interventional Oncology and the Intramural Research Program
of the National Institutes of Health (grant: 1Z01CL046011-01).
NR 52
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U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1051-0443
J9 J VASC INTERV RADIOL
JI J. Vasc. Interv. Radiol.
PD AUG
PY 2013
VL 24
IS 8
BP 1083
EP 1092
DI 10.1016/j.jvir.2013.04.019
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA 198LL
UT WOS:000322924300001
PM 23885909
ER
PT J
AU Herman, SEM
Barr, PM
McAuley, EM
Liu, D
Wiestner, A
Friedberg, JW
AF Herman, S. E. M.
Barr, P. M.
McAuley, E. M.
Liu, D.
Wiestner, A.
Friedberg, J. W.
TI Fostamatinib inhibits B-cell receptor signaling, cellular activation and
tumor proliferation in patients with relapsed and refractory chronic
lymphocytic leukemia
SO LEUKEMIA
LA English
DT Letter
ID TYROSINE KINASE; SYK; ANTIGEN; MIGRATION; INDICATE; DISODIUM
C1 [Herman, S. E. M.; McAuley, E. M.; Liu, D.; Wiestner, A.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Barr, P. M.; Friedberg, J. W.] Univ Rochester, Sch Med & Dent, Dept Med, Rochester, NY 14642 USA.
RP Herman, SEM (reprint author), NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
EM Adrian.Wiestner@nih.gov; Jonathan_Friedberg@URMC.Rochester.edu
OI Barr, Paul/0000-0002-9733-401X
FU Intramural NIH HHS [ZIA HL002346-09]; NCI NIH HHS [P50 CA13080503]
NR 15
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U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD AUG
PY 2013
VL 27
IS 8
BP 1769
EP 1773
DI 10.1038/leu.2013.37
PG 6
WC Oncology; Hematology
SC Oncology; Hematology
GA 197BP
UT WOS:000322823200024
PM 23385377
ER
PT J
AU Aalbers, AM
Calado, RT
Young, NS
Zwaan, CM
Wu, C
Kajigaya, S
Coenen, EA
Baruchel, A
Geleijns, K
de Haas, V
Kaspers, GJL
Kuijpers, TW
Reinhardt, D
Trka, J
Zimmermann, M
Pieters, R
van der Velden, VHJ
van den Heuvel-Eibrink, MM
AF Aalbers, A. M.
Calado, R. T.
Young, N. S.
Zwaan, C. M.
Wu, C.
Kajigaya, S.
Coenen, E. A.
Baruchel, A.
Geleijns, K.
de Haas, V.
Kaspers, G. J. L.
Kuijpers, T. W.
Reinhardt, D.
Trka, J.
Zimmermann, M.
Pieters, R.
van der Velden, V. H. J.
van den Heuvel-Eibrink, M. M.
TI Telomere length and telomerase complex mutations in pediatric acute
myeloid leukemia
SO LEUKEMIA
LA English
DT Letter
ID CELLS; ABERRATIONS; EXPRESSION
C1 [Aalbers, A. M.; Zwaan, C. M.; Coenen, E. A.; Pieters, R.; van den Heuvel-Eibrink, M. M.] Sophia Childrens Univ Hosp, Erasmus MC, Dept Pediat Oncol Hematol, Rotterdam, Netherlands.
[Aalbers, A. M.; Geleijns, K.; van der Velden, V. H. J.] Erasmus MC, Dept Immunol, Rotterdam, Netherlands.
[Aalbers, A. M.; Calado, R. T.; Young, N. S.; Wu, C.; Kajigaya, S.] NHLBI, Hematol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Calado, R. T.] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, Ribeirao Preto, SP, Brazil.
[Baruchel, A.] Hop Robert Debre, Dept Hematol, F-75019 Paris, France.
[Geleijns, K.] Erasmus MC, Dept Neurol, Rotterdam, Netherlands.
[de Haas, V.; Kaspers, G. J. L.] DCOG, The Hague, Netherlands.
[Kaspers, G. J. L.] Vrije Univ Amsterdam, Med Ctr, Dept Pediat Oncol Hematol, Amsterdam, Netherlands.
[Kuijpers, T. W.] Acad Med Ctr, Sanquin Res & Landsteiner Lab, Dept Blood Cell Res, Amsterdam, Netherlands.
[Kuijpers, T. W.] Emma Childrens Hosp, Acad Med Ctr, Dept Pediat Hematol Immunol & Infect Dis, Amsterdam, Netherlands.
[Reinhardt, D.; Zimmermann, M.] Hannover Med Sch, AML BFM Study Grp, Dept Pediat Hematol Oncol, Hannover, Germany.
[Trka, J.] Charles Univ Prague, Sch Med 2, Dept Pediat Hematol Oncol, Prague, Czech Republic.
RP Aalbers, AM (reprint author), Sophia Childrens Univ Hosp, Erasmus MC, Dept Pediat Oncol Hematol, Rotterdam, Netherlands.
EM m.vandenheuvel@erasmusmc.nl
RI Calado, Rodrigo/G-2619-2011
FU Intramural NIH HHS [Z99 HL999999, ZIA HL006089-04]
NR 15
TC 10
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U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD AUG
PY 2013
VL 27
IS 8
BP 1786
EP 1789
DI 10.1038/leu.2013.57
PG 4
WC Oncology; Hematology
SC Oncology; Hematology
GA 197BP
UT WOS:000322823200029
PM 23426163
ER
PT J
AU Brunner, CC
Stern, SH
Minniti, R
Parry, MI
Skopec, M
Chakrabarti, K
AF Brunner, Claudia C.
Stern, Stanley H.
Minniti, Ronaldo
Parry, Marie I.
Skopec, Marlene
Chakrabarti, Kish
TI CT head-scan dosimetry in an anthropomorphic phantom and associated
measurement of ACR accreditation-phantom imaging metrics under
clinically representative scan conditions
SO MEDICAL PHYSICS
LA English
DT Article
DE CT; dose; image quality; OSLDs
ID COMPUTED-TOMOGRAPHY; RADIATION-EXPOSURE; DOSE REDUCTION; ITERATIVE
RECONSTRUCTION; PERSPECTIVE; STRATEGIES; QUALITY; SYSTEM
AB Purpose: To measure radiation absorbed dose and its distribution in an anthropomorphic head phantom under clinically representative scan conditions in three widely used computed tomography (CT) scanners, and to relate those dose values to metrics such as high-contrast resolution, noise, and contrast-to-noise ratio (CNR) in the American College of Radiology CT accreditation phantom.
Methods: By inserting optically stimulated luminescence dosimeters (OSLDs) in the head of an anthropomorphic phantom specially developed for CT dosimetry (University of Florida, Gainesville), we measured dose with three commonly used scanners (GE Discovery CT750 HD, Siemens Definition, Philips Brilliance 64) at two different clinical sites (Walter Reed National Military Medical Center, National Institutes of Health). The scanners were set to operate with the same data-acquisition and image-reconstruction protocols as used clinically for typical head scans, respective of the practices of each facility for each scanner. We also analyzed images of the ACR CT accreditation phantom with the corresponding protocols. While the Siemens Definition and the Philips Brilliance protocols utilized only conventional, filtered back-projection (FBP) image-reconstruction methods, the GE Discovery also employed its particular version of an adaptive statistical iterative reconstruction (ASIR) algorithm that can be blended in desired proportions with the FBP algorithm. We did an objective image-metrics analysis evaluating the modulation transfer function (MTF), noise power spectrum (NPS), and CNR for images reconstructed with FBP. For images reconstructed with ASIR, we only analyzed the CNR, since MTF and NPS results are expected to depend on the object for iterative reconstruction algorithms.
Results: The OSLD measurements showed that the Siemens Definition and the Philips Brilliance scanners (located at two different clinical facilities) yield average absorbed doses in tissue of 42.6 and 43.1 mGy, respectively. The GE Discovery delivers about the same amount of dose (43.7 mGy) when run under similar operating and image-reconstruction conditions, i.e., without tube current modulation and ASIR. The image-metrics analysis likewise showed that the MTF, NPS, and CNR associated with the reconstructed images are mutually comparable when the three scanners are run with similar settings, and differences can be attributed to different edge-enhancement properties of the applied reconstruction filters. Moreover, when the GE scanner was operated with the facility's scanner settings for routine head exams, which apply 50% ASIR and use only approximately half of the 100%-FBP dose, the CNR of the images showed no significant change. Even though the CNR alone is not sufficient to characterize the image quality and justify any dose reduction claims, it can be useful as a constancy test metric.
Conclusions: This work presents a straightforward method to connect direct measurements of CT dose with objective image metrics such as high-contrast resolution, noise, and CNR. It demonstrates that OSLD measurements in an anthropomorphic head phantom allow a realistic and locally precise estimation of magnitude and spatial distribution of dose in tissue delivered during a typical CT head scan. Additional objective analysis of the images of the ACR accreditation phantom can be used to relate the measured doses to high contrast resolution, noise, and CNR. (C) 2013 American Association of Physicists in Medicine.
C1 [Brunner, Claudia C.; Stern, Stanley H.; Chakrabarti, Kish] US FDA, Silver Spring, MD 20993 USA.
[Minniti, Ronaldo] NIST, Gaithersburg, MD 20899 USA.
[Parry, Marie I.] Walter Reed Natl Mil Med Ctr, Bethesda, MD 20889 USA.
[Skopec, Marlene] NIH, Bethesda, MD 20892 USA.
RP Chakrabarti, K (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM kish.chakrabarti@fda.hhs.gov
FU FDA Critical Path Initiative
FX Claudia C. Brunner was funded by the FDA Critical Path Initiative. The
authors wish to acknowledge the invaluable help provided by Arvel J. New
(WRNMMC) and Fred Dowdell (NIH) in collecting data in clinical settings.
The authors further thank John Jaeckle and Paavana Sainath of GE for
lending us the GEPP and answering our questions as well as Dominic
Siewko of Philips for his help. Finally, the authors want to thank
Michelle O'Brien at NIST for her support in providing the x-ray
reference beams at NIST.
NR 39
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U1 1
U2 8
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 AUG
PY 2013
VL 40
IS 8
AR 081917
DI 10.1118/1.4815964
PG 12
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 195XC
UT WOS:000322735900039
PM 23927331
ER
PT J
AU Han, EY
Lee, C
Mcguire, L
Brown, TLY
Bolch, WE
AF Han, Eun Young
Lee, Choonsik
Mcguire, Lynn
Brown, Tracy L. Y.
Bolch, Wesley E.
TI Organ S values and effective doses for family members exposed to adult
patients following I-131 treatment: A Monte Carlo simulation study
SO MEDICAL PHYSICS
LA English
DT Article
DE I-131; S value; effective dose; thyroid; hybrid phantoms; Monte Carlo
transport
ID COMPUTATIONAL PHANTOMS; THERAPY; RELEASE; SCHEMA; POINT; LINE
AB Purpose: To calculate organ S values (mGy/Bq-s) and effective doses per time-integrated activity (mSv/Bq-s) for pediatric and adult family members exposed to an adult male or female patient treated with I-131 using a series of hybrid computational phantoms coupled with a Monte Carlo radiation transport technique.
Methods: A series of pediatric and adult hybrid computational phantoms were employed in the study. Three different exposure scenarios were considered: (1) standing face-to-face exposures between an adult patient and pediatric or adult family phantoms at five different separation distances; (2) an adult female patient holding her newborn child, and (3) a 1-yr-old child standing on the lap of an adult female patient. For the adult patient model, two different thyroid-related diseases were considered: hyperthyroidism and differentiated thyroid cancer (DTC) with corresponding internal distributions of I-131. A general purpose Monte Carlo code, MCNPX v2.7, was used to perform the Monte Carlo radiation transport.
Results: The S values show a strong dependency on age and organ location within the family phantoms at short distances. The S values and effective dose per time-integrated activity from the adult female patient phantom are relatively high at shorter distances and to younger family phantoms. At a distance of 1 m, effective doses per time-integrated activity are lower than those values based on the NRC (Nuclear Regulatory Commission) by a factor of 2 for both adult male and female patient phantoms. The S values to target organs from the hyperthyroid-patient source distribution strongly depend on the height of the exposed family phantom, so that their values rapidly decrease with decreasing height of the family phantom. Active marrow of the 10-yr-old phantom shows the highest S values among family phantoms for the DTC-patient source distribution. In the exposure scenario of mother and baby, S values and effective doses per time-integrated activity to the newborn and 1-yr-old phantoms for a hyperthyroid-patient source are higher than values for a DTC-patient source.
Conclusions: The authors performed realistic assessments of I-131 organ S values and effective dose per time-integrated activity from adult patients treated for hyperthyroidism and DTC to family members. In addition, the authors' studies consider Monte Carlo simulated "mother and baby/child" exposure scenarios for the first time. Based on these results, the authors reconfirm the strong conservatism underlying the point source method recommended by the US NRC. The authors recommend that various factors such as the type of the patient's disease, the age of family members, and the distance/posture between the patient and family members must be carefully considered to provide realistic dose estimates for patient-to-family exposures. (C) 2013 American Association of Physicists in Medicine.
C1 [Han, Eun Young] Univ Arkansas Med Sci, Dept Radiat Oncol, Little Rock, AR 72205 USA.
[Lee, Choonsik] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Mcguire, Lynn; Brown, Tracy L. Y.] Univ Arkansas Med Sci, Div Nucl Med, Dept Radiol, Little Rock, AR 72205 USA.
[Bolch, Wesley E.] Univ Florida, J Crayton Pruitt Family Dept Biomed Engn, Gainesville, FL 32611 USA.
RP Han, EY (reprint author), Univ Arkansas Med Sci, Dept Radiat Oncol, Little Rock, AR 72205 USA.
EM eyhan@uams.edu
NR 20
TC 5
Z9 5
U1 0
U2 5
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 AUG
PY 2013
VL 40
IS 8
AR 083901
DI 10.1118/1.4812425
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 195XC
UT WOS:000322735900069
PM 23927361
ER
PT J
AU Petrick, N
Sahiner, B
Armato, SG
Bert, A
Correale, L
Delsanto, S
Freedman, MT
Fryd, D
Gur, D
Hadjiiski, L
Huo, ZM
Jiang, YL
Morra, L
Paquerault, S
Raykar, V
Samuelson, F
Summers, RM
Tourassi, G
Yoshida, H
Zheng, B
Zhou, C
Chan, HP
AF Petrick, Nicholas
Sahiner, Berkman
Armato, Samuel G., III
Bert, Alberto
Correale, Loredana
Delsanto, Silvia
Freedman, Matthew T.
Fryd, David
Gur, David
Hadjiiski, Lubomir
Huo, Zhimin
Jiang, Yulei
Morra, Lia
Paquerault, Sophie
Raykar, Vikas
Samuelson, Frank
Summers, Ronald M.
Tourassi, Georgia
Yoshida, Hiroyuki
Zheng, Bin
Zhou, Chuan
Chan, Heang-Ping
TI Evaluation of computer-aided detection and diagnosis systems
SO MEDICAL PHYSICS
LA English
DT Article
DE computer-aided detection and diagnosis (CAD); computer-aided detection
(CADe); computer-aided diagnosis (CADx); performance assessment;
standalone performance; reader performance; clinical performance
ID OPERATING CHARACTERISTIC ANALYSIS; BREAST-CANCER DETECTION;
MAXIMUM-LIKELIHOOD-ESTIMATION; IMAGE DATABASE CONSORTIUM; SMALL
PULMONARY NODULES; MEMORIAL FUND LECTURE; CT COLONOGRAPHY; LUNG NODULES;
SCREENING MAMMOGRAPHY; OBSERVER-PERFORMANCE
AB Computer-aided detection and diagnosis (CAD) systems are increasingly being used as an aid by clinicians for detection and interpretation of diseases. Computer-aided detection systems mark regions of an image that may reveal specific abnormalities and are used to alert clinicians to these regions during image interpretation. Computer-aided diagnosis systems provide an assessment of a disease using image-based information alone or in combination with other relevant diagnostic data and are used by clinicians as a decision support in developing their diagnoses. While CAD systems are commercially available, standardized approaches for evaluating and reporting their performance have not yet been fully formalized in the literature or in a standardization effort. This deficiency has led to difficulty in the comparison of CAD devices and in understanding how the reported performance might translate into clinical practice. To address these important issues, the American Association of Physicists in Medicine (AAPM) formed the Computer Aided Detection in Diagnostic Imaging Subcommittee (CADSC), in part, to develop recommendations on approaches for assessing CAD system performance. The purpose of this paper is to convey the opinions of the AAPM CADSC members and to stimulate the development of consensus approaches and "best practices" for evaluating CAD systems. Both the assessment of a standalone CAD system and the evaluation of the impact of CAD on end-users are discussed. It is hoped that awareness of these important evaluation elements and the CADSC recommendations will lead to further development of structured guidelines for CAD performance assessment. Proper assessment of CAD system performance is expected to increase the understanding of a CAD system's effectiveness and limitations, which is expected to stimulate further research and development efforts on CAD technologies, reduce problems due to improper use, and eventually improve the utility and efficacy of CAD in clinical practice. (C) 2013 American Association of Physicists in Medicine.
C1 [Petrick, Nicholas; Sahiner, Berkman; Samuelson, Frank] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Armato, Samuel G., III; Jiang, Yulei] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA.
[Bert, Alberto; Correale, Loredana; Delsanto, Silvia; Morra, Lia] im3D SpA, I-10153 Turin, Italy.
[Freedman, Matthew T.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA.
[Fryd, David] Riverain Med, Miamisburg, OH 45342 USA.
[Gur, David] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15213 USA.
[Hadjiiski, Lubomir; Zhou, Chuan; Chan, Heang-Ping] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA.
[Huo, Zhimin] Carestream Hlth Inc, Rochester, NY 14615 USA.
[Raykar, Vikas] IBM Res, Nagawara Bangalore 560045, India.
[Summers, Ronald M.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Tourassi, Georgia] Oak Ridge Natl Lab, Computat Sci & Engn Div, Oak Ridge, TN 37831 USA.
[Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Yoshida, Hiroyuki] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Zheng, Bin] Univ Oklahoma, Sch Elect & Comp Engn, Norman, OK 73019 USA.
RP Chan, HP (reprint author), Univ Michigan, Dept Radiol, 1500 East Med Ctr Dr,MIB C479, Ann Arbor, MI 48109 USA.
EM chanhp@umich.edu
OI Bert, Alberto/0000-0001-8391-7508; Tourassi,
Georgia/0000-0002-9418-9638; Zheng, Bin/0000-0002-7682-6648
FU Intramural Research Program of the National Institutes of Health,
Clinical Center; University of Chicago; iCAD; Riverain Technologies
through Georgetown University Medical Center
FX The authors are grateful to the members and participants of the CADSC
who have contributed to the stimulating discussions during many meetings
and teleconferences. R. M. S. is supported in part by the Intramural
Research Program of the National Institutes of Health, Clinical Center;
the views expressed in this paper are the opinions of the authors and do
not necessarily represent the views of the National Institutes of Health
or the Department of Health and Human Services. S. G. A. and H.Y.
receive royalties and licensing fees through the University of Chicago
related to CAD. R. M. S. receives patent royalties and research support
related to CAD from iCAD. M. T. F. receives funding from Riverain
Technologies through Georgetown University Medical Center.
NR 139
TC 9
Z9 10
U1 4
U2 34
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 AUG
PY 2013
VL 40
IS 8
AR 087001
DI 10.1118/1.4816310
PG 17
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 195XC
UT WOS:000322735900073
PM 23927365
ER
PT J
AU Brosh, RM
AF Brosh, Robert M., Jr.
TI DNA helicases involved in DNA repair and their roles in cancer
SO NATURE REVIEWS CANCER
LA English
DT Review
ID WERNER-SYNDROME PROTEIN; ANEMIA GROUP J; BLOOMS-SYNDROME HELICASE;
DOUBLE-STRAND BREAKS; CROSS-LINK REPAIR; NUCLEOTIDE EXCISION-REPAIR;
MAINTAIN GENOME STABILITY; MODEL REPLICATION FORK; SYNDROME
GENE-PRODUCT; HUMAN RECQ1 HELICASE
AB Helicases have major roles in genome maintenance by unwinding structured nucleic acids. Their prominence is marked by various cancers and genetic disorders that are linked to helicase defects. Although considerable effort has been made to understand the functions of DNA helicases that are important for genomic stability and cellular homeostasis, the complexity of the DNA damage response leaves us with unanswered questions regarding how helicase-dependent DNA repair pathways are regulated and coordinated with cell cycle checkpoints. Further studies may open the door to targeting helicases in order to improve cancer treatments based on DNA-damaging chemotherapy or radiation.
C1 NIA, NIH, NIH Biomed Res Ctr, Lab Mol Gerontol, Baltimore, MD 21224 USA.
RP Brosh, RM (reprint author), NIA, NIH, NIH Biomed Res Ctr, Lab Mol Gerontol, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM broshr@mail.nih.gov
FU Intramural Research Program of the US National Institutes of Health
(NIH), National Institute on Aging (NIA)
FX This research was supported by the Intramural Research Program of the US
National Institutes of Health (NIH), National Institute on Aging (NIA).
I thank J. Burril of the NIA Visual Media Section for artwork in drafts
of figures 2,3 and 5. I express gratitude to M. Seidman, Y. Liu, V. Bohr
and W. Wang (NIA-NIH) for critically reading the manuscript, and S.
Matson (University of North Carolina at Chapel Hill) for introducing me
to the helicase field and for providing strong mentorship. I apologize
to those researchers whose published work on DNA helicases was not cited
owing to length restrictions.
NR 228
TC 92
Z9 93
U1 10
U2 76
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-175X
J9 NAT REV CANCER
JI Nat. Rev. Cancer
PD AUG
PY 2013
VL 13
IS 8
BP 542
EP 558
DI 10.1038/nrc3560
PG 17
WC Oncology
SC Oncology
GA 187YS
UT WOS:000322158200009
PM 23842644
ER
PT J
AU Hourigan, CS
Karp, JE
AF Hourigan, Christopher S.
Karp, Judith E.
TI Minimal residual disease in acute myeloid leukaemia
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Review
ID STEM-CELL TRANSPLANTATION; MULTIPARAMETER FLOW-CYTOMETRY; ACUTE
MYELOGENOUS LEUKEMIA; POLYMERASE-CHAIN-REACTION; ACUTE PROMYELOCYTIC
LEUKEMIA; TUMOR GENE-1 EXPRESSION; INTERNAL TANDEM DUPLICATION; TIME
QUANTITATIVE PCR; COMPLETE REMISSION; PERIPHERAL-BLOOD
AB Technological advances in the laboratory have led to substantial improvements in clinical decision making through the introduction of pretreatment prognostic risk stratification factors in acute myeloid leukaemia (AML). Unfortunately, similar progress has not been made in treatment response criteria, with the definition of 'complete remission' in AML largely unchanged for over half a century. Several clinical trials have demonstrated that high-sensitivity measurements of residual disease burden during or after treatment can be performed, that results are predictive for clinical outcome and can be used to improve outcomes by guiding additional therapeutic intervention to patients in clinical complete remission, but at increased relapse risk. We review these recent trials, the characteristics and challenges of the modalities currently used to detect minimal residual disease (MRD), and outline opportunities to both refine detection and improve clinical use of MRD measurements. MRD measurement is already the standard of care in other myeloid malignancies, such as chronic myelogenous leukaemia and acute promyelocytic leukaemia (APL). It is our belief that response criteria for non-APL AML should be updated to include assessment for molecular complete remission and recommendations for post-consolidation surveillance should include regular monitoring for molecular relapse as standard of care.
C1 [Hourigan, Christopher S.] NHLBI, Myeloid Malignancies Sect, Hematol Branch, Bethesda, MD 20892 USA.
[Karp, Judith E.] Sidney Kimmel Comprehens Ctr Johns Hopkins, Baltimore, MD 21231 USA.
RP Hourigan, CS (reprint author), NHLBI, Myeloid Malignancies Sect, Hematol Branch, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM hourigan@nih.gov
RI Hourigan, Christopher/S-2476-2016
OI Hourigan, Christopher/0000-0002-6189-8067
FU National Institutes of Health [P30CA006973]; Intramural Research Program
of the NIH, National Heart, Lung and Blood Institute
FX The authors wish to thank Gouri Bardhan, A. John Barrett, Minoo
Battiwalla, Luis Diaz, Meghali Goswami, Philip J. McCoy and Sandhya
Panch for useful discussions and Alan Hoofring of the NIH Medical Arts
Service for assistance in creating Figure 1. This research was supported
by National Institutes of Health grant P30CA006973 (JEK) and the
Intramural Research Program of the NIH, National Heart, Lung and Blood
Institute (CSH). Any views expressed here represent personal opinion and
do not necessarily reflect those of the U. S. Department of Health and
Human Services, or the United States federal government.
NR 138
TC 53
Z9 55
U1 4
U2 20
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4774
J9 NAT REV CLIN ONCOL
JI Nat. Rev. Clin. Oncol.
PD AUG
PY 2013
VL 10
IS 8
BP 460
EP 471
DI 10.1038/nrclinonc.2013.100
PG 12
WC Oncology
SC Oncology
GA 190XN
UT WOS:000322376900007
PM 23799371
ER
PT J
AU Gause, WC
Wynn, TA
Allen, JE
AF Gause, William C.
Wynn, Thomas A.
Allen, Judith E.
TI Type 2 immunity and wound healing: evolutionary refinement of adaptive
immunity by helminths
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Article
ID ALTERNATIVELY ACTIVATED MACROPHAGES; HAEMAPHYSALIS-LONGICORNIS TICKS;
INDUCED PULMONARY INFLAMMATION; DENDRITIC CELL-FUNCTION; REGULATORY
T-CELLS; HYGIENE HYPOTHESIS; GENE-EXPRESSION; LYMPHOID-CELLS; TH2
RESPONSES; MURINE SCHISTOSOMIASIS
AB Helminth-induced type 2 immune responses, which are characterized by the T helper 2 cell-associated cytokines interleukin-4 (IL-4) and IL-13, mediate host protection through enhanced tissue repair, the control of inflammation and worm expulsion. In this Opinion article, we consider type 2 immunity in the context of helminth-mediated tissue damage. We examine the relationship between the control of helminth infection and the mechanisms of wound repair, and we provide a new understanding of the adaptive type 2 immune response and its contribution to both host tolerance and resistance.
C1 [Gause, William C.] Rutgers State Univ, New Jersey Med Sch, Dept Med, Ctr Immun & Inflammat, Newark, NJ 07103 USA.
[Wynn, Thomas A.] NIAID, Immunopathogenesis Sect, Program Tissue Immun & Repair, NIH, Bethesda, MD 20892 USA.
[Wynn, Thomas A.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Allen, Judith E.] Univ Edinburgh, Sch Biol Sci, Ctr Immun Infect & Evolut, Edinburgh EH9 3JT, Midlothian, Scotland.
RP Gause, WC (reprint author), Rutgers State Univ, New Jersey Med Sch, Dept Med, Ctr Immun & Inflammat, Newark, NJ 07103 USA.
EM gausewc@umdnj.edu
RI Allen, Judith/C-9198-2011
OI Allen, Judith/0000-0002-3829-066X
FU US National Institutes of Health (NIH) [R01AI031678, R01AI066188];
Intramural Research Program from the NIH National Institute of Allergy
and Infectious Diseases
FX The authors wish to thank F. Finkelman at the Division of Allergy and
Immunology, Cincinnati Children's Hospital Medical Center, USA, for
providing excellent critical comments that strengthened this manuscript.
This work was partly supported by the US National Institutes of Health
(NIH) grants R01AI031678 and R01AI066188 awarded to W.C.G., and T.A.W.
is supported by the Intramural Research Program from the NIH National
Institute of Allergy and Infectious Diseases.
NR 92
TC 102
Z9 106
U1 2
U2 33
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1733
J9 NAT REV IMMUNOL
JI Nat. Rev. Immunol.
PD AUG
PY 2013
VL 13
IS 8
BP 607
EP 614
DI 10.1038/nri3476
PG 8
WC Immunology
SC Immunology
GA 188TS
UT WOS:000322217500014
PM 23827958
ER
PT J
AU Specks, U
Merkel, PA
Seo, P
Spiera, R
Langford, CA
Hoffman, GS
Kallenberg, CGM
Clair, EWS
Fessler, BJ
Ding, L
Viviano, L
Tchao, NK
Phippard, DJ
Asare, AL
Lim, N
Ikle, D
Jepson, B
Brunetta, P
Allen, NB
Fervenza, FC
Geetha, D
Keogh, K
Kissin, EY
Monach, PA
Peikert, T
Stegeman, C
Ytterberg, SR
Mueller, M
Sejismundo, LP
Mieras, K
Stone, JH
AF Specks, Ulrich
Merkel, Peter A.
Seo, Philip
Spiera, Robert
Langford, Carol A.
Hoffman, Gary S.
Kallenberg, Cees G. M.
Clair, E. William St.
Fessler, Barri J.
Ding, Linna
Viviano, Lisa
Tchao, Nadia K.
Phippard, Deborah J.
Asare, Adam L.
Lim, Noha
Ikle, David
Jepson, Brett
Brunetta, Paul
Allen, Nancy B.
Fervenza, Fernando C.
Geetha, Duvuru
Keogh, Karina
Kissin, Eugene Y.
Monach, Paul A.
Peikert, Tobias
Stegeman, Coen
Ytterberg, Steven R.
Mueller, Mark
Sejismundo, Lourdes P.
Mieras, Kathleen
Stone, John H.
CA RAVE-ITN Res Grp
TI Efficacy of Remission-Induction Regimens for ANCA-Associated Vasculitis
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID ANTIBODY-ASSOCIATED VASCULITIS; ANTINEUTROPHIL CYTOPLASMIC
AUTOANTIBODIES; WEGENERS-GRANULOMATOSIS; RANDOMIZED-TRIAL; SYSTEMIC
VASCULITIDES; RENAL VASCULITIS; CELL-ACTIVATION; CYCLOPHOSPHAMIDE;
MAINTENANCE; RITUXIMAB
AB Background
The 18-month efficacy of a single course of rituximab as compared with conventional immunosuppression with cyclophosphamide followed by azathioprine in patients with severe (organ-threatening) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is unknown.
Methods
In a multicenter, randomized, double-blind, double-dummy, noninferiority trial, we compared rituximab (375 mg per square meter of body-surface area administered once a week for 4 weeks) followed by placebo with cyclophosphamide administered for 3 to 6 months followed by azathioprine for 12 to 15 months. The primary outcome measure was complete remission of disease by 6 months, with the remission maintained through 18 months.
Results
A total of 197 patients were enrolled. As reported previously, 64% of the patients in the rituximab group, as compared with 53% of the patients in the cyclophosphamide-azathioprine group, had a complete remission by 6 months. At 12 and 18 months, 48% and 39%, respectively, of the patients in the rituximab group had maintained the complete remissions, as compared with 39% and 33%, respectively, in the comparison group. Rituximab met the prespecified criteria for noninferiority (P<0.001, with a noninferiority margin of 20%). There was no significant difference between the groups in any efficacy measure, including the duration of complete remission and the frequency or severity of relapses. Among the 101 patients who had relapsing disease at baseline, rituximab was superior to conventional immunosuppression at 6 months (P=0.01) and at 12 months (P=0.009) but not at 18 months (P=0.06), at which time most patients in the rituximab group had reconstituted B cells. There was no significant between-group difference in adverse events.
Conclusions
In patients with severe ANCA-associated vasculitis, a single course of rituximab was as effective as continuous conventional immunosuppressive therapy for the induction and maintenance of remissions over the course of 18 months. (Funded by the National Institute of Allergy and Infectious Diseases and others; RAVE ClinicalTrials.gov number, .)
C1 [Specks, Ulrich; Fervenza, Fernando C.; Keogh, Karina; Peikert, Tobias; Ytterberg, Steven R.; Mieras, Kathleen] Mayo Clin Fdn, Rochester, MN USA.
[Merkel, Peter A.; Kissin, Eugene Y.; Monach, Paul A.] Boston Univ, Med Ctr, Boston, MA USA.
[Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Seo, Philip; Geetha, Duvuru; Sejismundo, Lourdes P.] Johns Hopkins Univ, Baltimore, MD USA.
[Ding, Linna; Viviano, Lisa; Mueller, Mark] NIAID, Bethesda, MD 20892 USA.
[Tchao, Nadia K.; Phippard, Deborah J.; Asare, Adam L.; Lim, Noha] Immune Tolerance Network, Bethesda, MD USA.
[Spiera, Robert] Hosp Special Surg, New York, NY 10021 USA.
[Langford, Carol A.; Hoffman, Gary S.] Cleveland Clin Fdn, Cleveland, OH USA.
[Kallenberg, Cees G. M.; Stegeman, Coen] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands.
[Clair, E. William St.; Allen, Nancy B.] Duke Univ, Med Ctr, Durham, NC 27706 USA.
[Ikle, David; Jepson, Brett] Rho, Chapel Hill, NC USA.
[Fessler, Barri J.] Univ Alabama Birmingham, Birmingham, AL USA.
[Brunetta, Paul] Genentech Inc, San Francisco, CA USA.
RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, 55 Fruit St, Boston, MA 02114 USA.
EM jhstone@partners.org
OI Carey, John/0000-0001-7292-2328; molloy, Eleanor/0000-0001-6798-2158
FU NIH [N01-AI-15416, ITN021AI]; National Institute of Allergy and
Infectious Diseases; Juvenile Diabetes Research Foundation; Genentech;
Biogen Idec; National Center for Research Resources (NCRR) [UL1
RR024150-01, UL1 RR025005, UL1 RR025771, NIH M01 RR00533]; National
Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
[K24 AR049185, K23 AR052820, K24 AR02224]; Arthritis Foundation
Investigator Award
FX This research was performed as a project of the Immune Tolerance Network
(NIH contract N01-AI-15416; protocol number ITN021AI), an international
clinical research consortium head-quartered at the University of
California, San Francisco.; Supported by the National Institute of
Allergy and Infectious Diseases, the Juvenile Diabetes Research
Foundation, Genentech, and Biogen Idec. At the Mayo Clinic, the trial
was supported by a Clinical and Translational Science Award (CTSA) grant
(UL1 RR024150-01) from the National Center for Research Resources
(NCRR). At Johns Hopkins, the trial was supported by a CTSA grant (UL1
RR025005) from the NCRR and by grants (K24 AR049185, to Dr. Stone; and
K23 AR052820, to Dr. Seo) from the National Institute of Arthritis and
Musculoskeletal and Skin Diseases (NIAMS). At Boston University, the
trial was supported by CTSA grants (UL1 RR025771 and NIH M01 RR00533)
from the NCRR and a grant (K24 AR02224) from the NIAMS (all to Dr.
Merkel) and an Arthritis Foundation Investigator Award (to Dr. Monach).
NR 33
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U1 0
U2 11
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD AUG 1
PY 2013
VL 369
IS 5
BP 417
EP 427
DI 10.1056/NEJMoa1213277
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 193GQ
UT WOS:000322547400008
PM 23902481
ER
PT J
AU Zarin, DA
AF Zarin, Deborah A.
TI Participant-Level Data and the New Frontier in Trial Transparency
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
AB Medical progress is possible only because altruistic volunteers put themselves at risk in clinical trials. The results of those trials are then used to inform medical decisions. The traditional system of relying on investigators, sponsors, and journal editors to decide whether, when, and how to report trial results was based on trust. There was no way to know what trials had been conducted, what data were collected, how they were analyzed, and whether the reported data were complete and accurate. Policies mandating the registration of trials and the reporting of summary results were instituted to provide greater transparency. In turn, ...
C1 NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20892 USA.
RP Zarin, DA (reprint author), NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
NR 4
TC 24
Z9 24
U1 0
U2 6
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD AUG 1
PY 2013
VL 369
IS 5
BP 468
EP 469
DI 10.1056/NEJMe1307268
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 193GQ
UT WOS:000322547400015
PM 23902488
ER
PT J
AU Chew, EY
Clemons, TE
Agron, E
Sperduto, RD
SanGiovanni, JP
Kurinij, N
Davis, MD
AF Chew, Emily Y.
Clemons, Traci E.
Agron, Elvira
Sperduto, Robert D.
SanGiovanni, John Paul
Kurinij, Natalie
Davis, Matthew D.
CA Age-Related Eye Dis Study Res Grp
TI Long-Term Effects of Vitamins C and E, beta-Carotene, and Zinc on
Age-related Macular Degeneration AREDS Report No. 35
SO OPHTHALMOLOGY
LA English
DT Article
ID DIABETES-MELLITUS; EYE DISEASE; COMPLICATIONS; MORTALITY; TRIAL
AB Objective: To describe the long-term effects (10 years) of the Age-Related Eye Disease Study (AREDS) formulation of high-dose antioxidants and zinc supplement on progression of age-related macular degeneration (AMD).
Design: Multicenter, randomized, controlled, clinical trial followed by an epidemiologic follow-up study.
Participants: We enrolled 4757 participants with varying severity of AMD in the clinical trial; 3549 surviving participants consented to the follow-up study.
Methods: Participants were randomly assigned to antioxidants C, E, and beta-carotene and/or zinc versus placebo during the clinical trial. For participants with intermediate or advanced AMD in 1 eye, the AREDS formulation delayed the progression to advanced AMD. Participants were then enrolled in a follow-up study. Eye examinations were conducted with annual fundus photographs and best-corrected visual acuity assessments. Medical histories and mortality were obtained for safety monitoring. Repeated measures logistic regression was used in the primary analyses.
Main Outcome Measures: Photographic assessment of progression to, or history of treatment for, advanced AMD (neovascular [NV] or central geographic atrophy [CGA]), and moderate visual acuity loss from baseline (>= 15 letters).
Results: Comparison of the participants originally assigned to placebo in AREDS categories 3 and 4 at baseline with those originally assigned to AREDS formulation at 10 years demonstrated a significant (P<0.001) odds reduction in the risk of developing advanced AMD or the development of NV AMD (odds ratio [OR], 0.66, 95% confidence interval [CI], 0.53-0.83 and OR, 0.60; 95% CI, 0.47-0.78, respectively). No significant reduction (P = 0.93) was seen for the CGA (OR, 1.02; 95% CI, 0.71-1.45). A significant reduction (P = 0.002) for the development of moderate vision loss was seen (OR 0.71; 95% CI, 0.57-0.88). No adverse effects were associated with the AREDS formulation. Mortality was reduced in participants assigned to zinc, especially death from circulatory diseases.
Conclusions: Five years after the clinical trial ended, the beneficial effects of the AREDS formulation persisted for development of NV AMD but not for CGA. These results are consistent with the original recommendations that persons with intermediate or advanced AMD in 1 eye should consider taking the AREDS formulation. (C) 2013 by the American Academy of Ophthalmology.
C1 [Chew, Emily Y.; Agron, Elvira; SanGiovanni, John Paul] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Clemons, Traci E.; Sperduto, Robert D.] EMMES Corp, Rockville, MD USA.
[Kurinij, Natalie] NEI, Div Extramural Res, NIH, Bethesda, MD 20892 USA.
[Davis, Matthew D.] Univ Wisconsin, Madison, WI USA.
RP Chew, EY (reprint author), NEI, NIH, Bldg 10,CRC Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA.
EM echew@nei.nih.gov
FU National Eye Institute/National Institutes of Health, Department of
Health and Human Services, Bethesda, MD [NOI-EY-0-2127]
FX Supported by the intramural program funds and contracts AREDS (Contract
NOI-EY-0-2127) from the National Eye Institute/National Institutes of
Health, Department of Health and Human Services, Bethesda, MD.
NR 8
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U1 6
U2 50
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD AUG
PY 2013
VL 120
IS 8
BP 1604
EP +
DI 10.1016/j.ophtha.2013.01.021
PG 12
WC Ophthalmology
SC Ophthalmology
GA 196LW
UT WOS:000322778000022
PM 23582353
ER
PT J
AU Nussinov, R
AF Nussinov, Ruth
TI The spatial structure of cell signaling systems
SO PHYSICAL BIOLOGY
LA English
DT Article
ID NUCLEAR-MAGNETIC-RESONANCE; PROTEIN-PROTEIN INTERFACES; PLASMA-MEMBRANE;
ALLOSTERIC REGULATION; RECEPTOR CLUSTERS; SINGLE-MOLECULE; DRUG
DISCOVERY; CONFORMATIONAL SELECTION; INTERACTION NETWORKS; ENERGY
LANDSCAPES
AB The spatial structure of the cell is highly organized at all levels: from small complexes and assemblies, to local nano- and microclusters, to global, micrometer scales across and between cells. We suggest that this multiscale spatial cell organization also organizes signaling and coordinates cellular behavior. We propose a new view of the spatial structure of cell signaling systems. This new view describes cell signaling in terms of dynamic allosteric interactions within and among distinct, spatially organized transient clusters. The clusters vary over time and space and are on length scales from nanometers to micrometers. When considered across these length scales, primary factors in the spatial organization are cell membrane domains and the actin cytoskeleton, both also highly dynamic. A key challenge is to understand the interplay across these multiple scales, link it to the physicochemical basis of the conformational behavior of single molecules and ultimately relate it to cellular function. Overall, our premise is that at these scales, cell signaling should be thought of not primarily as a sequence of diffusion-controlled molecular collisions, but instead transient, allostery-driven cluster re-forming interactions.
C1 [Nussinov, Ruth] NCI, Basic Res Program, SAIC Frederick Inc, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
RP Nussinov, R (reprint author), NCI, Basic Res Program, SAIC Frederick Inc, Canc & Inflammat Program, Frederick, MD 21702 USA.
EM NussinoR@helix.nih.gov
FU NCI; National Institute of Health (NIH) [HHSN261200800001E]; Center for
Cancer Research
FX I thank the National Cancer Institute (NCI) group, Hyunbum Jang, Buyong
Ma and Chung-Jung Tsai for their many discussions over the years. This
project has been funded in whole or in part with Federal funds from the
NCI and the National Institute of Health (NIH), under contract number
HHSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does the mention of trade names, commercial products or
organizations imply endorsement by the U.S. Government. This research
was supported (in part) by the Intramural Research Program of the NIH,
the NCI and the Center for Cancer Research.
NR 175
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U1 4
U2 36
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 1478-3967
EI 1478-3975
J9 PHYS BIOL
JI Phys. Biol.
PD AUG
PY 2013
VL 10
IS 4
AR 045004
DI 10.1088/1478-3975/10/4/045004
PG 12
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 195KM
UT WOS:000322701100006
PM 23913102
ER
PT J
AU Lazar, J
O'Meara, CC
Sarkis, AB
Prisco, SZ
Xu, HY
Fox, CS
Chen, MH
Broeckel, U
Arnett, DK
Moreno, C
Provoost, AP
Jacob, HJ
AF Lazar, Jozef
O'Meara, Caitlin C.
Sarkis, Allison B.
Prisco, Sasha Z.
Xu, Haiyan
Fox, Caroline S.
Chen, Ming-Huei
Broeckel, Ulrich
Arnett, Donna K.
Moreno, Carol
Provoost, Abraham P.
Jacob, Howard J.
TI SORCS1 contributes to the development of renal disease in rats and
humans
SO PHYSIOLOGICAL GENOMICS
LA English
DT Article
DE kidney; SORCS1; proteinuria
ID GENOME-WIDE ASSOCIATION; CHRONIC KIDNEY-DISEASE; DIABETES SUSCEPTIBILITY
LOCI; QUANTITATIVE TRAIT LOCUS; DOUBLE CONGENIC RATS; FAWN-HOODED RAT;
GLOMERULAR-PERMEABILITY; MODULATES PROTEINURIA; CREATININE CLEARANCE;
ALZHEIMERS-DISEASE
AB Many lines of evidence demonstrate that genetic variability contributes to chronic kidney disease susceptibility in humans as well as rodent models. Little progress has been made in discovering causal kidney disease genes in humans mainly due to genetic complexity. Here, we use a minimal congenic mapping strategy in the FHH (fawn hooded hypertensive) rat to identify Sorcs1 as a novel renal disease candidate gene. We investigated the hypothesis that genetic variation in Sorcs1 influences renal disease susceptibility in both rat and human. Sorcs1 is expressed in the kidney, and knocking out this gene in a rat strain with a sensitized genome background produced increased proteinuria. In vitro knockdown of Sorcs1 in proximal tubule cells impaired protein trafficking, suggesting a mechanism for the observed proteinuria in the FHH rat. Since Sorcs1 influences renal function in the rat, we went on to test this gene in humans. We identified associations between single nucleotide polymorphisms in SORCS1 and renal function in large cohorts of European and African ancestry. The experimental data from the rat combined with association results from different ethnic groups indicates a role for SORCS1 in maintaining proper renal function.
C1 [Lazar, Jozef] Med Coll Wisconsin, Dept Dermatol, Milwaukee, WI 53226 USA.
[Lazar, Jozef; O'Meara, Caitlin C.; Sarkis, Allison B.; Prisco, Sasha Z.; Xu, Haiyan; Moreno, Carol; Jacob, Howard J.] Med Coll Wisconsin, Human & Mol Genet Ctr, Milwaukee, WI 53226 USA.
[O'Meara, Caitlin C.; Sarkis, Allison B.; Prisco, Sasha Z.; Moreno, Carol; Jacob, Howard J.] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA.
[Broeckel, Ulrich; Jacob, Howard J.] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA.
[Fox, Caroline S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Fox, Caroline S.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol Metab & Hypertens, Boston, MA 02115 USA.
[Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Arnett, Donna K.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.
[Provoost, Abraham P.] Erasmus MC, Rotterdam, Netherlands.
RP Jacob, HJ (reprint author), HRC5200,8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
EM jacob@mcw.edu
FU National Heart, Lung and Blood Institute [5RO1HL-069321]
FX This study was performed with financial support from National Heart,
Lung and Blood Institute Grant 5RO1HL-069321 to H. J. Jacob.
NR 65
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U1 0
U2 3
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1094-8341
J9 PHYSIOL GENOMICS
JI Physiol. Genomics
PD AUG
PY 2013
VL 45
IS 16
BP 720
EP 728
DI 10.1152/physiolgenomics.00089.2013
PG 9
WC Cell Biology; Genetics & Heredity; Physiology
SC Cell Biology; Genetics & Heredity; Physiology
GA 200UO
UT WOS:000323096600004
PM 23780848
ER
PT J
AU Keyes, KM
Eaton, NR
Krueger, RF
Skodol, AE
Wall, MM
Grant, B
Siever, LJ
Hasin, DS
AF Keyes, K. M.
Eaton, N. R.
Krueger, R. F.
Skodol, A. E.
Wall, M. M.
Grant, B.
Siever, L. J.
Hasin, D. S.
TI Thought disorder in the meta-structure of psychopathology
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE Dimensional; externalizing; internalizing; metastructure; psychosis;
thought disorders
ID COMMON MENTAL-DISORDERS; PSYCHIATRIC DIAGNOSTIC MODULES;
POSTTRAUMATIC-STRESS-DISORDER; GENERAL-POPULATION SAMPLE;
ALCOHOL-USE-DISORDER; IV AUDADIS-IV; PERSONALITY-DISORDERS;
GENDER-DIFFERENCES; BIPOLAR DISORDER; ROSCOMMON FAMILY
AB Background. Dimensional models of co-morbidity have the potential to improve the conceptualization of mental disorders in research and clinical work, yet little is known about how relatively uncommon disorders may fit with more common disorders. The present study estimated the meta-structure of psychopathology in the US general population focusing on the placement of five under-studied disorders sharing features of thought disorder : paranoid, schizoid, avoidant and schizotypal personality disorders, and manic episodes as well as bipolar disorder.
Method. Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions, a face-toface interview of 34 653 non-institutionalized adults in the US general population. The meta-structure of 16 DSM-IV Axis I and Axis II psychiatric disorders, as assessed by the Alcohol Use Disorder and Associated Disabilities Interview Schedule DSM-IV version (AUDADIS-IV), was examined using exploratory and confirmatory factor analysis.
Results. We document an empirically derived thought disorder factor that is a subdomain of the internalizing dimension, characterized by schizoid, paranoid, schizotypal and avoidant personality disorders as well as manic episodes. Manic episodes exhibit notable associations with both the distress subdomain of the internalizing dimension as well as the thought disorder subdomain. The structure was replicated for bipolar disorder (I or II) in place of manic episodes.
Conclusions. As our understanding of psychopathological meta-structure expands, incorporation of disorders characterized by detachment and psychoticism grows increasingly important. Disorders characterized by detachment and psychoticism may be well conceptualized, organized and measured as a subdimension of the internalizing spectrum of disorders. Manic episodes and bipolar disorder exhibit substantial co-morbidity across both distress and thought disorder domains of the internalizing dimension. Clinically, these results underscore the potential utility of conceptualizing patient treatment needs using an approach targeting psychopathological systems underlying meta-structural classification rubrics.
C1 [Keyes, K. M.; Hasin, D. S.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10032 USA.
[Keyes, K. M.; Skodol, A. E.; Wall, M. M.; Hasin, D. S.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
[Eaton, N. R.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA.
[Krueger, R. F.] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA.
[Skodol, A. E.] Univ Arizona, Coll Med, Tucson, AZ USA.
[Wall, M. M.] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY 10032 USA.
[Grant, B.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Bethesda, MD USA.
[Siever, L. J.] Mt Sinai Sch Med, Dept Psychiat, Bronx, NY USA.
RP Keyes, KM (reprint author), Columbia Univ, Dept Epidemiol, 722 West 168th St,503, New York, NY 10032 USA.
EM kmk2104@columbia.edu
FU National Institute on Alcoholism and Alcohol Abuse [K05 AA014223, U01
AA018111]; New York State Psychiatric Institute
FX This research was supported in part by grants from the National
Institute on Alcoholism and Alcohol Abuse (no. K05 AA014223 and U01
AA018111, both to D.S.H.), and support from the New York State
Psychiatric Institute.
NR 40
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U1 2
U2 10
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0033-2917
J9 PSYCHOL MED
JI Psychol. Med.
PD AUG
PY 2013
VL 43
IS 8
BP 1673
EP 1683
DI 10.1017/S0033291712002292
PG 11
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 187MJ
UT WOS:000322122900009
PM 23171498
ER
PT J
AU Barile, JP
Reeve, BB
Smith, AW
Zack, MM
Mitchell, SA
Kobau, R
Cella, DF
Luncheon, C
Thompson, WW
AF Barile, John P.
Reeve, Bryce B.
Smith, Ashley Wilder
Zack, Matthew M.
Mitchell, Sandra A.
Kobau, Rosemarie
Cella, David F.
Luncheon, Cecily
Thompson, William W.
TI Monitoring population health for Healthy People 2020: evaluation of the
NIH PROMISA (R) Global Health, CDC Healthy Days, and satisfaction with
life instruments
SO QUALITY OF LIFE RESEARCH
LA English
DT Article
DE Health-related quality of life; Well-being; Measurement invariance;
Structural equation modeling; Population health; Healthy People 2020
ID TESTING MEASUREMENT INVARIANCE; CONFIRMATORY FACTOR-ANALYSIS;
QUALITY-OF-LIFE; FIT INDEXES; DISABILITY; SCALE; ADULTS
AB Healthy People 2020 identified health-related quality of life and well-being (WB) as indicators of population health for the next decade. This study examined the measurement properties of the NIH PROMISA (R) Global Health Scale, the CDC Healthy Days items, and associations with the Satisfaction with Life Scale.
A total of 4,184 adults completed the Porter Novelli's HealthStyles mailed survey. Physical and mental health (9 items from PROMIS Global Scale and 3 items from CDC Healthy days measure), and 4 WB factor items were tested for measurement equivalence using multiple-group confirmatory factor analysis.
The CDC items accounted for similar variance as the PROMIS items on physical and mental health factors; both factors were moderately correlated with WB. Measurement invariance was supported across gender and age; the magnitude of some factor loadings differed between those with and without a chronic medical condition.
The PROMIS, CDC, and WB items all performed well. The PROMIS items captured a broad range of functioning across the entire continuum of physical and mental health, while the CDC items appear appropriate for assessing burden of disease for chronic conditions and are brief and easily interpretable. All three measures under study appear to be appropriate measures for monitoring several aspects of the Healthy People 2020 goals and objectives.
C1 [Barile, John P.] Univ Hawaii Manoa, Dept Psychol, Honolulu, HI 96822 USA.
[Reeve, Bryce B.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Reeve, Bryce B.] Univ N Carolina, Dept Hlth Policy & Management, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Smith, Ashley Wilder; Mitchell, Sandra A.] NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Zack, Matthew M.; Kobau, Rosemarie; Luncheon, Cecily; Thompson, William W.] US Ctr Dis Control & Prevent, Div Populat Hlth, NCCDPHP, Atlanta, GA 30331 USA.
[Cella, David F.] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA.
RP Barile, JP (reprint author), Univ Hawaii Manoa, Dept Psychol, 2530 Dole St,Sakamaki Hall C404, Honolulu, HI 96822 USA.
EM Barile@Hawaii.edu
RI Barile, John/F-9456-2015
OI Barile, John/0000-0003-4098-0640
FU National Institutes of Health [U54AR057951-02]
FX Barile and Luncheon were supported in part by an appointment to the
Research Participation Program for the Centers for Disease Control and
Prevention (CDC) administered by the Oak Ridge Institute for Science and
Education through an agreement between the US Department of Energy and
CDC. Cella was supported by a grant from the National Institutes of
Health to the PROMIS Statistical Center (U54AR057951-02). We would like
to thank Adam Burns and Bill Pollard of Porter Novelli for reviewing
drafts of this manuscript.
NR 47
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U1 0
U2 12
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
J9 QUAL LIFE RES
JI Qual. Life Res.
PD AUG
PY 2013
VL 22
IS 6
BP 1201
EP 1211
DI 10.1007/s11136-012-0246-z
PG 11
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 195XA
UT WOS:000322735700004
PM 23404737
ER
PT J
AU Kent, EE
Sender, LS
Morris, RA
Grigsby, TJ
Montoya, MJ
Ziogas, A
Anton-Culver, H
AF Kent, Erin E.
Sender, Leonard S.
Morris, Rebecca A.
Grigsby, Timothy J.
Montoya, Michael J.
Ziogas, Argyrios
Anton-Culver, Hoda
TI Multilevel socioeconomic effects on quality of life in adolescent and
young adult survivors of leukemia and lymphoma
SO QUALITY OF LIFE RESEARCH
LA English
DT Article
DE Adolescents and young adults; Quality of life; Socioeconomic status;
Health disparities; Leukemia; Lymphoma; Cancer; Cancer survivorship
ID CHILDHOOD-CANCER SURVIVOR; LONG-TERM SURVIVORS; NON-HODGKIN-LYMPHOMA;
HEALTH RESEARCH; SOCIAL SUPPORT; DISPARITIES; DIAGNOSIS; COHORT;
EPIDEMIOLOGY; VALIDATION
AB Cancer registry survival analyses have shown that adolescent and young adult patients with low socioeconomic status (SES) have reduced survival compared to those with higher SES. The objective of this study was to determine whether neighborhood- (nSES) and/or individual-level SES (iSES) also predicted current quality of life in adolescent and young adult survivors.
The Socioeconomics and Quality of Life study surveyed adolescent and young adult survivors of leukemia and lymphoma at least one year post-diagnosis using population-based ascertainment. Factor analysis was used to create a multidimensional age-relevant iSES score and compared with a preexisting census-block-group derived nSES score. Four quality of life domains were assessed: physical health, psychological and emotional well-being, social relationships, and life skills. Nested multivariable linear regression models were run to test the associations between both SES measures and quality of life and to compare the explanatory power of nSES and iSES.
Data from 110 individuals aged 16-40 were included in the final analysis. After adjustment for sociodemographic confounders, low nSES was associated only with poorer physical health, whereas low iSES was related to poorer quality of life in all four domains with iSES accounting for an additional 14, 12, 25, and 10 % of the variance, respectively.
Measures of SES at the individual as compared to the neighborhood level may be stronger indicators of outcomes in adolescents and young adults, which has important implications for SES measurement in the context of cancer surveillance.
C1 [Kent, Erin E.] NCI, Canc Prevent Fellowship Program, NIH, Bethesda, MD 20892 USA.
[Kent, Erin E.; Sender, Leonard S.; Ziogas, Argyrios; Anton-Culver, Hoda] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
[Sender, Leonard S.; Anton-Culver, Hoda] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Irvine, CA USA.
[Sender, Leonard S.; Morris, Rebecca A.] CHOC Childrens Hosp, Hyundai Canc Inst, Orange, CA USA.
[Grigsby, Timothy J.] Univ So Calif, Dept Prevent Med, Inst Hlth Promot & Dis Prevent, Los Angeles, CA 90089 USA.
[Montoya, Michael J.] Univ Calif Irvine, Dept Anthropol, Irvine, CA USA.
[Montoya, Michael J.] Univ Calif Irvine, Dept Chicano Latino Studies, Irvine, CA USA.
[Montoya, Michael J.] Univ Calif Irvine, Dept Populat Hlth & Prevent, Irvine, CA USA.
[Ziogas, Argyrios; Anton-Culver, Hoda] Univ Calif Irvine, Genet Epidemiol Res Inst, Irvine, CA USA.
RP Kent, EE (reprint author), NCI, Canc Prevent Fellowship Program, NIH, 6116 Execut Blvd,Room 404, Bethesda, MD 20892 USA.
EM Erin.Kent@nih.gov; leonardsender@gmail.com; rmorris.choc@gmail.com;
tjgrigsb@usc.edu; mmontoya@uci.edu; aziogas@uci.edu; hantoncu@uci.edu
FU UC; Centers for Disease Control and Prevention [R36DP002012-01]
FX This work was carried out as part of Erin Kent's doctoral dissertation
at the University of California, Irvine. Support for this work was
provided by a UC MEXUS dissertation grant and Centers for Disease
Control and Prevention R36 Public Health Dissertation Grant
R36DP002012-01). The authors thank undergraduate research assistants
Marym Mohammady and Priyanka Saxena for their assistance with study
recruitment coordination and clinical research coordinator Isabel Guzman
for her assistance with translation of the study documents into Spanish.
NR 53
TC 4
Z9 4
U1 3
U2 9
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
J9 QUAL LIFE RES
JI Qual. Life Res.
PD AUG
PY 2013
VL 22
IS 6
BP 1339
EP 1351
DI 10.1007/s11136-012-0254-z
PG 13
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 195XA
UT WOS:000322735700019
PM 22922952
ER
PT J
AU Hart, LA
Sibai, BM
AF Hart, Laura A.
Sibai, Baha M.
TI Seizures in pregnancy: Epilepsy, eclampsia, and stroke
SO SEMINARS IN PERINATOLOGY
LA English
DT Review
DE seizure; epilepsy; eclampsia; stroke; pregnancy
ID QUALITY STANDARDS SUBCOMMITTEE; TECHNOLOGY-ASSESSMENT SUBCOMMITTEE;
UPDATE MANAGEMENT ISSUES; EXPOSED IN-UTERO; LATE POSTPARTUM ECLAMPSIA;
ANTIEPILEPTIC DRUGS; PRACTICE PARAMETER; MAGNESIUM-SULFATE;
AMERICAN-ACADEMY; RISK-FACTORS
AB Seizures during pregnancy complicate <1% of all gestations; however, they are associated with increased adverse maternal and perinatal outcomes (acute and long term). The differential diagnosis of seizures in pregnancy is extensive. Determining the underlying etiology is crucial in the management of these patients. Medical providers caring for pregnant women should be educated about possible etiologies of seizures during pregnancy and the importance of prompt management of these women in a timely fashion. Evaluation and management should be performed in a stepwise fashion and may require a multidisciplinary approach with other specialties such as neurology. The objective of this review is to increase awareness and to provide a stepwise approach toward the diagnosis and management of pregnancies complicated by seizures. (c) 2013 Elsevier Inc. All rights reserved.
C1 [Hart, Laura A.; Sibai, Baha M.] Univ Texas Hlth Sci Ctr Houston, Dept Obstet Gynecol & Reprod Sci, Div Maternal Fetal Med, Houston, TX 77030 USA.
[Sibai, Baha M.] Eunice Kennedy Shriver NICHD Maternal Fetal Med N, Bethesda, MD USA.
RP Sibai, BM (reprint author), Univ Texas Hlth Sci Ctr Houston, Dept Obstet Gynecol & Reprod Sci, Div Maternal Fetal Med, 6431 Fannin,Suite 3-286, Houston, TX 77030 USA.
EM baha.m.sibai@uth.tmc.edu
NR 132
TC 13
Z9 15
U1 1
U2 11
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0146-0005
J9 SEMIN PERINATOL
JI Semin. Perinatol.
PD AUG
PY 2013
VL 37
IS 4
BP 207
EP 224
DI 10.1053/j.semperi.2013.04.001
PG 18
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 198SS
UT WOS:000322943200002
PM 23916020
ER
PT J
AU Margolis, R
Ludi, E
Pao, M
Wiener, L
AF Margolis, Rachel
Ludi, Erica
Pao, Maryland
Wiener, Lori
TI International Adaptation: Psychosocial and Parenting Experiences of
Caregivers Who Travel to the United States to Obtain Acute Medical Care
for Their Seriously Ill Child
SO SOCIAL WORK IN HEALTH CARE
LA English
DT Article
DE international medical travel; caregiver; pediatric; transnational
parenting; psychosocial; cultural adaptation
ID SOCIAL-WORK; MEANINGS; TOURISM
AB Despite the increasing trend of travel for medical purposes, little is known about the experience of parents and other caregivers who come to the United States specifically to obtain medical treatment for their seriously ill child. In this exploratory, descriptive qualitative study, we used a semi-structured narrative guide to conduct in-depth interviews with 22 Spanish- or English-speaking caregivers about the challenges encountered and adaptation required when entering a new medical and cultural environment. Caregivers identified the language barrier and transnational parenting as challenges while reporting hospital staff and their own families as major sources of support. Using the results of the study as a guide, clinical and program implications are provided and recommendations for social work practice discussed.
C1 [Margolis, Rachel] NIH, Ctr Clin, Dept Social Work, Bethesda, MD 20892 USA.
[Ludi, Erica; Pao, Maryland] NIMH, NIH, Bethesda, MD 20892 USA.
[Wiener, Lori] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Margolis, R (reprint author), NIH, 10 Clin Ctr,Room 2-3581, Bethesda, MD 20892 USA.
EM Rachel.margolis@nih.gov
FU Intramural NIH HHS [ZIA MH002922-04]
NR 22
TC 3
Z9 3
U1 0
U2 7
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 0098-1389
J9 SOC WORK HEALTH CARE
JI Soc. Work Health Care
PD AUG 1
PY 2013
VL 52
IS 7
BP 669
EP 683
DI 10.1080/00981389.2013.798391
PG 15
WC Social Work
SC Social Work
GA 201LV
UT WOS:000323144000004
PM 23947542
ER
PT J
AU Sri, T
Merideth, MA
Pulanic, TK
Childs, R
Stratton, P
AF Sri, T.
Merideth, M. A.
Pulanic, T. Klepac
Childs, R.
Stratton, P.
TI Human papillomavirus reactivation following treatment of genital
graft-versus-host disease
SO TRANSPLANT INFECTIOUS DISEASE
LA English
DT Article
DE human papillomavirus; graft-versus-host disease; immunosuppression; stem
cell transplantation; genital GVHD
ID STEM-CELL TRANSPLANTATION; LONG-TERM SURVIVORS; LICHEN-SCLEROSUS;
THERAPY
AB Vaginal chronic graft-versus-host disease (cGVHD) is a common complication of stem cell transplantation. Human papillomavirus (HPV) disease can reactivate after transplantation, presumably because of immune factors affecting systemic immunity, such as waning antibody titers, impaired HPV reactivation and spread has not been previously described, to our knowledge. A 30-year-old woman, 2years post transplant receiving systemic cyclosporine for cGVHD, was treated with vaginal dilators, topical corticosteroids, and estrogen for vaginal cGVHD. Colposcopy and biopsy for abnormal cytology revealed condylomatous cervicitis. Over the next 4months, while continuing dilator therapy, linear verrucous lesions developed in the vagina and vulva, and were successfully treated with laser therapy. Use of local immunosuppression and dilators for genital GVHD can enhance spread of HPV infection. Integration of HPV screening and treatment into the care of women with genital cGVHD and development of strategies to manage both conditions simultaneously are warranted.
C1 [Sri, T.] Epsom & St Helier Univ Hosp NHS Trust, London, England.
[Merideth, M. A.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Merideth, M. A.] NIH, Intramural Off Rare Dis, Off Director, Bethesda, MD 20892 USA.
[Pulanic, T. Klepac] Community Hlth Ctr East, Zagreb, Croatia.
[Pulanic, T. Klepac; Stratton, P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Childs, R.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Stratton, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Gynecol Consult Serv, Program Reprod & Adult Endocrinol, CRC, Bldg 10,Room 1-3140,10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA.
EM ps79c@nih.gov
FU NIH, National Heart, Lung and Blood Institute, Clinical Center; Eunice
Kennedy Shriver National Institute of Child Health and Human
Development; NIH Intramural Office of Rare Diseases; National Human
Genome Research Institute
FX This study was funded, in part, by the Intramural Program of the NIH,
National Heart, Lung and Blood Institute, Clinical Center, the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, the NIH Intramural Office of Rare Diseases, the National
Human Genome Research Institute, and clinical trial NCT00003838.
NR 8
TC 2
Z9 2
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-2273
J9 TRANSPL INFECT DIS
JI Transpl. Infect. Dis.
PD AUG
PY 2013
VL 15
IS 4
BP E148
EP E151
DI 10.1111/tid.12098
PG 4
WC Immunology; Infectious Diseases; Transplantation
SC Immunology; Infectious Diseases; Transplantation
GA 188UR
UT WOS:000322220900005
PM 23710698
ER
PT J
AU Liebschner, D
Dauter, M
Brzuszkiewicz, A
Dauter, Z
AF Liebschner, Dorothee
Dauter, Miroslawa
Brzuszkiewicz, Anna
Dauter, Zbigniew
TI On the reproducibility of protein crystal structures: five atomic
resolution structures of trypsin
SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
LA English
DT Article
ID INDEPENDENTLY REFINED MODELS; X-RAY CRYSTALLOGRAPHY; RADIATION-DAMAGE;
ACCURACY; DIFFRACTION; HYDRATION; GEOMETRY; DATABASE
AB Structural studies of proteins usually rely on a model obtained from one crystal. By investigating the details of this model, crystallographers seek to obtain insight into the function of the macromolecule. It is therefore important to know which details of a protein structure are reproducible or to what extent they might differ. To address this question, the high-resolution structures of five crystals of bovine trypsin obtained under analogous conditions were compared. Global parameters and structural details were investigated. All of the models were of similar quality and the pairwise merged intensities had large correlation coefficients. The C-alpha and backbone atoms of the structures superposed very well. The occupancy of ligands in regions of low thermal motion was reproducible, whereas solvent molecules containing heavier atoms (such as sulfur) or those located on the surface could differ significantly. The coordination lengths of the calcium ion were conserved. A large proportion of the multiple conformations refined to similar occupancies and the residues adopted similar orientations. More than three quarters of the water-molecule sites were conserved within 0.5 angstrom and more than one third were conserved within 0.1 angstrom. An investigation of the protonation states of histidine residues and carboxylate moieties was consistent for all of the models. Radiation-damage effects to disulfide bridges were observed for the same residues and to similar extents. Main-chain bond lengths and angles averaged to similar values and were in agreement with the Engh and Huber targets. Other features, such as peptide flips and the double conformation of the inhibitor molecule, were also reproducible in all of the trypsin structures. Therefore, many details are similar in models obtained from different crystals. However, several features of residues or ligands located in flexible parts of the macromolecule may vary significantly, such as side-chain orientations and the occupancies of certain fragments.
C1 [Liebschner, Dorothee; Brzuszkiewicz, Anna; Dauter, Zbigniew] NCI, Argonne Natl Lab, MCL, Synchrotron Radiat Res Sect, Argonne, IL 60439 USA.
[Dauter, Miroslawa] Argonne Natl Lab, Basic Res Program, SAIC Frederick Inc, Argonne, IL 60439 USA.
[Brzuszkiewicz, Anna] Univ Wroclaw, Fac Chem, PL-50383 Wroclaw, Poland.
RP Dauter, Z (reprint author), NCI, Argonne Natl Lab, MCL, Synchrotron Radiat Res Sect, Argonne, IL 60439 USA.
EM dauter@anl.gov
FU National Cancer Institute, National Institutes of Health [NO1-CO-12400];
NIH, National Cancer Institute, Center for Cancer Research; US
Department of Energy, Office of Science, Office of Basic Energy Sciences
[W-31-109-Eng-38]
FX This work was supported in part with Federal funds from the National
Cancer Institute, National Institutes of Health contract No.
NO1-CO-12400 and the Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does the mention of trade
names, commercial products or organizations imply endorsement by the US
Government. Diffraction data were collected on the NE-CAT beamline 24-ID
at the Advanced Photon Source, Argonne National Laboratory. Use of the
Advanced Photon Source was supported by the US Department of Energy,
Office of Science, Office of Basic Energy Sciences, under Contract No.
W-31-109-Eng-38.
NR 41
TC 23
Z9 24
U1 2
U2 23
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0907-4449
J9 ACTA CRYSTALLOGR D
JI Acta Crystallogr. Sect. D-Biol. Crystallogr.
PD AUG
PY 2013
VL 69
BP 1447
EP 1462
DI 10.1107/S0907444913009050
PN 8
PG 16
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA 191WJ
UT WOS:000322445100012
PM 23897468
ER
PT J
AU Jin, TC
Huang, M
Smith, P
Jiang, JS
Xiao, TS
AF Jin, Tengchuan
Huang, Mo
Smith, Patrick
Jiang, Jiansheng
Xiao, T. Sam
TI Structure of the caspase-recruitment domain from a zebrafish
guanylate-binding protein
SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION
COMMUNICATIONS
LA English
DT Article
ID IFN-INDUCIBLE GTPASES; CRYSTAL-STRUCTURE; SUPERFAMILY; INFLAMMASOME;
ACTIVATION; COMPLEX; CONSERVATION; ASSOCIATION; MECHANISMS; COMPONENTS
AB The caspase-recruitment domain (CARD) mediates homotypic protein-protein interactions that assemble large oligomeric signaling complexes such as the inflammasomes during innate immune responses. Structural studies of the mammalian CARDs demonstrate that their six-helix bundle folds belong to the death-domain superfamily, whereas such studies have not been reported for other organisms. Here, the zebrafish interferon-induced guanylate-binding protein 1 (zIGBP1) was identified that contains an N-terminal GTPase domain and a helical domain typical of the mammalian guanylate-binding proteins, followed by a FIIND domain and a C-terminal CARD similar to the mammalian inflammasome proteins NLRP1 and CARD8. The structure of the zIGBP1 CARD as a fusion with maltose-binding protein was determined at 1.47 angstrom resolution. This revealed a six-helix bundle fold similar to the NLRP1 CARD structure with the bent alpha 1 helix typical of all known CARD structures. The zIGBP1 CARD surface contains a positively charged patch near its alpha 1 and alpha 4 helices and a negatively charged patch near its alpha 2, alpha 3 and alpha 5 helices, which may mediate its interaction with partner domains. Further studies using binding assays and other analyses will be required in order to address the physiological function(s) of this zebrafish protein.
C1 [Jin, Tengchuan; Huang, Mo; Smith, Patrick; Jiang, Jiansheng; Xiao, T. Sam] NIAID, Struct Immunobiol Unit, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Xiao, TS (reprint author), NIAID, Struct Immunobiol Unit, Immunol Lab, NIH, 4 Mem Dr,Bldg 4,Room 228, Bethesda, MD 20892 USA.
EM xiaot@niaid.nih.gov
RI Xiao, Tsan/I-7616-2013; Xiao, Tsan/A-8590-2010; Jin,
Tengchuan/B-5883-2014
OI Xiao, Tsan/0000-0001-9688-475X; Jin, Tengchuan/0000-0002-1395-188X
FU National Cancer Institute [Y1-CO-1020]; National Institute of General
Medical Sciences [Y1-GM-1104]; Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, NIH
FX The authors would like to thank Dr Lars C. Pedersen at NIEHS for the
MBP-fusion plasmids and Dr Yang Wang at Illinois Institute of Technology
for the zebrafish cDNA. We are grateful to the beamline scientists at
the GM/CA-CAT, Advanced Photon Source for their support, which is funded
in whole or in part with federal funds from the National Cancer
Institute (Y1-CO-1020) and the National Institute of General Medical
Sciences (Y1-GM-1104). TSX is supported by the Division of Intramural
Research, National Institute of Allergy and Infectious Diseases, NIH.
The authors declare no conflict of interest.
NR 37
TC 4
Z9 4
U1 1
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1744-3091
J9 ACTA CRYSTALLOGR F
JI Acta Crystallogr. F-Struct. Biol. Cryst. Commun.
PD AUG
PY 2013
VL 69
BP 855
EP 860
DI 10.1107/S1744309113015558
PN 8
PG 6
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA 192UU
UT WOS:000322512300007
PM 23908027
ER
PT J
AU Schembre, SM
Wen, CK
Davis, JN
Shen, E
Nguyen-Rodrigugz, ST
Belcher, BR
Hsu, YW
Weigensberg, MJ
Goran, MI
Spruijt-Metz, D
AF Schembre, Susan M.
Wen, Cheng Kun
Davis, Jaimie N.
Shen, Ernest
Nguyen-Rodrigugz, Selena T.
Belcher, Britni R.
Hsu, Ya-Wen
Weigensberg, Marc J.
Goran, Michael I.
Spruijt-Metz, Donna
TI Eating breakfast more frequently is cross-sectionally associated with
greater physical activity and lower levels of adiposity in overweight
Latina and African American girls
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID BODY-MASS INDEX; WHITE ADOLESCENT GIRLS; UNITED-STATES; ENERGY-BALANCE;
COGNITIVE PERFORMANCE; DIETARY BEHAVIORS; NUTRIENT INTAKE; WEIGHT
STATUS; US CHILDREN; CONSUMPTION
AB Background: Eating breakfast is believed to promote a healthy body weight. Yet, few studies have examined the contribution of energy balance-related behavioral factors to this relation in minority youth.
Objective: We assessed the associations between breakfast consumption and dietary intake, physical activity (PA), and adiposity before and after accounting for energy intake and PA in minority girls.
Design: Cross-sectional data were obtained, on body mass index (BMI), percentage body fat (measured by BodPod), dietary intake (measured with 3-d dietary records), and PA (measured with 7-d accelerometry) from 87 Latina and African American girls 8-17 y of age (75% Latina, 80% overweight). Dietary records were used to categorize girls as more frequent breakfast eaters (MF; 2 or 3 of 3 d; n = 57) or less frequent breakfast eaters (LF; 0 or 1 of 3 d; n = 30). Chi-square tests, ANCOVA, and multiple regression analyses were conducted. Mediation was assessed with a Sobel test.
Results: Compared with the MF group, the LF group spent 30% less time (12.6 min/d) in moderate-to-vigorous-intensity PA (MVPA; P = 0.004) and had a higher percentage body fat (P = 0.029). MVPA accounted for 25% (95% CI: -8.8%, 58.1%; P = 0.139) of the relation between breakfast consumption. and percentage body fat. We were unable to show that energy intake or MVPA was a significant mediator of the relation between breakfast consumption and adiposity in this sample.
Conclusions: Evidence suggests that among predominantly overweight minority girls, MVPA, but not energy intake, was associated with both breakfast consumption and adiposity; however, a lack of power reduced our ability to detect a significant mediation effect. Other unobserved variables likely contribute to this relation.
C1 [Schembre, Susan M.] Univ Texas MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77230 USA.
[Schembre, Susan M.; Wen, Cheng Kun; Shen, Ernest; Goran, Michael I.; Spruijt-Metz, Donna] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Weigensberg, Marc J.] Univ So Calif, Keck Sch Med, Dept Pediat, Los Angeles, CA 90033 USA.
[Davis, Jaimie N.] Univ Texas Austin, Dept Nutr Sci, Austin, TX 78712 USA.
[Nguyen-Rodrigugz, Selena T.] Calif State Univ Long Beach, Dept Hlth Sci, NCLR CSULB Ctr Latino Community Hlth Evaluat & Le, Long Beach, CA USA.
[Belcher, Britni R.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Risk Factor Monitoring & Methods Branch,Appl Res, Bethesda, MD 20892 USA.
[Hsu, Ya-Wen] Chia Nan Univ Pharm & Sci, Dept Hosp, Tainan, Taiwan.
[Hsu, Ya-Wen] Chia Nan Univ Pharm & Sci, Hlth Care Adm, Tainan, Taiwan.
RP Schembre, SM (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Behav Sci, 1515 Holcombe Blvd, Houston, TX 77230 USA.
EM sschembre@mdanderson.org
FU University of Southern California Center for Transdisciplinary Research
on Energetics and Cancer [U54 CA 116848]; Eunice Kennedy Shriver
National Institute of Child Health and Human Development [R01 HD/HL
33064]; General Clinical Research Center NCRR/NIH [M01RR 00043]; Dr
Robert C and Veronica Atkins Foundation; National Cancer Institute
[T32CA009492]
FX Supported by the University of Southern California Center for
Transdisciplinary Research on Energetics and Cancer (U54 CA 116848); the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (R01 HD/HL 33064); General Clinical Research Center NCRR/NIH
(M01RR 00043); and the Dr Robert C and Veronica Atkins Foundation. SMS
was supported by a National Cancer Institute postdoctoral training grant
(T32CA009492).
NR 46
TC 10
Z9 10
U1 0
U2 18
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD AUG
PY 2013
VL 98
IS 2
BP 275
EP 281
DI 10.3945/ajcn.112.045849
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 189SA
UT WOS:000322287400005
PM 23803890
ER
PT J
AU Bailey, RL
Durazo-Arvizu, RA
Cannel, R
Green, R
Pfeiffer, CM
Sempos, CT
Carriquiry, A
Yetley, EA
AF Bailey, Regan L.
Durazo-Arvizu, Ramon A.
Cannel, Ralph
Green, Ralph
Pfeiffer, Christine M.
Sempos, Christopher T.
Carriquiry, Alicia
Yetley, Elizabeth A.
TI Modeling a methylmalonic acid-derived change point for serum vitamin
B-12 for adults in NHANES
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID NUTRITION EXAMINATION SURVEYS; LOCALLY WEIGHTED REGRESSION;
NATIONAL-HEALTH; DEFICIENCY; HOLOTRANSCOBALAMIN; COBALAMIN;
HOMOCYSTEINE; DETERMINANTS; POPULATION; BIOMARKERS
AB Background: No consensus exists about which cutoff point should be applied for serum vitamin B-12 (SB-12) concentrations to define vitamin B-12 status in population-based research.
Objective: The study's aim was to identify whether a change point exists at which the relation between plasma methylmalonic acid (MMA) and SB-12 changes slope to differentiate between inadequate and adequate vitamin B-12 status by using various statistical models.
Design: We used data on adults (>= 19 y; n = 12,683) from NHANES 1999-2004-a nationally representative, cross-sectional survey. We evaluated 6 piece-wise polynomial and exponential decay models that used different control levels for known covariates.
Results: The MMA-defined change point for SB-12 varied depending on the statistical model used. A linear-splines model was determined to best fit the data, as determined by the approximate permutation test; 3 slopes relating SB-12 and MMA and resulting in 2 change points and 3 subgroups were shown. The first group (SB-12 <126 pmol/L) was small and had the highest MMA concentration (median: 281 nmol/L; 95% CI: 245, 366 nmol/L; n = 157, 1.2%); many in this group could be considered at high risk of severe deficiency because combined abnormalities of MMA and homocysteine were very frequent and the concentrations themselves were significantly higher. The highest SB-12 group (SB-12 >287 pmol/L; n = 8569, 67.6%) likely had adequate vitamin B-12 status (median MMA: 120 nmol/L; 95% CI: 119, 125 nmol/L). The vitamin B-12 status of the sizable intermediate group (n = 3957, 33%) was difficult to interpret.
Conclusions: The 3 distinct slopes for the relation between SB-12 and MMA challenges the conventional use of one cutoff point for classifying vitamin B-12 status. In epidemiologic research, the use of one cutoff point would fail to separate the small, severely deficient group from the intermediate group that has neither normal nor clearly deficient vitamin B-12 concentrations (ie, unknown vitamin B-12 status). This intermediate group requires further characterization.
C1 [Bailey, Regan L.; Sempos, Christopher T.; Yetley, Elizabeth A.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Durazo-Arvizu, Ramon A.] Loyola Univ, Stritch Sch Med, Chicago, IL 60611 USA.
[Cannel, Ralph] New York Methodist Hosp, Dept Med, Brooklyn, NY USA.
[Cannel, Ralph] Weill Cornell Med Coll, New York, NY USA.
[Green, Ralph] UC Davis Med Ctr, Dept Pathol & Lab Med, Sacramento, CA USA.
[Carriquiry, Alicia] Iowa State Univ, Dept Stat, Ames, IA USA.
[Pfeiffer, Christine M.] CDC, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA.
RP Bailey, RL (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,2B03, Bethesda, MD 20892 USA.
EM baileyr@mail.nih.gov
NR 26
TC 7
Z9 8
U1 0
U2 4
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD AUG
PY 2013
VL 98
IS 2
BP 460
EP 467
DI 10.3945/ajcn.113.061234
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 189SA
UT WOS:000322287400027
PM 23803883
ER
PT J
AU Mondul, AM
Sampson, JN
Moore, SC
Weinstein, SJ
Evans, AM
Karoly, ED
Virtamo, J
Albanes, D
AF Mondul, Alison M.
Sampson, Joshua N.
Moore, Steven C.
Weinstein, Stephanie J.
Evans, Anne M.
Karoly, Edward D.
Virtamo, Jarmo
Albanes, Demetrius
TI Metabolomic profile of response to supplementation with beta-carotene in
the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID LUNG-CANCER; CYTOCHROME-P450 ENZYMES; INDUCTION; FERRETS; SYSTEMS; SMOKE
AB Background: Two chemoprevention trials found that supplementation with beta-carotene increased the risk of lung cancer and overall mortality. The biologic basis of these findings remains poorly understood.
Objective: The objective was to compare the on-study change in metabolomic profiles of men randomly assigned to receive or not receive beta-carotene supplements in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study.
Design: The ATBC Study was a randomized, double-blind, placebo-controlled, primary cancer prevention trial; participants were Finnish male smokers assigned to 1 of 4 intervention groups: 1) a-tocopherol, 2) beta-carotene, 3) both, or 4) placebo. Fifty participants with both baseline and follow-up fasting serum samples were randomly selected from each of these groups. Metabolomic profiling was conducted by mass spectrometry. The association between change in each metabolite over time and trial assignment (beta-carotene or no beta-carotene) was estimated by linear regression.
Results: We measured 489 metabolites, and 17 changed significantly (P < 0.05) in response to beta-carotene supplementation. More of these 17 metabolites were of xenobiotic origin than would be expected by chance (9 of 60, or 15%; P = 0.00004). We also found a suggestive association with 1,5-anhydroglucitol-a marker of glycemic control (beta = -0.379, P = 0.0071).
Conclusions: Male smokers supplemented with beta-carotene developed metabolomic profiles consistent with the induction of cytochrome P450 enzymes, the primary metabolizers of xenobiotics in humans. These findings may shed light on the increased mortality associated with beta-carotene supplementation in the ATBC Study and suggest the need to explore potential interactions between medication use and dietary supplements, particularly among smokers. This trial was registered at clinicaltrials.gov as NCT00342992.
C1 [Mondul, Alison M.; Moore, Steven C.; Weinstein, Stephanie J.; Albanes, Demetrius] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Bethesda, MD 20892 USA.
[Sampson, Joshua N.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Bethesda, MD 20892 USA.
[Evans, Anne M.; Karoly, Edward D.] Metabolon Inc, Durham, NC USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
RP Albanes, D (reprint author), 9609 Med Ctr Dr,6E342, Bethesda, MD 20892 USA.
EM daa@nih.gov
RI Albanes, Demetrius/B-9749-2015; Moore, Steven/D-8760-2016
OI Moore, Steven/0000-0002-8169-1661
FU National Cancer Institute, NIH, US Public Health Service [N01-CN-45165,
N01-RC-45035, N01-RC-37004, HHSN261201000006C, HHSN261200800001E]
FX Supported by the Intramural Research Program of the National Cancer
Institute, NIH, US Public Health Service (grant nos. N01-CN-45165,
N01-RC-45035, N01-RC-37004, HHSN261201000006C, and HHSN261200800001E).
NR 18
TC 9
Z9 9
U1 2
U2 12
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD AUG
PY 2013
VL 98
IS 2
BP 488
EP 493
DI 10.3945/ajcn.113.062778
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 189SA
UT WOS:000322287400030
PM 23803886
ER
PT J
AU Ohlhorst, SD
Russell, R
Bier, D
Klurfeld, DM
Li, ZP
Mein, JR
Milner, J
Ross, AC
Stover, P
Konopka, E
AF Ohlhorst, Sarah D.
Russell, Robert
Bier, Dennis
Klurfeld, David M.
Li, Zhaoping
Mein, Jonathan R.
Milner, John
Ross, A. Catharine
Stover, Patrick
Konopka, Emily
TI Nutrition research to affect food and a healthy life span
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID MEDITERRANEAN DIET; CHILDREN
AB Proper nutrition offers one of the most effective and least costly ways to decrease the burden of many diseases and their associated risk factors, including obesity. Nutrition research holds the key to increasing our understanding of the causes of obesity and its related comorbidities and thus holds promise to markedly influence global health and economies. After outreach to 75 thought leaders, the American Society for Nutrition (ASN) convened a Working Group to identify the nutrition research needs whose advancement will have the greatest projected impact on the future health and well-being of global populations. ASN's Nutrition Research Needs focus on the following high priority areas: 1) variability in individual responses to diet and foods; 2) healthy growth, development, and reproduction; 3) health maintenance; 4) medical management; 5) nutrition-related behaviors; and 6) food supply/environment. ASN hopes the Nutrition Research Needs will prompt collaboration among scientists across all disciplines to advance this challenging research agenda given the high potential for translation and impact on public health. Furthermore, ASN hopes the findings from the Nutrition Research Needs will stimulate the development and adoption of new and innovative strategies that can be applied toward the prevention and treatment of nutrition-related diseases. The multidisciplinary nature of nutrition research requires stakeholders with differing areas of expertise to collaborate on multifaceted approaches to establish the evidence-based nutrition guidance and policies that will lead to better health for the global population. In addition to the identified research needs, ASN also identified 5 tools that are critical to the advancement of the Nutrition Research Needs: 1) omics, 2) bioinformatics, 3) databases, 4) biomarkers, and 5) cost-effectiveness analysis.
