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 < 0.01). Endometrial cancer incidence increased over the entire time period among women ages 20-49 (1992-2002: 1.1%; 2003-2009: 2.1%; P-APC comparison = 0.21). Post-2002 increases in incidence among women ages 50-74 were specific to Type I endometrial tumors (1992-2002: -0.6%; 2003-2009: 1.6%; P-APC comparison < 0.01).
Discussion: The increase in endometrial cancer incidence rates after 2002 may be related to the widespread decrease in estrogen plus progestin MHT use, which has been reported to lower endometrial cancer risk in overweight and obese women. Published by Elsevier Ltd.
C1 [Wartko, Paige; Sherman, Mark E.; Yang, Hannah P.; Felix, Ashley S.; Brinton, Louise A.; Trabert, Britton] NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, Rockville, MD USA.
RP Trabert, B (reprint author), 6120 Executive Blvd, Rockville, MD 20852 USA.
EM britton.trabert@nih.gov
RI Brinton, Louise/G-7486-2015; Trabert, Britton/F-8051-2015; Felix,
Ashley/A-3240-2016
OI Brinton, Louise/0000-0003-3853-8562;
FU National Institutes of Health, Division of Cancer Epidemiology and
Genetics, National Cancer Institute, Department of Health and Human
Services
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, Division of Cancer Epidemiology and
Genetics, National Cancer Institute, Department of Health and Human
Services.
NR 15
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U1 0
U2 7
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 374
EP 377
DI 10.1016/j.canep.2013.03.008
PG 4
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 179FE
UT WOS:000321504300005
PM 23591011
ER
PT J
AU Stang, A
Jansen, L
Trabert, B
Rusner, C
Eberle, A
Katalinic, A
Emrich, K
Holleczek, B
Brenner, H
AF Stang, A.
Jansen, L.
Trabert, B.
Rusner, C.
Eberle, A.
Katalinic, A.
Emrich, K.
Holleczek, B.
Brenner, H.
CA GEKID Canc Survival Working Grp
TI Survival after a diagnosis of testicular germ cell cancers in Germany
and the United States, 2002-2006: A high resolution study by histology
and age
SO CANCER EPIDEMIOLOGY
LA English
DT Article
DE Testicular neoplasms; Germinoma; Seminoma; Nonseminomatous germ cell
tumor; Survival; Germany; United States
ID PERIOD ANALYSIS; TRENDS; EUROPE; CLASSIFICATION; TUMORS; WALES;
EUROCARE-4; CARCINOMA; MORTALITY; ENGLAND
AB Introduction: The aim of this study was to provide detailed age-specific (5-year age groups) and histology-specific (histologic subtypes of seminoma and nonseminoma) relative survival estimates of testicular germ cell cancer patients in Germany and the United States (U.S.) for the years 2002-2006 and to compare these estimates between countries. Methods: We pooled data from 11 cancer registries of Germany and used data from the U.S. (SEER-13 database) including 11,508 and 10,774 newly diagnosed cases (1997-2006) in Germany and the U.S., respectively. We estimated 5-year relative survival (5-year-RS) by histology and age based on period analysis. Results: 5-year-RS for testicular germ cell tumors was 96.7% and 96.3% in Germany and the U.S., respectively. 5-Year-RS for spermatocytic seminoma was close to 100% in both countries. 5-Year-RS for nonseminoma was lower than for classical seminoma in Germany (93.3% versus 97.6%) and the U.S. (91.0% versus 98.2%). Among nonseminomas, choriocarcinomas provided the lowest 5-year-RS in both countries (Germany 80.1%, U.S. 79.6%). Age-specific 5-year-RS for seminoma showed only little variation by age. 5-Year-RS for nonseminomas tended to be lower at higher ages, especially for malignant teratoma. Discussion: This is the first study that provides up-to-date survival estimates for testicular cancer by histology and age in Germany and the U.S. Survival after a diagnosis of testicular cancer is very comparable between Germany and the U.S. 5-Year-RS for spermatocytic seminoma was close to 100% and the lowest 5-year-RS occurred among choriocarcinoma. Higher age at diagnosis is associated with a poorer prognosis among nonseminoma patients. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Stang, A.; Rusner, C.] Univ Halle Wittenberg, Inst Klin Epidemiol, Med Fak, D-06097 Halle, Germany.
[Stang, A.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Jansen, L.; Brenner, H.] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Trabert, B.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Eberle, A.] Leibniz Inst Prevent Res & Epidemiol, Bremen, Germany.
[Katalinic, A.] Med Univ Lubeck, Inst Canc Epidemiol, Canc Registry Schleswig Holstein, Lubeck, Germany.
[Emrich, K.] Canc Registry Rhineland Palatinate, Inst Med Biostat Epidemiol & Informat, Mainz, Germany.
[Holleczek, B.] Saarland Canc Registry, Saarbrucken, Germany.
RP Stang, A (reprint author), Univ Halle Wittenberg, Inst Klin Epidemiol, Med Fak, Magdeburger Str 8, D-06097 Halle, Germany.
EM andreas.stang@uk-halle.de
RI Katalinic, Alexander/D-2512-2010; Trabert, Britton/F-8051-2015; Jansen,
Lina/D-7255-2016; Brenner, Hermann/B-4627-2017
OI Katalinic, Alexander/0000-0003-0490-1554; Jansen,
Lina/0000-0001-8004-4940; Brenner, Hermann/0000-0002-6129-1572
FU German Cancer Aid (Deutsche Krebshilfe) [108257]
FX This study was supported in part by a grant from the German Cancer Aid
(Deutsche Krebshilfe), no. 108257.
NR 34
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U1 0
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1877-7821
J9 CANCER EPIDEMIOL
JI Cancer Epidemiol.
PD AUG
PY 2013
VL 37
IS 4
BP 492
EP 497
DI 10.1016/j.canep.2013.03.017
PG 6
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 179FE
UT WOS:000321504300024
PM 23623488
ER
PT J
AU Surewaard, BGJ
de Haas, CJC
Vervoort, F
Rigby, KM
DeLeo, FR
Otto, M
van Strijp, JAG
Nijland, R
AF Surewaard, B. G. J.
de Haas, C. J. C.
Vervoort, F.
Rigby, K. M.
DeLeo, F. R.
Otto, M.
van Strijp, J. A. G.
Nijland, R.
TI Staphylococcal alpha-phenol soluble modulins contribute to neutrophil
lysis after phagocytosis
SO CELLULAR MICROBIOLOGY
LA English
DT Article
ID PANTON-VALENTINE LEUKOCIDIN; B TYPE-I; VIRULENCE DETERMINANTS; AUREUS
INFECTIONS; IMMUNE EVASION; TOXIN; MECHANISMS; PATHOGENESIS;
DESTRUCTION; EXPRESSION
AB Staphylococcus aureus community-acquired (CA) MRSA strains are highly virulent and can cause infections in otherwise healthy individuals. The most important mechanism of the host for clearing S.aureus is phagocytosis by neutrophils and subsequent killing of the pathogen. Especially CA-MRSA strains are very efficient in circumventing this neutrophil killing. Interestingly, only a relative small number of virulence factors have been associated with CA-MRSA, one of which are the phenol soluble modulins (PSMs). We have recently shown that the PSMs are functionally inhibited by serum lipoproteins, indicating that PSMs may exert their cytolytic function primarily in the intracellular environment. To further investigate the intracellular role of the PSMs we measured the effect of the -type and -type PSMs on neutrophil killing after phagocytosis. Using fluorescently labelled S.aureus, we measured bacterial survival after phagocytosis in a plate reader, which was employed next to flow cytometry and time-lapse microscopy. Phagocytosis of the CA-MRSA strain MW2 by human neutrophils resulted in rapid host cell death. Using mutant strains of MW2, we demonstrated that in the presence of serum, the intracellular expression of only the psm operon is both necessary and sufficient for both increasedneutrophil cell death and increased survival of S.aureus. Our results identify PSM peptides as prominent contributors to killing of neutrophils after phagocytosis, a finding with major implications for our understanding of S.aureus pathogenesis and strategies for S.aureus vaccine development.
C1 [Surewaard, B. G. J.; de Haas, C. J. C.; Vervoort, F.; van Strijp, J. A. G.; Nijland, R.] Univ Med Ctr Utrecht, Utrecht, Netherlands.
[Rigby, K. M.; DeLeo, F. R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Otto, M.] NIAID, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA.
RP van Strijp, JAG (reprint author), Univ Med Ctr Utrecht, Utrecht, Netherlands.
EM J.vanStrijp@umcutrecht.nl
RI van Strijp, Jos/J-9549-2014; Nijland, Reindert/B-8206-2008;
OI van Strijp, Jos/0000-0001-6253-0830; Nijland,
Reindert/0000-0003-0049-3768; DeLeo, Frank/0000-0003-3150-2516; Otto,
Michael/0000-0002-2222-4115
FU European Community [268324]; National Institute of Allergy and
Infectious Diseases, US National Institutes of Health
FX The authors thank Alexander Horswill for providing the GFP expression
plasmid pCM29. R. N. was partially funded by a Marie Curie European
Re-integration Grants (ERG) from the European Community's Seventh
Framework Programme, project number 268324. M. O., K. R. and F. D. are
supported by the Intramural Research Program of the National Institute
of Allergy and Infectious Diseases, US National Institutes of Health.
NR 45
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U1 0
U2 16
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1462-5814
J9 CELL MICROBIOL
JI Cell Microbiol.
PD AUG
PY 2013
VL 15
IS 8
BP 1427
EP 1437
DI 10.1111/cmi.12130
PG 11
WC Cell Biology; Microbiology
SC Cell Biology; Microbiology
GA 182QI
UT WOS:000321758400012
PM 23470014
ER
PT J
AU Gabriel, S
Blanchet, EM
Sebag, F
Chen, CC
Fakhry, N
Deveze, A
Barlier, A
Morange, I
Pacak, K
Taieb, D
AF Gabriel, Sophie
Blanchet, Elise M.
Sebag, Frederic
Chen, Clara C.
Fakhry, Nicolas
Deveze, Arnaud
Barlier, Anne
Morange, Isabelle
Pacak, Karel
Taieb, David
TI Functional characterization of nonmetastatic paraganglioma and
pheochromocytoma by F-18-FDOPA PET: focus on missed lesions
SO CLINICAL ENDOCRINOLOGY
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; MALIGNANT PHEOCHROMOCYTOMAS; EXTRAADRENAL
PARAGANGLIOMAS; IMAGING FEATURES; SCINTIGRAPHY; MUTATIONS; CELLS; SPECT;
GENE
AB Aims and methods To evaluate the clinical value of F-18-fluorodihydroxyphenylalanine (F-18-FDOPA) PET in relation to tumour localization and the patient's genetic status in a large series of pheochromocytoma/paraganglioma (PHEO/PGL) patients and to discuss in detail false-negative results.
A retrospective study of PGL patients who were investigated with F-18-FDOPA PET or PET/CT imaging in two academic endocrine tumour centres was conducted (La Timone University Hospital, Marseilles, France and National Institutes of Health (NIH), Bethesda, MD, USA).
Results One hundred sixteen patients (39.7% harbouring germline mutations in known disease susceptibility genes) were evaluated for a total of 195 PHEO/PGL foci. F-18-FDOPA PET correctly detected 179 lesions (91.8%) in 107 patients (92.2%).
Lesion-based sensitivities for parasympathetic PGLs (head, neck, or anterior/middle thoracic ones), PHEOs, and extra-adrenal sympathetic (abdominal or posterior thoracic) PGLs were 98.2% [96.5% for Timone and 100% for NIH], 93.9% [93.8 and 93.9%] and 70.3% [47.1 and 90%] respectively (P < 0.001).
Sympathetic (adrenal and extra-adrenal) SDHx-related PGLs were at a higher risk for negative F-18-FDOPA PET than non-SDHx-related PGLs (14/24 vs 0/62, respectively, P < 0.001). In contrast, the risk of negative F-18-FDOPA PET was lower for parasympathetic PGLs regardless of the genetic background (1/90 in SDHx vs 1/19 in non-SDHx tumours, P = 0.32).
F-18-FDOPA PET failed to detect two head and neck PGLs (HNPGL), likely due to their small size, whereas most missed sympathetic PGL were larger and may have exhibited a specific F-18-FDOPA-negative imaging phenotype. F-18-FDG PET detected all the missed sympathetic lesions.
Conclusions F-18-FDOPA PET appears to be a very sensitive functional imaging tool for HNPGL regardless of the genetic status of the tumours. Patients with false-negative tumours on F-18-FDOPA PET should be tested for SDHx mutations.
C1 [Gabriel, Sophie; Taieb, David] Aix Marseille Univ, CERIMED, La Timone Univ Hosp, Dept Nucl Med, Marseille, France.
[Blanchet, Elise M.; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Sebag, Frederic] Aix Marseille Univ, La Timone Univ Hosp, Dept Endocrine Surg, Marseille, France.
[Chen, Clara C.] NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA.
[Chen, Clara C.] NIH, Imaging Sci Dept, Ctr Clin, Bethesda, MD 20892 USA.
[Fakhry, Nicolas] Aix Marseille Univ, Dept Otorhinolaryngol Head & Neck Surg, La Timone Univ Hosp, Marseille, France.
[Deveze, Arnaud] Aix Marseille Univ, Dept Otorhinolaryngol Head & Neck Surg, North Hosp, Marseille, France.
[Barlier, Anne] Aix Marseille Univ, Concept Hosp, Lab Biochem & Mol Biol, Marseille, France.
[Morange, Isabelle] Aix Marseille Univ, Dept Endocrinol, La Timone Univ Hosp, Marseille, France.
RP Taieb, D (reprint author), Aix Marseille Univ, European Ctr Res Med Imaging CERIMED, La Timone Univ Hosp, Dept Nucl Med, Marseille, France.
EM david.taieb@ap-hm.fr
OI Barlier, Anne/0000-0002-3740-6173
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Development; National Institute of
Neurological Disorders and Stroke at the National Institutes of Health
FX The authors thank Victoria Martucci for her technical assistance in the
preparation of this manuscript. This research was supported by the
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Development and the National Institute of
Neurological Disorders and Stroke at the National Institutes of Health.
NR 25
TC 21
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U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0300-0664
J9 CLIN ENDOCRINOL
JI Clin. Endocrinol.
PD AUG
PY 2013
VL 79
IS 2
BP 170
EP 177
DI 10.1111/cen.12126
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 180CP
UT WOS:000321570800005
PM 23230826
ER
PT J
AU Swaroop, A
Sieving, PA
AF Swaroop, A.
Sieving, P. A.
TI The golden era of ocular disease gene discovery: Race to the finish
SO CLINICAL GENETICS
LA English
DT Article
DE clinical management; genetics; next-generation sequencing; ocular
disease; therapies; vision
ID COMPLEMENT FACTOR-H; LEBER CONGENITAL AMAUROSIS; MACULAR DEGENERATION;
RETINITIS-PIGMENTOSA; RPE65 MUTATIONS; SUSCEPTIBILITY; POLYMORPHISM;
THERAPY; RETINOBLASTOMA; PREDISPOSES
AB Within the last decade, technological advances have led to amazing genetic insights into Mendelian and multifactorial ocular diseases. We provide a perspective of the progress in gene discovery and discuss the implications. We believe that the time has come to redefine the goals and begin utilizing the genetic knowledge for clinical management and treatment design. The unbelievable opportunities now exist for those nimble enough to seize them.
C1 [Swaroop, A.; Sieving, P. A.] NEI, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Swaroop, A (reprint author), NEI, Natl Inst Hlth, Bethesda, MD 20892 USA.
EM swaroopa@nei.nih.gov
OI Swaroop, Anand/0000-0002-1975-1141
FU Intramural NIH HHS [ZIA EY000475-06]
NR 31
TC 6
Z9 6
U1 0
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9163
J9 CLIN GENET
JI Clin. Genet.
PD AUG
PY 2013
VL 84
IS 2
BP 99
EP 101
DI 10.1111/cge.12204
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA 179CN
UT WOS:000321495800001
PM 23713688
ER
PT J
AU Shiels, A
Hejtmancik, JF
AF Shiels, A.
Hejtmancik, J. F.
TI Genetics of human cataract
SO CLINICAL GENETICS
LA English
DT Review
DE cataract; genetics; lens; mutations
ID AGE-RELATED CATARACT; FLUID CIRCULATION MODEL; RISK-FACTORS; CONGENITAL
CATARACT; CHINESE POPULATION; CRITICAL-APPRAISAL; CORTICAL CATARACT; EYE
LENS; PROTEIN; EPHA2
AB The pathogenesis of inherited cataracts of all kinds recapitulates the developmental and cell biology of the lens. Just as each novel mutation provides additional information about the structural or functional biology of the affected gene, each newly identified gene provides insight into the developmental and cellular biology of the lens. The set of genes currently known to be associated with cataract is far from complete, especially for age-related cataract, and there is much additional information to be discovered through further genetic studies.
C1 [Shiels, A.] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA.
[Hejtmancik, J. F.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
RP Hejtmancik, JF (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
EM f3h@helix.nih.gov
FU NEI NIH HHS [R01 EY012284]
NR 45
TC 45
Z9 50
U1 4
U2 25
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9163
J9 CLIN GENET
JI Clin. Genet.
PD AUG
PY 2013
VL 84
IS 2
BP 120
EP 127
DI 10.1111/cge.12182
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 179CN
UT WOS:000321495800004
PM 23647473
ER
PT J
AU Ratnapriya, R
Chew, EY
AF Ratnapriya, R.
Chew, E. Y.
TI Age-related macular degenerationclinical review and genetics update
SO CLINICAL GENETICS
LA English
DT Review
DE age-related macular degeneration; disease management; exome-chip; GWAS;
rare-variant association; risk prediction; whole-exome sequencing;
whole-genome sequencing
ID COMPLEMENT FACTOR-H; GENOME-WIDE ASSOCIATION; FATTY-ACID INTAKE;
RISK-FACTORS; SUSCEPTIBILITY LOCI; APOLIPOPROTEIN-E; CLINICAL-TRIAL; EYE
DISEASE; VARIANT; RANIBIZUMAB
AB Age-related macular degeneration (AMD) is the leading cause of central vision impairment in persons over the age of 50 years in developed countries. Both genetic and non-genetic (environmental) factors play major roles in AMD etiology, and multiple gene variants and lifestyle factors such as smoking have been associated with the disease. While dissecting the basic etiology of the disease remains a major challenge, current genetic knowledge has provided opportunities for improved risk assessment, molecular diagnosis and clinical testing of genetic variants in AMD treatment and management. This review addresses the potential of translating the wealth of genetic findings for improved risk prediction and therapeutic intervention in AMD patients. Finally, we discuss the recent advancement in genetics and genomics and the future prospective of personalized medicine in AMD patients.
C1 [Ratnapriya, R.] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
[Chew, E. Y.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
RP Chew, EY (reprint author), NEI, Div Epidemiol & Clin Applicat, NIH, Bldg 10,CRC Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA.
EM echew@nei.nih.gov
FU Intramural NIH HHS [ZIA AT000018-02]
NR 71
TC 28
Z9 30
U1 0
U2 25
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9163
J9 CLIN GENET
JI Clin. Genet.
PD AUG
PY 2013
VL 84
IS 2
BP 160
EP 166
DI 10.1111/cge.12206
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 179CN
UT WOS:000321495800009
PM 23713713
ER
PT J
AU Blain, D
Goetz, KE
Ayyagari, R
Tumminia, SJ
AF Blain, D.
Goetz, K. E.
Ayyagari, R.
Tumminia, S. J.
TI eyeGENE (R): a vision community resource facilitating patient care and
paving the path for research through molecular diagnostic testing
SO CLINICAL GENETICS
LA English
DT Article
DE biorepository; clinical trials; diagnostic genotyping; eyeGENE; genetic
testing; ocular genetics; patient registry
ID LEBERS CONGENITAL AMAUROSIS; COMPLEMENT FACTOR-H; DOMINANT
RETINITIS-PIGMENTOSA; RETINAL GENE-THERAPY; HUMAN COLOR-VISION; MACULAR
DEGENERATION; MUTATIONS; DYSTROPHY; RPGR; RP2
AB Molecular genetics and genomics are revolutionizing the study and treatment of inherited eye diseases. In recognition of the impact of molecular genetics on vision and ophthalmology, the National Eye Institute established the National Ophthalmic Disease Genotyping and Phenotyping Network (eyeGENE (R)) as a multidirectional research initiative whereby a clinical component for patients diagnosed with inherited eye disease fosters research into the causes and mechanisms of these ophthalmic diseases. This is accomplished by broadening access to genetic diagnostic testing and maintaining a repository of DNA samples from clinically characterized individuals and their families to allow investigations of the causes, interventions, and management of genetic eye disorders. The eyeGENE (R) Network currently includes Clinical Laboratory Improvement Amendments (CLIA)-certified diagnostic laboratory partners, over 270 registered clinical organizations with 500 registered users from around the United States and Canada, and is now testing approximately 100 genes representing 35 inherited eye diseases. To date, the Network has received 4400 samples from individuals with rare inherited eye diseases, which are available for access by the vision research community. eyeGENE (R) is a model partnership between the U. S. federal government, eye health care providers, CLIA-approved molecular diagnostic laboratories, private industry, and scientists who represent a broad research constituency.
C1 [Blain, D.; Goetz, K. E.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Ayyagari, R.] Univ Calif, Jacobs Retina Ctr, Dept Ophthalmol, La Jolla, CA USA.
[Tumminia, S. J.] NEI, Off Director, NIH, Bethesda, MD 20892 USA.
RP Tumminia, SJ (reprint author), NEI, Off Director, NIH, 31 Ctr Dr,Room 6A03,POB 20814-2510, Bethesda, MD 20892 USA.
EM tumminias@nei.nih.gov
FU Department of Health and Human Services/National Institutes of
Health/National Eye Institute; [HHS-N-260-2007-00001-C]
FX The eyeGENE (R) Network is supported by the Department of Health and
Human Services/National Institutes of Health/National Eye Institute
intramural program under eyeGENE (R) - Protocol 06-EI-0236 which has
been funded in part under Contract No. HHS-N-260-2007-00001-C. The
authors would also like to thank Dr. Wadih Zein, National Eye Institute,
for providing the data and the photographs presented in the case studies
and the eyeGENE (R) Network participants for their valuable
contributions to this research.
NR 39
TC 8
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U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9163
J9 CLIN GENET
JI Clin. Genet.
PD AUG
PY 2013
VL 84
IS 2
BP 190
EP 197
DI 10.1111/cge.12193
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 179CN
UT WOS:000321495800013
PM 23662816
ER
PT J
AU Altarakemah, Y
Al-Sane, M
Lim, S
Kingman, A
Ismail, AI
AF Altarakemah, Yacoub
Al-Sane, Mona
Lim, Sungwoo
Kingman, Albert
Ismail, Amid I.
TI A new approach to reliability assessment of dental caries examinations
SO COMMUNITY DENTISTRY AND ORAL EPIDEMIOLOGY
LA English
DT Article
DE agreement; caries; epidemiology; reliability
ID ASSESSMENT SYSTEM ICDAS; IN-VITRO EXAMINATION; OCCLUSAL CARIES; CARIOUS
LESIONS; SCORING SYSTEMS; PRIMARY TEETH; REPRODUCIBILITY; PERFORMANCE;
PREVALENCE; ACCURACY
AB Objectives: The objective of this study is to evaluate reliability of the International Caries Detection and Assessment System (ICDAS) and identify sources of disagreement among eight Kuwaiti dentists with no prior knowledge of the system. Methods: A 90-min introductory e-course was introduced followed by an examination of extracted teeth using the ICDAS coding system on the first day. Then three sessions of clinical examinations were performed. This study only used the data from the last session where 705 tooth surfaces of 10 patients were examined to assess bias in caries examination and on which codes the examiners had the highest disagreement. Compared with the gold standard, we evaluated bias of the ICDAS coding using three approaches (Bland-Altman plot, maximum kappa statistic, and Bhapkar's chi-square test). Linear weighted kappa statistics were computed to assess interexaminer reliability. Results: Marginal ICDAS distributions for most examiners were significantly different from that of the gold standard (bias present). The primary source of these marginal differences was misclassifying sound surfaces as noncavitated lesions. Interexaminer reliability of the 3-level ICDAS (codes 0, 1-2, and 3-6) classification ranged between 0.43 and 0.73, indicating evidence of substantial inconsistency between examiners. The primary source of examiner differences was agreeing on diagnosing noncavitated lesions. Conclusion: This study highlights the importance of assessing both systematic and random sources of examiner agreement to correctly interpret kappa measures of reliability.
C1 [Altarakemah, Yacoub; Al-Sane, Mona] Kuwait Univ, Fac Dent, Kuwait 13110, Kuwait.
[Lim, Sungwoo; Ismail, Amid I.] Temple Univ, Kornberg Sch Dent, Philadelphia, PA 19122 USA.
[Kingman, Albert] NIDCR, NIH, Bethesda, MD USA.
RP Altarakemah, Y (reprint author), Kuwait Univ, Fac Dent, POB 24923, Kuwait 13110, Kuwait.
EM yacoub@hsc.edu.kw
NR 37
TC 9
Z9 10
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0301-5661
J9 COMMUNITY DENT ORAL
JI Community Dentist. Oral Epidemiol.
PD AUG
PY 2013
VL 41
IS 4
BP 309
EP 316
DI 10.1111/cdoe.12020
PG 8
WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational
Health
SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational
Health
GA 182NB
UT WOS:000321748900002
PM 23278284
ER
PT J
AU Li, WL
Mukouyama, YS
AF Li, Wenling
Mukouyama, Yoh-suke
TI Tissue-specific venous expression of the EPH family receptor EphB1 in
the skin vasculature
SO DEVELOPMENTAL DYNAMICS
LA English
DT Article
DE venous endothelial cell marker; venous development; EphB1; EphB4
ID CARDIOVASCULAR DEVELOPMENT; ARTERIAL DIFFERENTIATION; ENDOTHELIAL-CELLS;
ANGIOGENESIS; EPHRIN-B2; VEGF
AB Background: The major arteries and veins are formed early during development. The molecular tools to identify arterial and venous endothelial cells improve our understanding of arterial-venous differentiation and branching morphogenesis. Compared with arterial differentiation, relatively little is known about what controls venous development, due to lack of definitive molecular markers for venous endothelial cells. Results: Here we report that the antibody against EphB1, an EphB class receptor, makes it possible to establish a reliable whole-mount immunohistochemical analysis of venous identity with greater resolution than previously possible in embryonic and adult skin vasculature models. EphB1 expression is restricted to the entire venous vasculature throughout embryonic development to adulthood, whereas the previously established venous marker EphB4 is also detectable in lymphatic vasculature. This venous-restricted expression of EphB1 is established after the vascular remodeling of the primary capillary plexus has occurred. Compared with its venous-specific expression in the skin, however, EphB1 is not restricted to the venous vasculature in yolk sac, trunk and lung. Conclusions: These studies introduce EphB1 as a new venous-restricted marker in a tissue-specific and time-dependent manner. (C) 2013 Wiley Periodicals, Inc.
C1 [Li, Wenling; Mukouyama, Yoh-suke] NHLBI, Lab Stem Cell & Neurovasc Biol, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA.
RP Mukouyama, YS (reprint author), NHLBI, Lab Stem Cell & Neurovasc Biol, Genet & Dev Biol Ctr, NIH, Bldg 10-6C103,10 Ctr Dr, Bethesda, MD 20892 USA.
EM mukoyamay@mail.nih.gov
FU Intramural NIH HHS [ZIA HL005702-07]; NHLBI NIH HHS [HL005702-07, Z01
HL005702]
NR 25
TC 3
Z9 3
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1058-8388
J9 DEV DYNAM
JI Dev. Dyn.
PD AUG
PY 2013
VL 242
IS 8
BP 976
EP 988
DI 10.1002/dvdy.23985
PG 13
WC Anatomy & Morphology; Developmental Biology
SC Anatomy & Morphology; Developmental Biology
GA 183UT
UT WOS:000321843400009
PM 23649798
ER
PT J
AU Mattsson, K
Kallen, K
Longnecker, MP
Rignell-Hydbom, A
Rylander, L
AF Mattsson, K.
Kallen, K.
Longnecker, M. P.
Rignell-Hydbom, A.
Rylander, L.
TI Maternal smoking during pregnancy and daughters' risk of gestational
diabetes and obesity
SO DIABETOLOGIA
LA English
DT Article
DE Diabetes mellitus; Gestational diabetes; Intrauterine exposure; Maternal
smoking; Medical Birth Register; Obesity
ID SUBSEQUENT OBESITY; ADIPOSITY; CHILDHOOD; MELLITUS; METAANALYSIS;
OVERWEIGHT; EXPOSURE; WOMEN; FETAL
AB The primary aim of the study was to investigate the risk of developing gestational diabetes in women who were exposed to tobacco smoke in utero. Secondary aims were to assess the risk of obesity and non-gestational diabetes.
Data were retrieved from the Medical Birth Register of Sweden for women who were born in 1982 (when smoking data were first registered) or later and who had given birth to at least one child; 80,189 pregnancies were included. The associations between in utero smoking exposure (three categories: non-smokers, 1-9 cigarettes/day [moderately exposed] and > 9 cigarettes/day [heavily exposed]) and subsequent gestational diabetes (n = 291), non-gestational diabetes (n = 280) and obesity (n = 7,300) were assessed.
The adjusted ORs (aORs) of gestational diabetes were increased among women who were moderately (1.62, 95% CI 1.24, 2.13) and heavily (1.52, 95% CI 1.12, 2.06) exposed. The corresponding aORs of obesity were 1.36 (95% CI 1.28, 1.44) and 1.58 (95% CI 1.48, 1.68), respectively. A reduced OR for non-gestational diabetes was seen in the offspring of heavy smokers (aOR 0.66, 95% CI 0.45, 0.96).
Women exposed to smoking during fetal life were at higher risk of developing gestational diabetes and obesity.
C1 [Mattsson, K.; Kallen, K.; Rignell-Hydbom, A.; Rylander, L.] Lund Univ, Inst Lab Med, Div Occupat & Environm Med, SE-22185 Lund, Sweden.
[Longnecker, M. P.] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Mattsson, K (reprint author), Lund Univ, Inst Lab Med, Div Occupat & Environm Med, SE-22185 Lund, Sweden.
EM kristina.mattsson@med.lu.se
OI Mattsson, Kristina/0000-0002-9850-5888; Longnecker,
Matthew/0000-0001-6073-5322
FU Lund University and its Medical Faculty; Lund University and its
networks SIMSAM Early Life; Swedish Research Council; METALUND; Swedish
Council for Working Life and Social Research; Intramural Research
Program of the National Institutes of Health (NIH), National Institute
of Environmental Health Sciences (NIEHS)
FX The research was supported by Lund University and its Medical Faculty
and the networks SIMSAM Early Life (with funding from The Swedish
Research Council) and METALUND (with funding from Swedish Council for
Working Life and Social Research). The research was also supported in
part by the Intramural Research Program of the National Institutes of
Health (NIH), National Institute of Environmental Health Sciences
(NIEHS).
NR 28
TC 12
Z9 12
U1 1
U2 18
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD AUG
PY 2013
VL 56
IS 8
BP 1689
EP 1695
DI 10.1007/s00125-013-2936-7
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 176EB
UT WOS:000321285400003
PM 23699990
ER
PT J
AU Lee, HS
Briese, T
Winkler, C
Rewers, M
Bonifacio, E
Hyoty, H
Pflueger, M
Simell, O
She, JX
Hagopian, W
Lernmark, A
Akolkar, B
Krischer, JP
Ziegler, AG
AF Lee, H-S
Briese, T.
Winkler, C.
Rewers, M.
Bonifacio, E.
Hyoty, H.
Pflueger, M.
Simell, O.
She, J. X.
Hagopian, W.
Lernmark, A.
Akolkar, B.
Krischer, J. P.
Ziegler, A. G.
CA TEDDY Study Grp
TI Next-generation sequencing for viruses in children with rapid-onset type
1 diabetes
SO DIABETOLOGIA
LA English
DT Article
DE GB virus C; Human herpes virus 6; Human rhinovirus C; Infections; Islet
autoimmunity; Next-generation deep sequencing; Parvovirus B19; TEDDY
study; Type 1 diabetes mellitus
ID NO EVIDENCE; INFECTION; IDENTIFICATION; PATHOGENESIS; MELLITUS;
DISEASES; RISK
AB Viruses are candidate causative agents in the pathogenesis of autoimmune (type 1) diabetes. We hypothesised that children with a rapid onset of type 1 diabetes may have been exposed to such agents shortly before the initiation of islet autoimmunity, possibly at high dose, and thus study of these children could help identify viruses involved in the development of autoimmune diabetes.
We used next-generation sequencing to search for viruses in plasma samples and examined the history of infection and fever in children enrolled in The Environmental Determinants of Diabetes in the Young (TEDDY) study who progressed to type 1 diabetes within 6 months from the appearance of islet autoimmunity, and in matched islet-autoantibody-negative controls.
Viruses were not detected more frequently in plasma from rapid-onset patients than in controls during the period surrounding seroconversion. In addition, infection histories were found to be similar between children with rapid-onset diabetes and control children, although episodes of fever were reported less frequently in children with rapid-onset diabetes.
These findings do not support the presence of viraemia around the time of seroconversion in young children with rapid-onset type 1 diabetes.
C1 [Lee, H-S; Krischer, J. P.] Univ S Florida, Dept Pediat, Pediat Epidemiol Ctr, Tampa, FL 33620 USA.
[Briese, T.] Columbia Univ, Mailman Sch Publ Hlth, Ctr Infect & Immun, New York, NY USA.
[Briese, T.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
[Winkler, C.; Ziegler, A. G.] Forschergrp Diabet eV, Neuherberg, Germany.
[Winkler, C.; Pflueger, M.; Ziegler, A. G.] Helmholtz Zentrum Munchen, Diabet Res Inst, D-85764 Neuherberg, Germany.
[Winkler, C.; Pflueger, M.; Ziegler, A. G.] Tech Univ Munich, Klinikum Rechts Isar, Forschergrp Diabet, Neuherberg, Germany.
[Rewers, M.] Univ Colorado, Barbara Davis Ctr Childhood Diabet, Sch Med, Aurora, CO USA.
[Bonifacio, E.] Tech Univ Dresden, Ctr Regenerat Therapies Dresden, Dresden, Germany.
[Hyoty, H.] Univ Tampere, Dept Virol, FIN-33101 Tampere, Finland.
[Simell, O.] Turku Univ Cent Hosp, Dept Pediat, Turku, Finland.
[She, J. X.] Georgia Regents Univ, Med Coll Georgia, Ctr Biotechnol & Genom Med, Augusta, GA USA.
[Hagopian, W.] Pacific NW Diabet Res Inst, Seattle, WA USA.
[Lernmark, A.] Lund Univ, Dept Clin Sci, Skane Univ Hosp SUS, Malmo, Sweden.
[Akolkar, B.] Natl Inst Diabet & Digest & Kidney Disorders, Bethesda, MD USA.
[Ziegler, A. G.] Helmholtz Zentrum Munchen, D-85764 Neuherberg, Germany.
RP Ziegler, AG (reprint author), Helmholtz Zentrum Munchen, Ingolstodter Landstr 1, D-85764 Neuherberg, Germany.
EM anette-g.ziegler@helmholtz-muenchen.de
RI Ziegler, Anette-Gabriele/M-4614-2014; Bonifacio, Ezio/E-7700-2010
OI Ziegler, Anette-Gabriele/0000-0002-6290-5548; Bonifacio,
Ezio/0000-0002-8704-4713
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[DK 63829, 63861, 63821, 63865, 63863, 63836, 63790, UC4DK095300,
HHSN267200700014C]; National Institute of Allergy and Infectious
Diseases (NIAID); National Institute of Child Health and Human
Development (NICHD); National Institute of Environmental Health Sciences
(NIEHS); Juvenile Diabetes Research Foundation (JDRF); Centers for
Disease Control and Prevention (CDC)
FX The study was funded by DK 63829, 63861, 63821, 63865, 63863, 63836,
63790 and UC4DK095300 and contract number HHSN267200700014C from the
National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK), National Institute of Allergy and Infectious Diseases (NIAID),
National Institute of Child Health and Human Development (NICHD),
National Institute of Environmental Health Sciences (NIEHS), Juvenile
Diabetes Research Foundation (JDRF), and Centers for Disease Control and
Prevention (CDC).