C1 [Ohlhorst, Sarah D.; Konopka, Emily] Amer Soc Nutr, Bethesda, MD 20814 USA.
[Russell, Robert] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Russell, Robert] Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Bier, Dennis] Baylor Coll Med, USDA, ARS, Childrens Nutr Res Ctr,Dept Pediat, Houston, TX 77030 USA.
[Klurfeld, David M.] ARS, Human Nutr Program, USDA, Beltsville, MD USA.
[Li, Zhaoping] Univ Calif Los Angeles, Ctr Human Nutr, Los Angeles, CA USA.
[Li, Zhaoping] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Mein, Jonathan R.] Monsanto Vegetable Seed, Monsanto Ctr Food & Nutr Res, Kannapolis, NC USA.
[Milner, John] NCI, NIH, Bethesda, MD 20892 USA.
[Ross, A. Catharine] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA.
[Stover, Patrick] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
RP Ohlhorst, SD (reprint author), Amer Soc Nutr, 9650 Rockville Pike, Bethesda, MD 20814 USA.
EM sohlhorst@nutrition.org
FU NIDDK NIH HHS [R01 DK058144]
NR 12
TC 5
Z9 5
U1 1
U2 19
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD AUG
PY 2013
VL 98
IS 2
BP 620
EP 625
DI 10.3945/ajcn.113.067744
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 189SA
UT WOS:000322287400059
PM 23783290
ER
PT J
AU Costantine, MM
Mele, L
Landon, MB
Spong, CY
Ramin, SM
Casey, B
Wapner, RJ
Varner, MW
Rouse, DJ
Thorp, JM
Sciscione, A
Catalano, P
Caritis, SN
Sorokin, Y
Peaceman, AM
Tolosa, JE
Anderson, GD
AF Costantine, Maged M.
Mele, Lisa
Landon, Mark B.
Spong, Catherine Y.
Ramin, Susan M.
Casey, Brian
Wapner, Ronald J.
Varner, Michael W.
Rouse, Dwight J.
Thorp, John M., Jr.
Sciscione, Anthony
Catalano, Patrick
Caritis, Steve N.
Sorokin, Yoram
Peaceman, Alan M.
Tolosa, Jorge E.
Anderson, Garland D.
CA Eunice Kennedy Shriver Natl Inst C
TI Customized versus Population Approach for Evaluation of Fetal Overgrowth
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article
DE customized growth; adverse neonatal outcomes; gestational diabetes;
large for gestational age
ID BIRTH-WEIGHT STANDARDS; GROWTH STANDARDS; MORTALITY; INFANTS;
MULTICENTER; PREGNANCIES; MORBIDITY
AB Objective To compare the ability of customized versus normalized population fetal growth norms in identifying neonates at risk for adverse perinatal outcomes (APOs) associated with fetal overgrowth and gestational diabetes (GDM).
Study Design Secondary analysis of a multicenter treatment trial of mild GDM. The primary outcome was a composite of neonatal outcomes associated with fetal overgrowth and GDM. Birth weight percentiles were calculated using ethnicity-and gender-specific population and customized norms (Gardosi).
Results Two hundred three (9.8%) and 288 (13.8%) neonates were large for gestational age by population (LGApop) and customized (LGAcust) norms, respectively. Both LGApop and LGAcust were associated with the primary outcome and neonatal hyperinsulinemia, but neither was associated with hypoglycemia or hyperbilirubinemia. The ability of customized and population birth weight percentiles for predicting APOs were poor (area under the receiver operating characteristic curve < 0.6 for six of eight APOs).
Conclusion Neither customized nor normalized population norms better identify neonates at risk of APOs related to fetal overgrowth and GDM.
C1 [Costantine, Maged M.; Anderson, Garland D.] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA.
[Mele, Lisa] George Washington Univ, Ctr Biostat, Washington, DC USA.
[Landon, Mark B.] Ohio State Univ, Columbus, OH 43210 USA.
[Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Ramin, Susan M.] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA.
[Casey, Brian] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Wapner, Ronald J.] Columbia Univ, New York, NY USA.
[Varner, Michael W.] Univ Utah, Salt Lake City, UT USA.
[Rouse, Dwight J.] Univ Alabama Birmingham, Birmingham, AL USA.
[Thorp, John M., Jr.] Univ N Carolina, Chapel Hill, NC USA.
[Sciscione, Anthony] Drexel Univ, Philadelphia, PA 19104 USA.
[Catalano, Patrick] Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA.
[Caritis, Steve N.] Univ Pittsburgh, Pittsburgh, PA USA.
[Sorokin, Yoram] Wayne State Univ, Detroit, MI USA.
[Peaceman, Alan M.] Northwestern Univ, Chicago, IL 60611 USA.
[Tolosa, Jorge E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
RP Costantine, MM (reprint author), 301 Univ Blvd, Galveston, TX 77555 USA.
EM mmcostan@utmb.edu
RI Varner, Michael/K-9890-2013
OI caritis, steve/0000-0002-2169-0712; Peaceman, Alan/0000-0002-4515-4850;
Varner, Michael/0000-0001-9455-3973
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [HD53097, HD27915, HD34116, HD40485, HD34208, HD27869,
HD40500, HD40560, HD34136, HD40544, HD27860, HD40545, HD21410, HD27917,
HD40512, HD53118, HD36801]; General Clinical Research Centers Grant
[M01-RR00034]; National Center for Research Resources [UL1-RR024989,
M01-RR00080, UL1-RR025764, C06-RR11234]
FX The project described was supported by grants from the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(HD53097, HD27915, HD34116, HD40485, HD34208, HD27869, HD40500, HD40560,
HD34136, HD40544, HD27860, HD40545, HD21410, HD27917, HD40512, HD53118,
HD36801), General Clinical Research Centers Grant (M01-RR00034), and the
National Center for Research Resources (UL1-RR024989, M01-RR00080,
UL1-RR025764, C06-RR11234) and does not necessarily represent the
official views of the NICHD or the National Institutes of Health.
NR 31
TC 3
Z9 3
U1 1
U2 7
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
J9 AM J PERINAT
JI Am. J. Perinatol.
PD AUG
PY 2013
VL 30
IS 7
BP 565
EP 571
DI 10.1055/s-0032-1329188
PG 7
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 186DJ
UT WOS:000322021900007
PM 23147078
ER
PT J
AU Casagrande, SS
Cowie, CC
Fradkin, JE
AF Casagrande, Sarah Stark
Cowie, Catherine C.
Fradkin, Judith E.
TI Utility of the U.S. Preventive Services Task Force Criteria for Diabetes
Screening
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID LIFE-STYLE INTERVENTION; CORONARY-HEART-DISEASE; CARDIOVASCULAR-DISEASE;
CLINICAL-PRACTICE; GLUCOSE CONTROL; RISK; ADULTS; MELLITUS; HEMOGLOBIN;
REDUCTION
AB Background: Federal law requires certain private insurers to cover and waive patient cost sharing for preventive medical services that receive a grade of B or better from the U.S. Preventive Services Task Force (USPSTF). The USPSTF recommends that asymptomatic adults who have a blood pressure (BP) higher than 135/80 mmHg be screened for type 2 diabetes.
Purpose: The goals of this study were to determine the sensitivity and specificity of the USPSTF screening criteria and to determine the prevalence of cardiovascular risk factors and comorbidity among undiagnosed individuals by USPSTF criteria.
Methods: Data come from 7189 adults who participated in the 2003-2010 National Health and Nutrition Examination Survey; statistical analysis was conducted in 2011-2012. Participants with fasting plasma glucose >= 126 mg/dL or hemoglobin A1c (HbA1c) >= 6.5% who did not self-report a diagnosis of diabetes were categorized as having undiagnosed diabetes.
Results: Among people without diagnosed diabetes, 4.0% had undiagnosed diabetes. The proportion of adults with undiagnosed diabetes who were identified (sensitivity) using BP >135/80 mmHg as the screening standard was 44.4%; among individuals without undiagnosed diabetes, 74.8% had BP <= 135/80 mmHg (specificity). For those with undiagnosed diabetes, the prevalence of HbA1c 7.0%-<8.0% was 10.6% for those with BP <= 135/80 mmHg and 14.3% for those with BP > 135/80 mmHg; and 12.8% and 9.4% for HbA1c >= 8.0%, respectively. Elevated low-density lipoprotein (100-160 mg/dL) was similar by BP cut-point (52%-53%). For those with BP <= 135/80 mmHg, 16.7% had a history of cardiovascular disease and 22.9% had chronic kidney disease.
Conclusions: The USPSTF screening recommendations result in missing more than half of those who have undiagnosed diabetes, and a substantial proportion of these people have increased low-density lipoprotein and other cardiovascular risk factors. (C) 2013 American Journal of Preventive Medicine. All rights reserved.
C1 [Casagrande, Sarah Stark] Social & Sci Syst Inc, Silver Spring, MD USA.
[Cowie, Catherine C.; Fradkin, Judith E.] NIDDK, Div Diabet, Bethesda, MD USA.
RP Casagrande, SS (reprint author), 8757 Georgia Ave,12th Floor, Silver Spring, MD 20910 USA.
EM scasagrande@s-3.com
FU National Institute of Diabetes and Digestive and Kidney Diseases
[HHSN267200700001G]
FX This work was financially supported by the National Institute of
Diabetes and Digestive and Kidney Diseases (HHSN267200700001G). The
findings and conclusions in this report are those of the authors and do
not necessarily represent the views of the National Institute of
Diabetes and Digestive and Kidney Diseases.
NR 27
TC 15
Z9 15
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD AUG
PY 2013
VL 45
IS 2
BP 167
EP 174
DI 10.1016/j.amepre.2013.02.026
PG 8
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 187FO
UT WOS:000322102500005
PM 23867023
ER
PT J
AU Perkins, RB
Anderson, BL
Gorin, SS
Schulkin, JA
AF Perkins, Rebecca B.
Anderson, Britta L.
Gorin, Sherri Sheinfeld
Schulkin, Jay A.
TI Challenges in Cervical Cancer Prevention A Survey of U.S.
Obstetrician-Gynecologists
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID HUMAN-PAPILLOMAVIRUS VACCINATION; UNITED-STATES; HPV VACCINE;
SCREENING-INTERVALS; REGIONAL-VARIATIONS; YOUNG-WOMEN; RISK; CARE; PAP;
PHYSICIANS
AB Background: Current cervical cancer prevention recommendations include human papillomavirus (HPV) vaccination, Pap and HPV co-testing, and Pap testing at 3- to 5-year intervals.
Purpose: To examine attitudes, practice patterns, and barriers related to HPV vaccination and cervical cancer screening guidelines among U.S. obstetrician-gynecologists.
Methods: In 2011-2012, a national sample of members of the American Congress of Obstetricians and Gynecologists responded to a 15-item (some with multiple parts) questionnaire assessing sociodemographic characteristics, clinical practices, and perceived barriers to HPV vaccination and cervical cancer screening. Multivariate logistic regression was used to identify factors associated with guideline adherence. Analyses were conducted in 2012.
Results: A total of 366 obstetrician-gynecologists participated. Ninety-two percent of respondents offered HPV vaccination to patients, but only 27% estimated that most eligible patients received vaccination. Parent and patient refusals were commonly cited barriers to HPV vaccination. Approximately half of respondents followed guidelines to begin cervical cancer screening at age 21 years, discontinue screening at age 70 years or after hysterectomy, and appropriately utilize Pap and HPV co-testing. Most physicians continued to recommend annual Paps (74% aged 21-29 years, 53% aged >= 30 years). Physicians felt that patients were uncomfortable with extended screening intervals and were concerned that patients would not come for annual exams without concurrent Paps. Solo practitioners were less likely to follow both vaccination and screening guidelines than those in group practices.
Conclusions: This survey of obstetrician-gynecologists indicates persistent barriers to the adoption of HPV vaccination and cervical cancer screening guidelines. Interventions to promote guideline adherence may help improve the quality of cervical cancer prevention. (C) 2013 American Journal of Preventive Medicine
C1 [Perkins, Rebecca B.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Anderson, Britta L.; Schulkin, Jay A.] Amer Congress Obstetricians & Gynecologists, Washington, DC USA.
[Gorin, Sherri Sheinfeld] Natl Canc Inst SAIC, Outcomes Res Branch, Rockville, MD USA.
RP Perkins, RB (reprint author), Boston Univ, Sch Med, Dept Obstet & Gynecol, 85 E Concord St,6th Floor, Boston, MA 02118 USA.
EM Rebecca.perkins@bmc.org
OI Perkins, Rebecca/0000-0002-7054-3014
FU DHHS [UA6MC19010]; Health Resources and Services Administration;
Maternal and Child Health Research Program; American Cancer Society
[MRSG-09-151-01]
FX Funding for the research was provided by grant UA6MC19010, through DHHS,
Health Resources and Services Administration, Maternal and Child Health
Research Program and by an American Cancer Society Mentored Research
Scholar Grant (MRSG-09-151-01). No commercial support was obtained.
NR 42
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U1 1
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD AUG
PY 2013
VL 45
IS 2
BP 175
EP 181
DI 10.1016/j.amepre.2013.03.019
PG 7
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 187FO
UT WOS:000322102500006
PM 23867024
ER
PT J
AU Kumar, S
Nilsen, WJ
Abernethy, A
Atienza, A
Patrick, K
Pavel, M
Riley, WT
Shar, A
Spring, B
Spruijt-Metz, D
Hedeker, D
Honavar, V
Kravitz, R
Lefebvre, RC
Mohr, DC
Murphy, SA
Quinn, C
Shusterman, V
Swendeman, D
AF Kumar, Santosh
Nilsen, Wendy J.
Abernethy, Amy
Atienza, Audie
Patrick, Kevin
Pavel, Misha
Riley, William T.
Shar, Albert
Spring, Bonnie
Spruijt-Metz, Donna
Hedeker, Donald
Honavar, Vasant
Kravitz, Richard
Lefebvre, R. Craig
Mohr, David C.
Murphy, Susan A.
Quinn, Charlene
Shusterman, Vladimir
Swendeman, Dallas
TI Mobile Health Technology Evaluation The mHealth Evidence Workshop
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID RANDOMIZED-TRIAL; CELL PHONES; CARE; INTERVENTION; TIME
AB Creative use of new mobile and wearable health information and sensing technologies (mHealth) has the potential to reduce the cost of health care and improve well-being in numerous ways. These applications are being developed in a variety of domains, but rigorous research is needed to examine the potential, as well as the challenges, of utilizing mobile technologies to improve health outcomes. Currently, evidence is sparse for the efficacy of mHealth. Although these technologies may be appealing and seemingly innocuous, research is needed to assess when, where, and for whom mHealth devices, apps, and systems are efficacious.
In order to outline an approach to evidence generation in the field of mHealth that would ensure research is conducted on a rigorous empirical and theoretic foundation, on August 16, 2011, researchers gathered for the mHealth Evidence Workshop at NIH. The current paper presents the results of the workshop. Although the discussions at the meeting were cross-cutting, the areas covered can be categorized broadly into three areas: (1) evaluating assessments; (2) evaluating interventions; and (3) reshaping evidence generation using mHealth. This paper brings these concepts together to describe current evaluation standards, discuss future possibilities, and set a grand goal for the emerging field of mHealth research. Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine
C1 [Kumar, Santosh] Univ Memphis, Dept Comp Sci, Memphis, TN 38152 USA.
[Nilsen, Wendy J.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
[Atienza, Audie] NCI, Bethesda, MD 20892 USA.
[Riley, William T.] NHLBI, Bethesda, MD 20892 USA.
[Quinn, Charlene] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Abernethy, Amy] Duke Univ, Med Ctr, Dept Med, Durham, NC 27706 USA.
[Lefebvre, R. Craig] RTI Int, Hlth Commun & Mkt, Res Triangle Pk, NC USA.
[Patrick, Kevin] Univ Calif San Diego, Dept Prevent Med, La Jolla, CA 92093 USA.
[Spruijt-Metz, Donna] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Swendeman, Dallas] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Kravitz, Richard] Univ Calif Davis, Dept Internal Med, Sacramento, CA 95817 USA.
[Pavel, Misha; Honavar, Vasant] Natl Sci Fdn, Directorate Comp & Informat Sci & Engn, Arlington, VA 22230 USA.
[Shar, Albert] Robert Wood Johnson Fdn, Pioneer Portfolio, Princeton, NJ 08540 USA.
[Spring, Bonnie; Mohr, David C.] Northwestern Univ, Dept Prevent Med, Evanston, IL USA.
[Hedeker, Donald] Univ Illinois, Div Epidemiol & Biostat, Chicago, IL USA.
[Murphy, Susan A.] Univ Michigan, Dept Stat, Ann Arbor, MI 48109 USA.
[Shusterman, Vladimir] Univ Pittsburgh, Med Ctr, Noninvas Cardiac Elect Labs, Pittsburgh, PA USA.
[Shusterman, Vladimir] PinMed, Pittsburgh, PA USA.
RP Nilsen, WJ (reprint author), NIH, Off Behav & Social Sci Res, 31 Ctr Dr,Bldg 31,B1C19, Bethesda, MD 20892 USA.
EM nilsenwj@od.nih.gov
RI Honavar, Vasant/K-9835-2015; Emchi, Karma/Q-1952-2016;
OI Honavar, Vasant/0000-0001-5399-3489; Kravitz,
Richard/0000-0001-5575-529X
FU Intramural NIH HHS [Z99 OD999999]; NCATS NIH HHS [UL1 TR000150]; NIDA
NIH HHS [P50 DA010075]; NIMH NIH HHS [P30 MH058107]
NR 38
TC 127
Z9 129
U1 11
U2 85
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD AUG
PY 2013
VL 45
IS 2
BP 228
EP 236
DI 10.1016/j.amepre.2013.03.017
PG 9
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 187FO
UT WOS:000322102500013
PM 23867031
ER
PT J
AU Glasgow, RE
Riley, WT
AF Glasgow, Russell E.
Riley, William T.
TI Pragmatic Measures What They Are and Why We Need Them
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID PATIENT-REPORTED OUTCOMES; PRACTICAL CLINICAL-TRIALS; HEALTH-CARE;
DEPRESSION; VALIDITY; PROMIS; PHQ-9; RESPONSIVENESS; INDIVIDUALS;
SCIENCE
AB Pragmatic measures are important to facilitate implementation and dissemination, address stakeholder issues, and drive quality improvement. This paper proposes necessary and recommended criteria for pragmatic measures, provides examples of projects to develop and identify such measures, addresses potential concerns about these recommendations, and identifies areas for future research and application. Key criteria for pragmatic measures include importance to stakeholders in addition to researchers, low burden, broad applicability, sensitivity to change, and being actionable.
Examples of pragmatic measures are provided, including ones for different settings (e.g., primary care, hospital) and levels (e.g., individual, practitioner, setting) that illustrate approaches to produce broad-scale dissemination and the development of brief, standardized measures for use in pragmatic studies. There is an important need for pragmatic measures to facilitate pragmatic research, guide quality improvement, and inform progress on public health goals, but few examples are currently available. Development and evaluation of pragmatic measures and metrics would provide useful resources to advance science, policy, and practice. (C) 2013 Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine
C1 [Glasgow, Russell E.; Riley, William T.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
RP Glasgow, RE (reprint author), 9609 Med Ctr Dr,Room 4E440, Rockville, MD 20850 USA.
EM glasgowre@mail.nih.gov
NR 42
TC 35
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U1 1
U2 19
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD AUG
PY 2013
VL 45
IS 2
BP 237
EP 243
DI 10.1016/j.amepre.2013.03.010
PG 7
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 187FO
UT WOS:000322102500014
PM 23867032
ER
PT J
AU Hasin, DS
O'Brien, CP
Auriacombe, M
Borges, G
Bucholz, K
Budney, A
Compton, WM
Crowley, T
Ling, W
Petry, NM
AF Hasin, Deborah S.
O'Brien, Charles P.
Auriacombe, Marc
Borges, Guilherme
Bucholz, Kathleen
Budney, Alan
Compton, Wilson M.
Crowley, Thomas
Ling, Walter
Petry, Nancy M.
TI DSM-5 Criteria for Substance Use Disorders: Recommendations and
Rationale
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Review
ID NATIONAL EPIDEMIOLOGIC SURVEY; ITEM-RESPONSE THEORY; ALCOHOL-USE
DISORDERS; IV DIAGNOSTIC-CRITERIA; FAGERSTROM TOLERANCE QUESTIONNAIRE;
COMORBID PSYCHIATRIC-DISORDERS; MEASURING NICOTINE DEPENDENCE; CANNABIS
WITHDRAWAL SYNDROME; GENERAL-POPULATION SAMPLE; COMMON LATENT CONTINUUM
AB Since DSM-IV was published in 1994, its approach to substance use disorders has come under scrutiny. Strengths were identified (notably, reliability and validity of dependence), but concerns have also arisen. The DSM-5 Substance-Related Disorders Work Group considered these issues and recommended revisions for DSM-5. General concerns included whether to retain the division into two main disorders (dependence and abuse), whether substance use disorder criteria should be added or removed, and whether an appropriate substance use disorder severity indicator could be identified. Specific issues included possible addition of withdrawal syndrome's for several substances, alignment of nicotine criteria with those for other substances, addition of biomarkers, and inclusion of nonsubstance, behavioral addictions.
This article presents the major issues and evidence considered by the work group, which included literature reviews and extensive new data analyses. The work group recommendations for DSM-5 revisions included combining abuse and dependence criteria into a single substance use disorder based on consistent findings from over 200,000 study participants, dropping legal problems and adding craving as criteria, adding cannabis and caffeine withdrawal syndromes, aligning tobacco use disorder criteria with other substance use disorders, and moving gambling disorders to the chapter formerly reserved for substance-related disorders. The proposed changes overcome many problems, while further studies will be needed to address issues for which less data were available.
C1 [Hasin, Deborah S.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
Columbia Univ, Dept Psychiat, New York, NY USA.
Columbia Univ, Dept Epidemiol, New York, NY USA.
Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
Ctr Studies Addict, Philadelphia, PA USA.
Univ Bordeaux Segalen, Dept Addict Psychiat, Bordeaux, France.
Natl Inst Psychiat, Mexico City, DF, Mexico.
Univ Arkansas Med Sci, Dept Psychiat, Addict Res Ctr, Little Rock, AR 72205 USA.
Natl Inst Drug Abuse, Serv & Prevent Res, Div Epidemiol, Bethesda, MD USA.
Univ Colorado, Sch Med, Dept Psychiat, Aurora, CO USA.
Univ Colorado, Sch Med, Div Subst Dependence, Aurora, CO USA.
Univ Calif Los Angeles, Dept Psychiat & Biobehavioral Sci, Los Angeles, CA USA.
Univ Calif Los Angeles, Integrated Substance Abuse Programs, Los Angeles, CA USA.
Univ Connecticut, Ctr Hlth, Dept Psychiat, Farmington, CT USA.
Univ Connecticut, Ctr Hlth, Behav Cardiovasc Prevent Calhoun Cardiol Ctr, Farmington, CT USA.
San Diego VA Med Ctr, Dept Psychiat, San Diego, CA USA.
Natl Inst Alcohol Abuse & Alcoholism, Lab Epidemiol & Biometry, Bethesda, MD USA.
RP Hasin, DS (reprint author), New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
EM dsh2@columbia.edu
RI Auriacombe, Marc/A-6197-2017;
OI Auriacombe, Marc/0000-0002-8938-8683; Borges,
Guilherme/0000-0002-3269-0507
FU DETA Pharma; Mundipharma; Reckitt Benckiser Pharmaceuticals; G.W.
Pharmaceuticals; Alkermes; Braeburn Pharmaceuticals; Reckitt/Benckiser;
Titan Pharmaceuticals; U.S. World Meds; SGS North America; National
Institute on Alcohol Abuse and Alcoholism [K05AA014223, U01AA018111];
National Institute on Drug Abuse [R01DA018652]; New York State
Psychiatric Institute
FX Dr. Auriacombe has received research grants or advisory board fees from
DETA Pharma, Mundipharma, and Reckitt Benckiser Pharmaceuticals. Dr.
Budney has received consulting fees from G.W. Pharmaceuticals. Dr.
Compton has stock holdings in General Electric and Pfizer. Dr. Ling has
received consulting fees or research, grant, or travel support from
Alkermes, Braeburn Pharmaceuticals, Reckitt/Benckiser, Titan
Pharmaceuticals, U.S. World Meds, and SGS North America. The other
authors report no financial relationships with commercial interests.;
Supported by the National Institute on Alcohol Abuse and Alcoholism
(grants K05AA014223, U01AA018111), the National Institute on Drug Abuse
(R01DA018652), and the New York State Psychiatric Institute (to Dr.
Hasin).
NR 214
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U1 13
U2 104
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD AUG
PY 2013
VL 170
IS 8
BP 834
EP 851
DI 10.1176/appi.ajp.2013.12060782
PG 18
WC Psychiatry
SC Psychiatry
GA 194DO
UT WOS:000322611400008
PM 23903334
ER
PT J
AU Blasi, G
Napolitano, F
Ursini, G
Di Giorgio, A
Caforio, G
Taurisano, P
Fazio, L
Gelao, B
Attrotto, MT
Colagiorgio, L
Todarello, G
Piva, F
Papazacharias, A
Masellis, R
Mancini, M
Porcelli, A
Romano, R
Rampino, A
Quarto, T
Giulietti, M
Lipska, BK
Kleinman, JE
Popolizio, T
Weinberger, DR
Usiello, A
Bertolino, A
AF Blasi, Giuseppe
Napolitano, Francesco
Ursini, Gianluca
Di Giorgio, Annabella
Caforio, Grazia
Taurisano, Paolo
Fazio, Leonardo
Gelao, Barbara
Attrotto, Maria Teresa
Colagiorgio, Lucia
Todarello, Giovanna
Piva, Francesco
Papazacharias, Apostolos
Masellis, Rita
Mancini, Marina
Porcelli, Annamaria
Romano, Raffaella
Rampino, Antonio
Quarto, Tiziana
Giulietti, Matteo
Lipska, Barbara K.
Kleinman, Joel E.
Popolizio, Teresa
Weinberger, Daniel R.
Usiello, Alessandro
Bertolino, Alessandro
TI Association of GSK-3 beta Genetic Variation With GSK-3 beta Expression,
Prefrontal Cortical Thickness, Prefrontal Physiology, and Schizophrenia
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID SYNTHASE KINASE 3-BETA; WORKING-MEMORY PERFORMANCE; ATTENTIONAL CONTROL;
VAL(158)MET GENOTYPE; BIPOLAR DISORDER; CORTEX; BRAIN; ACTIVATION;
POLYMORPHISMS; TRANSCRIPTION
AB Objective: Glycogen synthase kinase 3 beta (GSK-3 beta) is an enzyme implicated in neurodevelopmental processes with a broad range of substrates mediating several canonical signaling pathways in the brain. The authors investigated the association of variation in the GSK-3 beta gene with a series of progressively more complex phenotypes of relevance to schizophrenia, a neurodevelopmental disorder with strong genetic risk.
Method: Based on computer predictions, the authors investigated in humans the association of GSK-3 beta functional variation with 1) GSK-3 beta mRNA expression from postmortem prefrontal cortex, 2) GSK-3 beta and beta-catenin protein expression from peripheral blood mononuclear cells (PBMCs), 3) prefrontal imaging phenotypes, and 4) diagnosis of schizophrenia.
Results: Consistent with predictions, the TT genotype of a single-nucleotide polymorphism in GSK-3 beta (rs12630592) was associated with reduced GSK-3 beta mRNA from postmortem prefrontal cortex. Furthermore, this genotype was associated with GSK-3 beta protein expression and kinase activity, as well as with downstream effects on beta-catenin expression in PBMCs. Finally, the TT genotype was associated with attenuated functional MRI prefrontal activity, reduced prefrontal cortical thickness, and diagnosis of schizophrenia.
Conclusions: These results suggest that GSK-3 beta variation is implicated in multiple phenotypes relevant to schizophrenia.
C1 [Bertolino, Alessandro] Univ Bari Aldo Moro, Dept Neurosci & Sense Organs, Grp Psychiat Neurosci, Bari, Italy.
CEINGE Biotecnol Avanzate, Naples, Italy.
IRCCS Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy.
Polytech Univ Marche, Dept Specialized Clin Sci & Odontostomatol, Ancona, Italy.
Aldo Moro Univ, Dept Biosci Biotechnol & Pharmacol Sci, Bari, Italy.
NIMH, Brain Disorders Branch, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA.
Lieber Inst Brain Dev, Baltimore, MD USA.
Univ Naples 2, Dept Environm Sci, Rome, Italy.
European Brain Res Inst, Rome, Italy.
RP Bertolino, A (reprint author), Univ Bari Aldo Moro, Dept Neurosci & Sense Organs, Grp Psychiat Neurosci, Bari, Italy.
EM alessandro.bertolino@uniba.it
RI Napolitano, Francesco/F-8691-2012; Bertolino, Alessandro/O-6352-2016;
Rampino, Antonio/Q-4465-2016; Di Giorgio, Annabella /D-7353-2017;
Lipska, Barbara/E-4569-2017;
OI Bertolino, Alessandro/0000-0002-1251-1380; Rampino,
Antonio/0000-0002-9654-3266; Di Giorgio, Annabella /0000-0001-7876-3495;
Papazacharias, Apostolos/0000-0001-5470-1601; Napolitano,
Francesco/0000-0003-0884-1851; PIVA, Francesco/0000-0003-1850-2482
FU CARIME Foundation; "Cassa di Risparmio di Puglia" Foundation;
Cooperativa "Fratello Sole"
FX Supported by the CARIME Foundation, the "Cassa di Risparmio di Puglia"
Foundation, and the Cooperativa "Fratello Sole."
NR 39
TC 26
Z9 26
U1 0
U2 7
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD AUG
PY 2013
VL 170
IS 8
BP 868
EP 876
DI 10.1176/appi.ajp.2012.12070908
PG 9
WC Psychiatry
SC Psychiatry
GA 194DO
UT WOS:000322611400011
PM 23598903
ER
PT J
AU Matthay, MA
Anversa, P
Bhattacharya, J
Burnett, BK
Chapman, HA
Hare, JM
Hei, DJ
Hoffman, AM
Kourembanas, S
McKenna, DH
Ortiz, LA
Ott, HC
Tente, W
Thebaud, B
Trapnell, BC
Weiss, DJ
Yuan, JXJ
Blaisdell, CJ
AF Matthay, Michael A.
Anversa, Piero
Bhattacharya, Jahar
Burnett, Bruce K.
Chapman, Harold A.
Hare, Joshua M.
Hei, Derek J.
Hoffman, Andrew M.
Kourembanas, Stella
McKenna, David H.
Ortiz, Luis A.
Ott, Harald C.
Tente, William
Thebaud, Bernard
Trapnell, Bruce C.
Weiss, Daniel J.
Yuan, Jason X. -J.
Blaisdell, Carol J.
TI Cell Therapy for Lung Diseases Report from an NIH-NHLBI Workshop,
November 13-14, 2012
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE mesenchymal stromal (stem) cells; epithelial and endothelial progenitor
cells; lung stem cells
ID MESENCHYMAL STEM-CELLS; ISCHEMIC CARDIOMYOPATHY; BRONCHOPULMONARY
DYSPLASIA; PULMONARY-HYPERTENSION; MITOCHONDRIAL TRANSFER;
RANDOMIZED-TRIAL; STROMAL CELLS; BASAL-CELLS; REGENERATION; INJURY
AB The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health convened the Cell Therapy for Lung Disease Working Group on November 13-14, 2012, to review and formulate recommendations for future research directions. The workshop brought together investigators studying basic mechanisms and the roles of cell therapy in preclinical models of lung injury and pulmonary vascular disease, with clinical trial experts in cell therapy for cardiovascular diseases and experts from the NHLBI Production Assistance for Cell Therapy program. The purpose of the workshop was to discuss the current status of basic investigations in lung cell therapy, to identify some of the scientific gaps in current knowledge regarding the potential roles and mechanisms of cell therapy in the treatment of lung diseases, and to develop recommendations to the NHLBI and the research community on scientific priorities and practical steps that would lead to first-in-human trials of lung cell therapy.
C1 [Matthay, Michael A.; Chapman, Harold A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Anversa, Piero] Harvard Univ, Sch Med, Dept Anesthesia & Med, Boston, MA USA.
[Bhattacharya, Jahar] Columbia Univ, Dept Med, New York, NY USA.
[Burnett, Bruce K.] Duke Univ, Sch Med, Duke Translat Med Inst, Durham, NC USA.
[Hare, Joshua M.] Univ Miami, Dept Med, Miami, FL USA.
[Hei, Derek J.] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA.
[Hoffman, Andrew M.] Tufts Univ, Dept Clin Sci, Cummings Sch Vet Med, North Grafton, MA USA.
[Kourembanas, Stella] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[McKenna, David H.] Univ Minnesota, Dept Mol & Cellular Therapeut, St Paul, MN 55108 USA.
[Ortiz, Luis A.] Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA USA.
[Ott, Harald C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Tente, William] Humacyte Inc, Res Triangle Pk, NC USA.
[Thebaud, Bernard] Univ Ottawa, Dept Pediat, Ottawa, ON K1N 6N5, Canada.
[Trapnell, Bruce C.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA.
[Weiss, Daniel J.] Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA.
[Yuan, Jason X. -J.] Univ Illinois, Dept Med, Coll Med Chicago, Chicago, IL USA.
[Blaisdell, Carol J.] NHLBI, Div Lung Dis, NIH, Bethesda, MD 20892 USA.
RP Blaisdell, CJ (reprint author), NHLBI, NIH, 6701 Rockledge Dr,10-042, Bethesda, MD 20892 USA.
EM blaisdellcj@nhlbi.nih.gov
RI ortiz, luis/H-9851-2013;
OI ortiz, luis/0000-0003-4510-7066
FU National Heart, Lung, and Blood Institute, National Institutes of Health
FX Supported by the National Heart, Lung, and Blood Institute, National
Institutes of Health.
NR 36
TC 8
Z9 8
U1 0
U2 16
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD AUG 1
PY 2013
VL 188
IS 3
BP 370
EP 375
DI 10.1164/rccm.201303-0522WS
PG 6
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 194GA
UT WOS:000322617800019
PM 23713908
ER
PT J
AU McCormack, FX
Travis, WD
Colby, TV
Henske, EP
Moss, J
AF McCormack, Francis X.
Travis, William D.
Colby, Thomas V.
Henske, Elizabeth P.
Moss, Joel
TI Characterization of Lymphangioleiomyomatosis as a Neoplastic Disease
Reply
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Letter
C1 [McCormack, Francis X.] Univ Cincinnati, Cincinnati, OH 45221 USA.
[Travis, William D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Colby, Thomas V.] Mayo Clin, Scottsdale, AZ USA.
[Henske, Elizabeth P.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Henske, Elizabeth P.] Harvard Univ, Sch Med, Boston, MA USA.
[Moss, Joel] NHLBI, Bethesda, MD 20892 USA.
RP McCormack, FX (reprint author), Univ Cincinnati, Cincinnati, OH 45221 USA.
OI McCormack, Francis/0000-0001-7168-9464
FU Intramural NIH HHS [ZIA HL002541-17]; NHLBI NIH HHS [R13 HL078191]
NR 1
TC 0
Z9 0
U1 0
U2 4
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD AUG 1
PY 2013
VL 188
IS 3
BP 398
EP 399
PG 4
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 194GA
UT WOS:000322617800024
PM 23905529
ER
PT J
AU Heimburger, DC
Warner, TL
Carothers, CL
Blevins, M
Thomas, Y
Gardner, P
Primack, A
Vermund, SH
AF Heimburger, Douglas C.
Warner, Tokesha L.
Carothers, Catherine Lem
Blevins, Meridith
Thomas, Yolanda
Gardner, Pierce
Primack, Aron
Vermund, Sten H.
TI Recruiting Trainees for a Global Health Research Workforce: The National
Institutes of Health Fogarty International Clinical Research Scholars
Program Selection Process
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID OPPORTUNITIES
AB Between 2004 and 2012, the National Institutes of Health Fogarty International Clinical Research Scholars (FICRS) Program provided 1-year mentored research training at low- and middle-income country sites for American and international health science doctoral students. We describe the centralized application process, US applicant characteristics, and predictors of selection/enrollment. FICRS received 1,084 applicants representing many health professions and biomedical disciplines at 132 US academic institutions; 219 students from 72 institutions were accepted and enrolled. Medical/osteopathic students comprised 88.9% of applicants and 85.8% of enrollees. Applicants from institutions with higher applicant numbers were two times as likely to be selected. In 2012, FICRS was decentralized among 20 institutions in five consortia (Global Health Fellows), with autonomous selection processes that emphasize post-doctoral trainees. If academia, government, or charitable foundations offer future opportunities to health professions students for international research, the FICRS experience predicts that they can attract substantial numbers of motivated trainees from diverse backgrounds.
C1 Vanderbilt Univ, Sch Med, Dept Med, Vanderbilt Inst Global Hlth, Nashville, TN 37203 USA.
Vanderbilt Univ, Sch Med, Dept Biostat, Vanderbilt Inst Global Hlth, Nashville, TN 37203 USA.
Vanderbilt Univ, Sch Med, Dept Pediat, Vanderbilt Inst Global Hlth, Nashville, TN 37203 USA.
Vanderbilt Univ, Fogarty Int Clin Res Scholars & Fellows Support C, Nashville, TN 37203 USA.
[Gardner, Pierce] SUNY Stony Brook, Sch Med, Stony Brook, NY 11794 USA.
[Thomas, Yolanda; Primack, Aron] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Heimburger, DC (reprint author), Vanderbilt Univ, Inst Global Hlth, 2525 West End Ave,Suite 750, Nashville, TN 37203 USA.
EM douglas.heimburger@vanderbilt.edu; tokesha.warner@vanderbilt.edu;
catherine.lem@vanderbilt.edu; meridith.blevins@vanderbilt.edu;
ythomas@ficrsconsultant.com; gardnep@mail.nih.gov; aprimack@rcn.com;
sten.vermund@vanderbilt.edu
RI yan, liu/A-1822-2015; Warner, Tokesha/M-4735-2014;
OI yan, liu/0000-0001-8517-1084; Warner, Tokesha/0000-0003-1809-102X;
Blevins, Meridith/0000-0002-3861-9859; Vermund, Sten/0000-0001-7289-8698
FU NIH Office of the Director; FIC, Office of AIDS Research; National
Cancer Institute; National Eye Institute; National Heart, Blood, and
Lung Institute; National Institute of Dental & Craniofacial Research;
National Institute on Drug Abuse; National Institute of Mental Health;
National Institute of Allergy and Infectious Diseases Health through the
Fogarty International Clinical Research Fellows Program at
Vanderbilt-AAMC [R24 TW007988]; American Recovery and Reinvestment Act
(ARRA); Vanderbilt Institute for Clinical and Translational Research
(VICTR, from the National Center for Research Resources) [UL1
RR024975-01]; National Center for Advancing Translational Sciences [2
UL1 TR000445-06]
FX This work was supported by the NIH Office of the Director, FIC, Office
of AIDS Research, National Cancer Institute, National Eye Institute,
National Heart, Blood, and Lung Institute, National Institute of Dental
& Craniofacial Research, National Institute on Drug Abuse, National
Institute of Mental Health, and National Institute of Allergy and
Infectious Diseases Health through the Fogarty International Clinical
Research Fellows Program at Vanderbilt-AAMC (R24 TW007988). Additional
support was received from the American Recovery and Reinvestment Act
(ARRA; http://recovery.nih.gov/) in 2010-2011 and the Vanderbilt
Institute for Clinical and Translational Research (VICTR, from the
National Center for Research Resources, Grant UL1 RR024975-01 and the
National Center for Advancing Translational Sciences, Grant 2 UL1
TR000445-06). The content is solely the responsibility of the authors
and does not necessarily represent the official views of the NIH. Study
data were collected and managed using Research Electronic Data Capture
(REDCap) tools hosted at Vanderbilt University
(https://redcap.vanderbilt.edu). We recognize the vital support of Drs.
Roger Glass, Kenneth Bridbord, and Myat Htoo Razak at the FIC: the
FICRS-F Site Principal Investigators and mentors; and participating NIH
institute and center directors and staff.
NR 9
TC 8
Z9 8
U1 0
U2 3
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD AUG
PY 2013
VL 89
IS 2
BP 281
EP 287
DI 10.4269/ajtmh.12-0677
PG 7
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 195DS
UT WOS:000322683100017
PM 23798584
ER
PT J
AU Layh-Schmitt, G
Yang, EY
Kwon, G
Colbert, RA
AF Layh-Schmitt, Gerlinde
Yang, Eva Y.
Kwon, Grace
Colbert, Robert A.
TI HLA-B27 Alters the Response to Tumor Necrosis Factor and Promotes
Osteoclastogenesis in Bone Marrow Monocytes From HLA-B27-Transgenic Rats
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; IFN-BETA
INDUCTION; ANKYLOSING-SPONDYLITIS; DENDRITIC CELLS; TRANSGENIC RATS;
FACTOR-ALPHA; INFLAMMATORY DISEASE; MINERAL DENSITY; RISK-FACTORS
AB Objective. To determine whether HLA-B27 expression alters the response of bone marrow monocytes from HLA-B27/human beta(2)-microglobulin-transgenic (B27-Tg) rats to tumor necrosis factor alpha (TNF alpha) and, if so, whether this affects the cells involved in bone homeostasis.
Methods. Bone marrow monocytes were treated with RANKL or with TNF alpha to promote osteoclast formation. Osteoclasts were quantified by counting. Gene expression was measured using quantitative polymerase chain reaction analysis, and protein was detected by enzyme-linked immunosorbent assay, immunoblotting, or immunofluorescence. Effects of endogenously produced cytokines on osteoclast formation were determined with neutralizing antibodies.
Results. TNF alpha treatment enhanced osteoclast formation 2.5-fold in HLA-B27-expressing cells as compared to wild-type or to HLA-B7/human beta(2)-microglobulin-expressing monocytes. TNF alpha induced similar to 4-fold up-regulation of HLA-B27, which was associated with the accumulation of misfolded heavy chains, binding of the endoplasmic reticulum (ER) chaperone BiP, and activation of an ER stress response, which was not seen with HLA-B7. No differences were seen with RANKL-induced osteoclastogenesis. Enhanced interleukin-1 alpha (IL-1 alpha) production from ER-stressed bone marrow monocytes from B27-Tg rats was found to be necessary and sufficient for enhanced osteoclast formation. However, bone marrow monocytes from B27-Tg rats also produced more interferon-beta (IFN beta), which attenuated the effect of IL-1 alpha on osteoclast formation.
Conclusion. HLA-B27-induced ER stress alters the response of bone marrow monocytes from B27-Tg rats to TNF alpha, which is associated with enhanced production of IL-1 alpha and IFN beta, cytokines that exhibit opposing effects on osteoclast formation. The altered response of cells expressing HLA-B27 to proinflammatory cytokines suggests that this class I major histocompatibility complex allele may contribute to the pathogenesis of spondyloarthritis and its unique phenotype through downstream effects involving alterations in bone homeostasis.
C1 [Layh-Schmitt, Gerlinde; Yang, Eva Y.; Kwon, Grace; Colbert, Robert A.] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Colbert, RA (reprint author), NIAMSD, Pediat Translat Res Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM colbertr@mail.nih.gov
FU NIH [R01-AR-046177, AR-048372]; NIH/National Institute of Arthritis and
Musculoskeletal and Skin Diseases [Z01-AR-041184]
FX Supported by NIH grants R01-AR-046177 and AR-048372, and by NIH/National
Institute of Arthritis and Musculoskeletal and Skin Diseases Intramural
Research Program grant Z01-AR-041184.
NR 42
TC 12
Z9 13
U1 1
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD AUG
PY 2013
VL 65
IS 8
BP 2123
EP 2131
DI 10.1002/art.38001
PG 9
WC Rheumatology
SC Rheumatology
GA 190HD
UT WOS:000322329100022
PM 23666508
ER
PT J
AU Belot, A
Kasher, PR
Trotter, EW
Foray, AP
Debaud, AL
Rice, GI
Szynkiewicz, M
Zabot, MT
Rouvet, I
Bhaskar, SS
Daly, SB
Dickerson, JE
Mayer, J
O'Sullivan, J
Juillard, L
Urquhart, JE
Fawdar, S
Marusiak, AA
Stephenson, N
Waszkowycz, B
Beresford, M
Biesecker, LG
Black, GM
Rene, C
Eliaou, JF
Fabien, N
Ranchin, B
Cochat, P
Gaffney, PM
Rozenberg, F
Lebon, P
Malcus, C
Crow, YJ
Brognard, J
Bonnefoy, N
AF Belot, Alexandre
Kasher, Paul R.
Trotter, Eleanor W.
Foray, Anne-Perrine
Debaud, Anne-Laure
Rice, Gillian I.
Szynkiewicz, Marcin
Zabot, Marie-Therese
Rouvet, Isabelle
Bhaskar, Sanjeev S.
Daly, Sarah B.
Dickerson, Jonathan E.
Mayer, Josephine
O'Sullivan, James
Juillard, Laurent
Urquhart, Jill E.
Fawdar, Shameem
Marusiak, Anna A.
Stephenson, Natalie
Waszkowycz, Bohdan
W. Beresford, Michael
Biesecker, Leslie G.
C. M. Black, Graeme
Rene, Celine
Eliaou, Jean-Francois
Fabien, Nicole
Ranchin, Bruno
Cochat, Pierre
Gaffney, Patrick M.
Rozenberg, Flore
Lebon, Pierre
Malcus, Christophe
Crow, Yanick J.
Brognard, John
Bonnefoy, Nathalie
TI Protein Kinase C Deficiency Causes Mendelian Systemic Lupus
Erythematosus With B Cell-Defective Apoptosis and Hyperproliferation
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID AUTOIMMUNITY; DELTA; ACTIVATION; MECHANISMS; TOLERANCE; MUTATION;
DISEASE; STIM1
AB Objective. Systemic lupus erythematosus (SLE) is a prototype autoimmune disease that is assumed to occur via a complex interplay of environmental and genetic factors. Rare causes of monogenic SLE have been described, providing unique insights into fundamental mechanisms of immune tolerance. The aim of this study was to identify the cause of an autosomalrecessive form of SLE.
Methods. We studied 3 siblings with juvenile-onset SLE from 1 consanguineous kindred and used next-generation sequencing to identify mutations in the disease-associated gene. We performed extensive biochemical, immunologic, and functional assays to assess the impact of the identified mutations on B cell biology.
Results. We identified a homozygous missense mutation in PRKCD, encoding protein kinase (PKC), in all 3 affected siblings. Mutation of PRKCD resulted in reduced expression and activity of the encoded protein PKC (involved in the deletion of autoreactive B cells), leading to resistance to B cell receptor- and calcium-dependent apoptosis and increased B cell proliferation. Thus, as for mice deficient in PKC delta, which exhibit an SLE phenotype and B cell expansion, we observed an increased number of immature B cells in the affected family members and a developmental shift toward naive B cells with an immature phenotype.
Conclusion. Our findings indicate that PKC is crucial in regulating B cell tolerance and preventing self-reactivity in humans, and that PKC deficiency represents a novel genetic defect of apoptosis leading to SLE.
C1 [Belot, Alexandre] Univ Lyon 1, INSERM, U1111, Hosp Civils Lyon,UMS3444,US8,Ctr Reference Malad, F-69365 Lyon, France.
[Belot, Alexandre; Foray, Anne-Perrine; Debaud, Anne-Laure; Juillard, Laurent; Bonnefoy, Nathalie] Univ Lyon, Lyon, France.
[Kasher, Paul R.; Rice, Gillian I.; Szynkiewicz, Marcin; Bhaskar, Sanjeev S.; Daly, Sarah B.; Dickerson, Jonathan E.; Mayer, Josephine; O'Sullivan, James; Urquhart, Jill E.; C. M. Black, Graeme; Crow, Yanick J.] Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.
[Kasher, Paul R.; Trotter, Eleanor W.; Rice, Gillian I.; Szynkiewicz, Marcin; Bhaskar, Sanjeev S.; Daly, Sarah B.; Dickerson, Jonathan E.; Mayer, Josephine; O'Sullivan, James; Urquhart, Jill E.; Fawdar, Shameem; Marusiak, Anna A.; Stephenson, Natalie; Waszkowycz, Bohdan; C. M. Black, Graeme; Crow, Yanick J.; Brognard, John] Univ Manchester, Manchester M13 9WL, Lancs, England.
[Trotter, Eleanor W.; Fawdar, Shameem; Marusiak, Anna A.; Stephenson, Natalie; Waszkowycz, Bohdan; Brognard, John] Paterson Inst Canc Res, Manchester M20 9BX, Lancs, England.
[Foray, Anne-Perrine; Bonnefoy, Nathalie] Univ Lyon 1, INSERM, U1111, Hosp Civils Lyon,UMS3444,US8, F-69365 Lyon, France.
[Debaud, Anne-Laure] Univ Lyon 1, INSERM, U1111, UMS3444,US8, F-69365 Lyon, France.
[Zabot, Marie-Therese; Rouvet, Isabelle] Grp Hosp Est, Ctr Biotechnol Cellulaire, Lyon, France.
[Zabot, Marie-Therese; Rouvet, Isabelle; Fabien, Nicole; Ranchin, Bruno; Malcus, Christophe] Hosp Civils Lyon, Lyon, France.
[Juillard, Laurent] Univ Lyon 1, Hosp Civils Lyon, Hop Edouard Herriot, F-69365 Lyon, France.
[W. Beresford, Michael] Univ Liverpool, Liverpool L69 3BX, Merseyside, England.
[Biesecker, Leslie G.] NIH, Bethesda, MD 20892 USA.
[Biesecker, Leslie G.] NIH, Intramural Sequencing Ctr, Rockville, MD USA.
[Rene, Celine] Ctr Hosp Reg Univ Montpellier, Montpellier, France.
[Rene, Celine] Univ Montpellier I, Montpellier, France.
[Eliaou, Jean-Francois] Univ Montpellier I, INSERM, U896, Ctr Hosp Reg Univ Montpellier,IRCM, Montpellier, France.
[Eliaou, Jean-Francois; Bonnefoy, Nathalie] Inst Reg Canc Montpellier, Montpellier, France.
[Fabien, Nicole] Ctr Hosp Lyon Sud, Lyon, France.
[Ranchin, Bruno] Ctr Reference Malad Renales Rares, Lyon, France.
[Cochat, Pierre] Univ Lyon 1, Hosp Civils Lyon, Ctr Reference Malad Renales Rares, F-69365 Lyon, France.
[Cochat, Pierre] Epidemiol Pharmacol Invest Clin Informat Med Mere, Lyon, France.
[Gaffney, Patrick M.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA.
[Rozenberg, Flore; Lebon, Pierre] Univ Paris 05, Paris, France.
[Malcus, Christophe] Hop Edouard Herriot, Lyon, France.
[Bonnefoy, Nathalie] Univ Montpellier I, INSERM, U896, IRCM, Montpellier, France.
RP Crow, YJ (reprint author), Univ Manchester, Manchester Acad Hlth Sci Ctr, Cent Manchester Univ Hosp NHS Fdn Trust, St Marys Hosp, Oxford Rd, Manchester M13 9WL, Lancs, England.
EM yanickcrow@mac.com; JBrognard@picr.man.ac.uk;
nathalie.bonnefoy@inserm.fr
RI Crow, Yanick/N-6120-2014; Urquhart, Jill/G-2282-2015; Rice,
Gillian/G-3128-2015; Bonnefoy, Nathalie/J-2536-2012;
OI Urquhart, Jill/0000-0002-5788-5511; Rice, Gillian/0000-0002-4223-0571;
Crow, Yanick/0000-0001-7211-7564; Black, Graeme/0000-0001-8727-6592
FU Hospices Civils de Lyon; Reseaux Thematiques de Recherche
Translationelle INSERM; Fondation pour la Recherche Medicale; Region
Rhone-Alpes; Societe Francaise de Rhumatologie; INSERM; Universite de
Lyon; NIH [RC2-AR-058959, R01-AI-063274]; Cancer Research UK
[C5759/A12328]; European Union [241779]
FX Supported by specific funding from the Hospices Civils de Lyon, the
Reseaux Thematiques de Recherche Translationelle INSERM, the Fondation
pour la Recherche Medicale, the Region Rhone-Alpes, and the Societe
Francaise de Rhumatologie (all to Dr. Belot) and by institutional grants
from INSERM and Universite de Lyon (to Dr. Bonnefoy). Dr. Gaffney's work
was supported by the NIH (grants RC2-AR-058959 and R01-AI-063274). Dr.
Brognard's work was supported by Cancer Research UK (grant
C5759/A12328). Work performed in the Crow laboratory contributing to
this research received funding from the European Union Seventh Framework
Programme (FP7/2007-2013 project NIMBL; 241779).
NR 27
TC 47
Z9 48
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD AUG
PY 2013
VL 65
IS 8
BP 2161
EP 2171
DI 10.1002/art.38008
PG 11
WC Rheumatology
SC Rheumatology
GA 190HD
UT WOS:000322329100026
PM 23666743
ER
PT J
AU Gokhale, NA
Zaremba, A
Janoshazi, AK
Weaver, JD
Shears, SB
AF Gokhale, Nikhil A.
Zaremba, Angelika
Janoshazi, Agnes K.
Weaver, Jeremy D.
Shears, Stephen B.
TI PPIP5K1 modulates ligand competition between diphosphoinositol
polyphosphates and PtdIns(3,4,5)P-3 for polyphosphoinositide-binding
domains
SO BIOCHEMICAL JOURNAL
LA English
DT Article
DE diphosphoinositol polyphosphate; inositol pyrophosphate;
phosphoinositide 3-kinase (PI3K); phosphoinositide
ID INOSITOL HEXAKISPHOSPHATE KINASE; PLECKSTRIN HOMOLOGY DOMAINS;
HYPEROSMOTIC STRESS; CELLULAR-RESPONSES; OSMOTIC-STRESS; PH DOMAINS;
PYROPHOSPHATES; CELLS; PROTEIN; IDENTIFICATION
AB We describe new signalling consequences for PPIP5K1 (diphosphoinositol pentakisphosphate kinase type 1)-mediated phosphorylation of InsP(6) and 5-InsP(7) to 1-InsP(7) and InsP(8). In NIH 3T3 cells, either hyperosmotic stress or receptor activation by PDGF (platelet-derived growth factor) promoted translocation of PPIP5K1 from the cytoplasm to the plasma membrane. The PBD1 (polyphosphoinositide-binding domain) in PPIP5K1 recapitulated that translocation. Mutagenesis of PBD1 to reduce affinity for PtdIns(3,4,5)P-3 prevented translocation. Using surface plasmon resonance, we found that PBD1 association with vesicular PtdIns(3,4,5)P-3 was inhibited by InsP6 and diphosphoinositol polyphosphates. However, the inhibition by PPIP5K1 substrates (IC50: 5-InsP(7) = 5 mu M and InsP(6) = 7 mu M) was substantially more potent than that of the PPIP5K1 products (IC50: InsP(8) = 32 mu M and 1-InsP(7) = 43 mu M). This rank order of ligand competition with PtdIns(3,4,5)P-3 was also exhibited by the PH (pleckstrin homology) domains of Akt (also known as protein kinase B), GRP1 (general receptor for phosphoinositides 1) and SIN1 (stress-activated protein kinase-interaction protein 1). We propose that, in vivo, PH domain binding of InsP(6) and 5-InsP(7) suppresses inappropriate signalling ('noise') from stochastic increases in PtdIns(3,4,5)P-3. That restraint may be relieved by localized depletion of InsP(6) and 5-InsP(7) at the plasma membrane following PPIP5K1 recruitment. We tested this hypothesis in insulin-stimulated L6 myoblasts, using mTOR (mechanistic/mammalian target of rapamycin)-mediated phosphorylation of Ala on Ser(473) as a readout for SIN 1-mediated translocation of mTORC (mTOR complex) 2 to the plasma membrane [Zoncu, Efeyan and Sabatini (2011) Nat. Rev. Mol. Cell Biol. 12, 21-35]. Knockdown of PPIP5K1 expression was associated with a 40% reduction in Ser(473) phosphorylation. A common feature of PtdIns(3,4,5)P-3-based signalling cascades may be their regulation by PPIP5K1.
C1 [Gokhale, Nikhil A.; Zaremba, Angelika; Janoshazi, Agnes K.; Weaver, Jeremy D.; Shears, Stephen B.] NIEHS, NIH, DHHS, Inositol Signaling Sect,Lab Signal Transduct, Res Triangle Pk, NC 27709 USA.
RP Shears, SB (reprint author), NIEHS, NIH, DHHS, Inositol Signaling Sect,Lab Signal Transduct, POB 12233, Res Triangle Pk, NC 27709 USA.
EM shears@niehs.nih.gov
FU National Institutes of Health (NIH)/NIEHS
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH)/NIEHS.
NR 70
TC 16
Z9 16
U1 0
U2 11
PU PORTLAND PRESS LTD
PI LONDON
PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND
SN 0264-6021
J9 BIOCHEM J
JI Biochem. J.
PD AUG 1
PY 2013
VL 453
BP 413
EP 426
DI 10.1042/BJ20121528
PN 3
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 190RU
UT WOS:000322358700010
PM 23682967
ER
PT J
AU Booth, GS
Gehrie, EA
Bolan, CD
Savani, BN
AF Booth, Garrett S.
Gehrie, Eric A.
Bolan, Charles D.
Savani, Bipin N.
TI Clinical Guide to ASO-Incompatible Allogeneic Stem Cell Transplantation
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Stem cell; Transplant; Blood group; Hemolysis; Transfusion
ID BONE-MARROW-TRANSPLANTATION; PASSENGER LYMPHOCYTE SYNDROME; SEVERE
HEMOLYTIC-ANEMIA; RED-CELL; IMMUNE HEMOLYSIS; ABO-INCOMPATIBILITY;
PLATELET TRANSFUSION; UNRELATED DONORS; PROGENITOR CELLS; BLOOD
AB The independent genomic inheritance of the human leukocyte antigen (HLA) and the ABO-blood group system allows for HLA-matched hematopoietic progenitor cell transplantation (HCT) to occur in donors who are not matched for ABO blood groups. In fact, nearly one-half of all HCT will involve recipient-donor ABO incompatibility. This places the recipient at increased risk for acute and delayed hemolytic reactions, delayed RBC engraftment, and pure red blood cell aplasia. Additionally, clinical and laboratory evaluation for potential non-ABO, minor RBC antigen-antibody discrepancies may be beneficial to facilitate safe transfusions before, during, and after transplantation. In addition to posing potential clinical risks, analyses of outcomes in ABO-incompatible HCT have yielded inconsistent results with respect to overall survival, relapse risk, incidence of acute or chronic graft-versus-host disease, and engraftment of platelets and granulocytes. As such, pretransplantation donor-recipient evaluation and management for ABO-incompatible HCT requires adopting unique strategies when major, minor, and bidirectional differences exist. These strategies have the potential to improve patient outcomes and allow for effective management of the blood bank inventory. The purpose of this article is to describe practical approaches to screening for and managing ABO-incompatible HCT, with the goal of reducing preventable morbidity and mortality after transplantation. (C) 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
C1 [Booth, Garrett S.; Gehrie, Eric A.] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA.
[Bolan, Charles D.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Hematol & Stem Cell Transplantat Sect, Div Hematol Oncol,Dept Med, Nashville, TN USA.
[Savani, Bipin N.] Vet Affairs Med Ctr, Nashville, TN 37212 USA.
RP Booth, GS (reprint author), Vanderbilt Univ, Med Ctr, 4650H TVC,1301 Med Ctr Dr, Nashville, TN 37232 USA.
EM garretts.booth@vanderbilt.edu
NR 75
TC 23
Z9 23
U1 5
U2 20
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD AUG
PY 2013
VL 19
IS 8
BP 1152
EP 1158
DI 10.1016/j.bbmt.2013.03.018
PG 7
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 194BW
UT WOS:000322607000006
PM 23571461
ER
PT J
AU Gadalla, SM
Sales-Bonfim, C
Carreras, J
Alter, BP
Antin, JH
Ayas, M
Bodhi, P
Davis, J
Davies, SM
Deconinck, E
Deeg, HJ
Duerst, RE
Fasth, A
Ghavamzadeh, A
Giri, N
Goldman, FD
Kolb, EA
Krance, R
Kurtzberg, J
Leung, WH
Srivastava, A
Or, R
Richman, CM
Rosenberg, PS
Codina, JSD
Shenoy, S
Socie, G
Tolar, J
Williams, KM
Eapen, M
Savage, SA
AF Gadalla, Shahinaz M.
Sales-Bonfim, Carmem
Carreras, Jeanette
Alter, Blanche P.
Antin, Joseph H.
Ayas, Mouhab
Bodhi, Prasad
Davis, Jeffrey
Davies, Stella M.
Deconinck, Eric
Deeg, H. Joachim
Duerst, Reggie E.
Fasth, Anders
Ghavamzadeh, Ardeshir
Giri, Neelam
Goldman, Frederick D.
Kolb, E. Anders
Krance, Robert
Kurtzberg, Joanne
Leung, Wing H.
Srivastava, Alok
Or, Reuven
Richman, Carol M.
Rosenberg, Philip S.
de Toledo Codina, Jose Sanchez
Shenoy, Shalini
Socie, Gerard
Tolar, Jakub
Williams, Kirsten M.
Eapen, Mary
Savage, Sharon A.
TI Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients
with Dyskeratosis Congenita
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Dyskeratosis congenita; Allogeneic transplantation; Long-term survival;
Pulmonary toxicity
ID BONE-MARROW FAILURE; TELOMERE BIOLOGY; APLASTIC-ANEMIA; MUTATIONS;
ENGRAFTMENT; DISORDERS; DISEASE
AB We describe outcomes after allogeneic transplantation in 34 patients with dyskeratosis congenita who underwent transplantation between 1981 and 2009. The median age at transplantation was 13 years (range, 2 to 35). Approximately 50% of transplantations were from related donors. Bone marrow was the predominant source of stem cells (24 of 34). The day-28 probability of neutrophil recovery was 73% and the day-100 platelet recovery was 72%. The day-100 probability of grade II to IV acute GVHD and the 3-year probability of chronic graft-versus-host disease were 24% and 37%, respectively. The 10-year probability of survival was 30%; 14 patients were alive at last follow-up. Ten deaths occurred within 4 months from transplaneation because of graft failure (n = 6) or other transplantation-related complications; 9 of these patients had undergone transplantation from mismatched related or from unrelated donors. Another 10 deaths occurred after 4 months; 6 of them occurred more than 5 years after transplantation, and 4 of these were attributed to pulmonary failure. Transplantation regimen intensity and transplantations from mismatched related or unrelated donors were associated with early mortality. Transplantation of grafts from HLA-matched siblings with cyclophosphamide-containing nonradiation regimens was associated with early low toxicity. Late mortality was attributed mainly to pulmonary complications and likely related to the underlying disease. (C) 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
C1 [Gadalla, Shahinaz M.; Alter, Blanche P.; Giri, Neelam; Rosenberg, Philip S.; Savage, Sharon A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Sales-Bonfim, Carmem] Univ Fed Parana, Hosp Clin Curitiba, BR-80060000 Curitiba, Parana, Brazil.
[Carreras, Jeanette; Eapen, Mary] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Dept Med, Milwaukee, WI 53226 USA.
[Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Ayas, Mouhab] King Faisal Specialist Hosp & Res Ctr, Dept Pediat Hematol Oncol, Riyadh 11211, Saudi Arabia.
[Bodhi, Prasad] Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA.
[Davis, Jeffrey] British Columbia Childrens Hosp, Dept Paediat, BMT Serv, Vancouver, BC V6H 3V4, Canada.
[Davies, Stella M.] Cincinnati Childrens Hosp, Cincinnati, OH USA.
[Deconinck, Eric] Hop Jean Minjoz, Serv Hematol D, F-25030 Besancon, France.
[Deeg, H. Joachim] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Duerst, Reggie E.] Childrens Mem Hosp, Chicago, IL 60614 USA.
[Fasth, Anders] Univ Gothenburg, Dept Pediat, Gothenburg, Sweden.
[Ghavamzadeh, Ardeshir] Univ Tehran Med Sci, Hematol Oncol & Stem Cell Transplantat Res Ctr, Tehran, Iran.
[Goldman, Frederick D.] Univ Alabama Birmingham, Birmingham, AL USA.
[Kolb, E. Anders] Alfred I Dupont Hosp Children, Wilmington, DE USA.
[Krance, Robert] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
[Kurtzberg, Joanne] Duke Univ, Med Ctr, Durham, NC USA.
[Leung, Wing H.] St Jude Childrens Res Hosp, Div Bone Marrow Transplantat, Memphis, TN 38105 USA.
[Srivastava, Alok] Christian Med Coll & Hosp, Dept Haematol, Vellore, Tamil Nadu, India.
[Or, Reuven] Hadassah Univ Hosp, Dept Bone Marrow Transplantat, IL-91120 Jerusalem, Israel.
[Richman, Carol M.] Univ Calif Davis, Davis Canc Ctr, Div Hematol Oncol, Sacramento, CA 95817 USA.
[de Toledo Codina, Jose Sanchez] Hosp Infantil Vall dHebron, Paediat Oncol Haematol & SCT Dept, Barcelona, Spain.
[Shenoy, Shalini] Washington Univ, St Louis Childrens Hosp, St Louis, MO 63110 USA.
[Socie, Gerard] Hosp St Louis, Paris, France.
[Tolar, Jakub] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA.
[Williams, Kirsten M.] George Washington Univ, Med Ctr, Childrens Natl Med Ctr, Ctr Canc & Blood Disorders,Div Blood & Marro Tran, Washington, DC 20037 USA.
[Williams, Kirsten M.] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
RP Eapen, M (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, 9200 West Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA.
EM meapen@mcw.edu
RI Savage, Sharon/B-9747-2015;
OI Savage, Sharon/0000-0001-6006-0740; Fasth, Anders/0000-0002-0033-740X;
Tolar, Jakub/0000-0002-0957-4380
FU National Cancer Institute [U24-CA76518]; National Heart Lung and Blood
Institute; National Institute of Allergy and Infectious Diseases, Heath
Resources and Services Administration [HHSH234200637015C]; intramural
program of the Division of Cancer Epidemiology and Genetics, National
Cancer Institute
FX Supported by a Public Health Service grant (U24-CA76518) from the
National Cancer Institute, the National Heart Lung and Blood Institute
and the National Institute of Allergy and Infectious Diseases, Heath
Resources and Services Administration (HHSH234200637015C) and the
intramural program of the Division of Cancer Epidemiology and Genetics,
National Cancer Institute (S.M.G., B.P.A., N.G., P.S.R., and S.A.S.).
The opinions, findings, and conclusions or recommendations expressed
herein are those of the authors and do not reflect the views of the
National Institutes of Health.
NR 24
TC 28
Z9 29
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD AUG
PY 2013
VL 19
IS 8
BP 1238
EP 1243
DI 10.1016/j.bbmt.2013.05.021
PG 6
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 194BW
UT WOS:000322607000018
PM 23751955
ER
PT J
AU Keimling, M
Renehan, AG
Behrens, G
Fischer, B
Hollenbeck, AR
Cross, AJ
Leitzmann, MF
AF Keimling, Marlen
Renehan, Andrew G.
Behrens, Gundula
Fischer, Beate
Hollenbeck, Albert R.
Cross, Amanda J.
Leitzmann, Michael F.
TI Comparison of Associations of Body Mass Index, Abdominal Adiposity, and
Risk of Colorectal Cancer in a Large Prospective Cohort Study
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID MESSENGER-RNA EXPRESSION; COLON-CANCER; POSTMENOPAUSAL WOMEN; WAIST
CIRCUMFERENCE; REPLACEMENT THERAPY; FAT DISTRIBUTION;
CARDIOVASCULAR-DISEASE; PHYSICAL-ACTIVITY; STEROID-HORMONES;
UNITED-STATES
AB Background: Increased body mass index (BMI) is an established colorectal cancer risk factor. High waist circumference or waist-hip-ratio (WHR) may better reflect an abnormal metabolic state and be more predictive of colorectal cancer risk than BMI.
Methods: We examined BMI, waist circumference, WHR, and hip circumference in relation to colorectal cancer risk among 203,177 participants followed for 10 years. We derived standardized colorectal cancer risk estimates for each anthropometric parameter and compared predictive characteristics (Harrell's C-index). In women, we examined whether hormone replacement therapy (HRT) use modified the associations between anthropometric measures and colorectal cancer.
Results: We ascertained 2,869 colorectal cancers. In men, increased colon cancer risks were associated with BMI [HR per SD, 1.14; 95% confidence interval (CI), 1.08-1.20], waist circumference (HR per SD, 1.17; 95% CI, 1.08-1.27), and WHR(HR per SD, 1.09; 95% CI, 1.04-1.14). In women, anthropometric variables were unrelated to colon cancer. For men and women, anthropometric variables were unrelated to rectal cancer. Compared with BMI, waist circumference and WHR did not materially influence colon cancer prediction models [C-index changes: -0.0041 and 0.0046 (men); 0.0004 and 0.0005 (women)]. In current HRT users, colon cancer was inversely or suggestively inversely associated with waist circumference (HR per SD, 0.78; 95% CI, 0.63-0.97) and WHR (HR per SD, 0.88; 95% CI, 0.76-1.01), but positively related to hip circumference (HR per SD, 1.39; 95% CI, 1.13-1.71).
Conclusion: BMI, waist circumference, and WHR show comparable positive associations with colon cancer in men. Associations between anthropometric measures and colon cancer are weak or null in women, but there is some evidence for effect modification by HRT.
Impact: These findings may improve our understanding of the relation of adiposity to colorectal cancer. (C) 2013 AACR.
C1 [Keimling, Marlen; Behrens, Gundula; Fischer, Beate; Leitzmann, Michael F.] Univ Regensburg, Med Ctr, Dept Epidemiol & Prevent Med, D-93053 Regensburg, Germany.
[Renehan, Andrew G.] Univ Manchester, Manchester Acad Hlth Sci Ctr, Inst Canc Sci, Manchester, Lancs, England.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
[Cross, Amanda J.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
RP Keimling, M (reprint author), Univ Regensburg, Med Ctr, Dept Epidemiol & Prevent Med, Franz Josef Str Allee 11, D-93053 Regensburg, Germany.
EM Marlen.Keimling@ukr.de
RI Renehan, Andrew/K-5992-2015;
OI Renehan, Andrew/0000-0003-4309-4396; Behrens,
Gundula/0000-0002-9355-6491
FU NIH, National Cancer Institute
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute.
NR 54
TC 15
Z9 15
U1 1
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD AUG
PY 2013
VL 22
IS 8
BP 1383
EP 1394
DI 10.1158/1055-9965.EPI-13-0353
PG 12
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 195NP
UT WOS:000322710100005
PM 23720402
ER
PT J
AU Mason, C
Xiao, LR
Duggan, C
Imayama, I
Foster-Schubert, KE
Kong, A
Campbell, KL
Wang, CY
Alfano, CM
Blackburn, GL
Pollack, M
McTiernan, A
AF Mason, Caitlin
Xiao, Liren
Duggan, Catherine
Imayama, Ikuyo
Foster-Schubert, Karen E.
Kong, Angela
Campbell, Kristin L.
Wang, Ching-Yun
Alfano, Catherine M.
Blackburn, George L.
Pollack, Michael
McTiernan, Anne
TI Effects of Dietary Weight Loss and Exercise on Insulin-Like Growth
Factor-I and Insulin-Like Growth Factor-Binding Protein-3 in
Postmenopausal Women: A Randomized Controlled Trial
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID IGF-I; CALORIE RESTRICTION; CANCER-RISK; INTERVENTION; INTERMITTENT;
OVERWEIGHT; HORMONE; DISEASE; OBESITY; MICE
AB High levels of insulin-like growth factor (IGF)-I may increase the risk of common cancers in humans. We hypothesized that weight loss induced by diet and/or exercise would reduce IGF-I in postmenopausal women. Four hundred and thirty nine overweight or obese [body mass index (BMI) >= 25 kg/m(2)] women (50-75 years) were randomly assigned to: (i) exercise (N = 117), (ii) dietary weight loss (N = 118), (iii) diet + exercise (N = 117), or (iv) control (N = 87). The diet intervention was a group-based program with a 10% weight loss goal. The exercise intervention was 45 minutes/day, 5 days/week of moderate-to-vigorous intensity activity. Fasting serum IGF-I and IGF-binding protein (IGFBP)-3 were measured at baseline and 12 months by radioimmunoassay. Higher baseline BMI was associated with lower IGF-I and IGF-I/IGFBP-3 molar ratio. Although no significant changes in either IGF-I or IGFBP-3 were detected in any intervention arm compared with control, the IGF-I/IGFBP-3 ratio increased significantly in the diet (+5.0%, P < 0.01) and diet + exercise (+5.4%, P < 0.01) groups compared with control. Greater weight loss was positively associated with change in both IGF-I (P-trend = 0.017) and IGF-I/IGFBP-3 ratio (P-trend < 0.001) in the diet group, but inversely with change in IGFBP-3 in the diet + exercise group (P-trend = 0.01). No consistent interaction effects with baseline BMI were detected. Modified IGF-I bioavailability is unlikely to be a mechanism through which caloric restriction reduces cancer risk in postmenopausal women. (C) 2013 AACR.
C1 [Mason, Caitlin; Xiao, Liren; Duggan, Catherine; Imayama, Ikuyo; Wang, Ching-Yun; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
[Foster-Schubert, Karen E.; Wang, Ching-Yun; McTiernan, Anne] Univ Washington, Seattle, WA 98195 USA.
[Kong, Angela] Univ Illinois, Chicago, IL USA.
[Campbell, Kristin L.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Pollack, Michael] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada.
[Alfano, Catherine M.] NCI, Off Canc Survivorship, Bethesda, MD 20892 USA.
[Blackburn, George L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Nutr, Boston, MA 02215 USA.
RP McTiernan, A (reprint author), Fred Hutchinson Canc Res Ctr, M4-B874,POB 19024, Seattle, WA 98109 USA.
EM amctiern@fhcrc.org
RI Duggan, Catherine/F-9414-2015
OI Duggan, Catherine/0000-0001-7369-4021
FU NIH [R01 CA102504, U54-CA116847, 5KL2RR025015-03]; Canadian Institutes
of Health Research; NCI [R25 CA094880, 2R25CA057699-16]
FX This study was supported by funding through NIH R01 CA102504 and
U54-CA116847. C. Mason and K.L. Campbell were supported by fellowships
from the Canadian Institutes of Health Research. K. E. Foster-Schubert
received support from NIH 5KL2RR025015-03. A. Kong was supported by NCI
R25 CA094880 and is now supported by NCI 2R25CA057699-16.
NR 25
TC 10
Z9 11
U1 0
U2 10
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD AUG
PY 2013
VL 22
IS 8
BP 1457
EP 1463
DI 10.1158/1055-9965.EPI-13-0337
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 195NP
UT WOS:000322710100012
PM 23756654
ER
PT J
AU Quinn, BJ
Dallos, M
Kitagawa, H
Kunnumakkara, AB
Memmott, RM
Hollander, MC
Gills, JJ
Dennis, PA
AF Quinn, Brendan J.
Dallos, Matthew
Kitagawa, Hiroshi
Kunnumakkara, Ajaikumar B.
Memmott, Regan M.
Hollander, M. Christine
Gills, Joell J.
Dennis, Phillip A.
TI Inhibition of Lung Tumorigenesis by Metformin Is Associated with
Decreased Plasma IGF-I and Diminished Receptor Tyrosine Kinase Signaling
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID GROWTH-FACTOR-I; BREAST-CANCER CELLS; K-RAS; DIABETIC-PATIENTS;
RESPIRATORY-CHAIN; DEPENDENT MANNER; TRANSGENIC MICE; PROTEIN-KINASE;
INSULIN; RISK
AB Metformin is the most commonly prescribed drug for type II diabetes and is associated with decreased cancer risk. Previously, we showed that metformin prevented tobacco carcinogen (NNK)-induced lung tumorigenesis in a non-diabetic mouse model, which was associated with decreased IGF-I/insulin receptor signaling but not activation of AMPK in lung tissues, as well as decreased circulating levels of IGF-I and insulin. Here, we used liver IGF-I-deficient (LID) mice to determine the importance of IGF-I in NNK-induced lung tumorigenesis and chemoprevention by metformin. LID mice had decreased lung tumor multiplicity and burden compared with wild-type (WT) mice. Metformin further decreased lung tumorigenesis in LID mice without affecting IGF-I levels, suggesting that metformin can act through IGF-I-independent mechanisms. In lung tissues, metformin decreased phosphorylation of multiple receptor tyrosine kinases (RTK) as well as levels of GTP-bound Ras independently of AMPK. Metformin also diminished plasma levels of several cognate ligands for these RTKs. Tissue distribution studies using [C-14]-metformin showed that uptake of metformin was high in liver but four-fold lower in lungs, suggesting that the suppression of RTK activation by metformin occurs predominantly via systemic, indirect effects. Systemic inhibition of circulating growth factors and local RTK signaling are new AMPK-independent mechanisms of action of metformin that could underlie its ability to prevent tobacco carcinogen-induced lung tumorigenesis. (C) 2013 AACR.
C1 [Quinn, Brendan J.; Dallos, Matthew; Kitagawa, Hiroshi; Kunnumakkara, Ajaikumar B.; Memmott, Regan M.; Gills, Joell J.; Dennis, Phillip A.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
[Hollander, M. Christine] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Dennis, PA (reprint author), Johns Hopkins Bayview Med Ctr, Dept Oncol, 4940 Eastern Ave,A113, Baltimore, MD 21224 USA.
EM pdennis@jhmi.edu
FU Intramural NIH HHS [ZIA SC010292-11]
NR 61
TC 24
Z9 25
U1 0
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD AUG
PY 2013
VL 6
IS 8
BP 801
EP 810
DI 10.1158/1940-6207.CAPR-13-0058-T
PG 10
WC Oncology
SC Oncology
GA 196IU
UT WOS:000322768600007
PM 23771523
ER
PT J
AU Sun, ZT
Chen, TY
Thorgeirsson, SS
Zhan, QM
Chen, JG
Park, JH
Lu, PX
Hsia, CC
Wang, NJ
Xu, LB
Lu, LL
Huang, F
Zhu, YR
Lu, JH
Ni, ZP
Zhang, QA
Wu, YY
Liu, GT
Wu, ZY
Qu, CF
Gail, MH
AF Sun, Zongtang
Chen, Taoyang
Thorgeirsson, Snorri S.
Zhan, Qimin
Chen, Jianguo
Park, Ju-Hyun
Lu, Peixin
Hsia, Chu Chieh
Wang, Nengjin
Xu, Libin
Lu, Lingling
Huang, Fei
Zhu, Yuanrong
Lu, Jianhua
Ni, Zhengping
Zhang, Qinan
Wu, Yuying
Liu, Guoting
Wu, Zhiyuan
Qu, Chunfeng
Gail, Mitchell H.
TI Dramatic reduction of liver cancer incidence in young adults: 28 year
follow-up of etiological interventions in an endemic area of China
SO CARCINOGENESIS
LA English
DT Article
ID HEPATITIS-B-VIRUS; HUMAN HEPATOCELLULAR CARCINOMAS; P53 GENE; TRENDS;
AFLATOXIN; EPIDEMIOLOGY; MORTALITY; UPDATE; QIDONG; RISK
AB Qidong City, China, has had high liver cancer incidence from endemic hepatitis B virus (HBV) infection and dietary exposure to aflatoxin. Based on etiologic studies, we began interventions in 1980 to reduce dietary aflatoxin and initiate neonatal HBV vaccination. We studied trends in liver cancer incidence rates in the 1.1 million inhabitants of Qidong and examined trends in aflatoxin exposure, staple food consumption, HBV infection markers and annual income. Aflatoxin exposure declined greatly in association with economic reform, increased earnings and educational programs to shift staple food consumption in the total population from moldy corn to fresh rice. A controlled neonatal HBV vaccination trial began in 1983 and ended in November, 1990, when vaccination was expanded to all newborns. Liver cancer incidence fell dramatically in young adults. Compared with 198083, the age-specific liver cancer incidence rates in 200508 significantly decreased 14-fold at ages 2024, 9-fold at ages 2529, 4-fold at ages 3034, 1.5-fold at ages 3539, 1.2-fold at ages 4044 and 1.4-fold at ages 4549, but increased at older ages. The 14-fold reduction at ages 2024 might reflect the combined effects of reduced aflatoxin exposure and partial neonatal HBV vaccination. Decrease incidence in age groups > 25 years could mainly be attributable to rapid aflatoxin reduction. Compared with 198083, liver cancer incidence in 199093 significantly decreased 3.4-fold at ages 2024, and 1.9-fold at ages 2529 when the first vaccinees were < 11 years old.
C1 [Sun, Zongtang; Zhan, Qimin; Hsia, Chu Chieh; Xu, Libin; Wu, Yuying; Liu, Guoting; Wu, Zhiyuan; Qu, Chunfeng] Chinese Acad Med Sci, Canc Inst & Hosp, State Key Lab Mol Oncol, Beijing 100021, Peoples R China.
[Chen, Taoyang; Chen, Jianguo; Lu, Peixin; Wang, Nengjin; Lu, Lingling; Huang, Fei; Zhu, Yuanrong; Lu, Jianhua; Ni, Zhengping; Zhang, Qinan] Qidong Liver Canc Inst, Qidong 226200, Jiangsu, Peoples R China.
[Thorgeirsson, Snorri S.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Park, Ju-Hyun] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Sun, ZT (reprint author), Chinese Acad Med Sci, Canc Inst & Hosp, State Key Lab Mol Oncol, 17 Nangli, Beijing 100021, Peoples R China.
EM ztsun8602@yahoo.com.cn; gailm@mail.nih.gov
FU Ministry of Science and Technology, China [36112(2), 75610237,
859140310, 2001BA703B06, 2006BA102A03]; National Cancer Institute,
National Institutes of Health, USA
FX Ministry of Science and Technology, China (36112(2), 75610237,
859140310, 2001BA703B06, 2006BA102A03); Intramural Research Program of
the National Cancer Institute, National Institutes of Health, USA.
NR 30
TC 18
Z9 19
U1 0
U2 10
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 AUG
PY 2013
VL 34
IS 8
BP 1800
EP 1805
DI 10.1093/carcin/bgt007
PG 6
WC Oncology
SC Oncology
GA 194XU
UT WOS:000322666800013
PM 23322152
ER
PT J
AU Padilla-Nash, HM
McNeil, NE
Yi, M
Nguyen, QT
Hu, Y
Wangsa, D
Mack, DL
Hummon, AB
Case, C
Cardin, E
Stephens, R
Difilippantonio, MJ
Ried, T
AF Padilla-Nash, Hesed M.
McNeil, Nicole E.
Yi, Ming
Quang-Tri Nguyen
Hu, Yue
Wangsa, Danny
Mack, David L.
Hummon, Amanda B.
Case, Chanelle
Cardin, Eric
Stephens, Robert
Difilippantonio, Michael J.
Ried, Thomas
TI Aneuploidy, oncogene amplification and epithelial to mesenchymal
transition define spontaneous transformation of murine epithelial cells
SO CARCINOGENESIS
LA English
DT Article
ID MAMMARY-GLAND ADENOCARCINOMAS; HUMAN BREAST-CANCER; BLADDER-CANCER;
GENOMIC IMBALANCES; CHROMOSOMAL INSTABILITY; MOUSE CHROMOSOMES;
COPY-NUMBER; EXPRESSION; TUMOR; CARCINOMA
AB Human epithelial cancers are defined by a recurrent distribution of specific chromosomal aneuploidies, a trait less typical for murine cancer models induced by an oncogenic stimulus. After prolonged culture, mouse epithelial cells spontaneously immortalize, transform and become tumorigenic. We assessed genome and transcriptome alterations in cultures derived from bladder and kidney utilizing spectral karyotyping, array CGH, FISH and gene expression profiling. The results show widespread aneuploidy, yet a recurrent and tissue-specific distribution of genomic imbalances, just as in human cancers. Losses of chromosome 4 and gains of chromosome 15 are common and occur early during the transformation process. Global gene expression profiling revealed early and significant transcriptional deregulation. Chromosomal aneuploidy resulted in expression changes of resident genes and consequently in a massive deregulation of the cellular transcriptome. Pathway interrogation of expression changes during the sequential steps of transformation revealed enrichment of genes associated with DNA repair, centrosome regulation, stem cell characteristics and aneuploidy. Genes that modulate the epithelial to mesenchymal transition and genes that define the chromosomal instability phenotype played a dominant role and were changed in a directionality consistent with loss of cell adhesion, invasiveness and proliferation. Comparison with gene expression changes during human bladder and kidney tumorigenesis revealed remarkable overlap with changes observed in the spontaneously transformed murine cultures. Therefore, our novel mouse models faithfully recapitulate the sequence of genomic and transcriptomic events that define human tumorigenesis, hence validating them for both basic and preclinical research.
C1 [Padilla-Nash, Hesed M.; McNeil, Nicole E.; Quang-Tri Nguyen; Hu, Yue; Wangsa, Danny; Case, Chanelle; Cardin, Eric; Difilippantonio, Michael J.; Ried, Thomas] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
[Yi, Ming; Stephens, Robert] SAIC Frederick Inc, Funct Genom Informat Syst Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Mack, David L.] Univ Washington, Dept Rehabil Med, Inst Stem Cell & Regenerat Med, Seattle, WA 98109 USA.
[Hummon, Amanda B.] Univ Notre Dame, Dept Chem & Biochem, Harper Canc Res Inst, South Bend, IN 46556 USA.
[Difilippantonio, Michael J.] NCI, DCTD, NIH, Bethesda, MD 20892 USA.
RP Padilla-Nash, HM (reprint author), NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
EM nashh@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research.
NR 42
TC 5
Z9 6
U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD AUG
PY 2013
VL 34
IS 8
BP 1929
EP 1939
DI 10.1093/carcin/bgt138
PG 11
WC Oncology
SC Oncology
GA 194XU
UT WOS:000322666800027
PM 23619298
ER
PT J
AU Zhang, ZR
Bonifacino, JS
Hegde, RS
AF Zhang, Zai-Rong
Bonifacino, Juan S.
Hegde, Ramanujan S.
TI Deubiquitinases Sharpen Substrate Discrimination during Membrane Protein
Degradation from the ER
SO CELL
LA English
DT Article
ID RETICULUM-ASSOCIATED DEGRADATION; ENDOPLASMIC-RETICULUM; VPU PROTEIN;
UBIQUITIN LIGASE; HIV-1 VPU; IN-VITRO; TRANSMEMBRANE DOMAIN; CYTOPLASMIC
DOMAIN; QUALITY-CONTROL; CD4
AB Newly synthesized membrane proteins are queried by ubiquitin ligase complexes and triaged between degradative and nondegradative fates. The mechanisms that convert modest differences in substrateligase interactions into decisive outcomes of ubiquitination are not well understood. Here, we reconstitute membrane protein recognition and ubiquitination in liposomes using purified components from a viral-mediated degradation pathway. We find that substrate-ligase interactions in the membrane directly influence processivity of ubiquitin attachment to modulate polyubiquitination. Unexpectedly, differential processivity alone could not explain the differential fates in cultured cells of degraded and nondegraded clients. Both computational and experimental analyses identified continuous deubiquitination as a prerequisite for maximal substrate discrimination. Deubiquitinases reduce polyubiquitin dwell times preferentially on clients that dissociate more rapidly from the ligase. This explains how small differences in substrate-ligase interaction can be amplified into larger differences in net degradation. These results provide a conceptual framework for substrate discrimination during membrane protein quality control.
C1 [Zhang, Zai-Rong; Bonifacino, Juan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
[Hegde, Ramanujan S.] MRC Lab Mol Biol, Cambridge CB2 0QH, England.
RP Zhang, ZR (reprint author), Yale Univ, Sch Med, Dept Cell Biol, Nanobiol Inst, Orange, CT 06477 USA.
EM zairong.zhang@gmail.com; rhegde@mrc-lmb.cam.ac.uk
RI Zhang, Zairong/G-1030-2013;
OI Bonifacino, Juan S./0000-0002-5673-6370; Hegde,
Ramanujan/0000-0001-8338-852X
FU NIH; Medical Research Council of the UK
FX We thank R. Deshaies, B. Schulman, X. Yang, H. Ploegh, and V. Denic for
reagents, M. Mariappan, J. Magada n, M.M. Babu, S. Shao, and M.
RodrigoBrenni for discussions, and A. Sharma for technical support. This
research was supported by the Intramural Research Program of the NIH,
Intramural AIDS Targeted Antiviral Program of the NIH, and the Medical
Research Council of the UK. Z.-R.Z. designed most of the experiments,
performed all of the experiments, analyzed data, and helped draft the
paper; R.S.H. conceived and guided the project, designed some of the
experiments, analyzed data, and wrote the paper with input from Z.-R.Z.;
J.S.B. provided advice, support, and comments on the paper.
NR 50
TC 26
Z9 26
U1 1
U2 21
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD AUG 1
PY 2013
VL 154
IS 3
BP 609
EP 622
DI 10.1016/j.cell.2013.06.038
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 194JY
UT WOS:000322629900014
PM 23890821
ER
PT J
AU Fox, E
Widemann, BC
Chuk, MK
Marcus, L
Aikin, A
Whitcomb, PO
Merino, MJ
Lodish, M
Dombi, E
Steinberg, SM
Wells, SA
Balis, FM
AF Fox, Elizabeth
Widemann, Brigitte C.
Chuk, Meredith K.
Marcus, Leigh
Aikin, Alberta
Whitcomb, Patricia O.
Merino, Maria J.
Lodish, Maya
Dombi, Eva
Steinberg, Seth M.
Wells, Samuel A.
Balis, Frank M.
TI Vandetanib in Children and Adolescents with Multiple Endocrine Neoplasia
Type 2B Associated Medullary Thyroid Carcinoma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID PROPHYLACTIC THYROIDECTOMY; RET PROTOONCOGENE; PROGNOSTIC-FACTORS; SERUM
CALCITONIN; SOLID TUMORS; CANCER; INHIBITOR; GROWTH; ZD6474; GUIDELINES
AB Purpose: Medullary thyroid carcinoma (MTC) is a manifestation of multiple endocrine neoplasia type 2 (MEN2) syndromes caused by germline, activating mutations in the RET (REarranged during Transfection) proto-oncogene. Vandetanib, a VEGF and EGF receptor inhibitor, blocks RET tyrosine kinase activity and is active in adults with hereditary MTC.
Experimental Design: We conducted a phase I/II trial of vandetanib for children (5-12 years) and adolescents (13-18 years) with MTC to define a recommended dose and assess antitumor activity. The starting dose was 100 mg/m(2) administered orally, once daily, continuously for 28-day treatment cycles. The dose could be escalated to 150 mg/m(2)/d after two cycles. Radiographic response to vandetanib was quantified using RECIST (v1.0), biomarker response was measured by comparing posttreatment serum calcitonin and carcinoembryonic antigen (CEA) levels to baseline, and a patient-reported outcome was used to assess clinical benefit.
Results: Sixteen patients with locally advanced or metastatic MTC received vandetanib for a median (range) 27 (2-52) cycles. Eleven patients remain on protocol therapy. Diarrhea was the primary dose-limiting toxicity. In subjects with M918T RET germline mutations (n = 15) the confirmed objective partial response rate was 47% (exact 95% confidence intervals, 21%-75%). Biomarker partial response was confirmed for calcitonin in 12 subjects and for CEA in 8 subjects.
Conclusion: Using an innovative trial design and selecting patients based on target gene expression, we conclude that vandetanib 100 mg/m(2)/d is a well-tolerated and highly active new treatment for children and adolescents with MEN2B and locally advanced or metastatic MTC. (C) 2013 AACR.
C1 [Fox, Elizabeth; Balis, Frank M.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
[Fox, Elizabeth; Widemann, Brigitte C.; Chuk, Meredith K.; Marcus, Leigh; Aikin, Alberta; Whitcomb, Patricia O.; Merino, Maria J.; Dombi, Eva; Steinberg, Seth M.; Wells, Samuel A.; Balis, Frank M.] NCI, Bethesda, MD 20892 USA.
[Lodish, Maya] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Fox, E (reprint author), Childrens Hosp Philadelphia, Div Oncol, Colket Translat Res Bldg 4016,3501 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM foxe@email.chop.edu
FU NIH, National Cancer Institute (NCI), Center for Cancer Research (CCR)
FX This research was supported, in part, by the Intramural Research Program
of the NIH, National Cancer Institute (NCI), Center for Cancer Research
(CCR). The clinical trial was investigator initiated and conducted under
an investigator IND (77,570; F.M. Balis and B.C. Widemann). Vandetanib
was supplied by AstraZeneca Pharmaceuticals LP under a Clinical Trial
Agreement with the CCR, NCI.
NR 35
TC 41
Z9 42
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD AUG 1
PY 2013
VL 19
IS 15
BP 4239
EP 4248
DI 10.1158/1078-0432.CCR-13-0071
PG 10
WC Oncology
SC Oncology
GA 193ZB
UT WOS:000322598900023
PM 23766359
ER
PT J
AU Ross, A
Friedmann, E
Bevans, M
Thomas, S
AF Ross, Alyson
Friedmann, Erika
Bevans, Margaret
Thomas, Sue
TI National survey of yoga practitioners: Mental and physical health
benefits
SO COMPLEMENTARY THERAPIES IN MEDICINE
LA English
DT Article
DE Yoga; Survey; Health
ID FREIBURG MINDFULNESS INVENTORY; HATHA YOGA; STRESS; DEPRESSION;
DISORDER; GENDER; ADULTS
AB Objectives: To describe yoga practice and health characteristics of individuals who practice yoga, and to explore their beliefs regarding the effects of their yoga practice on their health.
Design: A cross-sectional design with anonymous online surveys.
Setting: 4307 randomly selected individuals from 15 US Iyengar yoga studios (n = 18,160), representing 41 states; 1087 individuals responded, with 1045 (24.3%) surveys completed.
Outcome measures: Freiberg Mindfulness Inventory, Mental Health Continuum (subjective well-being), Multi-factor Screener (diet), PROMIS sleep disturbance, fatigue, and social support, International Physical Activity Questionnaire.
Results: Age: 19-87 years (M = 51.7 +/- 11.7), 84.2% female, 89.2% white, 87.4% well educated (>= bachelor's degree). Mean years of yoga practice = 11.4 (+/- 7.5). BMI = 12.1-49.4 (M = 23.1 +/- 3.9). Levels of obesity (4.9%), smoking (2%), and fruit and vegetable consumption (M = 6.1 +/- 1.1) were favorable compared to national norms. 60% reported at least one chronic/serious health condition, yet most reported very good (46.3%) or excellent (38.8%) general health. Despite high levels of depression (24.8%), nearly all were moderately mentally healthy (55.2%) or flourishing (43.8%). Participants agreed yoga improved: energy (84.5%), happiness (86.5%), social relationships (67%), sleep (68.5%), and weight (57.3%), and beliefs did not differ substantially according to race or gender. The more they practiced yoga, whether in years or in amount of class or home practice, the higher their odds of believing yoga improved their health.
Conclusions: Individuals who practice yoga are not free of health concerns, but most believe their health improved because of yoga. Yoga might be beneficial for a number of populations including elderly women and those with chronic health conditions. (c) 2013 Published by Elsevier Ltd.
C1 [Ross, Alyson; Friedmann, Erika; Thomas, Sue] Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA.
[Bevans, Margaret] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Ross, A (reprint author), Univ Maryland, Sch Nursing, 655 West Lombard St, Baltimore, MD 21201 USA.
EM Alyross1@verizon.net
OI Friedmann, Erika/0000-0003-2924-0449
FU Intramural NIH HHS [Z99 CL999999]
NR 38
TC 21
Z9 21
U1 9
U2 90
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0965-2299
J9 COMPLEMENT THER MED
JI Complement. Ther. Med.
PD AUG
PY 2013
VL 21
IS 4
BP 313
EP 323
DI 10.1016/j.ctim.2013.04.001
PG 11
WC Integrative & Complementary Medicine
SC Integrative & Complementary Medicine
GA 194BX
UT WOS:000322607100006
PM 23876562
ER
PT J
AU Chou, SP
Huang, B
Goldstein, R
Grant, BF
AF Chou, S. Patricia
Huang, Boji
Goldstein, Rise
Grant, Bridget F.
TI Temporal associations between physical illnesses and mental
disorders-Results from the Wave 2 National Epidemiologic Survey on
Alcohol and Related Conditions (NESARC)
SO COMPREHENSIVE PSYCHIATRY
LA English
DT Article
ID COMORBIDITY SURVEY REPLICATION; PSYCHIATRIC DIAGNOSTIC MODULES;
GENERAL-POPULATION SAMPLE; DSM-IV DISORDERS; ANXIETY DISORDERS; HEALTH
SURVEYS; PSYCHOLOGICAL STRESS; MEDICAL ILLNESS; DUODENAL-ULCER;
UNITED-STATES
AB Clinical and epidemiologic evidence has documented the significant associations between medical illnesses and psychiatric disorders. However, extensive research has focused on the comorbidity of medical conditions and depression, and most were cross sectional, focused on clinical samples, and grounded in DSM-III or DSM-III-R diagnostic criteria.
The current prospective investigation examined associations among medical conditions at baseline and incident psychiatric disorders over a 3-year follow-up, using data from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).
Overall, the 3-year incidence rates of DSM-IV substance use, mood and anxiety disorders ranged from 0.65% (bipolar II) to 5.2% (alcohol abuse). Multiple regression analysis was conducted to examine the prospective physical-mental associations, while controlling for sociodemographic characteristics, psychological stress and health-related risk factors, and comorbid physical and psychiatric disorders.
The present study represents, to our knowledge the largest population-based prospective study examining the physical mental associations. Our results showed distinctly different patterns of comorbidity of medical illnesses with substance use, mood, and anxiety disorders. Stomach ulcer/gastritis, hypertension and arthritis emerged to be significant predictors of incident psychiatric disorders.
C1 [Chou, S. Patricia; Huang, Boji; Goldstein, Rise; Grant, Bridget F.] NIH, NIAAA, Bethesda, MD 20892 USA.
RP Chou, SP (reprint author), NIH, NIAAA, LEB, Bldg 10, Bethesda, MD 20892 USA.
EM pchou@mail.nih.gov
OI Goldstein, Rise/0000-0002-9603-9473
FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); National
Institutes of Health, National Institute on Alcohol Abuse and Alcoholism
FX The National Epidemiologic Survey on Alcohol and Related Conditions
(NESARC) is funded by the National Institute on Alcohol Abuse and
Alcoholism (NIAAA) with supplemental support from the National Institute
on Drug Abuse (NIDA). This research was supported in part by the
Intramural Program of the National Institutes of Health, National
Institute on Alcohol Abuse and Alcoholism.
NR 51
TC 8
Z9 8
U1 2
U2 14
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0010-440X
J9 COMPR PSYCHIAT
JI Compr. Psychiat.
PD AUG
PY 2013
VL 54
IS 6
BP 627
EP 638
DI 10.1016/j.comppsych.2012.12.020
PG 12
WC Psychiatry
SC Psychiatry
GA 195DZ
UT WOS:000322683800006
PM 23522830
ER
PT J
AU Anthony, LG
Kenworthy, L
Yerys, BE
Jankowski, KF
James, JD
Harms, MB
Martin, A
Wallace, GL
AF Anthony, Laura Gutermuth
Kenworthy, Lauren
Yerys, Benjamin E.
Jankowski, Kathryn F.
James, Joette D.
Harms, Madeline B.
Martin, Alex
Wallace, Gregory L.
TI Interests in high-functioning autism are more intense, interfering, and
idiosyncratic than those in neurotypical development
SO DEVELOPMENT AND PSYCHOPATHOLOGY
LA English
DT Article
ID REPETITIVE BEHAVIORS; SPECTRUM DISORDERS; YOUNG-CHILDREN; DIAGNOSTIC
INTERVIEW; CIRCUMSCRIBED INTERESTS; EXECUTIVE FUNCTIONS; ATTENTION;
SYMPTOMS; INDIVIDUALS; ASSOCIATION
AB Although circumscribed interests are pathognomonic with autism, much about these interests remains unknown. Using the Interests Scale (IS), this study compares interests between 76 neurotypical (NT) individuals and 109 individuals with high-functioning autism spectrum disorder (HF-ASD) matched groupwise on age, IQ, and gender ratio. Participants and their parents/caregivers completed diagnostic measures (the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule; HF-ASD only), cognitive tests (Wechsler IQ Scales), and questionnaires (the Repetitive Behavior Scale-Revised, the Behavior Rating Inventory of Executive Function, and the Social Responsiveness Scale), in addition to the IS. Consistent with previous research, HF-ASD and NT individuals did not differ in number of interest areas, but the types of interests and intensity of those interests differed considerably. Using only the IS intensity score, 81% of individuals were correctly classified (NT or HF-ASD) in a logistic regression analysis. Among individuals with HF-ASD, Interests Scale scores were significantly related to Autism Diagnostic Observation Schedule, Behavior Rating Inventory of Executive Function, Repetitive Behavior Scale-Revised, and Social Responsiveness Scale scores, but they were not related to Autism Diagnostic Interview-Revised scores, IQ, gender, age, or psychotropic medication use. The type and intensity, but not the number, of interests distinguish high-functioning individuals with ASD from NT individuals.
C1 [Anthony, Laura Gutermuth; Kenworthy, Lauren; Yerys, Benjamin E.; Jankowski, Kathryn F.; James, Joette D.] George Washington Univ, Sch Med, Rockville, MD 20850 USA.
[Harms, Madeline B.; Martin, Alex; Wallace, Gregory L.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA.
RP Anthony, LG (reprint author), George Washington Univ, Sch Med, Ctr Autism Spectrum Disorders, 15245 Shady Grove Rd,Suite 350, Rockville, MD 20850 USA.
EM lanthony@childrensnational.org
OI Wallace, Gregory/0000-0003-0329-5054
FU Intramural NIH HHS [Z99 MH999999]; NICHD NIH HHS [P30 HD040677,
P30HD40677]; NIMH NIH HHS [R34 MH083053, 5K23MH086111, K23 MH086111, U54
MH066417]
NR 62
TC 4
Z9 4
U1 3
U2 12
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0954-5794
J9 DEV PSYCHOPATHOL
JI Dev. Psychopathol.
PD AUG
PY 2013
VL 25
IS 3
BP 643
EP 652
DI 10.1017/S0954579413000072
PG 10
WC Psychology, Developmental
SC Psychology
GA 187LO
UT WOS:000322120600006
PM 23880382
ER
PT J
AU Bornstein, MH
Hahn, CS
Suwalsky, JTD
AF Bornstein, Marc H.
Hahn, Chun-Shin
Suwalsky, Joan T. D.
TI Language and internalizing and externalizing behavioral adjustment:
Developmental pathways from childhood to adolescence
SO DEVELOPMENT AND PSYCHOPATHOLOGY
LA English
DT Article
ID 14-YEAR FOLLOW-UP; LIMITED ANTISOCIAL PATHWAYS; LIFE-COURSE-PERSISTENT;
ADULT LIFE; EPIDEMIOLOGIC SAMPLE; SOCIOECONOMIC-STATUS; DEPRESSIVE
SYMPTOMS; SOCIAL COMPETENCE; NATIONAL SAMPLE; YOUNG-CHILDREN
AB Two independent prospective longitudinal studies that cumulatively spanned the age interval from 4 years to 14 years used multiwave designs to investigate developmental associations between language and behavioral adjustment (internalizing and externalizing behavior problems). Altogether 224 children, their mothers, and teachers provided data. Series of nested path analysis models were used to determine the most parsimonious and plausible paths among the three constructs over and above stability in each across age and their covariation at each age. In both studies, children with poorer language skills in early childhood had more internalizing behavior problems in later childhood and in early adolescence. These developmental paths between language and behavioral adjustment held after taking into consideration children's nonverbal intellectual functioning, maternal verbal intelligence, education, parenting knowledge, and social desirability bias, as well as family socioeconomic status, and they applied equally to girls and boys.
C1 [Bornstein, Marc H.; Hahn, Chun-Shin; Suwalsky, Joan T. D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA.
EM Marc_H_Bornstein@nih.gov
FU Intramural NIH HHS [ZIA HD001119-26]
NR 122
TC 18
Z9 18
U1 2
U2 23
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0954-5794
J9 DEV PSYCHOPATHOL
JI Dev. Psychopathol.
PD AUG
PY 2013
VL 25
IS 3
BP 857
EP 878
DI 10.1017/S0954579413000217
PG 22
WC Psychology, Developmental
SC Psychology
GA 187LO
UT WOS:000322120600020
PM 23880396
ER
PT J
AU Maddukuri, VC
Russo, MW
Ahrens, WA
Emerson, SU
Engle, RE
Purcell, RH
Thompson, EB
Bonkovsky, HL
AF Maddukuri, Vinaya C.
Russo, Mark W.
Ahrens, William A.
Emerson, Suzanne U.
Engle, Ronald E.
Purcell, Robert H.
Thompson, Eric B.
Bonkovsky, Herbert L.
TI Chronic Hepatitis E with Neurologic Manifestations and Rapid Progression
of Liver Fibrosis in a Liver Transplant Recipient
SO DIGESTIVE DISEASES AND SCIENCES
LA English
DT Article
DE HEV; Hepatic; Transplantation; Chronic hepatitis; Peripheral Neuropathy;
Nervous system
ID E VIRUS
C1 [Maddukuri, Vinaya C.; Russo, Mark W.; Ahrens, William A.] Carolinas Med Ctr, Liver Biliary Pancreat Ctr, Charlotte, NC 28203 USA.
[Maddukuri, Vinaya C.; Russo, Mark W.; Ahrens, William A.] Carolinas Med Ctr, Liver Transplant Ctr, Charlotte, NC 28203 USA.
[Emerson, Suzanne U.; Engle, Ronald E.; Purcell, Robert H.] NIAID, Mol Hepatitis & Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Thompson, Eric B.] Carolinas Digest Hlth Associates, Charlotte, NC 28211 USA.
[Bonkovsky, Herbert L.] Carolinas Med Ctr, Liver Biliary Pancreat Ctr, Charlotte, NC 28202 USA.
[Bonkovsky, Herbert L.] Carolinas Med Ctr, Liver Transplant Ctr, Charlotte, NC 28202 USA.
RP Maddukuri, VC (reprint author), Carolinas Med Ctr, Liver Biliary Pancreat Ctr, 1540 Garden Terrace,Res Off Bldg,5th Floor,WS 7, Charlotte, NC 28203 USA.
EM vcmaddukuri@yahoo.com
FU Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases; Carolinas Medical
Center; [R01 DK 38825]; [U01 DK 065201]
FX This study was supported by a grant (R01 DK 38825) and contract (U01 DK
065201) and the Intramural Research Program of the National Institutes
of Health, National Institute of Allergy and Infectious Diseases and by
institutional funds from Carolinas Medical Center. This work was carried
out under an approved protocol of the Carolinas Medical Center, IRB
10-0709B, with the informed consent of the patient.
NR 5
TC 7
Z9 7
U1 0
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0163-2116
J9 DIGEST DIS SCI
JI Dig. Dis. Sci.
PD AUG
PY 2013
VL 58
IS 8
BP 2413
EP 2416
DI 10.1007/s10620-013-2628-7
PG 4
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 194RR
UT WOS:000322650900040
PM 23512404
ER
PT J
AU Galanopoulou, AS
Kokaia, M
Loeb, JA
Nehlig, A
Pitkanen, A
Rogawski, MA
Staley, KJ
Whittemore, VH
Dudek, FE
AF Galanopoulou, Aristea S.
Kokaia, Merab
Loeb, Jeffrey A.
Nehlig, Astrid
Pitkanen, Asla
Rogawski, Michael A.
Staley, Kevin J.
Whittemore, Vicky H.
Dudek, F. Edward
TI Epilepsy therapy development: Technical and methodologic issues in
studies with animal models
SO EPILEPSIA
LA English
DT Article
DE Pharmacokinetics; Video-electroencephalography; Regulatory requirements;
Nonpharmacological treatment; Infrastructure
ID SEIZURES; PUBLICATION; INJURY; DRUGS; RATS; ILAE
AB The search for new treatments for seizures, epilepsies, and their comorbidities faces considerable challenges. This is due in part to gaps in our understanding of the etiology and pathophysiology of most forms of epilepsy. An additional challenge is the difficulty in predicting the efficacy, tolerability, and impact of potential new treatments on epilepsies and comorbidities in humans, using the available resources. Herein we provide a summary of the discussions and proposals of the Working Group 2 as presented in the Joint American Epilepsy Society and International League Against Epilepsy Translational Workshop in London (September 2012). We propose methodologic and reporting practices that will enhance the uniformity, reliability, and reporting of early stage preclinical studies with animal seizure and epilepsy models that aim to develop and evaluate new therapies for seizures or epilepsies, using multidisciplinary approaches. The topics considered include the following: (1) implementation of better study design and reporting practices; (2) incorporation in the study design and analysis of covariants that may influence outcomes (including species, age, sex); (3) utilization of approaches to document target relevance, exposure, and engagement by the tested treatment; (4) utilization of clinically relevant treatment protocols; (5) optimization of the use of video-electroencephalography (EEG) recordings to best meet the study goals; and (6) inclusion of outcome measures that address the tolerability of the treatment or study end points apart from seizures. We further discuss the different expectations for studies aiming to meet regulatory requirements to obtain approval for clinical testing in humans. Implementation of the rigorous practices discussed in this report will require considerable investment in time, funds, and other research resources, which may create challenges for academic researchers seeking to contribute to epilepsy therapy discovery and development. We propose several infrastructure initiatives to overcome these barriers.
C1 [Galanopoulou, Aristea S.] Albert Einstein Coll Med, Lab Dev Epilepsy, Saul R Korey Dept Neurol, Dominick P Purpura Dept Neurosci, Bronx, NY 10461 USA.
[Kokaia, Merab] Univ Lund Hosp, Expt Epilepsy Grp, Div Neurol, Wallenberg Neurosci Ctr, S-22185 Lund, Sweden.
[Loeb, Jeffrey A.] Wayne State Univ, Dept Neurol, Detroit, MI USA.
[Loeb, Jeffrey A.] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
[Nehlig, Astrid] Hop Necker Enfants Malad, INSERM, U663, Paris, France.
[Pitkanen, Asla] Univ Eastern Finland, Dept Neurobiol, AI Virtanen Inst Mol Sci, Kuopio, Finland.
[Pitkanen, Asla] Kuopio Univ Hosp, Dept Neurol, SF-70210 Kuopio, Finland.
[Rogawski, Michael A.] Univ Calif Davis, Dept Neurol, Sch Med, Sacramento, CA 95817 USA.
[Staley, Kevin J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Staley, Kevin J.] Harvard Univ, Sch Med, Boston, MA USA.
[Whittemore, Vicky H.] NINDS, NIH, Bethesda, MD 20892 USA.
[Dudek, F. Edward] Univ Utah, Sch Med, Dept Neurosurg, Salt Lake City, UT USA.
RP Galanopoulou, AS (reprint author), Albert Einstein Coll Med, 1410 Pelham Pkwy South,Kennedy Ctr Rm 306, Bronx, NY 10461 USA.
EM aristea.galanopoulou@einstein.yu.edu
RI Rogawski, Michael/B-6353-2009
OI Rogawski, Michael/0000-0002-3296-8193
FU AES; ILAE; CURE; Epilepsy Therapy Project; Autism Speaks
FX We would like to acknowledge the invaluable advice during our
proceedings by H. Steve White (University of Utah, Salt lake City,
Utah), James Cloyd (Center for Orphan Drug Research, University of
Minnesota, Minneapolis, Minnesota, U. S. A.), and Elisabetta Vaudano
(Innovative Medicines Initiative, Brussels, Belgium). We would also like
to thank the AES, ILAE, CURE, Epilepsy Therapy Project, and Autism
Speaks for their financial support of the AES/ILAE Joint workshop in
London (September 2012).
NR 38
TC 19
Z9 19
U1 0
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD AUG
PY 2013
VL 54
SU 4
SI SI
BP 13
EP 23
DI 10.1111/epi.12295
PG 11
WC Clinical Neurology
SC Neurosciences & Neurology
GA 193TR
UT WOS:000322584900003
PM 23909850
ER
PT J
AU Brooks-Kayal, AR
Bath, KG
Berg, AT
Galanopoulou, AS
Holmes, GL
Jensen, FE
Kanner, AM
O'Brien, TJ
Whittemore, VH
Winawer, MR
Patel, M
Scharfman, HE
AF Brooks-Kayal, Amy R.
Bath, Kevin G.
Berg, Anne T.
Galanopoulou, Aristea S.
Holmes, Gregory L.
Jensen, Frances E.
Kanner, Andres M.
O'Brien, Terence J.
Whittemore, Vicky H.
Winawer, Melodie R.
Patel, Manisha
Scharfman, Helen E.
TI Issues related to symptomatic and disease-modifying treatments affecting
cognitive and neuropsychiatric comorbidities of epilepsy
SO EPILEPSIA
LA English
DT Review
DE Epilepsy; Comorbidity; Animal models; Biomarkers
ID TEMPORAL-LOBE EPILEPSY; TRAUMATIC BRAIN-INJURY; EARLY-LIFE SEIZURES;
INDUCED STATUS EPILEPTICUS; GENETIC ABSENCE EPILEPSY; DEPRESSIVE-LIKE
BEHAVIOR; ENVIRONMENTAL ENRICHMENT; SPATIAL MEMORY; KETOGENIC DIET;
IMMATURE RATS
AB Many symptoms of neurologic or psychiatric illness-such as cognitive impairment, depression, anxiety, attention deficits, and migraine-occur more frequently in people with epilepsy than in the general population. These diverse comorbidities present an underappreciated problem for people with epilepsy and their caregivers because they decrease quality of life, complicate treatment, and increase mortality. In fact, it has been suggested that comorbidities can have a greater effect on quality of life in people with epilepsy than the seizures themselves. There is increasing recognition of the frequency and impact of cognitive and behavioral comorbidities of epilepsy, highlighted in the 2012 Institute of Medicine report on epilepsy. Comorbidities have also been acknowledged, as a National Institutes of Health (NIH) Benchmark area for research in epilepsy. However, relatively little progress has been made in developing new therapies directed specifically at comorbidities. On the other hand, there have been many advances in understanding underlying mechanisms. These advances have made it possible to identify novel targets for therapy and prevention. As part of the International League Against Epilepsy/American Epilepsy Society workshop on preclinical therapy development for epilepsy, our working group considered the current state of understanding related to terminology, models, and strategies for therapy development for the comorbidities of epilepsy. Herein we summarize our findings and suggest ways to accelerate development of new therapies. We also consider important issues to improve research including those related to methodology, nonpharmacologic therapies, biomarkers, and infrastructure.
C1 [Brooks-Kayal, Amy R.] Univ Colorado, Dept Pediat, Sch Med, Childrens Hosp Colorado, Aurora, CO USA.
[Brooks-Kayal, Amy R.] Univ Colorado, Dept Neurol, Sch Med, Childrens Hosp Colorado, Aurora, CO USA.
[Brooks-Kayal, Amy R.] Univ Colorado, Dept Pharmaceut Sci, Sch Med, Childrens Hosp Colorado, Aurora, CO USA.
[Brooks-Kayal, Amy R.] Univ Colorado, Dept Pediat, Sch Pharm, Childrens Hosp Colorado, Aurora, CO USA.
[Brooks-Kayal, Amy R.] Univ Colorado, Dept Neurol, Sch Pharm, Childrens Hosp Colorado, Aurora, CO USA.
[Brooks-Kayal, Amy R.] Univ Colorado, Dept Pharmaceut Sci, Sch Pharm, Childrens Hosp Colorado, Aurora, CO USA.
[Bath, Kevin G.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA.
[Berg, Anne T.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL USA.
[Galanopoulou, Aristea S.] Albert Einstein Coll Med, Saul R Korey Dept Neurol, Dominick P Purpura Dept Neurosci, Lab Dev Epilepsy, Bronx, NY 10467 USA.
[Holmes, Gregory L.] Geisel Sch Med Dartmouth, Dept Neurol, Hanover, NH USA.
[Holmes, Gregory L.] Geisel Sch Med Dartmouth, Dept Pediat, Hanover, NH USA.
[Jensen, Frances E.] Univ Penn, Dept Neurol, Perlman Sch Med, Philadelphia, PA 19104 USA.
[Kanner, Andres M.] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.
[O'Brien, Terence J.] Univ Melbourne, Dept Med, Royal Melbourne Hosp, Melbourne Brain Ctr, Parkville, Vic 3052, Australia.
[Whittemore, Vicky H.] NINDS, NIH, Bethesda, MD 20892 USA.
[Winawer, Melodie R.] Columbia Univ, Dept Neurol, Gertrude H Sergievsky Ctr, New York, NY USA.
[Patel, Manisha] Univ Colorado, Dept Pharmaceut Sci, Skaggs Sch Pharm & Pharmaceut Sci, Aurora, CO USA.
[Scharfman, Helen E.] NYU, Dept Psychiat, Langone Med Ctr, Nathan S Kline Inst Psychiat Res, New York, NY 10016 USA.
[Scharfman, Helen E.] NYU, Dept Physiol, Langone Med Ctr, Nathan S Kline Inst Psychiat Res, New York, NY USA.
[Scharfman, Helen E.] NYU, Dept Neurosci, Langone Med Ctr, Nathan S Kline Inst Psychiat Res, New York, NY USA.
RP Brooks-Kayal, AR (reprint author), 13123 East 16th Ave,Box B155, Aurora, CO 80045 USA.
EM Amy.brooks-kayal@childrens-colorado.org
RI O'Brien, Terence/L-8102-2013;
OI O'Brien, Terence/0000-0002-7198-8621
FU CURE; AES; Epilepsy Foundation (EF); Colorado Center for Drug Discovery
(ARB-K); NARSAD; EF; Pediatric Epilepsy Foundation; Autism Speaks;
Heffer and Siegel Families Foundations; Office of the Director
[R21NS072099]; Alzheimer's Association; NYS Office of Mental Health;
[R01NS38595]; [R37NS31146]; [R21NS078333]; [R01NS020253];
[R01NS061991]; [RO1NS039587]; [R01NS37562]; [R21MH090606]
FX Funding sources: R01NS38595 and grants from CURE, AES, the Epilepsy
Foundation (EF) and the Colorado Center for Drug Discovery (ARB-K);
NARSAD and EF (KGB); R37NS31146 and a grant from the Pediatric Epilepsy
Foundation (ATB); R21NS078333 and R01NS020253 and grants from Autism
Speaks, CURE, Heffer and Siegel Families Foundations (ASG); R01NS061991
and CURE (MRW); RO1NS039587, CURE, and Office of the Director grant
R21NS072099 (MP); R01NS37562, R21MH090606, the Alzheimer's Association,
and NYS Office of Mental Health (HES).
NR 149
TC 48
Z9 49
U1 3
U2 21
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD AUG
PY 2013
VL 54
SU 4
SI SI
BP 44
EP 60
DI 10.1111/epi.12298
PG 17
WC Clinical Neurology
SC Neurosciences & Neurology
GA 193TR
UT WOS:000322584900006
PM 23909853
ER
PT J
AU Subar, AF
Midthune, D
Tasevska, N
Kipnis, V
Freedman, LS
AF Subar, A. F.
Midthune, D.
Tasevska, N.
Kipnis, V.
Freedman, L. S.
TI Checking for completeness of 24-h urine collection using para-amino
benzoic acid not necessary in the Observing Protein and Energy Nutrition
study
SO EUROPEAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
DE diet; nutrition assessment; urine specimen collection; statistical bias
ID PARA-AMINOBENZOIC ACID; DIETARY MEASUREMENT ERROR; BIOMARKER; NITROGEN;
VALIDATION; MARKER; QUESTIONNAIRE; EPIDEMIOLOGY; INDIVIDUALS; POTASSIUM
AB BACKGROUND/OBJECTIVES: The orally administered para-amino benzoic acid (PABA) is known to have near 100% excretion in urine and is used as a measure of 24-h urine collection completeness (referred to as PABAcheck). The purpose was to examine the effect of including urine collections deemed incomplete based on PABAcheck in a dietary measurement error study.
SUBJECTS/METHODS: The Observing Protein and Energy Nutrition (OPEN) study was conducted in 1999-2000 and included 484 men and women aged 40-69 years. A food frequency questionnaire and 24-h dietary recalls were evaluated using recovery biomarkers that included urinary nitrogen and potassium from two 24-h urine collections. Statistical modeling determined the measurement error properties of dietary assessment instruments. In the original analyses, PABAcheck was used as a measure of complete urine collection; incomplete collections were either excluded or adjusted to acceptable levels. The OPEN data were reanalyzed including all urine collections and by using criteria based on self-reported missing voids to assess the differences.
RESULTS: Means and coefficients of variation for biomarker-based protein and potassium intakes, and measurement error model-based correlations and attenuation factors were similar regardless of whether PABAcheck or missed voids were considered.
CONCLUSION: PABAcheck may not be required in large population-based biomarker studies. However, until there are more analyses evaluating the necessity of a PABAcheck, it is recommended that PABA be given to all participants, but not necessarily analyzed. Then, PABAcheck could be used selectively as a marker of completeness among the collections in which low levels of biomarker are detected or for which noncompliance is suspected.
C1 [Subar, A. F.; Tasevska, N.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Midthune, D.; Kipnis, V.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Freedman, L. S.] Sheba Med Ctr, Gertner Inst Epidemiol & Publ Hlth Policy, Tel Hashomer, Israel.
RP Subar, AF (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4005, Bethesda, MD 20892 USA.
EM subara@mail.nih.gov
RI Trivedi, Kruti/E-7558-2015
FU US National Cancer Institute
FX This work was funded by the US National Cancer Institute.
NR 26
TC 16
Z9 16
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0954-3007
EI 1476-5640
J9 EUR J CLIN NUTR
JI Eur. J. Clin. Nutr.
PD AUG
PY 2013
VL 67
IS 8
BP 863
EP 867
DI 10.1038/ejcn.2013.62
PG 5
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 197BL
UT WOS:000322822700013
PM 23486508
ER
PT J
AU Schnabel, RB
Rienstra, M
Sullivan, LM
Sun, JX
Moser, CB
Levy, D
Pencina, MJ
Fontes, JD
Magnani, JW
McManus, DD
Lubitz, SA
Tadros, TM
Wang, TJ
Ellinor, PT
Vasan, RS
Benjamin, EJ
AF Schnabel, Renate B.
Rienstra, Michiel
Sullivan, Lisa M.
Sun, Jenny X.
Moser, Carlee B.
Levy, Daniel
Pencina, Michael J.
Fontes, Joao D.
Magnani, Jared W.
McManus, David D.
Lubitz, Steven A.
Tadros, Thomas M.
Wang, Thomas J.
Ellinor, Patrick T.
Vasan, Ramachandran S.
Benjamin, Emelia J.
TI Risk assessment for incident heart failure in individuals with atrial
fibrillation
SO EUROPEAN JOURNAL OF HEART FAILURE
LA English
DT Article
DE Atrial fibrillation; Risk score; Epidemiology; Heart failure
ID EJECTION FRACTION; ONSET; SURVIVAL; CARDIOVERSION; TRENDS
AB Background Atrial fibrillation (AF) is a strong risk factor for heart failure (HF); HF onset in patients with AF is associated with increased morbidity and mortality. Risk factors that predict HF in individuals with AF in the community are not well established.
Methods and results We examined clinical variables related to the 10-year incidence of HF in 725 individuals (mean 73.3 years, 45% women) with documented AF in the Framingham Heart Study. Event rates for incident HF (n = 161, 48% in women) were comparable in women (4.30 per 100 person-years) and men (3.34 per 100 person-years). Age, body mass index, ECG LV hypertrophy, diabetes, significant murmur, and history of myocardial infarction were positively associated with incident HF in multivariable models (C-statistic 0.71; 95% confidence interval 0.67-0.75). We developed a risk algorithm for estimating absolute risk of HF in AF patients with good model fit and calibration (adjusted calibration chi(2) statistic 7.29; P-chi 2 = 0.61). Applying the algorithm, 47.6% of HF events occurred in the top tertile in men compared with 13.1% in the bottom tertile, and 58.4% in women in the upper tertile compared with 18.2% in the lowest category. For HF type, women had a non-significantly higher incidence of HF with preserved EF compared with men.
Conclusions We describe advancing age, LV hypertrophy, body mass index, diabetes, significant heart murmur, and history of myocardial infarction as clinical predictors of incident HF in individuals with AF. A risk algorithm may help identify individuals with AF at high risk of developing HF.
C1 [Schnabel, Renate B.; Rienstra, Michiel; Pencina, Michael J.; Fontes, Joao D.; Magnani, Jared W.; McManus, David D.; Tadros, Thomas M.; Wang, Thomas J.; Vasan, Ramachandran S.; Benjamin, Emelia J.] NHLBIs & Boston Univ Framingham Heart Study, Framingham, MA USA.
[Schnabel, Renate B.] Univ Heart Ctr Hamburg Eppendorf, Dept Gen & Intervent Cardiol, D-20246 Hamburg, Germany.
[Rienstra, Michiel] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
[Sullivan, Lisa M.; Sun, Jenny X.; Moser, Carlee B.; Pencina, Michael J.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Levy, Daniel] NHLBI, Ctr Populat Studies, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Magnani, Jared W.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Cardiovasc Med, Boston, MA 02118 USA.
[McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiol, Worcester, MA USA.
[Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Wang, Thomas J.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Evans Mem Med Dept, Boston, MA 02118 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
RP Schnabel, RB (reprint author), Univ Heart Ctr Hamburg Eppendorf, Dept Gen & Intervent Cardiol, Bldg East 70 O70,Martinistr 52, D-20246 Hamburg, Germany.
EM schnabelr@gmx.de
RI Schnabel, Renate/F-6527-2014;
OI Ramachandran, Vasan/0000-0001-7357-5970; Sullivan,
Lisa/0000-0003-0726-7149; Benjamin, Emelia/0000-0003-4076-2336;
Rienstra, Michiel/0000-0002-2581-070X
FU National Institutes of Health (NIH)/National Heart Lung, and Blood
Institute (NHLBI) [N01-HC-25195, 6R01-NS 17950]; NIH [HL092577-01A1,
1RC1HL101056, 1R01HL102214, 1R01AG028321, 5R21DA027021, 1RO1HL104156,
1K24HL105780, HL080124, HL077477, HL71039, 2K24 HL04334]; Deutsche
Forschungsgemeinschaft (German Research Foundation) [SCHN 1149/1-1, SCHN
1149/3-1]; Netherlands Organization for Scientific Research
[825.09.020]; Evans Center for Interdisciplinary Biomedical Research ARC
on 'Atrial Fibrillation' at Boston University
FX Supported by National Institutes of Health (NIH)/National Heart Lung,
and Blood Institute (NHLBI) contract N01-HC-25195; 6R01-NS 17950; NIH
grants HL092577-01A1 (P.T.E. and E.J.B.); 1RC1HL101056; 1R01HL102214;
1R01AG028321 (E.J.B.); 5R21DA027021, 1RO1HL104156, 1K24HL105780
(P.T.E.); HL080124, HL077477, and HL71039 (R.S.V.). NIH Research career
award 2K24 HL04334 (R.S.V.); Deutsche Forschungsgemeinschaft (German
Research Foundation) Research Fellowship SCHN 1149/1-1 and Emmy Noether
Program (SCHN 1149/3-1) (R.B.S.); M.R. is supported by a grant from the
Netherlands Organization for Scientific Research (Rubicon Grant
825.09.020). This work was partially supported by the Evans Center for
Interdisciplinary Biomedical Research ARC on 'Atrial Fibrillation' at
Boston University (http://www.bumc.bu.edu/evanscenteribr/)
NR 26
TC 20
Z9 21
U1 0
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1388-9842
J9 EUR J HEART FAIL
JI Eur. J. Heart Fail.
PD AUG
PY 2013
VL 15
IS 8
BP 843
EP 849
DI 10.1093/eurjhf/hft041
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 191CS
UT WOS:000322390800004
PM 23594831
ER
PT J
AU Hudson, J
Duncavage, E
Tamburrino, A
Salerno, P
Xi, LQ
Raffeld, M
Moley, J
Chernock, RD
AF Hudson, Jena
Duncavage, Eric
Tamburrino, Anna
Salerno, Paolo
Xi, Liqiang
Raffeld, Mark
Moley, Jeffrey
Chernock, Rebecca D.
TI Overexpression of miR-10a and miR-375 and downregulation of YAP1 in
medullary thyroid carcinoma
SO EXPERIMENTAL AND MOLECULAR PATHOLOGY
LA English
DT Article
DE Medullary thyroid carcinoma; microRNA; miR-375; miR-10a; miR-455; YAP1
ID MICRORNA EXPRESSION; PROGNOSTIC-FACTORS; HUMAN CANCER; MUTATIONS;
PROFILES; SURVIVAL; PATHWAY; TARGETS; ALPHA; RNAS
AB MicroRNAs are a primordial mechanism of gene expression control that appear to be crucial to cellular development and may play an important role in tumor development. Much is known about the genetics of medullary thyroid carcinomas, as approximately 25% are hereditary and harbor germ line activating mutations in the RET gene. Somatic RET mutations are also seen in roughly 50% of sporadic medullary thyroid carcinomas. Few studies, however, have evaluated the role of microRNA expression in these tumors. DNA and RNA were extracted from formalin-fixed paraffin-embedded tissue blocks of 15 medullary thyroid carcinomas 110 with RET mutations (3 hereditary) and 5 without RET mutations] and 5 non-tumor thyroid glands. miRNA expression of 754 targets was quantitated by real-time PCR using the ABI OpenArray miRNA assay. Three miRNAs showed significant differential expression and were validated in a larger cohort of 59 cases by real-time PCR. Expression of potential downstream targets and upstream regulators was also investigated by real-time PCR. miR-375 and miR-10a were significantly overexpressed, while miR-455 was underexpressed in medullary thyroid carcinomas. Expression of all 3 miRNAs was validated in the larger cohort of cases (miR-375, p = 3.3 x 10(-26); miR-10a, p = 5.6 x 10(-14); miR-455, p = 2.4 x 10(-4)). No significant differences in miRNA expression were found between RET mutation positive and negative tumors nor between sporadic and hereditary tumors. Expression of the potential downstream targets of miR-375, YAP1 (a growth inhibitor) and SLC16a2 (a transporter of thyroid hormone), was down-regulated in the tumors suggesting that miR-375 is a negative regulator of the expression of these genes. Thus, differential expression of miR-375, miR-10a and miR-455 may be important for tumor development and/or reflect C-cell lineage of medullary thyroid carcinoma. Furthermore, the growth inhibitor YAP1 is identified as a potential important downstream target of miR-375. (c) 2013 Elsevier Inc. All rights reserved.
C1 [Hudson, Jena; Duncavage, Eric; Chernock, Rebecca D.] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63110 USA.
[Tamburrino, Anna; Salerno, Paolo] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Xi, Liqiang; Raffeld, Mark] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Moley, Jeffrey] Washington Univ, Dept Surg, Sch Med, St Louis, MO 63110 USA.
[Chernock, Rebecca D.] Washington Univ, Dept Otolaryngol Head & Neck Surg, Sch Med, St Louis, MO 63110 USA.
RP Chernock, RD (reprint author), Washington Univ, Dept Pathol & Immunol, Sch Med, 660 S Euclid Ave,Campus Box 8118, St Louis, MO 63110 USA.
EM rchernock@path.wustl.edu
FU NCI Cancer Center [P30 CA91842]; ICTS/CTSA grant from the National
Center for Research Resources (NCRR), a component of the National
Institutes of Health (NIH) [UL1RR024992]; NIH Roadmap for Medical
Research
FX We thank Xiaopei Zhu M.D. for technical assistance with the PCR
experiments and James S Lewis Jr. for critical review of the manuscript.
We also thank Chris Sawyer and the Washington University Genome
Technology Access Core (GTAC) for their assistance in running the PCR
arrays. The GTAC is partially supported by NCI Cancer Center support
grant #P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA grant
#UL1RR024992 from the National Center for Research Resources (NCRR), a
component of the National Institutes of Health (NIH), and NIH Roadmap
for Medical Research.
NR 33
TC 24
Z9 30
U1 0
U2 16
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4800
J9 EXP MOL PATHOL
JI Exp. Mol. Pathol.
PD AUG
PY 2013
VL 95
IS 1
BP 62
EP 67
DI 10.1016/j.yexmp.2013.05.001
PG 6
WC Pathology
SC Pathology
GA 185TU
UT WOS:000321994000010
PM 23685355
ER
PT J
AU Dean, A
AF Dean, Ann
TI FUNCTIONAL ORGANIZATION OF beta-GLOBIN LOCUS CHROMATIN LOOP OVER LONG
DISTANCES
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Scientific Meeting of the
International-Society-for-Experimental-Hematology-and-Stem-Cells (ISEH)
CY AUG 22-25, 2013
CL Vienna, AUSTRIA
SP Int Soc Expt Hematol and Stem Cells (ISEH)
C1 [Dean, Ann] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-472X
J9 EXP HEMATOL
JI Exp. Hematol.
PD AUG
PY 2013
VL 41
IS 8
SU 1
BP S7
EP S7
PG 1
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA 199VY
UT WOS:000323024800024
ER
PT J
AU Haetscher, N
Feuermann, Y
Wingert, S
Thalheimer, F
Weiser, C
Kowarsch, A
Theis, F
Schroeder, T
Rieger, M
Hennighausen, L
AF Haetscher, Nadine
Feuermann, Yonatan
Wingert, Susanne
Thalheimer, Frederic
Weiser, Christian
Kowarsch, Andreas
Theis, Fabian
Schroeder, Timm
Rieger, Michael
Hennighausen, Lothar
TI THE CYTOKINE-INDUCED MICRORNA193B MODULATES CKIT EXPRESSION AND STAT5
SIGNALING
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Scientific Meeting of the
International-Society-for-Experimental-Hematology-and-Stem-Cells (ISEH)
CY AUG 22-25, 2013
CL Vienna, AUSTRIA
SP Int Soc Expt Hematol and Stem Cells (ISEH)
C1 [Haetscher, Nadine; Wingert, Susanne; Thalheimer, Frederic; Rieger, Michael] JW Goethe Univ Clin Frankfurt, Frankfurt, Hessen, Germany.
[Haetscher, Nadine; Wingert, Susanne; Thalheimer, Frederic; Rieger, Michael] Georg Speyer Haus, Stem Cell Biol & Stem Cell Therapy, Frankfurt, Germany.
[Feuermann, Yonatan; Hennighausen, Lothar] NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA.
[Kowarsch, Andreas; Theis, Fabian] Helmholtz Zentrum Munchen, Inst Bioinformat, Neuherberg, Germany.
[Schroeder, Timm] Helmholtz Zentrum Munchen, Stem Cell Dynam Res Unit, Neuherberg, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-472X
J9 EXP HEMATOL
JI Exp. Hematol.
PD AUG
PY 2013
VL 41
IS 8
SU 1
BP S45
EP S45
PG 1
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA 199VY
UT WOS:000323024800159
ER
PT J
AU Thalheimer, F
Wingert, S
De Giacomo, P
Kowarsch, A
Theis, F
Hennighausen, L
Schroeder, T
Rieger, M
AF Thalheimer, Frederic
Wingert, Susanne
De Giacomo, Pangrzio
Kowarsch, Andreas
Theis, Fabian
Hennighausen, Lothar
Schroeder, Timm
Rieger, Michael
TI EXTRINSICALLY REGULATED GADD45 gamma BALANCES HEMATOPOIETIC STEM CELL
SELF-RENEWAL AND DIFFERENTIATION
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Meeting Abstract
CT 42nd Annual Scientific Meeting of the
International-Society-for-Experimental-Hematology-and-Stem-Cells (ISEH)
CY AUG 22-25, 2013
CL Vienna, AUSTRIA
SP Int Soc Expt Hematol and Stem Cells (ISEH)
C1 [Thalheimer, Frederic; Wingert, Susanne; De Giacomo, Pangrzio; Rieger, Michael] Goethe Univ Hosp Frankfurt, LOEWE Ctr Cell & Gene Therapy, Frankfurt, Germany.
[Thalheimer, Frederic; Wingert, Susanne; Rieger, Michael] Georg Speyer Haus, Frankfurt, Germany.
[Kowarsch, Andreas; Theis, Fabian] Helmholtz Zentrum Munchen, Inst Bioinformat, Neuherberg, Germany.
[Hennighausen, Lothar] NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD USA.
[Schroeder, Timm] Helmholtz Zentrum Munchen, Stem Cell Dynam Res Unit, Neuherberg, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-472X
J9 EXP HEMATOL
JI Exp. Hematol.
PD AUG
PY 2013
VL 41
IS 8
SU 1
BP S41
EP S41
PG 1
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA 199VY
UT WOS:000323024800143
ER
PT J
AU Yardeni, T
Jacobs, K
Niethamer, TK
Ciccone, C
Anikster, Y
Kurochkina, N
Gahl, WA
Huizing, M
AF Yardeni, Tal
Jacobs, Katherine
Niethamer, Terren K.
Ciccone, Carla
Anikster, Yair
Kurochkina, Natalya
Gahl, William A.
Huizing, Marjan
TI Murine isoforms of UDP-GlcNAc 2-epimerase/ManNAc kinase: Secondary
structures, expression profiles, and response to ManNAc therapy
SO GLYCOCONJUGATE JOURNAL
LA English
DT Article
DE GNE myopathy; Isoforms; Mouse; UDP-GlcNAc 2-epimerase/ManNAc kinase
ID ACETYLGLUCOSAMINE 2-EPIMERASE/N-ACETYLMANNOSAMINE KINASE; INCLUSION-BODY
MYOPATHY; SIALIC-ACID BIOSYNTHESIS; SINGLE PATIENT RESPONSE; GNE GENE
LIPOPLEX; STRUCTURE PREDICTION; KEY ENZYME; N-ACETYLMANNOSAMINE;
FRAGMENT DATABASE; CRYSTAL-STRUCTURE
AB The bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) catalyzes the first two committed steps in sialic acid synthesis. Non-allosteric GNE gene mutations cause the muscular disorder GNE myopathy (also known as hereditary inclusion body myopathy), whose exact pathology remains unknown. Increased knowledge of GNE regulation, including isoform regulation, may help elucidate the pathology of GNE myopathy. While eight mRNA transcripts encoding human GNE isoforms are described, we only identified two mouse Gne mRNA transcripts, encoding mGne1 and mGne2, homologous to human hGNE1 and hGNE2. Orthologs of the other human isoforms were not identified in mice. mGne1 appeared as the ubiquitously expressed, major mouse isoform. The mGne2 encoding transcript is differentially expressed and may act as a tissue-specific regulator of sialylation. mGne2 expression appeared significantly increased the first 2 days of life, possibly reflecting the high sialic acid demand during this period. Tissues of the knock-in Gne p.M712T mouse model had similar mGne transcript expression levels among genotypes, indicating no effect of the mutation on mRNA expression. However, upon treatment of these mice with N-acetylmannosamine (ManNAc, a Gne substrate, sialic acid precursor, and proposed therapy for GNE myopathy), Gne transcript expression, in particular mGne2, increased significantly, likely resulting in increased Gne enzymatic activities. This dual effect of ManNAc supplementation (increased flux through the sialic acid pathway and increased Gne activity) needs to be considered when treating GNE myopathy patients with ManNAc. In addition, the existence and expression of GNE isoforms needs consideration when designing other therapeutic strategies for GNE myopathy.
C1 [Yardeni, Tal; Jacobs, Katherine; Niethamer, Terren K.; Ciccone, Carla; Gahl, William A.; Huizing, Marjan] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Yardeni, Tal; Anikster, Yair] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
[Kurochkina, Natalya] Sch Theoret Modeling, Dept Biophys, Chevy Chase, MD 20825 USA.
RP Huizing, M (reprint author), NHGRI, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1851 Bld 10,Rm 10C103, Bethesda, MD 20892 USA.
EM mhuizing@mail.nih.gov
FU National Human Genome Research Institute, National Institutes of Health,
Bethesda, Maryland, United States; School of Theoretical Modeling, Chevy
Chase, Maryland, United States
FX We greatly appreciate the expert laboratory work of Dr. Shelley
Hoogstraten-Miller, Katherine Berger, Katherine Patzel, and Adrian
Astiz-Martinez. The authors thank Theresa Calhoun for her skilled
assistance with mouse maintenance. We thank the HIBM Research group
(Encino, CA) for providing the knock-in Gne p. M712T mouse model. This
work was performed in partial fulfillment of the requirements for a PhD
degree of T.Y., Sackler Faculty of Medicine, Tel Aviv University,
Israel. This study was supported by the Intramural Research Program of
the National Human Genome Research Institute, National Institutes of
Health, Bethesda, Maryland, United States (T.Y., K.J., T.K.N., C. C., W.
A. G., and M. H.) and Research Funds of The School of Theoretical
Modeling, Chevy Chase, Maryland, United States (N.K.).
NR 41
TC 1
Z9 1
U1 0
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0282-0080
J9 GLYCOCONJUGATE J
JI Glycoconjugate J.
PD AUG
PY 2013
VL 30
IS 6
BP 609
EP 618
DI 10.1007/s10719-012-9459-1
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 190IN
UT WOS:000322332900007
PM 23266873
ER
PT J
AU Howden, R
Cooley, I
Van Dodewaard, C
Arthur, S
Cividanes, S
Leamy, L
Hartzell, KM
Gladwell, W
Martin, J
Scott, G
Ray, M
Mishina, Y
AF Howden, R.
Cooley, I.
Van Dodewaard, C.
Arthur, S.
Cividanes, S.
Leamy, L.
Hartzell, K. McCann
Gladwell, W.
Martin, J.
Scott, G.
Ray, M.
Mishina, Y.
TI Cardiac responses to 24 hrs hyperoxia in Bmp2 and Bmp4 heterozygous mice
SO INHALATION TOXICOLOGY
LA English
DT Article
DE Bone morphogenetic protein; electrophysiology; oxidative stress
ID HEART-RATE-VARIABILITY; BONE MORPHOGENETIC PROTEIN-2; OXIDATIVE STRESS;
OXYGEN-THERAPY; PARASYMPATHETIC REACTIVATION;
ATRIOVENTRICULAR-CONDUCTION; QT INTERVAL; MOUSE; INJURY; DISEASE
AB Background: Hyperoxia or clinical oxygen (O-2) therapy is known to result in increased oxidative burden. Therefore, understanding susceptibility to hyperoxia exposure is clinically important. Bone morphogenetic proteins (BMPs) 2 and 4 are involved in cardiac development and may influence responses to hyperoxia.
Methods: Bmp2(+/-), Bmp4(+/-) and wild-type mice were exposed to hyperoxia (100% O-2) for 24 hrs. Electrocardiograms (ECG) were recorded before and during exposure by radio-telemetry.
Results: At baseline, a significantly higher low frequency (LF) and total power (TP) heart rate variability (HRV) were found in Bmp2(+/-) mice only (p<0.05). Twenty-four hours hyperoxia-induced strain-independent reductions in heart rate, QTcB and ST-interval and increases in QRS, LF HRV and standard deviation of RR-intervals were observed. In Bmp4(+/-) mice only, increased PR-interval (PR-I) (24 hrs), P-wave duration (P-d; 18 and 21-24 hrs), PR-I minus P-d (PR-Pd; 24 hrs) and root of the mean squared differences of successive RR-intervals (24 hrs) were found during hyperoxia (p50.05).
Discussion: Elevated baseline LF and TP HRV in Bmp2(+/-) mice suggests an altered autonomic nervous system regulation of cardiac function in these mice. However, this was not related to strain specific differences in responses to 24 hrs hyperoxia. During hyperoxia, Bmp4(+/-) mice were the most susceptible in terms of atrioventricular conduction changes and risk of atrial fibrillation, which may have important implications for patients treated with O-2 who also harbor Bmp4 mutations. This study demonstrates significant ECG and HRV responses to 24 hrs hyperoxia in mice, which highlights the need to further work on the genetic mechanisms associated with cardiac susceptibility to hyperoxia.
C1 [Howden, R.; Cooley, I.; Van Dodewaard, C.; Arthur, S.; Cividanes, S.] Univ N Carolina, Lab Syst Physiol, Dept Kinesiol, Charlotte, NC 28223 USA.
[Leamy, L.] Univ N Carolina, Dept Biol, Charlotte, NC 28223 USA.
[Hartzell, K. McCann; Scott, G.; Ray, M.; Mishina, Y.] NIEHS, Knockout Core, Durham, NC USA.
[Gladwell, W.; Martin, J.] NIEHS, Lab Resp Biol, Durham, NC USA.
[Hartzell, K. McCann; Mishina, Y.] NIEHS, Lab Reprod & Dev Toxicol, Durham, NC USA.
[Mishina, Y.] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA.
RP Howden, R (reprint author), Univ N Carolina, Lab Syst Physiol, Dept Kinesiol, Charlotte, NC 28223 USA.
EM rhowden@uncc.edu
FU National Institutes of Health [ES071003-11]
FX This study is supported by the National Institutes of Health
(ES071003-11 to Y.M.).
NR 56
TC 0
Z9 0
U1 0
U2 2
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0895-8378
J9 INHAL TOXICOL
JI Inhal. Toxicol.
PD AUG
PY 2013
VL 25
IS 9
BP 509
EP 516
DI 10.3109/08958378.2013.808287
PG 8
WC Toxicology
SC Toxicology
GA 194NK
UT WOS:000322639800004
PM 23876042
ER
PT J
AU Erdelyi, K
Pacher, P
Virag, L
Szabo, C
AF Erdelyi, Katalin
Pacher, Pal
Virag, Laszlo
Szabo, Csaba
TI Role of poly(ADP-ribosyl)ation in a 'two-hit' model of hypoxia and
oxidative stress in human A549 epithelial cells in vitro
SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
LA English
DT Article
DE hypoxia; oxidative stress; lung; poly(ADP-ribose) polymerase; epithelial
cell; glutathione; DNA damage
ID ADP-RIBOSE SYNTHETASE; PARP INHIBITORS; NITRIC-OXIDE; INJURY;
PEROXYNITRITE; ACTIVATION; GLUTATHIONE; POLYMERASE; DEPLETION; DEATH
AB A preceding hypoxic insult can sensitize the cells or the organism to a subsequent, second insult. The aim of the present study was to investigate the molecular mechanism of this phenomenon (often termed 'two-hit' injury paradigm), in an in vitro model of hypoxia/oxidative stress injury in A549 epithelial cells, with special emphasis on the role of the nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1) in the process. Pre-exposure of the cells to 24 h hypoxia significantly reduced intracellular glutathione (GSH) levels, reduced mitochondrial activity and adenosine triphosphate (ATP) levels. However pre-exposure to hypoxia failed to induce any change in PARP-1 expression and activation, DNA single-strand breaks or plasma membrane integrity. Pre-exposure to hypoxia markedly increased the sensitivity of the cells to subsequent oxidative stress-induced DNA damage. Hydrogen peroxide (H2O2) induced a concentration-dependent increase in DNA breakage, PARP activation, depletion of intracellular ATP, inhibition of mitochondrial activity and two distinct parameters that quantify the breakdown of plasma membrane integrity (propidium iodide uptake or lactate dehydrogenase release). PARP-1 activation played a significant role in the H2O2-induced cell death response because PARP activation, depletion of intracellular ATP, inhibition of mitochondrial activity, and the breakdown of plasma membrane integrity were attenuated in cells with permanently silenced PARP-1. Based on measurement of the endogenous antioxidant GSH, we hypothesized that the mechanism of hypoxia-mediated enhancement of H2O2 involves depletion of the GSH during the hypoxic period, which renders the cells more sensitive to a subsequent DNA single-strand break elicited by H2O2. DNA strand breakage then activates PARP-1, leading to the inhibition of mitochondrial function, depletion of ATP and cell necrosis. PARP-1 deficiency protects against the cytotoxicity, to a lesser degree, by protecting against GSH depletion during the hypoxic period, and, to a larger degree, by maintaining mitochondrial function and preserving intracellular ATP levels during the subsequent oxidative stress period.
C1 [Erdelyi, Katalin; Pacher, Pal; Virag, Laszlo; Szabo, Csaba] Univ Texas Med Branch, Dept Anesthesiol, Galveston, TX 77555 USA.
[Erdelyi, Katalin; Pacher, Pal] NIAAA, Sect Oxidat Stress & Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
[Virag, Laszlo] Univ Debrecen, Med & Hlth Sci Ctr, Dept Med Chem, H-4010 Debrecen, Hungary.
[Szabo, Csaba] Shriners Hosp Children Galveston, Galveston, TX 77550 USA.
RP Szabo, C (reprint author), Univ Texas Med Branch, Dept Anesthesiol, 601 Harborside Dr,Bldg 21,Room 4-202D, Galveston, TX 77555 USA.
EM szabocsaba@aol.com
RI Pacher, Pal/B-6378-2008
OI Pacher, Pal/0000-0001-7036-8108
FU US National Institutes of Health [2P50 GM060338]
FX This study was supported by the US National Institutes of Health 2P50
GM060338 to C.S.
NR 40
TC 3
Z9 3
U1 0
U2 8
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1107-3756
EI 1791-244X
J9 INT J MOL MED
JI Int. J. Mol. Med.
PD AUG
PY 2013
VL 32
IS 2
BP 339
EP 346
DI 10.3892/ijmm.2013.1397
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 190VR
UT WOS:000322370800010
PM 23722590
ER
PT J
AU Haynie, DL
Farhat, T
Brooks-Russell, A
Wang, J
Barbieri, B
Iannotti, RJ
AF Haynie, Denise L.
Farhat, Tilda
Brooks-Russell, Ashley
Wang, Jing
Barbieri, Brittney
Iannotti, Ronald J.
TI Dating Violence Perpetration and Victimization Among U.S. Adolescents:
Prevalence, Patterns, and Associations With Health Complaints and
Substance Use
SO JOURNAL OF ADOLESCENT HEALTH
LA English
DT Article
DE Dating violence perpetration; Dating violence victimization; Physical
and verbal dating violence; Factor mixture model
ID SCHOOL-RELATED STRESS; ROMANTIC RELATIONSHIPS; PARTNER VIOLENCE;
MODEL-SELECTION; RISK; SYMPTOMS; EXPOSURE; IMPACT; ABUSE; WOMEN
AB Purpose: This research identified conceptually cohesive latent classes of youth dating violence (DV) and examined associations between covariates and classes by gender.
Methods: A nationally representative sample of 2,203 10th grade students completed assessments of physical and verbal DV victimization and perpetration, depressive symptoms, health complaints, and substance use. A Factor Mixture Model was used to identify patterns of DV. Gender differences among classes were examined for depressive symptoms, health complaints, and substance use.
Results: Prevalence of DV victimization was 35% and perpetration was 31%. A three-class model fit adequately and provided conceptual cohesion: Class 1 = non-involved (65%); Class 2 = victims/perpetrators of verbal DV (30%); and Class 3 = victims/perpetrators of verbal and physical DV (5%). Compared with Class 1 adolescents, those in Classes 2 and 3 were more likely to report depressive symptoms, psychological complaints, and alcohol use. Females in Classes 2 and 3 were also more likely to report physical complaints, cigarette use, and marijuana use. Among females involved in DV, those in Class 3 compared with Class 2 reported more depressive symptoms, physical and psychological complaints, and cigarette and marijuana use.
Conclusions: The three-class model distinguished involvement in verbal acts from involvement in verbal and physical acts. Adolescents involved in DV had similar probabilities of reporting perpetration and victimization, suggesting violence within relationships may be mutual. Involvement in DV was associated with more health issues and concurrent problem behaviors. For females in particular, the increased involvement in DV was associated with other health indicators. Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine.
C1 [Haynie, Denise L.; Farhat, Tilda; Brooks-Russell, Ashley; Barbieri, Brittney; Iannotti, Ronald J.] Eunice Kennedy Shriver Inst Child Hlth & Human De, Prevent Res Branch, Bethesda, MD 20892 USA.
[Wang, Jing] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
RP Haynie, DL (reprint author), Eunice Kennedy Shriver Inst Child Hlth & Human De, Prevent Res Branch, 6100 Execut Blvd,Rm 7B13 MSC 7510, Bethesda, MD 20892 USA.
EM Denise_Haynie@nih.gov
RI Brooks-Russell, Ashley/F-8364-2014;
OI Brooks-Russell, Ashley/0000-0002-7728-8423; Haynie,
Denise/0000-0002-8270-6079
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [HHSN267200800009C]; National Heart, Lung and Blood
Institute (NHLBI); National Institute on Alcohol Abuse and Alcoholism
(NIAAA); Maternal and Child Health Bureau (MCHB) of the Health Resources
and Services Administration (HRSA)
FX Thank you to Faith Summersett-Ringgold and Michele Kiely, Dr.P.H., for
their contributions to this paper. This project (contract number
HHSN267200800009C) was supported in part by the Intramural Research
Program of the Eunice Kennedy Shriver National Institute of Child Health
and Human Development (NICHD), and the National Heart, Lung and Blood
Institute (NHLBI), the National Institute on Alcohol Abuse and
Alcoholism (NIAAA), and Maternal and Child Health Bureau (MCHB) of the
Health Resources and Services Administration (HRSA), with supplemental
support from the National Institute on Drug Abuse (NIDA).
NR 39
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1054-139X
J9 J ADOLESCENT HEALTH
JI J. Adolesc. Health
PD AUG
PY 2013
VL 53
IS 2
BP 194
EP 201
DI 10.1016/j.jadohealth.2013.02.008
PG 8
WC Psychology, Developmental; Public, Environmental & Occupational Health;
Pediatrics
SC Psychology; Public, Environmental & Occupational Health; Pediatrics
GA 186SM
UT WOS:000322065100007
PM 23664626
ER
PT J
AU Iannotti, RJ
Wang, J
AF Iannotti, Ronald J.
Wang, Jing
TI Patterns of Physical Activity, Sedentary Behavior, and Diet in U.S.
Adolescents
SO JOURNAL OF ADOLESCENT HEALTH
LA English
DT Article
DE Adolescent obesity; Physical activity; Sedentary behavior; Diet; Body
mass index; Television
ID LATENT CLASS ANALYSIS; BODY-MASS INDEX; METABOLIC SYNDROME; US
ADOLESCENTS; HEALTH; CHILDREN; OBESITY; DETERMINANTS; ASSOCIATIONS;
RELIABILITY
AB Objective: To identify patterns in adolescents' obesogenic behaviors and their relations to physical and psychological health.
Methods: A nationally representative sample of 9,174 U. S. adolescents ages 11 to 16 years was surveyed on physical activity (PA), screen-based sedentary behavior (SB), frequency of consumption of healthy and unhealthy food items, weight status, weight control behavior, depression, physical symptoms, body dissatisfaction, overall health, and life satisfaction. Latent class analysis was used to identify patterns of PA, SB, and diet.
Results: A model with three latent classes best fit the data: Class 1 with high PA and high fruit and vegetable intake and low SB and intake of sweets, soft drinks, chips, and fries; Class 2 with high SB and high intake of sweets, soft drinks, chips, and fries; and Class 3 with low PA, low fruit and vegetable intake, and low intake of sweets, chips, and fries. Membership in the three classes was related to age, gender, race/ethnicity, and socioeconomic status. In addition, members of Class 1 (26.5%) were more likely to be of normal weight status and to fare well on most of the other health indices; of Class 2 (26.4%) were less likely to be trying to lose weight but scored poorly on the mental health indices; and of Class 3 (47.2%) were less likely to be underweight and reported greater body dissatisfaction.
Conclusions: Three prevalent patterns of adolescent obesogenic behaviors were identified and these patterns related to weight status, depression, and other indicators of physical and psychological health. Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine.
C1 [Iannotti, Ronald J.; Wang, Jing] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Bethesda, MD 20892 USA.
RP Iannotti, RJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, 6100 Execut Blvd,7B05, Bethesda, MD 20892 USA.
EM iannottr@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [N01-HD-5-3401]; Maternal and Child Health Bureau of the
Health Resources and Services Administration
FX This research was supported in part by the intramural research program
of the Eunice Kennedy Shriver National Institute of Child Health and
Human Development (Contract N01-HD-5-3401) and by the Maternal and Child
Health Bureau of the Health Resources and Services Administration with
the first author (Ronald J. Iannotti) as principal investigator. This
work was previously reported at the International Society for Behavioral
Nutrition and Physical Activity.
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U2 42
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1054-139X
J9 J ADOLESCENT HEALTH
JI J. Adolesc. Health
PD AUG
PY 2013
VL 53
IS 2
BP 280
EP 286
DI 10.1016/j.jadohealth.2013.03.007
PG 7
WC Psychology, Developmental; Public, Environmental & Occupational Health;
Pediatrics
SC Psychology; Public, Environmental & Occupational Health; Pediatrics
GA 186SM
UT WOS:000322065100020
PM 23642973
ER
PT J
AU Ives, ML
Ma, CS
Palendira, U
Chan, A
Bustamante, J
Boisson-Dupuis, S
Arkwright, PD
Engelhard, D
Averbuch, D
Magdorf, K
Roesler, J
Peake, J
Wong, M
Adelstein, S
Choo, S
Smart, JM
French, MA
Fulcher, DA
Cook, MC
Picard, C
Durandy, A
Tsumura, M
Kobayashi, M
Uzel, G
Casanova, JL
Tangye, SG
Deenick, EK
AF Ives, Megan L.
Ma, Cindy S.
Palendira, Umaimainthan
Chan, Anna
Bustamante, Jacinta
Boisson-Dupuis, Stephanie
Arkwright, Peter D.
Engelhard, Dan
Averbuch, Diana
Magdorf, Klaus
Roesler, Joachim
Peake, Jane
Wong, Melanie
Adelstein, Stephen
Choo, Sharon
Smart, Joanne M.
French, Martyn A.
Fulcher, David A.
Cook, Matthew C.
Picard, Capucine
Durandy, Anne
Tsumura, Miyuki
Kobayashi, Masao
Uzel, Gulbu
Casanova, Jean-Laurent
Tangye, Stuart G.
Deenick, Elissa K.
TI Signal transducer and activator of transcription 3 (STAT3) mutations
underlying autosomal dominant hyper-IgE syndrome impair human CD8(+)
T-cell memory formation and function
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Autosomal dominant hyper-IgE syndrome; STAT3; STAT1; IL-21; human CD8(+)
T cells; memory; differentiation
ID CHRONIC VIRAL-INFECTION; COMMON GAMMA-CHAIN; IL-21 RECEPTOR; IN-VIVO;
IFN-GAMMA; ADAPTIVE IMMUNITY; INBORN-ERRORS; CUTTING EDGE; NK CELLS;
IL-15
AB Background: The capacity of CD8(+) T cells to control infections and mediate antitumor immunity requires the development and survival of effector and memory cells. IL-21 has emerged as a potent inducer of CD8(+) T-cell effector function and memory development in mouse models of infectious disease. However, the role of IL-21 and associated signaling pathways in protective CD8(+) T-cell immunity in human subjects is unknown.
Objective: We sought to determine which signaling pathways mediate the effects of IL-21 on human CD8(+) T cells and whether defects in these pathways contribute to disease pathogenesis in patients with primary immunodeficiencies caused by mutations in components of the IL-21 signaling cascade.
Methods: Human primary immunodeficiencies resulting from monogenic mutations provide a unique opportunity to assess the requirement for particular molecules in regulating human lymphocyte function. Lymphocytes from patients with loss-offunction mutations in signal transducer and activator of transcription 1 (STAT1), STAT3, or IL-21 receptor (IL21R) were used to assess the respective roles of these genes in human CD8(+) T-cell differentiation in vivo and in vitro.
Results: Mutations in STAT3 and IL21R, but not STAT1, led to a decrease in multiple memory CD8(+) T-cell subsets in vivo, indicating that STAT3 signaling, possibly downstream of IL21R, regulates the memory cell pool. Furthermore, STAT3 was important for inducing the lytic machinery in IL-21-stimulated naive CD8(+) T cells. However, this defect was overcome by T-cell receptor engagement.
Conclusion: The IL-21R/STAT3 pathway is required for many aspects of human CD8(+) T-cell behavior but in some cases can be compensated byother signals. This helps explain the relatively mild susceptibility to viral disease observed in STAT3-and IL-21Rdeficient subjects.
C1 [Tangye, Stuart G.; Deenick, Elissa K.] St Vincents Hosp, Garvan Inst Med Res, Immunol Res Program, Darlinghurst, NSW 2010, Australia.
[Ives, Megan L.; Ma, Cindy S.; Palendira, Umaimainthan; Tangye, Stuart G.; Deenick, Elissa K.] Univ New S Wales, St Vincents Clin Sch, Sydney, NSW, Australia.
[Bustamante, Jacinta; Boisson-Dupuis, Stephanie; Picard, Capucine; Casanova, Jean-Laurent] Univ Paris 05, Necker Med Sch, Necker Branch,Sorbonne Paris Cite, Lab Human Genet Infect Dis,INSERM U90,Inst Imagin, Paris, France.
[Bustamante, Jacinta; Picard, Capucine] Hop Necker Enfants Malad, AP HP, Study Ctr Primary Immunodeficiencies, Paris, France.
[Boisson-Dupuis, Stephanie; Casanova, Jean-Laurent] Rockefeller Univ, Rockefeller Branch, Lab Human Genet Infect Dis, New York, NY 10021 USA.
[Arkwright, Peter D.] Univ Manchester, Royal Manchester Childrens Hospital;, Manchester M13 9PL, Lancs, England.
[Engelhard, Dan; Averbuch, Diana] Hadassah Hebrew Univ, Med Ctr, Dept Pediatr & Pediat Infect Dis, Jerusalem, Israel.
[Magdorf, Klaus] Humboldt Univ, Dept Pediat Pneumol & Immunol, Charite, Berlin, Germany.
Univ Clin Carl Gustav Carus, Dept Pediat, Dresden, Germany.
[Peake, Jane] Royal Childrens Hosp Brisbane, Dept Paediat & Child Hlth, Brisbane, Qld, Australia.
[Wong, Melanie] Childrens Hosp Westmead, Dept Immunol, Westmead, NSW, Australia.
[Adelstein, Stephen] Royal Prince Alfred Hosp, Sydney, NSW, Australia.
[Smart, Joanne M.] Royal Childrens Hosp Melbourne, Dept Allergy & Immunol, Melbourne, Vic, Australia.
[French, Martyn A.] Royal Perth Hosp, Dept Clin Immunol, Melbourne, Vic, Australia.
[French, Martyn A.] Univ Western Australia, Sch Pathol & Lab Med, Perth, WA 6009, Australia.
[Fulcher, David A.] Westmead Hosp, Inst Clin Pathol & Med Res, Dept Immunol, Westmead, NSW, Australia.
[Cook, Matthew C.] Australian Natl Univ, Sch Med, Canberra, ACT, Australia.
[Cook, Matthew C.] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia.
[Cook, Matthew C.] Canberra Hosp, Dept Immunol, Canberra, ACT, Australia.
[Durandy, Anne] Hop Necker Enfants Malad, INSERM, Unite U768, Paris, France.
[Durandy, Anne] Univ Paris 05, Sorbonne Paris Cite, Inst Imagine, Paris, France.
[Tsumura, Miyuki; Kobayashi, Masao] Hiroshima Univ, Grad Sch Biomed Sci, Dept Pediat, Hiroshima 730, Japan.
[Uzel, Gulbu] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Deenick, EK (reprint author), St Vincents Hosp, Garvan Inst Med Res, Immunol Res Program, 384 Victoria St, Darlinghurst, NSW 2010, Australia.
EM e.deenick@garvan.org.au
RI Tangye, Stuart/H-4023-2014; Peake, Jane/B-4488-2011; Adelstein,
Stephen/I-7936-2016;
OI Adelstein, Stephen/0000-0001-7221-6298; Deenick,
Elissa/0000-0002-9271-0004; Picard, Capucine/0000-0001-8788-5056;
Arkwright, Peter/0000-0002-7411-5375
FU National Health and Medical Research Council (NHMRC) of Australia;
Cancer Council NSW; Rockefeller University Center for 541 Clinical and
Translational science [5UL1RR024143]; NHMRC of Australia
FX Supported by project and program grants from the National Health and
Medical Research Council (NHMRC) of Australia (to E. K. D., S. G. T., C.
S. M., D. A. F., and M. C. C.), Cancer Council NSW (to S. G. T. and U.
P.), and Rockefeller University Center for 541 Clinical and
Translational science (5UL1RR024143, to J.-L. C.). C. S. M. is a
recipient of a Career Development Fellowship and S. G. T. is a recipient
of a Principal Research Fellowship from the NHMRC of Australia.
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U2 11
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD AUG
PY 2013
VL 132
IS 2
BP 400
EP +
DI 10.1016/j.jaci.2013.05.029
PG 21
WC Allergy; Immunology
SC Allergy; Immunology
GA 194KL
UT WOS:000322631700018
PM 23830147
ER
PT J
AU Milner, JD
AF Milner, Joshua D.
TI Patients informing immunobiology: How disorders of IL-21 receptor
signaling unravel pathways of CD8 T-cell function
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Editorial Material
ID MEMORY
C1 NIAID, Allerg Inflammat Unit, NIH, Lab Allerg Dis, Bethesda, MD 20892 USA.
RP Milner, JD (reprint author), NIAID, Allerg Inflammat Unit, NIH, Lab Allerg Dis, 9000 Rockville Pike,NIH Bldg 10-11D03, Bethesda, MD 20892 USA.
EM jdmilner@niaid.nih.gov
FU Intramural NIH HHS [ZIA AI001099-04]
NR 9
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Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD AUG
PY 2013
VL 132
IS 2
BP 412
EP 413
DI 10.1016/j.jaci.2013.06.024
PG 2
WC Allergy; Immunology
SC Allergy; Immunology
GA 194KL
UT WOS:000322631700019
PM 23905919
ER
PT J
AU Taiwo, B
Matining, RM
Zheng, L
Lederman, MM
Rinaldo, CR
Kim, PS
Berzins, BI
Kuritzkes, DR
Jennings, A
Eron, JJ
Wilson, CC
AF Taiwo, Babafemi
Matining, Roy M.
Zheng, Lu
Lederman, Michael M.
Rinaldo, Charles R.
Kim, Peter S.
Berzins, Baiba I.
Kuritzkes, Daniel R.
Jennings, Amy
Eron, Joseph J., Jr.
Wilson, Cara C.
TI Associations of T cell activation and inflammatory biomarkers with
virological response to darunavir/ritonavir plus raltegravir therapy
SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
LA English
DT Article
DE nucleos(t)ide sparing; soluble CD14; microbial translocation
ID ANTIRETROVIRAL THERAPY; HIV-INFECTION; DISEASE PROGRESSION; IMMUNE
ACTIVATION; PLASMA-LEVELS; RECONSTITUTION; CD4(+)
AB One of the goals of antiretroviral therapy (ART) is to attenuate HIV-induced systemic immune activation and inflammation. We determined the dynamics of biomarkers of immune activation, microbial translocation and inflammation during initial ART with a nucleos(t)ide-sparing regimen of darunavir/ritonavir plus raltegravir. We also evaluated associations between these biomarkers and the virological response to the regimen.
We determined baseline and week 24 and 48 levels of CD4 and CD8 T cell activation ( HLA-DR/CD38), interleukin-6 (IL-6), interferon--inducible protein-10 (IP-10), soluble CD14 (sCD14), D-dimer and lipopolysaccharide. Associations between the biomarkers at baseline were assessed using Spearmans rank correlation. The Wilcoxon signed rank test analysed changes from baseline. Comparisons between groups were made using the Wilcoxon rank sum test, and Cox proportional hazards models assessed predictors of virological failure (VF).
Assays were completed on 107 of 112 subjects after excluding five subjects who had only baseline samples. The subjects included were 94 (88) men with a median age of 37 years, a median baseline CD4 count of 261.5 cells/mm(3) and a median baseline viral load (VL) of 75 876 copies/mL. Subjects with a baseline VL 100000 copies/mL had higher baseline T cell activation, IL-6, IP-10, sCD14 and D-dimer. These biomarkers declined during treatment (P0.05). Although subjects who experienced VF had higher baseline CD4 T cell activation (P0.035), only baseline VL independently predicted VF (hazard ratio for 100000 versus 100000 copies/mL was 4.55.6, P0.002).
Darunavir/ritonavir plus raltegravir attenuated immune activation, inflammation and microbial translocation. T cell activation remained higher in subjects with VF than those without. Baseline VL 100000 copies/mL remained the primary driver of VF.
C1 [Taiwo, Babafemi; Berzins, Baiba I.] Northwestern Univ, Div Infect Dis, Chicago, IL 60611 USA.
[Matining, Roy M.; Zheng, Lu] Harvard Univ, Sch Publ Hlth, Stat Data Anal Ctr, Boston, MA 02115 USA.
[Lederman, Michael M.] Case Western Reserve Univ, Dept Med, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA.
[Rinaldo, Charles R.] Univ Pittsburgh, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA.
[Kim, Peter S.] NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA.
[Kuritzkes, Daniel R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Infect Dis, Cambridge, MA 02139 USA.
[Jennings, Amy] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA.
[Eron, Joseph J., Jr.] Univ N Carolina, Div Infect Dis, Chapel Hill, NC 27514 USA.
[Wilson, Cara C.] Univ Colorado, Div Infect Dis, Denver, CO 80262 USA.
RP Taiwo, B (reprint author), Northwestern Univ, Div Infect Dis, Chicago, IL 60611 USA.
EM b-taiwo@northwestern.edu
FU National Institute of Allergy and Infectious Diseases [U01AI068636,
U01AI68634]; National Institute of Mental Health (NIMH); National
Institute of Dental and Craniofacial Research (NIDCR); National Center
for Research Resources
FX Awards U01AI068636 and U01AI68634 from the National Institute of Allergy
and Infectious Diseases, the National Institute of Mental Health (NIMH)
and the National Institute of Dental and Craniofacial Research (NIDCR)
supported this study. The study was also supported in part by grants
funded by the National Center for Research Resources. Merck provided
raltegravir and Janssen Therapeutics provided darunavir.
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U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-7453
J9 J ANTIMICROB CHEMOTH
JI J. Antimicrob. Chemother.
PD AUG
PY 2013
VL 68
IS 8
BP 1857
EP 1861
DI 10.1093/jac/dkt120
PG 5
WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
GA 191JO
UT WOS:000322409400023
PM 23599363
ER
PT J
AU Miller, SC
Porcella, SF
Raffel, SJ
Schwan, TG
Barbour, AG
AF Miller, Shelley Campeau
Porcella, Stephen F.
Raffel, Sandra J.
Schwan, Tom G.
Barbour, Alan G.
TI Large Linear Plasmids of Borrelia Species That Cause Relapsing Fever
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID LYME-DISEASE SPIROCHETE; WHOLE-GENOME SEQUENCES; OUTER SURFACE PROTEIN;
FACTOR-H; ANTIGENIC VARIATION; ADAPTIVE EVOLUTION; CIRCULAR-PLASMID;
PURINE SALVAGE; IN-VITRO; BURGDORFERI
AB Borrelia species of relapsing fever (RF) and Lyme disease (LD) lineages have linear chromosomes and both linear and circular plasmids. Unique to RF species, and little characterized to date, are large linear plasmids of similar to 160 kb, or similar to 10% of the genome. By a combination of Sanger and next-generation methods, we determined the sequences of large linear plasmids of two New World species: Borrelia hermsii, to completion of its 174-kb length, and B. turicatae, partially to 114 kb of its 150 kb. These sequences were then compared to corresponding sequences of the Old World species B. duttonii and B. recurrentis and to plasmid sequences of LD Borrelia species. The large plasmids were largely colinear, except for their left ends, about 27 kb of which was inverted in New World species. Approximately 60% of the B. hermsii lp174 plasmid sequence was repetitive for 6 types of sequence, and half of its open reading frames encoded hypothetical proteins not discernibly similar to proteins in the database. The central similar to 25 kb of all 4 linear plasmids was syntenic for orthologous genes for plasmid maintenance or partitioning in Borrelia species. Of all the sequenced linear and circular plasmids in Borrelia species, the large plasmid's putative partition/replication genes were most similar to those of the 54-kb linear plasmids of LD species. Further evidence for shared ancestry was the observation that two of the hypothetical proteins were predicted to be structurally similar to the LD species' CspA proteins, which are encoded on the 54-kb plasmids.
C1 [Miller, Shelley Campeau; Barbour, Alan G.] Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA.
[Miller, Shelley Campeau; Barbour, Alan G.] Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA.
[Miller, Shelley Campeau; Barbour, Alan G.] Univ Calif Irvine, Dept Ecol & Evolutionary Biol, Irvine, CA 92717 USA.