NR 26
TC 11
Z9 12
U1 0
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD AUG
PY 2013
VL 56
IS 8
BP 1705
EP 1711
DI 10.1007/s00125-013-2924-y
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 176EB
UT WOS:000321285400005
PM 23657799
ER
PT J
AU Zhou, XL
Khan, SG
Tamura, D
Ueda, T
Boyle, J
Compe, E
Egly, JM
DiGiovanna, JJ
Kraemer, KH
AF Zhou, Xiaolong
Khan, Sikandar G.
Tamura, Deborah
Ueda, Takahiro
Boyle, Jennifer
Compe, Emmanuel
Egly, Jean-Marc
DiGiovanna, John J.
Kraemer, Kenneth H.
TI Abnormal XPD-induced nuclear receptor transactivation in DNA repair
disorders: trichothiodystrophy and xeroderma pigmentosum
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
DE TFIIH; DNA repair; transcription; vitamin D receptor; human development
ID NEUROLOGIC ABNORMALITIES; TRANSCRIPTION GENE; COCKAYNE-SYNDROME;
RESPONSIVE GENES; FACTOR TFIIH; SKIN-CANCER; MUTATIONS; ERCC2;
OSTEOPONTIN; PHOSPHORYLATION
AB XPD (ERCC2) is a DNA helicase involved in nucleotide excision repair and in transcription as a structural bridge tying the transcription factor IIH (TFIIH) core with the cdk-activating kinase complex, which phosphorylates nuclear receptors. Mutations in XPD are associated with several different phenotypes, including trichothiodystrophy (TTD), with sulfur-deficient brittle hair, bone defects, and developmental abnormalities without skin cancer, xeroderma pigmentosum (XP), with pigmentary abnormalities and increased skin cancer, or XP/TTD with combined features, including skin cancer. We describe the varied clinical features and mutations in nine patients examined at the National Institutes of Health who were compound heterozygotes for XPD mutations but had different clinical phenotypes: four TTD, three XP, and two combined XP/TTD. We studied TFIIH-dependent transactivation by nuclear receptor for vitamin D (VDR) and thyroid in cells from these patients. The vitamin D stimulation ratio of CYP24 and osteopontin was associated with specific pairs of mutations (reduced in 5, elevated in 1) but not correlated with distinct clinical phenotypes. Thyroid receptor stimulation ratio for KLF9 was not significantly different from normal. XPD mutations frequently were associated with abnormal VDR stimulation in compound heterozygote patients with TTD, XP, or XP/TTD.
C1 [Zhou, Xiaolong; Khan, Sikandar G.; Tamura, Deborah; Ueda, Takahiro; Boyle, Jennifer; DiGiovanna, John J.; Kraemer, Kenneth H.] NCI, Ctr Canc Res, Dermatol Branch, DNA Repair Sect, Bethesda, MD 20892 USA.
[Zhou, Xiaolong] NIH, Clin Res Training Program, Bethesda, MD 20892 USA.
[Ueda, Takahiro; Compe, Emmanuel; Egly, Jean-Marc] Inst Genet & Biol Mol & Cellulaire, Strasbourg, France.
[Ueda, Takahiro; Compe, Emmanuel; Egly, Jean-Marc] Inst Rech Cancers Appareil Digestif, Strasbourg, France.
RP Kraemer, KH (reprint author), NCI, Ctr Canc Res, Dermatol Branch, DNA Repair Sect, Bldg 37,Room 4002 MSC 4258, Bethesda, MD 20892 USA.
EM kraemerk@nih.gov
RI Compe, Emmanuel/N-8718-2016;
OI Zhou, Alan/0000-0002-6177-2472; Compe, Emmanuel/0000-0002-9189-7444
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health (NIH); European Research Council (ERC-TRANSREACT);
Clinical Research Training Program; NIH; Pfizer Inc.
FX This research was supported by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health (NIH) and by the European Research Council
(ERC-2008-TRANSREACT) (authors EC and J-ME). Support for author Zhou was
made possible through the Clinical Research Training Program, a
public-private partnership supported jointly by the NIH and Pfizer Inc.
(via a grant to the Foundation for NIH from Pfizer Inc.).
NR 47
TC 4
Z9 5
U1 2
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD AUG
PY 2013
VL 21
IS 8
BP 831
EP 837
DI 10.1038/ejhg.2012.246
PG 7
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 185FI
UT WOS:000321951100008
PM 23232694
ER
PT J
AU Moya, PR
Dodman, NH
Timpano, KR
Rubenstein, LM
Rana, Z
Fried, RL
Reichardt, LF
Heiman, GA
Tischfield, JA
King, RA
Galdzicka, M
Ginns, EI
Wendland, JR
AF Moya, Pablo R.
Dodman, Nicholas H.
Timpano, Kiara R.
Rubenstein, Liza M.
Rana, Zaker
Fried, Ruby L.
Reichardt, Louis F.
Heiman, Gary A.
Tischfield, Jay A.
King, Robert A.
Galdzicka, Marzena
Ginns, Edward I.
Wendland, Jens R.
TI Rare missense neuronal cadherin gene (CDH2) variants in specific
obsessive-compulsive disorder and Tourette disorder phenotypes
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
DE N-cadherin; CDH2; rare gene variants; canine compulsive disorder;
obsessive-compulsive disorder; Tourette disorder
ID DE-NOVO TRANSLOCATION; CELL-CELL-ADHESION; N-CADHERIN; BIPOLAR DISORDER;
ALPHA-CATENIN; SCHIZOPHRENIA; ASSOCIATION; EXPRESSION; MUTATIONS;
SUSCEPTIBILITY
AB The recent finding that the neuronal cadherin gene CDH2 confers a highly significant risk for canine compulsive disorder led us to investigate whether missense variants within the human ortholog CDH2 are associated with altered susceptibility to obsessive-compulsive disorder (OCD), Tourette disorder (TD) and related disorders. Exon resequencing of CDH2 in 320 individuals identified four non-synonymous single-nucleotide variants, which were subsequently genotyped in OCD probands, Tourette disorder probands and relatives, and healthy controls (total N=1161). None of the four variants was significantly associated with either OCD or TD. One variant, N706S, was found only in the OCD/TD groups, but not in controls. By examining clinical data, we found there were significant TD-related phenotype differences between those OCD probands with and without the N845S variant with regard to the co-occurrence of TD (Fisher's exact test P=0.014, OR=6.03). Both N706S and N845S variants conferred reduced CDH2 protein expression in transfected cells. Although our data provide no overall support for association of CDH2 rare variants in these disorders considered as single entities, the clinical features and severity of probands carrying the uncommon non-synonymous variants suggest that CDH2, along with other cadherin and cell adhesion genes, is an interesting gene to pursue as a plausible contributor to OCD, TD and related disorders with repetitive behaviors, including autism spectrum disorders.
C1 [Moya, Pablo R.; Rubenstein, Liza M.; Rana, Zaker; Fried, Ruby L.] NIMH, Clin Sci Lab, Intramural Res Program, Bethesda, MD 20819 USA.
[Dodman, Nicholas H.] Tufts Univ, Cummings Sch Vet Med, North Grafton, MA USA.
[Timpano, Kiara R.] Univ Miami, Coral Gables, FL 33124 USA.
[Reichardt, Louis F.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA USA.
[Heiman, Gary A.; Tischfield, Jay A.] Rutgers State Univ, Human Genet Inst New Jersey, Piscataway, NJ USA.
[Heiman, Gary A.; Tischfield, Jay A.] Rutgers State Univ, Dept Genet, Piscataway, NJ USA.
[King, Robert A.] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA.
[Galdzicka, Marzena; Ginns, Edward I.] Univ Massachusetts, Sch Med, UMass Mem Med Ctr, Mol Diagnost Lab, Worcester, MA USA.
[Galdzicka, Marzena; Ginns, Edward I.] Univ Massachusetts, Sch Med, UMass Mem Med Ctr, Clin Labs, Worcester, MA USA.
[Wendland, Jens R.] F Hoffman La Roche Ltd, Pharma Res & Early Dev, Basel, Switzerland.
RP Moya, PR (reprint author), NIMH, Clin Sci Lab, Intramural Res Program, NIH, 10-3D41,10 Ctr Dr, Bethesda, MD 20819 USA.
EM moyap@mail.nih.gov
OI Tischfield, Jay/0000-0003-3217-8287; Timpano, Kiara/0000-0002-0665-8722
FU New Jersey Center for Tourette Syndrome and Associated Disorders; NIMH
[R01MH092293]; Simons Foundation
FX We are indebted to Diane Kazuba and Brenda Justement for conducting
proband interviews, to Teresa Tolliver and Su-Jan Huang for excellent
technical assistance in DNA extraction and general lab assistance and to
Theresa DeGuzman for development of the OCD phenotype database and
editing and graphical assistance with this manuscript. GA Heiman, RA
King and JA Tischfield are supported by grants from the New Jersey
Center for Tourette Syndrome and Associated Disorders and NIMH
(R01MH092293). Support for the experimental studies was from the NIMH
Intramural Research Program and a grant from the Simons Foundation (LF
Reichardt).
NR 65
TC 9
Z9 9
U1 1
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD AUG
PY 2013
VL 21
IS 8
BP 850
EP 854
DI 10.1038/ejhg.2012.245
PG 5
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 185FI
UT WOS:000321951100011
PM 23321619
ER
PT J
AU Amin, N
Hottenga, JJ
Hansell, NK
Janssens, ACJW
de Moor, MHM
Madden, PAF
Zorkoltseva, IV
Penninx, BW
Terracciano, A
Uda, M
Tanaka, T
Esko, T
Realo, A
Ferrucci, L
Luciano, M
Davies, G
Metspalu, A
Abecasis, GR
Deary, IJ
Raikkonen, K
Bierut, LJ
Costa, PT
Saviouk, V
Zhu, G
Kirichenko, AV
Isaacs, A
Aulchenko, YS
Willemsen, G
Heath, AC
Pergadia, ML
Medland, SE
Axenovich, TI
de Geus, E
Montgomery, GW
Wright, MJ
Oostra, BA
Martin, NG
Boomsma, DI
van Duijn, CM
AF Amin, Najaf
Hottenga, Jouke-Jan
Hansell, Narelle K.
Janssens, A. Cecile J. W.
de Moor, Marleen H. M.
Madden, Pamela A. F.
Zorkoltseva, Irina V.
Penninx, Brenda W.
Terracciano, Antonio
Uda, Manuela
Tanaka, Toshiko
Esko, Tonu
Realo, Anu
Ferrucci, Luigi
Luciano, Michelle
Davies, Gail
Metspalu, Andres
Abecasis, Goncalo R.
Deary, Ian J.
Raikkonen, Katri
Bierut, Laura J.
Costa, Paul T.
Saviouk, Viatcheslav
Zhu, Gu
Kirichenko, Anatoly V.
Isaacs, Aaron
Aulchenko, Yurii S.
Willemsen, Gonneke
Heath, Andrew C.
Pergadia, Michele L.
Medland, Sarah E.
Axenovich, Tatiana I.
de Geus, Eco
Montgomery, Grant W.
Wright, Margaret J.
Oostra, Ben A.
Martin, Nicholas G.
Boomsma, Dorret I.
van Duijn, Cornelia M.
TI Refining genome-wide linkage intervals using a meta-analysis of
genome-wide association studies identifies loci influencing personality
dimensions
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
DE personality; KCNJ1; NEO; linkage; GSMA
ID A BEHAVIOR PATTERN; COGNITIVE IMPAIRMENT; SEARCH METAANALYSIS;
ALZHEIMERS-DISEASE; GENDER-DIFFERENCES; MAJOR DEPRESSION; LARGE
PEDIGREES; TRAITS; NEUROTICISM; POPULATION
AB Personality traits are complex phenotypes related to psychosomatic health. Individually, various gene finding methods have not achieved much success in finding genetic variants associated with personality traits. We performed a meta-analysis of four genome-wide linkage scans (N=6149 subjects) of five basic personality traits assessed with the NEO Five-Factor Inventory. We compared the significant regions from the meta-analysis of linkage scans with the results of a meta-analysis of genome-wide association studies (GWAS) (N similar to 17 000). We found significant evidence of linkage of neuroticism to chromosome 3p14 (rs1490265, LOD=4.67) and to chromosome 19q13 (rs628604, LOD=3.55); of extraversion to 14q32 (ATGG002, LOD=3.3); and of agreeableness to 3p25 (rs709160, LOD=3.67) and to two adjacent regions on chromosome 15, including 15q13 (rs970408, LOD=4.07) and 15q14 (rs1055356, LOD=3.52) in the individual scans. In the meta-analysis, we found strong evidence of linkage of extraversion to 4q34, 9q34, 10q24 and 11q22, openness to 2p25, 3q26, 9p21, 11q24, 15q26 and 19q13 and agreeableness to 4q34 and 19p13. Significant evidence of association in the GWAS was detected between openness and rs677035 at 11q24 (P-value=2.6 x 10(-06), KCNJ1). The findings of our linkage meta-analysis and those of the GWAS suggest that 11q24 is a susceptible locus for openness, with KCNJ1 as the possible candidate gene.
C1 [Amin, Najaf; Isaacs, Aaron; Aulchenko, Yurii S.; Oostra, Ben A.; van Duijn, Cornelia M.] Erasmus Univ, Dept Epidemiol & Biostat, Med Ctr, Unit Genet Epidemiol, NL-3000 DR Rotterdam, Netherlands.
[Hottenga, Jouke-Jan; de Moor, Marleen H. M.; Saviouk, Viatcheslav; Willemsen, Gonneke; de Geus, Eco; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
[Hansell, Narelle K.; Zhu, Gu; Medland, Sarah E.; Montgomery, Grant W.; Wright, Margaret J.; Martin, Nicholas G.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Janssens, A. Cecile J. W.] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Madden, Pamela A. F.; Bierut, Laura J.; Heath, Andrew C.; Pergadia, Michele L.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Zorkoltseva, Irina V.; Kirichenko, Anatoly V.; Axenovich, Tatiana I.] Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia.
[Penninx, Brenda W.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9713 AV Groningen, Netherlands.
[Penninx, Brenda W.] Leiden Univ, Dept Clin Psychol, Leiden, Netherlands.
[Penninx, Brenda W.] Leiden Univ, Dept Psychiat, Leiden, Netherlands.
[Penninx, Brenda W.] VU Univ Med Ctr Amsterdam, Dept Psychiat, EMGO Inst, Amsterdam, Netherlands.
[Terracciano, Antonio; Tanaka, Toshiko; Ferrucci, Luigi; Costa, Paul T.] NIA, NIH, Baltimore, MD 21224 USA.
[Uda, Manuela] CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy.
[Esko, Tonu; Realo, Anu; Metspalu, Andres] Univ Tartu, Estonian Genome Project, EE-50090 Tartu, Estonia.
[Esko, Tonu; Realo, Anu; Metspalu, Andres] Estonian Bioctr, Tartu, Estonia.
[Luciano, Michelle; Davies, Gail; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.
[Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Raikkonen, Katri] Univ Helsinki, Dept Psychol, SF-00100 Helsinki, Finland.
[Oostra, Ben A.] Erasmus Univ, Dept Clin Genet, Med Ctr, NL-3000 DR Rotterdam, Netherlands.
[van Duijn, Cornelia M.] Netherlands Consortium Hlth Aging, Ctr Med Syst Biol, The Hague, Netherlands.
[van Duijn, Cornelia M.] Natl Genom Initiat, The Hague, Netherlands.
RP van Duijn, CM (reprint author), Erasmus MC, Dept Epidemiol & Biostat, Unit Genet Epidemiol, Dr Molewaterpl 50,POB 1738, NL-3015 GE Rotterdam, Netherlands.
EM c.vanduijn@erasmusmc.nl
RI terracciano, antonio/B-1884-2008; Aulchenko, Yurii/M-8270-2013; Medland,
Sarah/C-7630-2013; de Geus, Eco/M-9318-2015; Montgomery,
Grant/B-7148-2008; Hansell, Narelle/A-4553-2016; Wright,
Margaret/A-4560-2016; Realo, Anu/M-9524-2016; Luciano,
Michelle/F-7277-2010;
OI Aulchenko, Yurii/0000-0002-7899-1575; Medland,
Sarah/0000-0003-1382-380X; de Geus, Eco/0000-0001-6022-2666; Montgomery,
Grant/0000-0002-4140-8139; Hansell, Narelle/0000-0002-8229-9741; Wright,
Margaret/0000-0001-7133-4970; Luciano, Michelle/0000-0003-0935-7682;
Janssens, A Cecile/0000-0002-6153-4976; Abecasis,
Goncalo/0000-0003-1509-1825; Esko, Tonu/0000-0003-1982-6569; Costa,
Paul/0000-0003-4375-1712; Raikkonen, Katri/0000-0003-3124-3470; Martin,
Nicholas/0000-0003-4069-8020
FU EUROSPAN (European Special Populations Research Network); European
Commission [018947, LSHG-CT-2006-01947]; Netherlands Organization for
Scientific Research; Erasmus MC; Center for Medical Systems Biology
(CMSB); Netherlands Brain Foundation (HersenStichting Nederland);
Netherlands Organization for Scientific Research (NWO) [575-25-006,
480-04-004, 904-61-090, 904-61-193, 400-05-717]; Spinozapremie SPI
[56-464-14192]; ZonMW [311-60008, 10-000-1002]; Center for Medical
Systems Biology (NWO Genomics), Neuroscience Campus Amsterdam; NIMH [R01
MH059160, MH081802]; Genetic Association Information Network (GAIN) of
the Foundation for the US National Institutes of Health; GAIN;
Australian Research Council [A7960034, A79906588, A79801419, DP0212016,
DP0343921]; Beyond Blue; Borderline Personality Disorder Research
Foundation; National Health and Medical Research Council [389891];
[EU/QLRT-2001-01254]
FX ERF: The genotyping for the ERF study was supported by EUROSPAN
(European Special Populations Research Network) and the European
Commission FP6 STRP Grant (018947; LSHG-CT-2006-01947). The ERF study
was further supported by grants from the Netherlands Organization for
Scientific Research, Erasmus MC, the Center for Medical Systems Biology
(CMSB) and the Netherlands Brain Foundation (HersenStichting Nederland).
We are grateful to all patients and their relatives, general
practitioners and neurologists for their contributions, and to P Veraart
for her help in genealogy, Jeannette Vergeer for the supervision of the
laboratory work and P Snijders for his help in data collection.; NTR: We
acknowledge financial support from the Netherlands Organization for
Scientific Research (NWO): Grants 575-25-006, 480-04-004, 904-61-090;
904-61-193, 400-05-717 and Spinozapremie SPI 56-464-14192. MHMdeM is
financially supported by ZonMW (Addiction) Grant number 311-60008. We
further acknowledge financial support from the Center for Medical
Systems Biology (NWO Genomics), Neuroscience Campus Amsterdam;
EU/QLRT-2001-01254; NIMH R01 MH059160; Geestkracht program of ZonMW
(10-000-1002); and matching funds from universities and mental health
care institutes involved in NESDA. Genotyping was funded by the Genetic
Association Information Network (GAIN) of the Foundation for the US
National Institutes of Health, and analysis was supported by grants from
GAIN and the NIMH (MH081802). Genotype data were obtained from dbGaP
(http://www.ncbi.nlm.nih.gov/dbgap, accession number phs000020.v1.p1).;
QIMR: We thank Marlene Grace and Ann Eldridge for sample collection;
Anjali Henders, Megan Campbell, Lisa Bowdler, Steven Crooks and staff of
the Molecular Epidemiology Laboratory for sample processing and
preparation; Harry Beeby, David Smyth and Daniel Park for IT support. We
acknowledge support from the Australian Research Council (A7960034,
A79906588, A79801419, DP0212016 and DP0343921), Beyond Blue and the
Borderline Personality Disorder Research Foundation. Genotyping was
funded by the National Health and Medical Research Council (Medical
Bioinformatics Genomics Proteomics Program, 389891). Further, we
gratefully acknowledge Drs Dale R Nyholt and especially Scott Gordon for
their substantial efforts involving the QC and preparation of the QIMR
and NAG/IRPG GWA data sets from which SNPs were selected. Dr Nyholt also
contributed 8% of the NAG/IRPG GWA cohort (NHMRC IDs 339462, 442981,
389938 and 496739). In addition, we thank him for helpful discussions
regarding methodology.
NR 65
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD AUG
PY 2013
VL 21
IS 8
BP 876
EP 882
DI 10.1038/ejhg.2012.263
PG 7
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 185FI
UT WOS:000321951100015
PM 23211697
ER
PT J
AU van Rhoon, GC
Samaras, T
Yarmolenko, PS
Dewhirst, MW
Neufeld, E
Kuster, N
AF van Rhoon, Gerard C.
Samaras, Theodoros
Yarmolenko, Pavel S.
Dewhirst, Mark W.
Neufeld, Esra
Kuster, Niels
TI CEM43A degrees C thermal dose thresholds: a potential guide for magnetic
resonance radiofrequency exposure levels?
SO EUROPEAN RADIOLOGY
LA English
DT Article
DE MRI; Thermal dose; Thermal threshold; Radiofrequency; CEM43 degrees C;
Safe exposure
ID DIAGNOSTIC ULTRASOUND; ELECTROMAGNETIC-FIELDS; TEMPERATURE THRESHOLD;
ABSORPTION RATE; BURN INJURY; BODY COIL; HYPERTHERMIA; HEAT; MR; SAR
AB To define thresholds of safe local temperature increases for MR equipment that exposes patients to radiofrequency fields of high intensities for long duration. These MR systems induce heterogeneous energy absorption patterns inside the body and can create localised hotspots with a risk of overheating.
The MRI + EUREKA research consortium organised a "Thermal Workshop on RF Hotspots". The available literature on thresholds for thermal damage and the validity of the thermal dose (TD) model were discussed.
The following global TD threshold guidelines for safe use of MR are proposed: 1. All persons: maximum local temperature of any tissue limited to 39 A degrees C
Persons with compromised thermoregulation AND (a) Uncontrolled conditions: maximum local temperature limited to 39 A degrees C
Controlled conditions: TD < 2 CEM43A degrees C
Persons with uncompromised thermoregulation AND (a) Uncontrolled conditions: TD < 2 CEM43A degrees C
Controlled conditions: TD < 9 CEM43A degrees C
The following definitions are applied: Controlled conditions A medical doctor or a dedicated trained person can respond instantly to heat-induced physiological stress
All persons with impaired systemic or reduced local thermoregulation
aEuro cent Standard MRI can cause local heating by radiofrequency absorption.
aEuro cent Monitoring thermal dose (in units of CEM43A degrees C) can control risk during MRI.
aEuro cent 9 CEM43A degrees C seems an acceptable thermal dose threshold for most patients.
aEuro cent For skin, muscle, fat and bone,16 CEM43A degrees C is likely acceptable.
C1 [van Rhoon, Gerard C.] Erasmus MC Canc Ctr, Dept Radiotherapy, Rotterdam, Netherlands.
[Samaras, Theodoros] Aristotle Univ Thessaloniki, Dept Phys, GR-54006 Thessaloniki, Greece.
[Yarmolenko, Pavel S.] Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA.
[Yarmolenko, Pavel S.] NIH, Ctr Intervent Oncol Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Dewhirst, Mark W.] Duke Univ, Dept Pathol, Durham, NC 27706 USA.
[Dewhirst, Mark W.] Duke Univ, Dept Radiat Oncol, Durham, NC USA.
[Neufeld, Esra; Kuster, Niels] ITIS Fdn, Zurich, Switzerland.
[van Rhoon, Gerard C.] Dept Radiat Oncol, Unit Hyperthermia, NL-3008 AE Rotterdam, Netherlands.
RP van Rhoon, GC (reprint author), Dept Radiat Oncol, Unit Hyperthermia, Room GS 02,Box 5201, NL-3008 AE Rotterdam, Netherlands.
EM g.c.vanrhoon@erasmusmc.nl
RI Samaras, Theodoros/I-5942-2012
OI Samaras, Theodoros/0000-0003-0170-4520
FU EUREKA [E4144]; CTI project MRI+ [9193.1]; The Netherlands Organization
for Health Research and Development ZonMw [85400003, 85800002]
FX This study was supported by the EUREKA (E4144) and CTI (9193.1) project
MRI+. This study was also supported by The Netherlands Organization for
Health Research and Development ZonMw project 85400003 and project
85800002.
NR 56
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U1 5
U2 21
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0938-7994
J9 EUR RADIOL
JI Eur. Radiol.
PD AUG
PY 2013
VL 23
IS 8
BP 2215
EP 2227
DI 10.1007/s00330-013-2825-y
PG 13
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 179MD
UT WOS:000321523500021
PM 23553588
ER
PT J
AU Ganini, D
Canistro, D
Jiang, JJ
Stadler, K
Mason, RP
Kadiiska, MB
AF Ganini, Douglas
Canistro, Donatella
Jiang, JinJie
Stadler, Krisztian
Mason, Ronald P.
Kadiiska, Maria B.
TI Ceruloplasmin (ferroxidase) oxidizes hydroxylamine probes: Deceptive
implications for free radical detection (vol 53, pg 1514, 2012)
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Correction
C1 [Ganini, Douglas; Jiang, JinJie; Mason, Ronald P.; Kadiiska, Maria B.] NIEHS, Free Rad Metab Sect, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
[Canistro, Donatella] Alma Mater Studiorum Univ Bologna, Mol Toxicol Unit, Dept Pharmacol, I-40126 Bologna, Italy.
[Stadler, Krisztian] Louisiana State Univ, Pennington Biomed Res Ctr, Oxidat Stress & Dis Lab, Baton Rouge, LA 70808 USA.
RP Kadiiska, MB (reprint author), NIEHS, Free Rad Metab Sect, Lab Toxicol & Pharmacol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM kadiiska@niehs.nih.gov
NR 1
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U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD AUG
PY 2013
VL 61
BP 10
EP 10
DI 10.1016/j.freeradbiomed.2013.03.013
PG 1
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 168EA
UT WOS:000320687300002
ER
PT J
AU Arguelles, S
Camandola, S
Hutchison, ER
Cutler, RG
Ayala, A
Mattson, MP
AF Argueelles, Sandro
Camandola, Simonetta
Hutchison, Emmette R.
Cutler, Roy G.
Ayala, Antonio
Mattson, Mark P.
TI Molecular control of the amount, subcellular location, and activity
state of translation elongation factor 2 in neurons experiencing stress
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Eukaryotic elongation factor 2; eEF-2; CRM1; 14.3.3; p53; Lipid
peroxidation; Hippocampal neurons; Free radicals
ID PROTEIN-SYNTHESIS; OXIDATIVE STRESS; EUKARYOTIC ELONGATION-FACTOR-2;
MAMMALIAN-CELLS; APOPTOSIS; RESPONSES; DISEASE; DEATH; P53;
HYDROPEROXIDE
AB Eukaryotic elongation factor 2 (eEF-2) is an important regulator of the protein translation machinery whereby it controls the movement of the ribosome along the mRNA. The activity of eEF-2 is regulated by changes in cellular energy status and nutrient availability and by posttranslational modifications such as phosphorylation and mono-ADP-ribosylation. However, the mechanisms regulating protein translation under conditions of cellular stress in neurons are unknown. Here we show that when rat hippocampal neurons experience oxidative stress (lipid peroxidation induced by exposure to cumene hydroperoxide; CH), eEF-2 is hyperphosphorylated and ribosylated, resulting in reduced translational activity. The degradation of eEF-2 requires calpain proteolytic activity and is accompanied by accumulation of eEF-2 in the nuclear compartment. The subcellular localization of both native and phosphorylated forms of eEF-2 is influenced by CRM1 and 14.3.3, respectively. In hippocampal neurons p53 interacts with nonphosphorylated (active) eEF-2, but not with its phosphorylated form. The p53-eEF-2 complexes are present in cytoplasm and nucleus, and their abundance increases when neurons experience oxidative stress. The nuclear localization of active eEF-2 depends upon its interaction with p53, as cells lacking p53 contain less active eEF-2 in the nuclear compartment. Overexpression of eEF-2 in hippocampal neurons results in increased nuclear levels of eEF-2 and decreased cell death after exposure to CH. Our results reveal novel molecular mechanisms controlling the differential subcellular localization and activity state of eEF-2 that may influence the survival status of neurons during periods of elevated oxidative stress. Published by Elsevier Inc.
C1 [Argueelles, Sandro; Camandola, Simonetta; Hutchison, Emmette R.; Cutler, Roy G.; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Argueelles, Sandro; Ayala, Antonio] Univ Seville, Dept Biochem & Mol Biol, Fac Pharm, E-41012 Seville, Spain.
[Hutchison, Emmette R.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA.
[Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
EM mattsonm@grc.nia.nih.gov
RI IBIS, ENVEJECIMIENTO/O-9381-2015;
OI Arguelles, Sandro/0000-0001-8450-3227
FU Ministerio de Educacion, Cultura y Deporte of Spain [EX2009-0918];
Ministerio de Ciencia e Innovacion [BFU2010-20882]; National Institute
on Aging
FX We thank Stephen H. Leppla and Christopher Bachran of the Laboratory of
Bacterial Diseases, National Institute of Allergy and Infectious
Diseases, National Institutes of Health (NIH), for providing fusion
protein FP59. We thank Myriam Gorospe and Jennifer L Martindale of the
Laboratory of Molecular Biology and Immunology, NIH, for technical
advice regarding protein synthesis assays. S.A.C. was supported by a
Ministerio de Educacion, Cultura y Deporte of Spain postdoctoral
fellowship (EX2009-0918) and A.A. was supported by Ministerio de Ciencia
e Innovacion BFU2010-20882. This work was supported in part by the
Intramural Research Program of the National Institute on Aging.
NR 37
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U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD AUG
PY 2013
VL 61
BP 61
EP 71
DI 10.1016/j.freeradbiomed.2013.03.016
PG 11
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 168EA
UT WOS:000320687300008
PM 23542375
ER
PT J
AU Lim, JC
Kim, G
Levine, RL
AF Lim, Jung Chae
Kim, Geumsoo
Levine, Rodney L.
TI Stereospecific oxidation of calmodulin by methionine sulfoxide reductase
A
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Calmodulin; Methionine oxidation; Methionine reduction; Methionine
sulfoxide reductase; Signaling; Free radicals
ID MEMBRANE CA-ATPASE; TARGET RECOGNITION; ESCHERICHIA-COLI; TERMINAL
DOMAIN; ACTIVATION; STRESS; PROTECTS; DAMAGE; CELLS; CALCINEURIN
AB Methionine sulfoxide reductase A has long been known to reduce S-methionine sulfoxide, both as a free amino acid and within proteins. Recently the enzyme was shown to be bidirectional, capable of oxidizing free methionine and methionine in proteins to S-methionine sulfoxide. A feasible mechanism for controlling the directionality has been proposed, raising the possibility that reversible oxidation and reduction of methionine residues within proteins is a redox-based mechanism for cellular regulation. We undertook studies aimed at identifying proteins that are subject to site-specific, stereospecific oxidation and reduction of methionine residues. We found that calmodulin, which has nine methionine residues, is such a substrate for methionine sulfoxide reductase A. When calmodulin is in its calcium-bound form, Met77 is oxidized to S-methionine sulfoxide by methionine sulfoxide reductase A. When methionine sulfoxide reductase A operates in the reducing direction, the oxidized calmodulin is fully reduced back to its native form. We conclude that reversible covalent modification of Met77 may regulate the interaction of calmodulin with one or more of its many targets. (C) 2013 Published by Elsevier Inc.
C1 [Lim, Jung Chae; Kim, Geumsoo; Levine, Rodney L.] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA.
RP Levine, RL (reprint author), NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA.
EM rlevine@nih.gov
RI Levine, Rodney/D-9885-2011
FU Intramural Research Program of the National Heart, Lung, and Blood
Institute
FX We are grateful to colleagues who provided thoughtful suggestions and
valuable biologicals: Hana Im, Sejong University, for the
alpha1-antitrypsin construct, and Claude Klee, National
Cancer Institute, for purified calcineurin and its substrate. From the
National Heart, Lung, and Blood Institute, we thank Faiyaz Khan and
Vincent Manganiello for purified phosphodiesterase 1 and its assay,
James Sellers for purified myosin light-chain kinase and its substrate,
Alan Remaley for apolipoprotein A, Ikuko Fujiwara for actin, Nelson Cole
for alpha-synuclein, and Duck-Yeon Lee for thioredoxin. We thank the
Biochemistry Core Facility of the National Heart, Lung, and Blood
Institute for providing access to its facilities and instruments. This
study was supported by the Intramural Research Program of the National
Heart, Lung, and Blood Institute.
NR 50
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U2 14
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD AUG
PY 2013
VL 61
BP 257
EP 264
DI 10.1016/j.freeradbiomed.2013.04.004
PG 8
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 168EA
UT WOS:000320687300026
PM 23583331
ER
PT J
AU Kumar, A
Ganini, D
Deterding, LJ
Ehrenshaft, M
Chatterjee, S
Mason, RP
AF Kumar, Ashutosh
Ganini, Douglas
Deterding, Leesa J.
Ehrenshaft, Marilyn
Chatterjee, Saurabh
Mason, Ronald P.
TI Immuno-spin trapping of heme-induced protein radicals: Implications for
heme oxygenase-1 induction and heme degradation
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Heme; Nitrone adducts; Peroxidase; Protein radical; Protein oxidation;
Oxidative stress
ID HYDROGEN-PEROXIDE; ANTIOXIDANT; OXIDATION; HEMOGLOBIN; BILIRUBIN;
BINDING; IDENTIFICATION; ENDOTHELIUM; TRANSPORT; DISEASE
AB Heme, in the presence of hydrogen peroxide, can act as a peroxidase. Intravascular hemolysis results in a massive release of heme into the plasma in several pathophysiological conditions such as hemolytic anemia, malaria, and sickle cell disease. Heme is known to induce heme oxygenase-1(HO-1) expression, and the extent of induction depends on the ratio of albumin to heme in plasma. HO-1 degrades heme and ultimately generates the antioxidant bilirubin. Heme also causes oxidative stress in cells, but whether it causes protein-radical formation has not yet been studied. In the literature, two purposes for the degradation of heme by HO-1 are discussed. One is the production of the antioxidant bilirubin and the other is the prevention of heme-dependent adverse effects. Here we have investigated heme-induced protein-radical formation, which might have pathophysiological consequences, and have used immuno-spin trapping to establish the formation of heme-induced protein radicals in two systems: human serum albumin (HSA)/H2O2 and human plasma/H2O2. We found that excess heme catalyzed the formation of HSA radicals in the presence of hydrogen peroxide. When heme and hydrogen peroxide were added to human plasma, heme was found to oxidize proteins, primarily and predominantly HSA; however, when HSA-depleted plasma was used, heme triggered the oxidation of several other proteins, including transferrin. Thus, HSA in plasma protected other proteins from heme/H2O2-induced oxidation. The antioxidants ascorbate and uric acid significantly attenuated protein-radical formation induced by heme/H2O2; however, bilirubin did not confer significant protection. Based on these findings, we conclude that heme is degraded by HO-1 because it is a catalyst of protein-radical formation and not merely to produce the relatively inefficient antioxidant bilirubin. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Kumar, Ashutosh; Ganini, Douglas; Ehrenshaft, Marilyn; Mason, Ronald P.] NIEHS, Free Rad Metab Grp, Labs Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA.
[Deterding, Leesa J.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA.
[Chatterjee, Saurabh] Univ S Carolina, Dept Environm Hlth Sci, Columbia, SC 29208 USA.