[Porcella, Stephen F.] NIAID, Genom Unit, Res Technol Branch, Rocky Mt Labs,NIH, Hamilton, MT USA.
[Raffel, Sandra J.; Schwan, Tom G.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA.
RP Miller, SC (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
EM smiller@mednet.ucla.edu
OI Barbour, Alan/0000-0002-0719-5248
FU NIH [AI24424]; National Institute of Allergy and Infectious Diseases
FX This work was supported by NIH grant AI24424 and the intramural program
of the National Institute of Allergy and Infectious Diseases.
NR 75
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U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
J9 J BACTERIOL
JI J. Bacteriol.
PD AUG
PY 2013
VL 195
IS 16
BP 3629
EP 3639
DI 10.1128/JB.00347-13
PG 11
WC Microbiology
SC Microbiology
GA 188VX
UT WOS:000322226100015
PM 23749977
ER
PT J
AU VanOrsdel, CE
Bhatt, S
Allen, RJ
Brenner, EP
Hobson, JJ
Jamil, A
Haynes, BM
Genson, AM
Hemm, MR
AF VanOrsdel, Caitlin E.
Bhatt, Shantanu
Allen, Rondine J.
Brenner, Evan P.
Hobson, Jessica J.
Jamil, Aqsa
Haynes, Brittany M.
Genson, Allyson M.
Hemm, Matthew R.
TI The Escherichia coli CydX Protein Is a Member of the CydAB Cytochrome bd
Oxidase Complex and Is Required for Cytochrome bd Oxidase Activity
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID TERMINAL OXIDASE; BACILLUS-SUBTILIS; QUINOL OXIDASE; GENE-PRODUCT;
IN-VITRO; OXYGEN; EXPRESSION; GROWTH; IDENTIFICATION; TRANSDUCTION
AB Cytochrome bd oxidase operons from more than 50 species of bacteria contain a short gene encoding a small protein that ranges from similar to 30 to 50 amino acids and is predicted to localize to the cell membrane. Although cytochrome bd oxidases have been studied for more than 70 years, little is known about the role of this small protein, denoted CydX, in oxidase activity. Here we report that Escherichia coli mutants lacking CydX exhibit phenotypes associated with reduced oxidase activity. In addition, cell membrane extracts from Delta cydX mutant strains have reduced oxidase activity in vitro. Consistent with data showing that CydX is required for cytochrome bd oxidase activity, copurification experiments indicate that CydX interacts with the CydAB cytochrome bd oxidase complex. Together, these data support the hypothesis that CydX is a subunit of the CydAB cytochrome bd oxidase complex that is required for complex activity. The results of mutation analysis of CydX suggest that few individual amino acids in the small protein are essential for function, at least in the context of protein overexpression. In addition, the results of analysis of the paralogous small transmembrane protein AppX show that the two proteins could have some overlapping functionality in the cell and that both have the potential to interact with the CydAB complex.
C1 [VanOrsdel, Caitlin E.; Allen, Rondine J.; Brenner, Evan P.; Hobson, Jessica J.; Jamil, Aqsa; Haynes, Brittany M.; Genson, Allyson M.; Hemm, Matthew R.] Towson Univ, Dept Biol Sci, Towson, MD 21252 USA.
[Bhatt, Shantanu] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD USA.
RP Hemm, MR (reprint author), Towson Univ, Dept Biol Sci, Towson, MD 21252 USA.
EM mhemm@towson.edu
FU National Institute of Allergies and Infectious Disease, National
Institutes of Health [1R15AI094548-01]; Eunice Kennedy Shriver National
Institute of Child Health and Human Development; Life Sciences
Foundation; Fisher College of Science and Mathematics; Towson University
FX This research was supported by an R15 grant (1R15AI094548-01) from the
National Institute of Allergies and Infectious Disease, National
Institutes of Health. It was also supported by funds to the Jess and
Mildred Fisher Endowed Chair of Biological Sciences at Towson
University, by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development, and by
postdoctoral fellowships from the Life Sciences Foundation (M.R.H.).
Students were supported by Undergraduate Research Grants from the Fisher
College of Science and Mathematics and from Towson University.
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U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
J9 J BACTERIOL
JI J. Bacteriol.
PD AUG
PY 2013
VL 195
IS 16
BP 3640
EP 3650
DI 10.1128/JB.00324-13
PG 11
WC Microbiology
SC Microbiology
GA 188VX
UT WOS:000322226100016
PM 23749980
ER
PT J
AU Bogoslovsky, T
Gong, YH
Maric, D
Qu, BX
Hallenbeck, J
Diaz-Arrastia, R
AF Bogoslovsky, Tanya
Gong, Yunhua
Maric, Dragan
Qu, Bao-Xi
Hallenbeck, John
Diaz-Arrastia, Ramon
TI A ROBUST METHOD OF ENUMERATION OF ENDOTHELIAL PROGENITOR AND ENDOTHELIAL
CELLS FROM PERIPHERAL BLOOD FOR MULTICENTER CLINICAL TRIALS
SO JOURNAL OF NEUROTRAUMA
LA English
DT Meeting Abstract
CT 31st Annual National Neurotrauma Symposium
CY AUG 04-07, 2013
CL Nashville, TN
C1 [Maric, Dragan; Hallenbeck, John] NINDS, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
J9 J NEUROTRAUM
JI J. Neurotrauma
PD AUG
PY 2013
VL 30
IS 15
BP A133
EP A133
PG 1
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA 191WY
UT WOS:000322446800248
ER
PT J
AU Buonora, JE
Mousseau, M
Latour, LL
Diaz-Arrastia, R
Pollard, HB
Rizoli, S
Baker, A
Rind, S
Mueller, GP
AF Buonora, John E.
Mousseau, Michael
Latour, Lawrence L.
Diaz-Arrastia, Ramon
Pollard, Harvey B.
Rizoli, Sandro
Baker, Andrew
Rind, Shawn
Mueller, Gregory P.
TI PEROXIREDOXIN 6: A NOVEL CANDIDATE BIOMARKER FOR TRAUMATIC BRAIN INJURY
(TBI)
SO JOURNAL OF NEUROTRAUMA
LA English
DT Meeting Abstract
CT 31st Annual National Neurotrauma Symposium
CY AUG 04-07, 2013
CL Nashville, TN
DE autoantigens; immune system; oxidative stress; profiling
C1 [Buonora, John E.; Mousseau, Michael; Pollard, Harvey B.; Mueller, Gregory P.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Latour, Lawrence L.] NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA.
[Diaz-Arrastia, Ramon] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
[Rizoli, Sandro] Sunnybrook Hlth Sci Ctr, Dept Surg & Crit Care Med, Toronto, ON, Canada.
[Baker, Andrew] Univ Toroto, St Michaels Hosp, Cara Phelan Ctr, Brain Injury Lab, Toronto, ON, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
J9 J NEUROTRAUM
JI J. Neurotrauma
PD AUG
PY 2013
VL 30
IS 15
BP A66
EP A67
PG 2
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA 191WY
UT WOS:000322446800122
ER
PT J
AU Dsurney, J
Butman, J
Latour, LL
van der Merwe, AJ
Constantin, A
Pham, D
Levy, S
Chan, L
AF Dsurney, John
Butman, John
Latour, Lawrence L.
van der Merwe, Andre J.
Constantin, Alexandra
Dzung Pham
Levy, Sarah
Chan, Leighton
TI ACUTE MRI IN THE EVALUATION OF TRAUMATIC BRAIN INJURY
SO JOURNAL OF NEUROTRAUMA
LA English
DT Meeting Abstract
CT 31st Annual National Neurotrauma Symposium
CY AUG 04-07, 2013
CL Nashville, TN
DE cognition; MRI; neuroimaging; neuropsychological; TBI
C1 [Dsurney, John; Levy, Sarah] NIH, Ctr Neurosci & Regenerat Med, Bethesda, MD USA.
[Butman, John; Constantin, Alexandra; Chan, Leighton] NIH, Bethesda, MD USA.
[Latour, Lawrence L.] NINDS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
J9 J NEUROTRAUM
JI J. Neurotrauma
PD AUG
PY 2013
VL 30
IS 15
BP A113
EP A113
PG 1
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA 191WY
UT WOS:000322446800211
ER
PT J
AU Pham, D
Chou, YY
Talbot, S
Kleper, V
Mongkolwat, P
Butman, J
AF Dzung Pham
Chou, Yi-Yu
Talbot, Skip
Kleper, Vladimir
Mongkolwat, Pattanasak
Butman, John
TI AIM: AN OPEN SOURCE SOFTWARE PLATFORM FOR ELECTRONIC ENTRY AND
MANAGEMENT OF TBI IMAGING FINDINGS
SO JOURNAL OF NEUROTRAUMA
LA English
DT Meeting Abstract
CT 31st Annual National Neurotrauma Symposium
CY AUG 04-07, 2013
CL Nashville, TN
DE common data elements; imaging; informatics; radiology reports; software
C1 [Talbot, Skip; Kleper, Vladimir; Mongkolwat, Pattanasak] Northwestern Univ, Evanston, IL 60208 USA.
[Butman, John] NIH, Ctr Clin, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
J9 J NEUROTRAUM
JI J. Neurotrauma
PD AUG
PY 2013
VL 30
IS 15
BP A119
EP A119
PG 1
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA 191WY
UT WOS:000322446800221
ER
PT J
AU Knutsen, AK
Latour, LL
Butman, J
Pham, D
AF Knutsen, Andrew K.
Latour, Lawrence L.
Butman, John
Dzung Pham
TI CHANGE IN BRAIN VOLUME AFTER TBI WITHIN 90 DAYS POST-INJURY DETECTED
USING MRI
SO JOURNAL OF NEUROTRAUMA
LA English
DT Meeting Abstract
CT 31st Annual National Neurotrauma Symposium
CY AUG 04-07, 2013
CL Nashville, TN
DE edema; longitudinal volume change; MRI
C1 [Latour, Lawrence L.; Butman, John] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
J9 J NEUROTRAUM
JI J. Neurotrauma
PD AUG
PY 2013
VL 30
IS 15
BP A115
EP A115
PG 1
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA 191WY
UT WOS:000322446800214
ER
PT J
AU Knutsen, AK
Magrath, E
McEntee, J
Prince, J
Bayly, P
Butman, J
Pham, D
AF Knutsen, Andrew K.
Magrath, Elizabeth
McEntee, Julie
Prince, Jerry
Bayly, Philip
Butman, John
Dzung Pham
TI IMPROVED MEASUREMENT OF BRAIN DEFORMATION DURING A MILD ACCELERATION
USING TAGGED MRI
SO JOURNAL OF NEUROTRAUMA
LA English
DT Meeting Abstract
CT 31st Annual National Neurotrauma Symposium
CY AUG 04-07, 2013
CL Nashville, TN
DE acceleration; biomechanics; brain deformation; MRI; tagging
C1 [Prince, Jerry] Johns Hopkins Univ, Baltimore, MD 21218 USA.
[Bayly, Philip] Washington Univ, St Louis, MO 63130 USA.
[Butman, John] NIH, Ctr Clin, Bethesda, MD USA.
RI Prince, Jerry/A-3281-2010
OI Prince, Jerry/0000-0002-6553-0876
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
J9 J NEUROTRAUM
JI J. Neurotrauma
PD AUG
PY 2013
VL 30
IS 15
BP A114
EP A115
PG 2
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA 191WY
UT WOS:000322446800213
ER
PT J
AU Li, NZ
Chou, YY
Joy, D
Shiee, N
Chan, L
Pham, D
Butman, J
AF Li, Ningzhi
Chou, Yiyu
Joy, David
Shiee, Navid
Chan, Leighton
Dzung Pham
Butman, John
TI SPATIAL DISTRIBUTION OF BRAIN MICROHEMORRHAGE RESULTING FROM TRAUMATIC
BRAIN INJURY (TBI)
SO JOURNAL OF NEUROTRAUMA
LA English
DT Meeting Abstract
CT 31st Annual National Neurotrauma Symposium
CY AUG 04-07, 2013
CL Nashville, TN
DE atlases; magnetic resonance imaging; microhemorrhages; registration;
susceptibility weighted imaging
C1 [Chan, Leighton; Butman, John] NIH, Ctr Clin, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
J9 J NEUROTRAUM
JI J. Neurotrauma
PD AUG
PY 2013
VL 30
IS 15
BP A116
EP A116
PG 1
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA 191WY
UT WOS:000322446800216
ER
PT J
AU Reger, M
Sagalyn, E
Holmes, A
AF Reger, Maxine
Sagalyn, Erica
Holmes, Andrew
TI MODELING ALCOHOL ABUSE IN THE TBI PATIENT: ETHANOL CONSUMPTION AND
SENSITIVITY FOLLOWING MOUSE CCI
SO JOURNAL OF NEUROTRAUMA
LA English
DT Meeting Abstract
CT 31st Annual National Neurotrauma Symposium
CY AUG 04-07, 2013
CL Nashville, TN
DE alcohol abuse; ethanol; TBI
C1 [Reger, Maxine; Sagalyn, Erica; Holmes, Andrew] NIAAA, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
J9 J NEUROTRAUM
JI J. Neurotrauma
PD AUG
PY 2013
VL 30
IS 15
BP A31
EP A31
PG 1
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA 191WY
UT WOS:000322446800053
ER
PT J
AU Stone, JR
Tustison, NJ
Wassermann, EM
Polejaeva, L
Tierney, M
McCarron, RM
LoPresti, M
Carr, WS
AF Stone, James R.
Tustison, Nicholas J.
Wassermann, Eric M.
Polejaeva, Lena
Tierney, Michael
McCarron, Richard M.
LoPresti, Matthew
Carr, Walter S.
TI NEUROIMAGING CORRELATES OF REPETITIVE BLAST EXPOSURE IN EXPERIENCED
MILITARY BREACHERS
SO JOURNAL OF NEUROTRAUMA
LA English
DT Meeting Abstract
CT 31st Annual National Neurotrauma Symposium
CY AUG 04-07, 2013
CL Nashville, TN
DE blast; breacher; DTI; MRI; TBI
C1 [Stone, James R.; Tustison, Nicholas J.] Univ Virginia, Charlottesville, VA 22903 USA.
[Wassermann, Eric M.; Polejaeva, Lena; Tierney, Michael] NINDS, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
J9 J NEUROTRAUM
JI J. Neurotrauma
PD AUG
PY 2013
VL 30
IS 15
BP A120
EP A121
PG 2
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA 191WY
UT WOS:000322446800224
ER
PT J
AU Villapol, S
Balarezo, M
Affram, K
Mitchell, K
Saavedra, JM
Symes, AJ
AF Villapol, Sonia
Balarezo, Maria
Affram, Kwame
Mitchell, Kendall
Saavedra, Juan M.
Symes, Aviva J.
TI LOW DOSE CANDESARTAN ADMINISTERED AFTER INJURY IS BENEFICIAL FOR
RECOVERY FROM CONTROLLED CORTICAL IMPACT INJURY IN MICE
SO JOURNAL OF NEUROTRAUMA
LA English
DT Meeting Abstract
CT 31st Annual National Neurotrauma Symposium
CY AUG 04-07, 2013
CL Nashville, TN
DE angiotensin blocker; lesion; microglia; rotarod
C1 [Villapol, Sonia; Balarezo, Maria; Affram, Kwame; Mitchell, Kendall; Symes, Aviva J.] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
[Villapol, Sonia; Balarezo, Maria; Affram, Kwame; Mitchell, Kendall; Symes, Aviva J.] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA.
[Villapol, Sonia; Saavedra, Juan M.] NIMH, Pharmacol Sect, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
J9 J NEUROTRAUM
JI J. Neurotrauma
PD AUG
PY 2013
VL 30
IS 15
BP A11
EP A12
PG 2
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA 191WY
UT WOS:000322446800019
ER
PT J
AU Wang, CY
Cogswell, ME
Loria, CM
Chen, TC
Pfeiffer, CM
Swanson, CA
Caldwell, KL
Perrine, CG
Carriquiry, AL
Liu, K
Sempos, CT
Gillespie, CD
Burt, VL
AF Wang, Chia-Yih
Cogswell, Mary E.
Loria, Catherine M.
Chen, Te-Ching
Pfeiffer, Christine M.
Swanson, Christine A.
Caldwell, Kathleen L.
Perrine, Cria G.
Carriquiry, Alicia L.
Liu, Kiang
Sempos, Christopher T.
Gillespie, Cathleen D.
Burt, Vicki L.
TI Urinary Excretion of Sodium, Potassium, and Chloride, but Not Iodine,
Varies by Timing of Collection in a 24-Hour Calibration Study
SO JOURNAL OF NUTRITION
LA English
DT Article
ID BLOOD-PRESSURE; SALT INTAKE; UNITED-STATES; METAANALYSIS; DISEASE;
HEALTH
AB Because of the logistic complexity, excessive respondent burden, and high cost of conducting 24-h urine collections in a national survey, alternative strategies to monitor sodium intake at the population level need to be evaluated. We conducted a calibration study to assess the ability to characterize sodium intake from timed-spot urine samples calibrated to a 24-h urine collection. In this report, we described the overall design and basic results of the study. Adults aged 18-39 y were recruited to collect urine for a 24-h period, placing each void in a separate container. Four timed-spot specimens (morning, afternoon, evening, and overnight) and the 24-h collection were analyzed for sodium, potassium, chloride, creatinine, and iodine. Of 481 eligible persons, 407 (54% female, 48% black) completed a 24-h urine collection. A subsample (n = 133) collected a second 24-h urine 4-11 d later. Mean sodium excretion was 3.54 +/- 1.51 g/d for males and 3.09 +/- 1.26 g/d for females. Sensitivity analysis excluding those who did not meet the expected creatinine excretion criterion showed the same results. Day-to-day variability for sodium, potassium, chloride, and iodine was observed among those collecting two 24-h urine samples (CV = 16-29% for 24-h urine samples and 21-41% for timed-spot specimens). Among all race-gender groups, overnight specimens had larger volumes (P < 0.01) and lower sodium (P < 0.01 to P = 0.26), potassium (P < 0.01), and chloride (P < 0.01) concentrations compared with other timed-spot urine samples, although the differences were not always significant. Urine creatinine and iodine concentrations did not differ by the timing of collection. The observed day-to-day and diurnal variations in sodium excretion illustrate the importance of accounting for these factors when developing calibration equations from this study.
C1 [Wang, Chia-Yih; Chen, Te-Ching; Burt, Vicki L.] Ctr Dis Control & Prevent, Div Hlth & Nutr Examinat Surveys, Natl Ctr Hlth Stat, Hyattsville, MD USA.
[Cogswell, Mary E.; Gillespie, Cathleen D.] Ctr Dis Control & Prevent, Div Heart Dis & Stroke Prevent, Atlanta, GA USA.
[Perrine, Cria G.] Ctr Dis Control & Prevent, Div Nutr Phys Act & Obes, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA.
[Pfeiffer, Christine M.; Caldwell, Kathleen L.] Ctr Dis Control & Prevent, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA USA.
[Loria, Catherine M.] NHLBI, Bethesda, MD 20892 USA.
[Swanson, Christine A.; Sempos, Christopher T.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Carriquiry, Alicia L.] Iowa State Univ, Dept Stat, Ames, IA USA.
[Liu, Kiang] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
RP Wang, CY (reprint author), Ctr Dis Control & Prevent, Div Hlth & Nutr Examinat Surveys, Natl Ctr Hlth Stat, Hyattsville, MD USA.
EM cwang@cdc.gov
FU U.S. government
FX Supported by the U.S. government. The findings and conclusions in this
manuscript are those of the authors and do not necessarily represent the
official position of the CDC, the NIH, or any other entity of the U.S.
government.
NR 36
TC 30
Z9 30
U1 3
U2 11
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
J9 J NUTR
JI J. Nutr.
PD AUG
PY 2013
VL 143
IS 8
BP 1276
EP 1282
DI 10.3945/jn.113.175927
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 190NU
UT WOS:000322348300012
PM 23761643
ER
PT J
AU Ohlhorst, SD
Russell, R
Bier, D
Klurfeld, DM
Li, Z
Mein, JR
Milner, J
Ross, AC
Stover, P
Konopka, E
AF Ohlhorst, Sarah D.
Russell, Robert
Bier, Dennis
Klurfeld, David M.
Li, Zhaoping
Mein, Jonathan R.
Milner, John
Ross, A. Catharine
Stover, Patrick
Konopka, Emily
TI Nutrition research to affect food and a healthy life span
SO JOURNAL OF NUTRITION
LA English
DT Article
ID MEDITERRANEAN DIET; CHILDREN
AB Proper nutrition offers one of the most effective and least costly ways to decrease the burden of many diseases and their associated risk factors, including obesity. Nutrition research holds the key to increasing our understanding of the causes of obesity and its related comorbidities and thus holds promise to markedly influence global health and economies. After outreach to 75 thought leaders, the American Society for Nutrition (ASN) convened a Working Group to identify the nutrition research needs whose advancement will have the greatest projected impact on the future health and well-being of global populations. ASN's Nutrition Research Needs focus on the following high priority areas: 1) variability in individual responses to diet and foods; 2) healthy growth, development, and reproduction; 3) health maintenance; 4) medical management; 5) nutrition-related behaviors; and 6) food supply/environment. ASN hopes the Nutrition Research Needs will prompt collaboration among scientists across all disciplines to advance this challenging research agenda given the high potential for translation and impact on public health. Furthermore, ASN hopes the findings from the Nutrition Research Needs will stimulate the development and adoption of new and innovative strategies that can be applied toward the prevention and treatment of nutrition-related diseases. The multidisciplinary nature of nutrition research requires stakeholders with differing areas of expertise to collaborate on multifaceted approaches to establish the evidence-based nutrition guidance and policies that will lead to better health for the global population. In addition to the identified research needs, ASN also identified 5 tools that are critical to the advancement of the Nutrition Research Needs: 1) omics, 2) bioinformatics, 3) databases, 4) biomarkers, and 5) cost-effectiveness analysis.
C1 [Ohlhorst, Sarah D.; Konopka, Emily] Amer Soc Nutr, Bethesda, MD 20814 USA.
[Russell, Robert] NIH Off Dietary Supplements, Bethesda, MD USA.
[Russell, Robert] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Bier, Dennis] Baylor Coll Med, USDA ARS, Childrens Nutr Res Ctr, Dept Pediat, Houston, TX 77030 USA.
[Klurfeld, David M.] USDA ARS, Human Nutr Program, Beltsville, MD USA.
[Li, Zhaoping] Univ Calif Los Angeles, Ctr Human Nutr, Los Angeles, CA USA.
[Li, Zhaoping] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Mein, Jonathan R.] Monsanto Ctr Food & Nutr Res, Kannapolis, NC USA.
[Milner, John] NIH Natl Canc Inst, Bethesda, MD USA.
[Ross, A. Catharine] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA.
[Stover, Patrick] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
RP Ohlhorst, SD (reprint author), Amer Soc Nutr, 9650 Rockville Pike, Bethesda, MD 20814 USA.
EM sohlhorst@nutrition.org
FU NIDDK NIH HHS [R01 DK058144]
NR 12
TC 4
Z9 4
U1 0
U2 13
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
J9 J NUTR
JI J. Nutr.
PD AUG
PY 2013
VL 143
IS 8
BP 1349
EP 1354
DI 10.3945/jn.113.180638
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 190NU
UT WOS:000322348300022
PM 23784071
ER
PT J
AU Mudhasani, R
Tran, JP
Retterer, C
Radoshitzky, SR
Kota, KP
Altamura, LA
Smith, JM
Packard, BZ
Kuhn, JH
Costantino, J
Garrison, AR
Schmaljohn, CS
Huang, IC
Farzan, M
Bavari, S
AF Mudhasani, Rajini
Tran, Julie P.
Retterer, Cary
Radoshitzky, Sheli R.
Kota, Krishna P.
Altamura, Louis A.
Smith, Jeffrey M.
Packard, Beverly Z.
Kuhn, Jens H.
Costantino, Julie
Garrison, Aura R.
Schmaljohn, Connie S.
Huang, I-Chueh
Farzan, Michael
Bavari, Sina
TI IFITM-2 and IFITM-3 but Not IFITM-1 Restrict Rift Valley Fever Virus
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID WEST NILE VIRUS; DENGUE VIRUS; GENE-EXPRESSION; M-RNA; PROTEINS; CELL;
ENTRY; PATHOGENESIS; INTERFERONS; PREVENTION
AB We show that interferon-induced transmembrane protein 1 (IFITM-1), IFITM-2, and IFITM-3 exhibit a broad spectrum of antiviral activity against several members of the Bunyaviridae family, including Rift Valley fever virus (RVFV), La Crosse virus, Andes virus, and Hantaan virus, all of which can cause severe disease in humans and animals. We found that RVFV was restricted by IFITM-2 and -3 but not by IFITM-1, whereas the remaining viruses were equally restricted by all IFITMs. Indeed, at low doses of alpha interferon (IFN-alpha), IFITM-2 and -3 mediated more than half of the antiviral activity of IFN-alpha against RVFV. IFITM-2 and -3 restricted RVFV infection mostly by preventing virus membrane fusion with endosomes, while they had no effect on virion attachment to cells, endocytosis, or viral replication kinetics. We found that large fractions of IFITM-2 and IFITM-3 occupy vesicular compartments that are distinct from the vesicles coated by IFITM-1. In addition, although overexpression of all IFITMs expanded vesicular and acidified compartments within cells, there were marked phenotypic differences among the vesicular compartments occupied by IFITMs. Collectively, our data provide new insights into the possible mechanisms by which the IFITM family members restrict distinct viruses.
C1 [Mudhasani, Rajini; Tran, Julie P.; Retterer, Cary; Radoshitzky, Sheli R.; Kota, Krishna P.; Altamura, Louis A.; Smith, Jeffrey M.; Costantino, Julie; Garrison, Aura R.; Schmaljohn, Connie S.; Bavari, Sina] US Army Med Res Inst Infect Dis, Frederick, MD USA.
[Packard, Beverly Z.] OncoImmunin Inc, Gaithersburg, MD USA.
[Kuhn, Jens H.] NIAID, Integrated Res Facil Ft Detrick, NIH, Frederick, MD USA.
[Huang, I-Chueh] Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA.
[Farzan, Michael] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, New England Primate Res Ctr, Southborough, MA 01772 USA.
RP Bavari, S (reprint author), US Army Med Res Inst Infect Dis, Frederick, MD USA.
EM sina.bavari@amedd.army.mil
RI Kuhn, Jens H./B-7615-2011
OI Kuhn, Jens H./0000-0002-7800-6045
FU Defense Threat Reduction Agency (DTRA); Joint Science and Technology
Office for Chem Bio Defense [TMTI0048_09_RD_T]; Faculty Research
Participation Program at the U.S. Army Medical Research and Materiel
Command; NIAID [HHSN272200200016I]
FX This study was supported by funding from the Defense Threat Reduction
Agency (DTRA), Joint Science and Technology Office for Chem Bio Defense
(proposal TMTI0048_09_RD_T), to S.B. This research by R.M. was supported
in part by an appointment to the Faculty Research Participation Program
at the U.S. Army Medical Research and Materiel Command administered by
the Oak Ridge Institute for Science and Education through an interagency
agreement between the U.S. Department of Energy and the U.S. Army
Medical Research and Materiel Command. J.H.K. performed this work as an
employee of Tunnell Consulting, Inc., a sub-contractor to Battelle
Memorial Institute, under its prime contract with NIAID, under contract
no. HHSN272200200016I.
NR 51
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U1 1
U2 11
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG
PY 2013
VL 87
IS 15
BP 8451
EP 8464
DI 10.1128/JVI.03382-12
PG 14
WC Virology
SC Virology
GA 180JO
UT WOS:000321590200018
PM 23720721
ER
PT J
AU Singhal, G
Leo, E
Setty, SKG
Pommier, Y
Thimmapaya, B
AF Singhal, Ghata
Leo, Elisabetta
Setty, Saayi Krushna Gadham
Pommier, Yves
Thimmapaya, Bayar
TI Adenovirus E1A Oncogene Induces Rereplication of Cellular DNA and Alters
DNA Replication Dynamics
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID C-MYC; DAMAGE RESPONSE; HUMAN-CELLS; S-PHASE; RETINOBLASTOMA PROTEIN;
TUMOR-SUPPRESSOR; GENOME STABILITY; GENE-EXPRESSION; G(1) EXIT; CYCLE
AB The oncogenic property of the adenovirus (Ad) transforming E1A protein is linked to its capacity to induce cellular DNA synthesis which occurs as a result of its interaction with several host proteins, including pRb and p300/CBP. While the proteins that contribute to the forced induction of cellular DNA synthesis have been intensively studied, the nature of the cellular DNA replication that is induced by E1A in quiescent cells is not well understood. Here we show that E1A expression in quiescent cells leads to massive cellular DNA rereplication in late S phase. Using a single-molecule DNA fiber assay, we studied the cellular DNA replication dynamics in E1A-expressing cells. Our studies show that the DNA replication pattern is dramatically altered in E1A-expressing cells, with increased replicon length, fork velocity, and interorigin distance. The interorigin distance increased by about 3-fold, suggesting that fewer DNA replication origins are used in E1A-expressing cells. These aberrant replication events led to replication stress, as evidenced by the activation of the DNA damage response. In earlier studies, we showed that E1A induces c-Myc as a result of E1A binding to p300. Using an antisense c-Myc to block c-Myc expression, our results indicate that induction of c-Myc in E1A-expressing cells contributes to the induction of host DNA replication. Together, our results suggest that the E1A oncogene-induced cellular DNA replication stress is due to dramatically altered cellular replication events and that E1A-induced c-Myc may contribute to these events.
C1 [Singhal, Ghata; Setty, Saayi Krushna Gadham; Thimmapaya, Bayar] Northwestern Univ, Dept Microbiol & Immunol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Leo, Elisabetta; Pommier, Yves] NCI, Lab Pharmacol & Mol Biol, Bethesda, MD 20892 USA.
RP Thimmapaya, B (reprint author), Northwestern Univ, Dept Microbiol & Immunol, Feinberg Sch Med, Chicago, IL 60611 USA.
EM b-thimmapaya@northwestern.edu
FU NIH/NCI [RO1CA 74403, R21AI094296]; Cancer Center Support grant [NCI
CA060553]; Center for Cancer Research intramural program of the NCI/NIH
FX This work was supported by NIH/NCI grants RO1CA 74403 and R21AI094296.
The Genomic Core and Flow Cytometry facilities used in this study were
supported by Cancer Center Support grant NCI CA060553. E. L. was
supported by the Center for Cancer Research intramural program of the
NCI/NIH.
NR 64
TC 3
Z9 3
U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG
PY 2013
VL 87
IS 15
BP 8767
EP 8778
DI 10.1128/JVI.00879-13
PG 12
WC Virology
SC Virology
GA 180JO
UT WOS:000321590200044
PM 23740993
ER
PT J
AU Sadjadpour, R
Donau, OK
Shingai, M
Buckler-White, A
Kao, S
Strebel, K
Nishimura, Y
Martin, MA
AF Sadjadpour, Reza
Donau, Olivia K.
Shingai, Masashi
Buckler-White, Alicia
Kao, Sandra
Strebel, Klaus
Nishimura, Yoshiaki
Martin, Malcolm A.
TI Emergence of gp120 V3 Variants Confers Neutralization Resistance in an
R5 Simian-Human Immunodeficiency Virus-Infected Macaque Elite
Neutralizer That Targets the N332 Glycan of the Human Immunodeficiency
Virus Type 1 Envelope Glycoprotein
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID ANTIBODY-RESPONSE; RAPID DEVELOPMENT; HUMORAL IMMUNITY; HIV-1 INFECTION;
POTENT; BROAD; EVOLUTION; SEQUENCE; SHIVAD8; ESCAPE
AB Neutralization-resistant simian-human immunodeficiency virus AD8 (SHIVAD8) variants that emerged in an infected macaque elite neutralizer targeting the human immunodeficiency virus type 1 (HIV-1) gp120 N332 glycan acquired substitutions of critical amino acids in the V3 region rather than losing the N332 glycosylation site. One of these resistant variants, carrying the full complement of gp120 V3 changes, was also resistant to the potent anti-HIV-1 monoclonal neutralizing antibodies PGT121 and 10-1074, both of which are also dependent on the presence of the gp120 N332 glycan.
C1 [Sadjadpour, Reza; Donau, Olivia K.; Shingai, Masashi; Buckler-White, Alicia; Kao, Sandra; Strebel, Klaus; Nishimura, Yoshiaki; Martin, Malcolm A.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
RP Martin, MA (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
EM malm@nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 29
TC 8
Z9 8
U1 0
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG
PY 2013
VL 87
IS 15
BP 8798
EP 8804
DI 10.1128/JVI.00878-13
PG 7
WC Virology
SC Virology
GA 180JO
UT WOS:000321590200047
PM 23720719
ER
PT J
AU Sukupolvi-Petty, S
Brien, JD
Austin, SK
Shrestha, B
Swayne, S
Kahle, K
Doranz, BJ
Johnson, S
Pierson, TC
Fremont, DH
Diamond, MS
AF Sukupolvi-Petty, Soila
Brien, James D.
Austin, S. Kyle
Shrestha, Bimmi
Swayne, Sherri
Kahle, Kristen
Doranz, Benjamin J.
Johnson, Syd
Pierson, Theodore C.
Fremont, Daved H.
Diamond, Michael S.
TI Functional Analysis of Antibodies against Dengue Virus Type 4 Reveals
Strain-Dependent Epitope Exposure That Impacts Neutralization and
Protection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID WEST-NILE-VIRUS; PROTEIN DOMAIN-III; CROSS-REACTIVE ANTIBODIES; HUMAN
DENDRITIC CELLS; ENVELOPE PROTEIN; MONOCLONAL-ANTIBODIES; FUSION-LOOP;
PHENOTYPIC CHARACTERIZATION; INFECTION ENHANCEMENT; MOLECULAR EVOLUTION
AB Although prior studies have characterized the neutralizing activities of monoclonal antibodies (MAbs) against dengue virus (DENV) serotypes 1, 2, and 3 (DENV-1, DENV-2, and DENV-3), few reports have assessed the activity of MAbs against DENV-4. Here, we evaluated the inhibitory activity of 81 new mouse anti-DENV-4 MAbs. We observed strain-and genotype-dependent differences in neutralization of DENV-4 by MAbs mapping to epitopes on domain II (DII) and DIII of the envelope (E) protein. Several anti-DENV-4 MAbs inefficiently inhibited at least one strain and/or genotype, suggesting that the exposure or sequence of neutralizing epitopes varies within isolates of this serotype. Remarkably, flavivirus cross-reactive MAbs, which bound to the highly conserved fusion loop in DII and inhibited infection of DENV-1, DENV-2, and DENV-3, more weakly neutralized five different DENV-4 strains encompassing the genetic diversity of the serotype after preincubation at 37 degrees C. However, increasing the time of preincubation at 37 degrees C or raising the temperature to 40 degrees C enhanced the potency of DII fusion loop-specific MAbs and some DIII-specific MAbs against DENV-4 strains. Prophylaxis studies in two new DENV-4 mouse models showed that neutralization titers of MAbs after preincubation at 37 degrees C correlated with activity in vivo. Our studies establish the complexity of MAb recognition against DENV-4 and suggest that differences in epitope exposure relative to other DENV serotypes affect antibody neutralization and protective activity.
C1 [Sukupolvi-Petty, Soila; Brien, James D.; Austin, S. Kyle; Shrestha, Bimmi; Diamond, Michael S.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
[Fremont, Daved H.; Diamond, Michael S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA.
[Diamond, Michael S.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
[Fremont, Daved H.; Diamond, Michael S.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA.
[Swayne, Sherri; Kahle, Kristen; Doranz, Benjamin J.] Integral Mol Inc, Philadelphia, PA USA.
[Johnson, Syd] MacroGenics Inc, Rockville, MD USA.
[Pierson, Theodore C.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Diamond, MS (reprint author), Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
EM diamond@borcim.wustl.edu
FU Burroughs Wellcome Fund; NIH [R01-AI077955, U01-AI061373]; NIAID
[HHSN272200900055C]
FX This work was supported by the Burroughs Wellcome Fund, NIH grants
R01-AI077955 and U01-AI061373, and NIAID contract HHSN272200900055C.
NR 89
TC 31
Z9 31
U1 0
U2 16
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG
PY 2013
VL 87
IS 16
BP 8826
EP 8842
DI 10.1128/JVI.01314-13
PG 17
WC Virology
SC Virology
GA 193CS
UT WOS:000322535600002
PM 23785205
ER
PT J
AU Matsuda, K
Brown, CR
Foley, B
Goeken, R
Whitted, S
Dang, Q
Wu, F
Plishka, R
Buckler-White, A
Hirscha, VM
AF Matsuda, Kenta
Brown, Charles R.
Foley, Brian
Goeken, Robert
Whitted, Sonya
Dang, Que
Wu, Fan
Plishka, Ronald
Buckler-White, Alicia
Hirscha, Vanessa M.
TI Laser Capture Microdissection Assessment of Virus Compartmentalization
in the Central Nervous Systems of Macaques Infected with Neurovirulent
Simian Immunodeficiency Virus
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CNS PENETRATION-EFFECTIVENESS; ANTIRETROVIRAL THERAPY; CHOROID-PLEXUS;
PROGRESSOR MACAQUES; CEREBROSPINAL-FLUID; HIV-INFECTION; BRAIN-REGIONS;
TYPE-1; SEQUENCES; ENCEPHALITIS
AB Nonhuman primate-simian immunodeficiency virus (SIV) models are powerful tools for studying the pathogenesis of human immunodeficiency virus type 1 (HIV-1) in the brain. Our laboratory recently isolated a neuropathogenic viral swarm, SIVsmH804E, a derivative of SIVsmE543-3, which was the result of sequential intravenous passages of viruses isolated from the brains of rhesus macaques with SIV encephalitis. Animals infected with SIVsmH804E or its precursor (SIVsmH783Br) developed SIV meningitis and/or encephalitis at high frequencies. Since we observed macaques with a combination of meningitis and encephalitis, as well as animals in which meningitis or encephalitis was the dominant component, we hypothesized that distinct mechanisms could be driving the two pathological states. Therefore, we assessed viral populations in the meninges and the brain parenchyma by laser capture microdissection. Viral RNAs were isolated from representative areas of the meninges, brain parenchyma, terminal plasma, and cerebrospinal fluid (CSF) and from the inoculum, and the SIV envelope fragment was amplified by PCR. Phylogenetic analysis of envelope sequences from the conventional progressors revealed compartmentalization of viral populations between the meninges and the parenchyma. In one of these animals, viral populations in meninges were closely related to those from CSF and shared signature truncations in the cytoplasmic domain of gp41, consistent with a common origin. Apart from magnetic resonance imaging (MRI) and positron-emission tomography (PET) imaging, CSF is the most accessible assess to the central nervous system for HIV-1-infected patients. However, our results suggest that the virus in the CSF may not always be representative of viral populations in the brain and that caution should be applied in extrapolating between the properties of viruses in these two compartments.
C1 [Matsuda, Kenta; Brown, Charles R.; Goeken, Robert; Whitted, Sonya; Dang, Que; Wu, Fan; Plishka, Ronald; Buckler-White, Alicia; Hirscha, Vanessa M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Foley, Brian] Los Alamos Natl Lab, Grp T 6, Los Alamos, NM USA.
RP Hirscha, VM (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
EM vhirsch@niaid.nih.gov
OI Foley, Brian/0000-0002-1086-0296
FU NIAID, NIH; JSPS Research Fellowship for Japanese Biomedical and
Behavioral Researchers at NIH
FX This work was supported by the intramural research program of NIAID,
NIH, and by a JSPS Research Fellowship for Japanese Biomedical and
Behavioral Researchers at NIH.
NR 47
TC 11
Z9 11
U1 3
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG
PY 2013
VL 87
IS 16
BP 8896
EP 8908
DI 10.1128/JVI.00874-13
PG 13
WC Virology
SC Virology
GA 193CS
UT WOS:000322535600008
PM 23720733
ER
PT J
AU Bamunusinghe, D
Chaturvedi, S
Seo, JK
Rao, ALN
AF Bamunusinghe, Devinka
Chaturvedi, Sonali
Seo, Jang-Kyun
Rao, A. L. N.
TI Mutations in the Capsid Protein of Brome Mosaic Virus Affecting
Encapsidation Eliminate Vesicle Induction In Planta: Implications for
Virus Cell-to-Cell Spread
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CHLOROTIC MOTTLE VIRUS; RNA REPLICATION COMPLEX; COAT PROTEIN;
ENDOPLASMIC-RETICULUM; MOVEMENT PROTEIN; NICOTIANA-BENTHAMIANA; VIRAL
REPLICASE; SUBGENOMIC RNA; INFECTION; MEMBRANES
AB Positive-strand RNA viruses are known to rearrange the endomembrane network to make it more conducive for replication, maturation, or egress. Our previous transmission electron microscopic (TEM) analysis showed that ectopic expression of wild-type (wt) capsid protein (CP) of Brome mosaic virus (BMV) has an intrinsic property of modifying the endoplasmic reticulum (ER) to induce vesicles similar to those present in wt BMV infection. In this study, we evaluated the functional significance of CP-mediated vesicle induction to the BMV infection cycle in planta. Consequently, the cytopathologic changes induced by wt CP or its mutants defective in virion assembly due to mutations engineered in either N- or C-proximal domains were comparatively analyzed by TEM in two susceptible (Nicotiana benthamiana and Chenopodium quinoa) and one nonhost (N. clevelandii) plant species. The results showed that in susceptible hosts, CP-mediated ER-derived vesicle induction is contingent on the expression of encapsidation-competent CP. In contrast, unlike in N. benthamiana and C. quinoa, transient expression of wt CP in nonhost N. clevelandii plants eliminated vesicle induction. Additionally, comparative source-to-sink analysis of virus spread in leaves of N. benthamiana and N. clevelandii coexpressing wt BMV and Cucumber mosaic virus (CMV) showed that despite trans-encapsidation, CMV failed to complement the defective cell-to-cell movement of BMV. The significance and relation of CP-mediated vesicle induction to virus cell-to-cell movement are discussed.
C1 [Bamunusinghe, Devinka; Chaturvedi, Sonali; Seo, Jang-Kyun; Rao, A. L. N.] Univ Calif Riverside, Dept Plant Pathol & Microbiol, Riverside, CA 92521 USA.
[Bamunusinghe, Devinka] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Seo, Jang-Kyun] Rural Dev Adm, Crop Protect Div, Natl Acad Agr Sci, Suwon, South Korea.
RP Rao, ALN (reprint author), Univ Calif Riverside, Dept Plant Pathol & Microbiol, Riverside, CA 92521 USA.
EM arao@ucr.edu
FU Committee on Research of the Riverside Division of the Academic Senate
FX This study was supported by a grant from the Committee on Research of
the Riverside Division of the Academic Senate.
NR 56
TC 2
Z9 2
U1 0
U2 16
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG
PY 2013
VL 87
IS 16
BP 8982
EP 8992
DI 10.1128/JVI.01253-13
PG 11
WC Virology
SC Virology
GA 193CS
UT WOS:000322535600016
PM 23741003
ER
PT J
AU Gurda, BL
DiMattia, MA
Miller, EB
Bennett, A
McKenna, R
Weichert, WS
Nelson, CD
Chen, WJ
Muzyczka, N
Olson, NH
Sinkovits, RS
Chiorini, JA
Zolotutkhin, S
Kozyreva, OG
Samulski, RJ
Baker, TS
Parrish, CR
Agbandje-McKenna, M
AF Gurda, Brittney L.
DiMattia, Michael A.
Miller, Edward B.
Bennett, Antonette
McKenna, Robert
Weichert, Wendy S.
Nelson, Christian D.
Chen, Wei-jun
Muzyczka, Nicholas
Olson, Norman H.
Sinkovits, Robert S.
Chiorini, John A.
Zolotutkhin, Sergei
Kozyreva, Olga G.
Samulski, R. Jude
Baker, Timothy S.
Parrish, Colin R.
Agbandje-McKenna, Mavis
TI Capsid Antibodies to Different Adeno-Associated Virus Serotypes Bind
Common Regions
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HEPARAN-SULFATE PROTEOGLYCAN; NEUTRALIZING MONOCLONAL-ANTIBODY; CILIATED
AIRWAY EPITHELIUM; CRYO-ELECTRON MICROSCOPY; MEDIATED GENE-TRANSFER;
TYPE-2 CAPSIDS; SIALIC-ACID; 3-DIMENSIONAL STRUCTURE; DIRECTED
EVOLUTION; IMMUNE-RESPONSES
AB Interactions between viruses and the host antibody immune response are critical in the development and control of disease, and antibodies are also known to interfere with the efficacy of viral vector-based gene delivery. The adeno-associated viruses (AAVs) being developed as vectors for corrective human gene delivery have shown promise in clinical trials, but preexisting antibodies are detrimental to successful outcomes. However, the antigenic epitopes on AAV capsids remain poorly characterized. Cryoelectron microscopy and three-dimensional image reconstruction were used to define the locations of epitopes to which monoclonal fragment antibodies (Fabs) against AAV1, AAV2, AAV5, and AAV6 bind. Pseudoatomic modeling showed that, in each serotype, Fabs bound to a limited number of sites near the protrusions surrounding the 3-fold axes of the T = 1 icosahedral capsids. For the closely related AAV1 and AAV6, a common Fab exhibited substoichiometric binding, with one Fab bound, on average, between two of the three protrusions as a consequence of steric crowding. The other AAV Fabs saturated the capsid and bound to the walls of all 60 protrusions, with the footprint for the AAV5 antibody extending toward the 5-fold axis. The angle of incidence for each bound Fab on the AAVs varied and resulted in significant differences in how much of each viral capsid surface was occluded beyond the Fab footprints. The AAV-antibody interactions showed a common set of footprints that overlapped some known receptor-binding sites and transduction determinants, thus suggesting potential mechanisms for virus neutralization by the antibodies.
C1 [Gurda, Brittney L.; DiMattia, Michael A.; Miller, Edward B.; Bennett, Antonette; McKenna, Robert; Agbandje-McKenna, Mavis] Univ Florida, Deptartment Biochem & Mol Biol, Gainesville, FL 32611 USA.
[Weichert, Wendy S.; Nelson, Christian D.; Parrish, Colin R.] Cornell Univ, Coll Vet Med, Baker Inst Anim Hlth, Dept Microbiol & Immunol, Ithaca, NY 14853 USA.
[Chen, Wei-jun; Muzyczka, Nicholas] Univ Florida, Dept Mol Genet & Microbiol, Gainesville, FL USA.
[Olson, Norman H.; Sinkovits, Robert S.; Baker, Timothy S.] Univ Calif San Diego, Dept Chem & Biochem, San Diego, CA 92103 USA.
[Olson, Norman H.; Sinkovits, Robert S.; Baker, Timothy S.] Univ Calif San Diego, Div Biol Sci, San Diego, CA 92103 USA.
[Chiorini, John A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
[Zolotutkhin, Sergei] Univ Florida, Dept Pediat, Div Cellular & Mol Therapy, Gainesville, FL USA.
[Kozyreva, Olga G.; Samulski, R. Jude] Univ N Carolina, Dept Pharmacol, Gene Therapy Ctr, Chapel Hill, NC USA.
RP Agbandje-McKenna, M (reprint author), Univ Florida, Deptartment Biochem & Mol Biol, Gainesville, FL 32611 USA.
EM mckenna@ufl.edu
OI Gurda, Brittney /0000-0002-0174-9385
FU NIH [R21AI072341, R01 AI072176-01, R01 GM082946, P01 HL112761, R37
GM-33050, 1S10 RR020016]; NIH Intramural funds; University of
California-San Diego (UCSD); Agouron Foundation
FX This project was funded in part by NIH grants R21AI072341 (to C. R. P.
and M.A.-M.), R01 AI072176-01 (to M. A.-M. and R.J.S.), R01 GM082946 (to
M. A.-M., R. M., N.M., and S.Z.), P01 HL112761 (to R.J.S), R37 GM-33050
(to T. S. B.), and 1S10 RR020016 (to T. S. B.), by NIH Intramural funds
(to J.A.C.), and by support from the University of California-San Diego
(UCSD) and the Agouron Foundation (to T. S. B.) to establish cryo-EM
facilities at UCSD.
NR 103
TC 26
Z9 26
U1 0
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG
PY 2013
VL 87
IS 16
BP 9111
EP 9124
DI 10.1128/JVI.00622-13
PG 14
WC Virology
SC Virology
GA 193CS
UT WOS:000322535600027
PM 23760240
ER
PT J
AU Li, J
Wang, X
Diaz, J
Tsang, SH
Buck, CB
You, JX
AF Li, Jing
Wang, Xin
Diaz, Jason
Tsang, Sabrina H.
Buck, Christopher B.
You, Jianxin
TI Merkel Cell Polyomavirus Large T Antigen Disrupts Host Genomic Integrity
and Inhibits Cellular Proliferation
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID DNA-DAMAGE RESPONSE; TUMOR-SPECIFIC SIGNATURE; REPLICATION PROTEIN-A;
INDUCED PHOSPHORYLATION; HUMAN CANCER; IN-VITRO; P53; ATM; INFECTION;
CARCINOMA
AB Clonal integration of Merkel cell polyomavirus (MCV) DNA into the host genome has been observed in at least 80% of Merkel cell carcinoma (MCC). The integrated viral genome typically carries mutations that truncate the C-terminal DNA binding and helicase domains of the MCV large T antigen (LT), suggesting a selective pressure to remove this MCV LT region during tumor development. In this study, we show that MCV infection leads to the activation of host DNA damage responses (DDR). This activity was mapped to the C-terminal helicase-containing region of the MCV LT. The MCV LT-activated DNA damage kinases, in turn, led to enhanced p53 phosphorylation, upregulation of p53 downstream target genes, and cell cycle arrest. Compared to the N-terminal MCV LT fragment that is usually preserved in mutants isolated from MCC tumors, full-length MCV LT shows a decreased potential to support cellular proliferation, focus formation, and anchorage-independent cell growth. These apparently antitumorigenic effects can be reversed by a dominant-negative p53 inhibitor. Our results demonstrate that MCV LT-induced DDR activates p53 pathway, leading to the inhibition of cellular proliferation. This study reveals a key difference between MCV LT and simian vacuolating virus 40 LT, which activates a DDR but inhibits p53 function. This study also explains, in part, why truncation mutations that remove the MCV LT C-terminal region are necessary for the oncogenic progression of MCV-associated cancers.
C1 [Li, Jing; Wang, Xin; Diaz, Jason; Tsang, Sabrina H.; You, Jianxin] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Buck, Christopher B.] NCI, Tumor Virus Mol Biol Sect, Cellular Oncol Lab, Bethesda, MD 20892 USA.
RP You, JX (reprint author), Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
EM jianyou@mail.med.upenn.edu
OI Buck, Christopher/0000-0003-3165-8094
FU HIV-Associated Malignancies Pilot Project Award (National Cancer
Institute), National Institutes of Health (NIH) [R01CA148768,
R01CA142723]; Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research
FX This study was supported by the HIV-Associated Malignancies Pilot
Project Award (National Cancer Institute), National Institutes of Health
(NIH) grants R01CA148768 and R01CA142723, and the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research.
NR 62
TC 25
Z9 25
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG
PY 2013
VL 87
IS 16
BP 9173
EP 9188
DI 10.1128/JVI.01216-13
PG 16
WC Virology
SC Virology
GA 193CS
UT WOS:000322535600032
PM 23760247
ER
PT J
AU Wan, HQ
Gao, J
Xu, KM
Chen, HJ
Couzens, LK
Rivers, KH
Easterbrook, JD
Yang, KV
Zhong, L
Rajabi, M
Ye, JQ
Sultana, I
Wan, XF
Liu, XF
Perez, DR
Taubenberger, JK
Eichelberger, MC
AF Wan, Hongquan
Gao, Jin
Xu, Kemin
Chen, Hongjun
Couzens, Laura K.
Rivers, Katie H.
Easterbrook, Judy D.
Yang, Kevin
Zhong, Lei
Rajabi, Mohsen
Ye, Jianqiang
Sultana, Ishrat
Wan, Xiu-Feng
Liu, Xiufan
Perez, Daniel R.
Taubenberger, Jeffery K.
Eichelberger, Maryna C.
TI Molecular Basis for Broad Neuraminidase Immunity: Conserved Epitopes in
Seasonal and Pandemic H1N1 as Well as H5N1 Influenza Viruses
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN AIRWAY EPITHELIUM; A-VIRUS; MONOCLONAL-ANTIBODIES;
CROSS-PROTECTION; ANTIGENIC DRIFT; VACCINE; INFECTION; NA;
HEMAGGLUTININ; IMMUNIZATION
AB Influenza A viruses, including H1N1 and H5N1 subtypes, pose a serious threat to public health. Neuraminidase (NA)-related immunity contributes to protection against influenza virus infection. Antibodies to the N1 subtype provide protection against homologous and heterologous H1N1 as well as H5N1 virus challenge. Since neither the strain-specific nor conserved epitopes of N1 have been identified, we generated a panel of mouse monoclonal antibodies (MAbs) that exhibit different reactivity spectra with H1N1 and H5N1 viruses and used these MAbs to map N1 antigenic domains. We identified 12 amino acids essential for MAb binding to the NA of a recent seasonal H1N1 virus, A/Brisbane/59/2007. Of these, residues 248, 249, 250, 341, and 343 are recognized by strain-specific group A MAbs, while residues 273, 338, and 339 are within conserved epitope(s), which allows cross-reactive group B MAbs to bind the NAs of seasonal H1N1 and the 1918 and 2009 pandemic (09pdm) H1N1 as well as H5N1 viruses. A single dose of group B MAbs administered prophylactically fully protected mice against lethal challenge with seasonal and 09pdm H1N1 viruses and resulted in significant protection against the highly pathogenic wild-type H5N1 virus. Another three N1 residues (at positions 396, 397, and 456) are essential for binding of cross-reactive group E MAbs, which differ from group B MAbs in that they do not bind 09pdm H1N1 viruses. The identification of conserved N1 epitopes reveals the molecular basis for NA-mediated immunity between H1N1 and H5N1 viruses and demonstrates the potential for developing broadly protective NA-specific antibody treatments for influenza.
C1 [Wan, Hongquan; Gao, Jin; Couzens, Laura K.; Rivers, Katie H.; Yang, Kevin; Rajabi, Mohsen; Sultana, Ishrat; Eichelberger, Maryna C.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
[Xu, Kemin; Chen, Hongjun; Perez, Daniel R.] Univ Maryland, Dept Vet Med, College Pk, MD 20742 USA.
[Xu, Kemin; Chen, Hongjun; Perez, Daniel R.] Virginia Maryland Reg Coll Vet Med, College Pk, MD USA.
[Easterbrook, Judy D.; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Zhong, Lei; Liu, Xiufan] Yangzhou Univ, Coll Vet Med, Anim Infect Dis Lab, Yangzhou, Jiangsu, Peoples R China.
[Ye, Jianqiang; Wan, Xiu-Feng] Mississippi State Univ, Coll Vet Med, Dept Basic Sci, Mississippi State, MS 39762 USA.
RP Eichelberger, MC (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
EM maryna.eichelberger@fda.hhs.gov
OI Perez, Daniel/0000-0002-6569-5689
FU Intramural Research Program of the NIH; NIAID; intramural FDA funds;
Major State Basic Research Development Program of China (973 Program)
[2011CB505003]; NIAID, NIH [HHSN266200700010C]; Oak Ridge Institute for
Science and Education
FX This work was supported in part by the Intramural Research Program of
the NIH and the NIAID (J.K.T.) and by intramural FDA funds. L.Z. and X.
L. were funded by the Major State Basic Research Development Program of
China (973 Program grant number 2011CB505003). K. X., H. C., and D. R.
P. were funded by contract HHSN266200700010C from the NIAID, NIH. L. K.
C., K.Y., M. R., and I. S. were supported by training funds administered
by the Oak Ridge Institute for Science and Education.
NR 46
TC 28
Z9 28
U1 1
U2 13
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG
PY 2013
VL 87
IS 16
BP 9290
EP 9300
DI 10.1128/JVI.01203-13
PG 11
WC Virology
SC Virology
GA 193CS
UT WOS:000322535600043
PM 23785204
ER
PT J
AU Li, Y
Wang, XH
Ni, T
Wang, FF
Lu, WG
Zhu, J
Xie, X
Zheng, ZM
AF Li, Yang
Wang, Xiaohong
Ni, Ting
Wang, Fenfen
Lu, Weiguo
Zhu, Jun
Xie, Xing
Zheng, Zhi-Ming
TI Human Papillomavirus Type 58 Genome Variations and RNA Expression in
Cervical Lesions
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID ROLLING-CIRCLE AMPLIFICATION; GENE-EXPRESSION; CELL-LINES; CANCER; DNA;
SEQUENCE; TRANSCRIPTION; POLYMERASE; CARCINOMA; DIFFERENTIATION
AB Human papillomavirus type 58 (HPV58) is relatively prevalent in China and other Asian countries. In this study, the HPV58 genome in cervical lesions was decoded from five grade 2 or 3 cervical intraepithelial neoplasia lesion (CIN2/3) samples and five cervical cancer tissues using rolling-circle amplification of total cell DNA and deep sequencing and verified by whole-genome cloning and sequencing. HPV58 isolates from China feature a total of 52 nucleotide substitutions (0.66%) from the reference HPV58 sequence, which appear mainly in two regions, with 12 from nucleotides (nt) 3430 to 4136 covering the E2/E4/E5 open reading frames (ORFs) and 13 from nt 4621 to 5540 covering the L2 ORF; these could be grouped as HPV58 Chinese Zhejiang-1, -2, and -3 (CNZJ-1, -2, and -3) according to their sequence similarities and restriction enzyme digestion. Phylogenetically, CNZJ-3 is similar to the reference HPV58 sublineage A1 sequence. The other two are close to sublineage A2. Analysis of cervical lesion-derived RNA revealed abundant HPV58 early transcripts spliced at the E6 and E1/E2 ORFs, where two 5' splice sites at nt 232 and nt 898 and two 3' splice sites at nt 510 and nt 3355 can be identified. Thus, our study represents the first genome-wide analysis of HPV58 and its expression in cervical lesions.
C1 [Li, Yang; Wang, Xiaohong; Zheng, Zhi-Ming] NCI, Tumor Virus RNA Biol Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Li, Yang; Wang, Fenfen; Lu, Weiguo; Xie, Xing] Zhejiang Univ, Sch Med, Womens Hosp, Dept Gynecol Oncol, Hangzhou 310003, Zhejiang, Peoples R China.
[Ni, Ting; Zhu, Jun] NHLBI, DNA Sequencing & Computat Biol Core, NIH, Bethesda, MD 20892 USA.
RP Zheng, ZM (reprint author), NCI, Tumor Virus RNA Biol Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
EM zhengt@exchange.nih.gov
FU Intramural Research Programs of the NCI, Center for Cancer Research;
NHLBI, NIH; Natural Science Foundation of China [NSFC 81172475]; Natural
Science Foundation of Zhejiang Province of China [LQ13H160003]; Zhejiang
University Women's Hospital
FX This study was supported by the Intramural Research Programs of the NCI,
Center for Cancer Research, and the NHLBI, NIH, and by the Natural
Science Foundation of China (NSFC 81172475) and the Natural Science
Foundation of Zhejiang Province of China (grant number LQ13H160003).
Y.L., a visiting fellow to NCI, was supported by Zhejiang University
Women's Hospital.
NR 33
TC 9
Z9 10
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG
PY 2013
VL 87
IS 16
BP 9313
EP 9322
DI 10.1128/JVI.01154-13
PG 10
WC Virology
SC Virology
GA 193CS
UT WOS:000322535600045
PM 23785208
ER
PT J
AU Kannian, P
Fernandez, S
Jones, KS
Green, PL
AF Kannian, Priya
Fernandez, Soledad
Jones, Kathryn S.
Green, Patrick L.
TI Human T Lymphotropic Virus Type 1 SU Residue 195 Plays a Role in
Determining the Preferential CD4(+) T Cell
Immortalization/Transformation Tropism
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HEPARAN-SULFATE PROTEOGLYCANS; HUMAN MONOCLONAL-ANTIBODIES;
LEUKEMIA-VIRUS; TRANSFORMATION TROPISM; GENE-PRODUCTS; HTLV-1; ENVELOPE;
IDENTIFICATION; DISEASE; GLYCOPROTEIN
AB Human T lymphotropic virus type 1 (HTLV-1) mainly causes adult T cell leukemia and predominantly immortalizes/transforms CD4(+) T cells in culture. HTLV-2 is aleukemic and predominantly immortalizes/transforms CD8(+) T cells in culture. We have shown previously that the viral envelope is the genetic determinant of the differential T cell tropism in culture. The surface component (SU) of the HTLV-1 envelope is responsible for binding to the cellular receptors for entry. Here, we dissect the HTLV-1 SU further to identify key domains that are involved in determining the immortalization tropism. We generated HTLV-1 envelope recombinant virus containing the HTLV-2 SU domain. HTLV-1/SU2 was capable of infecting and immortalizing freshly isolated peripheral blood mononuclear cells in culture. HTLV-1/SU2 shifted the CD4(+) T cell immortalization tropism of wildtype HTLV-1 (wtHTLV-1) to a CD8(+) T cell preference. Furthermore, a single amino acid substitution, N195D, in HTLV-1 SU (Ach. 195) resulted in a shift to a CD8(+) T cell immortalization tropism preference. Longitudinal phenotyping analyses of the in vitro transformation process revealed that CD4(+) T cells emerged as the predominant population by week 5 in wtHTLV-1 cultures, while CD8(+) T cells emerged as the predominant population by weeks 4 and 7 in wtHTLV-2 and Ach. 195 cultures, respectively. Our results indicate that SU domain independently influences the preferential T cell immortalization tropism irrespective of the envelope counterpart transmembrane (TM) domain. We further showed that asparagine at position 195 in HTLV-1 SU is involved in determining this CD4(+) T cell immortalization tropism. The slower emergence of the CD8(+) T cell predominance in Ach. 195-infected cultures suggests that other residues/domains contribute to this tropism preference.
C1 [Kannian, Priya; Green, Patrick L.] Ohio State Univ, Ctr Retrovirus Res, Columbus, OH 43210 USA.
[Kannian, Priya; Green, Patrick L.] Ohio State Univ, Dept Vet Biosci, Columbus, OH 43210 USA.
[Green, Patrick L.] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
[Fernandez, Soledad; Green, Patrick L.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
[Fernandez, Soledad; Green, Patrick L.] Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA.
[Fernandez, Soledad] Ohio State Univ, Arthur James Canc Hosp & Res Inst, Ctr Biostat, Columbus, OH 43210 USA.
[Jones, Kathryn S.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Basic Sci Program, Frederick, MD USA.
RP Green, PL (reprint author), Ohio State Univ, Ctr Retrovirus Res, Columbus, OH 43210 USA.
EM green.466@osu.edu
FU National Institutes of Health [CA100730, CA077556]; National Cancer
Institute, National Institutes of Health [HHSN26120080001E]; Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research
FX This work was supported by grants from the National Institutes of Health
(CA100730 and CA077556) to P. L. G. and in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract HHSN26120080001E (K.S.J.). This research was supported in part
by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research.
NR 39
TC 1
Z9 1
U1 0
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG
PY 2013
VL 87
IS 16
BP 9344
EP 9352
DI 10.1128/JVI.01079-13
PG 9
WC Virology
SC Virology
GA 193CS
UT WOS:000322535600048
PM 23785214
ER
PT J
AU Clements, ACA
Reid, HL
Kelly, GC
Hay, SI
AF Clements, Archie C. A.
Reid, Heidi L.
Kelly, Gerard C.
Hay, Simon I.
TI Further shrinking the malaria map: how can geospatial science help to
achieve malaria elimination?
SO LANCET INFECTIOUS DISEASES
LA English
DT Review
ID GEOGRAPHIC INFORMATION-SYSTEMS; DOMINANT ANOPHELES VECTORS; EAST-AFRICAN
HIGHLANDS; BIONOMIC PRECIS; CLIMATE-CHANGE; SPATIAL-DISTRIBUTION;
ENVIRONMENTAL DATA; TRANSMISSION RISK; SATELLITE IMAGERY;
DECISION-SUPPORT
AB Malaria is one of the biggest contributors to deaths caused by infectious disease. More than 30 countries have planned or started programmes to target malaria elimination, often with explicit support from international donors. The spatial distribution of malaria, at all levels of endemicity, is heterogeneous. Moreover, populations living in low-endemic settings where elimination efforts might be targeted are often spatially heterogeneous. Geospatial methods, therefore, can help design, target, monitor, and assess malaria elimination programmes. Rapid advances in technology and analytical methods have allowed the spatial prediction of malaria risk and the development of spatial decision support systems, which can enhance elimination programmes by enabling accurate and timely resource allocation. However, no framework exists for assessment of geospatial instruments. Research is needed to identify measurable indicators of elimination progress and to quantify the effect of geospatial methods in achievement of elimination outcomes.
C1 [Clements, Archie C. A.; Reid, Heidi L.; Kelly, Gerard C.] Univ Queensland, Sch Populat Hlth, Infect Dis Epidemiol Unit, Herston, Qld 4006, Australia.
[Hay, Simon I.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England.
[Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Clements, ACA (reprint author), Univ Queensland, Sch Populat Hlth, Infect Dis Epidemiol Unit, Herston Rd, Herston, Qld 4006, Australia.
EM a.clements@uq.edu.au
RI Hay, Simon/F-8967-2015
OI Hay, Simon/0000-0002-0611-7272
FU Australian National Health and Medical Research Council [631619];
Wellcome Trust [095066]; RAPIDD programme of the Science & Technology
Directorate, Department of Homeland Security; Fogarty International
Center, National Institutes of Health
FX We thank Dennis Shanks (Australian Army Malaria Institute, Brisbane,
QLD, Australia), Colleen Lau (University of Queensland, Brisbane, QLD,
Australia), and Lasse Vestergaard (WHO, Vanuatu), for providing comments
on the Review. We thank WHO for providing figure 3. ACAC is funded by a
career development award from the Australian National Health and Medical
Research Council (#631619). SIH is funded by a senior research
fellowship from the Wellcome Trust (#095066). This work forms part of
the output of MAP, principally funded by the Wellcome Trust. SIH also
acknowledges support from the RAPIDD programme of the Science &
Technology Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health. The funders had no
role in the preparation of the Review.
NR 93
TC 21
Z9 23
U1 3
U2 28
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 AUG
PY 2013
VL 13
IS 8
BP 709
EP 718
DI 10.1016/S1473-3099(13)70140-3
PG 10
WC Infectious Diseases
SC Infectious Diseases
GA 189VN
UT WOS:000322296500036
PM 23886334
ER
PT J
AU Huggins, CJ
Malik, R
Lee, S
Salotti, J
Thomas, S
Martin, N
Quinones, OA
Alvord, WG
Olanich, ME
Keller, JR
Johnson, PF
AF Huggins, Christopher J.
Malik, Radek
Lee, Sook
Salotti, Jacqueline
Thomas, Sara
Martin, Nancy
Quinones, Octavio A.
Alvord, W. Gregory
Olanich, Mary E.
Keller, Jonathan R.
Johnson, Peter F.
TI C/EBP gamma Suppresses Senescence and Inflammatory Gene Expression by
Heterodimerizing with C/EBP beta
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID BINDING-PROTEIN-BETA; ONCOGENE-INDUCED SENESCENCE; CELLULAR SENESCENCE;
TUMOR SUPPRESSION; SECRETORY PHENOTYPE; SKIN TUMORIGENESIS; CELLS; RAS;
IDENTIFICATION; SOFTWARE
AB C/EBP beta is an important regulator of oncogene-induced senescence (OIS). Here, we show that C/EBP gamma, a heterodimeric partner of C/EBP beta whose biological functions are not well understood, inhibits cellular senescence. Cebpg(-/-) mouse embryonic fibroblasts (MEFs) proliferated poorly, entered senescence prematurely, and expressed a proinflammatory gene signature, including elevated levels of senescence-associated secretory phenotype (SASP) genes whose induction by oncogenic stress requires C/EBP beta. The senescence-suppressing activity of C/EBP gamma required its ability to heterodimerize with C/EBP beta. Covalently linked C/EBP beta homodimers (beta similar to beta) inhibited the proliferation and tumorigenicity of Ras(V12)-transformed NIH 3T3 cells, activated SASP gene expression, and recruited the CBP coactivator in a Ras-dependent manner, whereas gamma similar to beta heterodimers lacked these capabilities and efficiently rescued proliferation of Cebpg(-/-) MEFs. C/EBP beta depletion partially restored growth of C/EBP gamma-deficient cells, indicating that the increased levels of C/EBP beta homodimers in Cebpg(-/-) MEFs inhibit proliferation. The proliferative functions of C/EBP gamma are not restricted to fibroblasts, as hematopoietic progenitors from Cebpg(-/-) bone marrow also displayed impaired growth. Furthermore, high CEBPG expression correlated with poorer clinical prognoses in several human cancers, and C/EBP gamma depletion decreased proliferation and induced senescence in lung tumor cells. Our findings demonstrate that C/EBP gamma neutralizes the cytostatic activity of C/EBP beta through heterodimerization, which prevents senescence and suppresses basal transcription of SASP genes.
C1 [Huggins, Christopher J.; Malik, Radek; Lee, Sook; Salotti, Jacqueline; Thomas, Sara; Martin, Nancy; Olanich, Mary E.; Keller, Jonathan R.; Johnson, Peter F.] NCI Frederick, Lab Canc Prevent, Ctr Canc Res, Frederick, MD USA.
[Quinones, Octavio A.; Alvord, W. Gregory] DMS Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Johnson, PF (reprint author), NCI Frederick, Lab Canc Prevent, Ctr Canc Res, Frederick, MD USA.
EM johnsope@mail.nih.gov
RI Malik, Radek/G-3578-2014
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
NR 47
TC 18
Z9 20
U1 1
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD AUG
PY 2013
VL 33
IS 16
BP 3242
EP 3258
DI 10.1128/MCB.01674-12
PG 17
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 188VM
UT WOS:000322224400015
PM 23775115
ER
PT J
AU Deng, T
Zhu, ZI
Zhang, SF
Leng, FF
Cherukuri, S
Hansen, L
Marino-Ramirez, L
Meshorer, E
Landsman, D
Bustin, M
AF Deng, Tao
Zhu, Z. Iris
Zhang, Shaofei
Leng, Fenfei
Cherukuri, Srujana
Hansen, Loren
Marino-Ramirez, Leonardo
Meshorer, Eran
Landsman, David
Bustin, Michael
TI HMGN1 Modulates Nucleosome Occupancy and DNase I Hypersensitivity at the
CpG Island Promoters of Embryonic Stem Cells
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID CHROMOSOMAL-PROTEIN HMGN1; CHROMATIN-BINDING; HISTONE H1;
GENE-REGULATION; LINKER HISTONE; MOBILITY; TRANSCRIPTION; MOUSE;
DIFFERENTIATION; BIOINFORMATICS
AB Chromatin structure plays a key role in regulating gene expression and embryonic differentiation; however, the factors that determine the organization of chromatin around regulatory sites are not fully known. Here we show that HMGN1, a nucleosome-binding protein ubiquitously expressed in vertebrate cells, preferentially binds to CpG island-containing promoters and affects the organization of nucleosomes, DNase I hypersensitivity, and the transcriptional profile of mouse embryonic stem cells and neural progenitors. Loss of HMGN1 alters the organization of an unstable nucleosome at transcription start sites, reduces the number of DNase I-hypersensitive sites genome wide, and decreases the number of nestin-positive neural progenitors in the subventricular zone (SVZ) region of mouse brain. Thus, architectural chromatin-binding proteins affect the transcription profile and chromatin structure during embryonic stem cell differentiation.
C1 [Deng, Tao; Zhang, Shaofei; Leng, Fenfei; Cherukuri, Srujana; Bustin, Michael] NCI, Prot Sect, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Zhu, Z. Iris; Hansen, Loren; Marino-Ramirez, Leonardo; Landsman, David] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Leng, Fenfei] Florida Int Univ, Dept Chem & Biochem, Miami, FL 33199 USA.
[Meshorer, Eran] Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Genet, Jerusalem, Israel.
RP Bustin, M (reprint author), NCI, Prot Sect, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
EM bustin@helix.nih.gov
RI Marino-Ramirez, Leonardo/I-5759-2013; Deng, Tao/J-2031-2015; Bustin,
Michael/G-6155-2015;
OI Marino-Ramirez, Leonardo/0000-0002-5716-8512; Landsman,
David/0000-0002-9819-6675
FU Intramural Research Program of the CCR; Intramural Research Program of
the NCI; Intramural Research Program of the NIH; Intramural Research
Program of the National Library of Medicine, NIH
FX This research was supported by the Intramural Research Programs of the
CCR, NCI, and NIH and of the National Library of Medicine, NIH.
NR 55
TC 15
Z9 15
U1 0
U2 9
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 AUG
PY 2013
VL 33
IS 16
BP 3377
EP 3389
DI 10.1128/MCB.00435-13
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 188VM
UT WOS:000322224400026
PM 23775126
ER
PT J
AU Simon-Loriere, E
Holmes, EC
Pagan, I
AF Simon-Loriere, Etienne
Holmes, Edward C.
Pagan, Israel
TI The Effect of Gene Overlapping on the Rate of RNA Virus Evolution
SO MOLECULAR BIOLOGY AND EVOLUTION
LA English
DT Article
DE overlapping genes; rate of evolution; RNA viruses; comparative genomics
ID SECONDARY STRUCTURE; READING FRAMES; IMMUNODEFICIENCY-VIRUS;
ANTAGONISTIC EPISTASIS; CODING REGIONS; PROTEIN; MUTATIONS;
IDENTIFICATION; FITNESS; COMPRESSION
AB Gene overlapping is widely employed by RNA viruses to generate genetic novelty while retaining a small genome size. However, gene overlapping also increases the deleterious effect of mutations as they affect more than one gene, thereby reducing the evolutionary rate of RNA viruses and hence their adaptive capacity. Although there is general agreement on the benefits of gene overlapping as a mechanism of genomic compression for rapidly evolving organisms, its effect on the pace of RNA virus evolution remains a source of debate. To address this issue, we collected sequence data from 117 instances of gene overlapping across 19 families, 30 genera, and 55 species of RNA viruses. On these data, we analyzed how genetic distances, selective pressures, and the distribution of RNA secondary structures and conserved protein functional domains vary between overlapping (OV) and nonoverlapping (NOV) regions. We show that gene overlapping generally results in a decrease in the rate of RNA virus evolution through a reduction in the frequency of synonymous mutations. However, this effect is less pronounced in genes with a terminal rather than an internal gene overlap, which might result from a greater proportion of protein functional conserved domains in NOV than in OV regions, in turn reducing the number of nonsynonymous mutations in the former. Overall, our analyses clarify the role of gene overlapping as a modulator of the evolutionary rates exhibited by RNA viruses and shed light on the factors that shape the genetic diversity of this important group of pathogens.
C1 [Simon-Loriere, Etienne] Inst Pasteur, Unite Genet Fonct Malad Infect, Paris, France.
[Simon-Loriere, Etienne] CNRS, URA CNRS3012, Paris, France.
[Holmes, Edward C.] Univ Sydney, Sch Biol Sci, Sydney Emerging Infect & Biosecur Inst, Sydney, NSW 2006, Australia.
[Holmes, Edward C.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Pagan, Israel] Ctr Biotecnol & Genom Plantas UPM INIA, Madrid, Spain.
RP Pagan, I (reprint author), Ctr Biotecnol & Genom Plantas UPM INIA, Madrid, Spain.
EM jesusisrael.pagan@upm.es
RI Pagan, Israel/H-1843-2015;
OI Pagan, Israel/0000-0001-8876-1194; Holmes, Edward/0000-0001-9596-3552; ,
Etienne/0000-0001-8420-7743
FU Marie Curie fellowship [PIOF-GA-2009-236470]; NIH/NIGMS [R01
GM080533-06]; NHMRC Australia Fellowship
FX This work was supported by Marie Curie fellowship PIOF-GA-2009-236470 to
I. P. and NIH/NIGMS grant R01 GM080533-06 and an NHMRC Australia
Fellowship to E.C.H.
NR 61
TC 13
Z9 13
U1 0
U2 19
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0737-4038
J9 MOL BIOL EVOL
JI Mol. Biol. Evol.
PD AUG
PY 2013
VL 30
IS 8
BP 1916
EP 1928
DI 10.1093/molbev/mst094
PG 13
WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
GA 183MQ
UT WOS:000321820400016
PM 23686658
ER
PT J
AU Nakajima, K
Jain, S
de Azua, IR
McMillin, SM
Rossi, M
Wess, J
AF Nakajima, Kenichiro
Jain, Shalini
de Azua, Inigo Ruiz
McMillin, Sara M.
Rossi, Mario
Wess, Juergen
TI Minireview: Novel Aspects of M-3 Muscarinic Receptor Signaling in
Pancreatic beta-Cells
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Review
ID PROTEIN-COUPLED RECEPTORS; GLUCAGON-LIKE PEPTIDE-1;
ACETYLCHOLINE-RECEPTOR; INSULIN-SECRETION; IN-VIVO; 7-TRANSMEMBRANE
RECEPTORS; TRANSCRIPTION FACTORS; RANDOM MUTAGENESIS; RELEASE; MICE
AB The release of insulin from pancreatic beta-cells is regulated by a considerable number of G protein-coupled receptors. During the past several years, we have focused on the physiological importance of beta-cell M-3 muscarinic acetylcholine receptors (M3Rs). At the molecular level, the M3R selectively activates G proteins of the G(q) family. Phenotypic analysis of several M3R mutant mouse models, including a mouse strain that lacks M3Rs only in pancreatic beta-cells, indicated that beta-cell M3Rs play a key role in maintaining blood glucose levels within a normal range. Additional studies with transgenic M3R mouse models strongly suggest that strategies aimed to enhance signaling through beta-cell M3Rs may prove useful in the treatment of type 2 diabetes. More recently, we analyzed transgenic mice that expressed an M3R-based designer receptor in a beta-cell-specific fashion, which enabled us to chronically activate a beta-cell G(q)-coupled receptor by a drug that is otherwise pharmacologically inert. Drug-dependent activation of this designer receptor stimulated the sequential activation of G(q), phospholipase C, ERK1/2, and insulin receptor substrate 2 signaling, thus triggering a series of events that greatly improved beta-cell function. Most importantly, chronic stimulation of this pathway protected mice against experimentally induced diabetes and glucose intolerance, induced either by streptozotocin or by the consumption of an energy-rich, high-fat diet. Because beta-cells are endowed with numerous receptors that mediate their cellular effects via activation of G(q)-type G proteins, these findings provide a rational basis for the development of novel antidiabetic drugs targeting this class of receptors.
C1 [Nakajima, Kenichiro; Jain, Shalini; de Azua, Inigo Ruiz; McMillin, Sara M.; Rossi, Mario; Wess, Juergen] NIDDK, Bioorgan Chem Lab, Mol Signaling Sect, Bethesda, MD 20892 USA.
RP Wess, J (reprint author), NIDDK, Bioorgan Chem Lab, Mol Signaling Sect, Bldg 8A,Room B1A-05,8 Ctr Dr, Bethesda, MD 20892 USA.
EM jurgenw@helix.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health.
NR 58
TC 9
Z9 9
U1 1
U2 6
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0888-8809
J9 MOL ENDOCRINOL
JI Mol. Endocrinol.
PD AUG
PY 2013
VL 27
IS 8
BP 1208
EP 1216
DI 10.1210/me.2013-1084
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 191WF
UT WOS:000322444700005
PM 23820900
ER
PT J
AU Thurin, K
Rasetti, R
Sambataro, F
Safrin, M
Chen, Q
Callicott, JH
Mattay, VS
Weinberger, DR
AF Thurin, K.
Rasetti, R.
Sambataro, F.
Safrin, M.
Chen, Q.
Callicott, J. H.
Mattay, V. S.
Weinberger, D. R.
TI Effects of ZNF804A on neurophysiologic measures of cognitive control
SO MOLECULAR PSYCHIATRY
LA English
DT Editorial Material
ID SCHIZOPHRENIA; ASSOCIATION; MECHANISMS
C1 [Thurin, K.; Rasetti, R.; Sambataro, F.; Safrin, M.; Chen, Q.; Callicott, J. H.; Mattay, V. S.; Weinberger, D. R.] NIMH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
[Sambataro, F.] UNIPr, Ist Italiano Tecnol, Brain Ctr Motor & Social Cognit, Parma, Italy.
[Chen, Q.; Mattay, V. S.; Weinberger, D. R.] Lieber Inst Brain Dev, Baltimore, MD USA.
RP Thurin, K (reprint author), NIMH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
EM drweinberger@libd.org
RI Callicott, Joseph/C-9102-2009; Sambataro, Fabio/E-3426-2010
OI Callicott, Joseph/0000-0003-1298-3334; Sambataro,
Fabio/0000-0003-2102-416X
FU Intramural NIH HHS [ZIC MH002905-05]
NR 10
TC 7
Z9 7
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD AUG
PY 2013
VL 18
IS 8
BP 852
EP 854
DI 10.1038/mp.2012.134
PG 4
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 191XM
UT WOS:000322448400004
PM 23032874
ER
PT J
AU Martinowich, K
Jimenez, DV
Zarate, CA
Manji, HK
AF Martinowich, K.
Jimenez, D. V.
Zarate, C. A., Jr.
Manji, H. K.
TI Rapid antidepressant effects: moving right along
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE BDNF; depression; ketamine; rapid-acting antidepressant; slow-wave
activity; synaptic potentiation
ID MAJOR DEPRESSIVE DISORDER; D-ASPARTATE ANTAGONIST; SLEEP SLOW WAVES;
RESISTANT BIPOLAR DEPRESSION; ACTIVITY-DEPENDENT SECRETION; MEDIAL
PREFRONTAL CORTEX; NEUROTROPHIC FACTOR BDNF; NMDA RECEPTOR BLOCKADE;
FORCED SWIMMING TEST; STAR-ASTERISK-D
AB Available treatments for depression have significant limitations, including low response rates and substantial lag times for response. Reports of rapid antidepressant effects of a number of compounds, including the glutamate N-methyl-D-aspartate receptor antagonist ketamine, have spurred renewed translational neuroscience efforts aimed at elucidating the molecular and cellular mechanisms of action that result in rapid therapeutic response. This perspective provides an overview of recent advances utilizing compounds with rapid-acting antidepressant effects, discusses potential mechanism of action and provides a framework for future research directions aimed at developing safe, efficacious antidepressants that achieve satisfactory remission not only by working rapidly but also by providing a sustained response.
C1 [Martinowich, K.; Jimenez, D. V.] Lieber Inst Brain Dev, Baltimore, MD USA.
[Martinowich, K.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Martinowich, K.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
[Zarate, C. A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Manji, H. K.] Janssen Res & Dev, Neurosci, Titusville, NJ 08560 USA.
RP Manji, HK (reprint author), Janssen Res & Dev, Neurosci, 1125 Trenton Harbourton Rd, Titusville, NJ 08560 USA.
EM HManji@its.jnj.com
RI Martinowich, Keri/F-9841-2012;
OI Martinowich, Keri/0000-0002-5237-0789
FU Intramural NIH HHS [ZIA MH002857-08, ZIA MH002927-03]
NR 103
TC 9
Z9 10
U1 1
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD AUG
PY 2013
VL 18
IS 8
BP 856
EP 863
DI 10.1038/mp.2013.55
PG 8
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 191XM
UT WOS:000322448400006
PM 23689537
ER
PT J
AU Hirvonen, J
Zanotti-Fregonara, P
Umhau, JC
George, DT
Rallis-Frutos, D
Lyoo, CH
Li, CT
Hines, CS
Sun, H
Terry, GE
Morse, C
Zoghbi, SS
Pike, VW
Innis, RB
Heilig, M
AF Hirvonen, J.
Zanotti-Fregonara, P.
Umhau, J. C.
George, D. T.
Rallis-Frutos, D.
Lyoo, C. H.
Li, C-T
Hines, C. S.
Sun, H.
Terry, G. E.
Morse, C.
Zoghbi, S. S.
Pike, V. W.
Innis, R. B.
Heilig, M.
TI Reduced cannabinoid CB1 receptor binding in alcohol dependence measured
with positron emission tomography
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE alcohol dependence; cannabinoid CB1 receptor; endocannabinoid; imaging;
positron emission tomography
ID ENDOCANNABINOID SYSTEM; NUCLEUS-ACCUMBENS; ETHANOL INTAKE; BRAIN;
ANTAGONIST; WITHDRAWAL; ADDICTION; STRESS; RATS; RADIOLIGAND
AB Brain cannabinoid CB1 receptors contribute to alcohol-related behaviors in experimental animals, but their potential role in humans with alcohol dependence is poorly understood. We measured CB1 receptors in alcohol dependent patients in early and protracted abstinence, and in comparison with control subjects without alcohol use disorders, using positron emission tomography and [F-18]FMPEP-d(2), a radioligand for CB1 receptors. We scanned 18 male in-patients with alcohol dependence twice, within 3-7 days of admission from ongoing drinking, and after 2-4 weeks of supervised abstinence. Imaging data were compared with those from 19 age-matched healthy male control subjects. Data were also analyzed for potential influence of a common functional variation (rs2023239) in the CB1 receptor gene (CNR1) that may moderate CB1 receptor density. On the first scan, CB1 receptor binding was 20-30% lower in patients with alcohol dependence than in control subjects in all brain regions and was negatively correlated with years of alcohol abuse. After 2-4 weeks of abstinence, CB1 receptor binding remained similarly reduced in these patients. Irrespective of the diagnostic status, C allele carriers at rs2023239 had higher CB1 receptor binding compared with non-carriers. Alcohol dependence is associated with a widespread reduction of cannabinoid CB1 receptor binding in the human brain and this reduction persists at least 2-4 weeks into abstinence. The correlation of reduced binding with years of alcohol abuse suggests an involvement of CB1 receptors in alcohol dependence in humans.
C1 [Hirvonen, J.; Zanotti-Fregonara, P.; Rallis-Frutos, D.; Lyoo, C. H.; Li, C-T; Hines, C. S.; Terry, G. E.; Morse, C.; Zoghbi, S. S.; Pike, V. W.; Innis, R. B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Umhau, J. C.; George, D. T.; Sun, H.; Heilig, M.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
RP Heilig, M (reprint author), NIAAA, Lab Clin & Translat Studies, Bldg 10,Room 1E-5334,10 Ctr Dr, Bethesda, MD 20892 USA.