RP Kumar, A (reprint author), NIEHS, Free Rad Metab Grp, Labs Toxicol & Pharmacol, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM kumara10@niehs.nih.gov
FU Intramural Research Program of the National Institutes of Health;
National Institute of Environmental Health Sciences; NIH; Pathway to
Independence Award [ES01-19875A]; [K99-R00]
FX The authors gratefully acknowledge Dr. Ann Motten and Mary Mason for
their valuable help in the preparation of the manuscript. This work has
been supported by the Intramural Research Program of the National
Institutes of Health and the National Institute of Environmental Health
Sciences. Saurabh Chatterjee is also supported by a K99-R00, NIH, and
Pathway to Independence Award (ES01-19875A). The authors declare no
conflict of interest.
NR 36
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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 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD AUG
PY 2013
VL 61
BP 265
EP 272
DI 10.1016/j.freeradbiomed.2013.04.026
PG 8
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 168EA
UT WOS:000320687300027
PM 23624303
ER
PT J
AU Kadiiska, MB
Basu, S
Brot, N
Cooper, C
Csallany, AS
Davies, MJ
George, MM
Murray, DM
Roberts, LJ
Shigenaga, MK
Sohal, RS
Stocker, R
Van Thiel, DH
Wiswedel, I
Hatch, GE
Mason, RP
AF Kadiiska, Maria B.
Basu, Samar
Brot, Nathan
Cooper, Christopher
Csallany, A. Saari
Davies, Michael J.
George, Magdalene M.
Murray, Dennis M.
Roberts, L. Jackson, II
Shigenaga, Mark K.
Sohal, Rajindar S.
Stocker, Roland
Van Thiel, David H.
Wiswedel, Ingrid
Hatch, Gary E.
Mason, Ronald P.
TI Biomarkers of oxidative stress study V: Ozone exposure of rats and its
effect on lipids, proteins, and DNA in plasma and urine
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Biomarkers; Oxidative stress; Ozone exposure; Rats
ID CHROMATOGRAPHY-MASS-SPECTROMETRY; LOW-DENSITY-LIPOPROTEIN;
BRONCHOALVEOLAR LAVAGE FLUID; IN-VIVO; METHIONINE OXIDATION;
ENZYME-IMMUNOASSAY; BIOLOGICAL-FLUIDS; BREATH CONDENSATE; ASSAY REVEALS;
LUNG INJURY
AB Ozone exposure effect on free radical-catalyzed oxidation products of lipids, proteins, and DNA in the plasma and urine of rats was studied as a continuation of the international Biomarker of Oxidative Stress Study (BOSS) sponsored by NIEHS/NIH. The goal was to identify a biomarker for ozone-induced oxidative stress and to assess whether inconsistent results often reported in the literature might be due to the limitations of the available methods for measuring the various types of oxidative products. The time- and dose-dependent effects of ozone exposure on rat plasma lipid hydroperoxides, malondialdehyde, F-2-isoprostanes, protein carbonyls, methionine oxidation, and tyrosine- and phenylalanine oxidation products, as well as urinary malondialdehyde and F-2-isoprostanes were investigated with various techniques. The criterion used to recognize a marker in the model of ozone exposure was that a significant effect could be identified and measured in a biological fluid seen at both doses at more than one time point. No statistically significant differences between the experimental and the control groups at either ozone dose and time point studied could be identified in this study. Tissue samples were not included. Despite all the work accomplished in the BOSS study of ozone, no available product of oxidation in biological fluid has yet met the required criteria of being a biomarker. The current negative findings as a consequence of ozone exposure are of great importance, because they document that in complex systems, as the present in vivo experiment, the assays used may not provide meaningful data of ozone oxidation, especially in human studies. Published by Elsevier Inc.
C1 [Kadiiska, Maria B.; Mason, Ronald P.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Basu, Samar] Uppsala Univ, Fac Med, Uppsala, Sweden.
[Basu, Samar] Univ Auvergne, Biochem Mol Biol & Nutr Dept, Clermont Ferrand, France.
[Brot, Nathan] Weill Cornell Med Coll, Dept Microbiol & Immunol, New York, NY USA.
[Cooper, Christopher] Univ Essex, Sch Biol Sci, Colchester CO4 3SQ, Essex, England.
[Csallany, A. Saari] Univ Minnesota, Dept Food Sci & Nutr, St Paul, MN USA.
[Davies, Michael J.] Univ Sydney, Heart Res Inst, Sydney, NSW 2006, Australia.
[George, Magdalene M.; Van Thiel, David H.] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
[Murray, Dennis M.] Northwest Life Sci Specialties LLC, Vancouver, WA USA.
[Roberts, L. Jackson, II] Vanderbilt Univ, Dept Med & Pharmacol, Nashville, TN 37235 USA.
[Shigenaga, Mark K.] Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA.
[Sohal, Rajindar S.] Univ So Calif, Los Angeles, CA USA.
[Stocker, Roland] Victor Chang Cardiac Res Inst, Darlinghurst, NSW, Australia.
[Wiswedel, Ingrid] Univ Magdeburg, D-39106 Magdeburg, Germany.
[Hatch, Gary E.] US EPA, Res Triangle Pk, NC 27711 USA.
RP Kadiiska, MB (reprint author), NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM Kadiiska@niehs.nih.gov
RI Davies, Michael/H-4939-2011;
OI Davies, Michael/0000-0002-5196-6919; Cooper, Chris/0000-0003-0381-3990
FU NIH, National Institute of Environmental Health Sciences
FX The research was supported by the Intramural Program of the NIH,
National Institute of Environmental Health Sciences. The research
described in this article has been reviewed by the National Health and
Environmental Effects Research Laboratory, United States Environmental
Protection Agency and approved for publication. Approval does not
signify that the contents necessarily reflect the views and policies of
the agency, nor does mention of trade names or commercial products
constitute endorsement or recommendation for use.
NR 73
TC 12
Z9 13
U1 2
U2 21
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD AUG
PY 2013
VL 61
BP 408
EP 415
DI 10.1016/j.freeradbiomed.2013.04.023
PG 8
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 168EA
UT WOS:000320687300039
PM 23608465
ER
PT J
AU Mitsunaga, M
Kosaka, N
Choyke, PL
Young, MR
Dextras, CR
Saud, SM
Colburn, NH
Sakabe, M
Nagano, T
Asanuma, D
Urano, Y
Kobayashi, H
AF Mitsunaga, Makoto
Kosaka, Nobuyuki
Choyke, Peter L.
Young, Matthew R.
Dextras, Christopher R.
Saud, Shakir M.
Colburn, Nancy H.
Sakabe, Masayo
Nagano, Tetsuo
Asanuma, Daisuke
Urano, Yasuteru
Kobayashi, Hisataka
TI Fluorescence endoscopic detection of murine colitis-associated colon
cancer by topically applied enzymatically rapid-activatable probe
SO GUT
LA English
DT Article
DE Colitis-associated colon cancer; fluorescence endoscopy; optical
molecular imaging; activatable probe; cancer; imaging; inflammatory
bowel disease; colorectal cancer; liver metastases; liver imaging;
colorectal metastases; image analysis; gastrointestinal endoscopy
ID INFLAMMATORY-BOWEL-DISEASE; GAMMA-GLUTAMYL-TRANSFERASE;
ULCERATIVE-COLITIS; COLORECTAL-CANCER; INTRAEPITHELIAL NEOPLASIA;
INTESTINAL CANCER; EXPRESSION; RISK; DYSPLASIA; CLASSIFICATION
AB Objectives
Screening colonoscopy to monitor for early colitis-associated colon cancer (CAC) is difficult due to the aberrant mucosal patterns associated with long-standing colitis. The aim of this study was to develop a rapid fluorescent detection method for use during colonoscopy for improving the detection of CAC utilising a topically applied enzymatically activatable probe (gGlu-HMRG) which fluoresces in the presence of -glutamyltranspeptidase (GGT), an enzyme associated with cancer.
Methods
Expression of GGT in colon cell lines was examined with fluorescence microscopy and flow cytometry. A mouse model (azoxymethane/dextran sulphate sodium) of CAC was used and mice were examined with white light and fluorescence colonoscopy before and after topical gGlu-HMRG administration.
Results
Expression of GGT, although variable, was higher in human colon cancer cells than normal human colon cells. Using fluorescence colonoscopy in mice, gGlu-HMRG fluorescent lesions were detected 5min after topical administration and fluorescence persisted for at least 30min. Fluorescence guided biopsy revealed all fluorescent lesions that contained cancer or dysplasia (n=16), whereas three out of 12 non-fluorescent lesions contained low grade dysplasia and others did not contain neoplastic histology. Microscopic inflammatory infiltration also had variable fluorescence but in general was much lower (approximate to 10-fold) in signal than cancer. Repeat fluorescence endoscopy allowed individual tumours to be monitored.
Conclusion
These results suggest that gGlu-HMRG can improve endoscopic detection of CAC with a higher target to background ratio than conventional white light colonoscopy. This could be of benefit to patients with long-standing colitis who must undergo repeated screening colonoscopies.
C1 [Mitsunaga, Makoto; Kosaka, Nobuyuki; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Young, Matthew R.; Dextras, Christopher R.; Saud, Shakir M.; Colburn, Nancy H.] NCI, Lab Canc Prevent, Frederick Natl Lab, Ctr Canc Res, Frederick, MD 21701 USA.
[Saud, Shakir M.] NCI, NIH, Nutr Sci Res Grp, Canc Prevent Div, Rockville, MD USA.
[Sakabe, Masayo; Nagano, Tetsuo] Univ Tokyo, Grad Sch Pharmaceut Sci, Tokyo, Japan.
[Asanuma, Daisuke; Urano, Yasuteru] Univ Tokyo, Tokyo, Japan.
RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room B3B69,MSC1088, Bethesda, MD 20892 USA.
EM kobayash@mail.nih.gov
FU Intramural Research Program of the US National Institutes of Health,
National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the US
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 37
TC 39
Z9 39
U1 3
U2 39
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0017-5749
EI 1468-3288
J9 GUT
JI Gut
PD AUG
PY 2013
VL 62
IS 8
BP 1179
EP 1186
DI 10.1136/gutjnl-2011-301795
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 176WQ
UT WOS:000321337600014
PM 22698650
ER
PT J
AU Yang, CY
Chen, YW
Guo, GN
Li, H
Cao, DY
Xu, H
Guo, S
Fei, L
Yan, WM
Ning, Q
Zheng, LX
Wu, YZ
AF Yang, Chengying
Chen, Yongwen
Guo, Guoning
Li, Hong
Cao, Dayan
Xu, Huan
Guo, Sheng
Fei, Lei
Yan, Weiming
Ning, Qing
Zheng, Lixin
Wu, Yuzhang
TI Expression of B and T lymphocyte attenuator (BTLA) in macrophages
contributes to the fulminant hepatitis caused by murine hepatitis virus
strain-3
SO GUT
LA English
DT Article
DE BTLA; Fulminant viral hepatitis; FGL2; TNF; immune; acute liver failure;
hepatobiliary pathology; infectious disease; inflammation;
immune-mediated liver damage; immunology in hepatology; vitamins;
immunology; inflammatory mechanisms; cell biology; cellular immunity;
cellular immunology
ID HERPESVIRUS ENTRY MEDIATOR; FGL2 PROTHROMBINASE; CELL-ACTIVATION;
INFECTION; MICE; DISEASE; SUSCEPTIBILITY; INFLAMMATION; PREVENTS;
SURVIVAL
AB Objectives
Fulminant viral hepatitis (FH) remains a serious clinical problem for which the underlying pathogenesis remains unclear. The B and T lymphocyte attenuator (BTLA) is an immunoglobulin-domain-containing protein that has the capacity to maintain peripheral tolerance and limit immunopathological damage during immune responses. However, its precise role in FH has yet to be investigated.
Design
BTLA-deficient (BTLA(-/-)) mice and their wild-type littermates were infected with murine hepatitis virus strain-3 (MHV-3), and the levels of tissue damage, cell apoptosis, serum liver enzymes, fibrinogen-like protein 2 (FGL2) and cytokine production were measured and compared. Survival rate was studied after MHV-3 infection with or without adoptive transferring macrophages.
Results
FGL2 production, liver and spleen damage, and mortality were significantly reduced in BTLA(-/-) mice infected with MHV-3. This effect is due to rapid, TRAIL (TNF-related apoptosis-inducing ligand)-dependent apoptosis of MHV-3-infected macrophages in BTLA(-/-) mice. The early loss of macrophages resulted in reduced pathogenic tumour necrosis factor (TNF) and FGL2 levels and lower viral titres. The importance of TNF in MHV-3-induced pathology was demonstrated by increased mortality in TNF-treated MHV-3-infected BTLA(-/-) mice, whereas TNF-/- mice were resistant to the infection. Moreover, adoptively transferring macrophages to BTLA(-/-) mice caused sensitisation, whereas blocking BTLA protected wild-type mice from virus-induced FH mortality.
Conclusions
BTLA promotes the pathogenesis of virus-induced FH by enhancing macrophage viability and function. Targeting BTLA may be a novel strategy for the treatment of FH.
C1 [Yang, Chengying; Chen, Yongwen; Cao, Dayan; Xu, Huan; Guo, Sheng; Fei, Lei; Wu, Yuzhang] Third Mil Med Univ, PLA, Inst Immunol, Deaprtment Basic Med, Chongqing 400038, Peoples R China.
[Guo, Guoning] Third Mil Med Univ, PLA, Dept Emergency, South West Hosp, Chongqing 400038, Peoples R China.
[Li, Hong] Third Mil Med Univ, Xinqiao Hosp, Dept Otorhinolaryngol & Head Neck Surg, Chongqing 400038, Peoples R China.
[Cao, Dayan] Third Mil Med Univ, Undergrad Adm Off, Chongqing 400038, Peoples R China.
[Yan, Weiming; Ning, Qing] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Infect Dis,Inst Infect Dis, Wuhan, Peoples R China.
[Zheng, Lixin] NIAID, Lab Immunol, Bethesda, MD USA.
RP Chen, YW (reprint author), Third Mil Med Univ, PLA, Inst Immunol, Chongqing 400038, Peoples R China.
EM yongwench@163.com; wuyuzhang@yahoo.com
OI cao, dayan/0000-0001-7648-3668
FU National Natural Science Foundation of China [30930086, 2007CB512805];
National Natural Science Foundation of China (NSFC) [81171585, 30971099,
30901347, 61141012]; Natural Science Foundation of Chongqing
[CSTC2011BB5037]
FX This work was supported by grants from The Major Program of National
Natural Science Foundation of China (30930086 and 2007CB512805) and the
General Program of National Natural Science Foundation of China (NSFC No
81171585, 30971099, 30901347 and 61141012) and Natural Science
Foundation of Chongqing (No CSTC2011BB5037).
NR 29
TC 5
Z9 5
U1 1
U2 6
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0017-5749
J9 GUT
JI Gut
PD AUG
PY 2013
VL 62
IS 8
BP 1204
EP 1213
DI 10.1136/gutjnl-2012-302239
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 176WQ
UT WOS:000321337600017
PM 22637698
ER
PT J
AU Rasch, EK
Gulley, SP
Chan, L
AF Rasch, Elizabeth K.
Gulley, Stephen P.
Chan, Leighton
TI Use of Emergency Departments among Working Age Adults with Disabilities:
A Problem of Access and Service Needs
SO HEALTH SERVICES RESEARCH
LA English
DT Article
DE (MeSH): persons with disabilities; emergency medical services; health
services accessibility
ID HEALTH-CARE SERVICES; MEDICAL-HOME; MASSACHUSETTS MEDICAID; DISEASE
MANAGEMENT; UNITED-STATES; PROGRAM; BARRIERS; PEOPLE; SATISFACTION;
ORGANIZATION
AB Objective. To examine the relationship between emergency department (ED) use and access to medical care and prescription medications among working age Americans with disabilities.
Data Source. Pooled data from the 2006-2008 Medical Expenditure Panel Survey (MEPS), a U. S. health survey representative of community-dwelling civilians.
Study Design. We compared the health and service utilization of two groups of people with disabilities to a contrast group without disability. We modeled ED visits on the basis of disability status, measures of health and health conditions, access to care, and sociodemographics.
Data Extraction. These variables were aggregated from the household component, the medical condition, and event files to provide average annual estimates for the period spanning 2006-2008.
Principal Findings. People with disabilities accounted for almost 40 percent of the annual visits made to U. S. EDs each year. Three key factors affect their ED use: access to regular medical care (including prescription medications), disability status, and the complexity of individuals' health profiles.
Conclusions. Given the volume of health conditions among people with disabilities, the ED will always play a role in their care. However, some ED visits could potentially be avoided if ongoing care were optimized.
C1 [Rasch, Elizabeth K.; Gulley, Stephen P.; Chan, Leighton] NIH, Mark O Hatfield Clin Res Ctr, Dept Rehabil Med, Bethesda, MD 20892 USA.
RP Rasch, EK (reprint author), NIH, Mark O Hatfield Clin Res Ctr, Dept Rehabil Med, 6100 Execut Blvd,Suite 3C01,MSC 7515, Bethesda, MD 20892 USA.
EM rasche@cc.nih.gov
FU National Institutes of Health, Clinical Research Center
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, Clinical Research Center. The authors
wish to thank Minh Huynh, Ph.D., for his statistical consultation. The
views expressed in this article are those of the authors and do not
necessarily reflect the official policy or position of the National
Institutes of Health or the U.S. government.
NR 45
TC 9
Z9 9
U1 2
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0017-9124
J9 HEALTH SERV RES
JI Health Serv. Res.
PD AUG
PY 2013
VL 48
IS 4
BP 1334
EP 1358
DI 10.1111/1475-6773.12025
PG 25
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 176IM
UT WOS:000321297600007
PM 23278461
ER
PT J
AU Jimenez-Morales, S
Martinez-Aguilar, N
Gamboa-Becerra, R
Jimenez-Ruiz, JL
Lopez-Ley, D
Lou, H
Saldana-Alvarez, Y
Dean, M
Orozco, L
AF Jimenez-Morales, Silvia
Martinez-Aguilar, Nora
Gamboa-Becerra, Roberto
Luis Jimenez-Ruiz, Juan
Lopez-Ley, Diana
Lou, Hong
Saldana-Alvarez, Yolanda
Dean, Michael
Orozco, Lorena
TI Polymorphisms in metalloproteinase-9 are associated with the risk for
asthma in Mexican pediatric patients
SO HUMAN IMMUNOLOGY
LA English
DT Article
ID INDUCED AIRWAY INFLAMMATION; MATRIX METALLOPROTEINASES; TISSUE
INHIBITOR; PATHOLOGICAL CONDITIONS; RHEUMATOID-ARTHRITIS;
GENETIC-VARIANTS; BRONCHIAL-ASTHMA; MMP-9 GENE;
MATRIX-METALLOPROTEINASE-9; DISEASE
AB Asthma is characterized by chronic airway inflammation, which induces airway remodelling of the extracellular matrix over time. Matrix metalloproteinases (MMPs) are involved in this process, and single-nucleotide polymorphisms (SNPs) in MMP genes may influence their mRNA expression levels or abilities to bind substrates and inhibitors, thereby contributing to asthma predisposition and severity. MMP-9 is highly expressed in airways and many studies support its involvement in asthma pathogenesis; however the contribution of MMP-9 SNPs is controversial. To investigate whether MMP-9 SNPs are associated with childhood-onset asthma in Mexican patients we conducted a case-control study including 403 children with clinical asthma diagnoses and 426 healthy controls from Mexico. The cases and controls were matched by ethnicity and gender. We found that the SNPs rs2274755, rs17577, and rs3918249 were associated with asthma risk. The most significant associations were with rs2274755 (OR = 2.10, 95% CI 1.31-3.39, P = 0.001) and rs17577 (OR = 2.07, 95% CI 1.29-3.30, P = 0.001); which were in strong linkage disequilibrium. Both SNPs were also associated with atopic asthma (OR = 2.38, 95% CI 1.44-196, P = 0.0005). The SNP rs3918249 exhibited a female gender-dependent association with asthma (OR = 1.66, 95% CI 1.14-2.43, P = 0.007). Our results suggest that MMP-9 polymorphisms could play a role in the susceptibility to childhood-onset asthma. (C) 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
C1 [Jimenez-Morales, Silvia; Gamboa-Becerra, Roberto; Luis Jimenez-Ruiz, Juan; Lopez-Ley, Diana; Saldana-Alvarez, Yolanda; Orozco, Lorena] Inst Nacl Med Genom, Lab Inmunogen & Enfermedades Metab, SS, Mexico City, DF, Mexico.
[Martinez-Aguilar, Nora] Hosp Pediat Coyoacan, SS, Mexico City, DF, Mexico.
[Lou, Hong] SAIC Frederick Inc, Natl Canc Inst Frederick, Basic Res Program, Human Genet Sect, Frederick, MD 21702 USA.
[Dean, Michael] Natl Canc Inst Frederick, Ctr Canc Res, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA.
RP Orozco, L (reprint author), Inst Nacl Med Genom, Perifer Sur 4809, Delegacion Tlalpan 14610, DF, Mexico.
EM lorozco@inmegen.gob.mx
RI Dean, Michael/G-8172-2012
OI Dean, Michael/0000-0003-2234-0631
FU Consejo Nacional de Ciencia y Tecnologia, Mexico (CONACyT)
[2011-C01-161936]
FX NMA, RGB, JLJR, DLL and YSA performed DNA biobank, SJM and RGB carried
the research and analyzed the data; NMA contributed with patients; HL
contributed the cell lines for the study; SJM, MD and LO designed the
research study and wrote the paper. This study was supported by a grant
from Consejo Nacional de Ciencia y Tecnologia, Mexico (CONACyT):
2011-C01-161936. The authors also would like to acknowledge the patients
and their families for their participation.
NR 53
TC 6
Z9 7
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0198-8859
J9 HUM IMMUNOL
JI Hum. Immunol.
PD AUG
PY 2013
VL 74
IS 8
BP 998
EP 1002
DI 10.1016/j.humimm.2013.04.036
PG 5
WC Immunology
SC Immunology
GA 183DY
UT WOS:000321795600018
PM 23639553
ER
PT J
AU Giorgio, E
Rolyan, H
Kropp, L
Chakka, AB
Yatsenko, S
Di Gregorio, E
Lacerenza, D
Vaula, G
Talarico, F
Mandich, P
Toro, C
Pierre, EE
Labauge, P
Capellari, S
Cortelli, P
Vairo, FP
Miguel, D
Stubbolo, D
Marques, LC
Gahl, W
Boespflug-Tanguy, O
Melberg, A
Hassin-Baer, S
Cohen, OS
Pjontek, R
Grau, A
Klopstock, T
Fogel, B
Meijer, I
Rouleau, G
Bouchard, JPL
Ganapathiraju, M
Vanderver, A
Dahl, N
Hobson, G
Brusco, A
Brussino, A
Padiath, QS
AF Giorgio, Elisa
Rolyan, Harshvardhan
Kropp, Laura
Chakka, Anish Baswanth
Yatsenko, Svetlana
Di Gregorio, Eleonora
Lacerenza, Daniela
Vaula, Giovanna
Talarico, Flavia
Mandich, Paola
Toro, Camilo
Pierre, Eleonore Eymard
Labauge, Pierre
Capellari, Sabina
Cortelli, Pietro
Vairo, Filippo Pinto
Miguel, Diego
Stubbolo, Danielle
Marques, Lourenco Charles
Gahl, William
Boespflug-Tanguy, Odile
Melberg, Atle
Hassin-Baer, Sharon
Cohen, Oren S.
Pjontek, Rastislav
Grau, Armin
Klopstock, Thomas
Fogel, Brent
Meijer, Inge
Rouleau, Guy
Bouchard, Jean-Pierre L.
Ganapathiraju, Madhavi
Vanderver, Adeline
Dahl, Niklas
Hobson, Grace
Brusco, Alfredo
Brussino, Alessandro
Padiath, Quasar Saleem
TI Analysis of LMNB1 Duplications in Autosomal Dominant Leukodystrophy
Provides Insights into Duplication Mechanisms and Allele-Specific
Expression
SO HUMAN MUTATION
LA English
DT Article
DE Lamin B1; leukodystrophy; ADLD; duplication Alu; NHEJ; FoSTeS; MMBIR
ID PELIZAEUS-MERZBACHER-DISEASE; LAMIN B1 DUPLICATIONS; DOUBLE-STRAND
BREAKS; GENE COPY-NUMBER; GENOMIC ARCHITECTURE; COMPLEX REARRANGEMENTS;
AUTONOMIC SYMPTOMS; INVERTED REPEATS; ALU ELEMENTS; RECOMBINATION
AB Autosomal dominant leukodystrophy (ADLD) is an adult onset demyelinating disorder that is caused by duplications of the lamin B1 (LMNB1) gene. However, as only a few cases have been analyzed in detail, the mechanisms underlying LMNB1 duplications are unclear. We report the detailed molecular analysis of the largest collection of ADLD families studied, to date. We have identified the minimal duplicated region necessary for the disease, defined all the duplication junctions at the nucleotide level and identified the first inverted LMNB1 duplication. We have demonstrated that the duplications are not recurrent; patients with identical duplications share the same haplotype, likely inherited from a common founder and that the duplications originated from intrachromosomal events. The duplication junction sequences indicated that nonhomologous end joining or replication-based mechanisms such fork stalling and template switching or microhomology-mediated break induced repair are likely to be involved. LMNB1 expression was increased in patients' fibroblasts both at mRNA and protein levels and the three LMNB1 alleles in ADLD patients show equal expression, suggesting that regulatory regions are maintained within the rearranged segment. These results have allowed us to elucidate duplication mechanisms and provide insights into allele-specific LMNB1 expression levels.
C1 [Giorgio, Elisa; Di Gregorio, Eleonora; Lacerenza, Daniela; Brusco, Alfredo; Brussino, Alessandro] Univ Turin, Dept Med Sci, Turin, Italy.
[Rolyan, Harshvardhan; Kropp, Laura; Padiath, Quasar Saleem] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA.
[Chakka, Anish Baswanth; Ganapathiraju, Madhavi] Univ Pittsburgh, Sch Med, Dept Biomed Informat, Pittsburgh, PA USA.
[Yatsenko, Svetlana] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
[Yatsenko, Svetlana] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA.
[Di Gregorio, Eleonora; Talarico, Flavia; Brusco, Alfredo] Az Osp Citta Salute & Sci, SCDU Med Genet, Turin, Italy.
[Vaula, Giovanna] Az Osp Citta Salute & Sci, Dept Neurosci, Turin, Italy.
[Mandich, Paola] Dept Biomed & NeuroMotor Sci DIBINEM Alma Mater S, Dept Neurol Ophthalmol & Genet, Bologna, Italy.
[Toro, Camilo; Gahl, William] NIH Off Rare Dis Res & NHGRI, NIH Undiagnosed Dis Program, Bethesda, MD USA.
[Pierre, Eleonore Eymard] CHU Clermont Ferrand, Dept Genet & Cytogenet, Clermont Ferrand, France.
[Labauge, Pierre] Ctr Hosp Univ Nimes, Hop Caremeau, Nimes, France.
[Capellari, Sabina; Cortelli, Pietro] Univ Bologna, IRCCS Ist Sci Neurol Bologna, Dept Biomed & NeuroMotor Sci DIBINEM Alma Mater S, I-40126 Bologna, Italy.
[Vairo, Filippo Pinto; Miguel, Diego] Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil.
[Vairo, Filippo Pinto; Miguel, Diego] Univ Fed Rio Grande do Sul, Porto Alegre, RS, Brazil.
[Stubbolo, Danielle; Hobson, Grace] Alfred I duPont Hosp Children, Wilmington, DE USA.
[Marques, Lourenco Charles] Univ Sao Paulo, Clin Hosp Ribeirao Preto, Dept Med Genet, Sao Paulo, Brazil.
[Boespflug-Tanguy, Odile] Paris Diderot Sorbonne Paris Cite Univ, Robert Debre Hosp, INSERM, Paris, France.
[Boespflug-Tanguy, Odile] AP HP, Reference Ctr Rare Dis Leukodystrophies, Child Neurol & Metab Disorders Dept, Paris, France.
[Melberg, Atle] Uppsala Univ, Dept Neurosci, Uppsala, Sweden.
[Hassin-Baer, Sharon; Cohen, Oren S.] Chaim Sheba Med Ctr, Dept Neurol, Parkinsons Dis & Movement Disorders Clin, Tel Aviv, Israel.
[Hassin-Baer, Sharon; Cohen, Oren S.] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel.
[Pjontek, Rastislav] Heidelberg Univ, Dept Neurol, Heidelberg, Germany.
[Grau, Armin] Klinikum Ludwigshafen, Dept Neurol, Ludwigshafen, Germany.
[Klopstock, Thomas] Univ Munich, Dept Neurol, Friedrich Baur Inst, D-80539 Munich, Germany.
[Klopstock, Thomas] German Ctr Vertigo & Balance Disorders, Munich, Germany.
[Klopstock, Thomas] DZNE German Ctr Neurodegenerat Dis, Munich, Germany.
[Fogel, Brent] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
[Meijer, Inge; Rouleau, Guy] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada.
[Bouchard, Jean-Pierre L.] CHA Hop Enfants Jesus, Dept Neurol Sci, Quebec City, PQ, Canada.
[Vanderver, Adeline] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA.
[Dahl, Niklas] Uppsala Univ Childrens Hosp, Rudbeck Lab, Clin Genet Sect, Dept Immunol Genet & Pathol, Uppsala, Sweden.
[Hobson, Grace] Univ Delaware, Dept Biol, Newark, DE USA.
[Hobson, Grace] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA.
RP Padiath, QS (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA.
EM alfredo.brusco@unito.it; qpadiath@pitt.edu
RI Di Gregorio, Eleonora/I-9393-2014; Vairo, Filippo/L-1256-2015; Brusco,
Alfredo/A-1811-2013;
OI Di Gregorio, Eleonora/0000-0003-0956-2379; Brusco,
Alfredo/0000-0002-8318-7231; Mandich, Paola/0000-0003-3123-3512;
Giorgio, Elisa/0000-0003-4076-4649; Cortelli, Pietro/0000-0002-3633-8818
FU Compagnia di San Paolo "Progetto Neuroscienze"; European Leukodystrophy
Association [2011-006C2]; Telethon Research Grant [GGP10184]; Swedish
Council; Selander Foundation [NIH R01NS058978]
FX Contract grant sponsors: Compagnia di San Paolo "Progetto Neuroscienze";
European Leukodystrophy Association (2011-006C2); Telethon Research
Grant (GGP10184); the Swedish Council; the Selander Foundation (NIH
R01NS058978).
NR 43
TC 16
Z9 16
U1 1
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-7794
J9 HUM MUTAT
JI Hum. Mutat.
PD AUG
PY 2013
VL 34
IS 8
BP 1160
EP 1171
DI 10.1002/humu.22348
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 182QX
UT WOS:000321759900015
PM 23649844
ER
PT J
AU McKee, MD
Yadav, MC
Foster, BL
Somerman, MJ
Farquharson, C
Millan, JL
AF McKee, M. D.
Yadav, M. C.
Foster, B. L.
Somerman, M. J.
Farquharson, C.
Millan, J. L.
TI Compounded PHOSPHO1/ALPL Deficiencies Reduce Dentin Mineralization
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Article
DE matrix vesicles; tissue-non-specific alkaline phosphatase; extracellular
matrix; extracellular matrix proteins; tooth; phosphatase
ID NONSPECIFIC ALKALINE-PHOSPHATASE; MATRIX VESICLES; INFANTILE
HYPOPHOSPHATASIA; SKELETAL MINERALIZATION; EPIPHYSEAL CARTILAGE; ROOT
DENTIN; CALCIFICATION; BONE; DEFECTS; MODEL
AB Phosphatases are involved in bone and tooth mineralization, but their mechanisms of action are not completely understood. Tissue-nonspecific alkaline phosphatase (TNAP, ALPL) regulates inhibitory extracellular pyrophosphate through its pyrophosphatase activity to control mineral propagation in the matrix; mice without TNAP lack acellular cementum, and have mineralization defects in dentin, enamel, and bone. PHOSPHO1 is a phosphatase found within membrane-bounded matrix vesicles in mineralized tissues, and double ablation of Alpl and Phospho1 in mice leads to a complete absence of skeletal mineralization. Here, we describe mineralization abnormalities in the teeth of Phospho1(-/-) mice, and in compound knockout mice lacking Phospho1 and one allele of Alpl (Phospho1(-/-);Alpl(+/-)). In wild-type mice, PHOSPHO1 and TNAP co-localized to odontoblasts at early stages of dentinogenesis, coincident with the early mineralization of mantle dentin. In Phospho1 knockout mice, radiography, micro-computed tomography, histology, and transmission electron microscopy all demonstrated mineralization abnormalities of incisor dentin, with the most remarkable findings being reduced overall mineralization coincident with decreased matrix vesicle mineralization in the Phospho1(-/-) mice, and the almost complete absence of matrix vesicles in the Phospho1(-/-);Alpl(+/-) mice, whose incisors showed a further reduction in mineralization. Results from this study support prominent non-redundant roles for both PHOSPHO1 and TNAP in dentin mineralization.
C1 [McKee, M. D.] McGill Univ, Fac Dent, Montreal, PQ, Canada.
[McKee, M. D.] McGill Univ, Fac Med, Dept Anat & Cell Biol, Montreal, PQ, Canada.
[Yadav, M. C.; Millan, J. L.] Sanford Burnham Med Res Inst, Sanford Childrens Hlth Res Ctr, La Jolla, CA USA.
[Foster, B. L.; Somerman, M. J.] NIAMSD, Lab Oral Connect Tissue Biol, NIH, Bethesda, MD 20892 USA.
[Farquharson, C.] Univ Edinburgh, Roslin Inst, Bone Biol Grp, Edinburgh, Midlothian, Scotland.
[Farquharson, C.] Univ Edinburgh, Royal Dick Sch Vet Studies, Edinburgh EH9 1QH, Midlothian, Scotland.
RP McKee, MD (reprint author), McGill Univ, Fac Dent, 3640 Univ St, Montreal, PQ, Canada.
EM marc.mckee@mcgill.ca
RI Foster, Brian/H-8375-2015
OI Foster, Brian/0000-0003-3444-0576
FU CIHR [MOP97858]; NIH [DE12889, AR53102]; Biotechnology and Biological
Sciences Research Council, UK (CF); NIAMS/NIH
FX This work was funded by the CIHR (MOP97858-MDM), the NIH (DE12889 and
AR53102-JLM), an Institute Strategic Program Grant from the
Biotechnology and Biological Sciences Research Council, UK (CF), and the
Intramural Program of NIAMS/NIH (MJS). MDM is a member of the FRQ-S
Network in Oral and Bone Health Research. The authors thank Lydia
Malynowsky and Valentin Nelea for assistance with microscopy, and Laura
Zweifler for assistance with antibody screening. The authors declare no
potential conflicts of interest with respect to the authorship
and/publication of this article.
NR 31
TC 14
Z9 15
U1 0
U2 11
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0022-0345
J9 J DENT RES
JI J. Dent. Res.
PD AUG
PY 2013
VL 92
IS 8
BP 721
EP 727
DI 10.1177/0022034513490958
PG 7
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 182JQ
UT WOS:000321738500009
PM 23694930
ER
PT J
AU Orlando, PA
Brown, JS
Gatenby, RA
Guliano, AR
AF Orlando, Paul A.
Brown, Joel S.
Gatenby, Robert A.
Guliano, Anna R.
TI The Ecology of Human Papillomavirus-Induced Epithelial Lesions and the
Role of Somatic Evolution in Their Progression
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE human papillomavirus; somatic evolution; partial differential equation
model
ID CERVICAL CARCINOGENESIS; STEM-CELLS; HPV-16 E5; EXPRESSION; TYPE-16;
CANCER; CYCLE; DNA; INFECTION; ADHESION
AB Background. Human papillomavirus (HPV) infection frequently induces hyperproliferation of epithelial cells, leading to both benign (warts) and malignant tumors (cervical cancer). We seek to understand how HPV may achieve these changes by modulating cellular population dynamics. Furthermore, HPV-induced lesion progression is generally understood as a series of molecular changes. As a complement to this approach, we investigate the role of phenotypic changes produced by natural selection during lesion progression.
Methods. We develop and numerically analyze spatially and evolutionarily explicit mathematical models of HPV-induced epithelial lesions.
Results. Infection of basal cells is a requirement for persistent infection. Increasing the maximum tissue density at which HPV-infected cells can divide and decreasing infected cell migration rate leads to large increases in the number of HPV-infected cells, and consequently, virions shed from the skin surface per day. Evolution by natural selection in an autonomous population of cells leads to tissue changes that are qualitatively similar to those observed during lesion progression.
Conclusions. HPV modulates cell population dynamics, which can be characterized by specific ecological parameters. As an unintended consequence, this ecological strategy of the virus may be successfully co-opted by autonomous host cells and play a role in lesion progression.
C1 [Orlando, Paul A.] NCI, Div Canc Prevent, Biometry Res Grp, Rockville, MD 20892 USA.
[Brown, Joel S.] Univ Illinois, Dept Biol Sci, Chicago, IL 60680 USA.
[Gatenby, Robert A.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Radiol, Tampa, FL 33682 USA.
[Guliano, Anna R.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Canc Epidemiol, Tampa, FL 33682 USA.
RP Orlando, PA (reprint author), NCI, Execut Plaza North,Ste 3131,6130 Execut Blvd,MSC, Rockville, MD 20892 USA.
EM paul.orlando@nih.gov
FU National Institutes of Health [1U54CA143970-01]
FX This work was supported by the National Institutes of Health (grant
1U54CA143970-01).
NR 29
TC 1
Z9 2
U1 0
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD AUG 1
PY 2013
VL 208
IS 3
BP 394
EP 402
DI 10.1093/infdis/jit172
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 178PB
UT WOS:000321458800005
PM 23599315
ER
PT J
AU Khurana, S
Wu, J
Dimitrova, M
King, LR
Manischewitz, J
Graham, BS
Ledgerwood, JE
Golding, H
AF Khurana, Surender
Wu, Jian
Dimitrova, Milena
King, Lisa R.
Manischewitz, Jody
Graham, Barney S.
Ledgerwood, Julie E.
Golding, Hana
TI DNA Priming Prior to Inactivated Influenza A(H5N1) Vaccination Expands
the Antibody Epitope Repertoire and Increases Affinity Maturation in a
Boost-Interval-Dependent Manner in Adults
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE H5N1; influenza; vaccine; antibody; affinity; Phage display; epitope;
hemagglutinin; SPR; immune response; virus
ID VIRUS; PROTECTION; VACCINES; AVIDITY
AB DNA priming improves the response to inactivated influenza A(H5N1) vaccination. We compared the immunogenicity of an H5 DNA prime (using strain A/Indonesia/5/2005) followed by an H5N1 monovalent inactivated vaccine boost at 4, 8, 12, 16, or 24 weeks to that of 2 doses of H5N1 monovalent inactivated vaccine in adults. Antibody epitope repertoires were elucidated by genome-fragment phage-display library analysis, and antibody avidities for HA1 and HA2 domains were measured by surface plasmon resonance. H5 DNA priming expanded the H5-specific antibody epitope repertoire and enhanced antibody avidity to the HA1 (but not the HA2) domain in an interval-dependent manner. Enhanced HA1 binding and avidity after an interval of >= 12 weeks between prime and boost correlated with improved neutralization of homologous and heterologous H5N1 strains.
C1 [Khurana, Surender; Wu, Jian; Dimitrova, Milena; King, Lisa R.; Manischewitz, Jody; Golding, Hana] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
[Graham, Barney S.; Ledgerwood, Julie E.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Khurana, S (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
EM surender.khurana@fda.hhs.gov
RI Wu, Jian/K-2038-2015
OI Wu, Jian/0000-0001-8011-9551
FU Food and Drug Administration; National Institutes of Health
FX This work was supported by the Food and Drug Administration and the
National Institutes of Health.
NR 15
TC 31
Z9 31
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD AUG 1
PY 2013
VL 208
IS 3
BP 413
EP 417
DI 10.1093/infdis/jit178
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 178PB
UT WOS:000321458800007
PM 23633404
ER
PT J
AU Ledgerwood, JE
Zephir, K
Hu, ZH
Wei, CJ
Chang, L
Enama, ME
Hendel, CS
Sitar, S
Bailer, RT
Koup, RA
Mascola, JR
Nabel, GJ
Graham, BS
AF Ledgerwood, Julie E.
Zephir, Kathryn
Hu, Zonghui
Wei, Chih-Jen
Chang, LeeJah
Enama, Mary E.
Hendel, Cynthia S.
Sitar, Sandra
Bailer, Robert T.
Koup, Richard A.
Mascola, John R.
Nabel, Gary J.
Graham, Barney S.
CA VRC 310 Study Team
TI Prime-Boost Interval Matters: A Randomized Phase 1 Study to Identify the
Minimum Interval Necessary to Observe the H5 DNA Influenza Vaccine
Priming Effect
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE Avian influenza; DNA vaccine; H5N1; boost interval; hemagglutination
inhibition
ID I CLINICAL-TRIAL; CANDIDATE VACCINE; VIRUS; IMMUNOGENICITY; ANTIBODIES;
SAFETY
AB Background. H5 DNA priming was previously shown to improve the antibody response to influenza A(H5N1) monovalent inactivated vaccine (MIV) among individuals for whom there was a 24-week interval between prime and boost receipt. This study defines the shortest prime-boost interval associated with an improved response to MIV.
Methods. We administered H5 DNA followed by MIV at intervals of 4, 8, 12, 16, or 24 weeks and compared responses to that of 2 doses of MIV (prime-boost interval, 24 weeks).
Results. H5 DNA priming with an MIV boost = 12 weeks later showed an improved response, with a positive hemagglutination inhibition (HAI) titer in 91% of recipients (geometric mean titer [GMT], 141-206), compared with 55%-70% of recipients with an H5 DNA and MIV prime-boost interval of <= 8 weeks (GMT, 51-70) and 44% with an MIV-MIV prime-boost interval of 24 weeks (GMT, 27).
Conclusion. H5 DNA priming enhances antibody responses after an MIV boost when the prime-boost interval is 12-24 weeks.
C1 [Ledgerwood, Julie E.; Zephir, Kathryn; Wei, Chih-Jen; Chang, LeeJah; Enama, Mary E.; Hendel, Cynthia S.; Sitar, Sandra; Bailer, Robert T.; Koup, Richard A.; Mascola, John R.; Nabel, Gary J.; Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Hu, Zonghui] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA.
RP Ledgerwood, JE (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 10,Rm 5-2436, Bethesda, MD 20892 USA.
EM ledgerwood@mail.nih.gov
FU National Institutes of Health Intramural Program
FX This work was supported by The National Institutes of Health Intramural
Program.
NR 15
TC 42
Z9 42
U1 0
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD AUG 1
PY 2013
VL 208
IS 3
BP 418
EP 422
DI 10.1093/infdis/jit180
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 178PB
UT WOS:000321458800008
PM 23633407
ER
PT J
AU Armah, GE
Kapikian, AZ
Vesikari, T
Cunliffe, N
Jacobson, RM
Burlington, DB
Ruiz, LP
AF Armah, George E.
Kapikian, Albert Z.
Vesikari, Timo
Cunliffe, Nigel
Jacobson, Robert M.
Burlington, D. Bruce
Ruiz, Leonard P., Jr.
TI Efficacy, Immunogenicity, and Safety of Two Doses of a Tetravalent
Rotavirus Vaccine RRV-TV in Ghana With the First Dose Administered
During the Neonatal Period
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE rotavirus; rotavirus infections; rotavirus vaccines; Ghana; randomized
controlled trial; diarrhea; infantile; gastroenteritis; humans; infant;
vaccines; attenuated
ID POLYMERASE CHAIN-REACTION; INTUSSUSCEPTION RISK; FINNISH CHILDREN;
HEALTH-BENEFITS; SEVERE DIARRHEA; INFANTS; GASTROENTERITIS; AGE;
ROTASHIELD; BIRTH
AB Background. Oral rhesus/rhesus-human reassortant rotavirus tetravalent vaccine (RRV-TV) was licensed in 1998 but withdrawn in 1999 due to a rare association with intussusception, which occurred disproportionately in infants receiving their first dose at >= 90 days of age. This study examined RRV-TV for the prevention of rotavirus gastroenteritis (RV-GE) in Ghana, West Africa, with infants receiving the first dose during the neonatal period and the second before 60 days of age.
Methods. In a double-blinded, randomized, placebo-controlled trial in Navrongo, Ghana, we recruited neonates to receive 2 doses of RRV-TV or placebo and followed them to age 12 months.
Results. In the intention-to-treat population of 998 infants, we measured a vaccine efficacy of 63.1% against RV-GE of any severity associated with any of the 4 serotypes represented in the vaccine and 60.7% against RV-GE associated with any rotavirus serotype.
Conclusions. RRV-TV in a 2-dose schedule with the first dose during the neonatal period is efficacious in preventing RV-GE in rural Ghana. Neonatal dosing results in early protection and may be the optimum schedule to avoid or significantly reduce intussusception, now reported to be associated in international settings with the 2 most widely marketed, licensed, live virus, oral rotavirus vaccines.
C1 [Armah, George E.] Univ Ghana, Coll Hlth Sci, Legon, Ghana.
[Kapikian, Albert Z.] NIAID, Epidemiol Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Vesikari, Timo] Univ Tampere, Vaccine Res Ctr, FIN-33101 Tampere, Finland.
[Cunliffe, Nigel] Univ Liverpool, Dept Clin Infect Microbiol & Immunol, Liverpool L69 3BX, Merseyside, England.
[Jacobson, Robert M.] Mayo Clin, Dept Pediat & Adolescent Med, Rochester, MN 55905 USA.
[Ruiz, Leonard P., Jr.] Int Med Fdn, Rochester, MN USA.
RP Jacobson, RM (reprint author), Mayo Clin, Desk Ba3B,200 1st St SW, Rochester, MN 55905 USA.
EM jacobson.robert@mayo.edu
OI Cunliffe, Nigel/0000-0002-5449-4988; Jacobson,
Robert/0000-0002-6355-8752
FU Noguchi Memorial Institute for Medical Research, University Of Ghana
FX G. E. A.'s institution, the Noguchi Memorial Institute for Medical
Research, University Of Ghana, received grant funds for his work as this
study's principal investigator. A. Z. K. is listed as an inventor on one
or more patents that relate to the tetravalent rhesus rotavirus vaccine
described in the enclosed manuscript. He assigned his rights to the US
Government as required by his status as an employee of the US
Government. Accordingly, the US Government, and not A. Z. K. personally,
controls these rights. Pursuant to the Federal Technology Transfer Act,
royalties that the US Government receives through licensing of these
rights are required to be distributed to the laboratory where the
invention was made and to inventors. A. Z. K. understands that US
Government ethics rules, to which he is subject, specifically exempt
Federal Technology Transfer Act payments from conflict of interest
prohibitions.
NR 46
TC 17
Z9 18
U1 3
U2 12
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD AUG 1
PY 2013
VL 208
IS 3
BP 423
EP 431
DI 10.1093/infdis/jit174
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 178PB
UT WOS:000321458800009
PM 23599316
ER
PT J
AU Maiga, M
Ammerman, NC
Maiga, MC
Tounkara, A
Siddiqui, S
Polis, M
Murphy, R
Bishai, WR
AF Maiga, Mamoudou
Ammerman, Nicole C.
Maiga, Mariama C.
Tounkara, Anatole
Siddiqui, Sophia
Polis, Michael
Murphy, Robert
Bishai, William R.
TI Adjuvant Host-Directed Therapy with Types 3 and 5 but Not Type 4
Phosphodiesterase Inhibitors Shortens the Duration of Tuberculosis
Treatment
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE tuberculosis; mouse model; phosphodiesterase inhibitor; rolipram;
cilomilast; cilostazol; sildenafil
ID PHARMACOKINETICS; RIFAMPIN; ROLIPRAM; MODEL; CHEMOTHERAPY; PYRAZINAMIDE;
CILOSTAZOL; ACTIVATION; DISEASE; SINGLE
AB Background. Shortening tuberculosis treatment could significantly improve patient adherence and decrease the development of drug resistance. Phosphodiesterase inhibitors (PDE-Is) have been shown to be beneficial in animal models of tuberculosis. We assessed the impact of PDE-Is on the duration of treatment in tuberculous mice.
Methods. We analyzed the time to death in Mycobacterium tuberculosis-infected mice receiving type 4 PDE-Is (rolipram and cilomilast) and the impact on bacterial burden, time to clearance, and relapse when types 3 and 5 PDE-Is (cilostazol and sildenafil, respectively) and rolipram were added to the standard treatment. We investigated pharmacokinetic interactions between PDE-Is (cilostazol and sildenafil) and rifampin.
Results. The type 4 PDE-Is rolipram and cilomilast accelerated the time to death in tuberculous mice. The addition of rolipram to standard tuberculosis treatment increased bacterial burden and did not decrease the time to bacterial clearance in the lung, while the addition of the cilostazol and sildenafil reduced the time to clearance by 1 month. Cilostazol and sildenafil did not have negative pharmacokinetic interactions with rifampin.
Conclusions. Type 4 PDE-Is may increase the severity of tuberculosis and should be carefully investigated for use in patients with latent or active tuberculosis. Cilostazol and sildenafil may benefit tuberculosis patients by shortening the duration of therapy.
C1 [Maiga, Mamoudou; Ammerman, Nicole C.; Maiga, Mariama C.; Bishai, William R.] Johns Hopkins Univ, Sch Med, Ctr TB Res, Baltimore, MD 21231 USA.
[Siddiqui, Sophia; Polis, Michael] NIAID, Div Clin Res, Bethesda, MD 20892 USA.
[Bishai, William R.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Murphy, Robert] Northwestern Univ, Div Infect Dis, Chicago, IL 60611 USA.
[Maiga, Mamoudou; Tounkara, Anatole] Univ Sci Tech & Technol Bamako, SEREFO HIV TB, Bamako, Mali.
[Ammerman, Nicole C.; Bishai, William R.] KwaZulu Natal Res Inst TB & HIV, Durban, South Africa.
RP Bishai, WR (reprint author), Johns Hopkins Univ, Sch Med, Ctr TB Res, 1550 Orleans St,Ste 103, Baltimore, MD 21231 USA.
EM wbishai@jhmi.edu
OI Polis, Michael/0000-0002-9151-2268; Murphy, Robert/0000-0003-3936-2052
FU National Institutes of Health [AI30036, AI37856, AI36973]; National
Institute of Allergy and Infectious Diseases Division of Intramural
Research; Fogarty International Center for the Advanced Study in the
Health Sciences [D43TW007995]; Howard Hughes Medical Institute
FX This work was supported by the National Institutes of Health (grants
AI30036, AI37856, and AI36973 to W. R. B.), the National Institute of
Allergy and Infectious Diseases Division of Intramural Research (award
to M. M.), the Fogarty International Center for the Advanced Study in
the Health Sciences (D43TW007995 to R. L. M. and A. T.), and the Howard
Hughes Medical Institute (to W. R. B.].
NR 25
TC 23
Z9 23
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD AUG 1
PY 2013
VL 208
IS 3
BP 512
EP 519
DI 10.1093/infdis/jit187
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 178PB
UT WOS:000321458800019
PM 23641020
ER
PT J
AU Tong, SYC
Sharma-Kuinkel, BK
Thaden, JT
Whitney, AR
Yang, SJ
Mishra, NN
Rude, T
Lilliebridge, RA
Selim, MA
Ahn, SH
Holt, DC
Giffard, PM
Bayer, AS
DeLeo, FR
Fowler, VG
AF Tong, Steven Y. C.
Sharma-Kuinkel, Batu K.
Thaden, Joshua T.
Whitney, Adeline R.
Yang, Soo-Jin
Mishra, Nagendra N.
Rude, Thomas
Lilliebridge, Rachael A.
Selim, Maria A.
Ahn, Sun Hee
Holt, Deborah C.
Giffard, Philip M.
Bayer, Arnold S.
DeLeo, Frank R.
Fowler, Vance G., Jr.
TI Virulence of Endemic Nonpigmented Northern Australian Staphylococcus
aureus Clone (Clonal Complex 75, S-argenteus) Is Not Augmented by
Staphyloxanthin
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE Staphylococcus aureus; staphyloxanthin; virulence; Australia; carotenoid
pigment
ID PANTON-VALENTINE LEUKOCIDIN; COMMUNITIES; BIOSYNTHESIS; EPIDEMIOLOGY;
DETERMINANT; STRAINS
AB Staphylococcus aureus clonal complex 75 (herein referred to as S. argenteus) lacks the carotenoid pigment operon, crtOPQMN, responsible for production of the putative virulence factor, staphyloxanthin. Although a common cause of community-onset skin infections among Indigenous populations in northern Australia, this clone is infrequently isolated from hospital-based patients with either bacteremic or nonbacteremic infections. We hypothesized that S. argenteus would have attenuated virulence compared to other S. aureus strains due to its staphyloxanthin "deficiency." Compared to prototypical S. aureus strains, S. argenteus was more susceptible to oxidative stress and neutrophil killing in vitro and had reduced virulence in murine sepsis and skin infection models. Transformation with pTX-crtOPQMN resulted in staphyloxanthin expression and increased resistance to oxidative stress in vitro. However, neither resistance to neutrophil killing nor in vivo virulence was increased. Thus, reduced virulence of S. argenteus in these models is due to mechanisms unrelated to lack of staphyloxanthin production.
C1 [Tong, Steven Y. C.; Sharma-Kuinkel, Batu K.; Thaden, Joshua T.; Rude, Thomas; Selim, Maria A.; Ahn, Sun Hee; Fowler, Vance G., Jr.] Duke Univ, Med Ctr, Durham, NC 27710 USA.
[Tong, Steven Y. C.; Lilliebridge, Rachael A.; Holt, Deborah C.; Giffard, Philip M.] Charles Darwin Univ, Menzies Sch Hlth Res, Darwin, NT 0909, Australia.
[Whitney, Adeline R.; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Yang, Soo-Jin; Mishra, Nagendra N.; Bayer, Arnold S.] LA Biomed Res Inst, Torrance, CA USA.
[Yang, Soo-Jin; Mishra, Nagendra N.; Bayer, Arnold S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
RP Fowler, VG (reprint author), Duke Univ, Dept Med, Div Infect Dis, Med Ctr, Hanes Bldg,Rm 153,Box 102359,Trent Dr, Durham, NC 27710 USA.
EM fowle003@mc.duke.edu
RI Giffard, Philip/N-2293-2013; Holt, Deborah/A-8002-2012;
OI DeLeo, Frank/0000-0003-3150-2516
FU Australian National Health and Medical Research Council Postdoctoral
Training Fellowship [508829]; Australian-American Fulbright Scholarship;
Royal Australasian College of Physicians, Bayer Medical Research
Fellowship; National Institutes of Health (NIH) [R01 AI068804, K24
AI093969]; NIH [RO1-AI039108-14]; Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, NIH
FX This work was supported by an Australian National Health and Medical
Research Council Postdoctoral Training Fellowship (grant 508829), an
Australian-American Fulbright Scholarship, and a Royal Australasian
College of Physicians, Bayer Medical Research Fellowship for S. Y. C.
T.; grants R01 AI068804 and K24 AI093969 from the National Institutes of
Health (NIH) for V. G. F.; RO1-AI039108-14 from the NIH for A. S. B.;
and the Intramural Research Program of the National Institute of Allergy
and Infectious Diseases, NIH.
NR 22
TC 16
Z9 16
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD AUG 1
PY 2013
VL 208
IS 3
BP 520
EP 527
DI 10.1093/infdis/jit173
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 178PB
UT WOS:000321458800020
PM 23599317
ER
PT J
AU Abbenhardt, C
McTiernan, A
Alfano, CM
Wener, MH
Campbell, KL
Duggan, C
Foster-Schubert, KE
Kong, A
Toriola, AT
Potter, JD
Mason, C
Xiao, L
Blackburn, GL
Bain, C
Ulrich, CM
AF Abbenhardt, C.
McTiernan, A.
Alfano, C. M.
Wener, M. H.
Campbell, K. L.
Duggan, C.
Foster-Schubert, K. E.
Kong, A.
Toriola, A. T.
Potter, J. D.
Mason, C.
Xiao, L.
Blackburn, G. L.
Bain, C.
Ulrich, C. M.
TI Effects of individual and combined dietary weight loss and exercise
interventions in postmenopausal women on adiponectin and leptin levels
SO JOURNAL OF INTERNAL MEDICINE
LA English
DT Article
DE adiponectin; diet and exercise intervention; leptin; randomized
controlled trial
ID BODY-MASS INDEX; INSULIN-RESISTANCE; METABOLIC SYNDROME; BREAST-CANCER;
CARDIOVASCULAR-DISEASE; CLINICAL-TRIAL; COLON-CANCER; OBESITY; RISK;
ADIPOKINES
AB BackgroundExcess body weight and a sedentary lifestyle are associated with the development of several diseases, including cardiovascular disease, diabetes and cancer in women. One proposed mechanism linking obesity to chronic diseases is an alteration in adipose-derived adiponectin and leptin levels. We investigated the effects of 12-month reduced calorie, weight loss and exercise interventions on adiponectin and leptin concentrations.
MethodsOverweight/obese postmenopausal women (n=439) were randomized as follows: (i) a reduced calorie, weight-loss diet (diet; N=118), (ii) moderate-to-vigorous intensity aerobic exercise (exercise; N=117), (iii) a combination of a reduced calorie, weight-loss diet and moderate-to-vigorous intensity aerobic exercise (diet+exercise; N=117), and (iv) control (N=87). The reduced calorie diet had a 10% weight-loss goal. The exercise intervention consisted of 45min of moderate-to-vigorous aerobic activity 5days per week. Adiponectin and leptin levels were measured at baseline and after 12months of intervention using a radioimmunoassay.
ResultsAdiponectin increased by 9.5% in the diet group and 6.6% in the diet+exercise group (both P0.0001 vs. control). Compared with controls, leptin decreased with all interventions (diet+exercise, -40.1%, P<0.0001; diet, -27.1%, P<0.0001; exercise, -12.7%, P=0.005). The results were not influenced by the baseline body mass index (BMI). The degree of weight loss was inversely associated with concentrations of adiponectin (diet, P-trend=0.0002; diet+exercise, P-trend=0.0005) and directly associated with leptin (diet, P-trend<0.0001; diet+exercise, P-trend<0.0001).
ConclusionWeight loss through diet or diet+exercise increased adiponectin concentrations. Leptin concentrations decreased in all of the intervention groups, but the greatest reduction occurred with diet+exercise. Weight loss and exercise exerted some beneficial effects on chronic diseases via effects on adiponectin and leptin.
C1 [Abbenhardt, C.; Toriola, A. T.; Ulrich, C. M.] Natl Ctr Tumor Dis, Div Prevent Oncol, Heidelberg, Germany.
[Abbenhardt, C.; Toriola, A. T.; Ulrich, C. M.] German Canc Res Ctr, D-69120 Heidelberg, Germany.
[Abbenhardt, C.; McTiernan, A.; Duggan, C.; Kong, A.; Potter, J. D.; Mason, C.; Xiao, L.; Bain, C.; Ulrich, C. M.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA USA.
[McTiernan, A.; Foster-Schubert, K. E.] Univ Washington, Sch Med, Seattle, WA USA.
[McTiernan, A.; Potter, J. D.; Ulrich, C. M.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA.
[Alfano, C. M.] NCI, Off Canc Survivorship, NIH, Bethesda, MD 20892 USA.
[Wener, M. H.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
[Campbell, K. L.] Univ British Columbia, Fac Med, Vancouver, BC, Canada.
[Kong, A.] Univ Illinois, Canc Educ & Career Dev Program, Chicago, IL USA.
[Toriola, A. T.] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA.
[Toriola, A. T.] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA.
[Potter, J. D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand.
[Blackburn, G. L.] Harvard Univ, Sch Med, Div Nutr, Boston, MA USA.
RP Ulrich, CM (reprint author), German Canc Res Ctr, Div Prevent Oncol Prevent Oncol, Natl Ctr Tumor Dis, Neuenheimer Feld 460, D-69120 Heidelberg, Germany.
EM neli.ulrich@nct-heidelberg.de
RI Duggan, Catherine/F-9414-2015;
OI Duggan, Catherine/0000-0001-7369-4021; Toriola,
Adetunji/0000-0003-1079-2606; Potter, John/0000-0001-5439-1500
FU National Cancer Institute at the National Institutes of Health
[U54-CA116847, R01 CA102504, 5KL2RR025015, R25 CA94880, R25 CA057699];
Canadian Institutes of Health Research
FX We would like to thank the study staff and the participants for their
dedication to the study. This work was supported by the National Cancer
Institute at the National Institutes of Health (grants U54-CA116847, R01
CA102504; 5KL2RR025015 to K. F. S; R25 CA94880 and R25 CA057699 to A.
K.); and the Canadian Institutes of Health Research (Fellowships to K.
L. C & C. M). None of the funding agencies were involved in the trial
design or conduct. During the trial, Dr. Alfano was a faculty member at
Ohio State University and relocated to the NCI following completion of
her efforts on the NEW trial.
NR 47
TC 36
Z9 37
U1 1
U2 20
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0954-6820
J9 J INTERN MED
JI J. Intern. Med.
PD AUG
PY 2013
VL 274
IS 2
BP 163
EP 175
DI 10.1111/joim.12062
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA 181JZ
UT WOS:000321665200009
PM 23432360
ER
PT J
AU Choi, JW
Kang, SM
Lee, Y
Hong, SH
Sanek, NA
Young, WS
Lee, HJ
AF Choi, Ji-Woong
Kang, Sung-Min
Lee, Youngkyun
Hong, Su-Hyung
Sanek, Nicholas A.
Young, W. Scott
Lee, Heon-Jin
TI MicroRNA profiling in the mouse hypothalamus reveals oxytocin-regulating
microRNA
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE AVP; deep sequencing; hypothalamus; microRNA; OXT
ID GENE-REGULATION; SMALL RNAS; EXPRESSION; VASOPRESSIN; SYSTEM; TARGETS;
ACID; RECOGNITION; PITUITARY; ESTROGEN
AB Oxytocin (Oxt), produced in the hypothalamic paraventricular and supraoptic nuclei for transport to and release from the posterior pituitary, was originally discovered through its role in lactation and parturition. Oxt also plays important roles in the central nervous system by influencing various behaviors. MicroRNAs (miRNAs), endogenous regulators of many genes, are a class of small non-coding RNAs that mediate post-transcriptional gene silencing. We performed miRNA expression profiling of the mouse hypothalamus by deep sequencing. Among the sequenced and cross-mapped small RNAs, expression of known miRNAs and unknown miRNAs candidates were analyzed. We investigated in detail one miRNA, miR-24, and found that it is a novel regulator of Oxt and controls both transcript and peptide levels of Oxt. These results provide insights into potential neurohypophysial hormone regulation mediated by miRNAs.
C1 [Choi, Ji-Woong; Kang, Sung-Min; Hong, Su-Hyung; Lee, Heon-Jin] Kyungpook Natl Univ, Dept Oral Microbiol, Sch Dent, Taegu 700412, South Korea.
[Lee, Youngkyun] Kyungpook Natl Univ, Dept Oral Biochem, Sch Dent, Taegu 700412, South Korea.
[Sanek, Nicholas A.; Young, W. Scott] NIMH, Sect Neural Gene Express, NIH, Bethesda, MD 20892 USA.
[Lee, Heon-Jin] Kyungpook Natl Univ, Brain Sci & Engn Inst, Taegu 700412, South Korea.
RP Lee, HJ (reprint author), Kyungpook Natl Univ, Dept Oral Microbiol, Sch Dent, 2177 Dalgubeol Daero, Taegu 700412, South Korea.
EM heonlee@knu.ac.kr
RI Young, W Scott/A-9333-2009;
OI Young, W Scott/0000-0001-6614-5112; , Heon-Jin/0000-0002-1911-5014
FU Basic Science Research Program through the National Research Foundation
of Korea (NRF); Ministry of Education, Science and Technology
[2011-0028240, 2011-0014086]; NIMH Intramural Research Program
[Z01-MH-002498-22]
FX This research was supported by Basic Science Research Program through
the National Research Foundation of Korea (NRF) funded by the Ministry
of Education, Science and Technology (2011-0028240 and 2011-0014086).
W.S.Y. and N.A.S. were supported by the NIMH Intramural Research Program
(Z01-MH-002498-22).
NR 47
TC 12
Z9 14
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2013
VL 126
IS 3
BP 331
EP 337
DI 10.1111/jnc.12308
PG 7
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 185PM
UT WOS:000321982000005
PM 23682839
ER
PT J
AU Kirkali, Z
AF Kirkali, Ziya
TI Can We Change Patient Behaviors to Improve Urological Health?
SO JOURNAL OF UROLOGY
LA English
DT Editorial Material
ID CANCER
C1 NIDDK, Bethesda, MD 20892 USA.
RP Kirkali, Z (reprint author), NIDDK, Bethesda, MD 20892 USA.
NR 8
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 0022-5347
J9 J UROLOGY
JI J. Urol.
PD AUG
PY 2013
VL 190
IS 2
BP 383
EP 384
DI 10.1016/j.juro.2013.05.025
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 178HJ
UT WOS:000321436600003
PM 23688639
ER
PT J
AU Narouz, MR
Soliman, SE
Bassily, RW
El-Sokkary, RI
Nasr, AZ
Nashed, MA
AF Narouz, Mina R.
Soliman, Sameh E.
Bassily, Rafik W.
El-Sokkary, Ramadan I.
Nasr, Adel Z.
Nashed, Mina A.
TI Regioselective Synthesis of Novel Mono-Substituted D-lactose Fatty Acid
Ester Derivatives
SO LETTERS IN ORGANIC CHEMISTRY
LA English
DT Article
DE Carbohydrate fatty acid monoesters; regioisomeric lactose fatty acid
esters; regioselective esterification and stannylene derivative
ID SUGAR ESTERS; CARBOHYDRATE; SOLVENT
AB Three regioisomers of lactose fatty acid monoesters at positions 3', 6' and 3 and other related compounds have been chemically synthesized. The 3'- and 6'-O-palmitoyl-D-lactose derivatives were prepared via the regioselective esterification at O-3' and O-6' of the dibutylstannylene derivatives obtained from benzyl 2,3,6-tri-O-benzyl-4-O-(2,6-di-O-benzyl-beta-D-galactopyranosyl)-beta-D-glucopyranoside (1) and benzyl 2,3,6-tri-O-benzyl-4-O-(2,3-di-O-benzyl-beta-D-galactopyranosyl)-beta-D-glucopyranoside (5), respectively, with the acid chloride, followed by hydrogenolysis of the benzyl groups. The 3-O-acyl-D-lactose derivatives were prepared via the regioselective esterification at O-3 of benzyl 2,6-di-O-benzyl-4-O-(2,6-di-O-benzyl-3,4-O-isopropylidene-beta-D-galactopyranosyl)-beta-D-glucopyranoside (9) using DCC coupling method with the free acids, followed by selective removal of the 3',4'-O-isopropylidene group, and then hydrogenolysis of the benzyl groups.
C1 [Narouz, Mina R.; Nasr, Adel Z.] Damanhour Univ, Fac Sci, Dept Chem, Damanhour, Beheira, Egypt.
[Soliman, Sameh E.; Bassily, Rafik W.; El-Sokkary, Ramadan I.; Nashed, Mina A.] Univ Alexandria, Fac Sci, Dept Chem, Alexandria 21321, Egypt.
[Soliman, Sameh E.] NIDDK, LBC, NIH, Bethesda, MD 20892 USA.
RP Nashed, MA (reprint author), Univ Alexandria, Fac Sci, Dept Chem, POB 426, Alexandria 21321, Egypt.
EM mina4na@yahoo.com
NR 15
TC 1
Z9 1
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 1570-1786
J9 LETT ORG CHEM
JI Lett. Org. Chem.
PD AUG
PY 2013
VL 10
IS 7
BP 502
EP 509
PG 8
WC Chemistry, Organic
SC Chemistry
GA 176UW
UT WOS:000321332300007
ER
PT J
AU Rodriguez-Arias, D
Tortosa, JC
Burant, CJ
Aubert, P
Aulisio, MP
Youngner, SJ
AF Rodriguez-Arias, D.
Tortosa, J. C.
Burant, C. J.
Aubert, P.
Aulisio, M. P.
Youngner, S. J.
TI One or two types of death? Attitudes of health professionals towards
brain death and donation after circulatory death in three countries
SO MEDICINE HEALTH CARE AND PHILOSOPHY
LA English
DT Article
DE Attitude to death; Tissue and organ procurement; Ethics; Attitude of
health personnel; Donation after circulatory death; Brain death; France;
Spain; United States
ID INTENSIVE-CARE-UNIT; ORGAN DONATION; CARDIAC DEATH; DONOR RULE;
CARDIOCIRCULATORY DEATH; UNCONTROLLED DONATION; LIFE-SUPPORT;
PERSPECTIVE; ACCEPTANCE; KNOWLEDGE
AB This study examined health professionals' (HPs) experience, beliefs and attitudes towards brain death (BD) and two types of donation after circulatory death (DCD)-controlled and uncontrolled DCD. Five hundred and eighty-seven HPs likely to be involved in the process of organ procurement were interviewed in 14 hospitals with transplant programs in France, Spain and the US. Three potential donation scenarios-BD, uncontrolled DCD and controlled DCD-were presented to study subjects during individual face-to-face interviews. Our study has two main findings: (1) In the context of organ procurement, HPs believe that BD is a more reliable standard for determining death than circulatory death, and (2) While the vast majority of HPs consider it morally acceptable to retrieve organs from brain-dead donors, retrieving organs from DCD patients is much more controversial. We offer the following possible explanations. DCD introduces new conditions that deviate from standard medical practice, allow procurement of organs when donors' loss of circulatory function could be reversed, and raises questions about "death" as a unified concept. Our results suggest that, for many HPs, these concerns seem related in part to the fact that a rigorous brain examination is neither clinically performed nor legally required in DCD. Their discomfort could also come from a belief that irreversible loss of circulatory function has not been adequately demonstrated. If DCD protocols are to achieve their full potential for increasing organ supply, the sources of HPs' discomfort must be further identified and addressed.
C1 [Rodriguez-Arias, D.] CSIC, Spanish Natl Res Council, CCHS, Inst Philosophy, Madrid 28037, Spain.
[Rodriguez-Arias, D.; Tortosa, J. C.] Univ Paris 05, Lab Eth Med, Paris, France.
[Tortosa, J. C.] Hop St Camille, Bry Sur Marne, France.
[Burant, C. J.] Case Western Reserve Univ, Frances Payne Bolton Sch Nursing, Cleveland, OH 44106 USA.
[Burant, C. J.] Louis Stokes Cleveland VA Med Ctr, Geriatr Res Educ & Clin Ctr, Cleveland, OH USA.
[Aubert, P.; Aulisio, M. P.; Youngner, S. J.] Case Western Reserve Univ, Dept Bioeth, Cleveland, OH 44106 USA.
[Aubert, P.] NIH, Bethesda, MD 20892 USA.
RP Rodriguez-Arias, D (reprint author), CSIC, Spanish Natl Res Council, CCHS, Inst Philosophy, C Albasanz 26-28, Madrid 28037, Spain.
EM rodavailg@gmail.com
RI Rodriguez-Arias, David/K-5894-2014
OI Rodriguez-Arias, David/0000-0002-4555-5259
NR 52
TC 6
Z9 7
U1 0
U2 23
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1386-7423
J9 MED HEALTH CARE PHIL
JI Med. Health Care Philos.
PD AUG
PY 2013
VL 16
IS 3
BP 457
EP 467
DI 10.1007/s11019-011-9369-1
PG 11
WC Ethics; History & Philosophy Of Science
SC Social Sciences - Other Topics; History & Philosophy of Science
GA 174BX
UT WOS:000321128900015
PM 22139386
ER
PT J
AU Ramirez, CM
Goedeke, L
Rotllan, N
Yoon, JH
Cirera-Salinas, D
Mattison, JA
Suarez, Y
de Cabo, R
Gorospe, M
Fernandez-Hernando, C
AF Ramirez, Cristina M.