EM markus.heilig@mail.nih.gov
FU Intramural Program of NIMH; Intramural Program of NIAAA; Academy of
Finland; Finnish Cultural Foundation; Finnish Foundation for Alcohol
Studies; Finnish Medical Foundation; Instrumentarium Foundation; Jalmari
and Rauha Ahokas Foundation; Paulo Foundation; Research Foundation of
Orion Corporation; Yrjo Jahnsson Foundation
FX We thank Kimberly Jenko, Kacey Anderson and David Clark for assisting in
the measurements of radioligand in plasma; Maria D Ferraris Araneta,
Gerald Hodges, William C Kreisl and Barbara Scepura as well as Chris
Geyer and the NIAAA nursing staff for subject recruitment and care; the
NIH PET Department for imaging; and the PMOD Technologies for providing
its image analysis and modeling software. This research was supported by
the Intramural Programs of NIMH and NIAAA. Jussi Hirvonen was supported
by personal grants from The Academy of Finland; The Finnish Cultural
Foundation; The Finnish Foundation for Alcohol Studies; The Finnish
Medical Foundation; The Instrumentarium Foundation; The Jalmari and
Rauha Ahokas Foundation; The Paulo Foundation; The Research Foundation
of Orion Corporation; and The Yrjo Jahnsson Foundation.
NR 49
TC 21
Z9 21
U1 1
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
EI 1476-5578
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD AUG
PY 2013
VL 18
IS 8
BP 916
EP 921
DI 10.1038/mp.2012.100
PG 6
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 191XM
UT WOS:000322448400013
PM 22776901
ER
PT J
AU Amin, MN
McLellan, JS
Huang, W
Orwenyo, J
Burton, DR
Koff, WC
Kwong, PD
Wang, LX
AF Amin, Mohammed N.
McLellan, Jason S.
Huang, Wei
Orwenyo, Jared
Burton, Dennis R.
Koff, Wayne C.
Kwong, Peter D.
Wang, Lai-Xi
TI Synthetic glycopeptides reveal the glycan specificity of
HIV-neutralizing antibodies
SO NATURE CHEMICAL BIOLOGY
LA English
DT Article
ID BETA-N-ACETYLGLUCOSAMINIDASE; CHEMOENZYMATIC SYNTHESIS;
TRANSGLYCOSYLATION ACTIVITY; GLYCOSYLATION; GLYCOPROTEINS; POTENT;
BROAD; RECOGNITION; OXAZOLINES; DOMAIN
AB A new class of glycan-reactive HIV-neutralizing antibodies, including PG9 and PG16, has been recently discovered that seem to recognize previously uncharacterized glycopeptide epitopes on HIV-1 gp120. However, further characterization and reconstitution of the precise neutralizing epitopes are complicated by the heterogeneity of glycosylation. We report here the design, synthesis and antigenic evaluation of new cyclic V1V2 glycopeptides carrying defined N-linked glycans at the conserved glycosylation sites (Asn160 and Asn156 or Asn173) derived from gp120 of two HIV-1 isolates. Antibody binding studies confirmed the necessity of a Man(5)GlcNAc(2) glycan at Asn160 for recognition by PG9 and PG16 and further revealed a critical role of a sialylated N-glycan at the secondary site (Asn156 or Asn173) in the context of glycopeptides for antibody binding. In addition to defining the glycan specificities of PG9 and PG16, the identified synthetic glycopeptides provide a valuable template for HIV-1 vaccine design.
C1 [Amin, Mohammed N.; Huang, Wei; Orwenyo, Jared; Wang, Lai-Xi] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
[Amin, Mohammed N.; Huang, Wei; Orwenyo, Jared; Wang, Lai-Xi] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA.
[McLellan, Jason S.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Burton, Dennis R.] Scripps Res Inst, Int AIDS Vaccine Initiat IAVI, Neutralizing Antibody Ctr, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Burton, Dennis R.] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA.
[Burton, Dennis R.] Massachusetts Gen Hosp, Massachusetts Inst Technol & Harvard, Ragon Inst, Cambridge, MA USA.
[Koff, Wayne C.] IAVI, New York, NY USA.
RP Wang, LX (reprint author), Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
EM LWang@som.umaryland.edu
FU National Institute of Allergy and Infectious Diseases (NIAID) (US
National Institutes of Health (NIH) [1R21AI101035]; International AIDS
Vaccine Initiative's Neutralizing Antibody Consortium; Intramural
Research Program of the Vaccine Research Center, NIAID-NIH
FX We thank S. Fan (University of Maryland) for providing the recombinant
Endo-D and K. Moremen and Y. Xiang (University of Georgia) for providing
the recombinant mouse alpha-1,2-mannosidase. This work is supported in
parts by grants from the National Institute of Allergy and Infectious
Diseases (NIAID) (US National Institutes of Health (NIH) grant
1R21AI101035 to L.-X. W.), the International AIDS Vaccine Initiative's
Neutralizing Antibody Consortium and by the Intramural Research Program
of the Vaccine Research Center, NIAID-NIH.
NR 42
TC 43
Z9 44
U1 3
U2 60
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1552-4450
EI 1552-4469
J9 NAT CHEM BIOL
JI Nat. Chem. Biol.
PD AUG
PY 2013
VL 9
IS 8
BP 521
EP 526
DI 10.1038/nchembio.1288
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 185FV
UT WOS:000321952700012
PM 23831758
ER
PT J
AU Lee, AS
Tang, C
Rao, MS
Weissman, IL
Wu, JC
AF Lee, Andrew S.
Tang, Chad
Rao, Mahendra S.
Weissman, Irving L.
Wu, Joseph C.
TI Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies
SO NATURE MEDICINE
LA English
DT Article
ID EMBRYONIC STEM; PARKINSONS-DISEASE; COPY NUMBER; REPROGRAMMING FACTORS;
C-MYC; EXPRESSION; GENERATION; TERATOMA; CULTURE; DIFFERENTIATION
AB Human pluripotent stem cells (PSCs) are a leading candidate for cell-based therapies because of their capacity for unlimited self renewal and pluripotent differentiation. These advances have recently culminated in the first-in-human PSC clinical trials by Geron, Advanced Cell Technology and the Kobe Center for Developmental Biology for the treatment of spinal cord injury and macular degeneration. Despite their therapeutic promise, a crucial hurdle for the clinical implementation of human PSCs is their potential to form tumors in vivo. In this Perspective, we present an overview of the mechanisms underlying the tumorigenic risk of human PSC-based therapies and discuss current advances in addressing these challenges.
C1 [Lee, Andrew S.; Tang, Chad; Weissman, Irving L.; Wu, Joseph C.] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
[Lee, Andrew S.; Wu, Joseph C.] Stanford Sch Med, Stanford Cardiovasc Inst, Stanford, CA USA.
[Lee, Andrew S.; Wu, Joseph C.] Stanford Univ, Dept Med, Div Cardiol, Sch Med, Stanford, CA 94305 USA.
[Tang, Chad] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA.
[Rao, Mahendra S.] NIH, Natl Ctr Regenerat Med, Bethesda, MD 20892 USA.
RP Wu, JC (reprint author), Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
EM mahendra.rao@nih.gov; irv@stanford.edu; joewu@stanford.edu
FU US National Institutes of Health [HL093172, HL099117, EB009689];
Burroughs Wellcome Fund Career Award in the Biomedical Sciences,
American Heart Association [EIA14420025]; California Institute of
Regenerative Medicine (CIRM) [DR2-05394, TR3-05556]; CIRM Tools
Technology II; Bio-X graduate student fellowship; Howard Hughes Medical
Institute research training fellowships
FX We thank A. Morris and J. Wha-Rhee for preparing the illustrations.
Because of space constraints, we were unable to include all relevant
studies regarding the tumorigenicity of pluripotent stem cells; we
apologize to those investigators whose valuable work we have omitted.
This work was supported in part by US National Institutes of Health
grants HL093172, HL099117 and EB009689, the Burroughs Wellcome Fund
Career Award in the Biomedical Sciences, American Heart Association
grant EIA14420025 and California Institute of Regenerative Medicine
(CIRM) grants DR2-05394 and TR3-05556 (J.C.W.); CIRM Tools & Technology
II (I.L.W.); a Bio-X graduate student fellowship (A.S.L.); and Howard
Hughes Medical Institute research training fellowships (A.S.L. and
C.T.).
NR 68
TC 126
Z9 130
U1 3
U2 51
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD AUG
PY 2013
VL 19
IS 8
BP 998
EP 1004
DI 10.1038/nm.3267
PG 7
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 196ML
UT WOS:000322779600025
PM 23921754
ER
PT J
AU Mazza, D
Mueller, F
Stasevich, TJ
McNally, JG
AF Mazza, Davide
Mueller, Florian
Stasevich, Timothy J.
McNally, James G.
TI Convergence of chromatin binding estimates in live cells
SO NATURE METHODS
LA English
DT Letter
ID FLUORESCENCE RECOVERY; DNA
C1 [Mazza, Davide] Ctr Imaging Sperimentale, Ist Sci Osped San Raffaele, Milan, Italy.
[Mazza, Davide] Univ Vita Salute San Raffaele, Milan, Italy.
[Mueller, Florian] CNRS, Ecole Normale Super, Inst Biol, UMR 8197, Paris, France.
[Mueller, Florian] CNRS, Inst Pasteur, Unit Imagerie & Modelisat, UMR 2582, Paris, France.
[Stasevich, Timothy J.] Osaka Univ, Grad Sch Frontier Biosci, Osaka, Japan.
[McNally, James G.] NCI, Fluorescence Imaging Grp, US Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Mazza, D (reprint author), Ctr Imaging Sperimentale, Ist Sci Osped San Raffaele, Milan, Italy.
EM mcnallyj@mail.nih.gov
RI Mueller, Florian/C-9075-2012; Mazza, Davide/R-5340-2016
OI Mueller, Florian/0000-0002-9622-4396; Mazza, Davide/0000-0003-2776-4142
FU Intramural NIH HHS
NR 8
TC 6
Z9 6
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1548-7091
J9 NAT METHODS
JI Nat. Methods
PD AUG
PY 2013
VL 10
IS 8
BP 691
EP 692
DI 10.1038/nmeth.2573
PG 3
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 191ZL
UT WOS:000322453600006
PM 23900248
ER
PT J
AU Gisselbrecht, SS
Barrera, LA
Porsch, M
Aboukhalil, A
Estep, PW
Vedenko, A
Palagi, A
Kim, Y
Zhu, XM
Busser, BW
Gamble, CE
Iagovitina, A
Singhania, A
Michelson, AM
Bulyk, ML
AF Gisselbrecht, Stephen S.
Barrera, Luis A.
Porsch, Martin
Aboukhalil, Anton
Estep, Preston W., III
Vedenko, Anastasia
Palagi, Alexandre
Kim, Yongsok
Zhu, Xianmin
Busser, Brian W.
Gamble, Caitlin E.
Iagovitina, Antonina
Singhania, Aditi
Michelson, Alan M.
Bulyk, Martha L.
TI Highly parallel assays of tissue-specific enhancers in whole Drosophila
embryos
SO NATURE METHODS
LA English
DT Article
ID CIS-REGULATORY MODULES; GENE-EXPRESSION; TRANSCRIPTION FACTORS; MESODERM
DEVELOPMENT; PHAGE PHI-C31; LAME DUCK; PROMOTERS; INTEGRASE;
IDENTIFICATION; DISSECTION
AB Transcriptional enhancers are a primary mechanism by which tissue-specific gene expression is achieved. Despite the importance of these regulatory elements in development, responses to environmental stresses and disease, testing enhancer activity in animals remains tedious, with a minority of enhancers having been characterized. Here we describe 'enhancer-FACS-seq' (eFS) for highly parallel identification of active, tissue-specific enhancers in Drosophila melanogaster embryos. Analysis of enhancers identified by eFS as being active in mesodermal tissues revealed enriched DNA binding site motifs of known and putative, previously uncharacterized mesodermal transcription factors. Naive Bayes classifiers using transcription factor binding site motifs accurately predicted mesodermal enhancer activity. Application of eFS to other cell types and organisms should accelerate the cataloging of enhancers and understanding how transcriptional regulation is encoded in them.
C1 [Gisselbrecht, Stephen S.; Barrera, Luis A.; Porsch, Martin; Aboukhalil, Anton; Vedenko, Anastasia; Palagi, Alexandre; Iagovitina, Antonina; Bulyk, Martha L.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
[Gisselbrecht, Stephen S.; Barrera, Luis A.; Porsch, Martin; Aboukhalil, Anton; Vedenko, Anastasia; Palagi, Alexandre; Iagovitina, Antonina; Bulyk, Martha L.] Harvard Univ, Sch Med, Boston, MA USA.
[Barrera, Luis A.; Bulyk, Martha L.] Harvard Univ, Sch Med, Div Hlth Sci & Technol, Harvard Massachusetts Inst Technol, Boston, MA USA.
[Barrera, Luis A.; Bulyk, Martha L.] Harvard Univ, Comm Higher Degrees Biophys, Cambridge, MA 02138 USA.
[Porsch, Martin] Univ Halle Wittenberg, Inst Comp Sci, D-06108 Halle, Germany.
[Aboukhalil, Anton] MIT, Dept Aeronaut & Astronaut, Cambridge, MA 02139 USA.
[Estep, Preston W., III] TeloMe Inc, Waltham, MA USA.
[Palagi, Alexandre] Univ Nice Sophia Antipolis, Polytech Nice Sophia, Dept Bioengn, F-06189 Nice, France.
[Kim, Yongsok; Zhu, Xianmin; Busser, Brian W.; Gamble, Caitlin E.; Singhania, Aditi; Michelson, Alan M.] NHLBI, Lab Dev Syst Biol, Genet & Dev Biol Ctr, US NIH, Bethesda, MD 20892 USA.
[Iagovitina, Antonina; Bulyk, Martha L.] Harvard Univ, Syst Biol Grad Program, Cambridge, MA 02138 USA.
[Bulyk, Martha L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
RP Bulyk, ML (reprint author), Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA.
EM mlbulyk@receptor.med.harvard.edu
OI Gisselbrecht, Stephen/0000-0001-8723-902X
FU US National Science Foundation; US National Institutes of Health [R01
HG005287]
FX This project was supported in part by a US National Science Foundation
Graduate Research Fellowship to L.A.B. and by grant R01 HG005287 from
the US National Institutes of Health to M.L.B. We thank G. Losyev and C.
Durkin for technical assistance, K.G. Guruharsha and K. VijayRaghavan
for sharing coordinates of the duf enhancer before its publication, R.P.
McCord, M. Markstein and O. Iartchouk for helpful discussion, and R.
Gordan, M. Markstein and T. Siggers for critical reading of the
manuscript.
NR 55
TC 26
Z9 26
U1 1
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1548-7091
J9 NAT METHODS
JI Nat. Methods
PD AUG
PY 2013
VL 10
IS 8
BP 774
EP +
DI 10.1038/NMETH.2558
PG 9
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 191ZL
UT WOS:000322453600029
PM 23852450
ER
PT J
AU Lee, SH
Kravitz, DJ
Baker, CI
AF Lee, Sue-Hyun
Kravitz, Dwight J.
Baker, Chris I.
TI Goal-dependent dissociation of visual and prefrontal cortices during
working memory
SO NATURE NEUROSCIENCE
LA English
DT Article
ID SHORT-TERM-MEMORY; NEURAL FRAMEWORK; CORTEX; OBJECTS; REPRESENTATIONS;
VISUALIZATION; INFORMATION; AREAS
AB To determine the specific contribution of brain regions to working memory, human participants performed two distinct tasks on the same visually presented objects. During the maintenance of visual properties, object identity could be decoded from extrastriate, but not prefrontal, cortex, whereas the opposite held for nonvisual properties. Thus, the ability to maintain information during working memory is a general and flexible cortical property, with the role of individual regions being goal-dependent.
C1 [Lee, Sue-Hyun; Kravitz, Dwight J.; Baker, Chris I.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
RP Lee, SH (reprint author), NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
EM sue-hyun.lee@nih.gov
RI Lee, Sue Hyun/F-5490-2015;
OI Baker, Chris/0000-0001-6861-8964
FU US National Institute of Mental Health Intramural Research Program
FX This work was supported by the US National Institute of Mental Health
Intramural Research Program. Thanks to S. Marrett and S. Inati for help
with data acquisition, E. Bilger and E. Aguila for data collection, A.
Harel and A. Martin for comments and members of the Laboratory of Brain
and Cognition for discussion.
NR 25
TC 35
Z9 35
U1 3
U2 27
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD AUG
PY 2013
VL 16
IS 8
BP 997
EP U35
DI 10.1038/nn.3452
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 190EV
UT WOS:000322323000008
PM 23817547
ER
PT J
AU Robertson, SD
Plummer, NW
de Marchena, J
Jensen, P
AF Robertson, Sabrina D.
Plummer, Nicholas W.
de Marchena, Jacqueline
Jensen, Patricia
TI Developmental origins of central norepinephrine neuron diversity
SO NATURE NEUROSCIENCE
LA English
DT Article
ID DOPAMINE-BETA-HYDROXYLASE; LOCUS-COERULEUS NEURONS; NORADRENERGIC
NEURONS; RAT-BRAIN; DEVELOPING HINDBRAIN; NERVOUS-SYSTEM; MESSENGER-RNA;
EXPOSURE; MICE; DISEASE
AB Central norepinephrine-producing neurons comprise a diverse population of cells differing in anatomical location, connectivity, function and response to disease and environmental insult. The mechanisms that generate this diversity are unknown. Here we elucidate the lineal relationship between molecularly distinct progenitor populations in the developing mouse hindbrain and mature norepinephrine neuron subtype identity. We have identified four genetically separable subpopulations of mature norepinephrine neurons differing in their anatomical location, axon morphology and efferent projection pattern. One of the subpopulations showed an unexpected projection to the prefrontal cortex, challenging the long-held belief that the locus coeruleus is the sole source of norepinephrine projections to the cortex. These findings reveal the embryonic origins of central norepinephrine neurons and provide multiple molecular points of entry for future study of individual norepinephrine circuits in complex behavioral and physiological processes including arousal, attention, mood, memory, appetite and homeostasis.
C1 [Robertson, Sabrina D.; Plummer, Nicholas W.; de Marchena, Jacqueline; Jensen, Patricia] NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Jensen, P (reprint author), NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
EM patricia.jensen@nih.gov
OI Plummer, Nicholas/0000-0003-2971-814X; Robertson,
Sabrina/0000-0003-4598-6929
FU Intramural Research Program of the US National Institutes of Health,
National Institute of Environmental Health Sciences [ZIA-ES-102805]
FX We thank S. Dymecki (Harvard Medical School) for Hoxa2-cre and RC::
FrePe mice and P. Charnay (INSERM) for Krox20cre mice. We thank T.
Wolfgang, G. Keeley and the National Institute of Environmental Health
Sciences Fluorescence Microscopy, Vivarium, Knockout Mice and Statistics
services for assistance. This research was supported by the Intramural
Research Program of the US National Institutes of Health, National
Institute of Environmental Health Sciences (ZIA-ES-102805).
NR 57
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U1 2
U2 14
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD AUG
PY 2013
VL 16
IS 8
BP 1016
EP U65
DI 10.1038/nn.3458
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 190EV
UT WOS:000322323000011
PM 23852112
ER
PT J
AU Matta, JA
Pelkey, KA
Craig, MT
Chittajallu, R
Jeffries, BW
McBain, CJ
AF Matta, Jose A.
Pelkey, Kenneth A.
Craig, Michael T.
Chittajallu, Ramesh
Jeffries, Brian W.
McBain, Chris J.
TI Developmental origin dictates interneuron AMPA and NMDA receptor subunit
composition and plasticity
SO NATURE NEUROSCIENCE
LA English
DT Article
ID LONG-TERM POTENTIATION; HIPPOCAMPAL INTERNEURONS; SILENT SYNAPSES;
GLUTAMATERGIC SYNAPSES; VISUAL-CORTEX; IN-VIVO; NEURONS; EXPERIENCE;
TRANSMISSION; PARVALBUMIN
AB Disrupted excitatory synapse maturation in GABAergic interneurons may promote neuropsychiatric disorders such as schizophrenia. However, establishing developmental programs for nascent synapses in GABAergic cells is confounded by their sparsity, heterogeneity and late acquisition of subtype-defining characteristics. We investigated synaptic development in mouse interneurons targeting cells by lineage from medial ganglionic eminence (MGE) or caudal ganglionic eminence (CGE) progenitors. MGE-derived interneuron synapses were dominated by GluA2-lacking AMPA-type glutamate receptors (AMPARs), with little contribution from NMDA-type receptors (NMDARs) throughout development. In contrast, CGE-derived cell synapses had large NMDAR components and used GluA2-containing AMPARs. In neonates, both MGE-and CGE-derived interneurons expressed primarily GluN2B subunit-containing NMDARs, which most CGE-derived interneurons retained into adulthood. However, MGE-derived interneuron NMDARs underwent a GluN2B-to-GluN2A switch that could be triggered acutely with repetitive synaptic activity. Our findings establish ganglionic eminence-dependent rules for early synaptic integration programs of distinct interneuron cohorts, including parvalbumin-and cholecystokinin-expressing basket cells.
C1 [Matta, Jose A.; Pelkey, Kenneth A.; Craig, Michael T.; Chittajallu, Ramesh; Jeffries, Brian W.; McBain, Chris J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurobiol, NIH, Bethesda, MD USA.
RP Pelkey, KA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurobiol, NIH, Bethesda, MD USA.
EM pelkeyk2@mail.nih.gov
RI Craig, Michael/E-7070-2011
OI Craig, Michael/0000-0001-8481-6709
FU Eunice Kennedy-Shriver National Institute of Child Health and Human
Development; PRAT Fellowship
FX D. Abebe and X. Yuan provided expert technical assistance. We thank S.
Anderson (University of Pennsylvania) for providing the Nkx2-1-cre
driver line and G. Fishell (New York University) for providing the RCE
reporter line. This work was supported by a Eunice Kennedy-Shriver
National Institute of Child Health and Human Development intramural
award to C.J.M. and a PRAT Fellowship to J.A.M.
NR 46
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U1 2
U2 18
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD AUG
PY 2013
VL 16
IS 8
BP 1032
EP U87
DI 10.1038/nn.3459
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 190EV
UT WOS:000322323000013
PM 23852113
ER
PT J
AU Seif, T
Chang, SJ
Simms, JA
Gibb, SL
Dadgar, J
Chen, BT
Harvey, BK
Ron, D
Messing, RO
Bonci, A
Hopf, FW
AF Seif, Taban
Chang, Shao-Ju
Simms, Jeffrey A.
Gibb, Stuart L.
Dadgar, Jahan
Chen, Billy T.
Harvey, Brandon K.
Ron, Dorit
Messing, Robert O.
Bonci, Antonello
Hopf, F. Woodward
TI Cortical activation of accumbens hyperpolarization-active NMDARs
mediates aversion-resistant alcohol intake
SO NATURE NEUROSCIENCE
LA English
DT Article
ID CUE-INDUCED REINSTATEMENT; COCAINE-SEEKING BEHAVIOR; NUCLEUS-ACCUMBENS;
PREFRONTAL CORTEX; GABA(A) RECEPTORS; ETHANOL-CONSUMPTION; ANIMAL-MODEL;
RATS; CORE; ADDICTION
AB Compulsive drinking despite serious adverse medical, social and economic consequences is a characteristic of alcohol use disorders in humans. Although frontal cortical areas have been implicated in alcohol use disorders, little is known about the molecular mechanisms and pathways that sustain aversion-resistant intake. Here, we show that nucleus accumbens core (NAcore) NMDA-type glutamate receptors and medial prefrontal (mPFC) and insula glutamatergic inputs to the NAcore are necessary for aversion-resistant alcohol consumption in rats. Aversion-resistant intake was associated with a new type of NMDA receptor adaptation, in which hyperpolarization-active NMDA receptors were present at mPFC and insula but not amygdalar inputs in the NAcore. Accordingly, inhibition of Grin2c NMDA receptor subunits in the NAcore reduced aversion-resistant alcohol intake. None of these manipulations altered intake when alcohol was not paired with an aversive consequence. Our results identify a mechanism by which hyperpolarization-active NMDA receptors under mPFC- and insula-to-NAcore inputs sustain aversion-resistant alcohol intake.
C1 [Seif, Taban; Chang, Shao-Ju; Simms, Jeffrey A.; Gibb, Stuart L.; Dadgar, Jahan; Ron, Dorit; Messing, Robert O.; Hopf, F. Woodward] Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, San Francisco, CA 94143 USA.
[Chen, Billy T.; Harvey, Brandon K.; Bonci, Antonello] Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA.
[Ron, Dorit; Messing, Robert O.; Bonci, Antonello; Hopf, F. Woodward] Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA USA.
[Bonci, Antonello] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD USA.
RP Hopf, FW (reprint author), Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, San Francisco, CA 94143 USA.
EM antonello.bonci@nih.gov; woody@gallo.ucsf.edu
RI Messing, Robert/D-3642-2015
OI Messing, Robert/0000-0002-5345-4431
FU NIAAA [RO1AA015358]; National Institute on Drug Abuse [F32DA028065];
NIAAA/NIH [RO1A/MH13438]; State of California for medical research for
alcohol substance abuse through the University of California San
Francisco
FX We thank V. Kharazia and the Gallo Center P50 National Institute on
Alcohol Abuse and Alcoholism (NIAAA) AA017072 Histology Core for
assistance with histology and R. Maiya for shRNA assistance. Supported
by NIAAA RO1AA015358 (F.W.H.), National Institute on Drug Abuse
F32DA028065 (T.S.), NIAAA/NIH RO1A/MH13438 (D.R.) and funds provided by
the State of California for medical research for alcohol substance abuse
through the University of California San Francisco (D.R., A.B., R.O.M.).
NR 60
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U1 1
U2 19
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
EI 1546-1726
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD AUG
PY 2013
VL 16
IS 8
BP 1094
EP U162
DI 10.1038/nn.3445
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 190EV
UT WOS:000322323000020
PM 23817545
ER
PT J
AU Brigman, JL
Daut, RA
Wright, T
Gunduz-Cinar, O
Graybeal, C
Davis, MI
Jiang, ZH
Saksida, LM
Jinde, S
Pease, M
Bussey, TJ
Lovinger, DM
Nakazawa, K
Holmes, A
AF Brigman, Jonathan L.
Daut, Rachel A.
Wright, Tara
Gunduz-Cinar, Ozge
Graybeal, Carolyn
Davis, Margaret I.
Jiang, Zhihong
Saksida, Lisa M.
Jinde, Seiichiro
Pease, Matthew
Bussey, Timothy J.
Lovinger, David M.
Nakazawa, Kazu
Holmes, Andrew
TI GluN2B in corticostriatal circuits governs choice learning and choice
shifting
SO NATURE NEUROSCIENCE
LA English
DT Article
ID MEDIAL PREFRONTAL CORTEX; RECEPTOR NR2A SUBUNIT; LONG-TERM DEPRESSION;
NMDA RECEPTORS; DORSOMEDIAL STRIATUM; BASAL-GANGLIA; MICE LACKING;
BEHAVIORAL FLEXIBILITY; ORBITOFRONTAL CORTEX; SYNAPTIC PLASTICITY
AB A choice that reliably produces a preferred outcome can be automated to liberate cognitive resources for other tasks. Should an outcome become less desirable, behavior must adapt in parallel or it becomes perseverative. Corticostriatal systems are known to mediate choice learning and flexibility, but the molecular mechanisms of these processes are not well understood. We integrated mouse behavioral, immunocytochemical, in vivo electrophysiological, genetic and pharmacological approaches to study choice. We found that the dorsal striatum (DS) was increasingly activated with choice learning, whereas reversal of learned choice engaged prefrontal regions. In vivo, DS neurons showed activity associated with reward anticipation and receipt that emerged with learning and relearning. Corticostriatal or striatal deletion of Grin2b (encoding the NMDA-type glutamate receptor subunit GluN2B) or DS-restricted GluN2B antagonism impaired choice learning, whereas cortical Grin2b deletion or OFC GluN2B antagonism impaired shifting. Our convergent data demonstrate how corticostriatal GluN2B circuits govern the ability to learn and shift choice behavior.
C1 [Brigman, Jonathan L.; Daut, Rachel A.; Wright, Tara; Gunduz-Cinar, Ozge; Graybeal, Carolyn; Pease, Matthew; Holmes, Andrew] NIAAA, Lab Behav & Genom Neurosci, NIH, Bethesda, MD USA.
[Davis, Margaret I.; Lovinger, David M.] NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD USA.
[Jiang, Zhihong; Jinde, Seiichiro; Nakazawa, Kazu] NIMH, Unit Genet Cognit & Behav, NIH, Bethesda, MD 20892 USA.
[Saksida, Lisa M.; Bussey, Timothy J.] Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England.
[Saksida, Lisa M.; Bussey, Timothy J.] MRC, Cambridge, England.
[Saksida, Lisa M.; Bussey, Timothy J.] Wellcome Trust Behav & Clin Neurosci Inst, Cambridge, England.
RP Holmes, A (reprint author), NIAAA, Lab Behav & Genom Neurosci, NIH, Bethesda, MD USA.
EM andrew.holmes@mail.nih.gov
RI Nakazawa, Kazutoshi/J-6195-2015; Brigman, Jonathan/O-4978-2016; Bussey,
Timothy/M-2758-2016; Saksida, Lisa/M-2753-2016; Gunduz Cinar,
Ozge/E-5756-2010
OI Nakazawa, Kazutoshi/0000-0001-5699-9093; Bussey,
Timothy/0000-0001-7518-4041; Saksida, Lisa/0000-0002-8416-8171; Davis,
Margaret/0000-0002-0489-8351; Gunduz Cinar, Ozge/0000-0002-3826-8905
FU NIAAA Intramural Research Program; Wellcome Trust; National Institute of
Mental Health Intramural Research Program
FX We are very grateful to G. Schoenbaum and A. Kravitz for discussions of
the in vivo recording results and to G. Luo for mutant genotyping.
J.L.B., C.G., T.W., M.I.D., R.A.D., M.P., O.G.-C., D.M.L. and A.H. were
supported by the NIAAA Intramural Research Program. L. M. S. and T.J.B.
were supported by The Wellcome Trust. Z.J. and K.N. were supported by
the National Institute of Mental Health Intramural Research Program.
NR 57
TC 42
Z9 42
U1 2
U2 22
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD AUG
PY 2013
VL 16
IS 8
BP 1101
EP U176
DI 10.1038/nn.3457
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 190EV
UT WOS:000322323000021
PM 23831965
ER
PT J
AU Rudebeck, PH
Saunders, RC
Prescott, AT
Chau, LS
Murray, EA
AF Rudebeck, Peter H.
Saunders, Richard C.
Prescott, Anna T.
Chau, Lily S.
Murray, Elisabeth A.
TI Prefrontal mechanisms of behavioral flexibility, emotion regulation and
value updating
SO NATURE NEUROSCIENCE
LA English
DT Article
ID PRIMATE ORBITOFRONTAL CORTEX; DECISION-MAKING; RHESUS-MONKEYS;
BASOLATERAL AMYGDALA; FRONTAL-CORTEX; FIBER PATHWAYS; REWARD VALUE;
REVERSAL; LESIONS; NEURONS
AB Two ideas have dominated neuropsychology concerning the orbitofrontal cortex (OFC). One holds that OFC regulates emotion and enhances behavioral flexibility through inhibitory control. The other ascribes to OFC a role in updating valuations on the basis of current motivational states. Neuroimaging, neurophysiological and clinical observations are consistent with either or both hypotheses. Although these hypotheses are compatible in principle, we present results supporting the latter view of OFC function and arguing against the former. We found that excitotoxic, fiber-sparing lesions confined to OFC in monkeys did not alter either behavioral flexibility, as measured by object reversal learning, or emotion regulation, as assessed by fear of snakes. A follow-up experiment indicated that a previously reported loss of inhibitory control resulted from damage to nearby fiber tracts and not from OFC dysfunction. Thus, OFC has a more specialized role in reward-guided behavior and emotion than has been thought, a function that includes value updating.
C1 [Rudebeck, Peter H.; Saunders, Richard C.; Prescott, Anna T.; Chau, Lily S.; Murray, Elisabeth A.] NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, US Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Rudebeck, PH (reprint author), NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, US Natl Inst Hlth, Bethesda, MD 20892 USA.
EM rudebeckp@mail.nih.gov
OI Rudebeck, Peter/0000-0002-1411-7555; Murray,
Elisabeth/0000-0003-1450-1642
FU Intramural Research Program of the US National Institute of Mental
Health
FX We thank D. Lundgren and E. Howland for assistance with data collection
and R. Reoli for help performing surgery. We also thank S. Wise and M.
Walton for comments on an earlier version of the manuscript. This work
was supported by the Intramural Research Program of the US National
Institute of Mental Health.
NR 49
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U1 3
U2 45
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD AUG
PY 2013
VL 16
IS 8
BP 1140
EP U225
DI 10.1038/nn.3440
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 190EV
UT WOS:000322323000026
PM 23792944
ER
PT J
AU Rouault, TA
AF Rouault, Tracey A.
TI Iron metabolism in the CNS: implications for neurodegenerative diseases
SO NATURE REVIEWS NEUROSCIENCE
LA English
DT Review
ID KINASE-ASSOCIATED NEURODEGENERATION; BLOOD-BRAIN-BARRIER; CERULOPLASMIN
GENE-MUTATIONS; TRANSVERSE RELAXATION RATES;
HALLERVORDEN-SPATZ-SYNDROME; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE;
FRIEDREICHS-ATAXIA; MOUSE MODEL; DYSTONIA-PARKINSONISM
AB Abnormal accumulation of brain iron has been detected in various neurodegenerative diseases, but the contribution of iron overload to pathology remains unclear. In a group of distinctive brain iron overload diseases known as 'neurodegeneration with brain iron accumulation' (NBIA) diseases, nine disease genes have been identified. Brain iron accumulation is observed in the globus pallidus and other brain regions in NBIA diseases, which are often associated with severe dystonia and gait abnormalities. Only two of these diseases, aceruloplasminaemia and neuroferritinopathy, are directly caused by abnormalities in iron metabolism, mainly in astrocytes and neurons, respectively. Understanding the early molecular pathophysiology of these diseases should aid insights into the role of iron and the design of specific therapeutic approaches.
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, Bethesda, MD 20892 USA.
RP Rouault, TA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, Bethesda, MD 20892 USA.
EM rouault@helix.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX The author thanks S. Hayflick and R. Vidal for generously sharing
images. The author gratefully acknowledges that the intramural programme
of the Eunice Kennedy Shriver National Institute of Child Health and
Human Development supported this work.
NR 141
TC 89
Z9 92
U1 8
U2 41
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-003X
J9 NAT REV NEUROSCI
JI Nat. Rev. Neurosci.
PD AUG
PY 2013
VL 14
IS 8
BP 551
EP 564
DI 10.1038/nrn3453
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 185WV
UT WOS:000322002100009
PM 23820773
ER
PT J
AU Sladewski, TE
Bookwalter, CS
Hong, MS
Trybus, KM
AF Sladewski, Thomas E.
Bookwalter, Carol S.
Hong, Myoung-Soon
Trybus, Kathleen M.
TI Single-molecule reconstitution of mRNA transport by a class V myosin
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID CIS-ACTING DETERMINANTS; ASYMMETRIC LOCALIZATION; STRUCTURAL ELEMENTS;
BUDDING YEAST; ASH1P; COMPLEX; MOTORS; IDENTIFICATION; RECOGNITION;
TRANSLATION
AB Molecular motors are instrumental in mRNA localization, which provides spatial and temporal control of protein expression and function. To obtain mechanistic insight into how a class V myosin transports mRNA, we performed single-molecule in vitro assays on messenger ribonucleoprotein (mRNP) complexes reconstituted from purified proteins and a localizing mRNA found in budding yeast. mRNA is required to form a stable, processive transport complex on actin-an elegant mechanism to ensure that only cargo-bound motors are motile. Increasing the number of localizing elements ('zip codes') on the mRNA, or configuring the track to resemble actin cables, enhanced run length and event frequency. In multi-zip-code mRNPs, motor separation distance varied during a run, thus showing the dynamic nature of the transport complex. Building the complexity of single-molecule in vitro assays is necessary to understand how these complexes function within cells.
C1 [Sladewski, Thomas E.; Bookwalter, Carol S.; Trybus, Kathleen M.] Univ Vermont, Dept Mol Physiol & Biophys, Burlington, VT 05405 USA.
[Hong, Myoung-Soon] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Trybus, KM (reprint author), Univ Vermont, Dept Mol Physiol & Biophys, Burlington, VT 05405 USA.
EM kathleen.trybus@uvm.edu
FU US National Institutes of Health [GM078097]
FX The authors thank M. Daniels for EM support and use of the National
Heart, Lung, and Blood Institute Electron Microscopy Core Facility. We
also thank G. Kennedy for technical assistance, D. Warshaw for use of
the TIRF microscope, E. Krementsova for protein expression and M.
Sckolnick, A. Hodges, H. Lu and S. Lowey for helpful discussions. This
work was supported by funds from the US National Institutes of Health
(GM078097 to K.M.T.).
NR 34
TC 20
Z9 20
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD AUG
PY 2013
VL 20
IS 8
BP 952
EP +
DI 10.1038/nsmb.2614
PG 8
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 195PH
UT WOS:000322715300008
PM 23812374
ER
PT J
AU Lu-Emerson, C
Snuderl, M
Kirkpatrick, ND
Goveia, J
Davidson, C
Huang, YH
Riedemann, L
Taylor, J
Ivy, P
Duda, DG
Ancukiewicz, M
Plotkin, SR
Chi, AS
Gerstner, ER
Eichler, AF
Dietrich, J
Stemmer-Rachamimov, AO
Batchelor, TT
Jain, RK
AF Lu-Emerson, Christine
Snuderl, Matija
Kirkpatrick, Nathaniel D.
Goveia, Jermaine
Davidson, Christian
Huang, Yuhui
Riedemann, Lars
Taylor, Jennie
Ivy, Percy
Duda, Dan G.
Ancukiewicz, Marek
Plotkin, Scott R.
Chi, Andrew S.
Gerstner, Elizabeth R.
Eichler, April F.
Dietrich, Jorg
Stemmer-Rachamimov, Anat O.
Batchelor, Tracy T.
Jain, Rakesh K.
TI Increase in tumor-associated macrophages after antiangiogenic therapy is
associated with poor survival among patients with recurrent glioblastoma
SO NEURO-ONCOLOGY
LA English
DT Article
DE antiangiogenic therapy; glioblastoma; myeloid cells; relapse
ID ANTI-VEGF THERAPY; HUMAN GLIOMAS; CLINICAL-TRIALS; BEVACIZUMAB;
PROGRESSION; INFILTRATION; METASTASIS; GROWTH; CANCER; CELLS
AB Antiangiogenic therapy is associated with increased radiographic responses in glioblastomas, but tumors invariably recur. Because tumor-associated macrophages have been shown to mediate escape from antiangiogenic therapy in preclinical models, we examined the role of macrophages in patients with recurrent glioblastoma. We compared autopsy brain specimens from 20 patients with recurrent glioblastoma who received antiangiogenic treatment and chemoradiation with 8 patients who received chemotherapy and/or radiotherapy without antiangiogenic therapy or no treatment. Tumor-associated macrophages were morphologically and phenotypically analyzed using flow cytometry and immunohistochemistry for CD68, CD14, CD163, and CD11b expression. Flow cytometry showed an increase in macrophages in the antiangiogenic-treated patients. Immunohistochemical analysis demonstrated an increase in CD68+ macrophages in the tumor bulk (P < .01) and infiltrative areas (P = .02) in antiangiogenic-treated patients. We also observed an increase in CD11b+ cells in the tumor bulk (P < .01) and an increase in CD163+ macrophages in infiltrative tumor (P = .02). Of note, an increased number of CD11b+ cells in bulk and infiltrative tumors (P = .05 and P = .05, respectively) correlated with poor overall survival among patients who first received antiangiogenic therapy at recurrence. In summary, recurrent glioblastomas showed an increased infiltration in myeloid populations in the tumor bulk and in the infiltrative regions after antiangiogenic therapy. Higher numbers of CD11b+ cells correlated with poor survival among these patients. These data suggest that tumor-associated macrophages may participate in escape from antiangiogenic therapy and may represent a potential biomarker of resistance and a potential therapeutic target in recurrent glioblastoma.
C1 [Lu-Emerson, Christine; Taylor, Jennie; Plotkin, Scott R.; Chi, Andrew S.; Gerstner, Elizabeth R.; Eichler, April F.; Dietrich, Jorg; Batchelor, Tracy T.] Massachusetts Gen Hosp, Dept Neurol, Ctr Canc, Boston, MA 02114 USA.
[Snuderl, Matija; Davidson, Christian; Stemmer-Rachamimov, Anat O.] Massachusetts Gen Hosp, Dept Pathol, Ctr Canc, Boston, MA 02114 USA.
[Kirkpatrick, Nathaniel D.; Goveia, Jermaine; Huang, Yuhui; Riedemann, Lars; Duda, Dan G.; Ancukiewicz, Marek; Jain, Rakesh K.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Kirkpatrick, Nathaniel D.; Goveia, Jermaine; Huang, Yuhui; Riedemann, Lars; Duda, Dan G.; Ancukiewicz, Marek; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA USA.
[Ivy, Percy] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Jain, RK (reprint author), Massachusetts Gen Hosp, Steele Lab, COX 734,100 Blossom St, Boston, MA 02114 USA.
EM jain@steele.mgh.harvard.edu
RI Riedemann, Lars/J-5725-2014;
OI Riedemann, Lars/0000-0002-9510-1845; Huang, Yuhui/0000-0003-1985-3575;
Snuderl, Matija/0000-0003-0752-0917
FU National Foundation for Cancer Research; National Institutes of Health
[R01CA129371, U01CA062490, K24CA 125440A, P01CA080124, R01CA163815,
R01CA159258]; Proton Beam/Federal Share Program; Harvard Clinical and
Translational Science Center (National Center for Research Resources);
Harvard Clinical and Translational Science Center (National Center for
Advancing Translational Sciences, National Institutes of Health )
[8UL1TR000170-05]; Harvard University
FX This work was funded by a the National Foundation for Cancer Research
grant (to R.K.J.), the National Institutes of Health (grants
R01CA129371, U01CA062490, K24CA 125440A to T.T.B.; P01CA080124,
R01CA163815 to R.K.J.; R01CA159258 to D.G.D.); Proton Beam/Federal Share
Program (to R.K.J. and D.G.D.), and the Harvard Clinical and
Translational Science Center (National Center for Research Resources and
the National Center for Advancing Translational Sciences, National
Institutes of Health Award 8UL1TR000170-05 and financial contributions
from Harvard University and its affiliated academic health care
centers).
NR 36
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U1 1
U2 9
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD AUG
PY 2013
VL 15
IS 8
BP 1079
EP 1087
DI 10.1093/neuonc/not082
PG 9
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 191PV
UT WOS:000322426000014
PM 23828240
ER
PT J
AU Vance, TM
Su, J
Fontham, ETH
Koo, SI
Chun, OK
AF Vance, Terrence M.
Su, Joseph
Fontham, Elizabeth T. H.
Koo, Sung I.
Chun, Ock K.
TI Dietary Antioxidants and Prostate Cancer: A Review
SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; GREEN-TEA-CATECHINS; VITAMIN-E;
BETA-CAROTENE; SELENIUM SUPPLEMENTATION; PLASMA ANTIOXIDANTS; PREVENTION
TRIAL; ALPHA-TOCOPHEROL; JAPANESE MEN; FOLLOW-UP
AB Prostate cancer is the most common noncutaneous cancer in men in the United States. Several studies have examined the relationship between prostate cancer and antioxidants; however, the results of these studies are inconsistent. This article provides a systematic review of studies on prostate cancer and antioxidant intake from diet and supplements. Tea and coffee appear to offer protection against advanced prostate cancer. Different forms of vitamin E appear to exert different effects on prostate cancer, with alpha-tocopherol potentially increasing and gamma-tocopherol potentially decreasing risk of the disease. There is no strong evidence for a beneficial effect of selenium, vitamin C, or beta-carotene, whereas lycopene appears to be negatively associated with risk of the disease. The effect of dietary antioxidants on prostate cancer remains undefined and inconclusive, with different antioxidants affecting prostate cancer risk differentially. Further studies are needed to clarify the relationship between antioxidants and prostate cancer risk and to delineate the underlying mechanisms.
C1 [Vance, Terrence M.; Koo, Sung I.; Chun, Ock K.] Univ Connecticut, Dept Nutr Sci, Storrs, CT 06269 USA.
[Su, Joseph] NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Fontham, Elizabeth T. H.] Louisiana State Univ, Hlth Sci Ctr, Dept Publ Hlth & Prevent Med, New Orleans, LA USA.
RP Chun, OK (reprint author), Univ Connecticut, Dept Nutr Sci, 3624 Horsebarn Rd Extens Unit 4017, Storrs, CT 06269 USA.
EM ock.chun@uconn.edu
FU NIH Cancer Epidemiology Small Grant [1R03CA159421-01A1]
FX This article was supported by the NIH Cancer Epidemiology Small Grant
#1R03CA159421-01A1.
NR 76
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U1 1
U2 42
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 0163-5581
J9 NUTR CANCER
JI Nutr. Cancer
PD AUG 1
PY 2013
VL 65
IS 6
BP 793
EP 801
DI 10.1080/01635581.2013.806672
PG 9
WC Oncology; Nutrition & Dietetics
SC Oncology; Nutrition & Dietetics
GA 194FP
UT WOS:000322616700002
PM 23909722
ER
PT J
AU Lee, RWY
Yoshida, S
Jung, ES
Mori, S
Baker, EH
Porter, FD
AF Lee, Ryan W. Y.
Yoshida, Shoko
Jung, Eun Sol
Mori, Susumu
Baker, Eva H.
Porter, Forbes D.
TI Corpus Callosum Measurements Correlate With Developmental Delay in
Smith-Lemli-Opitz Syndrome
SO PEDIATRIC NEUROLOGY
LA English
DT Article
ID DEFECTIVE CHOLESTEROL-BIOSYNTHESIS; AUTISM SPECTRUM DISORDERS; LIPID
RAFTS; OPTIZ-SYNDROME; AGENESIS; BRAIN; METAANALYSIS; INDIVIDUALS;
PHENOTYPE; DIAGNOSIS
AB BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is a multiple malformation, neurodevelopmental disorder of cholesterol metabolism caused by mutations in 7-dehydrocholesterol reductase. Corpus callosum (CC) malformations and developmental delay are common, but the relation between the two has not been evaluated. This study hypothesizes shorter callosal length and smaller area correlate with higher serum 7-dehydrocholesterol and increased severity of neurodevelopmental delay in SLOS. METHODS: Thirty-six individuals with SLOS (18M/18F) between 0.20 and 12.5 years.(mean = 3.9, SD = 3.6) and 36 typically developing controls (18 boys and 18 girls) between 0.12 and 12.8 years (mean = 4.0, SD = 3.6) were each imaged once on a 1.5T scanner. One midsagittal image per study was selected for manual CC measurement. Gross motor, fine motor, and language developmental quotients; anatomical severity score; and serum sterol levels were assessed. RESULTS: Shorter CC length and smaller area correlated with a lower developmental quotient in gross motor and language domains. Furthermore, length and area negatively correlated with a serum sterol precursors and severity score, and positively correlated with total cholesterol. Degree of developmental delay ranged from mild to severe, involving all domains. CONCLUSIONS: For individuals with SLOS, smaller callosal area and length are associated with higher 7-dehydrocholesterol, severity scores, and developmental delay. The relationship between callosal development and biochemical abnormalities in this cohort may lead to further studies supporting imaging biomarkers. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Lee, Ryan W. Y.; Jung, Eun Sol] Kennedy Krieger Inst, Dept Neurol & Dev Med, Baltimore, MD 21205 USA.
[Yoshida, Shoko; Mori, Susumu] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA.
[Baker, Eva H.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Porter, Forbes D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Lee, Ryan W. Y.; Porter, Forbes D.] US Dept HHS, Bethesda, MD USA.
RP Lee, RWY (reprint author), Kennedy Krieger Inst, Dept Neurol & Dev Med, 716 North Broadway St, Baltimore, MD 21205 USA.
EM leer@kennedykrieger.org
FU Eunice Kennedy Shriver National Institutes of Health;
Smith-Lemli-Opitz/RSH Foundation; National Institutes of Health Clinical
Center; National Institutes of Health Office of Rare Diseases; National
Institute of Child Health and Human Development
FX The authors report no conflicts of interest. This work was supported by
the intramural research program of the Eunice Kennedy Shriver National
Institutes of Health, the Smith-Lemli-Opitz/RSH Foundation, a Bench to
Bedside award from the National Institutes of Health Clinical Center,
the National Institutes of Health Office of Rare Diseases, and the
intramural research program of National Institute of Child Health and
Human Development. We also acknowledge the magnetic resonance imaging
technologists (Mary Busse RT, Lisa Catron RT, Bonita Damaska RT, Sandra
Hess RT, Sandra McKee RT, Scott Pryde RT, Maryanne Russell RT, Hugo
Sandoval RT, James Sedlacko RT, Ronald White RT, Betty Wise RT) and our
research coordinators Halima Goodwin CRNP and Sandra K. Conley CRNP. The
authors acknowledge Richard Kelley MD, PhD and Lisa Kratz PhD for their
work on the sterol assays, and Andrea Gropman MD for her clinical
evaluation of patients. The authors express appreciation to the families
and patients who participated in these studies.
NR 46
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U1 2
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0887-8994
J9 PEDIATR NEUROL
JI Pediatr. Neurol.
PD AUG
PY 2013
VL 49
IS 2
BP 107
EP 112
DI 10.1016/j.pediatrneurol.2013.03.015
PG 6
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA 192QI
UT WOS:000322499900006
PM 23859856
ER
PT J
AU Viswanathan, S
Rao, M
Keating, A
Srivastava, A
AF Viswanathan, Sowmya
Rao, Mahendra
Keating, Armand
Srivastava, Alok
TI Overcoming Challenges to Initiating Cell Therapy Clinical Trials in
Rapidly Developing Countries: India as a Model
SO STEM CELLS TRANSLATIONAL MEDICINE
LA English
DT Article
DE Cellular therapy; Clinical trials; Stem cells; Clinical translation
AB Increasingly, a number of rapidly developing countries, including India, China, Brazil, and others, are becoming global hot spots for the development of regenerative medicine applications, including stem cell-based therapies. Identifying and overcoming regulatory and translational research challenges and promoting scientific and ethical clinical trials with cells will help curb the growth of stem cell tourism for unproven therapies. It will also enable academic investigators, local regulators, and national and international biotechnology and biopharmaceutical companies to accelerate stem cell-based clinical research that could lead to effective innovative treatments in these regions. Using India as a model system and obtaining input from regulators, clinicians, academics, and industry representatives across the stem cell field in India, we reviewed the role of key agencies and processes involved in this field. We have identified areas that need attention and here provide solutions from other established and functioning models in the world to streamline and unify the regulatory and ethics approval processes for cell-based therapies. We also make recommendations to check the growth and functioning of clinics offering unproven treatments. Addressing these issues will remove considerable hurdles to both local and international investigators, accelerate the pace of research and development, and create a quality environment for reliable products to emerge. By doing so, these countries would have taken one important step to move to the forefront of stem cell-based therapeutics.
C1 [Viswanathan, Sowmya; Keating, Armand] Univ Hlth Network, Princess Margaret Hosp, Cell Therapy Program, Toronto, ON, Canada.
[Rao, Mahendra] NIH, NIH Ctr Regenerat Med, Bethesda, MD USA.
[Srivastava, Alok] Christian Med Coll & Hosp, Ctr Stem Cell Res, Vellore, Tamil Nadu, India.
RP Viswanathan, S (reprint author), Univ Hlth Network, Princess Margaret Hosp, 610 Univ Ave,Suite 5-303, Toronto, ON M5G 2M9, Canada.
EM Sowmya.viswanathan@uhnresearch.ca
FU Indian Council of Medical Research; Department of Biotechnology,
Ministry of Science and Technology, Government of India; Centre for Stem
Cell Research, a unit of inStem (Bangalore, India) at the Christian
Medical College (Vellore, India)
FX The workshop on Policies for Regulations of Cell Therapy Trials in India
at Vellore, India, was funded partly by the Indian Council of Medical
Research and the Department of Biotechnology, Ministry of Science and
Technology, Government of India, as well as the Centre for Stem Cell
Research, a unit of inStem (Bangalore, India) at the Christian Medical
College (Vellore, India).
NR 11
TC 6
Z9 6
U1 1
U2 21
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 2157-6564
J9 STEM CELL TRANSL MED
JI Stem Cells Transl. Med.
PD AUG
PY 2013
VL 2
IS 8
BP 607
EP 613
DI 10.5966/sctm.2013-0019
PG 7
WC Cell & Tissue Engineering
SC Cell Biology
GA 195DK
UT WOS:000322682300007
PM 23836804
ER
PT J
AU Zhang, K
Liu, WL
Locatis, C
Ackerman, M
AF Zhang, Kai
Liu, Wei-Li
Locatis, Craig
Ackerman, Michael
TI Uncompressed High-Definition Videoconferencing Tools for Telemedicine
and Distance Learning
SO TELEMEDICINE AND E-HEALTH
LA English
DT Article
DE videoconferencing; digital video; high-definition video; latency;
bandwidth requirement; cost efficiency; network communication
ID TELE-ENDOSCOPY; RELIABILITY; IMAGES; TELEDERMATOLOGY; ASSESSMENTS;
DIAGNOSIS
AB Uncompressed high-definition (HD) video image quality is superior to compressed HD video provided in most commercially available videoconferencing products. Uncompressed HD videoconferencing tools provide a more immersive experience because there is no reduction of image information and, in most cases, lower latency. Four open source uncompressed video applications are reviewed that have been tested at the National Library of Medicine: three transmitting uncompressed HD video and one transmitting loosely compressed standard-definition video. The technical requirements for implementing each are described, and test results in terms of image quality, latency, and application reliability are presented. Because the hardware and bandwidth requirements for uncompressed HD video are relatively high and most applications are still under development, they are generally not ready for mass deployment. Some are, however, ready for pilot testing and experimentation in clinical settings by either those who have or anticipate having bandwidth sufficient to support them or those interested in researching the effects higher-quality video may have on diagnostic and other clinical outcomes.
C1 [Zhang, Kai; Liu, Wei-Li; Locatis, Craig; Ackerman, Michael] NIH, Natl Lib Med, Bethesda, MD 20894 USA.
RP Zhang, K (reprint author), NIH, Off High Performance Comp & Commun, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM zhangkai@mail.nih.gov
FU National Library of Medicine
FX The DVTS research group provided detailed documents online for the
technologies developed for DVTS. Petr Holub and Martin Pulec of the
Computer Science Department of Masaryk University in the Czech Republic
provided technical support for UltraGrid. The iHDTV research group
provided support for setting up iHDTV. Fred Videon of the Computer
Science Department of the University of Washington provided support for
uncompressed/compressed HD CXP, and Benjamin Smith of the National
Center for Supercomputing Applications assisted with testing. This
research was supported by the National Library of Medicine intramural
research program.
NR 23
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Z9 2
U1 0
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1530-5627
J9 TELEMED E-HEALTH
JI Telemed. e-Health
PD AUG
PY 2013
VL 19
IS 8
BP 579
EP 584
DI 10.1089/tmj.2012.0219
PG 6
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 187IT
UT WOS:000322111300003
PM 23808905
ER
PT J
AU Ren, YJ
Zhang, SM
Mi, RF
Liu, QY
Zeng, XM
Rao, M
Hoke, A
Mao, HQ
AF Ren, Yong-Juan
Zhang, Shuming
Mi, Ruifa
Liu, Qiuyue
Zeng, Xianmin
Rao, Mahendra
Hoke, Ahmet
Mao, Hai-Quan
TI Enhanced differentiation of human neural crest stem cells towards the
Schwann cell lineage by aligned electrospun fiber matrix
SO ACTA BIOMATERIALIA
LA English
DT Article
DE Electrospun fibers; Neural crest stem cells; Schwann cells;
Differentiation; Alignment
ID PERIPHERAL-NERVE REGENERATION; RAT SPINAL-CORD; NEUROGENESIS; DENSITY;
PROLIFERATION; NANOFIBERS; INDUCTION; EXPANSION; CONDUIT
AB Human pluripotent stem cell-derived neural crest stem cells (NCSCs) provide a promising cell source for generating Schwann cells in the treatment of neurodegenerative diseases and traumatic injuries in the peripheral nervous system. Influencing cell behavior through a synthetic matrix topography has been shown to be an effective approach to directing stem cell proliferation and differentiation. Here we have investigated the effect of nanofiber topography on the differentiation of human embryonic stem cell-derived NCSCs towards the Schwann cell lineage. Using electrospun fibers of different diameters and alignments we demonstrated that aligned fiber matrices effectively induced cell alignment, and that fiber matrices with average diameters of 600 nm and 1.6 mu m most effectively promoted NCSC differentiation towards the Schwann cell lineage compared with random fibers and two-dimensional tissue culture plates. More importantly, human NCSCs that were predifferentiated in Schwann cell medium for 2 weeks exhibited higher sensitivity to the aligned fiber topography than undifferentiated NCSCs. This study provides an efficient protocol for Schwann cell derivation by combining an aligned nanofiber matrix and an optimized differentiation medium, and highlights the importance of matching extrinsic matrix signaling with cell intrinsic programming in a temporally specific manner. (C) 2013 Acts Materialia Inc. Published by Elsevier Ltd. All rights reserved.
C1 [Ren, Yong-Juan; Zhang, Shuming; Mao, Hai-Quan] Johns Hopkins Univ, Dept Mat Sci & Engn, Baltimore, MD 21218 USA.
[Ren, Yong-Juan; Zhang, Shuming; Mao, Hai-Quan] Johns Hopkins Sch Med, Translat Tissue Engn Ctr, Baltimore, MD 21287 USA.
[Mi, Ruifa; Hoke, Ahmet] Johns Hopkins Univ, Sch Med, Dept Neurol & Neurosurg, Baltimore, MD 21287 USA.
[Liu, Qiuyue; Zeng, Xianmin] Buck Inst Res Aging, Novato, CA 94945 USA.
[Rao, Mahendra] NIH, Ctr Regenerat Med, Bethesda, MD 20892 USA.
[Hoke, Ahmet] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA.
RP Mao, HQ (reprint author), Johns Hopkins Univ, Dept Mat Sci & Engn, 205 Maryland Hall, Baltimore, MD 21218 USA.
EM hmao@jhu.edu
OI Hoke, Ahmet/0000-0003-1215-3373
FU National Science Foundation [DMR-0748340]; Maryland Stem Cell Research
Fund [MSCRFE-0143, MSCRFE-0194]; Michael S. and Karen G. Ansari ALS
Center for Cell Therapy and Regeneration Research; California Institute
for Regenerative Medicine [TR-01856, CL1-00501]
FX This study was partially supported by Grants from the National Science
Foundation (Faculty Early Career Award DMR-0748340 (H.-Q.M.)), Maryland
Stem Cell Research Fund (MSCRFE-0143 (H.-Q.M.) and MSCRFE-0194 (A.H.)),
The Michael S. and Karen G. Ansari ALS Center for Cell Therapy and
Regeneration Research (A.H.), and California Institute for Regenerative
Medicine (Grants TR-01856 (X.Z.) and CL1-00501 (X.Z.)).
NR 38
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U1 1
U2 51
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1742-7061
J9 ACTA BIOMATER
JI Acta Biomater.
PD AUG
PY 2013
VL 9
IS 8
BP 7727
EP 7736
DI 10.1016/j.actbio.2013.04.034
PG 10
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 188QD
UT WOS:000322207700013
PM 23628775
ER
PT J
AU Moussouttas, M
Bhatnager, M
Huynh, T
Lai, E
Khoury, J
Dombrowski, K
DeCaro, M
Pacak, K
AF Moussouttas, Michael
Bhatnager, Meghna
Huynh, Thanh T.
Lai, Edwin W.
Khoury, John
Dombrowski, Keith
DeCaro, Matthew
Pacak, Karel
TI Association between sympathetic response, neurogenic cardiomyopathy, and
venous thromboembolization in patients with primary subarachnoid
hemorrhage
SO ACTA NEUROCHIRURGICA
LA English
DT Article
DE Subarachnoid hemorrhage; Sympathetic; Catecholamine; Neurogenic
cardiomyopathy; Venous; Thrombosis
ID CEREBROSPINAL-FLUID; EMOTIONAL EXCITEMENT; PLATELET REACTIVITY;
AFFECTIVE-ILLNESS; NERVOUS ACTIVITY; HEART-FAILURE; MENTAL STRESS;
PLASMA; NOREPINEPHRINE; ACTIVATION
AB Sympathetic activation promotes hemostasis, and subarachnoid hemorrhage (SAH) is associated with pronounced sympathetic activation. This investigation will assess whether catecholaminergic activity relates to venous thrombotic events in patients with acute SAH.
Observational study of consecutive SAH grade 3-5 patients requiring ventriculostomy insertion who did not undergo open surgical treatment of cerebral aneurysm. Cerebrospinal fluid (CSF) samples were obtained within 48 h of hemorrhage for assay of catecholamines, which were related to occurrence of deep venous thrombosis (DVT) and pulmonary embolization (PE).
Of the 92 subjects, mean age was 57 years, 76 % were female, and 57 % Caucasian; 11 % experienced lower extremity (LE) DVT, 12 % developed upper extremity (UE) or LE DVT, and 23 % developed any DVT/PE. Mean time to occurrence of UE/LE DVT was 7.8 days (+/-5.9 days), and mean time to development of PE was 8.8 days (+/-5.4 days).
In hazards analysis models, independent predictors of LE DVT included neurogenic cardiomyopathy (NC) [HR 4.97 (95%CI 1.32-18.7)], norepinephrine/3,4-dihydroxyphenylglycol ratio (NE/DHPG) [3.81 (2.04-7.14)], NE [5.91 (2.14-16.3)], and dopamine (DA) [2.27 (1.38-3.72)]. Predictors of UE/LE DVT included NC [5.78 (1.70-19.7)], cerebral infarction [4.01 (1.18-13.7)], NE [3.58 (1.40-9.19)], NE/DHPG [3.38 (1.80-6.33)] and DA [2.01 (1.20-3.35)]. Predictors of DVT/PE included Hunt-Hess grade (H/H) [3.02 (1.19-7.66)], NE [2.56 (1.23-5.37)] and 3,4-dihydroxyphenylalanine (DOPA) [3.49 (1.01-12.0)].
In severe SAH, central sympathetic activity and clinical manifestations of (nor)adrenergic activity relate to the development of venous thromboemboli. Catecholamine activation may promote hemostasis, or may represent a biomarker for venous thromboses.
C1 [Moussouttas, Michael] Capital Reg Med Ctr, Neurocrit Care Div, Capital Inst Neurosci, Trenton, NJ 08638 USA.
[Bhatnager, Meghna; Khoury, John; Dombrowski, Keith] Thomas Jefferson Med Ctr, Dept Neurol, Philadelphia, PA USA.
[Huynh, Thanh T.; Lai, Edwin W.; Pacak, Karel] NIH, Med Neuroendocrinol Sect, Program Reprod & Adult Endocrinol, Bethesda, MD 20892 USA.
[DeCaro, Matthew] Thomas Jefferson Med Ctr, Dept Med, Div Cardiol, Philadelphia, PA USA.
RP Moussouttas, M (reprint author), Capital Reg Med Ctr, Neurocrit Care Div, Capital Inst Neurosci, 750 Brunswick Ave, Trenton, NJ 08638 USA.
EM moussouttas@hotmail.com
FU Intramural Research Program of the National Institutes of Health
FX This research was sponsored in part by the Intramural Research Program
of the National Institutes of Health. The authors express their
gratitude to the nurses of the neurological intensive care unit from the
Jefferson Hospital of Neurosciences at Thomas Jefferson University
Medical Center for their assistance in this project.
NR 60
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U1 0
U2 7
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0001-6268
J9 ACTA NEUROCHIR
JI Acta Neurochir.
PD AUG
PY 2013
VL 155
IS 8
BP 1501
EP 1510
DI 10.1007/s00701-013-1725-x
PG 10
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 187JK
UT WOS:000322113500020
PM 23636336
ER
PT J
AU Stopponi, S
de Guglielmo, G
Somaini, L
Cippitelli, A
Cannella, N
Kallupi, M
Ubaldi, M
Heilig, M
Demopulos, G
Gaitanaris, G
Ciccocioppo, R
AF Stopponi, Serena
de Guglielmo, Giordano
Somaini, Lorenzo
Cippitelli, Andrea
Cannella, Nazzareno
Kallupi, Marsida
Ubaldi, Massimo
Heilig, Markus
Demopulos, Gregory
Gaitanaris, George
Ciccocioppo, Roberto
TI Activation of PPAR gamma by Pioglitazone Potentiates the Effects of
Naltrexone on Alcohol Drinking and Relapse in msP Rats
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Addiction; Abuse; Drug Seeking; Ethanol; Self-Administration
ID CORTICOTROPIN-RELEASING-FACTOR; ETHANOL-SEEKING BEHAVIOR;
RECEPTOR-GAMMA; INDUCED ANXIETY; ANIMAL-MODEL; REINSTATEMENT;
DEPENDENCE; STRESS; BRAIN; ABUSE
AB Background: Pioglitazone is a selective peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist used for the treatment of insulin resistance and type 2 diabetes. Previous studies conducted in our laboratory showed that activation of PPAR gamma by pioglitazone reduces alcohol drinking, stress-induced relapse, and alcohol withdrawal syndrome in rats. Pioglitazone was not able to prevent relapse elicited by alcohol cues. Conversely, the nonselective opioid antagonist naltrexone has been shown to reduce alcohol drinking and cue-but not stress-induced relapse in rodents.
Methods: Based on these findings, this study was sought to determine the efficacy of pioglitazone and naltrexone combination on alcohol intake and relapse behavior. Genetically selected alcohol-preferring Marchigian Sardinian (msP) rats were used for the study.
Results: Pioglitazone (10 and 30 mg/kg) and naltrexone (0.25 and 1.0 mg/kg) each individually reduced alcohol drinking in msP rats. The combination of the 2 drugs resulted in a more potent alcohol drinking reduction than single agents. Confirming previous studies, pioglitazone (10 and 30 mg/kg) significantly reduced relapse induced by the pharmacological stressor yohimbine (1.25 mg/kg) but not by cues predictive of alcohol availability. Conversely, naltrexone reduced reinstatement of drug seeking elicited by alcohol cues but not by yohimbine.
Conclusions: The drug combination was effective in reducing both relapse behaviors. These findings open new vistas in the use pioglitazone in combination with naltrexone for the treatment of alcoholism.
C1 [Stopponi, Serena; de Guglielmo, Giordano; Cippitelli, Andrea; Cannella, Nazzareno; Kallupi, Marsida; Ubaldi, Massimo; Ciccocioppo, Roberto] Univ Camerino, Sch Pharm, Pharmacol Unit, I-62032 Camerino, Italy.
[Somaini, Lorenzo] Hlth Local Unit, Addict Treatment Ctr, Biella, Italy.
[Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA.
[Demopulos, Gregory; Gaitanaris, George] Omeros Corp, Seattle, WA USA.
RP Ciccocioppo, R (reprint author), Univ Camerino, Sch Pharm, Pharmacol Unit, Via Madonna delle Carceri, I-62032 Camerino, Italy.
EM roberto.ciccocioppo@unicam.it
OI Heilig, Markus/0000-0003-2706-2482
FU University of Camerino
FX This study was supported by the University of Camerino (to RC). The
authors thank Rina Righi and Marino Cucculelli for expert technical
assistance.
NR 53
TC 17
Z9 17
U1 2
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD AUG
PY 2013
VL 37
IS 8
BP 1351
EP 1360
DI 10.1111/acer.12091
PG 10
WC Substance Abuse
SC Substance Abuse
GA 190GV
UT WOS:000322328300014
PM 23550625
ER
PT J
AU Rubinsky, AD
Dawson, DA
Williams, EC
Kivlahan, DR
Bradley, KA
AF Rubinsky, Anna D.
Dawson, Deborah A.
Williams, Emily C.
Kivlahan, Daniel R.
Bradley, Katharine A.
TI AUDIT-C Scores as a Scaled Marker of Mean Daily Drinking, Alcohol Use
Disorder Severity, and Probability of Alcohol Dependence in a US General
Population Sample of Drinkers
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE AUDIT-C; Alcohol Screening; Mean Daily Drinking; Alcohol Misuse
Severity; Alcohol Dependence
ID NATIONAL EPIDEMIOLOGIC SURVEY; PRIMARY-CARE PATIENTS; RISK DRINKING;
CONSUMPTION QUESTIONS; IDENTIFICATION TEST; UNITED-STATES; METAANALYSIS;
INTERVENTION; VALIDITY; IV
AB Background: Brief alcohol screening questionnaires are increasingly used to identify alcohol misuse in routine care, but clinicians also need to assess the level of consumption and the severity of misuse so that appropriate intervention can be offered. Information provided by a patient's alcohol screening score might provide a practical tool for assessing the level of consumption and severity of misuse.
Methods: This post hoc analysis of data from the 2001 to 2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) included 26,546 U. S. adults who reported drinking in the past year and answered additional questions about their consumption, including Alcohol Use Disorders Identification Test-Consumption questionnaire (AUDIT-C) alcohol screening. Linear or logistic regression models and postestimation methods were used to estimate mean daily drinking, the number of endorsed alcohol use disorder (AUD) criteria ("AUD severity"), and the probability of alcohol dependence associated with each individual AUDIT-C score (1 to 12), after testing for effect modification by gender and age.
Results: Among eligible past-year drinkers, mean daily drinking, AUD severity, and the probability of alcohol dependence increased exponentially across increasing AUDIT-C scores. Mean daily drinking ranged from < 0.1 to 18.0 drinks/d, AUD severity ranged from < 0.1 to 5.1 endorsed AUD criteria, and probability of alcohol dependence ranged from < 1 to 65% across scores 1 to 12. AUD severity increased more steeply across AUDIT-C scores among women than men. Both AUD severity and mean daily drinking increased more steeply across AUDIT-C scores among younger versus older age groups.
Conclusions: Results of this study could be used to estimate patient-specific consumption and severity based on age, gender, and alcohol screening score. This information could be integrated into electronic decision support systems to help providers estimate and provide feedback about patient-specific risks and identify those patients most likely to benefit from further diagnostic assessment.
C1 [Rubinsky, Anna D.; Williams, Emily C.; Kivlahan, Daniel R.; Bradley, Katharine A.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98108 USA.
[Rubinsky, Anna D.; Williams, Emily C.; Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Dawson, Deborah A.] NIAAA, Lab Epidemiol & Biometry, Div Clin & Biol Res, NIH, Bethesda, MD USA.
[Dawson, Deborah A.] Kelly Govt Serv Inc, Bethesda, MD USA.
[Kivlahan, Daniel R.; Bradley, Katharine A.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA.
[Kivlahan, Daniel R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA USA.
[Bradley, Katharine A.] Grp Hlth Res Inst, Seattle, WA USA.
RP Rubinsky, AD (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1660 S Columbian Way S-152, Seattle, WA 98108 USA.
EM anna.rubinsky@va.gov
FU U.S. Department of Veterans Affairs, Office of Research and Development,
Health Services Research and Development; Substance Use Disorders
Quality Enhancement Research Initiative; Agency for Healthcare Research
and Quality (AHRQ) National Research Services Award (NRSA) at the
University of Washington [T32 HS013853]
FX The research reported here was supported by the U.S. Department of
Veterans Affairs, Office of Research and Development, Health Services
Research and Development, and the Substance Use Disorders Quality
Enhancement Research Initiative. ADR was also supported by an Agency for
Healthcare Research and Quality (AHRQ) National Research Services Award
(NRSA) at the University of Washington (T32 HS013853). The views
expressed in this article are those of the authors and do not
necessarily reflect the position or policy of the Department of Veterans
Affairs, the United States Government, or any of the authors'
institutions.
NR 49
TC 36
Z9 36
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD AUG
PY 2013
VL 37
IS 8
BP 1380
EP 1390
DI 10.1111/acer.12092
PG 11
WC Substance Abuse
SC Substance Abuse
GA 190GV
UT WOS:000322328300017
PM 23906469
ER
PT J
AU Nevatte, T
O'Brien, PMS
Backstrom, T
Brown, C
Dennerstein, L
Endicott, J
Epperson, CN
Eriksson, E
Freeman, EW
Halbreich, U
Ismail, K
Panay, N
Pearlstein, T
Rapkin, A
Reid, R
Rubinow, D
Schmidt, P
Steiner, M
Studd, J
Sundstrom-Poromaa, I
Yonkers, K
AF Nevatte, Tracy
O'Brien, Patrick Michael Shaughn
Backstrom, Torbjorn
Brown, Candace
Dennerstein, Lorraine
Endicott, Jean
Epperson, C. Neill
Eriksson, Elias
Freeman, Ellen W.
Halbreich, Uriel
Ismail, Khalid
Panay, Nicholas
Pearlstein, Teri
Rapkin, Andrea
Reid, Robert
Rubinow, David
Schmidt, Peter
Steiner, Meir
Studd, John
Sundstrom-Poromaa, Inger
Yonkers, Kimberly
CA Int Soc Premenstrual Disorders
TI ISPMD consensus on the management of premenstrual disorders
SO ARCHIVES OF WOMENS MENTAL HEALTH
LA English
DT Article
DE Premenstrual syndrome; Premenstrual dysphoric disorder; Variant
premenstrual disorder; Core premenstrual disorder; Premenstrual
exacerbation; PMS; PMDD
ID SEROTONIN-REUPTAKE INHIBITORS; PLACEBO-CONTROLLED TRIAL;
COGNITIVE-BEHAVIORAL THERAPY; CYCLICAL ORAL NORETHISTERONE;
RANDOMIZED-CONTROLLED-TRIAL; CARBOHYDRATE-RICH BEVERAGE; LONG-TERM
TREATMENT; DYSPHORIC DISORDER; DOUBLE-BLIND; ADD-BACK
AB The second consensus meeting of the International Society for Premenstrual Disorders (ISPMD) took place in London during March 2011. The primary goal was to evaluate the published evidence and consider the expert opinions of the ISPMD members to reach a consensus on advice for the management of premenstrual disorders. Gynaecologists, psychiatrists, psychologists and pharmacologists each formally presented the evidence within their area of expertise; this was followed by an in-depth discussion leading to consensus recommendations. This article provides a comprehensive review of the outcomes from the meeting. The group discussed and agreed that careful diagnosis based on the recommendations and classification derived from the first ISPMD consensus conference is essential and should underlie the appropriate management strategy. Options for the management of premenstrual disorders fall under two broad categories, (a) those influencing central nervous activity, particularly the modulation of the neurotransmitter serotonin and (b) those that suppress ovulation. Psychotropic medication, such as selective serotonin reuptake inhibitors, probably acts by dampening the influence of sex steroids on the brain. Oral contraceptives, gonadotropin-releasing hormone agonists, danazol and estradiol all most likely function by ovulation suppression. The role of oophorectomy was also considered in this respect. Alternative therapies are also addressed, with, e.g. cognitive behavioural therapy, calcium supplements and Vitex agnus castus warranting further exploration.
C1 [Nevatte, Tracy] Keele Univ, Inst Sci & Technol Med, Stoke On Trent, Staffs, England.
[O'Brien, Patrick Michael Shaughn] Keele Univ, Sch Med, Acad Unit Obstet & Gynaecol, Univ Hosp North Staffordshire, Stoke On Trent, Staffs, England.
[Backstrom, Torbjorn] Norrland Univ Hosp, Umea Neurosteroid Res Ctr, Dept Clin Sci, Umea, Sweden.
[Brown, Candace] Univ Tennessee, Ctr Hlth Sci, Dept Psychiat, Memphis, TN 38163 USA.
[Brown, Candace] Univ Tennessee, Ctr Hlth Sci, Dept Obstet, Memphis, TN 38163 USA.
[Brown, Candace] Univ Tennessee, Ctr Hlth Sci, Dept Gynaecol, Memphis, TN 38163 USA.
[Dennerstein, Lorraine] Univ Melbourne, Dept Psychiat, Melbourne, Vic, Australia.
[Dennerstein, Lorraine] Natl Ageing Res Inst, Melbourne, Vic, Australia.
[Endicott, Jean] Columbia Univ, Dept Psychiat, New York, NY USA.
[Epperson, C. Neill] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Epperson, C. Neill] Univ Penn, Dept Obstet, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Epperson, C. Neill] Univ Penn, Dept Gynecol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Eriksson, Elias] Univ Gothenburg, Inst Neurosci & Physiol, Gothenburg, Sweden.
[Freeman, Ellen W.] Univ Penn, Dept Obstet Gynecol, Philadelphia, PA 19104 USA.
[Freeman, Ellen W.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Halbreich, Uriel] SUNY Buffalo, New York, NY USA.
[Halbreich, Uriel] WPA, New York, NY USA.
[Ismail, Khalid] Univ Birmingham, Sch Clin & Expt Med, Birmingham Womens Fdn Trust, Coll Med & Dent Sci, Birmingham, W Midlands, England.
[Panay, Nicholas] Univ London Imperial Coll Sci Technol & Med, Queen Charlottes Hosp, London, England.
[Panay, Nicholas] Univ London Imperial Coll Sci Technol & Med, Chelsea & Westminster Hosp, London, England.
[Pearlstein, Teri] Brown Univ, Dept Psychiat & Human Behav, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Rapkin, Andrea] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Genecol, Los Angeles, CA 90095 USA.
[Reid, Robert] Queens Univ, Kingston, ON, Canada.
[Rubinow, David] Univ N Carolina, Chapel Hill, NC USA.
[Schmidt, Peter] NIMH, Sect Behav Endocrinol, Bethesda, MD 20892 USA.
[Steiner, Meir] McMaster Univ, St Josephs Healthcare, Dept Psychiat Behav Neurosci Obstet & Gynaecol, Hamilton, ON L8P 3B6, Canada.
[Studd, John] Chelsea & Westminster Hosp, Dept Gynaecol, London, England.
[Sundstrom-Poromaa, Inger] UU, Dept Womens & Childrens Hlth, S-75185 Uppsala, Sweden.
[Yonkers, Kimberly] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.
[Yonkers, Kimberly] Dept Obstet, New Haven, CT USA.
[Yonkers, Kimberly] Dept Gynaecol, New Haven, CT USA.
RP Nevatte, T (reprint author), Keele Univ, Inst Sci & Technol Med, Stoke On Trent, Staffs, England.
EM t.nevatte@keele.ac.uk
RI Steiner, Meir /B-2121-2016;
OI Steiner, Meir/0000-0001-7838-2246; Sundstrom Poromaa,
Inger/0000-0002-2491-2042
FU Intramural NIH HHS [ZIA MH002865-08]; NIDA NIH HHS [K24 DA030301, R01
DA018359]
NR 106
TC 19
Z9 19
U1 1
U2 29
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 1434-1816
EI 1435-1102
J9 ARCH WOMEN MENT HLTH
JI Arch. Womens Ment. Health
PD AUG
PY 2013
VL 16
IS 4
BP 279
EP 291
DI 10.1007/s00737-013-0346-y
PG 13
WC Psychiatry
SC Psychiatry
GA 187JU
UT WOS:000322114700003
PM 23624686
ER
PT J
AU Wood, KC
Cortese-Krott, MM
Kovacic, JC
Noguchi, A
Liu, VB
Wang, X
Raghavachari, N
Boehm, M
Kato, GJ
Kelm, M
Gladwin, MT
AF Wood, Katherine C.
Cortese-Krott, Miriam M.
Kovacic, Jason C.
Noguchi, Audrey
Liu, Virginia B.
Wang, Xunde
Raghavachari, Nalini
Boehm, Manfred
Kato, Gregory J.
Kelm, Malte
Gladwin, Mark T.
TI Circulating Blood Endothelial Nitric Oxide Synthase Contributes to the
Regulation of Systemic Blood Pressure and Nitrite Homeostasis
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE blood; blood pressure; bone marrow transplant; nitric oxide synthase
ID ACUTE MYOCARDIAL-INFARCTION; ARGININE METHYL-ESTER; CELL-FREE
HEMOGLOBIN; NOS KNOCKOUT MICE; DEFICIENT MICE; PROGENITOR CELLS; DIETARY
NITRATE; STORAGE LESION; ISCHEMIA-REPERFUSION; PROTEIN EXPRESSION
AB Objective
Mice genetically deficient in endothelial nitric oxide synthase (eNOS(-/-)) are hypertensive with lower circulating nitrite levels, indicating the importance of constitutively produced nitric oxide (NO center dot) to blood pressure regulation and vascular homeostasis. Although the current paradigm holds that this bioactivity derives specifically from the expression of eNOS in endothelium, circulating blood cells also express eNOS protein. A functional red cell eNOS that modulates vascular NO center dot signaling has been proposed.
Approach and Results
To test the hypothesis that blood cells contribute to mammalian blood pressure regulation via eNOS-dependent NO center dot generation, we cross-transplanted wild-type and eNOS(-/-) mice, producing chimeras competent or deficient for eNOS expression in circulating blood cells. Surprisingly, we observed a significant contribution of both endothelial and circulating blood cell eNOS to blood pressure and systemic nitrite levels, the latter being a major component of the circulating NO center dot reservoir. These effects were abolished by the NOS inhibitor L-NG-nitroarginine methyl ester and repristinated by the NOS substrate l-arginine and were independent of platelet or leukocyte depletion. Mouse erythrocytes were also found to carry an eNOS protein and convert C-14-arginine into C-14-citrulline in NOS-dependent fashion.
Conclusions
These are the first studies to definitively establish a role for a blood-borne eNOS, using cross-transplant chimera models, that contributes to the regulation of blood pressure and nitrite homeostasis. This work provides evidence suggesting that erythrocyte eNOS may mediate this effect.
C1 [Wood, Katherine C.; Liu, Virginia B.; Wang, Xunde; Raghavachari, Nalini; Kato, Gregory J.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Kovacic, Jason C.; Boehm, Manfred] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
[Noguchi, Audrey] NHLBI, Murine Phenotyping Core, NIH, Bethesda, MD 20892 USA.
[Cortese-Krott, Miriam M.; Kelm, Malte] Univ Dusseldorf, Fac Med, Div Cardiol Pulmonol & Vasc Med, Cardiovasc Res Lab,Dept Internal Med, D-40225 Dusseldorf, Germany.
[Kovacic, Jason C.] Mt Sinai Hosp, Cardiovasc Inst, New York, NY 10029 USA.
[Gladwin, Mark T.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15213 USA.
[Gladwin, Mark T.] Univ Pittsburgh, Allergy & Crit Care Med, Pittsburgh, PA 15213 USA.
RP Gladwin, MT (reprint author), Univ Pittsburgh, Vasc Med Inst, NW 628 Montefiore Hosp,3459 5th Ave, Pittsburgh, PA 15213 USA.
EM malte.kelm@med.uni-duesseldorf.de; gladwinmt@upmc.edu
RI Kato, Gregory/I-7615-2014;
OI Kato, Gregory/0000-0003-4465-3217; Cortese-Krott, Miriam
/0000-0002-0593-1192
FU National Institutes of Health (NIH) [R01HL098032, RO1HL096973,
RC1DK085852]; Institute for Transfusion Medicine, Hemophilia Center of
Western Pennsylvania; Division of Intramural Research of the National
Heart, Lung and Blood Institute, NIH; Deutsche Forschungsgemeinschaft
[405/5-1, FOR809TP7 Me1821/3-1]; Forschungskommission of the Medical
Faculty of the Heinrich-Heine-University of Dusseldorf
FX This work was supported, in part, by National Institutes of Health (NIH)
grants R01HL098032, RO1HL096973, RC1DK085852, the Institute for
Transfusion Medicine, Hemophilia Center of Western Pennsylvania (M.T.
Gladwin), the Division of Intramural Research of the National Heart,
Lung and Blood Institute, NIH (G.J. Kato), the Deutsche
Forschungsgemeinschaft (405/5-1 and FOR809TP7 Me1821/3-1 to M. Kelm),
and the Forschungskommission of the Medical Faculty of the
Heinrich-Heine-University of Dusseldorf (to M. Cortese-Krott).
NR 62
TC 32
Z9 33
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD AUG
PY 2013
VL 33
IS 8
BP 1861
EP 1871
DI 10.1161/ATVBAHA.112.301068
PG 11
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 188IW
UT WOS:000322187600022
PM 23702660
ER
PT J
AU Simpson, EA
Ferrari, PF
AF Simpson, Elizabeth Ann
Ferrari, Pier Francesco
TI Mirror neurons are central for a second-person neuroscience: Insights
from developmental studies
SO BEHAVIORAL AND BRAIN SCIENCES
LA English
DT Editorial Material
AB Based on mirror neurons' properties, viewers are emotionally engaged when observing others - even when not actively interacting; therefore, characterizing non-participatory action-viewing as isolated may be misleading. Instead, we propose a continuum of socio-emotional engagement. We also highlight recent developmental work that uses a second-person perspective, investigating behavioral, physiological, and neural activity during caregiver-infant interactions.
C1 [Simpson, Elizabeth Ann; Ferrari, Pier Francesco] Univ Parma, Dipartimento Neurosci, I-43100 Parma, Italy.
[Simpson, Elizabeth Ann] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Comparat Ethol, Anim Ctr, Dickerson, MD 20842 USA.
RP Simpson, EA (reprint author), Univ Parma, Dipartimento Neurosci, I-43100 Parma, Italy.
EM simpsonea@mail.nih.gov; pierfrancesco.ferrari@unipr.it
OI Simpson, Elizabeth/0000-0003-2715-2533
FU NICHD NIH HHS [P01 HD064653]
NR 10
TC 0
Z9 0
U1 1
U2 8
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0140-525X
EI 1469-1825
J9 BEHAV BRAIN SCI
JI Behav. Brain Sci.
PD AUG
PY 2013
VL 36
IS 4
BP 438
EP 438
DI 10.1017/S0140525X12002051
PG 1
WC Psychology, Biological; Behavioral Sciences; Neurosciences
SC Psychology; Behavioral Sciences; Neurosciences & Neurology
GA 188VV
UT WOS:000322225700060
PM 23883767
ER
PT J
AU Runarsdottir, SB
Gudmundsson, G
Aspelund, T
Harris, TB
Launer, LJ
Gudnason, V
Gislason, T
AF Runarsdottir, Solrun Bjork
Gudmundsson, Gunnar
Aspelund, Thor
Harris, Tamara B.