Goedeke, Leigh
Rotllan, Noemi
Yoon, Je-Hyun
Cirera-Salinas, Daniel
Mattison, Julie A.
Suarez, Yajaira
de Cabo, Rafael
Gorospe, Myriam
Fernandez-Hernando, Carlos
TI MicroRNA 33 Regulates Glucose Metabolism
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID FORKHEAD TRANSCRIPTION FACTOR; FATTY-ACID SYNTHESIS; HEPATIC
GLUCONEOGENESIS; INSULIN SENSITIVITY; GENE-EXPRESSION; FACTOR FOXO1;
GLUCOSE-6-PHOSPHATASE GENE; CHOLESTEROL HOMEOSTASIS; COACTIVATOR PGC-1;
ADIPOSE-TISSUE
AB Metabolic diseases are characterized by the failure of regulatory genes or proteins to effectively orchestrate specific pathways involved in the control of many biological processes. In addition to the classical regulators, recent discoveries have shown the remarkable role of small noncoding RNAs (microRNAs [miRNAs]) in the posttranscriptional regulation of gene expression. In this regard, we have recently demonstrated that miR-33a and miR33b, intronic miRNAs located within the sterol regulatory element-binding protein (SREBP) genes, regulate lipid metabolism in concert with their host genes. Here, we show that miR-33b also cooperates with SREBP1 in regulating glucose metabolism by targeting phosphoenolpyruvate carboxykinase (PCK1) and glucose-6-phosphatase (G6PC), key regulatory enzymes of hepatic gluconeogenesis. Overexpression of miR-33b in human hepatic cells inhibits PCK1 and G6PC expression, leading to a significant reduction of glucose production. Importantly, hepatic SREBP1c/miR-33b levels correlate inversely with the expression of PCK1 and G6PC upon glucose infusion in rhesus monkeys. Taken together, these results suggest that miR-33b works in concert with its host gene to ensure a fine-tuned regulation of lipid and glucose homeostasis, highlighting the clinical potential of miR-33a/b as novel therapeutic targets for a range of metabolic diseases.
C1 [Ramirez, Cristina M.; Goedeke, Leigh; Rotllan, Noemi; Cirera-Salinas, Daniel; Suarez, Yajaira; Fernandez-Hernando, Carlos] NYU, Sch Med, Dept Med, New York, NY USA.
[Ramirez, Cristina M.; Goedeke, Leigh; Rotllan, Noemi; Cirera-Salinas, Daniel; Suarez, Yajaira; Fernandez-Hernando, Carlos] NYU, Sch Med, Dept Cell Biol, Leon H Charney Div Cardiol, New York, NY 10016 USA.
[Ramirez, Cristina M.; Goedeke, Leigh; Rotllan, Noemi; Cirera-Salinas, Daniel; Suarez, Yajaira; Fernandez-Hernando, Carlos] NYU, Sch Med, Marc & Ruti Bell Vasc Biol & Dis Program, New York, NY 10016 USA.
[Yoon, Je-Hyun; Gorospe, Myriam] NIA, Genet Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Mattison, Julie A.; de Cabo, Rafael] NIA, Translat Gerontol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Fernandez-Hernando, C (reprint author), NYU, Sch Med, Dept Med, New York, NY USA.
EM carlos.fernandez-hernando@nyumc.org
RI Rotllan, Noemi/P-1375-2014; de Cabo, Rafael/J-5230-2016;
OI Rotllan, Noemi/0000-0002-0587-8045; de Cabo, Rafael/0000-0002-3354-2442;
Ramirez, Cristina M/0000-0003-2589-0786; , rafael/0000-0003-2830-5693;
CIRERA SALINAS, DANIEL/0000-0003-2171-5032
FU National Institutes of Health [R01HL107953, R01HL106063, R01HL105945,
1F31AG043318-01]; American Heart Association [12POST9780016]; Deutsche
Forschungsgemeinschaft; Ministerio de Educacion; Intramural Research
Program of the NIH National Institute on Aging
FX This work was supported by the National Institutes of Health (grants
R01HL107953 and R01HL106063 to C.F.-H., R01HL105945 to Y.S., and
1F31AG043318-01 to L.G.), the American Heart Association (grant
12POST9780016 to C.M.R.), the Deutsche Forschungsgemeinschaft (to
D.C.-S.), and the Ministerio de Educacion (Programa Nacional de
Movilidad de Recursos Humanos del Plan Nacional de I-D + i 2008-2011 to
N.R.]). R.D.C. was supported by the Intramural Research Program of the
NIH National Institute on Aging.
NR 45
TC 43
Z9 44
U1 2
U2 20
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 15
BP 2891
EP 2902
DI 10.1128/MCB.00016-13
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 180SD
UT WOS:000321615500008
PM 23716591
ER
PT J
AU Lamichhane, TN
Blewett, NH
Crawford, AK
Cherkasova, VA
Iben, JR
Begley, TJ
Farabaugh, PJ
Maraia, RJ
AF Lamichhane, Tek N.
Blewett, Nathan H.
Crawford, Amanda K.
Cherkasova, Vera A.
Iben, James R.
Begley, Thomas J.
Farabaugh, Philip J.
Maraia, Richard J.
TI Lack of tRNA Modification Isopentenyl-A37 Alters mRNA Decoding and
Causes Metabolic Deficiencies in Fission Yeast
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID GALACTOSIDASE ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE;
PROTEIN-SYNTHESIS; SCHIZOSACCHAROMYCES-POMBE; CELL-DIVISION; RIBOSOME
BINDING; STRESS-RESPONSE; ANTICODON; TRANSLATION; MITOCHONDRIAL
AB tRNA isopentenyltransferases (Tit1) modify tRNA position 37, adjacent to the anticodon, to N-6-isopentenyladenosine (i6A37) in all cells, yet the tRNA subsets selected for modification vary among species, and their relevance to phenotypes is unknown. We examined the function of i6A37 in Schizosaccharomyces pombe tit1(+) and tit1-Delta cells by using a beta-galactosidase codon-swap reporter whose catalytic activity is sensitive to accurate decoding of codon 503. i6A37 increased the activity of tRNA(Cys) at a cognate codon and that of tRNA(Tyr) at a near-cognate codon, suggesting that i6A37 promotes decoding activity generally and increases fidelity at cognate codons while decreasing fidelity at noncognate codons. S. pombe cells lacking tit1(+) exhibit slow growth in glycerol or rapamycin. While existing data link wobble base U34 modifications to translation of functionally related mRNAs, whether this might extend to the anticodon-adjacent position 37 was unknown. Indeed, we found a biased presence of i6A37-cognate codons in high-abundance mRNAs for ribosome subunits and energy metabolism, congruent with the observed phenotypes and the idea that i6A37 promotes translational efficiency. Polysome profiles confirmed the decreased translational efficiency of mRNAs in tit1-Delta cells. Because subsets of i6A37-tRNAs differ among species, as do their cognate codon-sensitive mRNAs, these genomic variables may underlie associated phenotypic differences.
C1 [Lamichhane, Tek N.; Blewett, Nathan H.; Crawford, Amanda K.; Cherkasova, Vera A.; Iben, James R.; Maraia, Richard J.] NICHD, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Begley, Thomas J.] SUNY Albany, Coll Nanoscale Sci & Engn, Albany, NY 12222 USA.
[Farabaugh, Philip J.] Univ Maryland Baltimore Cty, Dept Biol Sci, Baltimore, MD 21228 USA.
[Maraia, Richard J.] US PHS, Commissioned Corps, Washington, DC USA.
RP Maraia, RJ (reprint author), NICHD, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
EM maraiar@mail.nih.gov
OI Farabaugh, Philip/0000-0002-5658-7141
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH; National
Institutes of Health [1R01ES017010]
FX The Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH, supports work in
the Maraia lab. Work in the Begley lab is supported by the National
Institutes of Health (grant 1R01ES017010).
NR 72
TC 22
Z9 22
U1 4
U2 11
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 15
BP 2918
EP 2929
DI 10.1128/MCB.00278-13
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 180SD
UT WOS:000321615500010
PM 23716598
ER
PT J
AU Chun, LS
Free, RB
Doyle, TB
Huang, XP
Rankin, ML
Sibley, DR
AF Chun, Lani S.
Free, R. Benjamin
Doyle, Trevor B.
Huang, Xi-Ping
Rankin, Michele L.
Sibley, David R.
TI D1-D2 Dopamine Receptor Synergy Promotes Calcium Signaling via Multiple
Mechanisms
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; MEDIUM SPINY NEURONS; PHOSPHOLIPASE-C;
STRIATAL NEURONS; LIPID RAFTS; CA-2+ MOBILIZATION; D1-LIKE RECEPTORS;
ADENYLYL-CYCLASE; GENE-EXPRESSION; MESSENGER-RNAS
AB The D-1 dopamine receptor (D1R) has been proposed to form a hetero-oligomer with the D(2 dop)amine receptor (D2R), which in turn results in a complex that couples to phospholipase C-mediated intracellular calcium release. We have sought to elucidate the pharmacology and mechanism of action of this putative signaling pathway. Dopamine dose-response curves assaying intracellular calcium mobilization in cells heterologously expressing the D-1 and D-2 subtypes, either alone or in combination, and using subtype selective ligands revealed that concurrent stimulation is required for coupling. Surprisingly, characterization of a putative D-1-D-2 heteromer-selective ligand, 6-chloro-2,3,4,5-tetrahydro-3-methyl-1-(3-methylphenyl)-1H-3-benzazepine- 7,8-diol (SKF83959), found no stimulation of calciumrelease, but it did find a broad range of cross-reactivity with other G protein-coupled receptors. In contrast, SKF83959 appeared to be an antagonist of calcium mobilization. Overexpression of G(q alpha) with the D-1 and D-2 dopamine receptors enhanced the dopamine-stimulated calcium response. However, this was also observed in cells expressing G(beta gamma) with only the D1R. Inactivation of G(i) or G(s) with pertussis or cholera toxin, respectively, largely, but not entirely, reduced the calcium response in D1R and D2R cotransfected cells. Moreover, sequestration of Gbg subunits through overexpression of G protein receptor kinase 2 mutants either completely or largely eliminated dopamine-stimulated calcium mobilization. Our data suggest that the mechanism of D1R/D2R-mediated calcium signaling involves more than receptor-mediated G(q) protein activation, may largely involve downstream signaling pathways, and may not be completely heteromer-specific. In addition, SKF83959 may not exhibit selective activation of D-1-D-2 heteromers, and its significant cross-reactivity to other receptors warrants careful interpretation of its use in vivo.
C1 [Chun, Lani S.; Free, R. Benjamin; Doyle, Trevor B.; Rankin, Michele L.; Sibley, David R.] NINDS, Mol Neuropharmacol Sect, NIH, Bethesda, MD 20892 USA.
[Chun, Lani S.] Johns Hopkins Univ, Cellular Mol Dev Biol & Biophys Program, Baltimore, MD USA.
[Huang, Xi-Ping] Univ N Carolina, Sch Med, NIMH, Psychoact Drug Screening Program,Dept Pharmacol, Chapel Hill, NC USA.
RP Sibley, DR (reprint author), NINDS, Mol Neuropharmacol Sect, NIH, 5625 Fishers Lane,Room 4S-04, Bethesda, MD 20892 USA.
EM sibleyd@helix.nih.gov
FU Intramural Research Program of the National Institutes of Health
[National Institute of Neurological Disorders and Stroke]; National
Institutes of Health National Institute of Mental Health Psychoactive
Drug Screening Program
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health [National Institute of Neurological
Disorders and Stroke]; and the National Institutes of Health National
Institute of Mental Health Psychoactive Drug Screening Program.
NR 70
TC 32
Z9 34
U1 1
U2 7
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD AUG
PY 2013
VL 84
IS 2
BP 190
EP 200
DI 10.1124/mol.113.085175
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 183QC
UT WOS:000321831100003
PM 23680635
ER
PT J
AU Ma, F
Lin, F
Chen, C
Cheng, J
Zeldin, DC
Wang, Y
Wang, DW
AF Ma, Fei
Lin, Fan
Chen, Chen
Cheng, Jennifer
Zeldin, Darryl C.
Wang, Yan
Wang, Dao Wen
TI Indapamide Lowers Blood Pressure by Increasing Production of
Epoxyeicosatrienoic Acids in the Kidney
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID SPONTANEOUSLY HYPERTENSIVE-RATS; AFFERENT ARTERIOLAR VASODILATION;
ACTIVATED PROTEIN-KINASE; LEFT-VENTRICULAR MASS; OXIDATIVE STRESS;
NITRIC-OXIDE; PPAR-ALPHA; RENAL FIBROSIS; EPOXYGENASE METABOLITES;
SUSTAINED-RELEASE
AB Diuretics are widely used in the treatment of hypertension, although the precise mechanisms remain unknown. Epoxyeicosatrienoic acids (EETs), cytochrome P450 (P450) epoxygenase metabolites of arachidonic acid, play critical roles in regulation of blood pressure. The present study was carried out to investigate whether EETs participate in the antihypertensive effect of thiazide diuretics [hydrochlorothiazide (HCTZ)] and thiazide-like diuretics (indapamide). Male spontaneously hypertensive rats (SHRs) were treated with indapamide or HCTZ for 8 weeks. Systolic blood pressure, measured via tail-cuff plethysmography and confirmed via intra-arterial measurements, was significantly decreased in indapamide- and HCTZ-treated SHRs compared with saline-treated SHRs. Indapamide increased kidney CYP2C23 expression, decreased soluble epoxide hydrolase expression, increased urinary and renovascular 11,12- and 14,15-EETs, and decreased production of 11,12-and 14,15-dihydroxyeicosatrienoic acids in SHRs. No effect on expression of CYP4A1 or CYP2J3, or on 20-hydroxyeicosatetraenoic acid production, was observed, suggesting indapamide specifically targets CYP2C23-derived EETs. Treatment of SHRs with HCTZ did not affect the levels of P450s or their metabolites. Increased cAMP activity and protein kinase A expression were observed in the renal microvessels of indapamide-treated SHRs. Indapamide ameliorated oxidative stress and inflammation in renal cortices by down-regulating the expression of p47phox, nuclear factor-kappa B, transforming growth factor-beta 1, and phosphorylated mitogen-activated protein kinase. Furthermore, the p47phox-lowering effect of indapamide in angiotensin II-treated rat mesangial cells was partially blocked by the presence of N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MS-PPOH) or CYP2C23 small interfering RNA. Together, these results indicate that the hypotensive effects of indapamide aremediated, at least in part, by the P450 epoxygenase system in SHRs, and provide novel insights into the blood pressure-lowering mechanisms of diuretics.
C1 [Ma, Fei; Lin, Fan; Chen, Chen; Wang, Yan; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Internal Med, Wuhan 430074, Peoples R China.
[Ma, Fei; Lin, Fan; Chen, Chen; Wang, Yan; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Inst Hypertens, Wuhan 430074, Peoples R China.
[Cheng, Jennifer; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
RP Wang, DW (reprint author), Tongji Med Coll, Tongji Hosp, Dept Internal Med, Wuhan 430030, Peoples R China.
EM newswang@tjh.tjmu.edu.cn; dwwang@tjh.tjmu.edu.cn
RI Chen, Chen/B-2080-2014
FU 973 Projects [2012CB517801, 2012CB518004]; National Nature Science
Foundation of China [31130031]; Key Project of The Ministry of Health of
China; Intramural Research Program of the National Institutes of Health
[National Institute of Environmental Health Sciences] [Z01 ES025034]
FX This work was supported by the 973 Projects [2012CB517801 and
2012CB518004]; National Nature Science Foundation of China [31130031];
Key Project of The Ministry of Health of China; and the Intramural
Research Program of the National Institutes of Health [National
Institute of Environmental Health Sciences] [Grant Z01 ES025034].
NR 50
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Z9 4
U1 0
U2 10
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD AUG
PY 2013
VL 84
IS 2
BP 286
EP 295
DI 10.1124/mol.113.085878
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 183QC
UT WOS:000321831100013
PM 23729436
ER
PT J
AU Chandler, M
de la Cruz, F
Dyda, F
Hickman, AB
Moncalian, G
Ton-Hoang, B
AF Chandler, Michael
de la Cruz, Fernando
Dyda, Fred
Hickman, Alison B.
Moncalian, Gabriel
Ton-Hoang, Bao
TI Breaking and joining single-stranded DNA: the HUH endonuclease
superfamily
SO NATURE REVIEWS MICROBIOLOGY
LA English
DT Review
ID ROLLING-CIRCLE REPLICATION; SITE-SPECIFIC RECOMBINATION; REPETITIVE
EXTRAGENIC PALINDROMES; ADENOASSOCIATED VIRUS TYPE-2; CONJUGATIVE
RELAXASE TRWC; PLASMID TRAI RELAXASE; IV SECRETION SYSTEM; GENE-A
PROTEIN; ACTIVE-SITE; BIOCHEMICAL-CHARACTERIZATION
AB HUH endonucleases are numerous and widespread in all three domains of life. The major function of these enzymes is processing a range of mobile genetic elements by catalysing cleavage and rejoining of single-stranded DNA using an active-site Tyr residue to make a transient 5'-phosphotyrosine bond with the DNA substrate. These enzymes have a key role in rolling-circle replication of plasmids and bacteriophages, in plasmid transfer, in the replication of several eukaryotic viruses and in various types of transposition. They have also been appropriated for cellular processes such as intron homing and the processing of bacterial repeated extragenic palindromes. Here, we provide an overview of these fascinating enzymes and their functions, using well-characterized examples of Rep proteins, relaxases and transposases, and we explore the molecular mechanisms used in their diverse activities.
C1 [Chandler, Michael; Ton-Hoang, Bao] CNRS, Lab Microbiol & Genet Mol, UMR 5100, F-31062 Toulouse, France.
[de la Cruz, Fernando; Moncalian, Gabriel] Univ Cantabria, Consejo Super Invest Cient SODERCA, Dept Biol Mol, Santander 39011, Spain.
[de la Cruz, Fernando; Moncalian, Gabriel] Univ Cantabria, Consejo Super Invest Cient SODERCA, Inst Biomed & Biotecnol Cantabria, Santander 39011, Spain.
[Dyda, Fred; Hickman, Alison B.] Natl Inst Diabet & Digest & Kidney Dis, Lab Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Chandler, M (reprint author), CNRS, Lab Microbiol & Genet Mol, UMR 5100, 118 Route Narbonne, F-31062 Toulouse, France.
EM Michael.Chandler@ibcg.biotoul.fr
RI de la Cruz, Fernando/L-2812-2014; Moncalian, Gabriel/K-3493-2014;
OI Moncalian, Gabriel/0000-0002-3007-6490; Chandler,
Michael/0000-0002-0292-6662; de la Cruz, Fernando/0000-0003-4758-6857
FU French Centre National de la Recherche Scientifique; US National
Institute of Diabetes and Digestive and Kidney Diseases; French Agence
National de Recherche [ANR-12-BSV8-0009-01]; Spanish Ministry of Science
and Innovation [BIO2010-14809]; Spanish Ministry of Education
[BFU2011-26608]; European Seventh Framework Program
[248919/FP7-ICT-2009-4, 282004/FP7-HEALTH.2011.2.3.1-2]
FX The authors thank C. Guynet, S. Messing and I. Molineau for discussions.
This work was supported by intramural funding from the French Centre
National de la Recherche Scientifique (to M. C. and B. T. H.) and the
Intramural Program of the US National Institute of Diabetes and
Digestive and Kidney Diseases (to A. B. H. and F. D.), and by grants
from the French Agence National de Recherche (ANR-12-BSV8-0009-01; to B.
T. H.), the Spanish Ministry of Science and Innovation (BIO2010-14809;
to G. M.), the Spanish Ministry of Education (BFU2011-26608; to
F.d.l.C.) and the European Seventh Framework Program
(248919/FP7-ICT-2009-4 and 282004/FP7-HEALTH.2011.2.3.1-2; to F.d.l.C.).
NR 119
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U1 2
U2 32
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1740-1526
J9 NAT REV MICROBIOL
JI Nat. Rev. Microbiol.
PD AUG
PY 2013
VL 11
IS 8
BP 525
EP 538
DI 10.1038/nrmicro3067
PG 14
WC Microbiology
SC Microbiology
GA 183OU
UT WOS:000321827300010
PM 23832240
ER
PT J
AU Wang, B
You, ZB
Oleson, EB
Cheer, JF
Myal, S
Wise, RA
AF Wang, Bin
You, Zhi-Bing
Oleson, Erik B.
Cheer, Joseph F.
Myal, Stephanie
Wise, Roy A.
TI Conditioned Contribution of Peripheral Cocaine Actions to Cocaine Reward
and Cocaine-Seeking
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE cocaine; reward; self-administration; peripheral actions; dopamine;
reinstatement
ID VENTRAL TEGMENTAL AREA; NUCLEUS-ACCUMBENS DOPAMINE; RELAPSE PREVENTION;
CUE-EXPOSURE; EXTINCTION; WITHDRAWAL; DRUG; RELEASE; BRAIN;
REINFORCEMENT
AB Cocaine has actions in the peripheral nervous system that reliably precede-and thus predict-its soon-to-follow central rewarding effects. In cocaine-experienced animals, the peripheral cocaine signal is relayed to the central nervous system, triggering excitatory input to the ventral tegmental origin of the mesocorticolimbic dopamine system, the system that mediates the rewarding effects of the drug. We used cocaine methiodide, a cocaine analog that does not cross the blood-brain barrier, to isolate the peripheral actions of cocaine and determine their central and behavioral effects in animals first trained to lever-press for cocaine hydrochloride (the centrally acting and abused form of the drug). We first confirmed with fast-scan cyclic voltammetry that cocaine methiodide causes rapid dopamine release from dopamine terminals in cocaine hydrochloride-trained rats. We then compared the ability of cocaine hydrochloride and cocaine methiodide to establish conditioned place preferences in rats with self-administration experience. While cocaine hydrochloride established stronger place preferences, cocaine methiodide was also effective and its effectiveness increased (incubated) over weeks of cocaine abstinence. Cocaine self-administration was extinguished when cocaine methiodide or saline was substituted for cocaine hydrochloride in the intravenous self-administration paradigm, but cocaine hydrochloride and cocaine methiodide each reinstated nonrewarded lever-pressing after extinction. Rats extinguished by cocaine methiodide substitution showed weaker cocaine-induced reinstatement than rats extinguished by saline substitution. These findings suggest that the conditioned peripheral effects of cocaine can contribute significantly to cocaine-induced (but not stress-induced) cocaine craving, and also suggest the cocaine cue as an important target for cue-exposure therapies for cocaine addiction.
C1 [Wang, Bin; You, Zhi-Bing; Myal, Stephanie; Wise, Roy A.] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
[Oleson, Erik B.; Cheer, Joseph F.] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA.
RP Wise, RA (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, 5500 Nathan Shock Dr,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM rwise@intra.nida.nih.gov
FU Intramural Research Program of the National Institutes of Health; NIH
[R01DA025890]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health and by NIH Grant R01DA025890 to JFC. We
thank Drs Patricio O'Donnell and Rose-Marie Karlsson for providing
animals with a history of cocaine self-administration for the
voltammetry component of the study.
NR 34
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U1 0
U2 14
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD AUG
PY 2013
VL 38
IS 9
BP 1763
EP 1769
DI 10.1038/npp.2013.75
PG 7
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 183NQ
UT WOS:000321823400016
PM 23535778
ER
PT J
AU Tejeda, HA
Counotte, DS
Oh, E
Ramamoorthy, S
Schultz-Kuszak, KN
Backman, CM
Chefer, V
O'Donnell, P
Shippenberg, TS
AF Tejeda, Hugo A.
Counotte, Danielle S.
Oh, Eric
Ramamoorthy, Sammanda
Schultz-Kuszak, Kristin N.
Baeckman, Cristina M.
Chefer, Vladmir
O'Donnell, Patricio
Shippenberg, Toni S.
TI Prefrontal Cortical Kappa-Opioid Receptor Modulation of Local
Neurotransmission and Conditioned Place Aversion
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE kappa-opioid receptors; prefrontal cortex; dopamine; GABA; glutamate;
aversion
ID IN-VIVO MICRODIALYSIS; NUCLEUS-ACCUMBENS; GLUTAMATE LEVELS;
EXTRACELLULAR GLUTAMATE; DOPAMINERGIC-NEURONS; CORTEX; RAT; MU;
DYNORPHIN; COCAINE
AB Kappa-opioid receptors (KORs) are important for motivation and other medial prefrontal cortex (mPFC)-dependent behaviors. Although KORs are present in the mPFC, their role in regulating transmission in this brain region and their contribution to KOR-mediated aversion are not known. Using in vivo microdialysis in rats and mice, we demonstrate that intra-mPFC administration of the selective KOR agonist U69,593 decreased local dopamine (DA) overflow, while reverse dialysis of the KOR antagonist nor-Binaltorphimine (nor-BNI) enhanced mPFC DA overflow. Extracellular amino-acid levels were also affected by KORs, as U69,593 reduced glutamate and GABA levels driven by the glutamate reuptake blocker, l-trans-pyrrolidine-2,4-dicarboxylate. Whole-cell recordings from mPFC layer V pyramidal neurons revealed that U69,593 decreased the frequency, but not amplitude, of glutamatergic mini EPSPs. To determine whether KOR regulation of mPFC DA overflow was mediated by KOR on DA terminals, we utilized a Cre recombinase-driven mouse line lacking KOR in DA neurons. In these mice, basal DA release or uptake was unaltered relative to controls, but attenuation of mPFC DA overflow by local U69,593 was not observed, indicating KOR acts directly on mPFC DA terminals to locally inhibit DA levels. Conditioning procedures were then used to determine whether mPFC KOR signaling was necessary for KOR-mediated aversion. U69,593-mediated conditioned place aversion was blocked by intra-mPFC nor-BNI microinjection. These findings demonstrate that mPFC KORs negatively regulate DA and amino-acid neurotransmission, and are necessary for KOR-mediated aversion.
C1 [Tejeda, Hugo A.; Oh, Eric; Baeckman, Cristina M.; Chefer, Vladmir; Shippenberg, Toni S.] NIDA, Integrat Neurosci Sect, Integrat Neuroscience Branch, Baltimore, MD USA.
[Tejeda, Hugo A.; Counotte, Danielle S.; O'Donnell, Patricio] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA.
[Ramamoorthy, Sammanda] Univ S Carolina, Dept Neurosci, Div Neurosci Res Med, Charleston, SC USA.
[O'Donnell, Patricio] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA.
RP Tejeda, HA (reprint author), Univ Maryland, Sch Med, Dept Anat & Neurobiol, 20 Penn St,Room S-251, Baltimore, MD 21201 USA.
EM tejedah@nida.nih.gov
OI O'Donnell, Patricio/0000-0001-7788-624X
FU National Institute on Drug Abuse Intramural Research Program; National
Institutes of Health [MH57683, MH083928]; National Science Foundation
Graduate Research Fellowship; Meyerhoff Graduate Fellowship; Ford
Foundation Predoctoral Fellowship
FX This work was supported by the National Institute on Drug Abuse
Intramural Research Program, grants from the National Institutes of
Health (PO, MH57683; TSS and SR, MH083928), a National Science
Foundation Graduate Research Fellowship (HAT), a Meyerhoff Graduate
Fellowship (HAT), and a Ford Foundation Predoctoral Fellowship (HAT).
The authors would like to thank Dr Jennifer Whistler for her generous
donation of the KORloxp mice. The authors would like to thank
Drs Brad Alger, Antonello Bonci, Joe Cheer, and Greg Elmer for their
helpful comments and discussion.
NR 45
TC 31
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U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD AUG
PY 2013
VL 38
IS 9
BP 1770
EP 1779
DI 10.1038/npp.2013.76
PG 10
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 183NQ
UT WOS:000321823400017
PM 23542927
ER
PT J
AU Hajnal, A
Thanos, PK
Volkow, ND
AF Hajnal, Andras
Thanos, Panayotis K.
Volkow, Nora D.
TI Notes on "Roux en Y Gastric Bypass Increases Ethanol Intake in the Rat"
by Davis et al.
SO OBESITY SURGERY
LA English
DT Letter
ID BARIATRIC SURGERY; CONSUMPTION; PREVALENCE; ABUSE
C1 [Hajnal, Andras] Penn State Univ, Dept Neural & Behav Sci, Coll Med, Hershey, PA 17033 USA.
[Hajnal, Andras] Penn State Univ, Dept Surg, Coll Med, Hershey, PA 17033 USA.
[Thanos, Panayotis K.; Volkow, Nora D.] NIAAA, Lab Neuroimaging, Intramural Program, NIH, Bethesda, MD USA.
[Thanos, Panayotis K.] Brookhaven Natl Lab, Behav Neuropharmacol & Neuroimaging Lab, Upton, NY 11973 USA.
RP Hajnal, A (reprint author), Penn State Univ, Dept Neural & Behav Sci, Coll Med, 500 Univ Dr,Mail Code H181, Hershey, PA 17033 USA.
EM ahajnal@psu.edu
OI Hajnal, Andras/0000-0001-7297-7134
FU NIDDK NIH HHS [R01 DK080899]
NR 9
TC 1
Z9 1
U1 1
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0960-8923
J9 OBES SURG
JI Obes. Surg.
PD AUG
PY 2013
VL 23
IS 8
BP 1317
EP 1317
DI 10.1007/s11695-013-0961-8
PG 1
WC Surgery
SC Surgery
GA 177QC
UT WOS:000321389200809
PM 23649870
ER
PT J
AU Zhao, W
Petit, E
Gafni, RI
Collins, MT
Robey, PG
Seton, M
Miller, KK
Mannstadt, M
AF Zhao, W.
Petit, E.
Gafni, R. I.
Collins, M. T.
Robey, P. G.
Seton, M.
Miller, K. K.
Mannstadt, M.
TI Mutations in NOTCH2 in patients with Hajdu-Cheney syndrome
SO OSTEOPOROSIS INTERNATIONAL
LA English
DT Article
DE Acroosteolysis; Exome sequencing; Hajdu-Cheney syndrome; NOTCH2;
Osteoporosis
ID OSTEOPOROSIS; ACTIVATION; DISORDER
AB The Hajdu-Cheney syndrome is a very rare disease that affects several organ system, leading to severe osteoporosis and other abnormalities. We describe clinical and genetic findings of nine patients with this disease.
The Hajdu-Cheney syndrome (HCS) is a rare autosomal dominant disorder characterized by severe osteoporosis, acroosteolysis of the distal phalanges, renal cysts, and other abnormalities. Recently, heterozygous mutations in NOTCH2 were identified as the cause of HCS.
Nine patients with typical presentations of HCS took part in this study: five affected patients from two small families and four sporadic cases. Peripheral blood DNA was obtained and exome sequencing performed in one affected individual per family and in all four sporadic cases. Sanger sequencing confirmed mutations in all patients.
One of the identified mutations was introduced in a plasmid encoding NOTCH2. Wild-type and mutant NOTCH2 were transiently expressed in HEK293 cells to assess intracellular localization after ligand activation. Deleterious heterozygous mutations in the last NOTCH2 exon were identified in all patients; five of the six mutations were novel.
Consistent with previous reports, all mutations are predicted to result in a loss of the proline/glutamic acid/serine/threonine sequence, which harbors signals for degradation, therefore suggesting activating mutations. One of the six mutations furthermore predicted disruption of the second nuclear localization signal of NOTCH2, but the mutant revealed normal nuclear localization after transfection, which is consistent with the proposed gain-of-function mechanism as the cause of this autosomal dominant disease. Our findings confirm that heterozygous NOTCH2 mutations are the cause of HCS and expand the mutational spectrum of this disorder.
C1 [Zhao, W.; Petit, E.; Mannstadt, M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[Seton, M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA.
[Gafni, R. I.; Collins, M. T.; Robey, P. G.] NIDCR, CSDB, NIH, Bethesda, MD USA.
[Miller, K. K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
RP Mannstadt, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Thier 10,55 Fruit St, Boston, MA 02114 USA.
EM mmannstadt@partners.org
RI Robey, Pamela/H-1429-2011
OI Robey, Pamela/0000-0002-5316-5576
FU NHGRI [U54 HG003067]; National Institute of Diabetes and Digestive and
Kidney Disease [K08-DK081669-01]; Division of Intramural Research,
NIDCR, a part of the Intramural Research Program of the NIH, DHHS
FX We like to thank all patients and family members who participated in
this study. We thank the Broad Institute for generating high-quality
sequence data supported by NHGRI funds (U54 HG003067, PI Eric Lander),
Harald Juppner for support and Spyros Artavanis-Tsakonas for the Notch2
cDNA plasmid. This research was supported, in part, by grants from the
National Institute of Diabetes and Digestive and Kidney Disease
(K08-DK081669-01 to M. M.) and by the Division of Intramural Research,
NIDCR, a part of the Intramural Research Program of the NIH, DHHS.
NR 25
TC 8
Z9 8
U1 0
U2 5
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-941X
EI 1433-2965
J9 OSTEOPOROSIS INT
JI Osteoporosis Int.
PD AUG
PY 2013
VL 24
IS 8
BP 2275
EP 2281
DI 10.1007/s00198-013-2298-5
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 181GH
UT WOS:000321655500015
PM 23389697
ER
PT J
AU Prentice, RL
Jackson, RD
Rossouw, JE
AF Prentice, R. L.
Jackson, R. D.
Rossouw, J. E.
TI Calcium supplements and cardiovascular risk in the Women's Health
Initiative: response to Bolland et al.
SO OSTEOPOROSIS INTERNATIONAL
LA English
DT Letter
ID VITAMIN-D; EVENTS; METAANALYSIS
C1 [Prentice, R. L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Jackson, R. D.] Ohio State Univ, Columbus, OH 43210 USA.
[Rossouw, J. E.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Prentice, RL (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave North,M3-A410,POB 19024, Seattle, WA 98109 USA.
EM rprentic@whi.org
NR 5
TC 1
Z9 1
U1 0
U2 6
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-941X
J9 OSTEOPOROSIS INT
JI Osteoporosis Int.
PD AUG
PY 2013
VL 24
IS 8
BP 2373
EP 2374
DI 10.1007/s00198-013-2359-9
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 181GH
UT WOS:000321655500028
PM 23563935
ER
PT J
AU Li, WW
Shi, XY
Wang, LP
Guo, TZ
Wei, TP
Cheng, KJ
Rice, KC
Kingery, WS
Clark, JD
AF Li, Wenwu
Shi, Xiaoyou
Wang, Liping
Guo, Tianzhi
Wei, Tzuping
Cheng, Kejun
Rice, Kenner C.
Kingery, Wade S.
Clark, J. David
TI Epidermal adrenergic signaling contributes to inflammation and pain
sensitization in a rat model of complex regional pain syndrome
SO PAIN
LA English
DT Article
DE Sympathetic signaling; Interleukin-6; Keratinocyte; Complex regional
pain syndrome
ID SYNDROME TYPE-I; TIBIA FRACTURE MODEL; FACTOR-KAPPA-B; NOCICEPTIVE
SENSITIZATION; PROINFLAMMATORY CYTOKINES; SYNDROME TYPE-1; NEUROGENIC
INFLAMMATION; SENSORY NEURONS; RECEPTOR; KERATINOCYTES
AB In many patients, the sympathetic nervous system supports pain and other features of complex regional pain syndrome (CRPS). Accumulating evidence suggests that interleukin (IL)-6 also plays a role in CRPS, and that catecholamines stimulate production of IL-6 in several tissues. We hypothesized that norepinephrine acting through specific adrenergic receptors expressed on keratinocytes stimulates the production of IL-6 and leads to nociceptive sensitization in a rat tibial fracture/cast model of CRPS. Our approach involved catecholamine depletion using 6-hydroxydopamine or, alternatively, guanethidine, to explore sympathetic contributions. Both agents substantially reduced nociceptive sensitization and selectively reduced the production of IL-6 in skin. Antagonism of IL-6 signaling using TB-2-081 also reduced sensitization in this model. Experiments using a rat keratinocyte cell line demonstrated relatively high levels of beta 2-adrenergic receptor (beta 2-AR) expression. Stimulation of this receptor greatly enhanced IL-6 expression when compared to the expression of IL-1 beta, tumor necrosis factor (TNF)-alpha, or nerve growth factor. Stimulation of the cells also promoted phosphorylation of the mitogen-activated protein kinases P38, extracellular signal-regulated kinase, and c-Jun amino-terminal kinase. Based on these in vitro results, we returned to animal testing and observed that the selective beta 2-AR antagonist butoxamine reduced nociceptive sensitization in the CRPS model, and that local injection of the selective beta 2-AR agonist terbutaline resulted in mechanical allodynia and the production of IL-6 in the cells of the skin. No increases in IL-1 beta, TNF-alpha, or nerve growth factor levels were seen, however. These data suggest that in CRPS, norepinephrine released from sympathetic nerve terminals stimulates beta 2-ARs expressed on epidermal keratinocytes, resulting in local IL-6 production, and ultimately, pain sensitization. Published by Elsevier B.V. on behalf of International Association for the Study of Pain.