Launer, Lenore J.
Gudnason, Vilmundur
Gislason, Thorarinn
TI Prevalence of Airflow Obstruction in Nonsmoking Older Individuals Using
Different Spirometric Criteria: The AGES Reykjavik Study
SO COPD-JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE
LA English
DT Article
DE Older individuals; Chronic Obstructive Pulmonary Disease; spirometry;
lower limit of normal; co-morbidities
ID MULTIPLE CHRONIC CONDITIONS; PULMONARY-DISEASE; REFERENCE VALUES;
FEV1/FVC RATIO; UNITED-STATES; LUNG-FUNCTION; PRIMARY-CARE; COPD;
DIAGNOSIS; POPULATION
AB Background: The prevalence and characteristics of airway obstruction in older individuals varies widely with the definition used. We used a random sample of never smoking older population in Iceland to compare the prevalence and clinical profile of subjects diagnosed with Chronic Obstructive Pulmonary Disease (COPD) based on different spirometric criteria. Material and methods: The study uses data from the Age, Gene/Environment Susceptibility-Reykjavik Study, comprising survivors from the Reykjavik Study. Procedures included standardized questionnaires and pre-bronchodilator spirometry for measurement of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Results: Total of 495 individuals (150 men and 345 women) met study criteria. Mean age 77 years (range 66-92 years) using fixed ratio (FEV1/FVC < 70%) up to 29% of the population were diagnosed with COPD Stage I. The prevalence of COPD increased with age. Only 7 among 495 (1.4%) were diagnosed with COPD using FEV1/FVC LLN and FEV1 LLN. Conclusion: Application of the GOLD criteria for diagnosis of COPD in older lifelong never smoking subjects identifies a substantial number of non-symptomatic subjects as having COPD. If airway obstruction is defined by FEV1/FVC and FEV1 being below the LLN using appropriate reference equations, only very few non-smoking older individuals fulfill the criteria for COPD.
C1 [Runarsdottir, Solrun Bjork; Gudmundsson, Gunnar; Gislason, Thorarinn] Landspitali Univ Hosp, Dept Resp Med & Sleep, IS-108 Reykjavik, Iceland.
[Gudmundsson, Gunnar; Aspelund, Thor; Gudnason, Vilmundur; Gislason, Thorarinn] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Harris, Tamara B.; Launer, Lenore J.] NIA, Labaratory Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
RP Gislason, T (reprint author), Landspitali Univ Hosp, Dept Resp Med & Sleep, E-7, IS-108 Reykjavik, Iceland.
EM thorarig@landspitali.is
RI Aspelund, Thor/C-5983-2008; Gudnason, Vilmundur/K-6885-2015;
Gudmundsson, Gunnar/F-1974-2013
OI Aspelund, Thor/0000-0002-7998-5433; Gudnason,
Vilmundur/0000-0001-5696-0084; Gudmundsson, Gunnar/0000-0002-7251-8322
FU NIH [N01-AG-1-2100]; NIA Intramural Research Program, Hjartavernd (the
Icelandic Heart Association); Althingi (the Icelandic Parliament)
FX The Ages Reykjavik study has been funded by NIH contract N01-AG-1-2100,
the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart
Association), and Althingi (the Icelandic Parliament).
NR 30
TC 2
Z9 2
U1 2
U2 3
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1541-2555
J9 COPD
JI COPD-J. Chronic Obstr. Pulm. Dis.
PD AUG
PY 2013
VL 10
IS 4
BP 493
EP 499
DI 10.3109/15412555.2013.773303
PG 7
WC Respiratory System
SC Respiratory System
GA 186TX
UT WOS:000322069500013
PM 23875743
ER
PT J
AU Liu, QY
Pedersen, OZ
Peng, J
Couture, LA
Rao, MS
Zeng, XM
AF Liu, Qiuyue
Pedersen, Oliver Z.
Peng, Jun
Couture, Larry A.
Rao, Mahendra S.
Zeng, Xianmin
TI Optimizing dopaminergic differentiation of pluripotent stem cells for
the manufacture of dopaminergic neurons for transplantation
SO CYTOTHERAPY
LA English
DT Article
DE cell therapy; dopaminergic neuron; GMP; human pluripotent stem cells
ID PARKINSONS-DISEASE; DEFINED CONDITIONS; PRECURSORS; SURVIVAL
AB Background aims. We have previously described a xeno-free scalable system to generate transplantable dopaminergic neurons from human pluripotent stem cells. However, several important questions remain to be answered about our cell therapy efforts. These include determining the exact time at which cells should be transplanted and whether cells at this stage can be frozen, shipped, thawed and injected without compromising their ability to mature and survive the transplantation procedure. We also needed to determine whether further optimization of the culture process could shorten the development time and reduce variability and whether a current Good Manufacture Practice (CGMP) facility could manufacture cells with fidelity. Methods. We developed an optimized protocol that included modulating the sonic hedgehog homolog gradient with bone morphogenetic proteins (BMP2) and addition of activin to the culture medium, which shortened the time to generate Lmx1A and FoxA2 immunoreactive cells by 4-6 days. Results. We showed that cells at this stage could be safely frozen and thawed while retaining an excellent ability to continue to mature in vitro and survive transplant in vivo. Importantly, we successfully adapted this process to a CGMP facility and manufactured two lots of transplant-ready dopaminergic neurons (>250 vials) under COMP-compatible conditions. In vitro characterization, including viability/recovery on thawing, whole genome expression as well as expression of midbrain/dopaminergic markers, showed that the cells manufactured under GMP-compatible conditions were similar to cells produced at lab scale. Conclusions. Our results suggest that this optimized protocol can be used to generate dopaminergic neurons for Investigational New Drug enabling studies.
C1 [Liu, Qiuyue; Pedersen, Oliver Z.; Peng, Jun; Zeng, Xianmin] Buck Inst Res Aging, Novato, CA 94945 USA.
[Couture, Larry A.] Bechman Res Inst, City Of Hope, CA USA.
[Rao, Mahendra S.] NIH, Natl Ctr Regenerat Med, Bethesda, MD 20892 USA.
RP Zeng, XM (reprint author), Buck Inst Res Aging, 8001 Redwood Blvd, Novato, CA 94945 USA.
EM xzeng@buckinstitute.org
FU California Institute for Regenerative Medicine [TR-01856, TG2-01155];
National Institutes of Health Center for Regenerative Medicine
FX This work was supported in part by California Institute for Regenerative
Medicine Grants TR-01856 and TG2-01155 to XZ and the National Institutes
of Health Center for Regenerative Medicine, a common fund initiative to
MSR. We thank all members of our laboratory for helpful discussions. QL
is currently affiliated with Key Laboratory of Farm Animal Genetic
Resources and Germplasm Innovation of Ministry of Agriculture, Institute
of Animal Science, Chinese Academy of Agricultural Sciences, Beijing,
China.
NR 20
TC 12
Z9 12
U1 1
U2 14
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1465-3249
J9 CYTOTHERAPY
JI Cytotherapy
PD AUG
PY 2013
VL 15
IS 8
BP 999
EP 1010
DI 10.1016/j.jcyt.2013.03.006
PG 12
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Hematology; Medicine, Research & Experimental
SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research
& Experimental Medicine
GA 185TT
UT WOS:000321993900011
PM 23664011
ER
PT J
AU Kodama, S
Negishi, M
AF Kodama, Susumu
Negishi, Masahiko
TI PXR cross-talks with internal and external signals in physiological and
pathophysiological responses
SO DRUG METABOLISM REVIEWS
LA English
DT Review
DE Cellular signal; gene regulation; nuclear receptor; pregnane X receptor;
xenobiotics
ID PREGNANE-X-RECEPTOR; INFLAMMATORY-BOWEL-DISEASE; NF-KAPPA-B;
CONSTITUTIVE-ANDROSTANE RECEPTOR; CYP3A4 GENE-EXPRESSION; BILE-ACID
METABOLISM; NUCLEAR RECEPTOR; PPAR-GAMMA; XENOBIOTIC RECEPTOR;
LIPID-METABOLISM
AB Pregnane X receptor (PXR), an orphan member of the nuclear receptor superfamily, is a major xeno-sensing transcription factor. In response to xenobiotic exposure, PXR regulates genes involved in the metabolism and transport of xenobiotics to protect the body from their harmful effects. Recent progress has revealed that PXR responds not only to such external signals but also to internal signals to help the body adapt to changes in the internal environment, including dysregulation of the immune system. PXR responds to external and internal signals by up-or down-regulating certain metabolic pathways and cellular signals through gene regulation. PXR is a potential therapeutic target for inflammatory as well as metabolic diseases, although its activation may also have unfavorable effects on human health. This review will discuss the recent progress in the understanding of the physiological and pathophysiological roles of PXR and their implications in human diseases and drug therapy by elucidating the molecular mechanisms underlying PXR-mediated gene regulation.
C1 [Kodama, Susumu] Tohoku Univ, Grad Sch Pharmaceut Sci, Div Drug Metab & Mol Toxicol, Aoba Ku, Sendai, Miyagi 9808578, Japan.
[Negishi, Masahiko] NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Kodama, S (reprint author), Tohoku Univ, Grad Sch Pharmaceut Sci, Div Drug Metab & Mol Toxicol, Aoba Ku, 6-3 Aramaki Aoba, Sendai, Miyagi 9808578, Japan.
EM kodama@m.tohoku.ac.jp
FU Japan Society for the Promotion of Science [24790142]; National
Institutes of Health and National Institute of Environmental Health
Sciences [Z01ES1005-01]
FX This work was supported by Grant-in-Aid for Young Scientists (B) from
the Japan Society for the Promotion of Science: 24790142 (SK) and by the
Intramural Research Program of the National Institutes of Health and
National Institute of Environmental Health Sciences: Z01ES1005-01 (MN).
NR 108
TC 10
Z9 11
U1 0
U2 14
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0360-2532
J9 DRUG METAB REV
JI Drug Metab. Rev.
PD AUG
PY 2013
VL 45
IS 3
BP 300
EP 310
DI 10.3109/03602532.2013.795585
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 186DR
UT WOS:000322022700002
PM 23701014
ER
PT J
AU Katz, AJ
Ryan, PB
Racoosin, JA
Stang, PE
AF Katz, Aaron J.
Ryan, Patrick B.
Racoosin, Judith A.
Stang, Paul E.
TI Assessment of Case Definitions for Identifying Acute Liver Injury in
Large Observational Databases
SO DRUG SAFETY
LA English
DT Article
ID 000 STATIN USERS; ADVERSE EVENTS; INCREASED RISK; UNITED-STATES;
ROSUVASTATIN; SAFETY; COHORT; DRUGS; POPULATION; HEPATITIS
AB Determining the aetiology of acute liver injury (ALI) may be challenging to both clinicians and researchers. Observational research is particularly useful in studying rare medical outcomes such as ALI; however, case definitions for ALI in previous observational studies lack consistency and sensitivity. ALI is a clinically important condition with various aetiologies, including drug exposure.
The aim of this study was to evaluate four distinct case definitions for ALI across a diverse set of large observational databases, providing a better understanding of ALI prevalence and natural history.
Seven healthcare databases: GE Healthcare, MarketScan(A (R)) Lab Database, Humana Inc., Partners HealthCare System, Regenstrief Institute, SDI Health (now IMS Health, Inc.), and the National Patient Care Database of the Veterans Health Administration.
We evaluated prevalence of ALI through the application of four distinct case definitions across seven observational healthcare databases. We described how laboratory and clinical characteristics of identified case populations varied across definitions and examined the prevalence of other hepatobiliary disorders among identified ALI cases that may decrease suspicion of drug-induced liver injury (DILI) in particular.
This study demonstrated that increasing the restrictiveness of the case definition resulted in fewer cases, but greater prevalence of ALI clinical features. Considerable heterogeneity in the frequency of laboratory testing and results observed among cases meeting the most restrictive definition suggests that the clinical features, monitoring patterns and suspicion of ALI are highly variable among patients.
Creation of four distinct case definitions and application across a disparate set of observational databases resulted in significant variation in the prevalence of ALI. A greater understanding of the natural history of ALI through examination of electronic healthcare data can facilitate development of reliable and valid ALI case definitions that may enhance the ability to accurately identify associations between ALI and drug exposures. Considerable heterogeneity in laboratory values and frequency of laboratory testing among individuals meeting the criteria for ALI suggests that the evaluation of ALI is highly variable.
C1 [Katz, Aaron J.] Univ N Carolina, UNC Eshelman Sch Pharm, Div Pharmaceut Policy & Outcomes, Chapel Hill, NC 27599 USA.
[Ryan, Patrick B.; Stang, Paul E.] Janssen Res & Dev, Titusville, NJ USA.
[Ryan, Patrick B.; Racoosin, Judith A.; Stang, Paul E.] Fdn Natl Inst Hlth, Observat Med Outcomes Partnership, Bethesda, MD USA.
[Racoosin, Judith A.] USFDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Katz, AJ (reprint author), Univ N Carolina, UNC Eshelman Sch Pharm, Div Pharmaceut Policy & Outcomes, CB 7573, Chapel Hill, NC 27599 USA.
EM aj_katz@unc.edu
FU Foundation for the National Institutes of Health
FX The OMOP is funded by the Foundation for the National Institutes of
Health through generous contributions from the following: Abbott, Amgen
Inc., AstraZeneca, Bayer Healthcare Pharmaceuticals, Inc., Bristol-Myers
Squibb, Eli Lilly & Company, GlaxoSmithKline, Johnson & Johnson,
Lundbeck, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation,
Pfizer Inc., Pharmaceutical Research Manufacturers of America (PhRMA),
Roche, Sanofi, Schering-Plough Corporation, and Takeda.
NR 29
TC 6
Z9 6
U1 0
U2 2
PU ADIS INT LTD
PI AUCKLAND
PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW
ZEALAND
SN 0114-5916
J9 DRUG SAFETY
JI Drug Saf.
PD AUG
PY 2013
VL 36
IS 8
BP 651
EP 661
DI 10.1007/s40264-013-0060-8
PG 11
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy;
Toxicology
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy;
Toxicology
GA 188DR
UT WOS:000322172800007
PM 23670723
ER
PT J
AU Kleinerman, RA
Smith, SA
Holowaty, E
Hall, P
Pukkala, E
Vaalavirta, L
Stovall, M
Weathers, R
Gilbert, E
Aleman, BMP
Kaijser, M
Andersson, M
Storm, H
Joensuu, H
Lynch, CF
Dores, GM
Travis, LB
Morton, LM
Curtis, RE
AF Kleinerman, Ruth A.
Smith, Susan A.
Holowaty, Eric
Hall, Per
Pukkala, Eero
Vaalavirta, Leila
Stovall, Marilyn
Weathers, Rita
Gilbert, Ethel
Aleman, Berthe M. P.
Kaijser, Magnus
Andersson, Michael
Storm, Hans
Joensuu, Heikki
Lynch, Charles F.
Dores, Graca M.
Travis, Lois B.
Morton, Lindsay M.
Curtis, Rochelle E.
TI Radiation Dose and Subsequent Risk for Stomach Cancer in Long-term
Survivors of Cervical Cancer
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID 2ND CANCERS; THERAPY
AB Purpose: To assess the dose-response relationship for stomach cancer after radiation therapy for cervical cancer.
Methods and Materials: We conducted a nested, matched case-control study of 201 cases and 378 controls among 53,547 5-year survivors of cervical cancer diagnosed from 1943 to 1995, from 5 international, population-based cancer registries. We estimated individual radiation doses to the site of the stomach cancer for all cases and to corresponding sites for the matched controls (overall mean stomach tumor dose, 2.56 Gy, range 0.03-46.1 and after parallel opposed pelvic fields, 1.63Gy, range 0.12-6.3).
Results: More than 90% of women received radiation therapy, mostly with external beam therapy in combination with brachytherapy. Stomach cancer risk was nonsignificantly increased (odds ratio 1.27-2.28) for women receiving between 0.5 and 4.9 Gy to the stomach cancer site and significantly increased at doses >= 5Gy (odds ratio 4.20, 95% confidence interval 1.41-13.4, P-trend=.047) compared with nonirradiated women. A highly significant radiation dose-response relationship was evident when analyses were restricted to the 131 cases (251 controls) whose stomach cancer was located in the middle and lower portions of the stomach (P-trend=.003), whereas there was no indication of increasing risk with increasing dose for 30 cases (57 controls) whose cancer was located in the upper stomach (P-trend=.23).
Conclusions: Our findings show for the first time a significant linear dose-response relationship for risk of stomach cancer in long-term survivors of cervical cancer. (C) 2013 Elsevier Inc.
C1 [Kleinerman, Ruth A.; Gilbert, Ethel; Dores, Graca M.; Morton, Lindsay M.; Curtis, Rochelle E.] NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Rockville, MD 20852 USA.
[Smith, Susan A.; Stovall, Marilyn; Weathers, Rita] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA.
[Holowaty, Eric] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Hall, Per] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Pukkala, Eero] Finnish Canc Registry, Inst Stat & Epidemiol Canc Res, FIN-00170 Helsinki, Finland.
[Vaalavirta, Leila; Joensuu, Heikki] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland.
[Aleman, Berthe M. P.] Netherlands Canc Inst, Dept Radiotherapy, Amsterdam, Netherlands.
[Kaijser, Magnus] Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.
[Andersson, Michael] Copenhagen Univ Hosp, Dept Oncol, Copenhagen, Denmark.
[Storm, Hans] Danish Canc Soc, Copenhagen, Denmark.
[Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
[Dores, Graca M.] Dept Vet Affairs Med Ctr, Oklahoma City, OK USA.
[Travis, Lois B.] Univ Rochester, Med Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA.
RP Kleinerman, RA (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, US Dept HHS,NIH, Rockville, MD 20852 USA.
EM kleinerr@mail.nih.gov
RI Morton, Lindsay/B-5234-2015;
OI Morton, Lindsay/0000-0001-9767-2310; Storm, Hans/0000-0001-7223-8198;
Kleinerman, Ruth/0000-0001-7415-2478; Joensuu,
Heikki/0000-0003-0281-2507
FU National Institutes of Health [NO1-CP-31157]; National Cancer Institute
[NO1-CP-31157]; Danish Cancer Society, Copenhagen, Denmark
[NO1-CP-31019]; Finnish Cancer Registry, Helsinki, Finland
[NO1-CP-31154]; Information Management Services, Silver Spring, MD
[N01-CP-31003]; Karolinska Institute, Stockholm, Sweden [NO1-CP-31156];
University of Iowa, Iowa City, IA [NO1-CP-31155]; University of Texas MD
Anderson Cancer Center, Houston, TX [N02-CP-55503]; Westat, Rockville,
MD [N02-CP-31136]
FX This research was supported in part by the intramural research program
of the National Institutes of Health and the National Cancer Institute,
and with contracts from the National Cancer Institute to Cancer Care
Ontario, Toronto, Canada (NO1-CP-31157); Danish Cancer Society,
Copenhagen, Denmark (NO1-CP-31019); Finnish Cancer Registry, Helsinki,
Finland (NO1-CP-31154); Information Management Services, Silver Spring,
MD (N01-CP-31003); Karolinska Institute, Stockholm, Sweden
(NO1-CP-31156); University of Iowa, Iowa City, IA (NO1-CP-31155);
University of Texas MD Anderson Cancer Center, Houston, TX
(N02-CP-55503); and Westat, Rockville, MD (N02-CP-31136).
NR 19
TC 11
Z9 11
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD AUG 1
PY 2013
VL 86
IS 5
BP 922
EP 929
DI 10.1016/j.ijrobp.2013.04.010
PG 8
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 182LI
UT WOS:000321743600027
PM 23707149
ER
PT J
AU Fasola, CE
Jones, JC
Huang, DD
Le, QT
Hoppe, RT
Donaldson, SS
AF Fasola, Carolina E.
Jones, Jennifer C.
Huang, Derek D.
Quynh-Thu Le
Hoppe, Richard T.
Donaldson, Sarah S.
TI Low-Dose Radiation Therapy (2 Gy x 2) in the Treatment of Orbital
Lymphoma
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID NON-HODGKINS-LYMPHOMA; INVOLVED-FIELD RADIOTHERAPY; MARGINAL ZONE;
COMPLICATIONS
AB Purpose: Low-dose radiation has become increasingly used in the management of indolent nonHodgkin lymphoma (NHL), but has not been studied specifically for cases of ocular adnexal involvement. The objective of this study is to investigate the effectiveness of low-dose radiation in the treatment of NHL of the ocular adnexa.
Methods and Materials: We reviewed the records of 20 NHL patients with 27 sites of ocular adnexal involvement treated with low-dose radiation consisting of 2 successive fractions of 2 Gy at our institution between 2005 and 2011. The primary endpoint of this study is freedom from local relapse (FFLR).
Results: At a median follow-up time of 26 months (range 7-92), the overall response rate for the 27 treated sites was 96%, with a complete response (CR) rate of 85% (n=23) and a partial response rate of 11% (n=3). Among all treated sites with CR, the 2-year FFLR was 100%, with no in-treatment field relapses. The 2-year freedom from regional relapse rate was 96% with 1 case of relapse within the ipsilateral orbit (outside of the treatment field). This patient underwent additional treatment with low-dose radiation of 4 Gy to the area of relapse achieving a CR and no evidence of disease at an additional 42 months of follow-up. Orbital radiation was well tolerated with only mild acute side effects (dry eye, conjunctivitis, transient periorbital edema) in 30% of treated sites without any reports of long-term toxicity.
Conclusions: Low-dose radiation with 2 Gy x 2 is effective and well tolerated in the treatment of indolent NHL of the ocular adnexa with high response rates and durable local control with the option of reirradiation in the case of locoregional relapse. (C) 2013 Elsevier Inc.
C1 [Fasola, Carolina E.; Quynh-Thu Le; Hoppe, Richard T.; Donaldson, Sarah S.] Stanford Univ, Dept Radiat Oncol, Stanford, CA 94305 USA.
[Jones, Jennifer C.] NCI, Vaccine Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Huang, Derek D.] Univ Calif Los Angeles Olive View, Dept Internal Med, Sylmar, CA USA.
RP Donaldson, SS (reprint author), Stanford Canc Ctr, Dept Radiat Oncol, 875 Blake Wilbur Dr, Stanford, CA 94305 USA.
EM sarah2@stanford.edu
RI Jones, Jennifer/C-8691-2015
OI Jones, Jennifer/0000-0002-9488-7719
NR 19
TC 12
Z9 13
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD AUG 1
PY 2013
VL 86
IS 5
BP 930
EP 935
DI 10.1016/j.ijrobp.2013.04.035
PG 6
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 182LI
UT WOS:000321743600028
PM 23726002
ER
PT J
AU Moroni, M
Ngudiankama, BF
Christensen, C
Olsen, CH
Owens, R
Lombardini, ED
Holt, RK
Whitnall, MH
AF Moroni, Maria
Ngudiankama, Barbara F.
Christensen, Christine
Olsen, Cara H.
Owens, Rossitsa
Lombardini, Eric D.
Holt, Rebecca K.
Whitnall, Mark H.
TI The Gottingen Minipig Is a Model of the Hematopoietic Acute Radiation
Syndrome: G-Colony Stimulating Factor Stimulates Hematopoiesis and
Enhances Survival From Lethal Total-Body gamma-Irradiation
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID NONHUMAN-PRIMATES; G-CSF; MYELOSUPPRESSION; COMBINATION; MANAGEMENT;
GROWTH; CELLS; SOON
AB Purpose: We are characterizing the Gottingen minipig as an additional large animal model for advanced drug testing for the acute radiation syndrome (ARS) to enhance the discovery and development of novel radiation countermeasures. Among the advantages provided by this model, the similarities to human hematologic parameters and dynamics of cell loss/recovery after irradiation provide a convenient means to compare the efficacy of drugs known to affect bone marrow cellularity and hematopoiesis.
Methods and Materials: Male Gottingen minipigs, 4 to 5 months old and weighing 9 to 11 kg, were used for this study. We tested the standard off-label treatment for ARS, rhG-CSF (Neupogen, 10 mu g/kg/day for 17 days), at the estimated LD70/30 total-body gamma-irradiation (TBI) radiation dose for the hematopoietic syndrome, starting 24 hours after irradiation.
Results: The results indicated that granulocyte colony stimulating factor (G-CSF) enhanced survival, stimulated recovery from neutropenia, and induced mobilization of hematopoietic progenitor cells. In addition, the administration of G-CSF resulted in maturation of monocytes/macrophages.
Conclusions: These results support continuing efforts toward validation of the minipig as a large animal model for advanced testing of radiation countermeasures and characterization of the pathophysiology of ARS, and they suggest that the efficacy of G-CSF in improving survival after total body irradiation may involve mechanisms other than increasing the numbers of circulating granulocytes. (C) 2013 Elsevier Inc.
C1 [Moroni, Maria; Owens, Rossitsa; Whitnall, Mark H.] Uniformed Serv Univ Hlth Sci, Armed Forces Radiobiol Res Inst, Radiat Countermeasures Program, Bethesda, MD 20814 USA.
[Ngudiankama, Barbara F.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
[Christensen, Christine] Uniformed Serv Univ Hlth Sci, Armed Forces Radiobiol Res Inst, Div Comparat Pathol, Bethesda, MD 20814 USA.
[Olsen, Cara H.] Uniformed Serv Univ Hlth Sci, Biostat Consulting Ctr, Bethesda, MD 20814 USA.
[Lombardini, Eric D.] Armed Forces Res Inst Med Sci, Dept Vet Med, Bangkok 10400, Thailand.
[Holt, Rebecca K.] Uniformed Serv Univ Hlth Sci, Armed Forces Radiobiol Res Inst, Dept Vet Sci, Bethesda, MD 20814 USA.
RP Moroni, M (reprint author), Armed Forces Radiobiol Res Inst, 8901 Wisconsin Ave, Bethesda, MD 20889 USA.
EM maria.moroni@usuhs.edu
FU National Institute of Allergy and Infectious Diseases [Y1-AI-1759-01];
Armed Forces Radiobiology Research Institute (AFRRI) [RBB2DG]
FX Supported by funding from National Institute of Allergy and Infectious
Diseases Y1-AI-1759-01 and Armed Forces Radiobiology Research Institute
(AFRRI) RBB2DG. The opinions or assertions contained herein are the
private views of the authors and are not necessarily those of AFRRI, the
Uniformed Services University of the Health Sciences, or the Department
of Defense. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 20
TC 18
Z9 19
U1 1
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD AUG 1
PY 2013
VL 86
IS 5
BP 986
EP 992
DI 10.1016/j.ijrobp.2013.04.041
PG 7
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 182LI
UT WOS:000321743600036
PM 23845847
ER
PT J
AU Johnston, SC
Easton, JD
Farrant, M
Barsan, W
Battenhouse, H
Conwit, R
Dillon, C
Elm, J
Lindblad, A
Morgenstern, L
Poisson, SN
Palesch, Y
AF Johnston, S. Claiborne
Easton, J. Donald
Farrant, Mary
Barsan, William
Battenhouse, Holly
Conwit, Robin
Dillon, Catherine
Elm, Jordan
Lindblad, Anne
Morgenstern, Lewis
Poisson, Sharon N.
Palesch, Yuko
TI Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke
(POINT) Trial: Rationale and design
SO INTERNATIONAL JOURNAL OF STROKE
LA English
DT Article
DE aspirin; clinical trial; clopidogrel; minor stroke; stroke prevention;
TIA
ID SHORT-TERM PROGNOSIS; HIGH-RISK PATIENTS; CEREBRAL-ISCHEMIA; ATTACK;
DETERIORATION; CLOPIDOGREL; IMPROVEMENT; DISEASE; ASPIRIN; INTERVENTION
AB BackgroundIschemic stroke and other vascular outcomes occur in 10-20% of patients in the three-months following a transient ischemic attack or minor ischemic stroke, and many are disabling. The highest risk period for these outcomes is the early hours and days immediately following the ischemic event. Aspirin is the most common antithrombotic treatment used for these patients.
AimThe aim of POINT is to determine whether clopidogrel plus aspirin taken <12h after transient ischemic attack or minor ischemic stroke symptom onset is more effective in preventing major ischemic vascular events at 90 days in the high-risk, and acceptably safe, compared with aspirin alone.
DesignPOINT is a prospective, randomized, double-blind, multicenter trial in patients with transient ischemic attack or minor ischemic stroke. Subjects are randomized to clopidogrel (600mg loading dose followed by 75mg/day) or matching placebo, and all will receive open-label aspirin 50-325mg/day, with a dose of 162mg daily for five-days followed by 81mg daily strongly recommended.
Study OutcomesThe primary efficacy outcome is the composite of new ischemic vascular events - ischemic stroke, myocardial infarction, or ischemic vascular death - by 90 days. The primary safety outcome is major hemorrhage, which includes symptomatic intracranial hemorrhage.
DiscussionAspirin is the most common antithrombotic given to patients with a stroke or transient ischemic attack, as it reduces the risk of subsequent stroke. This trial expects to determine whether more aggressive antithrombotic therapy with clopidogrel plus aspirin, initiated acutely, is more effective than aspirin alone.
C1 [Johnston, S. Claiborne; Easton, J. Donald; Farrant, Mary] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Johnston, S. Claiborne] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Barsan, William; Morgenstern, Lewis] Univ Michigan Hlth Syst, Ann Arbor, MI USA.
[Battenhouse, Holly; Dillon, Catherine] Med Univ S Carolina, Dept Publ Hlth Serv, Data Coordinat Unit, Charleston, SC 29425 USA.
[Conwit, Robin; Elm, Jordan; Palesch, Yuko] Natl Inst Neurol Disorders, Off Clin Res, Bethesda, MD USA.
[Lindblad, Anne] EMMES Corp, Rockville, MD USA.
[Poisson, Sharon N.] Univ Colorado, Sch Med, Dept Neurol, Denver, CO USA.
RP Johnston, SC (reprint author), UCSF Clin & Translat Sci Inst, UCSF Dept Neurol, Sandler Neurosci Bldg,675 Nelson Rising Lane, San Francisco, CA 94158 USA.
EM clay.johnston@ucsfmedctr.org
FU NIH [1U01 NS062835, UL1 RR024131, 2U01NS056975-06, U01NS073476-01, U01
NS 062835, 1U01NS062778, 1-U01-NS-069498-01]; American Heart
Association; AstraZeneca; EMMES; DoD; NEI; NINDS; Acucela
FX S. C. Johnston is funded by NIH grants 1U01 NS062835 and UL1 RR024131,
has received research support from the American Heart Association, is
coeditor of Journal Watch Neurology and vice editor of the Annals of
Neurology, is a coholder of a patent on an RNA panel to identify and
risk-stratify transient ischemic attacks, indirectly receives research
support from Sanofi (drug and placebo for this NIH-sponsored trial), and
receives research support from AstraZeneca. J. D. Easton is funded by
NIH grant 1U01 NS062835, is a consultant for Bristol-Myers Squibb;
receives research support from AstraZeneca, and is on data monitoring
noards for Daiichi-Sankyo, Schering-Plough Research Institute, Novartis,
Cerevast Therapeutics, Acorda Therapeutics, and Johnson and Johnson,
Inc. William Barsan is funded by NIH grants 2U01NS056975-06,
2U01NS056975-06, U01NS073476-01, U01 NS 062835, 1U01NS062778, and
1-U01-NS-069498-01. Anne Lindblad is an owner of The EMMES Corporation
and through her employment at EMMES is supported by grants and contracts
from the DoD, NEI, NINDS, and Acucela. Lewis Morgenstern is funded by
NIH grants U01 NS062835, R01 HL098065, R01 NS070941, R18 HS017690, R01
NS38916, R01 NS062675, and U01 NS056975. Mary Farrant, Holly
Battenhouse, Robin Conwit, Catherine Dillon, Jordan Elm, Sharon N.
Poisson, and Yuko Palesch declare no funding or potential conflict of
interest.
NR 27
TC 42
Z9 45
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1747-4930
J9 INT J STROKE
JI Int. J. Stroke
PD AUG
PY 2013
VL 8
IS 6
BP 479
EP 483
DI 10.1111/ijs.12129
PG 5
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 187YZ
UT WOS:000322159000028
PM 23879752
ER
PT J
AU Sridhar, SS
Mackenzie, MJ
Hotte, SJ
Mukherjee, SD
Tannock, IF
Murray, N
Kollmannsberger, C
Haider, MA
Chen, EX
Halford, R
Wang, LS
Ivy, SP
Moore, MJ
AF Sridhar, Srikala S.
Mackenzie, Mary J.
Hotte, Sebastien J.
Mukherjee, Som D.
Tannock, Ian F.
Murray, Nevin
Kollmannsberger, Christian
Haider, Masoom A.
Chen, Eric X.
Halford, Robert
Wang, Lisa
Ivy, S. Percy
Moore, Malcolm J.
TI A phase II study of cediranib (AZD 2171) in treatment naive patients
with progressive unresectable recurrent or metastatic renal cell
carcinoma. A trial of the PMH phase 2 consortium
SO INVESTIGATIONAL NEW DRUGS
LA English
DT Article
DE Cediranib; Advanced renal cell cancer; Angiogenesis inhibitor
ID INTERFERON-ALPHA; TARGETED THERAPY; FREE SURVIVAL; GROWTH; CANCER;
INHIBITOR; SUNITINIB; EFFICACY; AZD2171
AB Background Inhibition of angiogenesis has emerged as an effective therapeutic strategy in metastatic renal cell cancer (mRCC). In this single arm phase 2 study, we evaluated the efficacy and tolerability of cediranib (AZD2171) a potent angiogenesis inhibitor in first line mRCC. Methods Eligible patients who had no prior systemic therapy received cediranib 45 mg orally once daily continuously. The primary endpoint was objective response rate (ORR). Secondary endpoints were clinical benefit rate (ORR plus stable disease (SD) a parts per thousand yenaEuro parts per thousand 4 months), duration of response, progression free survival (PFS), median overall survival (OS), safety and tolerability. Results Between January 2006 and April 2008, 44 patients were accrued. The median age was 62 (range 44-83) and performance status was either 0 (22 patients) or 1 (22 patients). Of the 39 evaluable patients there were 15 (38 %) partial responses (95 % CI: 23-55 %); 18 stable disease (SD) for a clinical benefit rate of 33/39 = 85 % (95 % CI: 69-94 %) and 6 progressive disease. Median PFS was 8.9 months (95 % CI: 5.1-12.9); and median OS was 28.6 months (95 % CI: 18.2-37.3 months). The most frequent grade 3 or higher AEs included hypertension, fatigue, hand-foot syndrome and diarrhea. Conclusions Cediranib demonstrated significant anti-tumour activity in first line, treatment-naive mRCC, with efficacy parameters comparable to the other approved agents (sunitinib and pazopanib) in this setting. The main toxicities were fatigue, diarrhea and hypertension. Based on these encouraging results, further evaluation of cediranib in mRCC at a more tolerable dose of 30 mg daily appears warranted.
C1 [Sridhar, Srikala S.; Tannock, Ian F.; Haider, Masoom A.; Chen, Eric X.; Halford, Robert; Wang, Lisa; Moore, Malcolm J.] Princess Margaret Hosp, Toronto, ON M5G 2M9, Canada.
[Mackenzie, Mary J.] London Reg Canc Ctr, London, ON N6A 4L6, Canada.
[Hotte, Sebastien J.; Mukherjee, Som D.] Juravinski Canc Ctr, Hamilton, ON, Canada.
[Murray, Nevin; Kollmannsberger, Christian] BC Canc Agcy, Vancouver, BC, Canada.
[Ivy, S. Percy] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Sridhar, Srikala S.] Princess Margaret Hosp, Univ Hlth Network, Toronto, ON M5G 2M9, Canada.
RP Sridhar, SS (reprint author), Princess Margaret Hosp, Univ Hlth Network, 522,610 Univ Ave, Toronto, ON M5G 2M9, Canada.
EM srikala.sridhar@uhn.ca
FU NIH; NCI [N01CM17107, N01CM62203]
FX This project was supported by an NIH grant. NCI Contracts N01CM17107,
N01CM62203
NR 22
TC 12
Z9 13
U1 0
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-6997
J9 INVEST NEW DRUG
JI Invest. New Drugs
PD AUG
PY 2013
VL 31
IS 4
BP 1008
EP 1015
DI 10.1007/s10637-013-9931-1
PG 8
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 190IT
UT WOS:000322333600022
PM 23354849
ER
PT J
AU Marsh, AA
Finger, EC
Fowler, KA
Adalio, CJ
Jurkowitz, ITN
Schechter, JC
Pine, DS
Decety, J
Blair, RJR
AF Marsh, Abigail A.
Finger, Elizabeth C.
Fowler, Katherine A.
Adalio, Christopher J.
Jurkowitz, Ilana T. N.
Schechter, Julia C.
Pine, Daniel S.
Decety, Jean
Blair, R. J. R.
TI Empathic responsiveness in amygdala and anterior cingulate cortex in
youths with psychopathic traits
SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
LA English
DT Article
DE Psychopathy; adolescents; empathy; pain; amygdala; conduct disorder
ID CALLOUS-UNEMOTIONAL TRAITS; ONSET CONDUCT DISORDER; COGNITIVE
NEUROSCIENCE PERSPECTIVE; VENTROMEDIAL PREFRONTAL CORTEX; DISRUPTIVE
BEHAVIOR DISORDERS; ANTISOCIAL-BEHAVIOR; FACIAL EXPRESSIONS; CHILDREN;
PAIN; FEAR
AB Background: Psychopathic traits are associated with increases in antisocial behaviors such as aggression and are characterized by reduced empathy for others' distress. This suggests that psychopathic traits may also impair empathic pain sensitivity. However, whether psychopathic traits affect responses to the pain of others versus the self has not been previously assessed. Method: We used whole-brain functional magnetic resonance imaging to measure neural activation in 14 adolescents with oppositional defiant disorder or conduct disorder and psychopathic traits, as well as 21 healthy controls matched on age, gender, and intelligence. Activation in structures associated with empathic pain perception was assessed as adolescents viewed photographs of pain-inducing injuries. Adolescents imagined either that the body in each photograph was their own or that it belonged to another person. Behavioral and neuroimaging data were analyzed using random-effects analysis of variance. Results: Youths with psychopathic traits showed reduced activity within regions associated with empathic pain as the depicted pain increased. These regions included rostral anterior cingulate cortex, ventral striatum (putamen), and amygdala. Reductions in amygdala activity particularly occurred when the injury was perceived as occurring to another. Empathic pain responses within both amygdala and rostral anterior cingulate cortex were negatively correlated with the severity of psychopathic traits as indexed by PCL: YV scores. Conclusions: Youths with psychopathic traits show less responsiveness in regions implicated in the affective response to another's pain as the perceived intensity of this pain increases. Moreover, this reduced responsiveness appears to predict symptom severity.
C1 [Marsh, Abigail A.] Georgetown Univ, Dept Psychol, Washington, DC 20057 USA.
[Finger, Elizabeth C.] Univ Western Ontario, Dept Clin Neurol Sci, London, ON, Canada.
[Fowler, Katherine A.] Ctr Dis Control & Prevent, Div Violence Prevent, Atlanta, GA USA.
[Adalio, Christopher J.] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA.
[Jurkowitz, Ilana T. N.; Schechter, Julia C.; Pine, Daniel S.; Blair, R. J. R.] NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA.
[Decety, Jean] Univ Chicago, Dept Psychol, Chicago, IL 60637 USA.
[Decety, Jean] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA.
RP Marsh, AA (reprint author), Georgetown Univ, Dept Psychol, 37th & O St NW,WGR 302-A, Washington, DC 20057 USA.
EM aam72@georgetown.edu
RI Finger, Elizabeth/B-6453-2015
FU Intramural Research Program of the NIH:NIMH; NICHD [R03HD 06 4906]
FX This research was supported by the Intramural Research Program of the
NIH:NIMH and the NICHD (R03HD 06 4906). The authors thank Ken Towbin,
Andy Speer, and Steven Sinclair for their assistance with this research.
Data included in this manuscript were presented at the 2012 meeting of
the Social & Affective Neuroscience Society.
NR 51
TC 58
Z9 59
U1 7
U2 60
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9630
J9 J CHILD PSYCHOL PSYC
JI J. Child Psychol. Psychiatry
PD AUG
PY 2013
VL 54
IS 8
BP 900
EP 910
DI 10.1111/jcpp.12063
PG 11
WC Psychology, Developmental; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 185LY
UT WOS:000321970700010
PM 23488588
ER
PT J
AU Margolis, KL
Davis, BR
Baimbridge, C
Ciocon, JO
Cuyjet, AB
Dart, RA
Einhorn, PT
Ford, CE
Gordon, D
Hartney, TJ
Haywood, LJ
Holtzman, J
Mathis, DE
Oparil, S
Probstfield, JL
Simpson, LM
Stokes, JD
Wiegmann, TB
Williamson, JD
AF Margolis, Karen L.
Davis, Barry R.
Baimbridge, Charles
Ciocon, Jerry O.
Cuyjet, Aloysius B.
Dart, Richard A.
Einhorn, Paula T.
Ford, Charles E.
Gordon, David
Hartney, Thomas J.
Haywood, L. Julian
Holtzman, Jordan
Mathis, David E.
Oparil, Suzanne
Probstfield, Jeffrey L.
Simpson, Lara M.
Stokes, John D.
Wiegmann, Thomas B.
Williamson, Jeff D.
CA ALLHAT Collaborative Res Grp
TI Long-Term Follow-Up of Moderately Hypercholesterolemic Hypertensive
Patients Following Randomization to Pravastatin vs Usual Care: The
Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack
Trial (ALLHAT-LLT)
SO JOURNAL OF CLINICAL HYPERTENSION
LA English
DT Article
ID CARDIAC OUTCOMES; KIDNEY-DISEASE; MAJOR OUTCOMES; CHOLESTEROL;
SIMVASTATIN; MORTALITY; EFFICACY; THERAPY; SAFETY
AB The authors conducted a randomized, controlled, multicenter trial, in which they assigned well-controlled hypertensive participants aged 55 years and older with moderate hypercholesterolemia to receive pravastatin (n=5170) or usual care (n=5185) for 4 to 8 years, when trial therapy was discontinued. Passive surveillance using national databases to ascertain deaths and hospitalizations continued for a total follow-up of 8 to 13 years to assess whether mortality and morbidity differences persisted or new differences developed. During the post-trial period, fatal and nonfatal outcomes were available for 98% and 64% of participants, respectively. The primary outcome was all-cause mortality and the secondary outcomes included cardiovascular mortality, coronary heart disease (CHD), stroke, heart failure, cardiovascular disease, and end-stage renal disease. No significant differences appeared in mortality for pravastatin vs usual care (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.89-1.03) or other secondary outcomes. Similar to the previously reported in-trial result, there was a significant treatment effect for CHD in black patients (HR, 0.79; 95% CI, 0.64-0.98). However, the in-trial result showing a significant treatment by race effect did not remain significant during the entire follow-up (P=.08). These findings are consistent with evidence from other large trials that show statins prevent CHD and add evidence that they are effective for CHD prevention in black patients. (C) 2013 Wiley Periodicals, Inc.
C1 [Margolis, Karen L.] Hlth Partners Inst Educ & Res, Minneapolis, MN USA.
[Davis, Barry R.; Baimbridge, Charles; Ford, Charles E.; Simpson, Lara M.] Univ Texas Sch Publ Hlth, Houston, TX 77030 USA.
[Ciocon, Jerry O.] Cleveland Clin Florida, Weston, FL USA.
[Cuyjet, Aloysius B.] Nassau Univ Med Ctr, E Meadow, NY USA.
[Cuyjet, Aloysius B.] Marshfield Clin Res Fdn, Marshfield, WI USA.
[Einhorn, Paula T.; Gordon, David] NHLBI, Bethesda, MD 20892 USA.
[Hartney, Thomas J.] Vet Affairs Med Ctr Augusta, Augusta, GA USA.
[Haywood, L. Julian] LAC, Los Angeles, CA USA.
[Haywood, L. Julian] USC Med Ctr, Keck Sch Med, Los Angeles, CA USA.
[Holtzman, Jordan] Vet Affairs Med Ctr, Minneapolis, MN USA.
[Mathis, David E.] Mercer Univ, Macon, GA 31207 USA.
[Oparil, Suzanne] Univ Alabama Birmingham, Birmingham, AL USA.
[Probstfield, Jeffrey L.] Univ Washington, Med Ctr, Seattle, WA 98195 USA.
[Stokes, John D.] Christie Clin, Champaign, IL USA.
[Wiegmann, Thomas B.] Vet Affairs Med Ctr Kansas City, Kansas City, MO USA.
[Williamson, Jeff D.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
RP Davis, BR (reprint author), Univ Texas Sch Publ Hlth, 1200 Pressler St,W-916, Houston, TX 77030 USA.
EM barry.r.davis@uth.tmc.edu
FU National Heart, Lung, and Blood Institute (NHLBI) [NO1-HC-35130,
HHSN268201100036C]; Pfizer Inc.
FX This study was supported by contracts NO1-HC-35130 and HHSN268201100036C
with the National Heart, Lung, and Blood Institute (NHLBI). ALLHAT
investigators received contributions of study medications supplied by
Pfizer (amlodipine besylate and doxazosin mesylate), AstraZeneca
(atenolol and lisinopril), and Bristol-Myers Squibb (pravastatin), and
financial support provided by Pfizer Inc.
NR 22
TC 11
Z9 11
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1524-6175
J9 J CLIN HYPERTENS
JI J. Clin. Hypertens.
PD AUG
PY 2013
VL 15
IS 8
BP 542
EP 554
DI 10.1111/jch.12139
PG 13
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 188JG
UT WOS:000322188700006
PM 23889716
ER
PT J
AU Redd, AD
Collinson-Streng, A
Martens, C
Ricklefs, S
Mullis, CE
Manucci, J
Tobian, AAR
Selig, EJ
Laeyendecker, O
Sewankambo, N
Gray, RH
Serwadda, D
Wawer, MJ
Porcella, SF
Quinn, TC
AF Redd, Andrew D.
Collinson-Streng, Aleisha
Martens, Craig
Ricklefs, Stacy
Mullis, Caroline E.
Manucci, Jordyn
Tobian, Aaron A. R.
Selig, Ethan J.
Laeyendecker, Oliver
Sewankambo, Nelson
Gray, Ronald H.
Serwadda, David
Wawer, Maria J.
Porcella, Stephen F.
Quinn, Thomas C.
CA Rakai Hlth Sci Program
TI Identification of HIV Superinfection in Seroconcordant Couples in Rakai,
Uganda, by Use of Next-Generation Deep Sequencing (vol 49, pg 2859,
2011)
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Correction
C1 [Redd, Andrew D.] NIAID, Immunoregulat Lab, DIR, NIH, Baltimore, MD USA.
NIAID, Genom Unit, Res Technol Sect, Rocky Mt Labs,DIR,NIH, Hamilton, MT USA.
Johns Hopkins Univ, Johns Hopkins Med Inst, Baltimore, MD USA.
Rakai Hlth Sci Program, Kalisizo, Uganda.
Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
Makerere Univ, Sch Med, Kampala, Uganda.
Makerere Univ, Sch Publ Hlth, Kampala, Uganda.
RP Redd, AD (reprint author), NIAID, Immunoregulat Lab, DIR, NIH, Baltimore, MD USA.
NR 1
TC 0
Z9 0
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD AUG
PY 2013
VL 51
IS 8
BP 2805
EP 2805
DI 10.1128/JCM.01273-13
PG 1
WC Microbiology
SC Microbiology
GA 185FO
UT WOS:000321951800064
ER
PT J
AU Wertheimer, A
AF Wertheimer, Alan
TI Should "nudge' be salvaged?
SO JOURNAL OF MEDICAL ETHICS
LA English
DT Editorial Material
DE Autonomy; Behaviour Modification; Health Promotion; Public Health Ethics
C1 NIH, Dept Bioeth, Bethesda, MD 20892 USA.
RP Wertheimer, A (reprint author), NIH, Dept Bioeth, Bethesda, MD 20892 USA.
EM wertheimera@cc.nih.gov
NR 0
TC 4
Z9 4
U1 0
U2 4
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0306-6800
J9 J MED ETHICS
JI J. Med. Ethics
PD AUG
PY 2013
VL 39
IS 8
BP 498
EP 499
DI 10.1136/medethics-2012-101061
PG 2
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA 187KI
UT WOS:000322116600008
PM 23455011
ER
PT J
AU Jayasekara, PS
Barrett, MO
Ball, CB
Brown, KA
Kozma, E
Costanzi, S
Squarcialupi, L
Balasubramanian, R
Maruoka, H
Jacobson, KA
AF Jayasekara, P. Suresh
Barrett, Matthew O.
Ball, Christopher B.
Brown, Kyle A.
Kozma, Eszter
Costanzi, Stefano
Squarcialupi, Lucia
Balasubramanian, Ramachandran
Maruoka, Hiroshi
Jacobson, Kenneth A.
TI 4-Alkyloxyimino-cytosine nucleotides: tethering approaches to molecular
probes for the P2Y(6) receptor
SO MEDCHEMCOMM
LA English
DT Article
ID A(3) ADENOSINE RECEPTOR; SELECTIVE AGONISTS; FLOW-CYTOMETRY;
FLUORESCENT; DESENSITIZATION; MUTAGENESIS; ACTIVATION; ANALOGS; CELLS;
UDP
AB 4-Alkyloxyimino derivatives of pyrimidine nucleotides display high potency as agonists of certain G protein-coupled P2Y receptors (P2YRs). In an effort to functionalize a P2Y(6)R agonist for fluorescent labeling, we probed two positions (N-4 and gamma-phosphate of cytidine derivatives) with various functional groups, including alkynes for click chemistry. Functionalization of extended imino substituents at the 4 position of the pyrimidine nucleobase of CDP preserved P2Y(6)R potency generally better than gamma-phosphoester formation in CTP derivatives. Fluorescent Alexa Fluor 488 conjugate 16 activated the human P2Y(6)R expressed in 1321N1 human astrocytoma cells with an EC50 of 9 nM, and exhibited high selectivity for this receptor over other uridine nucleotide-activated P2Y receptors. Flow cytometry detected specific labeling with 16 to P2Y(6)R-expressing but not to wild-type 1321N1 cells. Additionally, confocal microscopy indicated both internalized 16 (t(1/2) of 18 min) and surface-bound fluorescence. Known P2Y(6)R ligands inhibited labeling. Theoretical docking of 16 to a homology model of the P2Y(6)R predicted electrostatic interactions between the fluorophore and extracellular portion of TM3. Thus, we have identified the N-4-benzyloxy group as a structurally permissive site for synthesis of functionalized congeners leading to high affinity molecular probes for studying the P2Y(6)R.
C1 [Jayasekara, P. Suresh; Kozma, Eszter; Squarcialupi, Lucia; Balasubramanian, Ramachandran; Maruoka, Hiroshi; Jacobson, Kenneth A.] Natl Inst Diabet & Digest & Kidney Dis, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Barrett, Matthew O.; Ball, Christopher B.; Brown, Kyle A.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA.
[Costanzi, Stefano] American Univ, Dept Chem, Washington, DC 20016 USA.
RP Jacobson, KA (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov
RI Costanzi, Stefano/G-8990-2013; Jacobson, Kenneth/A-1530-2009;
OI Jacobson, Kenneth/0000-0001-8104-1493; Costanzi,
Stefano/0000-0003-3183-7332
FU Intramural Research Program of the NIH, National Institute of Diabetes
and Digestive and Kidney Diseases; Hungarian-American Enterprise
Scholarship Foundation (HAESF); University of Florence, Italy; National
Institute of General Medical Sciences [GM38213]
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute of Diabetes and Digestive and Kidney
Diseases and a grant (GM38213) from the National Institute of General
Medical Sciences. We thank Noel Whittaker (NIDDK) for mass spectral
determinations. EK thanks the Hungarian-American Enterprise Scholarship
Foundation (HAESF) for financial support. LS thanks the University of
Florence, Italy for financial support.
NR 41
TC 8
Z9 8
U1 1
U2 15
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 2040-2503
J9 MEDCHEMCOMM
JI MedChemComm
PD AUG
PY 2013
VL 4
IS 8
BP 1156
EP 1165
DI 10.1039/c3md00132f
PG 10
WC Biochemistry & Molecular Biology; Chemistry, Medicinal
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 188CZ
UT WOS:000322170900004
PM 26161252
ER
PT J
AU Adongo, D
Fister, KR
Gaff, H
Hartley, D
AF Adongo, Donald
Fister, K. Renee
Gaff, Holly
Hartley, David
TI OPTIMAL CONTROL APPLIED TO RIFT VALLEY FEVER
SO NATURAL RESOURCE MODELING
LA English
DT Article
DE Optimal control; Rift Valley Fever; mosquito-borne pathogen; livestock;
mortality
ID CANCER-CHEMOTHERAPY
AB Rift Valley Fever (RVF) virus is a mosquito-born pathogen that infects livestock but it also has the capability to infect humans through direct or indirect contact with blood or organs of infected animals and by bites from infected mosquitos. The economic and social cost of the disease to rural populations can lead to a cascade of negative effects on the sustainability of animal and human populations. Vaccines exist to protect against this disease. Through a compartment model depicting the interactions leading to the spread of RVF in Aedes and Culex mosquitos and a livestock population, an optimal control problem is developed to minimize the number of vaccinated livestock at the final time while minimizing the negative effects of the infected Aedes and Culex mosquitos and the cost of the vaccination process. The unique optimal vaccination strategy is produced for given high transmission parameters and numerical results portray that vaccination depends on the level of effectiveness of the protocol.
C1 [Adongo, Donald; Fister, K. Renee] Murray State Univ, Dept Math & Stat, Murray, KY 42071 USA.
[Gaff, Holly] Old Dominion Univ, Dept Biol Sci, Norfolk, VA 23529 USA.
[Hartley, David] Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20057 USA.
[Hartley, David] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Fister, KR (reprint author), Murray State Univ, Dept Math & Stat, Murray, KY 42071 USA.
EM dadongo@murraystate.edu; kfister@murraystate.edu; hgaff@odu.edu;
dh268@georgetown.edu
OI Hartley, David/0000-0001-5202-6278; , David/0000-0003-2589-2538
FU National Science Foundation [DMS-0813563]; Old Dominion University
[10-209-710501]; Research and Policy for Infectious Disease Dynamics
(RAPIDD) program of the Science and Technology Directorate, Department
of Homeland Security and Fogarty International Center, National
Institutes of Health
FX Part of this work by Fister and Adongo has been made possible through a
collaborator grant from the National Science Foundation, DMS-0813563,
and through consulting work through Old Dominion University contract
number 10-209-710501. Hartley acknowledges support from the Research and
Policy for Infectious Disease Dynamics (RAPIDD) program of the Science
and Technology Directorate, Department of Homeland Security and Fogarty
International Center, National Institutes of Health.
NR 17
TC 2
Z9 2
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0890-8575
J9 NAT RESOUR MODEL
JI Nat. Resour. Model.
PD AUG
PY 2013
VL 26
IS 3
BP 385
EP 402
DI 10.1111/nrm.12006
PG 18
WC Environmental Sciences; Mathematics, Interdisciplinary Applications
SC Environmental Sciences & Ecology; Mathematics
GA 188ZF
UT WOS:000322235500006
ER
PT J
AU Berndt, SI
Skibola, CF
Joseph, V
Camp, NJ
Nieters, A
Wang, ZM
Cozen, W
Monnereau, A
Wang, SS
Kelly, RS
Lan, Q
Teras, LR
Chatterjee, N
Chung, CC
Yeager, M
Brooks-Wilson, AR
Hartge, P
Purdue, MP
Birmann, BM
Armstrong, BK
Cocco, P
Zhang, YW
Severi, G
Zeleniuch-Jacquotte, A
Lawrence, C
Burdette, L
Yuenger, J
Hutchinson, A
Jacobs, KB
Call, TG
Shanafelt, TD
Novak, AJ
Kay, NE
Liebow, M
Wang, AH
Smedby, KE
Adami, HO
Melbye, M
Glimelius, B
Chang, ET
Glenn, M
Curtin, K
Cannon-Albright, LA
Jones, B
Diver, WR
Link, BK
Weiner, GJ
Conde, L
Bracci, PM
Riby, J
Holly, EA
Smith, MT
Jackson, RD
Tinker, LF
Benavente, Y
Becker, N
Boffetta, P
Brennan, P
Foretova, L
Maynadie, M
McKay, J
Staines, A
Rabe, KG
Achenbach, SJ
Vachon, CM
Goldin, LR
Strom, SS
Lanasa, MC
Spector, LG
Leis, JF
Cunningham, JM
Weinberg, JB
Morrison, VA
Caporaso, NE
Norman, AD
Linet, MS
De Roos, AJ
Morton, LM
Severson, RK
Riboli, E
Vineis, P
Kaaks, R
Trichopoulos, D
Masala, G
Weiderpass, E
Chirlaque, MD
Vermeulen, RCH
Travis, RC
Giles, GG
Albanes, D
Virtamo, J
Weinstein, S
Clavel, J
Zheng, TZ
Holford, TR
Offit, K
Zelenetz, A
Klein, RJ
Spinelli, JJ
Bertrand, KA
Laden, F
Giovannucci, E
Kraft, P
Kricker, A
Turner, J
Vajdic, CM
Ennas, MG
Ferri, GM
Miligi, L
Liang, LM
Sampson, J
Crouch, S
Park, JH
North, KE
Cox, A
Snowden, JA
Wright, J
Carracedo, A
Lopez-Otin, C
Bea, S
Salaverria, I
Martin-Garcia, D
Campo, E
Fraumeni, JF
de Sanjose, S
Hjalgrim, H
Cerhan, JR
Chanock, SJ
Rothman, N
Slager, SL
AF Berndt, Sonja I.
Skibola, Christine F.
Joseph, Vijai
Camp, Nicola J.
Nieters, Alexandra
Wang, Zhaoming
Cozen, Wendy
Monnereau, Alain
Wang, Sophia S.
Kelly, Rachel S.
Lan, Qing
Teras, Lauren R.
Chatterjee, Nilanjan
Chung, Charles C.
Yeager, Meredith
Brooks-Wilson, Angela R.
Hartge, Patricia
Purdue, Mark P.
Birmann, Brenda M.
Armstrong, Bruce K.
Cocco, Pierluigi
Zhang, Yawei
Severi, Gianluca
Zeleniuch-Jacquotte, Anne
Lawrence, Charles
Burdette, Laurie
Yuenger, Jeffrey
Hutchinson, Amy
Jacobs, Kevin B.
Call, Timothy G.
Shanafelt, Tait D.
Novak, Anne J.
Kay, Neil E.
Liebow, Mark
Wang, Alice H.
Smedby, Karin E.
Adami, Hans-Olov
Melbye, Mads
Glimelius, Bengt
Chang, Ellen T.
Glenn, Martha
Curtin, Karen
Cannon-Albright, Lisa A.
Jones, Brandt
Diver, W. Ryan
Link, Brian K.
Weiner, George J.
Conde, Lucia
Bracci, Paige M.
Riby, Jacques
Holly, Elizabeth A.
Smith, Martyn T.
Jackson, Rebecca D.
Tinker, Lesley F.
Benavente, Yolanda
Becker, Nikolaus
Boffetta, Paolo
Brennan, Paul
Foretova, Lenka
Maynadie, Marc
McKay, James
Staines, Anthony
Rabe, Kari G.
Achenbach, Sara J.
Vachon, Celine M.
Goldin, Lynn R.
Strom, Sara S.
Lanasa, Mark C.
Spector, Logan G.
Leis, Jose F.
Cunningham, Julie M.
Weinberg, J. Brice
Morrison, Vicki A.
Caporaso, Neil E.
Norman, Aaron D.
Linet, Martha S.
De Roos, Anneclaire J.
Morton, Lindsay M.
Severson, Richard K.
Riboli, Elio
Vineis, Paolo
Kaaks, Rudolph
Trichopoulos, Dimitrios
Masala, Giovanna
Weiderpass, Elisabete
Chirlaque, Mara-Dolores
Vermeulen, Roel C. H.
Travis, Ruth C.
Giles, Graham G.
Albanes, Demetrius
Virtamo, Jarmo
Weinstein, Stephanie
Clavel, Jacqueline
Zheng, Tongzhang
Holford, Theodore R.
Offit, Kenneth
Zelenetz, Andrew
Klein, Robert J.
Spinelli, John J.
Bertrand, Kimberly A.
Laden, Francine
Giovannucci, Edward
Kraft, Peter
Kricker, Anne
Turner, Jenny
Vajdic, Claire M.
Ennas, Maria Grazia
Ferri, Giovanni M.
Miligi, Lucia
Liang, Liming
Sampson, Joshua
Crouch, Simon
Park, Ju-Hyun
North, Kari E.
Cox, Angela
Snowden, John A.
Wright, Josh
Carracedo, Angel
Lopez-Otin, Carlos
Bea, Silvia
Salaverria, Itziar
Martin-Garcia, David
Campo, Elias
Fraumeni, Joseph F., Jr.
de Sanjose, Silvia
Hjalgrim, Henrik
Cerhan, James R.
Chanock, Stephen J.
Rothman, Nathaniel
Slager, Susan L.
TI Genome-wide association study identifies multiple risk loci for chronic
lymphocytic leukemia
SO NATURE GENETICS
LA English
DT Article
ID AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; CANCER SUSCEPTIBILITY LOCI;
NON-HODGKIN-LYMPHOMA; FAS GENE-MUTATIONS; RECOMBINATION HOTSPOTS;
BREAST-CANCER; LINKAGE DISEQUILIBRIUM; EPIDEMIOLOGIC RESEARCH;
TERT-CLPTM1L LOCUS; COMMON VARIATION
AB Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 x 10(-14)), 18q21.33 (BCL2, P = 7.76 x 10(-11)), 11p15.5 (C11orf21, P = 2.15 x 10(-10)), 4q25 (LEF1, P = 4.24 x 10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 x 10(-9)), 9p21.3 (CDKN2B-AS1, P = 1.27 x 10(-8)), 18q21.32 (PMAIP1, P = 2.51 x 10(-8)), 15q15.1 (BMF, P = 2.71 x 10(-10)) and 2p22.2 (QPCT, P = 1.68 x 10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 x 10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 x 10(-8)) and 5p15.33 (TERT, P = 1.92 x 10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.
C1 [Berndt, Sonja I.; Lan, Qing; Chatterjee, Nilanjan; Chung, Charles C.; Hartge, Patricia; Purdue, Mark P.; Goldin, Lynn R.; Caporaso, Neil E.; Linet, Martha S.; Morton, Lindsay M.; Albanes, Demetrius; Weinstein, Stephanie; Sampson, Joshua; Fraumeni, Joseph F., Jr.; Chanock, Stephen J.; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 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.
[Skibola, Christine F.; Conde, Lucia] Univ Alabama Birmingham, Sch Publ Hlth, Birmingham, AL 35294 USA.
[Joseph, Vijai; Offit, Kenneth; Zelenetz, Andrew; Klein, Robert J.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
[Camp, Nicola J.; Curtin, Karen; Cannon-Albright, Lisa A.; Jones, Brandt] Univ Utah, Sch Med, Dept Internal Med, Salt Lake City, UT USA.
[Nieters, Alexandra] Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, Freiburg, Hesse, Germany.
[Wang, Zhaoming; Chung, Charles C.; Yeager, Meredith; Burdette, Laurie; Yuenger, Jeffrey; Hutchinson, Amy; Jacobs, Kevin B.] NCI, Canc Genom Res Lab, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Cozen, Wendy] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Monnereau, Alain; Clavel, Jacqueline] INSERM, U1018 EQ6, Villejuif, France.
[Monnereau, Alain] Inst Bergonie, Registre Hemopathies Malignes Gironde, Bordeaux, France.
[Wang, Sophia S.] City Hope Beckman Res Inst, Div Canc Etiol, Duarte, CA USA.
[Kelly, Rachel S.; Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC HPA Ctr Environm & Hlth, London, England.
[Teras, Lauren R.; Diver, W. Ryan] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Brooks-Wilson, Angela R.] BC Canc Agcy, Genome Sci Ctr, Vancouver, BC, Canada.
[Brooks-Wilson, Angela R.] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada.
[Birmann, Brenda M.; Bertrand, Kimberly A.; Laden, Francine; Giovannucci, Edward] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Birmann, Brenda M.; Bertrand, Kimberly A.; Laden, Francine; Giovannucci, Edward] Harvard Univ, Sch Med, Boston, MA USA.
[Armstrong, Bruce K.; Kricker, Anne] Univ Sydney, Sydney Sch Publ Hlth, Sydney, NSW 2006, Australia.
[Cocco, Pierluigi] Univ Cagliari, Dept Publ Hlth Clin & Mol Med, Cagliari, Italy.
[Zhang, Yawei; Zheng, Tongzhang] Yale Univ, Sch Publ Hlth, Dept Environm Hlth Sci, New Haven, CT USA.
[Severi, Gianluca; Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic, Australia.
[Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Populat Hlth, New York, NY USA.
[Lawrence, Charles] WESTAT Corp, Hlth Studies Sector, Rockville, MD 20850 USA.
[Call, Timothy G.; Kay, Neil E.] Mayo Clin, Coll Med, Div Hematol, Rochester, MN USA.
[Shanafelt, Tait D.; Novak, Anne J.] Mayo Clin, Coll Med, Dept Med, Rochester, MN USA.
[Liebow, Mark] Mayo Clin, Coll Med, Div Gen Internal Med, Rochester, MN USA.
[Wang, Alice H.; Rabe, Kari G.; Achenbach, Sara J.; Vachon, Celine M.; Norman, Aaron D.; Cerhan, James R.; Slager, Susan L.] Mayo Clin, Coll Med, Rochester, MN 55905 USA.
[Smedby, Karin E.] Karolinska Inst, Dept Med Solna, Stockholm, Sweden.
[Smedby, Karin E.; Glimelius, Bengt] Karolinska Inst, Karolinska Univ Hosp Solna, Dept Pathol & Oncol, Stockholm, Sweden.
[Adami, Hans-Olov; Weiderpass, Elisabete] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Adami, Hans-Olov; Trichopoulos, Dimitrios; Bertrand, Kimberly A.; Laden, Francine; Giovannucci, Edward; Kraft, Peter; Liang, Liming] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Melbye, Mads; Hjalgrim, Henrik] Statens Serum Inst, Div Hlth Surveillance & Res, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark.
[Glimelius, Bengt] Uppsala Univ, Dept Radiol Oncol & Radiat Sci, Uppsala, Sweden.
[Chang, Ellen T.] Exponent Inc, Hlth Sci, Ctr Epidemiol & Computat Biol, Menlo Pk, CA USA.
[Chang, Ellen T.] Stanford Univ, Sch Med, Div Epidemiol, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Glenn, Martha] Huntsman Canc Inst, Dept Internal Med, Salt Lake City, UT USA.
[Cannon-Albright, Lisa A.] George E Wahlen Dept Vet Affairs Med Ctr, Salt Lake City, UT USA.
[Link, Brian K.; Weiner, George J.] Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA.
[Bracci, Paige M.; Holly, Elizabeth A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 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 98104 USA.
[Benavente, Yolanda; de Sanjose, Silvia] Inst Invest Biomed Bellvitge IDIBELL, Canc Epidemiol Res Programme, Unit Infect & Canc UNIC, Barcelona, Spain.
[Benavente, Yolanda; Chirlaque, Mara-Dolores; de Sanjose, Silvia] CIBERESP, Barcelona, Spain.
[Becker, Nikolaus; Kaaks, Rudolph] German Canc Res Ctr, Div Canc Epidemiol, Baden, Switzerland.
[Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY 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, Czech Republic.
[Maynadie, Marc] Univ Burgundy, Registre Hemopathies Malignes Cote dOr, EA 4184, Dijon, France.
[McKay, James] Int Agcy Res Canc, Genet Sect, Genet Canc Susceptibil Grp, F-69372 Lyon, France.
[Staines, Anthony] Dublin City Univ, Sch Nursing & Human Sci, Dublin 9, Leinster, Ireland.
[Strom, Sara S.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Lanasa, Mark C.; Weinberg, J. Brice] Duke Univ, Dept Med, Durham, NC USA.
[Lanasa, Mark C.; Weinberg, J. Brice] VA Med Ctr, Durham, NC USA.
[Spector, Logan G.] Univ Minnesota, Div Epidemiol & Clin Res, Minneapolis, MN USA.
[Leis, Jose F.] Mayo Clin, Coll Med, Div Hematol & Oncol, Phoenix, AZ USA.
[Cunningham, Julie M.] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN USA.
[Morrison, Vicki A.] Minneapolis Vet Affairs Med Ctr, Minneapolis, MN USA.
[Severson, Richard K.] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI USA.
[Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England.
[Vineis, Paolo] Human Genet Fdn, Turin, Italy.
[Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece.
[Trichopoulos, Dimitrios] Hellen Hlth Fdn, Athens, Greece.
[Masala, Giovanna] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy.
[Weiderpass, Elisabete] Univ Tromso, Fac Hlth Sci, Dept Community Med, Breivika, Norway.
[Weiderpass, Elisabete] Canc Registry Norway, Oslo, Norway.
[Weiderpass, Elisabete] Samfundet Folkhalsan, Folkhalsan Res Ctr, Helsinki, Finland.
[Chirlaque, Mara-Dolores] Murcia Reg Hlth Author, Dept Epidemiol, Murcia, Spain.
[Vermeulen, Roel C. H.] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands.
[Vermeulen, Roel C. H.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Travis, Ruth C.] Univ Oxford, Canc Epidemiol Unit, Oxford, England.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis & Prevent, Helsinki, Finland.
[Holford, Theodore R.] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT USA.
[Klein, Robert J.] Mem Sloan Kettering Canc Ctr, Program Canc Biol & Genet, New York, NY 10021 USA.
[Spinelli, John J.] BC Canc Agcy, Canc Control Res, Vancouver, BC, Canada.
[Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Kraft, Peter; Liang, Liming] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Turner, Jenny] Macquarie Univ, Australian Sch Adv Med, Dept Pathol, Sydney, NSW 2109, Australia.
[Turner, Jenny] Douglass Hanly Moir Pathol, Dept Histopathol, Macquarie Pk, NSW, Australia.
[Vajdic, Claire M.] Univ New S Wales, Prince Wales Clin Sch, Sydney, NSW, Australia.
[Ennas, Maria Grazia] Univ Cagliari, Dept Biomed Sci, Cagliari, Italy.
[Ferri, Giovanni M.] Univ Bari, Interdisciplinary Dept Med, Bari, Italy.
[Miligi, Lucia] ISPO, Environm & Occupat Epidemiol Unit, Florence, Italy.
[Crouch, Simon] Univ York, Dept Hlth Sci, Epidemiol & Genet Unit, York YO10 5DD, N Yorkshire, England.
[Park, Ju-Hyun] Dongguk Univ Seoul, Seoul, South Korea.
[North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Cox, Angela; Snowden, John A.] Univ Sheffield, Dept Oncol, Sheffield, S Yorkshire, England.
[Snowden, John A.; Wright, Josh] Sheffield Teaching Hosp Natl Hlth Serv NHS Fdn Tr, Dept Haematol, Sheffield, S Yorkshire, England.
[Carracedo, Angel] Univ Santiago de Compostela, CIBERER, Genom Med Grp, Santiago De Compostela, Spain.
[Lopez-Otin, Carlos] Univ Oviedo, Inst Oncol, Dept Biochem & Mol Biol, Oviedo, Spain.
[Bea, Silvia; Salaverria, Itziar; Martin-Garcia, David; Campo, Elias] Univ Barcelona, Hosp Clin Barcelona, August Pi & Sunyer Biomed Res Inst IDIBAPS, Barcelona, Spain.
RP Slager, SL (reprint author), Mayo Clin, Coll Med, Rochester, MN 55905 USA.
EM slager@mayo.edu
RI Joseph, Vijai/J-9158-2013; Armstrong, Bruce/K-9464-2015; SALAVERRIA,
ITZIAR/L-2246-2015; Purdue, Mark/C-9228-2016; Klein, Robert/K-1888-2013;
Conde, Lucia/D-9295-2011; Spinelli, John/B-6210-2013; Tang,
Macy/B-9798-2014; Brooks-Wilson, Angela/E-9399-2012; de Sanjose
Llongueras, Silvia/H-6339-2014; Monnereau, Alain/L-1249-2014; Morton,
Lindsay/B-5234-2015; Albanes, Demetrius/B-9749-2015; Benavente,
Yolanda/H-9810-2014; Lopez-Otin, Carlos/C-6657-2013; Weiderpass,
Elisabete/M-4029-2016; Clavel, Jacqueline/Q-2750-2016; Vermeulen,
Roel/F-8037-2011; Bea, Silvia/K-7699-2014;
OI Staines, Anthony/0000-0001-9161-1357; Carracedo,
Angel/0000-0003-1085-8986; Masala, Giovanna/0000-0002-5758-9069;
albright, lisa/0000-0003-2602-3668; Cox, Angela/0000-0002-5138-1099;
Spector, Logan/0000-0003-2516-0222; Joseph, Vijai/0000-0002-7933-151X;
Armstrong, Bruce/0000-0001-8940-7525; SALAVERRIA,
ITZIAR/0000-0002-2427-9822; Purdue, Mark/0000-0003-1177-3108; Klein,
Robert/0000-0003-3539-5391; Brooks-Wilson, Angela/0000-0003-1009-6408;
Monnereau, Alain/0000-0002-5056-1397; Morton,
Lindsay/0000-0001-9767-2310; Lopez-Otin, Carlos/0000-0001-6964-1904;
Weiderpass, Elisabete/0000-0003-2237-0128; Clavel,
Jacqueline/0000-0002-3616-7676; Vermeulen, Roel/0000-0003-4082-8163;
Zelenetz, Andrew/0000-0003-1403-6883; Cerhan, James/0000-0002-7482-178X;
Ennas, Maria Grazia/0000-0002-9448-715X; Bea,
Silvia/0000-0001-7192-2385; Vajdic, Claire/0000-0002-3612-8298; Norman,
Aaron/0000-0002-4208-2708; Giles, Graham/0000-0003-4946-9099;
Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303; Campo,
elias/0000-0001-9850-9793
FU Division of Cancer Epidemiology and Genetics, NCI, US National
Institutes of Health
FX We thank C. Allmer, E. Angelucci, A. Bigelow, I. Brock, K. Butterbach,
A. Chabrier, D. Chan-Lam, J.M. Conners, D. Connley, M. Cornelis, K.
Corsano, C. Dalley, D. Cox, H. Cramp, R. Cutting, H. Dykes, L. Ershler,
A. Gabbas, R.P. Gallagher, R.D. Gascoyne, P. Hui, L. Irish, L. Jacobus,
S. Kaul, J. Lunde, M. McAdams, R. Montalvan, M. Rais, T. Rattle, L.
Rigacci, K. Snyder, G. Specchia, M. Stagner, P. Taylor, G. Thomas, C.
Tornow, G. Wood, M. Yang and M. Zucca for their assistance. The overall
GWAS project was supported by the intramural program of the Division of
Cancer Epidemiology and Genetics, NCI, US National Institutes of Health.
A full list of acknowledgments is provided in the Supplementary Note.
NR 63
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U1 1
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD AUG
PY 2013
VL 45
IS 8
BP 868
EP 876
DI 10.1038/ng.2652
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 190WW
UT WOS:000322374900008
PM 23770605
ER
PT J
AU Morrison, AC
Voorman, A
Johnson, AD
Liu, XM
Yu, J
Li, A
Muzny, D
Yu, FL
Rice, K
Zhu, CS
Bis, J
Heiss, G
O'Donnell, CJ
Psaty, BM
Cupples, LA
Gibbs, R
Boerwinkle, E
AF Morrison, Alanna C.
Voorman, Arend
Johnson, Andrew D.
Liu, Xiaoming
Yu, Jin
Li, Alexander
Muzny, Donna
Yu, Fuli
Rice, Kenneth
Zhu, Chengsong
Bis, Joshua
Heiss, Gerardo
O'Donnell, Christopher J.
Psaty, Bruce M.
Cupples, L. Adrienne
Gibbs, Richard
Boerwinkle, Eric
CA Cohorts Heart Aging Res Genetic
TI Whole-genome sequence-based analysis of high-density lipoprotein
cholesterol
SO NATURE GENETICS
LA English
DT Article
ID COMMON SNPS; ASSOCIATION; ANNOTATION; DISEASE; HDL; OREGANNO; MUTATION;
DATABASE; FAMILY; LIPIDS
AB We describe initial steps for interrogating whole-genome sequence data to characterize the genetic architecture of a complex trait, levels of high-density lipoprotein cholesterol (HDL-C). We report whole-genome sequencing and analysis of 962 individuals from the Cohorts for Heart and Aging Research in Genetic Epidemiology (CHARGE) studies. From this analysis, we estimate that common variation contributes more to heritability of HDL-C levels than rare variation, and screening for mendelian variants for dyslipidemia identified individuals with extreme HDL-C levels. Whole-genome sequencing analyses highlight the value of regulatory and non-protein-coding regions of the genome in addition to protein-coding regions.
C1 [Morrison, Alanna C.; Liu, Xiaoming; Li, Alexander; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA.
[Voorman, Arend; Rice, Kenneth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Johnson, Andrew D.; O'Donnell, Christopher J.; Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Yu, Jin; Muzny, Donna; Yu, Fuli; Gibbs, Richard; Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Zhu, Chengsong] Kansas State Univ, Dept Agron, Manhattan, KS 66506 USA.
[Bis, Joshua; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Bis, Joshua; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Bis, Joshua; Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98121 USA.
[Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
RP Boerwinkle, E (reprint author), Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA.
EM eric.boerwinkle@uth.tmc.edu
RI Liu, Xiaoming/C-2743-2008; Johnson, Andrew/G-6520-2013;
OI Liu, Xiaoming/0000-0001-8285-5528; Cupples, L.
Adrienne/0000-0003-0273-7965; Yu, Jin/0000-0002-2990-6602
FU NHLBI [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN268201100010C,
HHSN268201100011C, HHSN268201100012C, RC2HL102419-02, N01-HC-85239,
N01-HC-85079]; National Institute of Neurological Disorders and Stroke
(NINDS); National Institute on Aging (NIA) [AG-023629, AG-15928,
AG-20098, AG-027058]; NHLBI FHS [N01-HC-25195]; National Heart, Lung,
and Blood Institute [N01-HC-85086, N01-HC-35129, N01 HC-15103, N01
HC-55222, N01-HC-75150, N01-HC-45133, HHSN268201200036C, HL080295,
HL087652, HL105756]
FX Atherosclerosis Risk in Communities (ARIC) Study: This ARIC study is
carried out as a collaborative study supported by NHLBI contracts
HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN268201100010C,
HHSN268201100011C and HHSN268201100012C. The authors thank the staff and
participants of the ARIC study for their important contributions.
Ancillary study support has been provided by NHLBI-sponsored project
RC2HL102419-02.; Cardiovascular Health Study (CHS): This CHS research
was supported by NHLBI contracts N01-HC-85239, N01-HC-85079 through
N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150,
N01-HC-45133 and HHSN268201200036C and by NHLBI grants HL080295,
HL087652 and HL105756, with additional contribution from the National
Institute of Neurological Disorders and Stroke (NINDS). Additional
support was provided through AG-023629, AG-15928, AG-20098 and AG-027058
from the National Institute on Aging (NIA). See also https://chs-nhlbi.
org/CHSOverview.; Framingham Heart Study (FHS) of the NHLBI of the US
National Institutes of Health and Boston University School of Medicine:
This work was supported by the NHLBI FHS (contract N01-HC-25195).
NR 23
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U1 1
U2 15
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD AUG
PY 2013
VL 45
IS 8
BP 899
EP U29
DI 10.1038/ng.2671
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA 190WW
UT WOS:000322374900012
PM 23770607
ER
PT J
AU Anttila, V
Winsvold, BS
Gormley, P
Kurth, T
Bettella, F
McMahon, G
Kallela, M
Malik, R
de Vries, B
Terwindt, G
Medland, SE
Todt, U
McArdle, WL
Quaye, L
Koiranen, M
Ikram, MA
Lehtimaki, T
Stam, AH
Ligthart, L
Wedenoja, J
Dunham, I
Neale, BM
Palta, P
Hamalainen, E
Schurks, M
Rose, LM
Buring, JE
Ridker, PM
Steinberg, S
Stefansson, H
Jakobsson, F
Lawlor, DA
Evans, DM
Ring, SM
Farkkila, M
Artto, V
Kaunisto, MA
Freilinger, T
Schoenen, J
Frants, RR
Pelzer, N
Weller, CM
Zielman, R
Heath, AC
Madden, PAF
Montgomery, GW
Martin, NG
Borck, G
Gobel, H
Heinze, A
Heinze-Kuhn, K
Williams, FMK
Hartikainen, AL
Pouta, A
van den Ende, J
Uitterlinden, AG
Hofman, A
Amin, N
Hottenga, JJ
Vink, JM
Heikkila, K
Alexander, M
Muller-Myhsok, B
Schreiber, S
Meitinger, T
Wichmann, HE
Aromaa, A
Eriksson, JG
Traynor, BJ
Trabzuni, D
Rossin, E
Lage, K
Jacobs, SBR
Gibbs, JR
Birney, E
Kaprio, J
Penninx, BW
Boomsma, DI
van Duijn, C
Raitakari, O
Jarvelin, MR
Zwart, JA
Cherkas, L
Strachan, DP
Kubisch, C
Ferrari, MD
van den Maagdenberg, AMJM
Dichgans, M
Wessman, M
Smith, GD
Stefansson, K
Daly, MJ
Nyholt, DR
Chasman, DI
Palotie, A
AF Anttila, Verneri
Winsvold, Bendik S.
Gormley, Padhraig
Kurth, Tobias
Bettella, Francesco
McMahon, George
Kallela, Mikko
Malik, Rainer
de Vries, Boukje
Terwindt, Gisela
Medland, Sarah E.
Todt, Unda
McArdle, Wendy L.
Quaye, Lydia
Koiranen, Markku
Ikram, M. Arfan
Lehtimaki, Terho
Stam, Anine H.
Ligthart, Lannie
Wedenoja, Juho
Dunham, Ian
Neale, Benjamin M.
Palta, Priit
Hamalainen, Eija
Schuerks, Markus
Rose, Lynda M.
Buring, Julie E.
Ridker, Paul M.
Steinberg, Stacy
Stefansson, Hreinn
Jakobsson, Finnbogi
Lawlor, Debbie A.
Evans, David M.
Ring, Susan M.
Farkkila, Markus
Artto, Ville
Kaunisto, Mari A.
Freilinger, Tobias
Schoenen, Jean
Frants, Rune R.
Pelzer, Nadine
Weller, Claudia M.
Zielman, Ronald
Heath, Andrew C.
Madden, Pamela A. F.
Montgomery, Grant W.
Martin, Nicholas G.
Borck, Guntram
Goebel, Hartmut
Heinze, Axel
Heinze-Kuhn, Katja
Williams, Frances M. K.
Hartikainen, Anna-Liisa
Pouta, Anneli
van den Ende, Joyce
Uitterlinden, Andre G.
Hofman, Albert
Amin, Najaf
Hottenga, Jouke-Jan
Vink, Jacqueline M.
Heikkila, Kauko
Alexander, Michael
Muller-Myhsok, Bertram
Schreiber, Stefan
Meitinger, Thomas
Wichmann, Heinz Erich
Aromaa, Arpo
Eriksson, Johan G.
Traynor, Bryan J.
Trabzuni, Daniah
Rossin, Elizabeth
Lage, Kasper
Jacobs, Suzanne B. R.
Gibbs, J. Raphael
Birney, Ewan
Kaprio, Jaakko
Penninx, Brenda W.
Boomsma, Dorret I.
van Duijn, Cornelia
Raitakari, Olli
Jarvelin, Marjo-Riitta
Zwart, John-Anker
Cherkas, Lynn
Strachan, David P.
Kubisch, Christian
Ferrari, Michel D.
van den Maagdenberg, Arn M. J. M.
Dichgans, Martin
Wessman, Maija
Smith, George Davey
Stefansson, Kari
Daly, Mark J.
Nyholt, Dale R.
Chasman, Daniel I.
Palotie, Aarno
CA North Amer Brain Expression
UK Brain Expression Consortium
Int Headache Genetics Consortium
TI Genome-wide meta-analysis identifies new susceptibility loci for
migraine
SO NATURE GENETICS
LA English
DT Article
ID TRANSFORMING-GROWTH-FACTOR; NEURITE OUTGROWTH; DOWN-REGULATION;
HUMAN-DISEASE; ASSOCIATION; EXPRESSION; PROTEIN; FAMILY; PROTEOLYSIS;
POPULATION
AB Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood. We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases) and 95,425 population-matched controls. We identified 12 loci associated with migraine susceptibility (P < 5 x 10(-8)). Five loci are new: near AJAP1 at 1p36, near TSPAN2 at 1p13, within FHL5 at 6q16, within C7orf10 at 7p14 and near MMP16 at 8q21. Three of these loci were identified in disease subgroup analyses. Brain tissue expression quantitative trait locus analysis suggests potential functional candidate genes at four loci: APOA1BP, TBC1D7, FUT9, STAT6 and ATP5B.
C1 [Anttila, Verneri; Winsvold, Bendik S.; Gormley, Padhraig; Palta, Priit; Hamalainen, Eija; Palotie, Aarno] Wellcome Trust Sanger Inst, Cambridge, England.
[Anttila, Verneri; Palta, Priit; Hamalainen, Eija; Kaunisto, Mari A.; Kaprio, Jaakko; Wessman, Maija; Palotie, Aarno] Univ Helsinki, FIMM, Helsinki, Finland.
[Anttila, Verneri; Neale, Benjamin M.; Rossin, Elizabeth; Lage, Kasper; Daly, Mark J.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Anttila, Verneri; Kurth, Tobias; Neale, Benjamin M.; Rose, Lynda M.; Buring, Julie E.; Ridker, Paul M.; Rossin, Elizabeth; Lage, Kasper; Daly, Mark J.; Chasman, Daniel I.] Harvard Univ, Sch Med, Boston, MA USA.
[Anttila, Verneri; Neale, Benjamin M.; Rossin, Elizabeth; Lage, Kasper; Jacobs, Suzanne B. R.; Daly, Mark J.; Palotie, Aarno] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[Winsvold, Bendik S.; Zwart, John-Anker] Oslo Univ Hosp, Dept Neurol, Oslo, Norway.