C1 [Li, Wenwu; Shi, Xiaoyou; Wang, Liping; Guo, Tianzhi; Wei, Tzuping; Kingery, Wade S.] Vet Affairs Palo Alto Hlth Care Syst, Phys Med & Rehabil Serv, Palo Alto, CA 94304 USA.
[Li, Wenwu; Shi, Xiaoyou; Clark, J. David] Vet Affairs Palo Alto Hlth Care Syst, Anesthesia Serv, Palo Alto, CA 94304 USA.
[Li, Wenwu; Shi, Xiaoyou; Clark, J. David] Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA.
[Cheng, Kejun; Rice, Kenner C.] NIDA, NIH, Bethesda, MD 20892 USA.
[Cheng, Kejun; Rice, Kenner C.] NIAAA, Bethesda, MD USA.
RP Clark, JD (reprint author), Vet Affairs Palo Alto Hlth Care Syst, Anesthesia Serv, 3801 Miranda Ave, Palo Alto, CA 94304 USA.
EM djclark@stanford.edu
FU National Institutes of Health [NS072168, NS072143]; Department of
Veterans Affairs [F7137R]; National Institute on Drug Abuse; National
Institute on Alcohol Abuse and Alcoholism
FX This study was supported by National Institutes of Health grants
NS072168 and NS072143, and Department of Veterans Affairs Rehabilitation
Research and Development Merit grant F7137R. A portion of this work was
supported by the Intramural Research Programs of the National Institute
on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism.
NR 59
TC 20
Z9 20
U1 0
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD AUG
PY 2013
VL 154
IS 8
BP 1224
EP 1236
DI 10.1016/j.pain.2013.03.033
PG 13
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 176XF
UT WOS:000321339400010
PM 23718987
ER
PT J
AU Kolb, EA
Gorlick, R
Reynolds, CP
Kang, MH
Carol, H
Lock, R
Keir, ST
Maris, JM
Billups, CA
DesJardins, C
Kurmasheva, RT
Houghton, PJ
Smith, MA
AF Kolb, E. Anders
Gorlick, Richard
Reynolds, C. Patrick
Kang, Min H.
Carol, Hernan
Lock, Richard
Keir, Stephen T.
Maris, John M.
Billups, Catherine A.
DesJardins, Christopher
Kurmasheva, Raushan T.
Houghton, Peter J.
Smith, Malcolm A.
TI Initial testing (stage 1) of eribulin, a novel tubulin binding agent, by
the pediatric preclinical testing program
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE developmental therapeutics; PI3K inhibitor; preclinical testing
ID MALIGNANT SOLID TUMORS; HIGH-DOSE METHOTREXATE; SOFT-TISSUE SARCOMA;
ADJUVANT CHEMOTHERAPY; HALICHONDRIN-B; VINCRISTINE SULFATE; WILMS TUMOR;
PHASE-II; IN-VITRO; MESYLATE
AB Background Antimitotic agents are essential components for curative therapy of pediatric acute leukemias and many solid tumors. Eribulin is a novel agent that differs from both Vinca alkaloids and taxanes in its mode of binding to tubulin polymers. Procedures Eribulin was tested against the PPTP in vitro cell line panel at concentrations from 0.1nM to 1.0M and against the PPTP in vivo xenograft panels at a dose of 1mg/kg (solid tumors) or 1.5mg/kg (ALL models) using a q4dx3 schedule repeated at Day 21. Results In vitro eribulin demonstrated cytotoxic activity, with a median relative IC50 value of 0.27nM, (range <0.1-14.8nM). Eribulin was well tolerated in vivo, and all 43 xenograft models were considered evaluable for efficacy. Eribulin induced significant differences in event-free survival (EFS) distribution compared to control in 29 of 35 (83%) of the solid tumors and in 8 of 8 (100%) of the ALL xenografts. Objective responses were observed in 18 of 35 (51%) solid tumor xenografts. Complete responses (CR) or maintained CR were observed in panels of Wilms tumor, Ewing sarcoma, rhabdomyosarcoma, glioblastoma, and osteosarcoma xenografts. All eight ALL xenografts achieved CR or MCR. Conclusions The high level of activity observed for eribulin against the PPTP preclinical models makes this an interesting agent to consider for pediatric evaluation. The activity pattern observed for eribulin in the solid tumor panels is equal or superior to that observed previously for vincristine. Pediatr Blood Cancer 2013;601325-1332. (c) 2013 Wiley Periodicals, Inc.
C1 [Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE 19803 USA.
[Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
[Reynolds, C. Patrick; Kang, Min H.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA.
[Carol, Hernan; Lock, Richard] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia.
[Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA.
[Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA.
[Maris, John M.] Abramson Family Canc Res Inst, Philadelphia, PA USA.
[Billups, Catherine A.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[DesJardins, Christopher] Eisai Inc, Andover, MA USA.
[Kurmasheva, Raushan T.; Houghton, Peter J.] Nationwide Childrens Hosp, Columbus, OH USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Kolb, EA (reprint author), Alfred I DuPont Hosp Children, Dept Oncol, 1600 Rockland Rd, Wilmington, DE 19803 USA.
EM eakolb@nemours.org
RI Houghton, Peter/E-3265-2011; Lock, Richard/G-4253-2013;
OI Reynolds, C. Patrick/0000-0002-2827-8536
FU National Cancer Institute [NO1-CM-42216, CA21765, CA108786]
FX Grant sponsor: National Cancer Institute; Grant numbers: NO1-CM-42216;
CA21765; CA108786
NR 42
TC 25
Z9 26
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD AUG
PY 2013
VL 60
IS 8
BP 1325
EP 1332
DI 10.1002/pbc.24517
PG 8
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 164HL
UT WOS:000320399800020
PM 23553917
ER
PT J
AU Brehm, C
Huenecke, S
Pfirrmann, V
Rossig, C
Mackall, CL
Bollard, CM
Gottschalk, S
Schlegel, PG
Klingebiel, T
Bader, P
AF Brehm, Claudia
Huenecke, Sabine
Pfirrmann, Verena
Rossig, Claudia
Mackall, Crystal L.
Bollard, Catherine M.
Gottschalk, Stephen
Schlegel, Paul G.
Klingebiel, Thomas
Bader, Peter
TI Highlights of the Third International Conference on Immunotherapy in
Pediatric Oncology
SO PEDIATRIC HEMATOLOGY AND ONCOLOGY
LA English
DT Article
DE ADCC; antibody-based immunotherapy; CAR; chimeric antigen receptor; CIK;
cytokine-induced killer cells; hematopoietic stem cell transplantation;
HSCT; immunotherapy; natural killer cells NK; oncology
ID STEM-CELL TRANSPLANTATION; NATURAL-KILLER-CELLS; CLINICAL-SCALE
GENERATION; MESENCHYMAL STROMAL CELLS; ACUTE MYELOID-LEUKEMIA;
VERSUS-HOST-DISEASE; T-CELLS; NK CELLS; IN-VIVO; BRENTUXIMAB VEDOTIN
AB The third International Conference on Immunotherapy in Pediatric Oncology was held in Frankfurt/Main, Germany, October 1-2, 2012. Major topics of the conference included (i) cellular therapies using antigen-specific and gene-modified T cells for targeting leukemia and pediatric solid tumors; (ii) overcoming hurdles and barriers with regard to immunogenicity, immune escape, and the role of tumor microenvironment; (iii) vaccine strategies and antigen presentation; (iv) haploidentical transplantation and innate immunity; (v) the role of immune cells in allogeneic transplantation; and (vi) current antibody/immunoconjugate approaches for the treatment of pediatric malignancies. During the past decade, major advances have been made in improving the efficacy of these modalities and regulatory hurdles have been taken. Nevertheless, there is still a long way to go to fully exploit the potential of immunotherapeutic strategies to improve the cure of children and adolescents with malignancies. This and future meetings will support new collaborations and insights for further translational and clinical immunotherapy studies.
C1 [Brehm, Claudia; Huenecke, Sabine; Pfirrmann, Verena; Klingebiel, Thomas; Bader, Peter] Univ Hosp Children & Adolescents, Dept Stem Cell Transplantat & Immunol, JW Goethe Univ Hosp, D-60590 Frankfurt, Germany.
[Rossig, Claudia] Univ Childrens Hosp Munster, Dept Pediat Hematol & Oncol, Munster, Germany.
[Mackall, Crystal L.] NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Bollard, Catherine M.; Gottschalk, Stephen] Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Ctr Cell & Gene Therapy,Texas Childrens Canc Ctr, Houston, TX 77030 USA.
[Schlegel, Paul G.] Univ Wurzburg, Univ Childrens Hosp Wurzburg, Dept Pediat Hematol & Oncol, Ctr Comprehens Canc, Wurzburg, Germany.
RP Bader, P (reprint author), Univ Hosp Children & Adolescents, Dept Stem Cell Transplantat & Immunol, Theodor Stern Kai 7, D-60590 Frankfurt, Germany.
EM peter.bader@kgu.de
FU Hessisches Ministerium fur Wissenschaft und Kunst (HMWK)
FX This meeting was generously supported by the "Kind-Philipp-Stiftung fur
Leukamieforschung," "AdolfMesser Stiftung," "Hilfe fur krebskranke
Kinder Frankfurt e.V.," and "LOEWE Center for Cell and Gene Therapy
Frankfurt funded by: Hessisches Ministerium fur Wissenschaft und Kunst
(HMWK)".
NR 78
TC 2
Z9 4
U1 0
U2 6
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0888-0018
J9 PEDIATR HEMAT ONCOL
JI Pediatr. Hematol. Oncol.
PD AUG
PY 2013
VL 30
IS 5
BP 349
EP 366
DI 10.3109/08880018.2013.802106
PG 18
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 182VH
UT WOS:000321772400001
PM 23758210
ER
PT J
AU Ito, S
Barrett, AJ
AF Ito, Sawa
Barrett, A. John
TI Response to the Letter: Allogeneic Hematopoietic Stem Cell
Transplantation for Treatment of Gaucher Disease
SO PEDIATRIC HEMATOLOGY AND ONCOLOGY
LA English
DT Letter
ID MIGLUSTAT; TYPE-3
C1 [Ito, Sawa; Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Ito, S (reprint author), NHLBI, Hematol Branch, NIH, Ctr Dr Bldg 10, Bethesda, MD 20892 USA.
EM itos2@nhlbi.nih.gov
NR 9
TC 0
Z9 0
U1 0
U2 1
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0888-0018
J9 PEDIATR HEMAT ONCOL
JI Pediatr. Hematol. Oncol.
PD AUG
PY 2013
VL 30
IS 5
BP 462
EP 463
DI 10.3109/08880018.2013.793758
PG 2
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 182VH
UT WOS:000321772400015
PM 23848391
ER
PT J
AU Palvinskaya, T
Antkowiak, M
Burg, E
Lenox, CC
Ubags, N
Cramer, A
Rincon, M
Dixon, AE
Fessler, MB
Poynter, ME
Suratt, BT
AF Palvinskaya, Tatsiana
Antkowiak, Maryellen
Burg, Elianne
Lenox, Christopher C.
Ubags, Niki
Cramer, Angela
Rincon, Mercedes
Dixon, Anne E.
Fessler, Michael B.
Poynter, Matthew E.
Suratt, Benjamin T.
TI Effects of acute and chronic low density lipoprotein exposure on
neutrophil function
SO PULMONARY PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
DE Neutrophil; Cholesterol; Dyslipidemia; Chemotaxis; Cytokines; Immunity;
Innate
ID ACUTE LUNG INJURY; BODY-MASS INDEX; POLYMORPHONUCLEAR LEUKOCYTES;
SUPPRESSOR-CELLS; OBESITY; ATHEROSCLEROSIS; MACROPHAGES; MICE;
HYPERCHOLESTEROLEMIA; METAANALYSIS
AB Mounting evidence suggests that obesity and the metabolic syndrome have significant but often divergent effects on the innate immune system. These effects have been best established in monocytes and macrophages, particularly as a consequence of the hypercholesterolemic state. We have recently described defects in neutrophil function in the setting of both obesity and hypercholesterolemia, and hypothesized that exposure to elevated levels of lipoproteins, particularly LDL its oxidized forms, contributed to these defects. As a model of chronic cholesterol exposure, we examined functional responses of bone marrow neutrophils isolated from non-obese mice with diet-induced hypercholesterolemia compared to normal cholesterol controls. Chemotaxis, calcium flux, CD11b display, and F-actin polymerization were assayed in response to several chemoattractants, while neutrophil cytokine transcriptional response was determined to LPS. Following this, the acute effects of isolated LDL and its oxidized forms on normal neutrophils were assayed using the same functional assays. We found that neutrophils from non-obese hypercholesterolemic mice had blunted chemotaxis, altered calcium flux, and normal to augmented CD11b display with prolonged actin polymerization in response to stimuli. In response to acute exposure to lipoproteins, neutrophils showed chemotaxis to LDL which increased with the degree of LDL oxidation. Paradoxically, LDL oxidation yielded the opposite effect on LDL-induced CD11b display and actin polymerization, and both native and oxidized LDL were found to induce neutrophil transcription of the monocyte chemoattractant MCP-1. Together these findings suggest that chronic hypercholesterolemia impairs neutrophil functional responses, and these defects may be in part due to protracted signaling responses to LDL and its oxidized forms. (c) 2012 Elsevier Ltd. All rights reserved.
C1 [Palvinskaya, Tatsiana; Antkowiak, Maryellen; Burg, Elianne; Lenox, Christopher C.; Ubags, Niki; Cramer, Angela; Rincon, Mercedes; Dixon, Anne E.; Poynter, Matthew E.; Suratt, Benjamin T.] Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA.
[Ubags, Niki] Maastricht Univ, Med Ctr, Dept Resp Med, NL-6202 AZ Maastricht, Netherlands.
[Fessler, Michael B.] NIEHS, Lab Resp Biol, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Suratt, BT (reprint author), Univ Vermont, Coll Med, Dept Med, 89 Beaumont Ave,Given E407A, Burlington, VT 05405 USA.
EM benjamin.suratt@uvm.edu
FU National Institutes of Health [RO1 HL084200, RO1 HL089177, NCRR
P20RR15557]; Intramural Research Program of the National Institutes of
Health, National Institute of Environmental Health Sciences
FX This work was supported by Grants RO1 HL084200, RO1 HL089177, and NCRR
P20RR15557 from the National Institutes of Health, and by the Intramural
Research Program of the National Institutes of Health, National
Institute of Environmental Health Sciences.
NR 35
TC 4
Z9 4
U1 0
U2 7
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1094-5539
J9 PULM PHARMACOL THER
JI Pulm. Pharmacol. Ther.
PD AUG
PY 2013
VL 26
IS 4
BP 405
EP 411
DI 10.1016/j.pupt.2012.10.002
PG 7
WC Pharmacology & Pharmacy; Respiratory System
SC Pharmacology & Pharmacy; Respiratory System
GA 177WT
UT WOS:000321406800002
PM 23084986
ER
PT J
AU Gowdy, KM
Fessler, MB
AF Gowdy, Kymberly M.
Fessler, Michael B.
TI Emerging roles for cholesterol and lipoproteins in lung disease
SO PULMONARY PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
DE Pulmonary disease; Dyslipidemia; Statins; Metabolic syndrome;
Inflammation; Cholesterol
ID APOLIPOPROTEIN-A-I; OBSTRUCTIVE PULMONARY-DISEASE; COMMUNITY-ACQUIRED
PNEUMONIA; CONVERTING ENZYME-INHIBITORS; RANDOMIZED CONTROLLED-TRIAL;
RECEPTOR AGONIST TREATMENT; SMOOTH-MUSCLE-CELLS; PRIOR STATIN USE;
HOST-DEFENSE; DIETARY-CHOLESTEROL
AB Dyslipidemia, the condition of elevated serum triglycerides, elevated low-density lipoprotein cholesterol, and/or low high-density lipoprotein cholesterol, is a public health problem of growing concern. Dyslipidemia clusters with other disorders of the metabolic syndrome that together influence, and may derive from, chronic inflammation. While best recognized as a risk factor for atherosclerotic cardiovascular disease, lipid dysregulation has recently been shown to influence a variety of disease processes in several organ systems. This review highlights our current understanding of the role of cholesterol and its homeostatic trafficking in pulmonary physiology and pathophysiology. Gene-targeted mice deficient in regulatory proteins that govern reverse cholesterol transport (e.g., ATP Binding Cassette transporter G1, apolipoprotein E) have recently been shown to have abnormal lung physiology, including dysregulated pulmonary innate and adaptive immune responses to the environment. It has also recently been shown that diet-induced dyslipidemia alters trafficking of immune cells to the lung in a manner that may have important implications for the pathogenesis of acute lung injury, asthma, pneumonia, and other lung disorders. Conversely, cholesterol-targeting pharmacologic agents, such as statins, apolipoprotein mimetic peptides, and Liver X Receptor agonists, have shown early promise in the treatment of several lung disorders. An improved understanding of the precise molecular mechanisms by which cholesterol and its trafficking modify pulmonary immunity will be required before the full implications of dyslipidemia as a lung disease modifier, and the full potential of lipid-targeting agents as pulmonary therapeutics, can be realized. Published by Elsevier Ltd.
C1 [Gowdy, Kymberly M.; Fessler, Michael B.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
RP Gowdy, KM (reprint author), NIEHS, Lab Resp Biol, NIH, 111 TW Alexander Dr,POB 12233,MD D2-01, Res Triangle Pk, NC 27709 USA.
EM gowdykm@niehs.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Institute of Environmental Health Sciences [Z01 ES102005]
FX The authors thank Sue Edelstein for figure design and Drs. Don Cook and
Bethany Hsia for critical review of the manuscript. This work was
supported in part by the Intramural Research Program of the National
Institutes of Health, National Institute of Environmental Health
Sciences (Z01 ES102005).
NR 101
TC 24
Z9 25
U1 0
U2 15
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1094-5539
J9 PULM PHARMACOL THER
JI Pulm. Pharmacol. Ther.
PD AUG
PY 2013
VL 26
IS 4
BP 430
EP 437
DI 10.1016/j.pupt.2012.06.002
PG 8
WC Pharmacology & Pharmacy; Respiratory System
SC Pharmacology & Pharmacy; Respiratory System
GA 177WT
UT WOS:000321406800006
PM 22706330
ER
PT J
AU Ferreira, JR
Padilla, R
Urkasemsin, G
Yoon, K
Goeckner, K
Hu, WS
Ko, CC
AF Ferreira, Joao R.
Padilla, Ricardo
Urkasemsin, Ganokon
Yoon, Kun
Goeckner, Kelly
Hu, Wei-Shou
Ko, Ching-Chang
TI Titanium-Enriched Hydroxyapatite-Gelatin Scaffolds with Osteogenically
Differentiated Progenitor Cell Aggregates for Calvaria Bone Regeneration
SO TISSUE ENGINEERING PART A
LA English
DT Article
ID MESENCHYMAL STEM-CELLS; GROWTH-FACTOR; RAT TIBIAE; MARROW; EXPANSION;
TISSUE; DEFECTS; REPAIR; ULTRASTRUCTURE; NANOCOMPOSITES
AB Adequate bony support is the key to re-establish both function and esthetics in the craniofacial region. Autologous bone grafting has been the gold standard for regeneration of problematic large bone defects. However, poor graft availability and donor-site complications have led to alternative bone tissue-engineering approaches combining osteoinductive biomaterials and three-dimensional cell aggregates in scaffolds or constructs. The goal of the present study was to generate novel cell aggregate-loaded macroporous scaffolds combining the osteoinductive properties of titanium dioxide (TiO2) with hydroxyapatite-gelatin nanocomposites (HAP-GEL) for regeneration of craniofacial defects. Here we investigated the in vivo applicability of macroporous (TiO2)-enriched HAP-GEL scaffolds with undifferentiated and osteogenically differentiated multipotent adult progenitor cell (MAPC and OD-MAPC, respectively) aggregates for calvaria bone regeneration. The silane-coated HAP-GEL with and without TiO2 additives were polymerized and molded to produce macroporous scaffolds. Aggregates of the rat MAPC were precultured, loaded into each scaffold, and implanted to rat calvaria critical-size defects to study bone regeneration. Bone autografts were used as positive controls and a poly(lactic-co-glycolic acid) (PLGA) scaffold for comparison purposes. Preimplanted scaffolds and calvaria bone from pig were tested for ultimate compressive strength with an Instron 4411 (R) and for porosity with microcomputerized tomography (mu CT). Osteointegration and newly formed bone (NFB) were assessed by mu CT and nondecalcified histology, and quantified by calcium fluorescence labeling. Results showed that the macroporous TiO2-HAP-GEL scaffold had a comparable strength relative to the natural calvaria bone (13.8 +/- 4.5 MPa and 24.5 +/- 8.3 MPa, respectively). Porosity was 1.52 +/- 0.8 mm and 0.64 +/- 0.4 mm for TiO2-HAP-GEL and calvaria bone, respectively. At 8 and 12 weeks postimplantation into rat calvaria defects, greater osteointegration and NFB were significantly present in the TiO2-enriched HAP-GEL constructs with OD-MAPCs, compared to the undifferentiated MAPC-loaded constructs, cell-free HAP-GEL with and without titanium, and PLGA scaffolds. The tissue-engineered TiO2-enriched HAP-GEL constructs with OD-MAPC aggregates present a potential useful therapeutic approach for calvaria bone regeneration.
C1 [Ferreira, Joao R.] NIDCR, Bethesda, MD 20892 USA.
[Ferreira, Joao R.; Padilla, Ricardo; Yoon, Kun; Goeckner, Kelly; Ko, Ching-Chang] Univ N Carolina, Sch Dent, Chapel Hill, NC USA.
[Urkasemsin, Ganokon] Mahidol Univ, Fac Vet Sci, Dept Preclin & Appl Anim Sci, Phutthamonthon, Thailand.
[Urkasemsin, Ganokon] N Carolina State Univ, Coll Vet Med, Raleigh, NC USA.
[Hu, Wei-Shou] Univ Minnesota, Minneapolis, MN USA.
[Ko, Ching-Chang] N Carolina State Univ, Raleigh, NC 27695 USA.
RP Ferreira, JR (reprint author), NIDCR, Matrix & Morphogenesis Sect, LCDB, 30 Convent Dr,Room 429, Bethesda, MD 20892 USA.
EM andraderequicj@nidcr.nih.gov; koc@dentistry.unc.edu
RI Ferreira, Joao/M-1517-2016; Ferreira, Joao/G-4015-2013
OI Ferreira, Joao/0000-0002-4230-4593; Ferreira, Joao/0000-0002-2411-6273
FU FCT-Portuguese Foundation for Science and Technology
[SFRH/BD/36841/2007]; NIH/NIDCR [K08DE018695]; NC Biotech Center;
American Association for Orthodontist Foundation
FX We would like to acknowledge Mr. Michael Vick, Dr. Weihan Hsieh, and Dr.
Faiz Malabari for their surgical assistance and to Professor Eric
Everett and Dr. Brandon Frederick for technical support with mu CT
imaging. Also, our thanks go to Mrs. Sandra Horton at the North Carolina
State University for processing calvaria tissue specimens and to Mrs.
Victoria Madden at the UNC Microscopy Services Laboratory for processing
in vitro cell matrices for electron microscopy. Joao Ferreira was
supported by the doctoral fellowship of FCT-Portuguese Foundation for
Science and Technology (SFRH/BD/36841/2007). This work was supported, in
part, by grants from the NIH/NIDCR (K08DE018695), NC Biotech Center,
American Association for Orthodontist Foundation awarded to C.-C. Ko.
All authors reported no conflict of interests. Dr. Ko is the cofounder
of Ironwood Materials Science, Inc. This work, however, was not
supported by any company and does not relate to any commercialized
products.
NR 51
TC 7
Z9 8
U1 0
U2 29
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3341
J9 TISSUE ENG PT A
JI Tissue Eng. Part A
PD AUG
PY 2013
VL 19
IS 15-16
BP 1803
EP 1816
DI 10.1089/ten.tea.2012.0520
PG 14
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA 172XJ
UT WOS:000321039800015
PM 23495972
ER
PT J
AU Hoenerhoff, MJ
Pandiri, AR
Snyder, SA
Hong, HHL
Ton, TV
Peddada, S
Shockley, K
Witt, K
Chan, P
Rider, C
Kooistra, L
Nyska, A
Sills, RC
AF Hoenerhoff, Mark J.
Pandiri, Arun R.
Snyder, Stephanie A.
Hong, Hue-Hua L.
Thai-Vu Ton
Peddada, Shyamal
Shockley, Keith
Witt, Kristine
Chan, Po
Rider, Cynthia
Kooistra, Linda
Nyska, Abraham
Sills, Robert C.
TI Hepatocellular Carcinomas in B6C3F1 Mice Treated with Ginkgo biloba
Extract for Two Years Differ from Spontaneous Liver Tumors in Cancer
Gene Mutations and Genomic Pathways
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE carcinogenesis; toxicogenomics; liver; microarray; molecular pathology
ID BETA-CATENIN; MOUSE-LIVER; EXPRESSION ANALYSIS; CELL-PROLIFERATION;
INDUCED DAMAGE; EGB 761; ANTIOXIDANT; INDUCTION; CALPAIN; CARCINOGENESIS
AB Ginkgo biloba leaf extract (GBE) has been used for centuries in traditional Chinese medicine and today is used as an herbal supplement touted for improving neural function and for its antioxidant and anticancer effects. Herbal supplements have the potential for consumption over extended periods of time, with a general lack of sufficient data on long-term carcinogenicity risk. Exposure of B6C3F1 mice to GBE in the 2-year National Toxicology Program carcinogenicity bioassay resulted in a dose-dependent increase in hepatocellular tumors, including hepatocellular carcinoma (HCC). We show that the mechanism of hepatocarcinogenesis in GBE exposed animals is complex, involving alterations in H-ras and Ctnnb1 mutation spectra, WNT pathway dysregulation, and significantly altered gene expression associated with oncogenesis, HCC development, and chronic xenobiotic and oxidative stress compared to spontaneous HCC. This study provides a molecular context for the genetic changes associated with hepatocarcinogenesis in GBE exposed mice and illustrates the marked differences between these tumors and those arising spontaneously in the B6C3F1 mouse. The molecular changes observed in HCC from GBE-treated animals may be of relevance to those seen in human HCC and other types of cancer, and provide important data on potential mechanisms of GBE hepatocarcinogenesis.
C1 [Hoenerhoff, Mark J.; Snyder, Stephanie A.; Hong, Hue-Hua L.; Thai-Vu Ton; Sills, Robert C.] NIEHS, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA.
[Hoenerhoff, Mark J.; Snyder, Stephanie A.; Hong, Hue-Hua L.; Thai-Vu Ton; Peddada, Shyamal; Shockley, Keith; Witt, Kristine; Chan, Po; Rider, Cynthia; Sills, Robert C.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Peddada, Shyamal; Shockley, Keith] NIEHS, Bioinformat & Biostat Branch, Res Triangle Pk, NC 27709 USA.
[Witt, Kristine] NIEHS, Genet Toxicol Grp, Biomol Screening Branch, Res Triangle Pk, NC 27709 USA.
[Chan, Po; Rider, Cynthia] NIEHS, Toxicol Branch, Res Triangle Pk, NC 27709 USA.
[Pandiri, Arun R.] Expt Pathol Labs, Res Triangle Pk, NC USA.
[Kooistra, Linda] Pathol Associates North Carolina, Charles River Labs, Durham, NC USA.
[Nyska, Abraham] Integrated Lab Syst Inc, Res Triangle Pk, NC USA.
RP Hoenerhoff, MJ (reprint author), NIEHS, Invest Pathol Grp, Cellular & Mol Pathol Branch, 111 TW Alexander Dr, Res Triangle Pk, NC 27519 USA.
EM hoenerhm@niehs.nih.gov
FU National Institutes of Environmental Health Sciences (NIEHS), National
Institutes of Health; Division of the National Toxicology Program
FX This work was supported by the National Institutes of Environmental
Health Sciences (NIEHS), National Institutes of Health, and The Division
of the National Toxicology Program. This article may be the work product
of an employee or group of employees of the National Institute of
Environmental Health Sciences (NIEHS), National Institutes of Health
(NIH); however, the statements, opinions, or conclusions contained
therein do not necessarily represent the statements, opinions or
conclusions of NIEHS, NIH, or the United States government.
NR 60
TC 9
Z9 10
U1 0
U2 14
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD AUG
PY 2013
VL 41
IS 6
BP 826
EP 841
DI 10.1177/0192623312467520
PG 16
WC Pathology; Toxicology
SC Pathology; Toxicology
GA 184NQ
UT WOS:000321898400002
PM 23262642
ER
PT J
AU Deleaval, F
Bouvier, A
Finet, G
Cloutier, G
Yazdani, SK
Le Floc'h, S
Clarysse, P
Pettigrew, RI
Ohayon, J
AF Deleaval, Flavien
Bouvier, Adeline
Finet, Gerard
Cloutier, Guy
Yazdani, Saami K.
Le Floc'h, Simon
Clarysse, Patrick
Pettigrew, Roderic I.
Ohayon, Jacques
TI THE INTRAVASCULAR ULTRASOUND ELASTICITY-PALPOGRAPHY TECHNIQUE REVISITED:
A RELIABLE TOOL FOR THE IN VIVO DETECTION OF VULNERABLE CORONARY
ATHEROSCLEROTIC PLAQUES
SO ULTRASOUND IN MEDICINE AND BIOLOGY
LA English
DT Article
DE Atherosclerosis; Vulnerable plaques; Elastography; Coronary disease;
Inverse problem
ID CIRCUMFERENTIAL STRESS; RADIOFREQUENCY DATA; CAP THICKNESS; WORKING
GROUP; ELASTOGRAPHY; RUPTURE; MODEL; STABILITY; ARTERIES; IMPACT
AB Critical to the detection of vulnerable plaques (VPs) is quantification of their mechanical properties. On the basis of intravascular ultrasound (IVUS) echograms and strain images, E. I. Cespedes, C. L. de Korte CL and A. F. van der Steen (Ultrasound Med Biol 2000; 26: 385-396) proposed an elasticity-palpography technique (E-PT) to estimate the apparent stress-strain modulus palpogram of the thick endoluminal layer of the arterial wall. However, this approach suffers from major limitations because it was developed for homogeneous, circular and concentric VPs. The present study was therefore designed to improve the E-PT by considering the anatomic shape of the VP. This improved E-PT was successfully applied to six coronary lesions of patients imaged in vivo with IVUS. Our results indicate that the mean relative error of the stress-strain modulus decreased from 61.02 +/- 9.01% to 15.12 +/- 12.57% when the IE-PT was used instead of the E-PT. The accuracy of the stress-strain modulus palpograms computed using the improved theoretical framework was also investigated with respect to noise, which may affect prediction of plaque vulnerability. (E-mail: jacques.ohayon@imag.fr) (C) 2013 World Federation for Ultrasound in Medicine & Biology.
C1 [Deleaval, Flavien; Bouvier, Adeline; Ohayon, Jacques] In3S, CNRS, UMR 5525, UJF,Lab TIMC IMAG DyCTiM, Grenoble, France.
[Finet, Gerard] Hosp Civils Lyon, Dept Hemodynam & Intervent Cardiol, Lyon, France.
[Finet, Gerard] Univ Lyon 1, INSERM U886, Lyon, France.
[Cloutier, Guy] Univ Montreal Hosp Res Ctr CRCHUM, Lab Biorheol & Med Ultrason, Montreal, PQ, Canada.
[Yazdani, Saami K.; Ohayon, Jacques] Univ S Alabama, Dept Mech Engn, Mobile, AL 36688 USA.
[Le Floc'h, Simon] Univ Montpellier 2, Lab LMGC, CNRS, UMR 5508, Montpellier, France.
[Clarysse, Patrick] CNRS, UMR 5220, INSERM U1044, Lab CREATIS, Lyon, France.
[Pettigrew, Roderic I.] NIDDK, Lab Integrat Cardiovasc Imaging Sci, NIH, Bethesda, MD 20892 USA.
Univ Savoie, Polytech Annecy Chambery, Le Bourget Du Lac, France.
RP Ohayon, J (reprint author), In3S, CNRS, UMR 5525, UJF,Lab TIMC IMAG DyCTiM, Grenoble, France.
EM jacques.ohayon@imag.fr
RI Ohayon, Jacques/M-6576-2014; Clarysse, Patrick/G-6371-2014
OI Clarysse, Patrick/0000-0002-5495-7655
FU Agence Nationale de la Recherche (ANR), France (ATHEBIOMECH project);
Natural Sciences and Engineering Research Council of Canada [NSERC
323405-06]; Canadian Institutes of Health Research [CIHR CPG-80085]; ANR
(MELANII Project) [09-BLANC-0423]; NSERC [STPGP-381136-09]; la Region
Rhone-Alpes, France
FX Grant support was provided by the Agence Nationale de la Recherche
(ANR), France (ATHEBIOMECH project), and by the collaborative health
research joint program of the Natural Sciences and Engineering Research
Council of Canada (NSERC 323405-06) and the Canadian Institutes of
Health Research (CIHR CPG-80085). This research is now supported by a
joint international program of the ANR (MELANII Project 09-BLANC-0423)
and NSERC Strategic Grant STPGP-381136-09. Flavien Deleaval held a
doctoral fellowship from la Region Rhone-Alpes, France (2010-2013).
NR 43
TC 8
Z9 8
U1 0
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-5629
J9 ULTRASOUND MED BIOL
JI Ultrasound Med. Biol.
PD AUG
PY 2013
VL 39
IS 8
BP 1469
EP 1481
DI 10.1016/j.ultrasmedbio.2013.03.001
PG 13
WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
GA 178IS
UT WOS:000321441900017
PM 23727295
ER
PT J
AU Brinster, LR
Omeir, RL
Foseh, GS
Macauley, JN
Snoy, PJ
Beren, JJ
Teferedegne, B
Peden, K
Lewis, AM
AF Brinster, Lauren R.
Omeir, Romelda L.
Foseh, Gideon S.
Macauley, Juliete N.
Snoy, Philip J.
Beren, Joel J.
Teferedegne, Belete
Peden, Keith
Lewis, Andrew M., Jr.
TI Failure-to-Thrive Syndrome Associated with Tumor Formation by
Madin-Darby Canine Kidney Cells in Newborn Nude Mice
SO COMPARATIVE MEDICINE
LA English
DT Article
ID EPITHELIAL-MESENCHYMAL TRANSITIONS; HUMAN-MELANOMA CELLS; TUMORIGENIC
PHENOTYPE; RECEPTOR ANTAGONIST; LINE MDCK; EXPRESSION; CACHEXIA; SYSTEM;
GROWTH; VIRUS
AB Tumors that formed in newborn nude mice that were inoculated with 10(7) Madin-Darby canine kidney (MDCK) cells were associated with a failure-to-thrive (FTT) syndrome consisting of growth retardation, lethargy, weakness, and dehydration. Scoliosis developed in 41% of affected pups. Pups were symptomatic by week 2; severely affected pups became moribund and required euthanasia within 3 to 4 wk. Mice with FTT were classified into categories of mild, moderate, and severe disease by comparing their weight with that of age-matched normal nude mice. The MDCK-induced tumors were adenocarcinomas that invaded adjacent muscle, connective tissue, and bone; 6 of the 26 pups examined had lung metastases. The induction of FTT did not correlate with cell-line aggressiveness as estimated by histopathology or the efficiency of tumor formation (tumor-forming dose 50% endpoint range = 10(2.8) to 10(7.5)); however, tumor invasion of the paravertebral muscles likely contributed to the scoliosis noted. In contrast to the effect of MDCK cells, tumor formation observed in newborn mice inoculated with highly tumorigenic, human-tumor derived cell lines was not associated with FTT development. We suggest that tumor formation and FTT are characteristics of these MDCK cell inocula and that FTT represents a new syndrome that may be similar to the cachexia that develops in humans with cancer or other diseases.