[Winsvold, Bendik S.; Zwart, John-Anker] Univ Oslo, Oslo, Norway.
[Kurth, Tobias] INSERM, Neuroepidemiol U708, Bordeaux, France.
[Kurth, Tobias] Univ Bordeaux, Bordeaux, France.
[Kurth, Tobias; Rose, Lynda M.; Buring, Julie E.; Ridker, Paul M.; Chasman, Daniel I.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA.
[Bettella, Francesco; Steinberg, Stacy; Stefansson, Hreinn; Stefansson, Kari] deCODE Genet, Reykjavik, Iceland.
[McMahon, George; McArdle, Wendy L.; Lawlor, Debbie A.; Evans, David M.; Ring, Susan M.; Smith, George Davey] Univ Bristol, Univ Bristol Med Res Council MRC Integrat Epidemi, Bristol, Avon, England.
[Kallela, Mikko; Farkkila, Markus; Artto, Ville] Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland.
[Malik, Rainer; Freilinger, Tobias; Dichgans, Martin] Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany.
[de Vries, Boukje; Frants, Rune R.; Weller, Claudia M.; van den Maagdenberg, Arn M. J. M.] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands.
[Terwindt, Gisela; Stam, Anine H.; Pelzer, Nadine; Zielman, Ronald; Ferrari, Michel D.; van den Maagdenberg, Arn M. J. M.] Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands.
[Medland, Sarah E.; Montgomery, Grant W.; Martin, Nicholas G.; Nyholt, Dale R.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Todt, Unda; Borck, Guntram; Kubisch, Christian] Univ Ulm, Inst Human Genet, D-89069 Ulm, Germany.
[Quaye, Lydia; Williams, Frances M. K.; Cherkas, Lynn] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England.
[Koiranen, Markku; Pouta, Anneli; Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland.
[Koiranen, Markku; Pouta, Anneli; Jarvelin, Marjo-Riitta] Oulu Univ Hosp, Unit Primary Care, Oulu, Finland.
[Ikram, M. Arfan; van den Ende, Joyce; Hofman, Albert; Amin, Najaf; van Duijn, Cornelia] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Ikram, M. Arfan] Erasmus Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands.
[Ikram, M. Arfan] Erasmus Univ, Med Ctr, Dept Neurol, Rotterdam, Netherlands.
[Lehtimaki, Terho] Fimlab Labs, Dept Clin Chem, Tampere, Finland.
[Lehtimaki, Terho] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland.
[Ligthart, Lannie; Hottenga, Jouke-Jan; Vink, Jacqueline M.; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
[Ligthart, Lannie; Penninx, Brenda W.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.
[Wedenoja, Juho; Heikkila, Kauko; Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland.
[Dunham, Ian; Birney, Ewan] European Mol Biol Lab, European Bioinformat Inst, Cambridge, England.
[Schuerks, Markus] Univ Hosp Essen, Dept Neurol, Essen, Germany.
[Ridker, Paul M.] Harvard Univ, Sch Med, Dept Epidemiol, Boston, MA USA.
[Jakobsson, Finnbogi] Landspitali Univ Hosp, Dept Neurol, Reykjavik, Iceland.
[Kaunisto, Mari A.; Eriksson, Johan G.; Wessman, Maija] Folkhalsan Res Ctr, Helsinki, Finland.
[Freilinger, Tobias] Klinikum Univ Munchen, Dept Neurol, Munich, Germany.
[Schoenen, Jean] Univ Liege, Dept Neurol, Headache Res Unit, Liege, Belgium.
[Schoenen, Jean] Univ Liege, GIGA Neurosci, Liege, Belgium.
[Heath, Andrew C.; Madden, Pamela A. F.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Goebel, Hartmut; Heinze, Axel; Heinze-Kuhn, Katja] Kiel Pain & Headache Ctr, Kiel, Germany.
[Hartikainen, Anna-Liisa; Pouta, Anneli] Univ Hosp Oulu, Dept Clin Sci Obstet & Gynecol, Oulu, Finland.
[Hartikainen, Anna-Liisa; Pouta, Anneli] Univ Oulu, Med Res Ctr, Oulu, Finland.
[Pouta, Anneli; Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Dept Children Young People & Families, Helsinki, Finland.
[Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Alexander, Michael] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany.
[Alexander, Michael] Univ Bonn, Inst Human Genet, Bonn, Germany.
[Muller-Myhsok, Bertram] Max Planck Inst Psychiat, D-80804 Munich, Germany.
[Muller-Myhsok, Bertram; Dichgans, Martin] Munich Cluster Syst Neurol SyNergy, Munich, Germany.
[Schreiber, Stefan] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany.
[Schreiber, Stefan] Univ Kiel, Dept Internal Med 1, Kiel, Germany.
[Meitinger, Thomas] Helmholtz Ctr Munich, Inst Human Genet, Neuherberg, Germany.
[Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-80290 Munich, Germany.
[Wichmann, Heinz Erich] Univ Munich, Inst Med Informat Verarbeitung Biometrie & Epidem, Munich, Germany.
[Wichmann, Heinz Erich] Helmholtz Ctr Munich, Inst Epidemiol 1, Neuherberg, Germany.
[Wichmann, Heinz Erich] Univ Munich, Klinikum Grosshadern, D-80539 Munich, Germany.
[Aromaa, Arpo; Eriksson, Johan G.] Natl Inst Hlth & Welf, Helsinki, Finland.
[Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Dept Gen Practice, Helsinki, Finland.
[Eriksson, Johan G.] Vaasa Cent Hosp, Vaasa, Finland.
[Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.
[Traynor, Bryan J.; Gibbs, J. Raphael] NIA, Neurogenet Lab, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Trabzuni, Daniah; Gibbs, J. Raphael] UCL, Inst Neurol, Dept Mol Neurosci, London, England.
[Trabzuni, Daniah] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia.
[Rossin, Elizabeth] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Lage, Kasper] Massachusetts Gen Hosp, Massachusetts Gen Hosp Children, Pediat Surg Res Labs, Boston, MA 02114 USA.
[Lage, Kasper] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark.
[Lage, Kasper] Univ Copenhagen, Ctr Prot Res, Copenhagen, Denmark.
[Kaprio, Jaakko] Natl Inst Hlth & Welf, Dept Mental Hlth & Alcohol Res, Helsinki, Finland.
[Penninx, Brenda W.] Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands.
[Penninx, Brenda W.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9713 AV Groningen, Netherlands.
[Penninx, Brenda W.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
[Raitakari, Olli] Univ Turku, Turku Univ Hosp, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
[Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland.
[Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Fac Med, MRC Hlth Protect Agcy HPA Ctr Environm & Hlth, Sch Publ Hlth,Dept Epidemiol & Biostat, London, England.
[Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland.
[Strachan, David P.] Univ London, Div Populat Hlth Sci & Educ, London, England.
[Stefansson, Kari] Univ Iceland, Sch Med, Reykjavik, Iceland.
RP Palotie, A (reprint author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge, England.
EM anttila@atgu.mgh.harvard.edu; ap8@sanger.ac.uk
RI Kubisch, Christian/F-1893-2011; Schreiber, Stefan/B-6748-2008;
Singleton, Andrew/C-3010-2009; Kurth, Tobias/A-9243-2012; Weale,
Michael/F-2587-2010; Nyholt, Dale/C-8384-2013; Medland,
Sarah/C-7630-2013; Borck, Guntram/F-1868-2015; Montgomery,
Grant/B-7148-2008; Meitinger, Thomas/O-1318-2015; Davey Smith,
George/A-7407-2013; Trabzuni, Daniah/C-4034-2012; Traynor,
Bryan/G-5690-2010
OI Palta, Priit/0000-0001-9320-7008; Wedenoja, Juho/0000-0002-6155-0378;
Kaunisto, Mari/0000-0002-6946-9195; Kaprio, Jaakko/0000-0002-3716-2455;
Lawlor, Debbie A/0000-0002-6793-2262; Winsvold, Bendik
Slagsvold/0000-0003-4171-8919; Martin, Nicholas/0000-0003-4069-8020;
Anttila, Verneri/0000-0002-0073-4675; Ikram, Mohammad
Arfan/0000-0003-0372-8585; Gormley, Padhraig/0000-0002-8908-6968;
Williams, Frances/0000-0002-2998-2744; Stefansson,
Hreinn/0000-0002-9331-6666; Dunham, Ian/0000-0003-2525-5598; Birney,
Ewan/0000-0001-8314-8497; Jarvelin, Marjo-Riitta/0000-0002-2149-0630;
Eriksson, Johan/0000-0002-2516-2060; Evans, David/0000-0003-0663-4621;
Kubisch, Christian/0000-0003-4220-0978; Schreiber,
Stefan/0000-0003-2254-7771; Kurth, Tobias/0000-0001-7169-2620; Weale,
Michael/0000-0003-4593-1186; Medland, Sarah/0000-0003-1382-380X;
Montgomery, Grant/0000-0002-4140-8139; Davey Smith,
George/0000-0002-1407-8314; Trabzuni, Daniah/0000-0003-4826-9570;
FU Intramural NIH HHS [Z01 AG000949-02]; Medical Research Council
[G0802462, G1001799, G9815508, MC_UU_12013/1, MC_UU_12013/4,
MC_UU_12013/5]; NIAAA NIH HHS [K05 AA017688]; NIGMS NIH HHS [T32
GM007753]; Wellcome Trust [089062, 092731]
NR 52
TC 119
Z9 119
U1 6
U2 53
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD AUG
PY 2013
VL 45
IS 8
BP 912
EP U255
DI 10.1038/ng.2676
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 190WW
UT WOS:000322374900015
PM 23793025
ER
PT J
AU Martin, M
Masshofer, L
Temming, P
Rahmann, S
Metz, C
Bornfeld, N
van de Nes, J
Klein-Hitpass, L
Hinnebusch, AG
Horsthemke, B
Lohmann, DR
Zeschnigk, M
AF Martin, Marcel
Masshoefer, Lars
Temming, Petra
Rahmann, Sven
Metz, Claudia
Bornfeld, Norbert
van de Nes, Johannes
Klein-Hitpass, Ludger
Hinnebusch, Alan G.
Horsthemke, Bernhard
Lohmann, Dietmar R.
Zeschnigk, Michael
TI Exome sequencing identifies recurrent somatic mutations in EIF1AX and
SF3B1 in uveal melanoma with disomy 3
SO NATURE GENETICS
LA English
DT Article
ID MICROSATELLITE ANALYSIS; SPLICING FACTOR; IN-VIVO; INITIATION; REVEALS;
BINDING; ABERRATIONS; SELECTION; FIDELITY; CELLS
AB Gene expression profiles and chromosome 3 copy number divide uveal melanomas into two distinct classes correlating with prognosis(1-3). Using exome sequencing, we identified recurrent somatic mutations in EIF1AX and SF3B1, specifically occurring in uveal melanomas with disomy 3, which rarely metastasize. Targeted resequencing showed that 24 of 31 tumors with disomy 3 (77%) had mutations in either EIF1AX (15; 48%) or SF3B1 (9; 29%). Mutations were infrequent (2/35; 5.7%) in uveal melanomas with monosomy 3, which are associated with poor prognosis(2). Resequencing of 13 uveal melanomas with partial monosomy 3 identified 8 tumors with a mutation in either SF3B1 (7; 54%) or EIF1AX (1; 8%). All EIF1AX mutations caused in-frame changes affecting the N terminus of the protein, whereas 17 of 19 SF3B1 mutations encoded an alteration of Arg625. Resequencing of ten uveal melanomas with disomy 3 that developed metastases identified SF3B1 mutations in three tumors, none of which targeted Arg625.
C1 [Martin, Marcel; Masshoefer, Lars; Rahmann, Sven; Horsthemke, Bernhard; Lohmann, Dietmar R.; Zeschnigk, Michael] Univ Duisburg Essen, Fac Med, Inst Human Genet, Essen, Germany.
[Martin, Marcel] Tech Univ Dortmund, Dortmund, Germany.
[Temming, Petra] Univ Hosp Essen, Dept Pediat Haematol & Oncol, Essen, Germany.
[Metz, Claudia; Bornfeld, Norbert] Univ Duisburg Essen, Dept Ophthalmol, Fac Med, Essen, Germany.
[van de Nes, Johannes] Univ Duisburg Essen, Inst Pathol & Neuropathol, Fac Med, Essen, Germany.
[Klein-Hitpass, Ludger] Univ Duisburg Essen, Inst Cell Biol, Biochip Lab, Fac Med, Essen, Germany.
[Hinnebusch, Alan G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, US Natl Inst Hlth, Bethesda, MD USA.
[Lohmann, Dietmar R.; Zeschnigk, Michael] Univ Duisburg Essen, Eye Canc Res Grp, Fac Med, Essen, Germany.
RP Zeschnigk, M (reprint author), Univ Duisburg Essen, Fac Med, Inst Human Genet, Essen, Germany.
EM michael.zeschnigk@uni-due.de
RI Temming, Petra/M-4743-2016
OI Martin, Marcel/0000-0002-0680-200X; Temming, Petra/0000-0002-8138-0441
FU Deutsche Krebshilfe (DKF) [108612]; Mercator Research Center Ruhr
[Pr-2010-0016]; Wilhelm Sander Stiftung [2012.006.1]; US National
Institutes of Health
FX We thank M. Klutz and D. Falkenstein for technical assistance and H.-J.
Ludecke for elaborate discussion. This work was supported by the
Deutsche Krebshilfe (DKF, 108612), the Mercator Research Center Ruhr
(Pr-2010-0016) and the Wilhelm Sander Stiftung (2012.006.1) and by the
Intramural Research Program of the US National Institutes of Health.
NR 34
TC 92
Z9 94
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD AUG
PY 2013
VL 45
IS 8
BP 933
EP U296
DI 10.1038/ng.2674
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA 190WW
UT WOS:000322374900019
PM 23793026
ER
PT J
AU Karami, S
Bassig, B
Stewart, PA
Lee, KM
Rothman, N
Moore, LE
Lan, Q
AF Karami, Sara
Bassig, Bryan
Stewart, Patricia A.
Lee, Kyoung-Mu
Rothman, Nathaniel
Moore, Lee E.
Lan, Qing
TI Occupational trichloroethylene exposure and risk of lymphatic and
haematopoietic cancers: a meta-analysis
SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Review
ID NON-HODGKINS-LYMPHOMA; AIRCRAFT MANUFACTURING WORKERS;
EXTENDED-FOLLOW-UP; ORGANIC-SOLVENTS; EPIDEMIOLOGIC EVIDENCE;
CHLORINATED SOLVENTS; MALIGNANT-LYMPHOMAS; AEROSPACE WORKERS;
MULTIPLE-MYELOMA; PUBLICATION BIAS
AB The carcinogenic potential of trichloroethylene (TCE) continues to generate much controversy, even after the US Environmental Protection Agency raised its classification to carcinogenic to humans'. We conducted a meta-analysis of published cohort and case-control studies exploring occupational TCE exposure in relation to five different lymphatic and haematopoietic cancers: non-Hodgkin's lymphoma (NHL, N=24), Hodgkin's lymphoma (HL, N=13), multiple myeloma (MM, N=11), leukaemia (N=12) and chronic/small lymphocytic leukaemia (CLL/SLL, N=7). Studies published between 1950 and 2011 were identified through a PubMed Medline search. All studies included in analyses were classified as those that assessed either occupational TCE exposure specifically (TCE-exposure' studies) or a broader classification of all chlorinated solvents (chlorinated solvent-exposure' studies). A significantly raised summary estimate for NHL was seen for all cohort and case-control TCE-exposure' studies combined (N=19; relative risk (RR)=1.32, 95% CI 1.14 to 1.54; I-2=25.20; p-heterogeneity=0.12) and for cohort TCE-exposure' studies (N=10; RR=1.52, 95% CI 1.29 to 1.79; I-2=7.09; p-heterogeneity=0.63). A non-significant but raised summary estimate was seen for NHL case-control TCE-exposure' studies. No significant association with NHL risk was detected overall for any chlorinated solvent-exposure' studies. Summary estimates for occupational TCE exposure were not associated with risk of HL, MM, leukaemia or CLL/SLL. Our updated meta-analysis of NHL, which incorporates new analytical results from three cohort and four case-control studies, supports an association between occupational TCE exposure and NHL.
C1 [Karami, Sara; Bassig, Bryan; Stewart, Patricia A.; Lee, Kyoung-Mu; Rothman, Nathaniel; Moore, Lee E.; Lan, Qing] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Rockville, MD 20852 USA.
[Stewart, Patricia A.; Lee, Kyoung-Mu] Stewart Exposure Assessments LLC, Arlington, VA USA.
[Lee, Kyoung-Mu] Korea Natl Open Univ, Dept Environm Hlth, Seoul, South Korea.
RP Karami, S (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, 6120 Executive Blvd,EPS 8102, Rockville, MD 20852 USA.
EM moorele@mail.nih.gov
NR 75
TC 9
Z9 12
U1 1
U2 35
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1351-0711
J9 OCCUP ENVIRON MED
JI Occup. Environ. Med.
PD AUG
PY 2013
VL 70
IS 8
BP 591
EP 599
DI 10.1136/oemed-2012-101212
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 187JR
UT WOS:000322114400012
PM 23723297
ER
PT J
AU Guo, B
Fan, XR
Fang, ZZ
Cao, YF
Hu, CM
Yang, JL
Zhang, YY
He, RR
Zhu, X
Yu, ZW
Sun, XY
Hong, M
Yang, L
AF Guo, Bin
Fan, Xu-Ran
Fang, Zhong-Ze
Cao, Yun-Feng
Hu, Cui-Min
Yang, Julin
Zhang, Yan-Yan
He, Rong-Rong
Zhu, Xu
Yu, Zhen-Wen
Sun, Xiao-Yu
Hong, Mo
Yang, Lu
TI Deglycosylation of Liquiritin Strongly Enhances its Inhibitory Potential
Towards UDP-Glucuronosyltransferase (UGT) Isoforms
SO PHYTOTHERAPY RESEARCH
LA English
DT Article
DE UDP-glucuronosyltransferase; licorice; liquiritin; liquiritigenin
ID DRUG-DRUG INTERACTIONS
AB The detailed mechanisms on licorice-drug interaction remain to be unclear. The aim of the present study is to investigate the inhibition of important UGT isoforms by two important ingredients of licorice, liquiritin, and liquiritigenin. The results showed that liquiritigenin exhibited stronger inhibition towards all the tested UGT isoforms than liquiritin. Data fitting using Dixon and Lineweaver-Burk plots demonstrated the competitive inhibition of liquiritigenin towards UGT1A1 and UGT1A9-mediated 4-MU glucuronidation reaction. The inhibition kinetic parameters (K-i) were calculated to be 9.1 and 3.2M for UGT1A1 and UGT1A9, respectively. Substrate-dependent inhibition behaviour was also observed for UGT1A1 in the present study. All these results will be helpful for understanding the deep mechanism of licorice-drug interaction. However, when translating these in vitro parameters into in vivo situations, more complex factors should be considered, such as substrate-dependent inhibition of UGT isoforms, the contribution of UGT1A1 and UGT1A9 towards the metabolism of drugs, and many factors affecting the abundance of ingredients in the licorice. Copyright (c) 2012 John Wiley & Sons, Ltd.
C1 [Guo, Bin] Liaoning Med Univ, Affiliated Hosp 1, Jinzhou 121001, Peoples R China.
[Fan, Xu-Ran; Fang, Zhong-Ze; Cao, Yun-Feng; Zhang, Yan-Yan; Zhu, Xu; Yu, Zhen-Wen; Sun, Xiao-Yu; Hong, Mo; Yang, Lu] Chinese Acad Sci, Dalian Inst Chem Phys, Joint Ctr Translat Med, Dalian 116023, Peoples R China.
[Fan, Xu-Ran; Fang, Zhong-Ze; Cao, Yun-Feng; Zhang, Yan-Yan; Zhu, Xu; Yu, Zhen-Wen; Sun, Xiao-Yu; Hong, Mo; Yang, Lu] Liaoning Med Univ, Affiliated Hosp 1, Dalian 116023, Peoples R China.
[He, Rong-Rong] Jinan Univ, Coll Pharm, Guangzhou 510632, Guangdong, Peoples R China.
[Fang, Zhong-Ze; Hu, Cui-Min] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Yang, Julin] Ningbo Coll Hlth Sci, Ningbo 315100, Zhejiang, Peoples R China.
RP Guo, B (reprint author), Liaoning Med Univ, Affiliated Hosp 1, Jinzhou 121001, Peoples R China.
EM Guobin@163.com
NR 19
TC 14
Z9 14
U1 2
U2 20
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0951-418X
J9 PHYTOTHER RES
JI Phytother. Res.
PD AUG
PY 2013
VL 27
IS 8
BP 1232
EP 1236
DI 10.1002/ptr.4855
PG 5
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 187JV
UT WOS:000322114900019
PM 23065713
ER
PT J
AU Lindgren, ME
Fagundes, CP
Alfano, CM
Povoski, SP
Agnese, DM
Arnold, MW
Farrar, WB
Yee, LD
Carson, WE
Schmidt, CR
Kiecolt-Glaser, JK
AF Lindgren, Monica E.
Fagundes, Christopher P.
Alfano, Catherine M.
Povoski, Stephen P.
Agnese, Doreen M.
Arnold, Mark W.
Farrar, William B.
Yee, Lisa D.
Carson, William E.
Schmidt, Carl R.
Kiecolt-Glaser, Janice K.
TI Beta-blockers may reduce intrusive thoughts in newly diagnosed cancer
patients
SO PSYCHO-ONCOLOGY
LA English
DT Article
DE stress; PTSD; propranolol; intrusions; cancer; oncology
ID POSTTRAUMATIC-STRESS-DISORDER; PRIMARY BREAST-CANCER; QUALITY-OF-LIFE;
EMOTIONAL DISTRESS; TRAUMATIC STRESS; SYMPTOMS; PROPRANOLOL; GROWTH;
PTSD; SURVIVORS
AB Objective A cancer diagnosis provokes significant levels of emotional distress, with intrusive thoughts being the most common manifestation among breast cancer survivors. Cancer-related intrusive thoughts can take the form of emotional memories, flashbacks, nightmares, and intrusive images. Emotional arousal after a severe life stressor prolongs adrenergic activation, which in turn may increase risk for post-traumatic symptomatology. However, antihypertensive beta-blockers block adrenergic activation and are known to reduce traumatic memories and related psychological distress. Thus, the current study examined the association between beta-blocker use and the severity of cancer-related intrusive thoughts and related symptoms following a cancer diagnosis.
Methods The 174 breast and 36 female colorectal cancer patients who had recently undergone diagnostic screening or biopsy included 39 beta-blocker users and 171 non-users. Prior to any cancer treatment including surgery, participants completed questionnaires that included the Impact of Events Scale and the Center for Epidemiological Studies Depression Scale. Analyses controlled for age, education, cancer stage, cancer type, days since diagnosis, marital status, depression, and comorbidities.
Results Although the high rates of cancer-related distress in this sample were similar to those of other studies with recently diagnosed patients, beta-blocker users endorsed 32% fewer cancer-related intrusive thoughts than non-users.
Conclusions Recently diagnosed cancer patients using beta-blockers reported less cancer-related psychological distress. These results suggest that beta-blocker use may benefit cancer patients' psychological adjustment following diagnosis, and provide a promising direction for future investigations on the pharmacological benefits of beta-blockers for cancer-related distress. Copyright (c) 2012 John Wiley & Sons, Ltd.
C1 [Lindgren, Monica E.; Fagundes, Christopher P.; Kiecolt-Glaser, Janice K.] Ohio State Univ, Coll Med, Inst Behav Med Res, Columbus, OH 43210 USA.
[Lindgren, Monica E.; Kiecolt-Glaser, Janice K.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA.
[Alfano, Catherine M.; Kiecolt-Glaser, Janice K.] NCI, Bethesda, MD 20892 USA.
[Povoski, Stephen P.; Agnese, Doreen M.; Arnold, Mark W.; Farrar, William B.; Yee, Lisa D.; Carson, William E.; Schmidt, Carl R.] Ohio State Univ, Coll Med, Dept Surg, Columbus, OH 43210 USA.
[Kiecolt-Glaser, Janice K.] Ohio State Univ, Coll Med, Dept Psychiat, Columbus, OH 43210 USA.
RP Kiecolt-Glaser, JK (reprint author), Ohio State Univ, Coll Med, Inst Behav Med Res, 460 Med Ctr Dr, Columbus, OH 43210 USA.
EM Janice.Kiecolt-Glaser@osumc.edu
RI Kiecolt-Glaser, Janice/A-3236-2009; Carson, William/E-2846-2011;
Povoski, Stephen/E-3887-2011; Agnese, Doreen/I-1351-2012
OI Kiecolt-Glaser, Janice/0000-0003-4900-9578;
FU National Institutes of Health [CA131029, CA126857, UL1RR025755,
CA16058]; American Cancer Society [PF-11-007-01-CPPB]; National Cancer
Institute Research Supplement to Promote Diversity in Health-Related
Research [CA126857]
FX Work on this project was supported in part by National Institutes of
Health grants CA131029, CA126857, UL1RR025755, and CA16058, an American
Cancer Society Postdoctoral Fellowship Grant PF-11-007-01-CPPB, and a
National Cancer Institute Research Supplement to Promote Diversity in
Health-Related Research to the first author CA126857.
NR 48
TC 13
Z9 13
U1 0
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1057-9249
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD AUG
PY 2013
VL 22
IS 8
BP 1889
EP 1894
DI 10.1002/pon.3233
PG 6
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA 186CP
UT WOS:000322019800027
PM 23255459
ER
PT J
AU Concheiro, M
Gonzalez-Colmenero, E
Lendoiro, E
Concheiro-Guisan, A
de Castro, A
Cruz-Landeira, A
Lopez-Rivadulla, M
AF Concheiro, Marta
Gonzalez-Colmenero, Eva
Lendoiro, Elena
Concheiro-Guisan, Ana
de Castro, Ana
Cruz-Landeira, Angelines
Lopez-Rivadulla, Manuel
TI Alternative Matrices for Cocaine, Heroin, and Methadone In Utero Drug
Exposure Detection
SO THERAPEUTIC DRUG MONITORING
LA English
DT Article
DE placenta; umbilical cord; meconium; hair; drugs of abuse
ID UMBILICAL-CORD TISSUE; AMNIOTIC-FLUID; NEONATAL OUTCOMES; HAIR ANALYSIS;
BIOLOGICAL MATRICES; PRENATAL EXPOSURE; MECONIUM ANALYSIS; FETAL
TOXICOLOGY; ILLICIT DRUGS; ABUSE
AB Introduction: Drug determination in biological matrices from the mother and the newborn is an objective measure of maternal and fetal drug exposure. The aim of this study was to compare maternal hair, meconium, umbilical cord, and placenta for detecting in utero drug exposure to cocaine, opiates, methadone, and amphetamines.Method: Maternal hair, meconium, umbilical cord, and placenta were collected from 175 mother-newborn dyads. Maternal hair (segmented in trimesters) and meconium specimens were analyzed for cocaine, opiates, methadone, and amphetamines. If either maternal hair or meconium tested positive, umbilical cord and placenta were analyzed. Analyses were performed by liquid chromatography tandem mass spectrometry.Results: In hair, 24 participants tested positive; 21 for cocaine [cocaine 20-50,605, benzoylecgonine (BE) 17-46,668 pg/mg], 7 for methadone (76-26,845 pg/mg), 2 for opiates (morphine 298-2398 pg/mg, codeine 65-914 pg/mg, 6-acetylmorphine 1635-15,657 pg/mg), and 1 for amphetamines (amphetamine 1990 pg/mg, 3,4-methylenedioxyamphetamine 30 pg/mg, 3,4-methylenedioxymethamphetamine 294 pg/mg). In meconium, 6 were positive; 5 for methadone [methadone 88-3752, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) 642-25,179 ng/g], 3 for cocaine (cocaine 7, BE 79, hydroxybenzoylecgonine 5-135, ecgonine-methyl ester 2-56 ng/g), and 2 for opiates (morphine 152-1025, morphine-3-glucuronide 22-23, codeine 4-34 ng/g). Placenta and umbilical cord were positive in 5 and 6 cases, respectively; 5 for methadone in placenta (methadone 7-543, EDDP 10-51 ng/g) and cord (methadone 3-183, EDDP 2-109 ng/g); 1 for cocaine in placenta (cocaine 7, BE 2 ng/g) and cord (BE 6 ng/g); and 1 for opiates in placenta (morphine 6, morphine-3-glucuronide 48 ng/g), and 2 in cord (morphine 2, morphine-3-glucuronide 15-38, morphine-6-glucuronide 5 ng/g). Meconium, placenta, and umbilical cord only tested positive if hair concentrations were greater than Society of Hair Testing cutoffs.Conclusions: Maternal hair is the most sensitive specimen to detect drug consumption during pregnancy. Placenta and umbilical cord could be alternatives to meconium for detecting high in utero drug exposure.
C1 [Concheiro, Marta; Lendoiro, Elena; de Castro, Ana; Cruz-Landeira, Angelines; Lopez-Rivadulla, Manuel] Univ Santiago Compostela, Inst Ciencias Forenses, Secc Toxicol, Santiago De Compostela, Spain.
[Concheiro, Marta] NIDA, IRP, NIH, Baltimore, MD 21224 USA.
[Gonzalez-Colmenero, Eva; Concheiro-Guisan, Ana] Univ Vigo, Complejo Hosp, Secc Neonatol, Vigo 36310, Spain.
[de Castro, Ana] Cienytech SL, Dept Desarrollo & Validac Metodos Cromatog, Santiago De Compostela, Spain.
RP Concheiro, M (reprint author), NIDA, NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 200,Room 05A729, Baltimore, MD 21224 USA.
EM marta.concheiro-guisan@nih.gov
RI DE CASTRO, ANA/M-5159-2015;
OI DE CASTRO, ANA/0000-0002-9832-012X; CRUZ LANDEIRA,
ANGELINES/0000-0003-1382-4546
FU Ministerio de Sanidad, Plan Nacional Sobre Drogas, Gobierno de Espana
[2011/097]; Conselleria de Cultura, Educacion e Ordenacion
Universitaria, Xunta de Galicia [PRE/2011/072]; Ministerio de Ciencia e
Innovacion, Gobierno de Espana [PTQ-10-03936]
FX This study was supported by Ministerio de Sanidad, Plan Nacional Sobre
Drogas, Gobierno de Espana (2011/097 Project). E. Lendoiro thanks
Conselleria de Cultura, Educacion e Ordenacion Universitaria, Xunta de
Galicia, for her predoctoral contract (No PRE/2011/072), and A. de
Castro thanks Ministerio de Ciencia e Innovacion, Gobierno de Espana,
for her contract (Torres Quevedo Program, PTQ-10-03936).
NR 30
TC 7
Z9 7
U1 2
U2 17
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0163-4356
J9 THER DRUG MONIT
JI Ther. Drug Monit.
PD AUG
PY 2013
VL 35
IS 4
BP 502
EP 509
DI 10.1097/FTD.0b013e31828a6148
PG 8
WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology
SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology
GA 188OP
UT WOS:000322202600010
PM 23851907
ER
PT J
AU Sanders, JM
Knudsen, GA
Birnbaum, LS
AF Sanders, J. Michael
Knudsen, Gabriel A.
Birnbaum, Linda S.
TI The Fate of -Hexabromocyclododecane in Female C57BL/6 Mice
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE hexabromocyclododecane; toxicokinetics; mouse; brominated flame
retardant; disposition; risk assessment; persistent organic pollutant
ID BROMINATED FLAME RETARDANTS; TETRABROMOBISPHENOL-A; REPEATED EXPOSURE;
WISTAR RATS; HBCD; METABOLISM; GAMMA; CYTOCHROME-P450; TOXICOKINETICS;
STEREOISOMERS
AB 1,2,5,6,9,10-Hexabromocyclododecane (HBCD) is a high production volume cycloaliphatic used as an additive flame retardant primarily in polystyrene foam building materials. HBCD mixtures contain three major stereoisomers, alpha (), beta (), and gamma (), at a typical ratio of 1.2:0.6:8.2. The toxicokinetic properties of the and isomers differ. For instance, -HBCD has greater bioavailability and potential for accumulation in mice than -HBCD. The present study reports comparative kinetics data for -HBCD needed to support toxicological evaluations of HBCD mixtures. Results indicated that a single oral dose of 3mg/kg of [C-14]-labeled -HBCD was absorbed rapidly ( 85% total dose) in the female C57BL/6 mouse. The C-max for -HBCD-derived radioactivity in tissues, except adipose, was observed 3h following gavage. Approximately 90% of the administered dose was excreted in urine and feces within 24h, primarily as -HBCD-derived metabolites. A portion of the dose (circa 9%) was excreted in feces as -HBCD. Oral administration of 30 or 100mg/kg of -HBCD resulted initially in slower rates of [C-14] elimination; however, cumulative excretion data were similar across the dosing range 4 days postdosing. Residual concentrations of [C-14] in tissues were highest in adipose and liver. -HBCD-derived radioactivity accumulated in most tissues following four consecutive daily oral doses of 3mg/kg. The extent of metabolism and excretion of -HBCD in female C57BL/6 mice was similar to that for -HBCD. The potential for accumulation of -HBCD-derived material in most tissues appeared to be less than for -HBCD.
C1 [Sanders, J. Michael; Knudsen, Gabriel A.; Birnbaum, Linda S.] NCI, Toxicol & Toxicokinet Grp, Basic Res Lab, Ctr Canc Res, Res Triangle Pk, NC 27709 USA.
RP Sanders, JM (reprint author), NIEHS, POB 12233,MD C2-02, Res Triangle Pk, NC 27709 USA.
EM sander10@mail.nih.gov
RI Knudsen, Gabriel/G-3706-2013
OI Knudsen, Gabriel/0000-0002-7208-6451
FU Intramural Research Program of the National Cancer Institute
FX This research was conducted by employees of the National Institutes of
Health and was funded by the Intramural Research Program of the National
Cancer Institute.
NR 36
TC 9
Z9 9
U1 1
U2 43
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD AUG
PY 2013
VL 134
IS 2
BP 251
EP 257
DI 10.1093/toxsci/kft121
PG 7
WC Toxicology
SC Toxicology
GA 186CU
UT WOS:000322020300003
PM 23733921
ER
PT J
AU Seth, RK
Kumar, A
Das, S
Kadiiska, MB
Michelotti, G
Diehl, AM
Chatterjee, S
AF Seth, Ratanesh Kumar
Kumar, Ashutosh
Das, Suvarthi
Kadiiska, Maria B.
Michelotti, Gregory
Diehl, Anna Mae
Chatterjee, Saurabh
TI Environmental ToxinLinked Nonalcoholic Steatohepatitis and Hepatic
Metabolic Reprogramming in Obese Mice
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE bromodichloromethane; hepatocyte; lipid peroxidation; fibrosis; Glut-1;
glycolysis; gluconeogenesis; PPAR-; SREBP-1c; tumor necrosis factor; ob;
ob mice
ID FATTY LIVER-DISEASE; INSULIN-RESISTANCE; LEPTIN RESISTANCE;
BROMODICHLOROMETHANE METABOLISM; GENETIC POLYMORPHISMS; ACTIVATION;
CELLS; NASH; TRIHALOMETHANES; INFLAMMATION
AB Obesity is associated with strong risks of development of chronic inflammatory liver disease and metabolic syndrome following a second hit. This study tests the hypothesis that free radical metabolism of low chronic exposure to bromodichloromethane (BDCM), a disinfection byproduct of drinking water, causes nonalcoholic steatohepatitis (NASH), mediated by cytochrome P450 isoform CYP2E1 and adipokine leptin. Using diet-induced obese mice (DIO), mice deficient in CYP2E1, and mice with spontaneous knockout of the leptin gene, we show that BDCM caused increased lipid peroxidation and increased tyrosine nitration in DIO mice, events dependent on reductive metabolism by CYP2E1. DIO mice, exposed to BDCM, exhibited increased hepatic leptin levels and higher levels of proinflammatory gene expression and Kupffer cell activation. Obese mice exposed to BDCM also showed profound hepatic necrosis, Mallory body formation, collagen deposition, and higher alpha smooth muscle actin expression, events that are hallmarks of NASH. The absence of CYP2E1 gene in mice that were fed with a high-fat diet did not show NASH symptoms and were also protected from hepatic metabolic alterations in Glut-1, Glut-4, phosphofructokinase and phosphoenolpyruvate carboxykinase gene expressions (involved in carbohydrate metabolism), and UCP-1, PGC-1, SREBP-1c, and PPAR- genes (involved in hepatic fat metabolism). Mice lacking the leptin gene were significantly protected from both NASH and metabolic alterations following BDCM exposure, suggesting that higher levels of leptin induction by BDCM in the liver contribute to the development of NASH and metabolic alterations in obesity. These results provide novel insights into BDCM-induced NASH and hepatic metabolic reprogramming and show the regulation of obesity-linked susceptibility to NASH by environmental factors, CYP2E1, and leptin.
C1 [Seth, Ratanesh Kumar; Das, Suvarthi; Chatterjee, Saurabh] Univ S Carolina, Arnold Sch Publ Hlth, Dept Environm Hlth Sci, Environm Hlth & Dis Lab, Columbia, SC 29208 USA.
[Kumar, Ashutosh; Kadiiska, Maria B.] NIEHS, Free Radical Metab Grp, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA.
[Michelotti, Gregory; Diehl, Anna Mae] Duke Univ, Div Gastroenterol, Durham, NC 27707 USA.
RP Chatterjee, S (reprint author), Univ S Carolina, Dept Environm Hlth Sci, Environm Hlth & Dis Lab, Rm 417,921 Assembly St, Columbia, SC 29208 USA.
EM schatt@mailbox.sc.edu
RI Seth, Ratanesh/M-3700-2016;
OI Michelotti, Gregory/0000-0002-7908-1979; Seth,
Ratanesh/0000-0002-7078-0052
FU National Institutes of Health [4R00ES019875-02, R01-DK053792]
FX This work has been supported by National Institutes of Health Pathway to
Independence Award (4R00ES019875-02 to S. C.), National Institutes of
Health (R01-DK053792 to A.M.D.).
NR 44
TC 18
Z9 18
U1 0
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD AUG
PY 2013
VL 134
IS 2
BP 291
EP 303
DI 10.1093/toxsci/kft104
PG 13
WC Toxicology
SC Toxicology
GA 186CU
UT WOS:000322020300007
PM 23640861
ER
PT J
AU Nilubol, N
Weisbrod, AB
Weinstein, LS
Simonds, WF
Jensen, RT
Phan, GQ
Hughes, MS
Libutti, SK
Marx, S
Kebebew, E
AF Nilubol, Naris
Weisbrod, Allison B.
Weinstein, Lee S.
Simonds, William F.
Jensen, Robert T.
Phan, Giao Q.
Hughes, Marybeth S.
Libutti, Steven K.
Marx, Stephen
Kebebew, Electron
TI Utility of Intraoperative Parathyroid Hormone Monitoring in Patients
with Multiple Endocrine Neoplasia Type 1-Associated Primary
Hyperparathyroidism Undergoing Initial Parathyroidectomy
SO WORLD JOURNAL OF SURGERY
LA English
DT Article
ID MINIMALLY INVASIVE PARATHYROIDECTOMY; ASSAY; DISEASE; CRITERIA; SURGERY;
ADENOMA
AB Intraoperative parathyroid hormone monitoring (IOPTH) is a widely used adjunct for primary hyperparathyroidism (pHPT). However, the benefit of IOPTH in familial pHPT, such as in multiple endocrine neoplasia type I (MEN1), remains unclear.
We performed a retrospective analysis of 52 patients with MEN1-associated pHPT undergoing initial parathyroidectomy with IOPTH monitoring at our institution. Parathyroid hormone (PTH) levels were measured before skin incision and 10 min after resection of the last parathyroid gland. Variables analyzed included percent drop of PTH from baseline and the final PTH level compared to the normal reference range (RR).
A total of 52 patients underwent initial subtotal parathyroidectomy with IOPTH. An IOPTH decrease cutoff of a parts per thousand yen75 % from baseline had the highest biochemical cure rate (87 %). In the remaining 13 % who met this cutoff, all had persistent pHPT, with a parts per thousand yen90 % drop of PTH from baseline. The remaining patients, who did not meet the a parts per thousand yen75 % cutoff, were cured. Follow-up was available for three of four patients with final IOPTH levels above the RR: one had persistent pHPT, two had hypoparathyroidism (50 %). When a postresection PTH level was within the RR, 88 % of patients were cured. While considered cured from pHPT, 7 % of patients in this group developed permanent hypoparathyroidism. When the final PTH level dropped below the RR, 28 % developed permanent hypoparathyroidism.
A cutoff in IOPTH decrease of a parts per thousand yen75 % from baseline has the highest biochemically cure rate in patients with pHPT associated with MEN1. However, a 75 % cutoff in IOPTH decrease does not exclude persistent pHPT. The absolute IOPTH value does not accurately predict postoperative hypoparathyroidism.
C1 [Nilubol, Naris; Weisbrod, Allison B.; Kebebew, Electron] NCI, Endocrine Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Weinstein, Lee S.; Simonds, William F.; Marx, Stephen] NIDDK, Metab Dis Branch, NIH, Bethesda, MD USA.
[Jensen, Robert T.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA.
[Phan, Giao Q.; Hughes, Marybeth S.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20816 USA.
[Libutti, Steven K.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Surg, Bronx, NY 10467 USA.
RP Nilubol, N (reprint author), NCI, Endocrine Oncol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,MSC1201 Room 3-3940, Bethesda, MD 20892 USA.
EM niluboln@mail.nih.gov
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health
FX The research was supported in part by the Intramural Research Program of
the Center for Cancer Research, National Cancer Institute, National
Institutes of Health.
NR 26
TC 5
Z9 5
U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-2313
J9 WORLD J SURG
JI World J.Surg.
PD AUG
PY 2013
VL 37
IS 8
BP 1966
EP 1972
DI 10.1007/s00268-013-2054-1
PG 7
WC Surgery
SC Surgery
GA 186EA
UT WOS:000322023600031
PM 23722465
ER
PT J
AU Mullis, CE
Munshaw, S
Grabowski, MK
Eshleman, SH
Serwadda, D
Brookmeyer, R
Nalugoda, F
Kigozi, G
Kagaayi, J
Tobian, AAR
Wawer, M
Gray, RH
Quinn, TC
Laeyendecker, O
AF Mullis, Caroline E.
Munshaw, Supriya
Grabowski, Mary K.
Eshleman, Susan H.
Serwadda, David
Brookmeyer, Ronald
Nalugoda, Fred
Kigozi, Godfrey
Kagaayi, Joseph
Tobian, Aaron A. R.
Wawer, Maria
Gray, Ronald H.
Quinn, Thomas C.
Laeyendecker, Oliver
TI Differential Specificity of HIV Incidence Assays in HIV Subtypes A and
D-Infected Individuals from Rakai, Uganda
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID CAPTURE ENZYME-IMMUNOASSAY; DISEASE PROGRESSION; SEROCONVERSION;
DISTRICT; AFRICA
AB Assays to determine HIV incidence from cross-sectional surveys have exhibited a high rate of false-recent misclassification in Kenya and Uganda where HIV subtypes A and D predominate. Samples from individuals infected with HIV for at least 2 years with known infecting subtype (133 subtype A, 373 subtype D) were tested using the BED-CEIA and an avidity assay. Both assays had a higher rate of false-recent misclassification for subtype D compared to subtype A (13.7% vs. 6.0%, p = 0.02 for BED-CEIA; 11.0% vs. 1.5%, p < 0.001 for avidity). For subtype D samples, false-recent misclassification by the BED-CEIA was also more frequent in women than men (15.0% vs. 5.6%, p = 0.002), and for samples where that had an amino acid other than lysine at position 12 in the BED-CEIA peptide coding region (p = 0.002). Furthermore in subtype D-infected individuals, samples misclassified by one assay were 3.5 times more likely to be misclassified by the other assay. Differential misclassification by infecting subtype of long-term infected individuals as recently infected makes it difficult to use these assays individually to estimate population level incidence without precise knowledge of the distribution of these subtypes within populations where subtype A and D cocirculate. The association of misclassification of the BED-CEIA with the avidity assay in subtype D-infected individuals limits the utility of using these assays in combination within this population.
C1 [Mullis, Caroline E.; Munshaw, Supriya; Quinn, Thomas C.; Laeyendecker, Oliver] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Grabowski, Mary K.; Wawer, Maria; Gray, Ronald H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Eshleman, Susan H.; Tobian, Aaron A. R.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Serwadda, David; Nalugoda, Fred; Kigozi, Godfrey; Kagaayi, Joseph; Wawer, Maria; Gray, Ronald H.] Rakai Hlth Sci Program, Rakai, Uganda.
[Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda.
[Brookmeyer, Ronald] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA.
[Quinn, Thomas C.; Laeyendecker, Oliver] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Baltimore, MD USA.
RP Laeyendecker, O (reprint author), NIAID, LIR, NIH, 855 North Wolfe St,Room 538A, Baltimore, MD 21205 USA.
EM olaeyen1@jhmi.edu
OI Laeyendecker, Oliver/0000-0002-6429-4760
FU HIV Prevention Trials Network (HPTN); National Institute of Allergy and
Infectious Diseases (NIAID); National Institute of Mental Health (NIMH);
National Institute on Drug Abuse (NIDA); Office of AIDS Research, of the
National Institutes of Health (NIH); Department of Health and Human
Services (DHHS) [U01-AI068613, UM1-AI068613]; Bill and Melinda Gates
[22006]; NIAID [U01 A1 61171]; Division of Intramural Research, NIAID,
NIH [NIAID R01AI095068]
FX This work was supported by (1) The HIV Prevention Trials Network (HPTN)
sponsored by the National Institute of Allergy and Infectious Diseases
(NIAID), the National Institute of Mental Health (NIMH), the National
Institute on Drug Abuse (NIDA), Office of AIDS Research, of the National
Institutes of Health (NIH), and Department of Health and Human Services
(DHHS) (grants U01-AI068613 and UM1-AI068613). (2) The Bill and Melinda
Gates 22006, NIAID U01 A1 61171. (3) The Division of Intramural
Research, NIAID, NIH. (4) NIAID R01AI095068.
NR 25
TC 6
Z9 6
U1 1
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD AUG
PY 2013
VL 29
IS 8
BP 1146
EP 1150
DI 10.1089/aid.2012.0105
PG 5
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 185EW
UT WOS:000321949400008
PM 23641870
ER
PT J
AU Monach, PA
Warner, RL
Tomasson, G
Specks, U
Stone, JH
Ding, L
Fervenza, FC
Fessler, BJ
Hoffman, GS
Ikle, D
Kallenberg, CGM
Krischer, J
Langford, CA
Mueller, M
Seo, P
St Clair, EW
Spiera, R
Tchao, N
Ytterberg, SR
Johnson, KJ
Merkel, PA
AF Monach, Paul A.
Warner, Roscoe L.
Tomasson, Gunnar
Specks, Ulrich
Stone, John H.
Ding, Linna
Fervenza, Fernando C.
Fessler, Barri J.
Hoffman, Gary S.
Ikle, David
Kallenberg, Cees G. M.
Krischer, Jeffrey
Langford, Carol A.
Mueller, Mark
Seo, Philip
St Clair, E. William
Spiera, Robert
Tchao, Nadia
Ytterberg, Steven R.
Johnson, Kent J.
Merkel, Peter A.
TI Serum proteins reflecting inflammation, injury and repair as biomarkers
of disease activity in ANCA-associated vasculitis
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Article
DE Autoimmune Diseases; Chemokines; Cytokines
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; SOLUBLE ADHESION MOLECULES; ANTINEUTROPHIL
CYTOPLASMIC ANTIBODIES; C-REACTIVE PROTEIN; B-CELL CHEMOKINE;
WEGENERS-GRANULOMATOSIS; FOLLOW-UP; E-SELECTIN; MATRIX
METALLOPROTEINASES; ELEVATED PRODUCTION
AB Objective To identify circulating proteins that distinguish between active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and remission in a manner complementary to markers of systemic inflammation.
Methods Twenty-eight serum proteins representing diverse aspects of the biology of AAV were measured before and 6months after treatment in a large clinical trial of AAV. Subjects (n=186) enrolled in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial were studied. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were available for comparison. The primary outcome was the ability of markers to distinguish severe AAV (Birmingham Vasculitis Activity Score for Wegener's granulomatosis (BVAS/WG)3 at screening) from remission (BVAS/WG=0 at month 6), using areas under receiver operating characteristic (ROC) curve (AUC).
Results All subjects had severe active vasculitis (median BVAS/WG=8) at screening. In the 137 subjects in remission at month 6, 24 of the 28 markers showed significant declines. ROC analysis indicated that levels of CXCL13 (BCA-1), matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinases-1 (TIMP-1) best discriminated active AAV from remission (AUC>0.8) and from healthy controls (AUC>0.9). Correlations among these markers and with ESR or CRP were low.
Conclusions Many markers are elevated in severe active AAV and decline with treatment, but CXCL13, MMP-3 and TIMP-1 distinguish active AAV from remission better than the other markers studied, including ESR and CRP. These proteins are particularly promising candidates for future studies to address unmet needs in the assessment of patients with AAV.
C1 [Monach, Paul A.; Tomasson, Gunnar; Merkel, Peter A.] Boston Univ, Sch Med, Vasculitis Ctr, Rheumatol Sect, Boston, MA USA.
[Monach, Paul A.; Tomasson, Gunnar; Merkel, Peter A.] Boston Univ, Sch Med, Clin Epidemiol Unit, Boston, MA USA.
[Warner, Roscoe L.; Johnson, Kent J.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Specks, Ulrich] Mayo Clin, Coll Med, Div Pulm & Crit Care Med, Rochester, MN USA.
[Stone, John H.] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA.
[Ding, Linna] Natl Inst Allergy & Infect Dis, Bethesda, MD USA.
[Fervenza, Fernando C.] Mayo Clin, Coll Med, Div Nephrol & Hypertens, Rochester, MN USA.
[Fessler, Barri J.] Univ Alabama, Div Clin Immunol & Rheumatol, Birmingham, MN USA.
[Hoffman, Gary S.] Cleveland Clin, Ctr Vasculitis Care & Res, Cleveland, OH 44106 USA.
[Ikle, David] Rho, Chapel Hill, NC USA.
[Kallenberg, Cees G. M.] Univ Groningen, Univ Med Ctr Groningen, Dept Rheumatol & Clin Immunol, Groningen, Netherlands.
[Krischer, Jeffrey] Univ S Florida, Coll Med, Dept Pediat, Tampa, FL 33612 USA.
[Mueller, Mark] Immune Tolerance Network, Bethesda, MD USA.
[Seo, Philip] Johns Hopkins Univ, Div Rheumatol, Baltimore, MD USA.
[St Clair, E. William] Duke Univ, Div Rheumatol & Immunol, Durham, NC USA.
[Spiera, Robert] Hosp Special Surg, Div Rheumatol, New York, NY 10021 USA.
[Tchao, Nadia] Immune Tolerance Network, San Francisco, CA USA.
[Ytterberg, Steven R.] Mayo Clin, Coll Med, Div Rheumatol, Rochester, MN USA.
[Merkel, Peter A.] Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA.
RP Merkel, PA (reprint author), Univ Penn, Div Rheumatol, 8th Floor Penn Tower,3400 Spruce St, Philadelphia, PA 19104 USA.
EM pmerkel@upenn.edu
FU Vasculitis Clinical Research Consortium; National Institute of Arthritis
and Musculoskeletal and Skin Diseases [U54AR057319, RC1 AR058303, P60
AR047785]; National Center for Research Resources [U54 RR019497];
National Institute of Neurological Disorders and Stroke [NS064808];
Office of Rare Diseases Research; Immune Tolerance Network (NIH) [N01
AI15416]; National Institute of Allergy and Infectious Diseases;
Juvenile Diabetes Research Foundation; Genentech; Biogen Idec; National
Center for Research Resources (NCRR), at Johns Hopkins University
[RR024150-01]; NCRR [RR025005]; Boston University; National Institutes
of Health [M01 RR00533]; Arthritis Foundation; [K24 AR049185]; [K23
AR052820]; [K24 AR02224]
FX This work was sponsored by the Vasculitis Clinical Research Consortium
which has received support from the National Institute of Arthritis and
Musculoskeletal and Skin Diseases (U54AR057319, RC1 AR058303 and P60
AR047785), the National Center for Research Resources (U54 RR019497),
the National Institute of Neurological Disorders and Stroke (NS064808),
and the Office of Rare Diseases Research. The RAVE Trial was performed
with the support of the Immune Tolerance Network (NIH Contract N01
AI15416), an international clinical research consortium supported by the
National Institute of Allergy and Infectious Diseases and the Juvenile
Diabetes Research Foundation (see online appendix for the list of all
members of the RAVE-ITN Research Group). Genentech and Biogen Idec
provided the study medications and partial funding. At the Mayo Clinic
and Foundation, the trial was supported by a Clinical and Translational
Science Award from the National Center for Research Resources (NCRR)
(RR024150-01), at Johns Hopkins University, by grants from the NCRR
(RR025005) and career development awards (K24 AR049185 to JHS, and K23
AR052820 to PS), and at Boston University, by a Clinical and
Translational Science Award (RR 025771), grants from the National
Institutes of Health (M01 RR00533) and a career development award (K24
AR02224 to Dr Peter A Merkel). Dr Paul A Monach was supported by an
Arthritis Investigator Award from the Arthritis Foundation.
NR 54
TC 22
Z9 24
U1 0
U2 5
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-4967
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD AUG
PY 2013
VL 72
IS 8
BP 1342
EP 1350
DI 10.1136/annrheumdis-2012-201981
PG 9
WC Rheumatology
SC Rheumatology
GA 176WW
UT WOS:000321338400015
PM 22975753
ER
PT J
AU Carroll, MW
Jeon, D
Mountz, JM
Lee, JD
Jeong, YJ
Zia, N
Lee, M
Lee, J
Via, LE
Lee, S
Eum, SY
Lee, SJ
Goldfeder, LC
Cai, Y
Jin, B
Kim, Y
Oh, T
Chen, RY
Dodd, LE
Gu, WJ
Dartois, V
Park, SK
Kim, CT
Barry, CE
Cho, SN
AF Carroll, Matthew W.
Jeon, Doosoo
Mountz, James M.
Lee, Jong Doo
Jeong, Yeon Joo
Zia, Nadeem
Lee, Myungsun
Lee, Jongseok
Via, Laura E.
Lee, Soyoung
Eum, Seok-Yong
Lee, Sung-Joong
Goldfeder, Lisa C.
Cai, Ying
Jin, Boyoung
Kim, Youngran
Oh, Taegwon
Chen, Ray Y.
Dodd, Lori E.
Gu, Wenjuan
Dartois, Veronique
Park, Seung-Kyu
Kim, Cheon Tae
Barry, Clifton E., III
Cho, Sang-Nae
TI Efficacy and Safety of Metronidazole for Pulmonary Multidrug-Resistant
Tuberculosis
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID MYCOBACTERIUM-TUBERCULOSIS; NONREPLICATING PERSISTENCE; BACTERICIDAL
ACTIVITY; NEUROPATHY; MODEL; COMBINATIONS; PHARMACOKINETICS; DELAMANID;
PA-824; TRIAL
AB Pulmonary lesions from active tuberculosis patients are thought to contain persistent, nonreplicating bacilli that arise from hypoxic stress. Metronidazole, approved for anaerobic infections, has antituberculosis activity against anoxic bacilli in vitro and in some animal models and may target persistent, nonreplicating bacilli. In this double-blind, placebo-controlled trial, pulmonary multidrug-resistant tuberculosis subjects were randomly assigned to receive metronidazole (500 mg thrice daily) or placebo for 8 weeks in addition to an individualized background regimen. Outcomes were measured radiologically (change on high-resolution computed tomography [HRCT]), microbiologically (time to sputum smear and culture conversion), and clinically (status 6 months after stopping therapy). Enrollment was stopped early due to excessive peripheral neuropathies in the metronidazole arm. Among 35 randomized subjects, 31 (15 metronidazole, 16 placebo) were included in the modified intent-to-treat analysis. There were no significant differences by arm in improvement of HRCT lesions from baseline to 2 or 6 months. More subjects in the metronidazole arm converted their sputum smear (P = 0.04) and liquid culture (P = 0.04) to negative at 1 month, but these differences were lost by 2 months. Overall, 81% showed clinical success 6 months after stopping therapy, with no differences by arm. However, 8/16 (50%) of subjects in the metronidazole group and 2/17 (12%) of those in the placebo group developed peripheral neuropathy. Subjects who received metronidazole were 4.3-fold (95% confidence interval [CI], 1.1 to 17.1) more likely to develop peripheral neuropathies than subjects who received placebo. Metronidazole may have increased early sputum smear and culture conversion but was too neurotoxic to use over the longer term. Newer nitroimidazoles with both aerobic and anaerobic activity, now in clinical trials, may increase the sterilizing potency of future treatment regimens.
C1 [Carroll, Matthew W.; Via, Laura E.; Goldfeder, Lisa C.; Cai, Ying; Chen, Ray Y.; Barry, Clifton E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Jeon, Doosoo; Park, Seung-Kyu; Kim, Cheon Tae] Natl Masan Hosp, Chang Won, South Korea.
[Mountz, James M.; Zia, Nadeem] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15260 USA.
[Lee, Jong Doo] Yonsei Univ, Coll Med, Dept Nucl Med, Seoul, South Korea.
[Jeong, Yeon Joo] Pusan Natl Univ, Sch Med, Dept Diagnost Radiol, Pusan, South Korea.
[Lee, Myungsun; Lee, Jongseok; Lee, Soyoung; Eum, Seok-Yong; Lee, Sung-Joong; Jin, Boyoung; Kim, Youngran; Cho, Sang-Nae] Int TB Res Ctr, Chang Won, South Korea.
[Oh, Taegwon; Cho, Sang-Nae] Yonsei Univ, Coll Med, Inst Immunol & Immunol Dis, Seoul, South Korea.
[Dodd, Lori E.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Gu, Wenjuan] SAIC Frederick Inc, Biostat Res Branch, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Dartois, Veronique] Univ Med & Dent New Jersey, Publ Hlth Res Inst, Newark, NJ 07103 USA.
[Cho, Sang-Nae] Yonsei Univ, Coll Med, Dept Microbiol, Seoul, South Korea.
RP Cho, SN (reprint author), Int TB Res Ctr, Chang Won, South Korea.
EM cbarry@niaid.nih.gov; raycho@yonsei.ac.kr
RI Barry, III, Clifton/H-3839-2012;
OI Via, Laura/0000-0001-6074-9521; Chen, Ray/0000-0001-6344-1442
FU Intramural Research Program, National Institute of Allergy and
Infectious Diseases, National Institutes of Health; Ministry of Health
and Welfare, South Korea; Bill and Melinda Gates Foundation through the
Grand Challenges in Global Health Program; National Cancer Institute,
National Institutes of Health [HHSN261200800001E]
FX This work was supported (in part) by the Intramural Research Program,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health; (in part) by the Ministry of Health and Welfare,
South Korea; (in part) by the Bill and Melinda Gates Foundation through
the Grand Challenges in Global Health Program (to Douglas Young,
Imperial College, London); and (in part) by the National Cancer
Institute, National Institutes of Health, under contract no.
HHSN261200800001E.
NR 32
TC 19
Z9 20
U1 1
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD AUG
PY 2013
VL 57
IS 8
BP 3903
EP 3909
DI 10.1128/AAC.00753-13
PG 7
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 182RO
UT WOS:000321761800056
PM 23733467
ER
PT J
AU Kenney, J
Rodriguez, A
Kizima, L
Seidor, S
Menon, R
Jean-Pierre, N
Pugach, P
Levendosky, K
Derby, N
Gettie, A
Blanchard, J
Piatak, M
Lifson, JD
Paglini, G
Zydowsky, TM
Robbiani, M
Romero, JAF
AF Kenney, Jessica
Rodriguez, Aixa
Kizima, Larisa
Seidor, Samantha
Menon, Radhika
Jean-Pierre, Ninochka
Pugach, Pavel
Levendosky, Keith
Derby, Nina
Gettie, Agegnehu
Blanchard, James
Piatak, Michael, Jr.
Lifson, Jeffrey D.
Paglini, Gabriela
Zydowsky, Thomas M.
Robbiani, Melissa
Fernandez Romero, Jose A.
TI A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide,
Is Safe and Effective against Simian-Human Immunodeficiency Virus and
Herpes Simplex Virus 2 Infection In Vivo
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID CANDIDATE TOPICAL MICROBICIDES; PLACEBO-CONTROLLED TRIAL; CARRAGUARD
VAGINAL GEL; PREEXPOSURE PROPHYLAXIS; ENTRY INHIBITOR; HIV PREVENTION;
SPL7013 GEL; VIRAL LOAD; WOMEN; TRANSMISSION
AB We previously showed that a prototype gel comprising zinc acetate (ZA) in carrageenan (CG) protected mice against vaginal and rectal herpes simplex virus 2 (HSV-2) challenge as well as macaques against vaginal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) challenge. In this work, we modified buffers and cosolvents to obtain a stable, nearly iso-osmolal formulation and evaluated its safety and efficacy against SHIV-RT and HSV-2. In vitro toxicity to lactobacilli and Candida albicans was determined. Macaques were given daily doses of ZA and CG (ZA/CG) or CG alone vaginally for 14 days and challenged with SHIV-RT 24 h later. Mice were challenged vaginally or rectally with HSV-2 immediately after a single gel treatment to measure efficacy or vaginally 12 h after daily gel treatment for 7 days to evaluate the gel's impact on susceptibility to HSV-2 infection. The modified ZA/CG neither affected the viability of lactobacilli or C. albicans nor enhanced vaginal HSV-2 infection after daily ZA/CG treatment. Vaginal SHIV-RT infection of macaques was reduced by 66% (P = 0.006) when macaques were challenged 24 h after the last dose of gel. We observed 60% to 80% uninfected mice after vaginal (P < 0.0001) and rectal (P = 0.008) high-dose HSV-2 challenge. The modified ZA/CG gel is safe and effective in animal models and represents a potential candidate to limit the transmission of HIV and HSV-2.
C1 [Kenney, Jessica; Rodriguez, Aixa; Kizima, Larisa; Seidor, Samantha; Menon, Radhika; Jean-Pierre, Ninochka; Pugach, Pavel; Levendosky, Keith; Derby, Nina; Zydowsky, Thomas M.; Robbiani, Melissa; Fernandez Romero, Jose A.] Populat Council, Ctr Biomed Res, New York, NY 10021 USA.
[Gettie, Agegnehu] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10021 USA.
[Blanchard, James] Tulane Univ, Tulane Natl Primate Res Ctr, Covington, LA USA.
[Piatak, Michael, Jr.; Lifson, Jeffrey D.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD USA.
[Paglini, Gabriela; Fernandez Romero, Jose A.] Univ Nacl Cordoba, Fac Ciencias Med, Inst Virol JM Vanella, RA-5000 Cordoba, Argentina.
RP Romero, JAF (reprint author), Populat Council, Ctr Biomed Res, 1230 York Ave, New York, NY 10021 USA.
EM jromero@popcouncil.org
FU Swedish Ministry of Foreign Affairs; Swedish International Development
Cooperation Agency; TNPRC National Institutes of Health (NIH) [RR00164];
National Cancer Institute, NIH [HHSN261200800001E]
FX This study was made possible by the generous support of the American
people through the U.S. Agency for International Development (USAID;
GPO-A-00-04-00019-00. This work was also supported by the Swedish
Ministry of Foreign Affairs, the Swedish International Development
Cooperation Agency, and the TNPRC National Institutes of Health (NIH;
base grant RR00164) and with federal funds from the National Cancer
Institute, NIH, under contract HHSN261200800001E.
NR 62
TC 18
Z9 19
U1 0
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD AUG
PY 2013
VL 57
IS 8
BP 4001
EP 4009
DI 10.1128/AAC.00796-13
PG 9
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 182RO
UT WOS:000321761800070
PM 23752515
ER
PT J
AU Alter, BP
Rosenberg, PS
Day, T
Menzel, S
Giri, N
Savage, SA
Thein, SL
AF Alter, Blanche P.
Rosenberg, Philip S.
Day, Thomas
Menzel, Stephan
Giri, Neelam
Savage, Sharon A.
Thein, Swee Lay
TI Genetic regulation of fetal haemoglobin in inherited bone marrow failure
syndromes
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE dyskeratosis congenita; Fanconi anaemia; fetal haemoglobin; inherited
bone marrow failure syndromes; quantitative trait loci
AB Patients with inherited bone marrow failure syndromes (IBMFS) have stress erythropoiesis', with anaemia, macrocytosis, increased fetal haemoglobin (Hb F) and high erythropoietin levels. In haemoglobinopathies, Hb F levels are regulated by 3 quantitative trait loci, HBS1L-MYB, BCL11A and Xmn1-HBG2. In our study of 97 patients with an IBMFS, increased Hb F was associated with young age, male gender, anaemia, high erythropoietin levels, and alternative alleles in Xmn1-HBG2 [adjusted P=004 for the total group, driven by Fanconi anaemia (P=002) and dyskeratosis congenita (P=009)]. Thus Hb F is regulated in IBMFS by Xmn1-HBG2, as it is in the haemoglobinopathies.
C1 [Alter, Blanche P.; Giri, Neelam; Savage, Sharon A.] NCI, Clin Genet Branch, Div Clin Epidemiol & Genet, Bethesda, MD 20892 USA.
[Rosenberg, Philip S.] NCI, Biostat Branch, Div Clin Epidemiol & Genet, Bethesda, MD 20892 USA.
[Day, Thomas; Menzel, Stephan; Thein, Swee Lay] Kings Coll London, Dept Mol Haematol, London, England.
RP Alter, BP (reprint author), NCI, NIH, DCEG, CGB Branch, 9609 Med Ctr Dr,Rm 6E452, Bethesda, MD 20892 USA.
EM alterb@mail.nih.gov
RI Savage, Sharon/B-9747-2015;
OI Savage, Sharon/0000-0001-6006-0740; Day, Thomas/0000-0001-8391-7903
FU National Institutes of Health; National Cancer Institute; Westat,
Incorporated; Medical Research Council (MRC, UK) [G0001249 ID 56477];
[N02-CP-91026]; [N02-CP-11019]; [HHSN261200655001C]
FX We are extremely grateful to all subjects for their enthusiastic
participation in the IBMFS study. This research was supported in part by
the Intramural Research Program of the National Institutes of Health and
the National Cancer Institute (B.P.A., N.G., S.A.S., P.S.R.), and by
contracts N02-CP-91026, N02-CP-11019 and HHSN261200655001C with Westat,
Incorporated; and the Medical Research Council (MRC, UK) G0001249 ID
56477 (S.L.T.). B.P.A. and S.L.T. designed the study, analysed data, and
wrote the paper. TD and SM performed the research and analysed data.
P.S.R. analysed data and wrote the paper. N.G. and S.A.S. provided
clinical material and samples. All authors reviewed and edited the final
manuscript.
NR 7
TC 2
Z9 2
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD AUG
PY 2013
VL 162
IS 4
BP 542
EP 546
DI 10.1111/bjh.12399
PG 5
WC Hematology
SC Hematology
GA 186EQ
UT WOS:000322025200017
PM 23713742
ER
PT J
AU Bosire, C
Stampfer, MJ
Subar, AF
Wilson, KM
Park, Y
Sinha, R
AF Bosire, Claire
Stampfer, Meir J.
Subar, Amy F.
Wilson, Kathryn M.
Park, Yikyung
Sinha, Rashmi
TI Coffee consumption and the risk of overall and fatal prostate cancer in
the NIH-AARP Diet and Health Study
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Coffee; Caffeine; Prostatic neoplasms; Prospective studies
ID RETIRED-PERSONS DIET; AMERICAN-ASSOCIATION; NATIONAL-INSTITUTES; COHORT;
PROGRESSION; SMOKING; HAWAII
AB Evidence on the association between coffee consumption and prostate cancer risk is inconsistent; furthermore, few studies have examined the relationship between coffee consumption and fatal prostate cancer. The aim of this study was to investigate whether coffee intake is associated with the risk of overall and fatal prostate cancer.
We conducted a prospective analysis among 288,391 men in the National Institutes of Health AARP Diet and Health Study who were between 50 and 71 years old at baseline in 1995-1996. Coffee consumption was assessed at baseline. Cox proportional hazards models were used to calculate the age- and multivariable-adjusted hazard ratios (HR)s and 95 % confidence intervals (CIs).
Over 11 years of follow-up, 23,335 cases of prostate cancer were ascertained, including 2,927 advanced and 917 fatal cases. Coffee consumption was not significantly associated with prostate cancer risk. The multivariable-adjusted HRs (95 % CI), comparing those who drank six or more cups per day to nondrinker, were as follows: 0.94 (0.86-1.02), p trend = 0.08 for overall prostate cancer, 1.13 (0.91-1.40), p trend = 0.62 for advanced prostate cancer, and 0.79 (0.53-1.17), p trend = 0.20 for fatal prostate cancer. The findings remained nonsignificant when we stratified by prostate-specific antigen testing history or restricted to nonsmokers.
We found no statistically significant association between coffee consumption and the risk of overall, advanced, or fatal prostate cancer in this cohort, though a modest reduction in risk could not be excluded.
C1 [Bosire, Claire; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Stampfer, Meir J.; Wilson, Kathryn M.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Stampfer, Meir J.; Wilson, Kathryn M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, Boston, MA 02115 USA.
[Subar, Amy F.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Park, Yikyung; Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Bosire, C (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 655 Huntington Ave, Boston, MA 02115 USA.
EM bosirec@mail.harvard.edu
RI Sinha, Rashmi/G-7446-2015;
OI Sinha, Rashmi/0000-0002-2466-7462; Park, Yikyung/0000-0002-6281-489X
FU National Cancer Institute, National Institutes of Health; National
Cancer Institute at the National Institutes of Health [R25 CA098566];
Florida Department of Health (FDOH)
FX This research was supported in part by the Intermural Research Program
of the National Cancer Institute, National Institutes of Health. C.
Bosire was supported in part by the National Cancer Institute at the
National Institutes of Health (training grant R25 CA098566). The authors
thank Sigurd Hermansen and Kerry Grace Morrissey from Westat Inc.
(Rockville, Maryland) for study outcomes ascertainment and management
and Leslie Carroll at Information Management Services (Silver Spring,
Maryland) for data support and analysis. Cancer incidence data from the
Atlanta metropolitan area were collected by the Georgia Center for
Cancer Statistics, Department of Epidemiology, Rollins School of Public
Health, Emory University. Cancer incidence data from California were
collected by the California Department of Health Services, Cancer
Surveillance Section. Cancer incidence data from the Detroit
metropolitan area were collected by the Michigan Cancer Surveillance
Program, Community Health Administration, State of Michigan. The Florida
cancer incidence data used in this report were collected by the Florida
Cancer Data System (FCDC) under contract with the Florida Department of
Health (FDOH). (The views expressed herein are solely those of the
authors and do not necessarily reflect those of the FCDC or FDOH.).
Cancer incidence data from Louisiana were collected by the Louisiana
Tumor Registry, Louisiana State University Medical Center in New
Orleans. Cancer incidence data from New Jersey were collected by the New
Jersey State Cancer Registry, Cancer Epidemiology Services, New Jersey
State Department of Health and Senior Services. Cancer incidence data
from North Carolina were collected by the North Carolina Central Cancer
Registry. Cancer incidence data from Pennsylvania were supplied by the
Division of Health Statistics and Research, Pennsylvania Department of
Health, Harrisburg, Pennsylvania (The Pennsylvania Department of Health
specifically disclaims responsibility for any analyses, interpretations
or conclusions.). Cancer incidence data from Arizona were collected by
the Arizona Cancer Registry, Division of Public Health Services, Arizona
Department of Health Services. Cancer incidence data from Texas were
collected by the Texas Cancer Registry, Cancer Epidemiology and
Surveillance Branch, Texas Department of State Health Services. Cancer
incidence data from Nevada were collected by the Nevada Central Cancer
Registry, Center for Health Data and Research, Bureau of Health Planning
and Statistics, State Health Division, State of Nevada Department of
Health and Human Services.
NR 27
TC 14
Z9 16
U1 1
U2 20
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD AUG
PY 2013
VL 24
IS 8
BP 1527
EP 1534
DI 10.1007/s10552-013-0229-6
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 182RK
UT WOS:000321761400006
PM 23681472
ER
PT J
AU Magalona, SC
Rasetti, R
Chen, JS
Chen, Q
Gold, I
Decot, H
Callicott, JH
Berman, KF
Apud, JA
Weinberger, DR
Mattay, VS
AF Magalona, Sophia C.
Rasetti, Roberta
Chen, Jingshan
Chen, Qiang
Gold, Ian
Decot, Heather
Callicott, Joseph H.
Berman, Karen F.
Apud, Jose A.
Weinberger, Daniel R.
Mattay, Venkata S.
TI Effect of Tolcapone on Brain Activity During a Variable Attentional
Control Task: A Double-Blind, Placebo-Controlled, Counter-Balanced Trial
in Healthy Volunteers
SO CNS DRUGS
LA English
DT Article
ID CATECHOL-O-METHYLTRANSFERASE; ANTERIOR CINGULATE CORTEX; RAT PREFRONTAL
CORTEX; EVENT-RELATED FMRI; SELECTIVE ATTENTION; PARKINSONS-DISEASE;
FUNCTIONAL MRI; WORKING-MEMORY; VAL(158)MET GENOTYPE; ACTIVATION
PATTERNS
AB Attention is the capacity to flexibly orient behaviors and thoughts towards a goal by selecting and integrating relevant contextual information. The dorsal cingulate (dCC) and prefrontal (PFC) cortices play critical roles in attention. Evidence indicates that catechol-O-methyltransferase (COMT) modulates dopaminergic tone in the PFC and dCC.
In this study, we explored the effect of tolcapone, a CNS penetrant COMT inhibitor that increases cortical dopamine levels, on brain activity during a Variable Attentional Control (VAC) task.
We performed a double-blinded, placebo-controlled, counter-balanced trial with tolcapone (Tasmar, tablets, 100 mg three times a day for 1 day and then 200 mg three times a day for 6 days; ClinicalTrials.gov identifier: NCT00044083).
The study was conducted in the Clinical Center of the National Institute of Mental Health from 2005 to 2009.
Twenty healthy volunteers (11 males; mean age = 32.7 years) with good imaging and performance data on both arms of the study were investigated.
Participants underwent 3T blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) while performing the event-related VAC task, which varies attention over three levels of load: LOW, INT (intermediate), and HIGH.
Changes in behavioral data and individual contrast images were analyzed using ANOVA with drug and task load as co-factors.
There was a significant main effect of increasing task load, with resulting decreased accuracy and increased reaction time. While there was no significant effect of tolcapone on these behavioral measures, the neuroimaging data showed a significant effect on load-related changes in dCC, with significantly lower dCC activation on tolcapone compared with placebo. Further, neural activity in dCC correlated positively with COMT enzyme activity (i.e., lower COMT activity and presumably more dopamine was associated with lower activation in dCC, i.e., more efficient information processing).
Our results show that pharmacological reduction of COMT activity modulates the engagement of attentional mechanisms, selectively enhancing the efficiency of dCC processing in healthy volunteers, reflected as decreased activity for the same level of performance.
C1 [Magalona, Sophia C.; Rasetti, Roberta; Chen, Jingshan; Gold, Ian; Decot, Heather; Callicott, Joseph H.; Berman, Karen F.; Apud, Jose A.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
[Chen, Qiang; Weinberger, Daniel R.; Mattay, Venkata S.] Lieber Inst Brain Dev, Baltimore, MD 21205 USA.
[Weinberger, Daniel R.] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD USA.
[Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD USA.
[Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
RP Mattay, VS (reprint author), Lieber Inst Brain Dev, Johns Hopkins Med Campus,855 North Wolfe St, Baltimore, MD 21205 USA.
EM anand.mattay@libd.org
RI Callicott, Joseph/C-9102-2009
OI Callicott, Joseph/0000-0003-1298-3334
FU Weinberger Lab in the Intramural Research Program of the National
Institute of Mental Health, NIH, Bethesda, MD, USA; Lieber Institute for
Brain Development
FX This research was supported by direct funding of the Weinberger Lab in
the Intramural Research Program of the National Institute of Mental
Health, NIH, Bethesda, MD 20892, USA. and the Lieber Institute for Brain
Development.
NR 57
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U1 1
U2 7
PU ADIS INT LTD
PI AUCKLAND
PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW
ZEALAND
SN 1172-7047
J9 CNS DRUGS
JI CNS Drugs
PD AUG
PY 2013
VL 27
IS 8
BP 663
EP 673
DI 10.1007/s40263-013-0082-x
PG 11
WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 185GW
UT WOS:000321956300007
PM 23794107
ER
PT J
AU Fessler, EB
Chibane, FL
Wang, ZF
Chuang, DM
AF Fessler, Emily B.
Chibane, Fairouz L.
Wang, Zhifei
Chuang, De-Maw
TI Potential Roles of HDAC Inhibitors in Mitigating Ischemia-induced Brain
Damage and Facilitating Endogenous Regeneration and Recovery
SO CURRENT PHARMACEUTICAL DESIGN
LA English
DT Article
DE Histone deacetylase inhibitors; ischemia; stroke; neuroprotection;
anti-inflammation; angiogenesis; neurogenesis; functional recovery
ID HISTONE DEACETYLASE INHIBITORS; FOCAL CEREBRAL-ISCHEMIA;
ENDOPLASMIC-RETICULUM STRESS; AMYOTROPHIC-LATERAL-SCLEROSIS; CHRONIC
VALPROATE TREATMENT; MOOD STABILIZERS LITHIUM; NITRIC-OXIDE SYNTHASE;
SUBEROYLANILIDE HYDROXAMIC ACID; PROTECTS DOPAMINERGIC-NEURONS;
TRANSIENT GLOBAL-ISCHEMIA
AB Ischemic stroke is a leading cause of death and disability worldwide, with few available treatment options. The pathophysiology of cerebral ischemia involves both early phase tissue damage, characterized by neuronal death, inflammation, and blood-brain barrier breakdown, followed by late phase neurovascular recovery. It is becoming clear that any promising treatment strategy must target multiple points in the evolution of ischemic injury to provide substantial therapeutic benefit. Histone deacetylase (HDAC) inhibitors are a class of drugs that increase the acetylation of histone and non-histone proteins to activate transcription, enhance gene expression, and modify the function of target proteins. Acetylation homeostasis is often disrupted in neurological conditions, and accumulating evidence suggests that HDAC inhibitors have robust protective properties in many preclinical models of these disorders, including ischemic stroke. Specifically, HDAC inhibitors such as trichostatin A, valproic acid, sodium butyrate, sodium 4-phenylbutyrate, and suberoylanilide hydroxamic acid have been shown to provide robust protection against excitotoxicity, oxidative stress, ER stress, apoptosis, inflammation, and blood-brain barrier breakdown. Concurrently, these agents can also promote angiogenesis, neurogenesis and stem cell migration to dramatically reduce infarct volume and improve functional recovery after experimental cerebral ischemia. In the following review, we discuss the mechanisms by which HDAC inhibitors exert these protective effects and provide evidence for their strong potential to ultimately improve stroke outcome in patients.
C1 [Fessler, Emily B.; Chibane, Fairouz L.; Wang, Zhifei; Chuang, De-Maw] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, NIH, 10 Ctr Dr,MSC 1363, Bethesda, MD 20892 USA.
EM chuang@mail.nih.gov
RI Wang, Zhifei/I-2787-2013
FU Intramural Research Program of the National Institute of Mental Health
(NIMH); National Institutes of Health (NIH); Hsu family gift fund
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health (NIMH), National Institutes of
Health (NIH), and the Hsu family gift fund. The authors would like to
thank members of the Molecular Neurobiology Section, NIMH, NIH for their
helpful discussions and assistance.
NR 195
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U1 4
U2 18
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1381-6128
J9 CURR PHARM DESIGN
JI Curr. Pharm. Design
PD AUG
PY 2013
VL 19
IS 28
BP 5105
EP 5120
PG 16
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 176XZ
UT WOS:000321341400009
PM 23448466
ER
PT J
AU Lee, SI
Conrad, T
Jones, SM
Lagziel, A
Starost, MF
Belyantseva, IA
Friedman, TB
Morell, RJ
AF Lee, Sue I.
Conrad, Travis
Jones, Sherri M.
Lagziel, Ayala
Starost, Matthew F.
Belyantseva, Inna A.
Friedman, Thomas B.
Morell, Robert J.
TI A null mutation of mouse Kcna10 causes significant vestibular and mild
hearing dysfunction (vol 300, pg 1, 2013)
SO HEARING RESEARCH
LA English
DT Correction
C1 [Lee, Sue I.; Conrad, Travis; Lagziel, Ayala; Belyantseva, Inna A.; Friedman, Thomas B.; Morell, Robert J.] Natl Inst Deafness & Other Commun Disorders, Sect Human Genet, Mol Genet Lab, NIH, Rockville, MD 20850 USA.
[Conrad, Travis] Univ Maryland, Dept Hearing & Speech Sci, College Pk, MD 20742 USA.
[Jones, Sherri M.] Univ Nebraska, Lincoln, NE USA.
[Starost, Matthew F.] NIH, Off Res Serv, Div Vet Resources, Bethesda, MD USA.
RP Morell, RJ (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Human Genet, Mol Genet Lab, NIH, 5 Res Ct,2A-19, Rockville, MD 20850 USA.
EM morellr@nidcd.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-5955
J9 HEARING RES
JI Hear. Res.
PD AUG
PY 2013
VL 302
BP 83
EP 83
DI 10.1016/j.heares.2013.05.008
PG 1
WC Audiology & Speech-Language Pathology; Neurosciences;
Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Neurosciences & Neurology;
Otorhinolaryngology
GA 186OZ
UT WOS:000322055300009
ER
PT J
AU Policastro, PF
Raffel, SJ
Schwan, TG
AF Policastro, Paul F.
Raffel, Sandra J.
Schwan, Tom G.
TI Borrelia hermsii Acquisition Order in Superinfected Ticks Determines
Transmission Efficiency
SO INFECTION AND IMMUNITY
LA English
DT Article
ID ANAPLASMA-MARGINALE STRAINS; BORNE RELAPSING FEVER; ORNITHODOROS-HERMSI;
PARASITE VIRULENCE; B1B LYMPHOCYTES; PURINE SALVAGE; CULTIVATION;
PHYSIOLOGY; EVOLUTION; PROTEIN
AB Multilocus sequence typing of Borrelia hermsii isolates reveals its divergence into two major genomic groups (GG), but no differences in transmission efficiency or host pathogenicity are associated with these genotypes. To compare GGI and GGII in the tick-host infection cycle, we first determined if spirochetes from the two groups could superinfect the tick vector Ornithodoros hermsi. We infected mice with isolates from each group and fed ticks sequentially on these mice. We then fed the infected ticks on naive mice and measured GGI and GGII spirochete densities in vector and host, using quantitative PCR of genotype-specific chromosomal DNA sequences. Sequential feedings resulted in dual tick infections, showing that GGI or GGII primary acquisition did not block superinfection by a secondary agent. On transmission to naive mice at short intervals after acquisition, ticks with primary GGI and secondary GGII spirochete infections caused mixed GGI and GGII infections in mice. However, ticks with primary GGII and secondary GGI spirochete infections caused only GGII infections with all isolate pairs examined. At longer intervals after acquisition, the exclusion of GGI by GGII spirochetes declined and cotransmission predominated. We then examined GGI and GGII spirochetemia in mice following single inoculation and coinoculation by needle and found that GGI spirochete densities were reduced on multiple days when coinoculated with GGII. These findings indicate that dual GGI-GGII spirochete infections can persist in ticks and that transmission to a vertebrate host is dependent on the order of tick acquisition and the interval between acquisition and transmission events.
C1 [Policastro, Paul F.; Raffel, Sandra J.; Schwan, Tom G.] NIAID, Med Entomol Sect, Lab Zoonot Pathogens, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
RP Policastro, PF (reprint author), NIAID, Med Entomol Sect, Lab Zoonot Pathogens, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
EM ppolicastro@niaid.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, Bethesda, MD
FX This project was supported by the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Bethesda, MD.
NR 33
TC 6
Z9 6
U1 1
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD AUG
PY 2013
VL 81
IS 8
BP 2899
EP 2908
DI 10.1128/IAI.00542-13
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 180TY
UT WOS:000321622700026
PM 23716615
ER
PT J
AU Via, LE
Weiner, DM
Schimel, D
Lin, PL
Dayao, E
Tankersley, SL
Cai, Y
Coleman, MT
Tomko, J
Paripati, P
Orandle, M
Kastenmayer, RJ
Tartakovsky, M
Rosenthal, A
Portevin, D
Eum, SY
Lahouar, S
Gagneux, S
Young, DB
Flynn, JL
Barry, CE
AF Via, Laura E.
Weiner, Danielle M.
Schimel, Daniel
Lin, Philana Ling
Dayao, Emmanuel
Tankersley, Sarah L.
Cai, Ying
Coleman, M. Teresa
Tomko, Jaime
Paripati, Praveen
Orandle, Marlene
Kastenmayer, Robin J.
Tartakovsky, Michael
Rosenthal, Alexander
Portevin, Damien
Eum, Seok Yong
Lahouar, Saher
Gagneux, Sebastien
Young, Douglas B.
Flynn, JoAnne L.
Barry, Clifton E., III
TI Differential Virulence and Disease Progression following Mycobacterium
tuberculosis Complex Infection of the Common Marmoset (Callithrix
jacchus)
SO INFECTION AND IMMUNITY
LA English
DT Article
ID W-BEIJING STRAINS; RABBIT MODEL; GUINEA-PIGS; MOUSE MODEL; PULMONARY
TUBERCULOSIS; FRANCISELLA-TULARENSIS; CYNOMOLGUS MACAQUES;
IMMUNE-RESPONSE; LUNG PATHOLOGY; IN-VIVO
AB Existing small-animal models of tuberculosis (TB) rarely develop cavitary disease, limiting their value for assessing the biology and dynamics of this highly important feature of human disease. To develop a smaller primate model with pathology similar to that seen in humans, we experimentally infected the common marmoset (Callithrix jacchus) with diverse strains of Mycobacterium tuberculosis of various pathogenic potentials. These included recent isolates of the modern Beijing lineage, the Euro-American X lineage, and M. africanum. All three strains produced fulminant disease in this animal with a spectrum of progression rates and clinical sequelae that could be monitored in real time using 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT). Lesion pathology at sacrifice revealed the entire spectrum of lesions observed in human TB patients. The three strains produced different rates of progression to disease, various extents of extrapulmonary dissemination, and various degrees of cavitation. The majority of live births in this species are twins, and comparison of results from siblings with different infecting strains allowed us to establish that the infection was highly reproducible and that the differential virulence of strains was not simply host variation. Quantitative assessment of disease burden by FDG-PET/CT provided an accurate reflection of the pathology findings at necropsy. These results suggest that the marmoset offers an attractive small-animal model of human disease that recapitulates both the complex pathology and spectrum of disease observed in humans infected with various M. tuberculosis strain clades.
C1 [Via, Laura E.; Weiner, Danielle M.; Schimel, Daniel; Dayao, Emmanuel; Tankersley, Sarah L.; Cai, Ying; Barry, Clifton E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Lin, Philana Ling] UPMC, Childrens Hosp Pittsburgh, Pittsburgh, PA USA.
[Coleman, M. Teresa] Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA USA.
[Tomko, Jaime; Flynn, JoAnne L.] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA USA.
[Paripati, Praveen; Lahouar, Saher] NET ESolut Corp, Mclean, VA USA.
[Orandle, Marlene; Kastenmayer, Robin J.] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA.
[Tartakovsky, Michael; Rosenthal, Alexander] NIAID, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA.
[Portevin, Damien; Young, Douglas B.] MRC Natl Inst Med Res, London, England.
[Eum, Seok Yong] Int TB Res Ctr, Chang Won, South Korea.
[Gagneux, Sebastien] Swiss Trop & Publ Hlth Inst, Basel, Switzerland.
[Gagneux, Sebastien] Univ Basel, Basel, Switzerland.
RP Barry, CE (reprint author), NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM cbarry@niaid.nih.gov
RI Barry, III, Clifton/H-3839-2012;
OI Via, Laura/0000-0001-6074-9521
FU Intramural Research Program of the NIAID; TB Drug Accelerator Program of
the Bill and Melinda Gates Foundation; Career Development Fellowship
from the MRC-UK
FX Funding for this study was provided (in part) by the Intramural Research
Program of the NIAID (to C.E.B.) and (in part) by the TB Drug
Accelerator Program of the Bill and Melinda Gates Foundation (to
J.L.F.). D.P. held a Career Development Fellowship from the MRC-UK.
NR 63
TC 39
Z9 39
U1 0
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD AUG
PY 2013
VL 81
IS 8
BP 2909
EP 2919
PG 11
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 180TY
UT WOS:000321622700027
PM 23716617
ER
PT J
AU Dulebohn, DP
Bestor, A
Rosa, PA
AF Dulebohn, Daniel P.
Bestor, Aaron
Rosa, Patricia A.
TI Borrelia burgdorferi Linear Plasmid 28-3 Confers a Selective Advantage
in an Experimental Mouse-Tick Infection Model
SO INFECTION AND IMMUNITY
LA English
DT Article
ID LYME-DISEASE SPIROCHETE; ACQUIRING SURFACE-PROTEINS; GENE-EXPRESSION;
COMPETITIVE ADVANTAGE; CIRCULAR PLASMIDS; VIBRIO-CHOLERAE; MAMMALIAN
HOST; FACTOR-H; GENOME; AGENT
AB Borrelia burgdorferi, the bacterium that causes Lyme disease, has a unique segmented genome consisting of numerous linear and circular plasmids and a linear chromosome. Many of these genetic elements have been found to encode factors critical for B. burgdorferi to complete the infectious cycle. However, several plasmids remain poorly characterized, and their roles during infection with B. burgdorferi have not been elucidated. To more fully characterize the role of one of the four 28-kb linear plasmids, lp28-3, we generated strains specifically lacking lp28-3 and assayed the contribution of genes carried by lp28-3 to B. burgdorferi infection. We found that lp28-3 does not carry any genes that are strictly required for infection of a mouse or tick and that lp28-3-deficient spirochetes are competent at causing a disseminated infection. Interestingly, spirochetes containing lp28-3 were at a selective advantage compared to lp28-3-deficient spirochetes when coinjected into a mouse, and this advantage was reflected in the population of spirochetes acquired by feeding ticks. Our data demonstrate that genes carried by lp28-3, although not essential, contribute to the fitness of B. burgdorferi during infection.
C1 [Dulebohn, Daniel P.; Bestor, Aaron; Rosa, Patricia A.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, Div Intramural Res,NIH, Hamilton, MT 59840 USA.
RP Dulebohn, DP (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, Div Intramural Res,NIH, Hamilton, MT 59840 USA.
EM dulebohnd@niaid.nih.gov
FU Intramural Research Program of the NIH, NIAID
FX This research was supported by the Intramural Research Program of the
NIH, NIAID.
NR 56
TC 3
Z9 3
U1 1
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD AUG
PY 2013
VL 81
IS 8
BP 2986
EP 2996
DI 10.1128/IAI.00219-13
PG 11
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 180TY
UT WOS:000321622700034
PM 23753630
ER
PT J
AU Biesecker, BB
Peay, HL
AF Biesecker, Barbara Bowles
Peay, Holly Landrum
TI Genomic sequencing for psychiatric disorders: promise and challenge
SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE Ethics; psychiatric genetics; sequencing
ID BIPOLAR DISORDER; INCIDENTAL FINDINGS; ATTITUDES; RISK; SCHIZOPHRENIA;
PERCEPTIONS; INFORMATION; FAMILIES; DISEASE
AB Whole genome/exome sequencing (WGS/WES) integration into medicine will yield a new disease paradigm moving from clinical to molecular diagnosis. This paradigm will present significant challenges in the interpretation of sequence data and clinicians will face dilemmas about if, when and how to offer information to patients. Sequencing will ultimately reshape psychiatry in predicting disease risk and lead to greater understanding of aetiology, prognosis and/or treatment response. This commentary on the ethics of returning WGS/WES results describes the nature of the data as a dynamic health resource, the importance of understanding participant motivations, determinations of personal utility and potential effects of WGS/WES on self-concept and well-being. As this technology unfurls, ethical challenges will not be novel but they will be compounded by the volume and scope of the data. Research into participant/patient perceptions, preferences and outcomes will identify areas of caution and prepare psychiatrists for eventual integration into clinical care.
C1 [Biesecker, Barbara Bowles; Peay, Holly Landrum] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA.
RP Biesecker, BB (reprint author), NHGRI Bldg 31,Room B1B36 31,Ctr Dr MSC 2073, Bethesda, MD 20892 USA.
EM barbarab@mail.nih.gov
FU Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health
FX This research was funded by the Intramural Research Program of the
National Human Genome Research Institute, National Institutes of Health.
NR 23
TC 4
Z9 4
U1 1
U2 11
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1461-1457
J9 INT J NEUROPSYCHOPH
JI Int. J. Neuropsychopharmacol.
PD AUG
PY 2013
VL 16
IS 7
BP 1667
EP 1672
DI 10.1017/S146114571300014X
PG 6
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 179US
UT WOS:000321547500020
PM 23575420
ER
PT J
AU Cui, CY
Klar, J
Georgii-Heming, P
Frojmark, AS
Baig, SM
Schlessinger, D
Dahl, N
AF Cui, Chang-Yi
Klar, Joakim
Georgii-Heming, Patrik
Frojmark, Anne-Sophie
Baig, Shahid M.
Schlessinger, David
Dahl, Niklas
TI Frizzled6 Deficiency Disrupts the Differentiation Process of Nail
Development
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID ONYCHO-DERMAL DYSPLASIA; LAMELLAR ICHTHYOSIS; R-SPONDIN-4 RSPO4;
MISSENSE MUTATION; BETA-CATENIN; CELL-DEATH; HAIR; GENE; LIMB; SKIN
AB Nails protect the soft tissue of the tips of digits. The molecular mechanism of nail (and claw) development is largely unknown, but we have recently identified a Wnt receptor gene, Frizzled6 (Fzd6), that is mutated in a human autosomal-recessive nail dysplasia. To investigate the action of Fzd6 in claw development at the molecular level, we compared gene expression profiles of digit tips of wild-type and Fzd6(-/-) mice, and showed that Fzd6 regulates the transcription of a striking number of epidermal differentiation related genes. Sixty-three genes encoding keratins (Krts), keratin-associated proteins, and transglutaminases (Tgms) and their substrates were significantly downregulated in the knockout mice. Among them, four hard Krts, Krt86, Krt81, Krt34, and Krt31; two epithelial Krts, Krt6a and Krt6b; and Tgm 1 were already known to be involved in nail abnormalities when dysregulated. Immunohistochemical studies revealed decreased expression of Krt86, Krt6b, and involucrin in the epidermal portion of the claw field in the knockout embryos. We further showed that Dkk4, a Wnt antagonist, was significantly downregulated in Fzd6(-/-) mice along with Wnt, Bmp, and Hh family genes; and Dkk4 transgenic mice showed a subtly but appreciably modified claw phenotype. Thus, Fzd6-mediated Wnt signaling likely regulates the overall differentiation process of nail/claw formation.
C1 [Cui, Chang-Yi; Schlessinger, David] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Klar, Joakim; Georgii-Heming, Patrik; Frojmark, Anne-Sophie; Dahl, Niklas] Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, Rudbeck Lab, S-75185 Uppsala, Sweden.
[Baig, Shahid M.] NIBGE, Human Mol Genet Lab, Hlth Biotechnol Div, Faisalabad, Pakistan.
RP Dahl, N (reprint author), Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, Rudbeck Lab, S-75185 Uppsala, Sweden.
EM niklas.dahl@igp.uu.se
RI Baig, Shahid Mahmood /I-7309-2015
FU NIH, National Institute on Aging; Swedish Research Council
[K2010-66X-10829-17-3, 621-2009-4629]; Uppsala University; Science for
Life laboratory; Swedish Society for Medical Research
FX We thank Yulan Piao for help for expression profiling and Alexei Sharov
for statistical analysis. This work was supported in part by the
Intramural Research Program of the NIH, National Institute on Aging, the
Swedish Research Council (grant numbers K2010-66X-10829-17-3 and
621-2009-4629), Uppsala University, and Science for Life laboratory. JK
is supported by the Swedish Society for Medical Research.
NR 36
TC 12
Z9 13
U1 1
U2 15
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD AUG
PY 2013
VL 133
IS 8
BP 1990
EP 1997
DI 10.1038/jid.2013.84
PG 8
WC Dermatology
SC Dermatology
GA 185BD
UT WOS:000321939300014
PM 23439395
ER
PT J
AU Butman, JA
Nduom, E
Kim, HJ
Lonser, RR
AF Butman, John A.
Nduom, Edjah
Kim, H. Jeffrey
Lonser, Russell R.
TI Imaging detection of endolymphatic sac tumor-associated hydrops Clinical
article
SO JOURNAL OF NEUROSURGERY
LA English
DT Article
DE endolymphatic sac tumor; hydrops; imaging; von Hippel-Lindau disease;
oncology
ID HIPPEL-LINDAU-DISEASE; MORBID HEARING-LOSS; ORIGIN
AB Object. To determine if physiologically based MRI sequences can be used to detect endolymphatic sac tumor (ELST)-associated hydrops, the authors performed contrast-enhanced delayed FLAIR imaging in consecutive ELST patients with clinical findings consistent with hydrops.
Methods. Consecutive patients with von Hippel-Lindau (VHL) disease and clinical findings of endolymphatic hydrops and ELSTs underwent contrast-enhanced delayed FLAIR MRI. Clinical, audiological, operative, and imaging findings were analyzed.
Results. Three patients (2 male, 1 female) with 4 ELSTs (1 patient had bilateral ELSTs) were identified who had clinical findings consistent with endolymphatic hydrops. Computed tomography and MRI evidence of an ELST was found in all patients. Their mean age at initial evaluation was 39.7 years (range 28-51 years). All patients demonstrated progressive sensorineural hearing loss that was associated with episodic vertigo and tinnitus. Contrast-enhanced delayed FLAIR MRI clearly demonstrated dilation of the membranous labyrinth consistent with hydrops in the affected ears but not the unaffected ears. Two patients underwent resection of the associated ELST that resulted in stabilization of progressive hearing loss, as well as amelioration of tinnitus and vertigo.
Conclusions. Contrast-enhanced delayed FLAIR MRI can be used to detect ELST-associated hydrops. Noninvasive MRI detection of hydrops can permit earlier detection of ELSTs in patients with VIM disease and provides direct insight into a mechanism that underlies ELST-associated audiovestibular morbidity.
C1 [Butman, John A.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA.
[Nduom, Edjah] NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA.
[Kim, H. Jeffrey] Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, Bethesda, MD USA.
[Nduom, Edjah] Emory Univ, Dept Neurol Surg, Atlanta, GA 30322 USA.
[Kim, H. Jeffrey] Georgetown Univ, Med Ctr, Dept Otolaryngol Head & Neck Surg, Washington, DC 20007 USA.
[Lonser, Russell R.] Ohio State Univ, Dept Neurol Surg, Columbus, OH 43210 USA.
RP Lonser, RR (reprint author), Ohio State Univ, Dept Neurol Surg, N1019 Doan Hall,410 West 10th Ave, Columbus, OH 43210 USA.
EM russell.lonser@osumc.edu
RI Butman, John/J-2780-2013
OI Butman, John/0000-0002-1547-9195
FU National Institutes of Health Clinical Center; National Institute of
Neurological Disorders and Stroke of the National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institutes of Health Clinical Center and the National Institute
of Neurological Disorders and Stroke of the National Institutes of
Health.
NR 14
TC 2
Z9 2
U1 0
U2 4
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
J9 J NEUROSURG
JI J. Neurosurg.
PD AUG
PY 2013
VL 119
IS 2
BP 406
EP 411
DI 10.3171/2013.2.JNS12608
PG 6
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 187CL
UT WOS:000322094400021
PM 23472846
ER
PT J
AU Nduom, EK
Yang, CZ
Merrill, MJ
Zhuang, ZP
Lonser, RR
AF Nduom, Edjah K.
Yang, Chunzhang
Merrill, Marsha J.
Zhuang, Zhengping
Lonser, Russell R.
TI Characterization of the blood-brain barrier of metastatic and primary
malignant neoplasms Laboratory investigation
SO JOURNAL OF NEUROSURGERY
LA English
DT Article
DE blood-brain barrier; brain metastasis; brain tumor; contrast
enhancement; glioma; oncology
ID CENTRAL-NERVOUS-SYSTEM; HUMAN GLIOBLASTOMA-MULTIFORME; FOCAL ASTROCYTE
LOSS; VASCULAR-PERMEABILITY; ENDOTHELIAL-CELLS; TIGHT JUNCTIONS; TUMORS;
PROTEINS; DEXAMETHASONE; EXPRESSION
AB Object. The astrocytic contribution to the blood-brain barrier (BBB) in metastatic and primary malignant brain tumors is not well understood. To better understand the vascular properties associated with metastatic and primary malignant brain tumors, the authors systematically analyzed the astrocytic component of the BBB in brain neoplasms.
Methods. Twelve patients who underwent resection of metastatic or primary brain neoplasms (4 metastatic lesions, 2 low-grade astrocytomas, 2 anaplastic astrocytomas, and 4 glioblastoma multiforme) were included. Clinical, MRI, operative, histopathological and immunohistochemical (glial fibrillary acidic protein [GFAP], CD31, and aquaporin 4 [AQ4]) findings were analyzed.
Results. Intratumoral regions of MRI enhancement corresponded with breakdown of the normal astrocyte-endothelial cell relationship in the BBB in metastatic deposits and malignant gliomas. Metastases demonstrated lack of perivascular GFAP and AQ4 on CD31-positive intratumoral vessels. At the metastasis-brain interface, normalization of GFAP and AQ4 staining associated with intraparenchymal vessels was observed. Intratumoral vasculature in enhancing regions of high-grade gliomas revealed gaps in GFAP and AQ4 staining consistent with disintegration of the normal astrocyte-endothelial cell association in the BBB. Intratumoral vasculature in low-grade and nonenhancing regions of high-grade gliomas maintained the normal astrocyte-endothelial cell relationship seen in an intact BBB, with GFAP- and AQ4-positive glial processes that were uniformly associated with the CD31-positive vasculature.
Conclusions. Regions of MRI enhancement in metastatic and primary malignancies correspond to areas of breakdown of the physiological astrocyte-endothelial cell relationship of the BBB, including loss of normal peri-vascular astrocytic architecture on GFAP and AQ4 immunohistochemistry. Nonenhancing areas are associated with preservation of the normal astrocyte-endothelial cell relationship of the intact BBB.
C1 [Nduom, Edjah K.; Yang, Chunzhang; Merrill, Marsha J.; Zhuang, Zhengping; Lonser, Russell R.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Nduom, Edjah K.] Emory Univ, Dept Neurol Surg, Atlanta, GA 30322 USA.
[Lonser, Russell R.] Ohio State Univ, Dept Neurol Surg, Columbus, OH 43210 USA.
RP Lonser, RR (reprint author), Ohio State Univ, Dept Neurol Surg, Wexner Med Ctr, 410 West 10th Ave,N1047 Doan Hall, Columbus, OH 43210 USA.
EM russell.lonser@osumc.edu
FU National Institute of Neurological Disorders and Stroke at the National
Institutes of Health
FX This work was supported by the intramural program of the National
Institute of Neurological Disorders and Stroke at the National
Institutes of Health.
NR 37
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Z9 21
U1 1
U2 13
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
J9 J NEUROSURG
JI J. Neurosurg.
PD AUG
PY 2013
VL 119
IS 2
BP 427
EP 433
DI 10.3171/2013.3.JNS122226
PG 7
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 187CL
UT WOS:000322094400024
PM 23621605
ER
PT J
AU Akhtar, A
Kama, AK
AF Akhtar, Anjum
Kama, Ayeesha Kamran
TI SCAST: Angiotensin receptor blocker in acute stroke, Shall we control
blood pressure after an acute stroke?
SO JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Kama, Ayeesha Kamran] Aga Khan Univ Hosp, Stroke Serv & Vasc Fellowship Program, Int Cerebrovasc Translat Clin Res Training Pr, Fogarty Int Ctr, Karachi, Pakistan.
Aga Khan Univ Hosp, Natl Inst Neurol Disorders & Stroke, Karachi, Pakistan.
RP Kama, AK (reprint author), Aga Khan Univ Hosp, Stroke Serv & Vasc Fellowship Program, Int Cerebrovasc Translat Clin Res Training Pr, Fogarty Int Ctr, Karachi, Pakistan.
EM ayeesha.kamal@aku.edu
NR 1
TC 0
Z9 0
U1 0
U2 0
PU PAKISTAN MEDICAL ASSOC
PI KARACHI
PA PMA HOUSE, AGA KHAN III RD, KARACHI, 00000, PAKISTAN
SN 0030-9982
J9 J PAK MED ASSOC
JI J. Pak. Med. Assoc.
PD AUG
PY 2013
VL 63
IS 8
BP 1069
EP 1069
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 184HT
UT WOS:000321881400030
ER
PT J
AU Morton, LM
AF Morton, Lindsay M.
TI Dissecting lymphoma incidence to inform epidemiologic and clinical
research
SO LEUKEMIA & LYMPHOMA
LA English
DT Editorial Material
ID NON-HODGKINS-LYMPHOMA; UNITED-STATES; CLASSIFICATION; TIME
C1 [Morton, Lindsay M.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
RP Morton, LM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS 7040,MSC 7238, Rockville, MD 20852 USA.
EM mortonli@mail.nih.gov
RI Morton, Lindsay/B-5234-2015
OI Morton, Lindsay/0000-0001-9767-2310
NR 15
TC 2
Z9 2
U1 0
U2 0
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1042-8194
J9 LEUKEMIA LYMPHOMA
JI Leuk. Lymphoma
PD AUG
PY 2013
VL 54
IS 8
BP 1575
EP 1576
DI 10.3109/10428194.2013.774000
PG 2
WC Oncology; Hematology
SC Oncology; Hematology
GA 182SG
UT WOS:000321763800002
PM 23391143
ER
PT J
AU Kim, CJ
Freedman, DM
Curtis, RE
de Gonzalez, AB
Morton, LM
AF Kim, Clara J.
Freedman, D. Michal
Curtis, Rochelle E.
de Gonzalez, Amy Berrington
Morton, Lindsay M.
TI Risk of non-Hodgkin lymphoma after radiotherapy for solid cancers
SO LEUKEMIA & LYMPHOMA
LA English
DT Article
DE Second malignancies; radiotherapy; non-Hodgkin lymphoma
ID ATOMIC-BOMB SURVIVORS; IONIZING-RADIATION; MULTIPLE-MYELOMA;
CERVICAL-CANCER; 2ND CANCERS; X-RAYS; MORTALITY; LEUKEMIA; WORKERS;
EPIDEMIOLOGY
AB Ionizing radiation increases risk for acute leukemia, but less is known about radiation and risk of other hematologic malignancies such as non-Hodgkin lymphoma (NHL). We compared second primary NHL incidence among patients who did and did not receive initial radiotherapy for first primary solid malignancy during 1981-2007 reported in nine Surveillance, Epidemiology, and End Results (SEER) Program population-based cancer registries. We identified 5590 second NHL cases among 1 450 962 1-year cancer survivors. NHL risk was increased after initial radiotherapy for all solid cancers combined (multivariate Poisson regression relative risk [RR]: 1.13, 95% confidence interval [CI]: 1.06-1.20), non-small cell lung cancer (RR: 1.53, 95% CI: 1.08-2.17) and prostate cancer (RR: 1.19, 95% CI: 1.09-1.32). NHL risk increased with longer latency after radiotherapy for non-small cell lung cancer (p(trend) = 0.003) but decreased for prostate cancer (p(trend) = 0.017). There was no clear NHL risk pattern by NHL subtype or age. Our study provides limited evidence that radiotherapy for solid malignancy is associated with increased risk of subsequent NHL.
C1 [Kim, Clara J.; Freedman, D. Michal; Curtis, Rochelle E.; de Gonzalez, Amy Berrington; Morton, Lindsay M.] NCI, Radiat Epidemiol Branch, Rockville, MD 20852 USA.
RP Kim, CJ (reprint author), NCI, Radiat Epidemiol Branch, 6120 Execut Blvd,EPS 7051, Rockville, MD 20852 USA.
EM kimcj2@mail.nih.gov
RI Morton, Lindsay/B-5234-2015
OI Morton, Lindsay/0000-0001-9767-2310
FU Intramural NIH HHS [ZIA CP010170-12]
NR 46
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Z9 1
U1 0
U2 1
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1042-8194
J9 LEUKEMIA LYMPHOMA
JI Leuk. Lymphoma
PD AUG
PY 2013
VL 54
IS 8
BP 1691
EP 1697
DI 10.3109/10428194.2012.753543
PG 7
WC Oncology; Hematology
SC Oncology; Hematology
GA 182SG
UT WOS:000321763800020
PM 23193978
ER
PT J
AU Myles, IA
Fontecilla, NM
Valdez, PA
Vithayathil, PJ
Naik, S
Belkaid, Y
Ouyang, WJ
Datta, SK
AF Myles, Ian A.
Fontecilla, Natalia M.
Valdez, Patricia A.
Vithayathil, Paul J.
Naik, Shruti
Belkaid, Yasmine
Ouyang, Wenjun
Datta, Sandip K.
TI Signaling via the IL-20 receptor inhibits cutaneous production of IL-1
beta and IL-17A to promote infection with methicillin-resistant
Staphylococcus aureus
SO NATURE IMMUNOLOGY
LA English
DT Article
ID T-CELLS; RHEUMATOID-ARTHRITIS; IMMUNE-RESPONSES; HOST-DEFENSE; KAPPA-B;
GENE-EXPRESSION; INNATE; CYTOKINES; INFLAMMATION; PSORIASIS
AB Staphylococcus aureus causes most infections of human skin and soft tissue and is a major infectious cause of mortality. Host defense mechanisms against S. aureus are incompletely understood. Interleukin 19 (IL-19), IL-20 and IL-24 signal through type I and type II IL-20 receptors and are associated with inflammatory skin diseases such as psoriasis and atopic dermatitis. We found here that those cytokines promoted cutaneous infection with S. aureus in mice by downregulating IL-1 beta- and IL-17A-dependent pathways. We noted similar effects of those cytokines in human keratinocytes after exposure to S. aureus, and antibody blockade of the IL-20 receptor improved outcomes in infected mice. Our findings identify an immunosuppressive role for IL-19, IL-20 and IL-24 during infection that could be therapeutically targeted to alter susceptibility to infection.
C1 [Myles, Ian A.; Fontecilla, Natalia M.; Valdez, Patricia A.; Vithayathil, Paul J.; Datta, Sandip K.] NIAID, Bacterial Pathogenesis Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Naik, Shruti; Belkaid, Yasmine] NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Ouyang, Wenjun] Genentech Inc, Dept Immunol, San Francisco, CA 94080 USA.
RP Datta, SK (reprint author), NIAID, Bacterial Pathogenesis Unit, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM dattas@niaid.nih.gov
OI Ouyang, Wenjun/0000-0002-1811-5864
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases (US National Institutes of Health)
FX We thank Y. Iwakura (University of Tokyo) for Il17a-/- mice;
J. O'Shea (National Institute of Arthritis, Musculoskeletal and Skin
Diseases) for Stat3WT/Delta V463 mice; F. DeLeo (Rocky
Mountain Labs, National Institute of Allergy and Infectious Diseases)
for the clinical isolate of MRSA USA300 (LAC strain); A. Costanzo and J.
Jameson (The Scripps Research Institute) for PAM 2-12 cells; A. Coxon
(National Cancer Institute) for foreskin samples; and F. DeLeo and J.
O'Shea for critical reading of the manuscript. Supported by the
Intramural Research Program of the National Institute of Allergy and
Infectious Diseases (US National Institutes of Health).
NR 50
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Z9 36
U1 0
U2 12
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD AUG
PY 2013
VL 14
IS 8
BP 804
EP +
DI 10.1038/ni.2637
PG 10
WC Immunology
SC Immunology
GA 185ZN
UT WOS:000322010600009
PM 23793061
ER
PT J
AU Brubaker, L
Rickey, L
Dyer, K
Markland, A
Sirls, L
Norton, P
Casiano, E
Paraiso, MF
Ghetti, C
Rahn, D
Litman, H
Kusek, J
AF Brubaker, L.
Rickey, L.
Dyer, K.
Markland, A.
Sirls, L.
Norton, P.
Casiano, E.
Paraiso, Fidela M.
Ghetti, C.
Rahn, D.
Litman, H.
Kusek, J.
TI SELF-REPORTED PATIENT PREPAREDNESS IS ASSOCIATED WITH SUI SURGERY
SATISFACTION
SO NEUROUROLOGY AND URODYNAMICS
LA English
DT Meeting Abstract
CT 43rd Annual Meeting of the International-Continence-Society (ICS)
CY AUG 26-30, 2013
CL Barcelona, SPAIN
SP Int Continence Soc (ICS)
C1 [Brubaker, L.] Loyola Univ, Med Ctr, Dept OB Gyne Female Pelv Med & Reconstruct Surg, New Orleans, LA 70118 USA.
[Rickey, L.] Univ Maryland, College Pk, MD 20742 USA.
[Dyer, K.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Markland, A.] Univ Alabama Birmingham, Birmingham, AL USA.
[Sirls, L.] Beaumont Hosp, Beaumont, TX USA.
[Norton, P.] Univ Utah, Salt Lake City, UT 84112 USA.
[Casiano, E.] Univ Texas San Antonio, San Antonio, TX 78249 USA.
[Paraiso, Fidela M.] Cleveland Clin, Cleveland, OH 44195 USA.
[Ghetti, C.] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Kusek, J.] NIDDK, 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 0733-2467
J9 NEUROUROL URODYNAM
JI Neurourol. Urodyn.
PD AUG
PY 2013
VL 32
IS 6
MA 181
BP 773
EP 774
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 178HP
UT WOS:000321437700182
ER
PT J
AU Jelovsek, JE
AF Jelovsek, J. E.
TI A MODEL FOR PREDICTING THE RISK OF DE NOVO STRESS URINARY INCONTINENCE
IN WOMEN UNDERGOING PELVIC ORGAN PROLAPSE SURGERY
SO NEUROUROLOGY AND URODYNAMICS
LA English
DT Meeting Abstract
CT 43rd Annual Meeting of the International-Continence-Society (ICS)
CY AUG 26-30, 2013
CL Barcelona, SPAIN
SP Int Continence Soc (ICS)
C1 [Jelovsek, J. E.] Cleveland Clin, NICHD Pelv Floor Disorders Network, Cleveland, OH 44106 USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0733-2467
J9 NEUROUROL URODYNAM
JI Neurourol. Urodyn.
PD AUG
PY 2013
VL 32
IS 6
MA 206
BP 808
EP 809
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 178HP
UT WOS:000321437700207
ER
PT J
AU Laslo, M
Sun, XP
Hsiao, CT
Wu, WW
Shen, RF
Zou, SG
AF Laslo, Mara
Sun, Xiaoping
Hsiao, Cheng-Te
Wu, Wells W.
Shen, Rong-Fong
Zou, Sige
TI A botanical containing freeze dried acai pulp promotes healthy aging and
reduces oxidative damage in sod1 knockdown flies
SO AGE
LA English
DT Article
DE Aging intervention; Acai; Superoxide dismutase 1; Lifespan; Oxidative
stress; Reproductive aging; Drosophila melanogaster
ID EXTENDS LIFE-SPAN; AMYOTROPHIC-LATERAL-SCLEROSIS; ZINC
SUPEROXIDE-DISMUTASE; AMAZONIAN PALM BERRY; OLERACEAE MART. ACAI;
DROSOPHILA-MELANOGASTER; ALZHEIMERS-DISEASE; MASS-SPECTROMETRY; IMPROVES
HEALTH; LABEL-FREE
AB Superoxide dismutase 1 (SOD1), a critical enzyme against oxidative stress, is implicated in aging and degenerative diseases. We previously showed that a nutraceutical containing freeze-dried a double dagger ai pulp promotes survival of flies fed a high-fat diet or sod1 knockdown flies fed a standard diet. Here, we investigated the effect of a double dagger ai supplementation initiated at the early or late young adulthood on lifespan, physiological function, and oxidative damage in sod1 knockdown flies. We found that A double dagger ai supplementation extended lifespan even when started at the age of 10 days, which is the time shortly before the mortality rate of flies accelerated. Life-long a double dagger ai supplementation increased lifetime reproductive output in sod1 knockdown flies. Our molecular studies indicate that a double dagger ai supplementation reduced the protein levels of genes involved in oxidative stress response, cellular growth, and nutrient metabolism. A double dagger ai supplementation also affected the protein levels of ribosomal proteins. In addition, a double dagger ai supplementation decreased the transcript levels of genes involved in oxidative stress response and gluconeogenesis, while increasing the transcript levels of mitochondrial biogenesis genes. Moreover, a double dagger ai supplementation reduced the level of 4-hydroxynonenal-protein adducts, a lipid peroxidation marker. Our findings suggest that a double dagger ai supplementation promotes healthy aging in sod1-deficient flies partly through reducing oxidative damage, and modulating nutrient metabolism and oxidative stress response pathways. Our findings provide a foundation to further evaluate the viability of using a double dagger ai as an effective dietary intervention to promote healthy aging and alleviate symptoms of diseases with a high level of oxidative stress.
C1 [Laslo, Mara; Sun, Xiaoping; Hsiao, Cheng-Te; Zou, Sige] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA.
[Wu, Wells W.] NIA, Lab Clin Invest, Baltimore, MD 21224 USA.
[Shen, Rong-Fong] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
RP Zou, SG (reprint author), NIA, Lab Expt Gerontol, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM zous@grc.nia.nih.gov
FU National Institute on Aging, NIH; NIH Office of Dietary Supplements
FX We thank Alex Schauss to provide us the acai pulp extract and thank Ed
Spangler, Alex Schauss, Don Ingram, Jim Carey, and Pablo Liedo for
critical reading of the manuscript. This work was supported by funding
from the Intramural Research Program of the National Institute on Aging,
NIH to S.Z. and a research grant from the NIH Office of Dietary
Supplements to X.P. and S.Z.
NR 64
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Z9 3
U1 2
U2 19
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0161-9152
J9 AGE
JI Age
PD AUG
PY 2013
VL 35
IS 4
BP 1117
EP 1132
DI 10.1007/s11357-012-9437-3
PG 16
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 179UQ
UT WOS:000321547300008
PM 22639178
ER
PT J
AU Broer, L
Demerath, EW
Garcia, ME
Homuth, G
Kaplan, RC
Lunetta, KL
Tanaka, T
Tranah, GJ
Walter, S
Arnold, AM
Atzmon, G
Harris, TB
Hoffmann, W
Karasik, D
Kiel, DP
Kocher, T
Launer, LJ
Lohman, KK
Rotter, JI
Tiemeier, H
Uitterlinden, AG
Wallaschofski, H
Bandinelli, S
Dorr, M
Ferrucci, L
Franceschini, N
Gudnason, V
Hofman, A
Liu, Y
Murabito, JM
Newman, AB
Oostra, BA
Psaty, BM
Smith, AV
van Duijn, CM
AF Broer, L.
Demerath, E. W.
Garcia, M. E.
Homuth, G.
Kaplan, R. C.
Lunetta, K. L.
Tanaka, T.
Tranah, G. J.
Walter, S.
Arnold, A. M.
Atzmon, G.
Harris, T. B.
Hoffmann, W.
Karasik, D.
Kiel, D. P.
Kocher, T.
Launer, L. J.
Lohman, K. K.
Rotter, J. I.
Tiemeier, H.
Uitterlinden, A. G.
Wallaschofski, H.
Bandinelli, S.
Doerr, M.
Ferrucci, L.
Franceschini, N.
Gudnason, V.
Hofman, A.
Liu, Y.
Murabito, J. M.
Newman, A. B.
Oostra, B. A.
Psaty, B. M.
Smith, A. V.
van Duijn, C. M.
TI Association of heat shock proteins with all-cause mortality
SO AGE
LA English
DT Article
DE Heat shock proteins; HEAT shock factor 2; All-cause mortality
ID LIFE-SPAN EXTENSION; CAENORHABDITIS-ELEGANS; DROSOPHILA-MELANOGASTER;
EXTENDED LONGEVITY; STRESS-RESPONSE; THERMAL-STRESS; GENE; HORMESIS;
HEAT-SHOCK-PROTEIN-70; RESISTANCE
AB Experimental mild heat shock is widely known as an intervention that results in extended longevity in various models along the evolutionary lineage. Heat shock proteins (HSPs) are highly upregulated immediately after a heat shock. The elevation in HSP levels was shown to inhibit stress-mediated cell death, and recent experiments indicate a highly versatile role for these proteins as inhibitors of programmed cell death. In this study, we examined common genetic variations in 31 genes encoding all members of the HSP70, small HSP, and heat shock factor (HSF) families for their association with all-cause mortality. Our discovery cohort was the Rotterdam study (RS1) containing 5,974 participants aged 55 years and older (3,174 deaths). We assessed 4,430 single nucleotide polymorphisms (SNPs) using the HumanHap550K Genotyping BeadChip from Illumina. After adjusting for multiple testing by permutation analysis, three SNPs showed evidence for association with all-cause mortality in RS1. These findings were followed in eight independent population-based cohorts, leading to a total of 25,007 participants (8,444 deaths). In the replication phase, only HSF2 (rs1416733) remained significantly associated with all-cause mortality. Rs1416733 is a known cis-eQTL for HSF2. Our findings suggest a role of HSF2 in all-cause mortality.
C1 [Broer, L.; Tiemeier, H.; Uitterlinden, A. G.; Hofman, A.; van Duijn, C. M.] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
[Broer, L.; Tiemeier, H.; van Duijn, C. M.] Netherlands Consortium Hlth Aging, Rotterdam, Netherlands.
[Demerath, E. W.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Garcia, M. E.; Harris, T. B.; Launer, L. J.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
[Homuth, G.] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
[Kaplan, R. C.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Lunetta, K. L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Lunetta, K. L.; Karasik, D.; Kiel, D. P.; Murabito, J. M.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Tanaka, T.; Ferrucci, L.] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Tranah, G. J.] Calif Pacific Med Ctr, San Francisco, CA USA.
[Walter, S.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA.
[Arnold, A. M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Atzmon, G.] Albert Einstein Coll Med, Inst Aging Res, Bronx, NY 10467 USA.
[Atzmon, G.] Albert Einstein Coll Med, Diabet Res Ctr, Bronx, NY 10467 USA.
[Atzmon, G.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA.
[Atzmon, G.] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10467 USA.
[Hoffmann, W.] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany.
[Karasik, D.; Kiel, D. P.] Hebrew Senior Life Inst Aging Res, Boston, MA USA.
[Karasik, D.; Kiel, D. P.] Harvard Univ, Sch Med, Boston, MA USA.
[Kocher, T.] Ernst Moritz Arndt Univ Greifswald, Sch Dent, Greifswald, Germany.
[Lohman, K. K.] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA.
[Rotter, J. I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Tiemeier, H.] Erasmus MC, Dept Psychiat, Rotterdam, Netherlands.
[Uitterlinden, A. G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Wallaschofski, H.] Ernst Moritz Arndt Univ Greifswald, Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany.
[Bandinelli, S.] ASF, Geriatr Unit, Florence, Italy.
[Doerr, M.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Franceschini, N.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Gudnason, V.; Smith, A. V.] Iceland Heart Assoc, Kopavogur, Iceland.
[Gudnason, V.; Smith, A. V.] Univ Iceland, Reykjavik, Iceland.
[Liu, Y.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
[Murabito, J. M.] Boston Univ, Sch Med, Gen Internal Med Sect, Dept Med, Boston, MA 02118 USA.
[Newman, A. B.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
[Oostra, B. A.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands.
[Psaty, B. M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Psaty, B. M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Psaty, B. M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Psaty, B. M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Unit, Seattle, WA USA.
RP van Duijn, CM (reprint author), Erasmus MC, Dept Epidemiol, Dr Molewaterpl 50,POB 2040, NL-3000 CA Rotterdam, Netherlands.
EM c.vanduijn@erasmusmc.nl
RI Gudnason, Vilmundur/K-6885-2015; Newman, Anne/C-6408-2013; Smith,
Albert/K-5150-2015;
OI Tiemeier, Henning/0000-0002-4395-1397; Kiel,
Douglas/0000-0001-8474-0310; Gudnason, Vilmundur/0000-0001-5696-0084;
Newman, Anne/0000-0002-0106-1150; Smith, Albert/0000-0003-1942-5845;
Murabito, Joanne/0000-0002-0192-7516; Lunetta,
Kathryn/0000-0002-9268-810X; Karasik, David/0000-0002-8826-0530
FU Netherlands Genomics Initiative/Netherlands Consortium for Healthy Aging
[050-060-810]; Netherlands Organisation for Scientific Research (NWO)
[904-61-090, 904-61-193, 480-04-004, 400-05-717, SPI 56-464-1419,
175.010.2005.011, 911-03-012]; Netspar-Living longer for a good health;
National Heart, Lung, and Blood Institute [N01-HC-85079, N01-HC-85080,
N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085,
N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150,
N01-HC-45133, U01 HL080295, R01 HL087652]; National Institute of Aging
[R01 AG031890, R01AG029451]; National Center for Research Resources
[M01-RR00425]; National Institute of Diabetes and Digestive and Kidney
Diseases [DK063491]; National Heart, Lung and Blood Institute
[N01-HC-25195, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019,
N01-HC-55020, N01-HC-55021, N01-HC-55022]; Affymetrix, Inc
[N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of
Medicine at Boston University School of Medicine; Boston Medical Center;
NIH [N01-AG-12100]; Hjartavernd (the Icelandic Heart Association);
Althingi (the Icelandic Parliament); Italian Ministry of Health
[ICS110.1/RF97.71]; U.S. National Institute on Aging [263 MD 9164, 263
MD 821336]; NIH, National Institute on Aging; MedStar Research
Institute; NIA [N01AG62101, N01AG62103, N01AG62106, 1R03AG032498-01,
1R01AG032098-01A1]; National Institutes of Health [HHSN268200782096C];
Federal Ministry of Education and Research [01ZZ9603, 01ZZ0103,
01ZZ0403, 03ZIK012]; Ministry of Cultural Affairs; Social Ministry of
the Federal State of Mecklenburg-West Pomerania; Siemens Healthcare,
Erlangen, Germany; Federal State of Mecklenburg-West Pomerania;
[AG033193]; [AG081220]; [NS17950]; [P30AG013846]; [1R01AG028321];
[AR/AG 41398]
FX Rotterdam study: The Rotterdam Study is supported by Netherlands
Genomics Initiative/Netherlands Consortium for Healthy Aging
(050-060-810); Netherlands Organisation for Scientific Research (NWO)
(904-61-090, 904-61-193, 480-04-004, 400-05-717, SPI 56-464-1419,
175.010.2005.011 and 911-03-012); Netspar-Living longer for a good
health.; Cardiovascular health study: The CHS research reported in this
article was supported by contract numbers N01-HC-85079 through
N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150,
N01-HC-45133, grant numbers U01 HL080295, and R01 HL087652 from the
National Heart, Lung, and Blood Institute, the National Institute of
Aging R01 AG031890 with additional contribution from the National
Institute of Neurological Disorders and Stroke. A full list of principal
CHS investigators and institutions can be found at
http://www.chs-nhlbi.org/pi.htm. DNA handling and genotyping was
supported in part by National Center for Research Resources grant
M01-RR00425 to the Cedars-Sinai General Clinical Research Center
Genotyping core and National Institute of Diabetes and Digestive and
Kidney Diseases grant DK063491 to the Southern California Diabetes
Endocrinology Research Center.; Framingham heart study: The Framingham
study phenotype-genotype analyses were supported by the National
Institute of Aging grant number R01AG029451 (PI: JMM). The Framingham
Heart Study of the National Heart Lung and Blood Institute of the
National Institutes of Health and Boston University School of Medicine
were supported by the National Heart, Lung and Blood Institute's
Framingham Heart Study Contract No. N01-HC-25195 and its contract with
Affymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278).
Analyses reflect intellectual input and resource development from the
Framingham Heart Study investigators participating in the SNP Health
Association Resource (SHARe) project. A portion of this research was
conducted using the Linux Cluster for Genetic Analysis (LinGA-II) funded
by the Robert Dawson Evans Endowment of the Department of Medicine at
Boston University School of Medicine and Boston Medical Center. This
research was additionally supported by the following grants: AG033193,
AG081220, NS17950, P30AG013846, 1R01AG028321, and AR/AG 41398.;
Atherosclerosis risk in communities study: The Atherosclerosis Risk in
Communities Study is carried out as a collaborative study supported by
National Heart, Lung, and Blood Institute contracts N01-HC-55015,
N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021,
and N01-HC-55022. The authors thank the staff and participants of the
ARIC study for their important contributions.; Age, gene/environment
susceptibility-Reykjavik study: The Age, Gene/Environment
Susceptibility-Reykjavik Study is funded by NIH contract N01-AG-12100,
the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart
Association), and the Althingi (the Icelandic Parliament). Genotyping
was conducted at the NIA IRP Laboratory of Neurogenetics.; Invecchiare
nel Chianti: The InCHIANTI study baseline (1998-2000) was supported as a
"targeted project" (ICS110.1/RF97.71) by the Italian Ministry of Health
and in part by the U.S. National Institute on Aging (Contracts: 263 MD
9164 and 263 MD 821336).; Baltimore longitudinal study of ageing: The
BLSA was supported in part by the Intramural Research Program of the
NIH, National Institute on Aging. A portion of that support was through
a R&D contract with MedStar Research Institute.; Health, aging and body
composition: This research is supported in part by the Intramural
Research Program of the NIH, National Institute on Aging. This research
was supported by NIA contracts N01AG62101, N01AG62103, N01AG62106, and
NIA grant 1R03AG032498-01. The genome-wide association study was funded
by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences
and genotyping services were provided by the Center for Inherited
Disease Research (CIDR). CIDR is fully funded through a federal contract
from the National Institutes of Health to The Johns Hopkins University,
contract number HHSN268200782096C.; Study of health in Pomerania: SHIP
is part of the Community Medicine Research net of the University of
Greifswald, Germany, which is funded by the Federal Ministry of
Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403),
the Ministry of Cultural Affairs as well as the Social Ministry of the
Federal State of Mecklenburg-West Pomerania. Genome-wide data have been
supported by the Federal Ministry of Education and Research (grant no.
03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany
and the Federal State of Mecklenburg-West Pomerania. The University of
Greifswald is a member of the "Center of Knowledge Interchange" program
of the Siemens AG.
NR 37
TC 1
Z9 2
U1 3
U2 16
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0161-9152
J9 AGE
JI Age
PD AUG
PY 2013
VL 35
IS 4
BP 1367
EP 1376
DI 10.1007/s11357-012-9417-7
PG 10
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 179UQ
UT WOS:000321547300027
PM 22555621
ER
PT J
AU von Bonsdorff, MB
Muller, M
Aspelund, T
Garcia, M
Eiriksdottir, G
Rantanen, T
Gunnarsdottir, I
Birgisdottir, BE
Thorsdottir, I
Sigurdsson, G
Gudnason, V
Launer, L
Harris, TB
AF von Bonsdorff, Mikaela B.
Muller, Majon
Aspelund, Thor
Garcia, Melissa
Eiriksdottir, Gudny
Rantanen, Taina
Gunnarsdottir, Ingibjorg
Birgisdottir, Bryndis Eva
Thorsdottir, Inga
Sigurdsson, Gunnar
Gudnason, Vilmundur
Launer, Lenore
Harris, Tamara B.
CA Age Gene Environm Susceptibility-R
TI Persistence of the effect of birth size on dysglycaemia and type 2
diabetes in old age: AGES-Reykjavik Study
SO AGE
LA English
DT Article
DE Aging; Birth size; Type 2 diabetes; Dysglycaemia; Birth weight;
AGES-Reykjavik Study
ID IMPAIRED GLUCOSE-TOLERANCE; FASTING PLASMA-GLUCOSE; BETA-CELL FUNCTION;
INSULIN CONCENTRATIONS; CHILDHOOD GROWTH; RISK-FACTORS; FOLLOW-UP;
WEIGHT; FETAL; POPULATION
AB We studied the effect of birth size on glucose and insulin metabolism among old non-diabetic individuals. We also explored the combined effect of birth size and midlife body mass index (BMI) on type 2 diabetes in old age. Our study comprised 1,682 Icelanders whose birth records included anthropometrical data. The same individuals had participated in the prospective population-based Reykjavik Study, where BMI was assessed at a mean age of 47 years, and in the AGES-Reykjavik Study during 2002 to 2006, where fasting glucose, insulin and HbA(1c) were measured and homeostasis model assessment for the degree of insulin resistance (HOMA-IR) calculated at a mean age of 75.5 years. Type 2 diabetes was determined as having a history of diabetes, using glucose-modifying medication or fasting glucose of > 7.0 mmol/l. Of the participants, 249 had prevalent type 2 diabetes in old age. Lower birth weight and body length were associated with higher fasting glucose, insulin, HOMA-IR and HbA(1c) among old non-diabetic individuals. Higher birth weight and ponderal index at birth decreased the risk for type 2 diabetes in old age, odds ratio (OR), 0.61 [95 % confidence interval (CI), 0.48-0.79] and 0.96 (95 % CI, 0.92-1.00), respectively. Compared with those with high birth weight and low BMI in midlife, the odds of diabetes was almost five-fold for individuals with low birth weight and high BMI (OR, 4.93; 95 % CI, 2.14-11.37). Excessive weight gain in adulthood might be particularly detrimental to the health of old individuals with low birth weight.
C1 [von Bonsdorff, Mikaela B.; Muller, Majon; Garcia, Melissa; Launer, Lenore; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
[von Bonsdorff, Mikaela B.; Rantanen, Taina] Univ Jyvaskyla, Gerontol Res Ctr, Jyvaskyla 40014, Finland.
[von Bonsdorff, Mikaela B.; Rantanen, Taina] Univ Jyvaskyla, Dept Hlth Sci, Jyvaskyla 40014, Finland.
[Muller, Majon] Vrije Univ Amsterdam, Med Ctr Amsterdam, Dept Internal Med, Amsterdam, Netherlands.
[Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Aspelund, Thor; Sigurdsson, Gunnar; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Gunnarsdottir, Ingibjorg; Birgisdottir, Bryndis Eva; Thorsdottir, Inga] Univ Iceland, Unit Nutr Res, Reykjavik, Iceland.
[Gunnarsdottir, Ingibjorg; Birgisdottir, Bryndis Eva; Thorsdottir, Inga] Natl Univ Hosp Iceland, Landspitali, Reykjavik, Iceland.
RP von Bonsdorff, MB (reprint author), Univ Jyvaskyla, Gerontol Res Ctr, POB 35, Jyvaskyla 40014, Finland.
EM mikaela.vonbonsdorff@jyu.fi
RI Aspelund, Thor/C-5983-2008; von Bonsdorff, Mikaela/A-5218-2015;
Gudnason, Vilmundur/K-6885-2015; Gunnarsdottir, Ingibjorg/L-9371-2015;
Birgisdottir, Bryndis/M-1504-2015; Rantanen, Taina/O-6579-2016
OI Gunnarsdottir, Ingibjorg/0000-0001-9447-8627; Aspelund,
Thor/0000-0002-7998-5433; von Bonsdorff, Mikaela/0000-0001-8530-5230;
Gudnason, Vilmundur/0000-0001-5696-0084; Rantanen,
Taina/0000-0002-1604-1945
FU National Institutes of Health [N01-AG-1-2100]; National Institute on
Aging Intramural Research Program; Hjartavernd (the Icelandic Heart
Association); Althingi (the Icelandic Parliament); Icelandic Heart
Association; Academy of Finland; University of Jyvaskyla; Yrjo Jahnsson
Foundation; Fulbright Center; Finland-US Educational Exchange
Commission; Icelandic Research Council; University of Iceland
FX The AGES-Reykjavik Study was supported by a grant from the National
Institutes of Health (N01-AG-1-2100), National Institute on Aging
Intramural Research Program, Hjartavernd (the Icelandic Heart
Association) and the Althingi (the Icelandic Parliament). The Reyjavik
Study was funded by the Icelandic Heart Association. M.B.vB. was
supported by grants from the Academy of Finland; University of
Jyvaskyla; Yrjo Jahnsson Foundation and Fulbright Center, the Finland-US
Educational Exchange Commission. I. T. was supported by grants from The
Icelandic Research Council and Research Fund of the University of
Iceland. The Gerontology Research Center is a joint effort between the
University of Jyvaskyla and the University of Tampere, Finland.
NR 33
TC 2
Z9 2
U1 0
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0161-9152
J9 AGE
JI Age
PD AUG
PY 2013
VL 35
IS 4
BP 1401
EP 1409
DI 10.1007/s11357-012-9427-5
PG 9
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 179UQ
UT WOS:000321547300030
PM 22588637
ER
PT J
AU Lu, J
Vallabhaneni, H
Yin, JH
Liu, Y
AF Lu, Jian
Vallabhaneni, Haritha
Yin, Jinhu
Liu, Yie
TI Deletion of the major peroxiredoxin Tsa1 alters telomere length
homeostasis
SO AGING CELL
LA English
DT Article
DE peroxiredoxin; reactive oxygen species; telomerase; telomere length
ID GENOME-WIDE SCREEN; SACCHAROMYCES-CEREVISIAE; YEAST TELOMERASE;
CHROMOSOMAL REARRANGEMENTS; OXIDATIVE STRESS; BASE DAMAGE; EST GENES;
DNA; ELONGATION; SENESCENCE
AB Reactive oxygen species (ROS) are proposed to play a major role in telomere length alterations during aging. The mechanisms by which ROS disrupt telomeres remain unclear. In Saccharomyces cerevisiae, telomere DNA consists of TG((1-3)) repeats, which are maintained primarily by telomerase. Telomere length maintenance can be modulated by the expression level of telomerase subunits and telomerase activity. Additionally, telomerase-mediated telomere repeat addition is negatively modulated by the levels of telomere-bound Rap1-Rif1-Rif2 protein complex. Using a yeast strain defective in the major peroxiredoxin Tsa1 that is involved in ROS neutralization, we have investigated the effect of defective ROS detoxification on telomere DNA, telomerase, telomere-binding proteins, and telomere length. Surprisingly, the tsa1 mutant does not show significant increase in steady-state levels of oxidative DNA lesions at telomeres. The tsa1 mutant displays abnormal telomere lengthening, and reduction in oxidative exposure alleviates this phenotype. The telomere lengthening in the tsa1 cells was abolished by disruption of Est2, subtelomeric DNA, Rap1 C-terminus, or Rif2, but not by Rif1 deletion. Although telomerase expression and activity are not altered, telomere-bound Est2 is increased, while telomere-bound Rap1 is reduced in the tsa1 mutant. We propose that defective ROS scavenging can interfere with pathways that are critical in controlling telomere length homeostasis.
C1 [Lu, Jian; Vallabhaneni, Haritha; Yin, Jinhu; Liu, Yie] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
RP Liu, Y (reprint author), NIA, Lab Mol Gerontol, 251 Bayview Dr,Suite 100,Rm 06B121, Baltimore, MD 21224 USA.
EM liuyie@mail.nih.gov
FU Intramural Research Program of the NIA, National Institutes of Health
FX We sincerely thank Drs. Anders Bystrom, Kurt W. Runge, Katherine L.
Friedman, Stephane Marcand, and Virginia Zakian for providing us with
yeast strains and plasmids; Drs. Vilhelm Bohr, David Wilson, Sarah I.
West, and Kent Horvath for critical reading of the manuscript. This work
was supported by funds from the Intramural Research Program of the NIA,
National Institutes of Health.
NR 45
TC 4
Z9 4
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9718
J9 AGING CELL
JI Aging Cell
PD AUG
PY 2013
VL 12
IS 4
BP 635
EP 644
DI 10.1111/acel.12085
PG 10
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 182WP
UT WOS:000321775800011
PM 23590194
ER
PT J
AU Mercken, EM
Crosby, SD
Lamming, DW
JeBailey, L
Krzysik-Walker, S
Villareal, DT
Capri, M
Franceschi, C
Zhang, YQ
Becker, K
Sabatini, DM
de Cabo, R
Fontana, L
AF Mercken, Evi M.
Crosby, Seth D.
Lamming, Dudley W.
JeBailey, Lellean
Krzysik-Walker, Susan
Villareal, Dennis T.
Capri, Miriam
Franceschi, Claudio
Zhang, Yongqing
Becker, Kevin
Sabatini, David M.
de Cabo, Rafael
Fontana, Luigi
TI Calorie restriction in humans inhibits the PI3K/AKT pathway and induces
a younger transcription profile
SO AGING CELL
LA English
DT Article
DE caloric restriction; human; insulin; IGF-1 signaling; skeletal muscle
ID GENE SET ENRICHMENT; DIETARY RESTRICTION; ENDURANCE EXERCISE; LONG;
MUSCLE
AB Caloric restriction (CR) and down-regulation of the insulin/IGF pathway are the most robust interventions known to increase longevity in lower organisms. However, little is known about the molecular adaptations induced by CR in humans. Here, we report that long-term CR in humans inhibits the IGF-1/insulin pathway in skeletal muscle, a key metabolic tissue. We also demonstrate that CR induces dramatic changes of the skeletal muscle transcriptional profile that resemble those of younger individuals. Finally, in both rats and humans, CR evoked similar responses in the transcriptional profiles of skeletal muscle. This common signature consisted of three key pathways typically associated with longevity: IGF-1/insulin signaling, mitochondrial biogenesis, and inflammation. Furthermore, our data identify promising pathways for therapeutic targets to combat age-related diseases and promote health in humans.
C1 [Mercken, Evi M.; de Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA.
[Crosby, Seth D.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63108 USA.
[Lamming, Dudley W.; Sabatini, David M.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
[Lamming, Dudley W.; Sabatini, David M.] MIT, Dept Biol, Cambridge, MA 02139 USA.
[Lamming, Dudley W.; Sabatini, David M.] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA.
[Lamming, Dudley W.; Sabatini, David M.] Broad Inst Harvard & MIT, Cambridge Ctr 7, Cambridge, MA 02142 USA.
[Lamming, Dudley W.; Sabatini, David M.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
[JeBailey, Lellean] GeneGo Inc, St Joseph, MI 49085 USA.
[Krzysik-Walker, Susan] NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA.
[Villareal, Dennis T.; Fontana, Luigi] Washington Univ, Sch Med, Div Geriatr & Nutr Sci, St Louis, MO 63108 USA.
[Capri, Miriam; Franceschi, Claudio] Univ Bologna ALMA MATER STUDIORUM, CIG, I-40126 Bologna, Italy.
[Capri, Miriam; Franceschi, Claudio] Univ Bologna ALMA MATER STUDIORUM, Dept Expt Diagnost & Specialty Med, I-40126 Bologna, Italy.
[Zhang, Yongqing; Becker, Kevin] NIA, Gene Express & Genom Unit, NIH, Baltimore, MD 21224 USA.
[Fontana, Luigi] Univ Salerno, Sch Med, Dept Med, I-84081 Salerno, Italy.
[Fontana, Luigi] CEINGE Biotecnol Avanzate, I-80145 Naples, Italy.
RP Fontana, L (reprint author), Washington Univ, Sch Med, Div Geriatr & Nutr Sci, St Louis, MO 63108 USA.
EM decabora@grc.nia.nih.gov; lfontana@dom.wustl.edu
RI Fontana, Luigi/K-4773-2013; de Cabo, Rafael/J-5230-2016; Capri,
Miriam/K-4700-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; Capri, Miriam/0000-0001-9077-0401;
Becker, Kevin/0000-0002-6794-6656; , rafael/0000-0003-2830-5693
FU AFAR (American Federation for Aging Research); National Center for
Research Resources [UL1 RR024992]; National Institute of Diabetes And
Digestive And Kidney Diseases [P30DK056341]; National Institute on
Aging-Intramural Research Program; Longer Life Foundation (an
RGA/Washington University Partnership); Bakewell Foundation; NCI Cancer
Center Support Grant [P30 CA91842]; ICTS/CTSA Grant from the National
Center for Research Resources (NCRR), a component of the National
Institutes of Health (NIH) [UL1RR024992]; NIH Roadmap for Medical
Research
FX Supported by grants from AFAR (American Federation for Aging Research),
the National Center for Research Resources (UL1 RR024992), the National
Institute of Diabetes And Digestive And Kidney Diseases (P30DK056341).
This research was supported in part by the National Institute on
Aging-Intramural Research Program, the Longer Life Foundation (an
RGA/Washington University Partnership), the Bakewell Foundation, and a
donation from the Calorie Restriction Society and the Scott and Annie
Appleby Charitable Trust. The funding agencies had no role in the
analysis or interpretation of the data or in the decision to submit the
report for publication. We thank William Wood and Elin Lehrmann for help
with microarray processing and Kevin Becker for microarray data
analysis. We also thank the Genome Technology Access Center in the
Department of Genetics at Washington University School of Medicine for
help with genomic analysis. The Center is partially supported by NCI
Cancer Center Support Grant #P30 CA91842 to the Siteman Cancer Center
and by ICTS/CTSA Grant# UL1RR024992 from the National Center for
Research Resources (NCRR), a component of the National Institutes of
Health (NIH), and NIH Roadmap for Medical Research. DWL is a Charles A.
King Trust Postdoctoral Fellow; DMS is an Investigator of the Howard
Hughes Medical Institute. This publication is solely the responsibility
of the authors and does not necessarily represent the official view of
NCRR or NIH. Data have been deposited at the Gene Expression Omnibus
(http://www.ncbi.nlm.nih.gov/geo/) under accession code .
NR 26
TC 54
Z9 54
U1 3
U2 31
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9718
J9 AGING CELL
JI Aging Cell
PD AUG
PY 2013
VL 12
IS 4
BP 645
EP 651
DI 10.1111/acel.12088
PG 7
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 182WP
UT WOS:000321775800012
PM 23601134
ER
PT J
AU Takeuchi, DT
Link, BG
Shariff-Marco, S
Spittel, ML
Srinivasan, S
AF Takeuchi, David T.
Link, Bruce G.
Shariff-Marco, Salma
Spittel, Michael L.
Srinivasan, Shobha
TI Introduction
SO AMERICAN BEHAVIORAL SCIENTIST
LA English
DT Editorial Material
C1 [Takeuchi, David T.] Boston Coll, Grad Sch Social Work, Chestnut Hill, MA 02467 USA.
[Link, Bruce G.; Shariff-Marco, Salma] Columbia Univ, New York, NY USA.
[Shariff-Marco, Salma] Canc Prevent Inst Calif, Fremont, CA USA.
[Spittel, Michael L.] NIH, Off Behav & Social Sci, Washington, DC USA.
[Srinivasan, Shobha] NIH, Ctr Populat Hlth & Hlth Disparities, Washington, DC USA.
RP Takeuchi, DT (reprint author), Boston Coll, McGuinn Hall, Chestnut Hill, MA 02467 USA.
EM takeuchi@bc.edu
RI Link, Bruce/N-9087-2013;
OI Link, Bruce/0000-0001-9980-7450
NR 0
TC 0
Z9 0
U1 1
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0002-7642
J9 AM BEHAV SCI
JI Am. Behav. Sci.
PD AUG
PY 2013
VL 57
IS 8
SI SI
BP 1011
EP 1013
DI 10.1177/0002764213487350
PG 3
WC Psychology, Clinical; Social Sciences, Interdisciplinary
SC Psychology; Social Sciences - Other Topics
GA 181XR
UT WOS:000321704500001
ER
PT J
AU Lee, J
Romero, R
Xu, Y
Miranda, J
Yoo, W
Chaemsaithong, P
Kusanovic, JP
Chaiworapongsa, T
Tarca, AL
Korzeniewski, SJ
Hassan, SS
Than, NG
Yoon, BH
Kim, CJ
AF Lee, JoonHo
Romero, Roberto
Xu, Yi
Miranda, Jezid
Yoo, Wonsuk
Chaemsaithong, Piya
Kusanovic, Juan Pedro
Chaiworapongsa, Tinnakorn
Tarca, Adi L.
Korzeniewski, Steven J.
Hassan, Sonia S.
Than, Nandor Gabor
Yoon, Bo Hyun
Kim, Chong Jai
TI Detection of Anti-HLA Antibodies in Maternal Blood in the Second
Trimester to Identify Patients at Risk of Antibody-Mediated Maternal
Anti-Fetal Rejection and Spontaneous Preterm Delivery
SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
LA English
DT Review
DE Flow cytometry; preterm birth; rejection; transplantation
ID REGULATORY T-CELLS; SOLID-ORGAN TRANSPLANTATION; AMNIOTIC-FLUID
INTERLEUKIN-6; CLINICAL-SIGNIFICANCE; INTRAAMNIOTIC INFECTION; MICROBIAL
INVASION; CERVICAL LENGTH; CHRONIC CHORIOAMNIONITIS;
PROGESTERONE-RECEPTOR; ALLOGRAFT-REJECTION
AB Problem
Maternal anti-fetal rejection is a mechanism of disease in spontaneous preterm labor. The objective of this study was to determine whether the presence of human leukocyte antigen (HLA) panel-reactive antibodies (PRA) during the second trimester increases the risk of spontaneous preterm delivery.
Methods of study
This longitudinal case-control study included pregnant women with spontaneous preterm deliveries (n = 310) and control patients with normal term pregnancies (n = 620), matched for maternal age and gravidity. Maternal plasma samples obtained at 14-16, 16-20, 20-24, and 24-28weeks of gestation were analyzed for HLA class I and class II PRA positivity using flow cytometry. The fetal HLA genotype and maternal HLA alloantibody epitope were determined for a subset of patients with positive HLA PRA.
Results
(i) Patients with spontaneous preterm delivery were more likely to exhibit HLA class I (adjusted OR=2.54, P<0.0001) and class II (adjusted OR=1.98, P=0.002) PRA positivity than those delivering at term; (ii) HLA class I PRA positivity for patients with spontaneous preterm delivery between 28 and 34weeks (adjusted OR=2.88; P=0.001) and after 34weeks of gestation (adjusted OR=2.53; P<0.0001) was higher than for those delivering at term; (iii) HLA class II PRA positivity for patients with spontaneous preterm delivery after 34weeks of gestation was higher than for those delivering at term (adjusted OR=2.04; P=0.002); (iv) multiparous women were at a higher risk for HLA class I PRA positivity than nulliparous women (adjusted OR=0.097, P<0.0001 for nulliparity); (v) nulliparous women had a higher rate of HLA class I PRA positivity with advancing gestational age (P=0.001); and (vi) 78% of women whose fetuses were genotyped had alloantibodies specific against fetal HLA class I antigens.
Conclusion
Pregnant women with positive HLA class I or class II PRA during the second trimester are at an increased risk of spontaneous preterm delivery due to antibody-mediated maternal anti-fetal rejection.
C1 [Lee, JoonHo; Romero, Roberto; Xu, Yi; Miranda, Jezid; Chaemsaithong, Piya; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Tarca, Adi L.; Korzeniewski, Steven J.; Hassan, Sonia S.; Than, Nandor Gabor; Kim, Chong Jai] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Lee, JoonHo; Romero, Roberto; Xu, Yi; Miranda, Jezid; Chaemsaithong, Piya; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Tarca, Adi L.; Korzeniewski, Steven J.; Hassan, Sonia S.; Than, Nandor Gabor; Kim, Chong Jai] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI 48201 USA.
[Miranda, Jezid; Chaemsaithong, Piya; Chaiworapongsa, Tinnakorn; Korzeniewski, Steven J.; Hassan, Sonia S.; Than, Nandor Gabor] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Yoo, Wonsuk] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Biostat & Epidemiol Div, Memphis, TN 38163 USA.
[Kusanovic, Juan Pedro] Pontificia Univ Catolica Chile, Sch Med, Dept Obstet & Gynecol, Santiago, Chile.
[Kusanovic, Juan Pedro] Hosp Dr Sotero del Rio, Ctr Res & Innovat Maternal Fetal Med CIMAF, Santiago, Chile.
[Tarca, Adi L.] Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA.
[Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea.
[Kim, Chong Jai] Univ Ulsan, Dept Pathol, Asan Med Ctr, Coll Med, Seoul 138736, South Korea.
[Kim, Chong Jai] Wayne State Univ, Sch Med, Dept Pathol, Hutzel Womens Hosp, Detroit, MI 48201 USA.
RP Kim, CJ (reprint author), Univ Ulsan, Dept Pathol, Asan Med Ctr, Coll Med, 88 Olympic Ro,43 Gil, Seoul 138736, South Korea.
EM romeror@mail.nih.gov; ckim@amc.seoul.kr
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Department of Health and
Human Services (NICHD/NIH); NICHD, NIH [HHSN275201300006C]
FX This research was supported, in part, by the Perinatology Research
Branch, Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, Department of Health and Human Services (NICHD/NIH); and, in
part, with Federal funds from NICHD, NIH under Contract No.
HHSN275201300006C.
NR 145
TC 10
Z9 12
U1 1
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1046-7408
J9 AM J REPROD IMMUNOL
JI Am. J. Reprod. Immunol.
PD AUG
PY 2013
VL 70
IS 2
BP 162
EP 175
DI 10.1111/aji.12141
PG 14
WC Immunology; Reproductive Biology
SC Immunology; Reproductive Biology
GA 179VB
UT WOS:000321548400007
PM 23841577
ER
PT J
AU Christie, KM
Meyerowitz, BE
Stanton, AL
Rowland, JH
Ganz, PA
AF Christie, Kysa M.
Meyerowitz, Beth E.
Stanton, Annette L.
Rowland, Julia H.
Ganz, Patricia A.
TI Characteristics of Breast Cancer Survivors That Predict Partners'
Participation in Research
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Article
DE Couple/partner; Recruitment; Retention; Breast cancer; Socioeconomic
status; Quality of life
ID COUPLE-BASED INTERVENTIONS; TRIAL; RECRUITMENT; ADJUSTMENT; CHALLENGES;
RETENTION; SCALES; SF-36; WOMEN; LIFE
AB Psycho-oncology couples' research frequently includes fewer than 50 % of those eligible.
This research examined individual and relationship characteristics associated with recruitment and retention of breast cancer survivors' partners.
Investigators asked survivors from the Moving Beyond Cancer trial for permission to invite their partners to a parallel, longitudinal study.
Of 384 survivors with male partners, 280 survivors provided consent to contact partners, and 164 partners completed both assessments. Backward stepwise regression indicated that greater family income and support from a partner and helpful other increased the likelihood of survivor consent to contact her partner. Greater family income, better survivor physical and emotional quality of life, and white ethnicity increased the likelihood of partner participation.
Breast cancer patients who are ethnic minorities, have lower socioeconomic status, or have poorer physical and mental quality of life appear less likely to participate in psycho-oncology couples' research, whereas women with supportive partners might be overrepresented.
C1 [Christie, Kysa M.; Meyerowitz, Beth E.] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA.
[Stanton, Annette L.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA.
[Rowland, Julia H.] NCI, Off Canc Survivorship, Bethesda, MD 20892 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, UCLA Sch Med, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, UCLA Sch Med, Jonsson Comprehens Canc Ctr, UCLA LIVESTRONG Survivorship Ctr Excellence, Los Angeles, CA USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, UCLA Sch Publ Hlth, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, UCLA Sch Publ Hlth, Jonsson Comprehens Canc Ctr, UCLA LIVESTRONG Survivorship Ctr Excellence, Los Angeles, CA USA.
RP Meyerowitz, BE (reprint author), Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA.
EM meyerow@usc.edu
FU NCI NIH HHS [CA63028]
NR 20
TC 7
Z9 8
U1 2
U2 13
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD AUG
PY 2013
VL 46
IS 1
BP 107
EP 113
DI 10.1007/s12160-013-9477-7
PG 7
WC Psychology, Multidisciplinary
SC Psychology
GA 180GC
UT WOS:000321580800014
PM 23456213
ER
PT J
AU Wang, Z
Zhang, XX
Huang, P
Zhao, WD
Liu, DB
Nie, LM
Yue, XY
Wang, SJ
Ma, Y
Kiesewetter, D
Niu, G
Chen, XY
AF Wang, Zhe
Zhang, Xiaoxiang
Huang, Peng
Zhao, Weidong
Liu, Dingbin
Nie, Liming
Yue, Xuyi
Wang, Shouju
Ma, Ying
Kiesewetter, Dale
Niu, Gang
Chen, Xiaoyuan
TI Dual-factor triggered fluorogenic nanoprobe for ultrahigh contrast and
subdiffraction fluorescence imaging
SO BIOMATERIALS
LA English
DT Article
DE Fluorescence imaging; Subdiffraction imaging; Fluorogenic PLGA
nanoparticle; BODIPY NIR dye; pH sensitive; Molecular binding
ID BODIPY DERIVATIVES; NANOPARTICLES; CELLS; PROTEINS; THERAPY; SURGERY;
PROBES; LIGHT; DOTS; DYES
AB Ultrahigh contrast fluorescence molecular imaging has long been pursued over the past few decades from basic sciences to clinics. Although new classes of near-infrared (NIR) molecular probes are emerging, the requirement of fluorophores with high quantum yield, high signal to noise (S/N) ratio, and being activatable to microenvironment changes can hardly be fulfilled. In this study, a new NIR dye embedded fluorogenic nanoprobe (fg-nanoprobe) was developed for ultrahigh contrast in vitro and in vivo imaging with negligible background interference. The achieved S/N ratio was found to be attributed to the synergistic effects of the cellular compartmental triggered fluorogenicity and pH tunable fluorescence on/off character. In addition, this constructed fluorogenic nanoprobe could be coupled with image processing method for super-resolution subdiffraction imaging. The developed fg-nanoprobe integrated photophysical merits of the synthesized NIR fluorophore and advantages of engineered nanoparticle for enhanced fluorescence molecular imaging. This probe may open another avenue for ultrahigh contrast fluorescence molecular imaging in the future. Published by Elsevier Ltd.
C1 [Wang, Zhe; Zhang, Xiaoxiang; Huang, Peng; Liu, Dingbin; Nie, Liming; Yue, Xuyi; Wang, Shouju; Ma, Ying; Kiesewetter, Dale; Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
[Zhao, Weidong] NINDS, Synapt Transmiss Sect, NIH, Bethesda, MD 20892 USA.
[Yue, Xuyi] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361102, Peoples R China.
RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
EM shawn.chen@nih.gov
RI Huang, Peng/H-9985-2013; Nie, Liming/F-7718-2016; Huang,
Peng/R-2480-2016
OI Huang, Peng/0000-0003-3651-7813
FU National Basic Research Program of China (973 program) [2013CB733802];
Henry M. Jackson Foundation; NIBIB/NIH, U.S.A.
FX This work was supported, in part, by the National Basic Research Program
of China (973 program, 2013CB733802), Henry M. Jackson Foundation and
the Intramural Research Program (IRP), NIBIB/NIH, U.S.A.
NR 31
TC 10
Z9 10
U1 3
U2 81
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0142-9612
J9 BIOMATERIALS
JI Biomaterials
PD AUG
PY 2013
VL 34
IS 26
BP 6194
EP 6201
DI 10.1016/j.biomaterials.2013.05.004
PG 8
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 173KY
UT WOS:000321079600012
PM 23721793
ER
PT J
AU Patel, PR
Sun, HM
Li, SQ
Shen, M
Khan, J
Thomas, CJ
Davis, MI
AF Patel, Paresma R.
Sun, Hongmao
Li, Samuel Q.
Shen, Min
Khan, Javed
Thomas, Craig J.
Davis, Mindy I.
TI Identification of potent Yes1 kinase inhibitors using a library
screening approach
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Yes1; Kinase; Screening; HTS; Small molecule; Inhibitor;
Rhabdomyosarcoma
ID CHRONIC MYELOID-LEUKEMIA; TYROSINE KINASE; C-YES; SRC; CANCER;
DASATINIB; DISCOVERY; RECEPTOR; CELLS; SELECTIVITY
AB Yes1 kinase has been implicated as a potential therapeutic target in a number of cancers including melanomas, breast cancers, and rhabdomyosarcomas. Described here is the development of a robust and miniaturized biochemical assay for Yes1 kinase that was applied in a high throughput screen (HTS) of kinase-focused small molecule libraries. The HTS provided 144 (17% hit rate) small molecule compounds with IC50 values in the sub-micromolar range. Three of the most potent Yes1 inhibitors were then examined in a cell-based assay for inhibition of cell survival in rhabdomyosarcoma cell lines. Homology models of Yes1 were generated in active and inactive conformations, and docking of inhibitors supports binding to the active conformation (DFG-in) of Yes1. This is the first report of a large high throughput enzymatic activity screen for identification of Yes1 kinase inhibitors, thereby elucidating the polypharmacology of a variety of small molecules and clinical candidates. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
C1 [Patel, Paresma R.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Basic Sci Program, Frederick, MD 21702 USA.
[Patel, Paresma R.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Sun, Hongmao; Shen, Min; Thomas, Craig J.; Davis, Mindy I.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Li, Samuel Q.; Khan, Javed] NCI, Oncogen Sect, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Davis, MI (reprint author), NIH, Natl Ctr Adv Translat Sci, Bldg 10, Bethesda, MD 20892 USA.
EM davismi2@mail.nih.gov
RI Khan, Javed/P-9157-2014
OI Khan, Javed/0000-0002-5858-0488
FU Division of Preclinical Innovation, National Center for Advancing
Translational Sciences; Molecular Libraries Initiative of the National
Institutes of Health Roadmap for Medical Research; National Human Genome
Research Institute; National Cancer Institute, Center for Cancer
Research; Frederick National Laboratory for Cancer Research, National
Institutes of Health [HHSN261200800001E, U54CA143930]
FX The authors would like to thank Paul Shinn, Danielle VanLeer, Crystal
McKnight, and Misha Itkin for assistance with compound management.
Lesley Mathews, Marc Ferrer, Rajarshi Guha, and Scott Martin are thanked
for helpful discussions. We would like to thank William J. Zuercher and
David Drewry for valuable discussions and GlaxoSmithKline for access to
the GSK Published Kinase Inhibitor Set. This work was supported by the
Division of Preclinical Innovation, National Center for Advancing
Translational Sciences; the Molecular Libraries Initiative of the
National Institutes of Health Roadmap for Medical Research; the
Intramural Research Program of the National Human Genome Research
Institute; the Intramural Research Program of the National Cancer
Institute, Center for Cancer Research and the Frederick National
Laboratory for Cancer Research, National Institutes of Health including
contract HHSN261200800001E and grant #U54CA143930. 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.
NR 39
TC 13
Z9 13
U1 1
U2 15
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD AUG 1
PY 2013
VL 23
IS 15
BP 4398
EP 4403
DI 10.1016/j.bmcl.2013.05.072
PG 6
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 179CO
UT WOS:000321495900024
PM 23787099
ER
PT J
AU Liu, YJ
Garnham, CP
Roll-Mecak, A
Tanner, ME
AF Liu, Yanjie
Garnham, Christopher P.
Roll-Mecak, Antonina
Tanner, Martin E.
TI Phosphinic acid-based inhibitors of tubulin polyglutamylases
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Inhibitor; Tubulin; Post-translational modification; Ligase; Phosphinic
acid
ID GAMMA-GLUTAMATE SYNTHETASE; D-ALANINE LIGASE; ALPHA-TUBULIN; TYROSINE
LIGASE; POSTTRANSLATIONAL MODIFICATIONS; PEPTIDOGLYCAN BIOSYNTHESIS;
ADDING ENZYME; BETA-TUBULIN; CANCER CELLS; PEPTIDES
AB Tubulin is subject to a reversible post-translational modification involving polyglutamylation and deglutamylation of glutamate residues in its C-terminal tail. This process plays key roles in regulating the function of microtubule associated proteins, neuronal development, and metastatic progression. This study describes the synthesis and testing of three phosphinic acid-based inhibitors that have been designed to inhibit both the glutamylating and deglutamylating enzymes. The compounds were tested against the polyglutamylase TTLL7 using tail peptides as substrates (100 mu M) and the most potent inhibitor displayed an IC50 value of 150 mu M. The incorporation of these compounds into tubulin C-terminal tail peptides may lead to more potent TTLL inhibitors. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Liu, Yanjie; Tanner, Martin E.] Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1, Canada.
[Garnham, Christopher P.; Roll-Mecak, Antonina] NINDS, Cell Biol & Biophys Unit, Bethesda, MD 20892 USA.
[Garnham, Christopher P.; Roll-Mecak, Antonina] NHLBI, Bethesda, MD 20892 USA.
RP Roll-Mecak, A (reprint author), NINDS, Cell Biol & Biophys Unit, Bethesda, MD 20892 USA.
EM Antonina@mail.nih.gov; mtanner@chem.ubc.ca
FU Natural Sciences and Engineering Research Council of Canada (NSERC);
National Institutes of Health (NIH)
FX We thank Duck-Yeon Lee from the Biochemistry Core Facility of the
National Heart, Lung and Blood Institute (NHLBI) for his suggestions and
assistance with experiments. This research was supported by the Natural
Sciences and Engineering Research Council of Canada (NSERC) (M.E.T.) and
the intramural program of the National Institutes of Health (NIH)
(A.R.-M.).
NR 45
TC 5
Z9 5
U1 0
U2 25
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD AUG 1
PY 2013
VL 23
IS 15
BP 4408
EP 4412
DI 10.1016/j.bmcl.2013.05.069
PG 5
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 179CO
UT WOS:000321495900026
PM 23777780
ER
PT J
AU Heinrich, TA
da Silva, RS
Miranda, KM
Switzer, CH
Wink, DA
Fukuto, JM
AF Heinrich, Tassiele A.
da Silva, Roberto S.
Miranda, Katrina M.
Switzer, Christopher H.
Wink, David A.
Fukuto, Jon M.
TI Biological nitric oxide signalling: chemistry and terminology
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Review
DE nitric oxide; nitrogen oxides; nitrogen dioxide; dinitrogen trioxide;
peroxynitrite; metal nitrosyls; nitrosation; nitrosylation; nitrosative
stress; nitrosative signalling
ID LOW-DENSITY-LIPOPROTEIN; S-NITROSYLATION; IRON(III) PORPHYRINS;
HYDROGEN-PEROXIDE; REDUCTIVE NITROSYLATION; MICROBIAL PATHOGENESIS;
TYROSINE NITRATION; CHEMICAL BIOLOGY; CELLULAR-DAMAGE; BREAST-CANCER
AB Biological nitrogen oxide signalling and stress is an area of extreme clinical, pharmacological, toxicological, biochemical and chemical research interest. The utility of nitric oxide and derived species as signalling agents is due to their novel and vast chemical interactions with a variety of biological targets. Herein, the chemistry associated with the interaction of the biologically relevant nitrogen oxide species with fundamental biochemical targets is discussed. Specifically, the chemical interactions of nitrogen oxides with nucleophiles (e.g. thiols), metals (e.g. hemeproteins) and paramagnetic species (e.g. dioxygen and superoxide) are addressed. Importantly, the terms associated with the mechanisms by which NO (and derived species) react with their respective biological targets have been defined by numerous past chemical studies. Thus, in order to assist researchers in referring to chemical processes associated with nitrogen oxide biology, the vernacular associated with these chemical interactions is addressed.
C1 [Heinrich, Tassiele A.; da Silva, Roberto S.] Fac Ciencias Farmaceut Ribeirao Preto USP, Ribeirao Preto, Brazil.
[Miranda, Katrina M.] Univ Arizona, Dept Chem & Biochem, Tucson, AZ USA.
[Switzer, Christopher H.; Wink, David A.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA.
[Fukuto, Jon M.] Sonoma State Univ, Dept Chem, Rohnert Pk, CA 94928 USA.
RP Fukuto, JM (reprint author), Sonoma State Univ, Dept Chem, Rohnert Pk, CA 94928 USA.
EM fukuto@sonoma.edu
NR 73
TC 43
Z9 44
U1 1
U2 59
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1188
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD AUG
PY 2013
VL 169
IS 7
BP 1417
EP 1429
DI 10.1111/bph.12217
PG 13
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 181VN
UT WOS:000321697700002
PM 23617570
ER
PT J
AU Rusner, C
Trabert, B
Katalinic, A
Kieschke, J
Emrich, K
Stang, A
AF Rusner, Carsten
Trabert, Britton
Katalinic, Alexander
Kieschke, Joachim
Emrich, Katharina
Stang, Andreas
CA Network German Canc Registries GEK
TI Incidence patterns and trends of malignant gonadal and extragonadal germ
cell tumors in Germany, 1998-2008
SO CANCER EPIDEMIOLOGY
LA English
DT Article
DE Extragonadal germ cell tumors; Germ cell tumors; Incidence; Cancer
registry; Testicular neoplasms; Ovarian neoplasms
AB Background: Malignant gonadal (GGCT) and extragonal germ cell tumors [GCT (EGCT)] are thought to originate from primordial germ cells. In contrast to well reported population-based data of GGCTs in males, analyses of GGCTs in females and EGCTs in both sexes remain limited.
Methods: In a pooling project of nine population-based cancer registries in Germany for the years 1998-2008, 16,883 malignant GCTs and their topographical sites were identified using ICD-O morphology and topography for persons aged 15 years and older. We estimated age-specific and age-standardized incidence rates.
Results: Among males, the incidence of testicular GCTs increased over time. In contrast, there was no increase in the incidence of EGCTs. Among females, rates of ovarian GCTs were stable, while rates of EGCTs declined over time. The most frequent extragonadal sites were mediastinum among males and placenta among females.
Conclusions: Our results underline different incidence trends and distinct age-specific incidence patterns of malignant GGCTs and EGCTs, as reported recently by several population-based registries. The differences suggest that GGCT and EGCT may have different etiologies. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Rusner, Carsten; Stang, Andreas] Univ Halle Wittenberg, Fac Med, Inst Clin Epidemiol, D-06097 Halle, Saale, Germany.
[Trabert, Britton] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Katalinic, Alexander] Canc Registry Schleswig Holstein, D-23538 Lubeck, Germany.
[Kieschke, Joachim] Canc Registry Lower Saxony, D-26121 Oldenburg, Germany.
[Emrich, Katharina] Canc Registry Rhineland Palatinate, D-55131 Mainz, Germany.
[Stang, Andreas] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA.
RP Rusner, C (reprint author), Univ Halle Wittenberg, Fac Med, Inst Clin Epidemiol, Magdeburger Str 8, D-06097 Halle, Saale, Germany.
EM carsten.rusner@medizin.uni-halle.de
RI Katalinic, Alexander/D-2512-2010; Trabert, Britton/F-8051-2015
OI Katalinic, Alexander/0000-0003-0490-1554;
FU Deutsche Forschungsgemeinschaft (DFG) [RU 1659/1-1]; National Cancer
Institute, NIH, DHHS
FX This work was supported by grants of the Deutsche Forschungsgemeinschaft
(DFG) [grant-number RU 1659/1-1]. Dr. Trabert was supported by the
intramural research program of the National Cancer Institute, NIH, DHHS.
NR 15
TC 14
Z9 15
U1 0
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1877-7821
J9 CANCER EPIDEMIOL
JI Cancer Epidemiol.
PD AUG
PY 2013
VL 37
IS 4
BP 370
EP 373
DI 10.1016/j.canep.2013.04.003
PG 4
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 179FE
UT WOS:000321504300004
PM 23683844
ER
PT J
AU Wartko, P
Sherman, ME
Yang, HP
Felix, AS
Brinton, LA
Trabert, B
AF Wartko, Paige
Sherman, Mark E.
Yang, Hannah P.
Felix, Ashley S.
Brinton, Louise A.
Trabert, Britton
TI Recent changes in endometrial cancer trends among menopausal-age US
women
SO CANCER EPIDEMIOLOGY
LA English
DT Article
DE Endometrial cancer; Incidence; Trends; Menopausal-age women; Menopausal
hormone therapy
ID HORMONE-REPLACEMENT THERAPY; BODY-MASS INDEX; BREAST-CANCER;
UNITED-STATES; METAANALYSIS; PREVALENCE; RISK
AB Background: Changes in endometrial cancer incidence rates after the precipitous decline in menopausal hormone therapy (MHT) use in 2002 have not been evaluated.
Methods: Using data from the Surveillance, Epidemiology, and End Results Program from 1992 to 2009 (SEER 13), we identified 63 428 incident endometrial cancer cases among women ages 20-74. We compared annual percent change (APC) in endometrial cancer incidence rates from 1992 to 2002 to rates from 2003 to 2009.
Results: In contrast to the constant endometrial cancer rate pattern observed from 1992 to 2002 (APC 0.0%), rates increased after 2002 in women 50-74 years old (2.5%; P-APC comparison < 0.0