C1 [Brinster, Lauren R.] NIH, Div Vet Resources, Bethesda, MD 20892 USA.
[Omeir, Romelda L.; Foseh, Gideon S.; Macauley, Juliete N.; Teferedegne, Belete; Peden, Keith; Lewis, Andrew M., Jr.] CBER, Off Vaccines, Div Viral Prod, Bethesda, MD USA.
[Snoy, Philip J.; Beren, Joel J.] CBER, Food & Drug Adm, Div Vet Serv, Bethesda, MD USA.
RP Lewis, AM (reprint author), CBER, Off Vaccines, Div Viral Prod, Bethesda, MD USA.
EM andrew.lewis@fda.hhs.gov
FU Division of Microbiology and Infectious Diseases of NIAID; CBER-FDA
[YI-AI-4893-02NIAID]
FX This research was supported in part by a contract from the Division of
Microbiology and Infectious Diseases of NIAID through an interagency
agreement with CBER-FDA under contract number YI-AI-4893-02NIAID.
NR 40
TC 2
Z9 2
U1 0
U2 2
PU AMER ASSOC LABORATORY ANIMAL SCIENCE
PI MEMPHIS
PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA
SN 1532-0820
J9 COMPARATIVE MED
JI Comparative Med.
PD AUG
PY 2013
VL 63
IS 4
BP 323
EP 330
PG 8
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA AN7VT
UT WOS:000340809800004
PM 24209967
ER
PT J
AU McCully, CM
Pastakia, D
Bacher, J
Thomas, ML
Steffen-Smith, EA
Saleem, K
Murphy, RF
Walbridge, S
Brinster, L
Widemann, BC
Warren, KE
AF McCully, Cynthia M.
Pastakia, Devang
Bacher, John
Thomas, Marvin L., III
Steffen-Smith, Emilie A.
Saleem, Kadharbatcha
Murphy, Robert F.
Walbridge, Stuart
Brinster, Lauren
Widemann, Brigitte C.
Warren, Katherine E.
TI Model for Concomitant Microdialysis Sampling of the Pons and Cerebral
Cortex in Rhesus Macaques (Macaca mulatta)
SO COMPARATIVE MEDICINE
LA English
DT Article
ID CEREBROSPINAL-FLUID; CALIBRATION; ZIDOVUDINE; MONKEY; BRAIN
AB Pediatric diffuse intrinsic pontine gliomas are aggressive brainstem tumors that fail to respond to treatment. We hypothesize that the protective features of the pons may hinder chemotherapeutic agents from entering pontine tissue compared with cortical brain tissue. To test this hypothesis, we developed a unique nonhuman primate model using microdialysis, a continuous in vivo extracellular sampling technique, to compare drug exposure concurrently in pontine tissue, cortical tissue, CSF, and plasma after intravenous administration of chemotherapeutic agents. The surgical coordinates and approach for microdialysis cannula-probe placement were determined in 5 adult male rhesus monkeys (Macaca mulatta) by using MRI. Microdialysis cannulas-probes were implanted stereotactically in the brain, retrodialysis was performed to measure relative recovery, and a 1-h intravenous infusion of temozolomide was administered. Continuous microdialysis samples were collected from the pons and cortex over 4 h with concurrent serial plasma and CSF samples. Postsurgical verification of microdialysis cannula-probe placement was obtained via MRI in 3 macaques and by gross pathology in all 5 animals. The MRI-determined coordinates and surgical methodologies resulted in accurate microdialysis probe placement in the pons and cortex in 4 of the 5 macaques. Histologic examination from these 4 animals revealed negligible tissue damage to the pontine and cortical tissue from microdialysis. One macaque was maintained for 8 wk and had no deficits attributed to the procedure. This animal model allows for the determination of differences in CNS penetration of chemotherapeutic agents in the pons, cortex, and CSF after systemic drug administration.
C1 [McCully, Cynthia M.; Pastakia, Devang; Steffen-Smith, Emilie A.; Murphy, Robert F.; Widemann, Brigitte C.; Warren, Katherine E.] NCI, Bethesda, MD 20892 USA.
[Bacher, John; Thomas, Marvin L., III; Brinster, Lauren] Off Res Serv, Bethesda, MD USA.
[Saleem, Kadharbatcha] NIMH, Bethesda, MD 20892 USA.
[Walbridge, Stuart] NINDS, Bethesda, MD 20892 USA.
RP McCully, CM (reprint author), NCI, Bethesda, MD 20892 USA.
EM mccullyc@mail.nih.gov
OI Saleem, Kadharbatcha S/0000-0002-4450-9234
FU National Cancer Institute; Laboratory Animal Science Program; National
Institutes of Neurologic Disorders and Stroke; Nonhuman Primate Staff
FX We thank the National Cancer Institute, Laboratory Animal Science
Program, Nonhuman Primate Staff, for their support and excellent animal
care. Also, thank you to Renee Hill and Joelle Sarlls, National
Institutes of Neurologic Disorders and Stroke, for their expertise and
support.
NR 13
TC 1
Z9 1
U1 0
U2 1
PU AMER ASSOC LABORATORY ANIMAL SCIENCE
PI MEMPHIS
PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA
SN 1532-0820
J9 COMPARATIVE MED
JI Comparative Med.
PD AUG
PY 2013
VL 63
IS 4
BP 355
EP 360
PG 6
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA AN7VT
UT WOS:000340809800009
PM 24209972
ER
PT J
AU Khavrutskii, L
Yeh, J
Timofeeva, O
Tarasov, SG
Pritt, S
Stefanisko, K
Tarasova, N
AF Khavrutskii, Lyuba
Yeh, Joanna
Timofeeva, Olga
Tarasov, Sergey G.
Pritt, Samuel
Stefanisko, Karen
Tarasova, Nadya
TI Protein Purification-free Method of Binding Affinity Determination by
Microscale Thermophoresis
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Molecular Biology; Issue 78; Biochemistry; Cellular Biology; Genetics;
Chemistry; Pharmacology; Intracellular Signaling Peptides and Proteins;
Proteins; protein-inhibitor interaction; KD; transcription factor;
ligand binding; binding affinity; thermophoresis; fluorescence;
microscopy
AB Quantitative characterization of protein interactions is essential in practically any field of life sciences, particularly drug discovery. Most of currently available methods of K-D determination require access to purified protein of interest, generation of which can be time-consuming and expensive. We have developed a protocol that allows for determination of binding affinity by microscale thermophoresis (MST) without purification of the target protein from cell lysates. The method involves overexpression of the GFP-fused protein and cell lysis in non-denaturing conditions. Application of the method to STAT3-GFP transiently expressed in HEK293 cells allowed to determine for the first time the affinity of the well-studied transcription factor to oligonucleotides with different sequences. The protocol is straightforward and can have a variety of application for studying interactions of proteins with small molecules, peptides, DNA, RNA, and proteins.
C1 [Khavrutskii, Lyuba; Yeh, Joanna; Pritt, Samuel; Stefanisko, Karen; Tarasova, Nadya] NCI, Canc & Inflammat Program, Bethesda, MD 20892 USA.
[Khavrutskii, Lyuba] SAIC Frederick Inc, Basic Sci Program, Ft Detrick, MD 21702 USA.
[Timofeeva, Olga] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20057 USA.
[Timofeeva, Olga] Georgetown Univ, Med Ctr, Dept Radiat Med, Washington, DC 20057 USA.
[Tarasov, Sergey G.] NCI, Struct Biophys Lab, Bethesda, MD 20892 USA.
RP Tarasova, N (reprint author), NCI, Canc & Inflammat Program, Bethesda, MD 20892 USA.
EM Nadya.Tarasova@nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; NCI; Calidris Therapeutics; American Cancer
Society [IRG 97-152-17]; National Cancer Institute, NIH
[HHSN26120080001E]
FX This work was partially supported by the Intramural Research Program of
the NIH, National Cancer Institute, Center for Cancer Research;
Collaborative Research Agreement between NCI and Calidris Therapeutics;
American Cancer Society grant IRG 97-152-17 to O.T; and federal funds
from the National Cancer Institute, NIH, under contract
HHSN26120080001E.
NR 15
TC 2
Z9 2
U1 1
U2 9
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD AUG
PY 2013
IS 78
AR UNSP e50541
DI 10.3791/50541
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36RH
UT WOS:000209228000034
ER
PT J
AU Sassa, A
Beard, WA
Shock, DD
Wilson, SH
AF Sassa, Akira
Beard, William A.
Shock, David D.
Wilson, Samuel H.
TI Steady-state, Pre-steady-state, and Single-turnover Kinetic Measurement
for DNA Glycosylase Activity
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Chemistry; Issue 78; Biochemistry; Genetics; Molecular Biology;
Microbiology; Structural Biology; Chemical Biology; Eukaryota; Amino
Acids; Peptides; and Proteins; Nucleic Acids; Nucleotides; and
Nucleosides; Enzymes and Coenzymes; Life Sciences (General); enzymology;
rapid quench-flow; active site titration; steady-state;
pre-steady-state; single-turnover; kinetics; base excision repair; DNA
glycosylase; 8-oxo-7; 8-dihydroguanine; 8-oxoG; sequencing
AB Human 8-oxoguanine DNA glycosylase (OGG1) excises the mutagenic oxidative DNA lesion 8-oxo-7,8-dihydroguanine (8-oxoG) from DNA. Kinetic characterization of OGG1 is undertaken to measure the rates of 8-oxoG excision and product release. When the OGG1 concentration is lower than substrate DNA, time courses of product formation are biphasic; a rapid exponential phase (i.e. burst) of product formation is followed by a linear steady-state phase. The initial burst of product formation corresponds to the concentration of enzyme properly engaged on the substrate, and the burst amplitude depends on the concentration of enzyme. The first-order rate constant of the burst corresponds to the intrinsic rate of 8-oxoG excision and the slower steady-state rate measures the rate of product release (product DNA dissociation rate constant, k(off)). Here, we describe steady-state, pre-steady-state, and single-turnover approaches to isolate and measure specific steps during OGG1 catalytic cycling. A fluorescent labeled lesion-containing oligonucleotide and purified OGG1 are used to facilitate precise kinetic measurements. Since low enzyme concentrations are used to make steady-state measurements, manual mixing of reagents and quenching of the reaction can be performed to ascertain the steady-state rate (k(off)). Additionally, extrapolation of the steady-state rate to a point on the ordinate at zero time indicates that a burst of product formation occurred during the first turnover (i.e. y-intercept is positive). The first-order rate constant of the exponential burst phase can be measured using a rapid mixing and quenching technique that examines the amount of product formed at short time intervals (<1 sec) before the steady-state phase and corresponds to the rate of 8-oxoG excision (i.e. chemistry). The chemical step can also be measured using a single-turnover approach where catalytic cycling is prevented by saturating substrate DNA with enzyme (E>S). These approaches can measure elementary rate constants that influence the efficiency of removal of a DNA lesion.
C1 [Sassa, Akira; Beard, William A.; Shock, David D.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, Bethesda, MD 20892 USA.
EM wilson5@niehs.nih.gov
FU National Institutes of Health Research Project Grant in the Intramural
Research Program [Z01-ES050158]; NIEHS
FX We thank Dr. Julie K. Horton for critical reading of the manuscript and
Dr. Rajendra Prasad for helpful suggestions and discussions. Portions of
this research were originally published in The Journal of Biological
Chemistry, Sassa A et. al., "DNA Sequence Context Effects on the
Glycosylase Activity of Human 8-Oxoguanine DNA Glycosylase." J Biol
Chem. 287, 36702-36710 (2012)2. This work was supported, in
whole or in part, by National Institutes of Health Research Project
Grant Z01-ES050158 in the Intramural Research Program, NIEHS.
NR 24
TC 2
Z9 2
U1 1
U2 5
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD AUG
PY 2013
IS 78
AR UNSP e50695
DI 10.3791/50695
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36RH
UT WOS:000209228000052
PM 23995844
ER
PT J
AU Scimemi, A
Diamond, JS
AF Scimemi, Annalisa
Diamond, Jeffrey S.
TI Deriving the Time Course of Glutamate Clearance with a Deconvolution
Analysis of Astrocytic Transporter Currents
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Neurobiology; Issue 78; Neuroscience; Biochemistry; Molecular Biology;
Cellular Biology; Anatomy; Physiology; Biophysics; Astrocytes; Synapses;
Glutamic Acid; Membrane Transport Proteins; Astrocytes; glutamate
transporters; uptake; clearance; hippocampus; stratum radiatum; CA1;
gene; brain; slice; animal model
AB The highest density of glutamate transporters in the brain is found in astrocytes. Glutamate transporters couple the movement of glutamate across the membrane with the co-transport of 3 Na+ and 1 H+ and the counter-transport of 1 K+. The stoichiometric current generated by the transport process can be monitored with whole-cell patch-clamp recordings from astrocytes. The time course of the recorded current is shaped by the time course of the glutamate concentration profile to which astrocytes are exposed, the kinetics of glutamate transporters, and the passive electrotonic properties of astrocytic membranes. Here we describe the experimental and analytical methods that can be used to record glutamate transporter currents in astrocytes and isolate the time course of glutamate clearance from all other factors that shape the waveform of astrocytic transporter currents. The methods described here can be used to estimate the lifetime of flash-uncaged and synaptically-released glutamate at astrocytic membranes in any region of the central nervous system during health and disease.
C1 [Scimemi, Annalisa; Diamond, Jeffrey S.] NINDS, Synapt Physiol Sect, NIH, Bethesda, MD 20892 USA.
RP Scimemi, A (reprint author), NINDS, Synapt Physiol Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM scimemia@ninds.nih; govscimemia@gmail.com
RI Diamond, Jeffrey/C-1835-2015;
OI Diamond, Jeffrey/0000-0002-1770-2629; Scimemi,
Annalisa/0000-0003-4975-093X
FU National Institute of Neurological Disorders and Stroke Intramural
Research Program [NS002986]
FX This work was supported by the National Institute of Neurological
Disorders and Stroke Intramural Research Program (NS002986). AS wrote
the manuscript and implemented the deconvolution analysis. JSD developed
the initial version of the deconvolution analysis and commented on the
text.
NR 21
TC 0
Z9 0
U1 1
U2 2
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD AUG
PY 2013
IS 78
AR UNSP e50708
DI 10.3791/50708
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36RH
UT WOS:000209228000053
ER
PT J
AU Young, LR
Lee, HS
Inoue, Y
Moss, J
Singer, LG
Strange, C
Nakata, K
Barker, AF
Chapman, JT
Brantly, ML
Stocks, JM
Brown, KK
Lynch, JP
Goldberg, HJ
Downey, GP
Swigris, JJ
Taveira-DaSilva, AM
Krischer, JP
Trapnell, BC
McCormack, FX
AF Young, Lisa R.
Lee, Hye-Seung
Inoue, Yoshikazu
Moss, Joel
Singer, Lianne G.
Strange, Charlie
Nakata, Koh
Barker, Alan F.
Chapman, Jeffrey T.
Brantly, Mark L.
Stocks, James M.
Brown, Kevin K.
Lynch, Joseph P., III
Goldberg, Hilary J.
Downey, Gregory P.
Swigris, Jeffrey J.
Taveira-DaSilva, Angelo M.
Krischer, Jeffrey P.
Trapnell, Bruce C.
McCormack, Francis X.
CA MILES Trial Grp
TI Serum VEGF-D concentration as a biomarker of lymphangioleiomyomatosis
severity and treatment response: a prospective analysis of the
Multicenter International Lymphangioleiomyomatosis Efficacy of Sirolimus
(MILES) trial
SO LANCET RESPIRATORY MEDICINE
LA English
DT Article
ID TUBEROUS SCLEROSIS COMPLEX; GROWTH FACTOR-D; SPORADIC
LYMPHANGIOLEIOMYOMATOSIS; ANGIOMYOLIPOMA; LYMPHANGIOGENESIS; EVEROLIMUS;
MECHANISM; THERAPY; SAFETY; CELLS
AB Background VEGF-D is a lymphangiogenic growth factor that has a key role in tumour metastasis. Serum VEGF-D concentrations are increased in most patients with lymphangioleiomyomatosis, a rare neoplasm associated with mTOR-activating tuberous sclerosis gene mutations, lymphadenopathy, metastatic spread, and pulmonary cyst formation. We used data from the Multicenter International Lymphangioleiomyomatosis Efficacy of Sirolimus (MILES) trial to assess the usefulness of serum VEGF-D concentration as a marker of severity and therapeutic response to sirolimus in patients with lymphangioleiomyomatosis.
Methods In the MILES trial, patients with lymphangioleiomyomatosis who had forced expiratory volume in 1 second (FEV1) of 70% or less of predicted were randomly assigned (1:1) to 12 months masked treatment with sirolimus or placebo. Serum VEGF-D concentrations were measured at baseline, 6 months, and 12 months. We used a linear regression model to assess associations of baseline VEGF-D concentrations with markers of disease severity, and a linear mixed effects model to assess the associations of VEGF-D concentrations with between-group differences in clinical, physiological, and patient-reported outcomes.
Findings We included 42 patients from the placebo group and 45 from the sirolimus group in our analysis. Baseline VEGF-D concentrations in individual patients varied from 0.34 ng/mL to 16.7 ng/mL. Baseline VEGF-D concentrations were higher in patients who needed supplemental oxygen than in those who did not need supplemental oxygen (1.7 ng/mL [IQR 0.99-3.36] vs 0.84 ng/mL [0.52-1.39]; p<0.0001) and in those who had a bronchodilator response than in those who did not (2.01 ng/mL [0.99-2.86] vs 1.00 ng/mL [0.61-2.15]; 0.0273). Median serum VEGF-D concentrations were similar at baseline in the sirolimus and placebo groups, and fell from baseline at 6 and 12 months in the sirolimus group but remained roughly stable in the placebo group. Each one-unit increase in baseline log(VEGF-D) was associated with a between-group difference in baseline-to-12-month FEV1 change of 134 mL (p=0.0007). In the sirolimus group, improvement in baseline-to-12-month FEV1 occurred in 15 of 23 (65%) VEGF-D responders (ie, those in whom baseline-to-12-month VEGF-D concentrations decreased by more than they did in any patients in the placebo group) and four of 15 (27%) VEGF-D non-responders (p=0.0448).
Interpretation Serum VEGF-D is a biologically plausible and useful biomarker in lymphangioleiomyomatosis that correlates with disease severity and treatment response. Measurement of serum VEGF-D concentrations could inform the risk-benefit analysis of sirolimus therapy in patients with lymphangioleiomyomatosis and reduce the numbers of patients needed for clinical trials.
C1 [Young, Lisa R.] Vanderbilt Univ, Div Pediat Pulm Med & Allergy, Sch Med, Nashville, TN 37232 USA.
[Young, Lisa R.] Vanderbilt Univ, Div Pulm, Sch Med, Nashville, TN 37232 USA.
[Young, Lisa R.] Vanderbilt Univ, Div Crit Care, Sch Med, Nashville, TN 37232 USA.
[Lee, Hye-Seung; Krischer, Jeffrey P.] Univ S Florida, Dept Pediat, Pediat Epidemiol Ctr, Tampa, FL 33620 USA.
[Inoue, Yoshikazu] Natl Hosp Org Kinki Chuo Chest Med Ctr, Dept Diffuse Lung Dis & Resp Failure, Clin Res Ctr, Osaka, Japan.
[Moss, Joel; Taveira-DaSilva, Angelo M.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Singer, Lianne G.] Univ Toronto, Dept Med, Div Respirol, Toronto, ON, Canada.
[Strange, Charlie] Med Univ S Carolina, Div Pulm & Crit Care Med, Charleston, SC 29425 USA.
[Nakata, Koh] Niigata Univ, Med & Dent Hosp, Biosci Med Res Ctr, Niigata, Japan.
[Barker, Alan F.] Oregon Hlth & Sci Univ, Div Pulm & Crit Care, Portland, OR 97201 USA.
[Chapman, Jeffrey T.] Cleveland Clin Fdn, Res Inst, Cleveland, OH 44195 USA.
[Brantly, Mark L.] Univ Florida, Div Pulm & Crit Care, Gainesville, FL USA.
[Stocks, James M.] Univ Texas Hlth Sci Ctr Tyler, Tyler, TX USA.
[Brown, Kevin K.; Downey, Gregory P.; Swigris, Jeffrey J.] Natl Jewish Hlth, Dept Med, Denver, CO USA.
[Lynch, Joseph P., III] Univ Calif Los Angeles, Div Pulm & Crit Care Med, Los Angeles, CA USA.
[Goldberg, Hilary J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care, Boston, MA 02115 USA.
[Trapnell, Bruce C.] Cincinnati Childrens Hosp Med Ctr, Div Pulm Biol, Cincinnati, OH 45229 USA.
[Trapnell, Bruce C.] Cincinnati Childrens Hosp Med Ctr, Perinatal Inst, Cincinnati, OH 45229 USA.
[Trapnell, Bruce C.; McCormack, Francis X.] Univ Cincinnati, Coll Med, Div Pulm Crit Care & Sleep Med, Cincinnati, OH USA.
RP Young, LR (reprint author), Vanderbilt Univ, Div Pulm Med, Sch Med, 2200 Childrens Way, Nashville, TN 37232 USA.
EM lisa.young@vanderbilt.edu; frank.mccormack@uc.edu
OI McCormack, Francis/0000-0001-7168-9464; Strange,
Charlie/0000-0002-8109-8067; Downey, Gregory/0000-0003-3253-5862;
Singer, Lianne/0000-0002-2693-8676
FU National Institutes of Health Institutional Clinical and Translational
Science Award at Cincinnati Children's Hospital Medical Center
[1UL1RR02631401]; Department of Defense [W81XWH-10-1-0885]
FX Funding for the VEGF-D testing, validation, and analysis was provided by
the National Institutes of Health Institutional Clinical and
Translational Science Award (1UL1RR02631401) at Cincinnati Children's
Hospital Medical Center (to LRY and FXM), and Department of Defense
(W81XWH-10-1-0885; to LRY and FXM). Funding for the MILES trial was as
previously reported.18 We thank Leslie Korbee, Peter
Gulleman, and Elke Grassman for assistance with analysis of VEGF-D
samples.
NR 27
TC 40
Z9 42
U1 0
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-2600
J9 LANCET RESP MED
JI Lancet Resp. Med.
PD AUG
PY 2013
VL 1
IS 6
BP 445
EP 452
DI 10.1016/S2213-2600(13)70090-0
PG 8
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA AQ3JV
UT WOS:000342689600018
PM 24159565
ER
PT J
AU Papineni, RVL
Prasanna, PG
Ahmed, MM
AF Papineni, Rao V. L.
Prasanna, Pataje G.
Ahmed, Mansoor M.
TI Translational Cancer Research Preface
SO TRANSLATIONAL CANCER RESEARCH
LA English
DT Editorial Material
C1 [Papineni, Rao V. L.] Univ Kansas, Med Ctr, Sch Med, Dept Mol & Integrat Physiol, Lawrence, KS 66045 USA.
[Prasanna, Pataje G.] NCI, Radiat Res Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Ahmed, Mansoor M.] NCI, RDB, RRP, DCTD,NIH, Rockville, MD 20850 USA.
RP Papineni, RVL (reprint author), Univ Kansas, Med Ctr, Sch Med, Dept Mol & Integrat Physiol, Lawrence, KS 66045 USA.
EM Papineni@graduate.hku.hk
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AME PUBL CO
PI SHEUNG WAN
PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG
00000, PEOPLES R CHINA
SN 2218-676X
EI 2219-6803
J9 TRANSL CANCER RES
JI Transl. Cancer Res.
PD AUG
PY 2013
VL 2
IS 4
BP 227
EP 227
DI 10.3978/j.issn.2218-676X.2013.08.14
PG 1
WC Oncology
SC Oncology
GA V42WF
UT WOS:000209643200001
ER
PT J
AU Siskind, CE
Panchal, S
Smith, CO
Feely, SME
Dalton, JC
Schindler, AB
Krajewski, KM
AF Siskind, Carly E.
Panchal, Seema
Smith, Corrine O.
Feely, Shawna M. E.
Dalton, Joline C.
Schindler, Alice B.
Krajewski, Karen M.
TI A Review of Genetic Counseling for Charcot Marie Tooth Disease (CMT)
SO JOURNAL OF GENETIC COUNSELING
LA English
DT Review
DE Charcot Marie Tooth disease; CMT; Hereditary motor and sensory
neuropathy; Genetic counseling; Genetic subtypes; Psychosocial concerns;
Ethical concerns
ID HEREDITARY MOTOR NEUROPATHY; RNA SYNTHETASE MUTATIONS;
NEUROFILAMENT-LIGHT GENE; SPINAL MUSCULAR-ATROPHY; VOCAL CORD PARESIS;
EARLY-ONSET SEVERE; PRESSURE PALSIES; GDAP1 GENE; DEMYELINATING
NEUROPATHY; PROTEIN-DEGRADATION
AB Charcot Marie Tooth disease (CMT) encompasses the inherited peripheral neuropathies. While four genes have been found to cause over 90 % of genetically identifiable causes of CMT (PMP22, GJB1, MPZ, MFN2), at least 51 genes and loci have been found to cause CMT when mutated, creating difficulties for clinicians to find a genetic subtype for families. Here, the classic features of CMT as well as characteristic features of the most common subtypes of CMT are described, as well as methods for narrowing down the possible subtypes. Psychosocial concerns particular to the CMT population are identified. This is the most inclusive publication for CMT-specific genetic counseling.
C1 [Siskind, Carly E.] Stanford Hosp & Clin, Dept Neurosci, Stanford, CA 94305 USA.
[Panchal, Seema] Mt Sinai Hosp, Familial Breast Canc Clin, Marvelle Koffler Breast Ctr, Toronto, ON M5G 1X5, Canada.
[Panchal, Seema] Univ Toronto, Dept Med Genet & Microbiol, Toronto, ON, Canada.
[Smith, Corrine O.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
[Feely, Shawna M. E.] Univ Iowa Hlth Care, Dept Neurol, Iowa City, IA USA.
[Dalton, Joline C.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA.
[Schindler, Alice B.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
[Krajewski, Karen M.] Wayne State Univ, Dept Neurol, Detroit, MI USA.
RP Siskind, CE (reprint author), Stanford Hosp & Clin, Dept Neurosci, 300 Pasteur Dr,M-C 5235, Stanford, CA 94305 USA.
EM csiskind@stanfordmed.org
NR 106
TC 9
Z9 15
U1 0
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1059-7700
J9 J GENET COUNS
JI J. Genet. Couns.
PD AUG
PY 2013
VL 22
IS 4
BP 422
EP 436
DI 10.1007/s10897-013-9584-4
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA 176ER
UT WOS:000321287000003
PM 23604902
ER
PT J
AU Morris, BA
Hadley, DW
Koehly, LM
AF Morris, Bronwyn A.
Hadley, Donald W.
Koehly, Laura M.
TI The Role of Religious and Existential Well-being in Families with Lynch
Syndrome: Prevention, Family Communication, and Psychosocial Adjustment
SO JOURNAL OF GENETIC COUNSELING
LA English
DT Article
DE Lynch syndrome; Hereditary nonpolyposis colon cancer; Religious;
Existential; Psychosocial; Cancer prevention
ID NONPOLYPOSIS COLORECTAL-CANCER; PSYCHOLOGICAL ADJUSTMENT;
FUTURE-DIRECTIONS; BREAST-CANCER; HEALTH; SPIRITUALITY; STRESS;
KNOWLEDGE; IMPACT; MODEL
AB This study explored the role of religious (RWB) and existential well-being (EWB) on psychosocial factors, support network characteristics, and screening practices in families with Lynch syndrome, also referred to as hereditary nonpolyposis colon cancer (HNPCC). Participants were individuals with Lynch syndrome associated cancers and their first-degree relatives at risk of inheriting an identified deleterious mutation. Analyses considered both family RWB and EWB norms and individual deviations from that norm. Analyses controlled for age, gender, cancer diagnosis, number of respondents, and network size. Higher family RWB was associated with increased depressive symptoms (p < .05) and avoidant cognitions (p < .05). Higher family EWB was related to decreased depression symptoms (p < .001). Higher family EWB was associated with fecal occult blood testing (p < .01), and family communication about genetic counselling and testing (p < .01). Analyses pointed to individual effects of EWB above and beyond family-level effects. Individuals with lower EWB than their family had lower perceived risk for colorectal cancer (p < .05), communicated disease risk information to less family members (p < .05), and were less likely to undergo recent colonoscopies (p < .05). Participants with lower EWB than their family also had higher cancer worry (p < .01) and increased depressive symptoms (p < .001). Findings indicate the importance of assessing individuals within the context of their family network and being aware of family characteristics which may impact individual adjustment to disease risk. Interventions considering family-level factors may provide efficient pathways to improving psychosocial factors, screening practices, communication about disease risk and genetic testing, and cancer prevention.
C1 [Morris, Bronwyn A.; Hadley, Donald W.; Koehly, Laura M.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA.
[Morris, Bronwyn A.] Griffith Univ, Griffith Hlth Inst, Southport, Qld 4222, Australia.
[Hadley, Donald W.] NHGRI, Off Clin Director, Bethesda, MD 20892 USA.
RP Morris, BA (reprint author), Griffith Univ, Griffith Hlth Inst, Bldg G05 2-44,Gold Coast Campus, Southport, Qld 4222, Australia.
EM b.morris@griffith.edu.au
FU Division of Intramural Research Program of the National Human Genome
Research Institute [ZO1-HG200335]
FX This research was supported by the Division of Intramural Research
Program of the National Human Genome Research Institute (ZO1-HG200335,
PI: Koehly).
NR 42
TC 3
Z9 3
U1 1
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1059-7700
J9 J GENET COUNS
JI J. Genet. Couns.
PD AUG
PY 2013
VL 22
IS 4
BP 482
EP 491
DI 10.1007/s10897-013-9571-9
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 176ER
UT WOS:000321287000008
PM 23345057
ER
PT J
AU Shrivastava, S
TrehanPati, N
Patra, S
Kottilil, S
Pande, C
Trivedi, SS
Sarin, SK
AF Shrivastava, S.
TrehanPati, N.
Patra, S.
Kottilil, S.
Pande, C.
Trivedi, S. S.
Sarin, S. K.
TI Increased regulatory T cells and impaired functions of circulating CD8 T
lymphocytes is associated with viral persistence in Hepatitis B
virus-positive newborns
SO JOURNAL OF VIRAL HEPATITIS
LA English
DT Article
DE CD8 T-cell dysfunction; HBV-positive newborns; Peripheral Blood
Mononuclear cells; regulatory T cells; T-cell function; T-cell receptor
ID ZETA-CHAIN EXPRESSION; NATURAL-HISTORY; IMMUNE-RESPONSE;
DOWN-REGULATION; CANCER PATIENTS; CD3-ZETA CHAIN; INFECTION; DISEASE;
TOLERANCE; APOPTOSIS
AB Hepatitis B Virus (HBV) infection in infancy or early childhood leads to high rate of persistent infection (25-90%). The immunological basis of high rate of viral persistence in vertically acquired HBV infections is not completely understood. CD8 T cells play a pivotal role in clearing the Hepatitis B virus infection in adults. Herein, we sought to delineate the role of T cells in viral persistence in HBsAg+ve newborns. At birth peripheral and cord blood of HBsAg+ve (N = 12), HBsAg-ve (N = 10) and healthy newborns (HC: N = 15) were evaluated for T-cell frequency and functionality by flow cytometry. No significant differences were observed in the frequency of CD8 and CD4 T cells in all the three groups. However, significantly higher frequency of FoxP3 expressing regulatory T cells were observed in HBsAg+ve (63.79%) compared with HBsAg-ve (28.12%) and HC (11.06%) (P < 0.05). Moreover, HBsAg+ve newborns showed functional defect in CD8 T cells by decreased IFN-gamma production and lower CD107A expression (cytotoxic capacity) compared with HBsAg-ve and HC, which positively correlated with decreased TCR zeta-chain expression CD8 T cells (r(2) > 0.93, P < 0.05). Despite equal frequency of CD8 T cells in all the three groups, CD8 T cells in HBsAg+ve newborns are dysfunctional. An expansion of regulatory T cells and impaired TCR signalling may represent the immune tolerant state of the adaptive immune system in response to chronic HBV infection.
C1 [Shrivastava, S.; TrehanPati, N.; Sarin, S. K.] Inst Liver & Biliary Sci, New Delhi 110070, India.
[Shrivastava, S.; Kottilil, S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Patra, S.; Trivedi, S. S.] Lady Hardinge Med Coll & Hosp, New Delhi, India.
[Patra, S.; Trivedi, S. S.] Smt SK Hosp, New Delhi, India.
[Pande, C.] GB Pant Hosp, Dept Gastroenterol, New Delhi, India.
RP Sarin, SK (reprint author), Dept Hepatol, New Delhi 110070, India.
EM shivsarin@gmail.com
FU Department of Biotechnology [BT/PR7647/MED/14/1053/2006]; Reproductive
Health and Nutrition Department, Indian Council of Medical Research,
India [3/1/2/26/2010-RHN]
FX This study was supported by the grant from Department of Biotechnology
(Sanction letter no. BT/PR7647/MED/14/1053/2006) and first author was
awarded with Senior Research fellowship for 3/1/2/26/2010-RHN conducting
this work from Reproductive Health and Nutrition Department, Indian
Council of Medical Research, India.
NR 29
TC 5
Z9 7
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1352-0504
J9 J VIRAL HEPATITIS
JI J. Viral Hepatitis
PD AUG
PY 2013
VL 20
IS 8
BP 582
EP 591
DI 10.1111/jvh.12078
PG 10
WC Gastroenterology & Hepatology; Infectious Diseases; Virology
SC Gastroenterology & Hepatology; Infectious Diseases; Virology
GA 174WU
UT WOS:000321188600009
PM 23808997
ER
PT J
AU Woodson, SE
Freiberg, AN
Holbrook, MR
AF Woodson, Sara E.
Freiberg, Alexander N.
Holbrook, Michael R.
TI Coagulation factors, fibrinogen and plasminogen activator inhibitor-1,
are differentially regulated by yellow fever virus infection of
hepatocytes
SO VIRUS RESEARCH
LA English
DT Article
DE Yellow fever virus; Asibi virus; 17-D vaccine; Hepatocytes; Fibrinogen;
Plasminogen activator inhibitor-1
ID ACUTE-PHASE PROTEINS; C-REACTIVE PROTEIN; VACCINE-STRAIN;
GENE-EXPRESSION; ASIBI STRAIN; BIOSYNTHESIS; FIBRINOLYSIS; PATHOGENESIS;
INFLAMMATION; INTERFERON
AB Yellow fever virus (YFV) infection poses a great risk to un-vaccinated individuals living or traveling in the endemic regions of Africa and South America. It is estimated that approximately 30,000 people die each year of this disease. The liver is the main target of YFV, where as many as 80% of the hepatocytes may become involved in the infection. The overwhelming infection of the liver is associated with the observed hemorrhagic disease manifestations such as petechiae, ecchymoses, and hematemesis which are all thought to be linked with the observed coagulation abnormalities that include prolonged clotting times, reduction in clotting factors, fibrin-split products (D-dimers) and elevated prothrombin times. Many factors involved in the coagulation pathway are produced by hepatocytes, such as fibrinogen (FBG) and plasminogen activator inhibitor-1 (PAI-1). Both of these proteins have been indicated in another flavivirus related disease, dengue, as having roles related to the bleeding abnormalities observed and overall outcome of infection. In this study we wanted to determine if FBG and PAI-1 expression levels by human hepatocytes was disrupted or altered by infection with either wild-type Asibi or vaccine strain17-D YFVs. Our findings indicate that YFV infection does affect the transcriptional and translational expression of FBG and PAI-1 in human hepatocytes and that these results are further affected by IL-6 during early stages of infection. These results may lead to further understanding of the molecular mechanism associated with bleeding abnormalities observed during late stage YFV infection. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Woodson, Sara E.; Freiberg, Alexander N.; Holbrook, Michael R.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77550 USA.
[Woodson, Sara E.; Freiberg, Alexander N.; Holbrook, Michael R.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77550 USA.
[Holbrook, Michael R.] NIAID, Integrated Res Facil, Frederick, MD 21702 USA.
RP Holbrook, MR (reprint author), NIAID, Integrated Res Facil, 8200 Res Plaza, Frederick, MD 21702 USA.
EM Michael.holbrook@nih.gov
NR 41
TC 4
Z9 4
U1 1
U2 16
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1702
J9 VIRUS RES
JI Virus Res.
PD AUG
PY 2013
VL 175
IS 2
BP 155
EP 159
DI 10.1016/j.virusres.2013.04.013
PG 5
WC Virology
SC Virology
GA 172BP
UT WOS:000320975200009
PM 23639427
ER
PT J
AU Harmon, W
Guleria, I
Ikle, D
Armstrong, B
Spaneas, L
Morrison, Y
Bridges, N
Sayegh, M
Chandraker, A
AF Harmon, W.
Guleria, I.
Ikle, D.
Armstrong, B.
Spaneas, L.
Morrison, Y.
Bridges, N.
Sayegh, M.
Chandraker, A.
TI CHILDREN DEVELOP DE NOVO ANTI-HLA ANTIBODIES (ABS) FOLLOWING KIDNEY
TRANSPLANTATION AT A HIGHER INCIDENCE THAN ADULTS: AN ANALYSIS OF THE
NIH CTOT/CCTPT-02 STUDY
SO PEDIATRIC TRANSPLANTATION
LA English
DT Meeting Abstract
C1 [Harmon, W.; Guleria, I.; Spaneas, L.; Sayegh, M.; Chandraker, A.] Boston Childrens Hosp, Boston, MA USA.
[Harmon, W.; Guleria, I.; Spaneas, L.; Sayegh, M.; Chandraker, A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Ikle, D.; Armstrong, B.] RHO, Chapel Hill, NC USA.
[Morrison, Y.; Bridges, N.] NIAID, 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 1397-3142
J9 PEDIATR TRANSPLANT
JI Pediatr. Transplant.
PD AUG
PY 2013
VL 17
SU 1
MA 11
BP 45
EP 45
PG 1
WC Pediatrics; Transplantation
SC Pediatrics; Transplantation
GA 178IC
UT WOS:000321439600012
ER
PT J
AU Rice, OV
Heidbreder, CA
Gardner, EL
Schonhar, CD
Ashby, CR
AF Rice, Onarae V.
Heidbreder, Christian A.
Gardner, Eliot L.
Schonhar, Charles D.
Ashby, Charles R., Jr.
TI The selective D3 receptor antagonist SB-277011A attenuates
morphine-triggered reactivation of expression of cocaine-induced
conditioned place preference
SO SYNAPSE
LA English
DT Article
DE dopamine; D3 receptor; cocaine; conditioned place preference
ID DOPAMINE D-3 RECEPTORS; SELF-ADMINISTRATION BEHAVIOR; DRUG-SEEKING
BEHAVIOR; INDUCED REINSTATEMENT; HEROIN-SEEKING; BRAIN REWARD;
PHARMACOLOGICAL ACTIONS; GLUTAMATE TRANSMISSION; ANHEDONIA HYPOTHESIS;
NUCLEUS-ACCUMBENS
AB We examined the effect of acute administration of the selective D3 receptor antagonist SB-277011A on morphine-triggered reactivation of cocaine-induced conditioned place preference (CPP) in adult male Sprague-Dawley rats. Repeated pairing of animals with 15 mg/kg i.p. of cocaine HCl or vehicle to cue-specific CPP chambers produced a significant CPP response compared to animals paired only with vehicle in both chambers. Expression of the CPP response to cocaine was then extinguished by repeatedly giving the animals vehicle injections in the cocaine-paired chambers. The magnitude of the CPP response after extinction was not significantly different from that of animals paired only with vehicle. Expression of the extinguished CPP response was reactivated by acute administration of 5 mg/kg i.p. of morphine but not by vehicle. Acute administration of 6 or 12 mg/kg i.p. (but not 3 mg/kg) of SB-277011A significantly attenuated morphine-triggered reactivation of the cocaine-induced CPP. SB-277011A itself (12 mg/kg i.p.) did not reactivate the extinguished CPP response. Overall, SB-277011A decreases the incentive motivational actions of morphine. The present findings suggest that central D3 dopamine receptors are involved in relapse to cocaine-seeking behavior, that a final common neural mechanism exists to mediate the incentive motivational effects of psychostimulants and opiates, and that selective dopamine D3 receptor antagonists constitute promising compounds for treating addiction. Synapse 67:469-475, 2013. (c) 2013 Wiley Periodicals, Inc.
C1 [Rice, Onarae V.; Schonhar, Charles D.] Furman Univ, Dept Psychol, Greenville, SC 29613 USA.
[Heidbreder, Christian A.] Reckitt Benckiser Pharmaceut, Global Res & Dev, Richmond, VA 23235 USA.
[Gardner, Eliot L.] NIDA, Neuropsychopharmacol Sect, Chem Biol Res Branch, Intramural Res Program,NIH,NIH Biomed Res Ctr, Baltimore, MD 21224 USA.
[Ashby, Charles R., Jr.] St Johns Univ, Coll Pharm & Allied Hlth Profess, Dept Pharmaceut Sci, Jamaica, NY 11439 USA.
RP Ashby, CR (reprint author), St Johns Univ, Coll Pharm & Allied Hlth Profess, Dept Pharmaceut Sci, 8000 Utopia Pkwy, Jamaica, NY 11439 USA.
EM ashbyc@stjohns.edu
FU National Institute of General Medical Sciences (NIGMS) [P20GM103499]
FX Contract grant sponsor: National Institute of General Medical Sciences
(NIGMS); Contract grant number: P20GM103499.
NR 72
TC 9
Z9 9
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0887-4476
J9 SYNAPSE
JI Synapse
PD AUG
PY 2013
VL 67
IS 8
BP 469
EP 475
DI 10.1002/syn.21653
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 169KB
UT WOS:000320777800002
PM 23404528
ER
PT J
AU Zhang, J
Tuo, JS
Cao, XG
Shen, DF
Li, W
Chan, CC
AF Zhang, Jun
Tuo, Jingsheng
Cao, Xiaoguan
Shen, Defen
Li, Wei
Chan, Chi-Chao
TI Early degeneration of photoreceptor synapse in Ccl2/Cx3cr1-deficient
mice on Crb1rd8 background
SO SYNAPSE
LA English
DT Article
DE age-related macular degeneration; cone synapse degeneration; rod synapse
plasticity; animal model
ID AGE-RELATED MACULOPATHY; ROD BIPOLAR CELLS; EXPERIMENTAL
RETINAL-DETACHMENT; MACULAR DEGENERATION; CONE PHOTORECEPTOR; MOUSE
MODEL; RETINITIS-PIGMENTOSA; MAMMALIAN RETINA; CHEMOKINE RECEPTORS;
ELECTRON-MICROSCOPY
AB Photoreceptor ribbon synapse releases glutamate to postsynaptic targets. The synaptic ribbon may play multiple roles in ribbon synapse development, synaptic vesicle recycling, and synaptic transmission. Age-related macular degeneration (AMD) patients appear to have fewer or no detectable synaptic ribbons as well as abnormal swelling in the photoreceptor terminals in the macula. However, reports on changes of photoreceptor synapses in AMD are scarce and photoreceptor type and quantity affected in early AMD is still unclear. Here, we employed multiple anatomical techniques to investigate these questions in Ccl2-/-/Cx3cr1-/- mouse on Crb1rd8 background (DKO rd8) at one month of age. We found that approximately 17% of photoreceptors over the focal lesion were lost. Immunostaining for synapse-associated proteins (CtBP2, synaptophysin, and vesicular glutamate transporter 1) showed significantly reduced expression and ectopic localization. Cone opsins demonstrated dramatic reduction in expression (S-opsins) and extensive mislocalization (M-opsins). Quantitative ultrastructural analysis confirmed a significant decrease in the number of cone terminals and nuclei, numerous vacuoles in remaining cone terminals, reduction in the number of synaptic ribbons in photoreceptor terminals, and ectopic rod ribbon synapses. In addition, glutamate receptor immunoreactivity on aberrant sprouting of rod bipolar cells and horizontal cells were identified at the ectopic synapses. These results indicate that synaptic alterations occur at the early stages of disease and cones are likely more susceptible to damage caused by DKO rd8 mutation. They provide a new insight into potential mechanism of vision function lost due to synaptic degeneration before cell death in the early stages of AMD. Synapse 67:515-531, 2013. (c) 2013 Wiley Periodicals, Inc.
C1 [Zhang, Jun; Chan, Chi-Chao] NEI, Histol Core, NIH, Bethesda, MD 20892 USA.
[Tuo, Jingsheng; Cao, Xiaoguan; Shen, Defen; Chan, Chi-Chao] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Cao, Xiaoguan] Peking Univ, Dept Ophthalmol, Peoples Hosp, Beijing 100871, Peoples R China.
[Li, Wei] NEI, Unit Retinal Neurophysiol, NIH, Bethesda, MD 20892 USA.
RP Chan, CC (reprint author), NEI, NIH, 10 Ctr Dr,Bldg 10,Rm 10N103, Bethesda, MD 20892 USA.
EM junzhang@ninds.nih.gov; chanc@nei.nih.gov
OI Tuo, Jingsheng/0000-0002-1372-7810
FU National Eye Institute, NIH
FX Contract grant sponsor: Intramural Research Program of National Eye
Institute, NIH.
NR 82
TC 5
Z9 5
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0887-4476
J9 SYNAPSE
JI Synapse
PD AUG
PY 2013
VL 67
IS 8
BP 515
EP 531
DI 10.1002/syn.21674
PG 17
WC Neurosciences
SC Neurosciences & Neurology
GA 169KB
UT WOS:000320777800006
PM 23592324
ER
PT J
AU Mahamat, A
Dussart, P
Bouix, A
Carvalho, L
Eltges, F
Matheus, S
Miller, MA
Quenel, P
Viboud, C
AF Mahamat, A.
Dussart, P.
Bouix, A.
Carvalho, L.
Eltges, F.
Matheus, S.
Miller, M. A.
Quenel, P.
Viboud, C.
TI Climatic drivers of seasonal influenza epidemics in French Guiana,
2006-2010
SO JOURNAL OF INFECTION
LA English
DT Article
DE Influenza; Seasonality; Tropical; Climate; Rainfall; Humidity;
Times-series; ARIMA; Dynamic regression
ID TIME-SERIES ANALYSIS; EPIDEMIOLOGIC DYNAMICS; SENTINEL SURVEILLANCE; A
VIRUS; TRANSMISSION; CIRCULATION; RESISTANCE; PATTERNS; TROPICS; IMPACT
AB Objectives: Influenza seasonality remains poorly studied in Equatorial regions. Here we assessed the seasonal characteristics and environmental drivers of influenza epidemics in French Guiana, where influenza surveillance was established in 2006.
Methods: Sentinel GPs monitored weekly incidence of Influenza-like illnesses (ILI) from January 2006 through December 2010 and collected nasopharyngeal specimens from patients for virological confirmation. Times series analysis was used to investigate relationship between ILI and climatic parameters (rainfall and specific humidity).
Results: Based on 1533 viruses identified during the study period, we observed marked seasonality in the circulation of influenza virus in the pre-pandemic period, followed by year-round activity in the post-pandemic period, with a peak in the rainy season. ILI incidence showed seasonal autoregressive variation based on ARIMA analysis. Multivariate dynamic regression revealed that a 1 mm increase of rainfall resulted in an increase of 0.33% in ILI incidence one week later, adjusting for specific humidity (SH). Conversely, an increase of 1 g/kg of SH resulted in a decrease of 11% in ILI incidence 3 weeks later, adjusting for rainfall.
Conclusions: Increased rainfall and low levels of specific humidity favour influenza transmission in French Guiana. (C) 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
C1 [Mahamat, A.; Miller, M. A.; Viboud, C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Mahamat, A.] Cayenne Gen Hosp, Infect Dis & Trop Med Unit, Cayenne, France.
[Mahamat, A.] Univ Antilles Guyane, EA 3595, Cayenne, France.
[Dussart, P.; Matheus, S.; Quenel, P.] Pasteur Inst Guyane, Cayenne, France.
[Bouix, A.] GP Sentinel Network Influenza Surveillance, Cayenne, France.
[Carvalho, L.] French Inst Publ Hlth Surveillance, Reg Off, Cayenne, France.
[Eltges, F.] Reg Hlth Agcy, Cayenne, French Guiana, France.
RP Mahamat, A (reprint author), Unite Malad Infect & Trop, Ave Flamboyants, F-97306 Cayenne, Guyane, France.
EM mahamataba@gmail.com
RI QUENEL, PHILIPPE/J-4351-2015
OI QUENEL, PHILIPPE/0000-0003-3361-3623
FU "Investissement d'Avenir" grant (CEBA) [ANR-10-LABX-0025]; Office of
Global Affairs' International Influenza Unit in the Office of the
Secretary of the Department of Health and Human Services
FX This research was conducted in the context of the Multinational
Influenza Seasonal Mortality Study (MISMS), an ongoing international
collaborative effort to understand influenza epidemiological and
evolutionary patterns, led by the Fogarty International Center, National
Institutes of Health. Funding for this project comes from the Office of
Global Affairs' International Influenza Unit in the Office of the
Secretary of the Department of Health and Human Services. This work has
benefited from an "Investissement d'Avenir" grant managed by Agence
Nationale de la Recherche (CEBA, ref. ANR-10-LABX-0025). The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 28
TC 12
Z9 12
U1 0
U2 13
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0163-4453
J9 J INFECTION
JI J. Infect.
PD AUG
PY 2013
VL 67
IS 2
BP 141
EP 147
DI 10.1016/j.jinf.2013.03.018
PG 7
WC Infectious Diseases
SC Infectious Diseases
GA 166ZR
UT WOS:000320600300006
PM 23597784
ER
PT J
AU Phillips, DD
Garboczi, DN
Singh, K
Hu, ZL
Leppla, SH
Leysath, CE
AF Phillips, Damilola D.
Garboczi, David N.
Singh, Kavita
Hu, Zonglin
Leppla, Stephen H.
Leysath, Clinton E.
TI The sub-nanomolar binding of DNA-RNA hybrids by the single-chain Fv
fragment of antibody S9.6
SO JOURNAL OF MOLECULAR RECOGNITION
LA English
DT Article
DE Monoclonal antibody; scFv; antibody sequence; DNA-RNA hybrids
ID SOLUTION HYBRIDIZATION ASSAY; MONOCLONAL-ANTIBODY; RIBOSOMAL-RNA;
HYPERVARIABLE REGIONS; IMMUNODETECTION; BACTERIA
AB The monoclonal antibody S9.6 binds DNA-RNA hybrids with high affinity, making it useful in research and diagnostic applications, such as in microarrays and in the detection of R-loops. A single-chain variable fragment (scFv) of S9.6 was produced, and its affinities for various synthetic nucleic acid hybrids were measured by surface plasmon resonance (SPR). S9.6 exhibits dissociation constants of approximately 0.6nM for DNA-RNA and, surprisingly, 2.7nM for RNA-RNA hybrids that are AU-rich. The affinity of the S9.6 scFv did not appear to be strongly influenced by various buffer conditions or by ionic strength below 500mM NaCl. The smallest epitope that was strongly bound by the S9.6 scFv contained six base pairs of DNA-RNA hybrid. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Phillips, Damilola D.; Hu, Zonglin; Leppla, Stephen H.; Leysath, Clinton E.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Garboczi, David N.; Singh, Kavita] NIAID, Struct Biol Sect, Res Technol Branch, NIH, Rockville, MD 20852 USA.
RP Leysath, CE (reprint author), NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike,Bldg 33 Room 1W20B-5, Bethesda, MD 20892 USA.
EM leysathce@niaid.nih.gov
FU NIH, National Institute of Allergy and Infectious Diseases
FX The authors thank Dr. Larry Lantz for purification of S9.6 IgG from
hybridoma cells. This research was supported by the Intramural Research
Program of the NIH, National Institute of Allergy and Infectious
Diseases.
NR 26
TC 16
Z9 16
U1 2
U2 19
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0952-3499
J9 J MOL RECOGNIT
JI J. Mol. Recognit.
PD AUG
PY 2013
VL 26
IS 8
BP 376
EP 381
DI 10.1002/jmr.2284
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 167GF
UT WOS:000320618700006
PM 23784994
ER
PT J
AU Robles, C
Viscidi, R
Malats, N
Silverman, DT
Tardon, A
Garcia-Closas, R
Serra, C
Carrato, A
Herranz, J
Lloreta, J
Rothman, N
Real, FX
de Sanjose, S
Kogevinas, M
AF Robles, Claudia
Viscidi, Raphael
Malats, Nuria
Silverman, Debra T.
Tardon, Adonina
Garcia-Closas, Reina
Serra, Consol
Carrato, Alfredo
Herranz, Jesus
Lloreta, Josep
Rothman, Nathaniel
Real, Francisco X.
de Sanjose, Silvia
Kogevinas, Manolis
TI Bladder cancer and seroreactivity to BK, JC and Merkel cell
polyomaviruses: The Spanish bladder cancer study
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE seroepidemiology; BK polyomavirus; Merkel cell polyomavirus; JCV
polyomavirus and bladder cancer
ID RENAL-TRANSPLANTATION; VIRUS INFECTION; CARCINOMA; ANTIBODY; RISK;
INDIVIDUALS
AB An infectious etiology for bladder cancer has long been suspected. Merkel cell virus (MCV), BKV and JCV polyomaviruses are possible causative agents but data remain scarce. Therefore, we evaluated the seroresponse to these three polyomaviruses in association with bladder cancer risk. 1,135 incident bladder cancer subjects from five Spanish regions and 982 hospital controls matched by sex, age and region were included. 99% of cases were urothelial-cell carcinomas. Antibody response against MCV, BKV and JCV was measured by enzyme immunoassay using Virus-Like-Particles. Our results show a similar seroprevalence in cases and controls: 64/60% for BKV, 83/82% for MCV and 87/83% for JCV. However, among seropositive subjects, higher median seroreactivities were observed in cases compared to controls for BKV (0.84 vs. 0.70, p-value=0.009) and MCV (1.81 vs. 0.65, p-value<0.001). Increased bladder cancer risk was observed for BKV (OR=1.4, 95%CI 1.041.8) and for MCV (OR=1.5, 95%CI 1.21.9), when comparing highest to lowest seroreactivity tertiles. The associations of BKV and MCV with bladder cancer were independent of each other and neither smoking status nor disease stage and grade modified them. Furthermore, no association was observed between seroresponse to JCV and bladder cancer. Therefore, we conclude that BKV and MCV polyomavirus infection could be related to an increased bladder cancer risk.
C1 [Robles, Claudia; de Sanjose, Silvia] IDIBELL, Catalan Inst Oncol, Canc Epidemiol Res Programme, Unit Infect & Canc UNIC, Barcelona 08908, Spain.
[Viscidi, Raphael] Johns Hopkins Univ, Sch Med, Dept Pediat, Stanley Div Dev Neurovirol, Baltimore, MD 21287 USA.
[Malats, Nuria; Herranz, Jesus] Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid 28029, Spain.
[Silverman, Debra T.; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA.
[Tardon, Adonina] Univ Oviedo, E-33006 Oviedo, Spain.
[Tardon, Adonina; de Sanjose, Silvia; Kogevinas, Manolis] CIBER Epidemiol & Salud Publ CIBERESP, Barcelona 08036, Spain.
[Garcia-Closas, Reina] Hosp Univ Canarias, Tenerife 38320, Spain.
[Serra, Consol] Consorci Hosp Parc Tauli, Sabadell 08208, Spain.
[Carrato, Alfredo] Hosp Gen Univ Elche, Elche 03203, Spain.
[Carrato, Alfredo] Hosp Ramon & Cajal, E-28034 Madrid, Spain.
[Lloreta, Josep; Kogevinas, Manolis] Hosp del Mar Res Inst IMIM, Barcelona 08003, Spain.
[Real, Francisco X.] Spanish Natl Canc Res Ctr CNIO, Epithelial Carcinogenesis Grp, Madrid 28029, Spain.
[Real, Francisco X.] Univ Pompeu Fabra, Dept Expt & Hlth Sci, Barcelona 08003, Spain.
[Kogevinas, Manolis] Natl Sch Publ Hlth, Athens, AL 35611 USA.
[Kogevinas, Manolis] Ctr Res Environm Epidemiol CREAL, Barcelona 08003, Spain.
RP Kogevinas, M (reprint author), Ctr Res Environm Epidemiol CREAL, Doctor Aiguader 88, Barcelona 08003, Spain.
EM kogevinas@creal.cat
RI Serra, C/E-6879-2014; Herranz Valera, Jesus/M-8657-2014; de Sanjose
Llongueras, Silvia/H-6339-2014; Lloreta, J/I-2112-2014; Malats,
Nuria/H-7041-2015; Real Arribas, Francisco/H-5275-2015; Robles,
Claudia/G-5210-2015; Kogevinas, Manolis/C-3918-2017
OI Serra, C/0000-0001-8337-8356; Herranz Valera, Jesus/0000-0002-7385-1311;
Lloreta, J/0000-0003-1644-9470; Malats, Nuria/0000-0003-2538-3784; Real
Arribas, Francisco/0000-0001-9501-498X; Robles,
Claudia/0000-0003-3788-827X;
FU National Institutes of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics [NCI N02-CP-11015]; Spanish Ministry of
Health [98/1274, 365 00/0745, PI061614, G03/174, RD06/0020/0095]
FX Grant sponsor: National Institutes of Health, National Cancer Institute,
Division of Cancer Epidemiology and Genetics; Grant number: Intramural
Research Program NCI N02-CP-11015; Grant sponsor: Spanish Ministry of
Health; Grant numbers: 98/1274; 365 00/0745; PI061614; G03/174 and CR
supported by RD06/0020/0095.
NR 25
TC 7
Z9 7
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD AUG 1
PY 2013
VL 133
IS 3
BP 597
EP 603
DI 10.1002/ijc.28053
PG 7
WC Oncology
SC Oncology
GA 149AC
UT WOS:000319289400008
PM 23355322
ER
PT J
AU Hodge, JW
Garnett, CT
Farsaci, B
Palena, C
Tsang, KY
Ferrone, S
Gameiro, SR
AF Hodge, James W.
Garnett, Charlie T.
Farsaci, Benedetto
Palena, Claudia
Tsang, Kwong-Yok
Ferrone, Soldano
Gameiro, Sofia R.
TI Chemotherapy-induced immunogenic modulation of tumor cells enhances
killing by cytotoxic T lymphocytes and is distinct from immunogenic cell
death
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE docetaxel; immunogenic cell death; immunogenic modulation; calreticulin;
antigen-processing machinery; T-cell response
ID ANTIGEN-PROCESSING MACHINERY; HUMAN CARCINOEMBRYONIC ANTIGEN;
BREAST-CANCER CELLS; CALRETICULIN EXPOSURE; MONOCLONAL-ANTIBODIES;
IN-VITRO; VACCINE; DOCETAXEL; RESISTANCE; EXPRESSION
AB Certain chemotherapeutic regimens trigger cancer cell death while inducing dendritic cell maturation and subsequent immune responses. However, chemotherapy-induced immunogenic cell death (ICD) has thus far been restricted to select agents. In contrast, several chemotherapeutic drugs modulate antitumor immune responses, despite not inducing classic ICD. In addition, in many cases tumor cells do not die after treatment. Here, using docetaxel, one of the most widely used cancer chemotherapeutic agents, as a model, we examined phenotypic and functional consequences of tumor cells that do not die from ICD. Docetaxel treatment of tumor cells did not induce ATP or high-mobility group box 1 (HMGB1) secretion, or cell death. However, calreticulin (CRT) exposure was observed in all cell lines examined after chemotherapy treatment. Killing by carcinoembryonic antigen (CEA), MUC-1, or PSA-specific CD8+ CTLs was significantly enhanced after docetaxel treatment. This killing was associated with increases in components of antigen-processing machinery, and mediated largely by CRT membrane translocation, as determined by functional knockdown of CRT, PERK, or CRT-blocking peptide. A docetaxel-resistant cell line was selected (MDR-1+, CD133+) by continuous exposure to docetaxel. These cells, while resistant to direct cytostatic effects of docetaxel, were not resistant to the chemomodulatory effects that resulted in enhancement of CTL killing. Here, we provide an operational definition of immunogenic modulation, where exposure of tumor cells to nonlethal/sublethal doses of chemotherapy alters tumor phenotype to render the tumor more sensitive to CTL killing. These observations are distinct and complementary to ICD and highlight a mechanism whereby chemotherapy can be used in combination with immunotherapy.
C1 [Hodge, James W.; Garnett, Charlie T.; Farsaci, Benedetto; Palena, Claudia; Tsang, Kwong-Yok; Gameiro, Sofia R.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Ferrone, Soldano] Univ Pittsburgh, Inst Canc, Canc Immunol Program, Pittsburgh, PA USA.
RP Hodge, JW (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B13, Bethesda, MD 20892 USA.
EM jh241d@nih.gov
RI Farsaci, Benedetto/L-9837-2014; Hodge, James/D-5518-2015;
OI Farsaci, Benedetto/0000-0001-8275-2561; Hodge,
James/0000-0001-5282-3154; Garnett-Benson, Charlie/0000-0002-0238-3303
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX Grant sponsors: Intramural Research Program of the Center for Cancer
Research, National Cancer Institute, National Institutes of Health
NR 50
TC 55
Z9 56
U1 1
U2 35
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD AUG 1
PY 2013
VL 133
IS 3
BP 624
EP 636
DI 10.1002/ijc.28070
PG 13
WC Oncology
SC Oncology
GA 149AC
UT WOS:000319289400011
PM 23364915
ER
PT J
AU Sulzer, J
Haller, S
Scharnowski, F
Weiskopf, N
Birbaumer, N
Blefari, ML
Bruehl, AB
Cohen, LG
deCharms, RC
Gassert, R
Goebel, R
Herwig, U
LaConte, S
Linden, D
Luft, A
Seifritz, E
Sitaram, R
AF Sulzer, J.
Haller, S.
Scharnowski, F.
Weiskopf, N.
Birbaumer, N.
Blefari, M. L.
Bruehl, A. B.
Cohen, L. G.
deCharms, R. C.
Gassert, R.
Goebel, R.
Herwig, U.
LaConte, S.
Linden, D.
Luft, A.
Seifritz, E.
Sitaram, R.
TI Real-time fMRI neurofeedback: Progress and challenges
SO NEUROIMAGE
LA English
DT Review
DE Real-time fMRI; Neurofeedback; Operant conditioning; Brain-computer
interface
ID BRAIN-COMPUTER INTERFACES; RESONANCE-IMAGING FMRI; MINIMALLY CONSCIOUS
STATE; SLOW CORTICAL POTENTIALS; GOAL-DIRECTED THINKING; FUNCTIONAL MRI;
CORTEX ACTIVITY; SELF-REGULATION; MOTOR IMAGERY; PANIC DISORDER
AB In February of 2012, the first international conference on real time functional magnetic resonance imaging (rtfMRI) neurofeedback was held at the Swiss Federal Institute of Technology Zurich (ETHZ), Switzerland. This review summarizes progress in the field, introduces current debates, elucidates open questions, and offers viewpoints derived from the conference. The review offers perspectives on study design, scientific and clinical applications, rtfMRI learning mechanisms and future outlook. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Sulzer, J.; Blefari, M. L.; Gassert, R.] ETH, Swiss Fed Inst Technol, Dept Hlth Sci & Technol, CH-8092 Zurich, Switzerland.
[Haller, S.] Univ Geneva, Univ Hosp Geneva, CH-1211 Geneva, Switzerland.
[Scharnowski, F.] Univ Geneva, Dept Radiol & Med Informat CIBM, CH-1211 Geneva, Switzerland.
[Scharnowski, F.] Ecole Polytech Fed Lausanne, Swiss Inst Technol Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland.
[Weiskopf, N.] UCL, Wellcome Trust Ctr Neuroimaging, UCL Inst Neurol, London WC1E 6BT, England.
[Birbaumer, N.] Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72074 Tubingen, Germany.
[Birbaumer, N.] Osped San Camillo, IRCCS, I-30126 Venice, Italy.
[Bruehl, A. B.; Herwig, U.; Seifritz, E.] Zurich Univ Hosp Psychiat, Dept Psychiat Psychotherapy & Psychosomat, CH-8032 Zurich, Switzerland.
[Cohen, L. G.] NIH, Bethesda, MD 20892 USA.
[deCharms, R. C.] Omneuron Inc, Menlo Pk, CA 94025 USA.
[Goebel, R.] Univ Maastricht, Dept Neurocognit, NL-6200 Maastricht, Netherlands.
[Herwig, U.] Univ Ulm, Dept Psychiat & Psychotherapy 3, D-89069 Ulm, Germany.
[LaConte, S.] Virginia Tech, Caril Res Inst, Blacksburg, VA 24016 USA.
[Linden, D.] Cardiff Univ, Cardiff CF10 3AT, S Glam, Wales.
[Luft, A.] Univ Zurich Hosp, Dept Neurol, Zurich, Switzerland.
[Luft, A.] Univ Zurich, CH-8008 Zurich, Switzerland.
[Sitaram, R.] Univ Florida, Dept Biomed Engn, Gainesville, FL 32611 USA.
[Sitaram, R.] Sri Chitra Tirunal Inst Med Sci & Technol, Trivandrum, Kerala, India.
RP Sulzer, J (reprint author), Leonhardstr 27 B9-2, CH-8092 Zurich, Switzerland.
EM jamessulzer@gmail.com; sven.haller@hcuge.ch;
scharnowski.frank@gmail.com; n.weiskopf@ucl.ac.uk;
ranganatha.sitaram@bme.ufl.edu
RI Gassert, Roger/B-6351-2011; Weiskopf, Nikolaus/B-9357-2008; Scharnowski,
Frank/A-2367-2010; Centre d'imagerie Biomedicale, CIBM/B-5740-2012;
Bruhl, Annette/A-5272-2013; Linden, David/C-7355-2013;
OI Gassert, Roger/0000-0002-6373-8518; Weiskopf,
Nikolaus/0000-0001-5239-1881; Bruhl, Annette/0000-0003-4704-4986;
Sitaram, Ranganatha/0000-0002-8577-8035; Linden,
David/0000-0002-5638-9292; Haller, Sven/0000-0001-7433-0203
FU Swiss National Science Foundation [31CO30_139955]; Zurich Neuroscience
Center (ZNZ); Philips Medical; ETHZ; University of Zurich; Deutsche
Forschungsgemeinschaft (DFG); European Research Council (ERC); German
Ministry of Education and Research (BMBF); European Union; Swiss
National Fund
FX The authors would like to thank the sponsors of the event, including the
Swiss National Science Foundation (project #31CO30_139955), the Zurich
Neuroscience Center (ZNZ), Philips Medical, ETHZ, and the University of
Zurich. NB is supported by the Deutsche Forschungsgemeinschaft (DFG,
Koselleck Grant) and a European Research Council (ERC) grant and a
Computational Neuroscience Grant (Bernstein) from the German Ministry of
Education and Research (BMBF). FS is supported by the Swiss National
Fund and a Marie-Curie Re-integration Grant of the European Union.
NR 140
TC 105
Z9 107
U1 11
U2 126
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD AUG 1
PY 2013
VL 76
IS 1
BP 386
EP 399
DI 10.1016/j.neuroimage.2013.03.033
PG 14
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 146KP
UT WOS:000319090300036
PM 23541800
ER
PT J
AU Hasley, RB
Hong, CW
Li, WQ
Friesen, T
Nakamura, Y
Kim, GY
Park, JH
Hixon, JA
Durum, S
Hu, ZH
Sneller, MC
Oguariri, R
Imamichi, T
Lane, HC
Catalfamo, M
AF Hasley, Rebecca B.
Hong, Changwan
Li, Wenqing
Friesen, Travis
Nakamura, Yoriko
Kim, Grace Y.
Park, Jung-Hyun
Hixon, Julie A.
Durum, Scott
Hu, Zonghui
Sneller, Michael C.
Oguariri, Raphael
Imamichi, Tomozumi
Lane, H. Clifford
Catalfamo, Marta
TI HIV immune activation drives increased Eomes expression in memory CD8 T
cells in association with transcriptional downregulation of CD127
SO AIDS
LA English
DT Article
DE CD127; Eomes; HIV; T-bet; T-box transcription factors
ID INTERLEUKIN-7 RECEPTOR EXPRESSION; ACTIVE ANTIRETROVIRAL THERAPY;
CHRONIC VIRAL-INFECTION; VIRUS TYPE-1 INFECTION; FACTOR EOMESODERMIN;
DIFFERENTIATION; EFFECTOR; SUBSETS; PLASMA; IL-7
AB Background: During HIV infection distinct mechanisms drive immune activation of the CD4 and CD8 T cells leading to CD4 T-cell depletion and expansion of the CD8 T-cell pool. This immune activation is polyclonal and extends beyond HIV-specific T cells. One consequence of this immune activation is a profound decrease in IL-7R alpha (CD127) expression on memory CD8 T cells. The mechanisms leading to this are unknown and because of the potential impact of reduced IL-7 signaling in memory T cells specific to HIV and other pathogens, in the present study we examined the molecular mechanisms implicated in this downregulation of CD127.
Methods: Membrane bound (mIL7RA) and soluble (sIL7RA) mRNA expression was determined by qRT-PCR. CD127, Eomesodermin (Eomes) and T-bet expression in healthy controls and HIV-infected patients were studied by flow cytometry.
Results: CD127 downregulation occurs at the transcriptional level for both mIL7RA and sIL7RA alternative spliced forms in the CD127(low) memory CD8 T cells. CD127(low) memory CD8 T cells exhibited increased Eomes expression and an 'effector-like' gene profile. These changes were associated with higher HIV-RNA levels. Following combination antiretroviral therapy (cART), there was an increase in CD127 expression over an extended period of time (>5 months) which was associated with decreased Eomes expression.
Conclusion: CD127 is downregulated at a transcriptional level in memory CD8 T cells in association with upregulation of Eomes expression. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Hasley, Rebecca B.; Friesen, Travis; Nakamura, Yoriko; Sneller, Michael C.; Lane, H. Clifford; Catalfamo, Marta] NIAID, CMRS Lab Immunoregulat, Bethesda, MD 20892 USA.
[Hong, Changwan; Kim, Grace Y.; Park, Jung-Hyun] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Li, Wenqing; Hixon, Julie A.; Durum, Scott] NCI, Mol Immunoregulat Lab, NIH, Frederick, MD 21701 USA.
[Hu, Zonghui] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Oguariri, Raphael; Imamichi, Tomozumi] NIAID, Collaborat Clin Res Branch, NIH, Frederick, MD USA.
RP Catalfamo, M (reprint author), NIAID, CMRS Lab Immunoregulat, NIH, Bldg 10,Room 11B07,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM catalfam@mail.nih.gov
FU NIAID, NIH
FX This research was supported by the Intramural Research Program of the
NIAID, NIH.
NR 68
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U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD JUL 31
PY 2013
VL 27
IS 12
BP 1867
EP 1877
DI 10.1097/QAD.0b013e3283618487
PG 11
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 301IK
UT WOS:000330525800004
PM 23965471
ER
PT J
AU Shapiro, RL
Kitch, D
Ogwu, A
Hughes, MD
Lockman, S
Powis, K
Souda, S
Moffat, C
Moyo, S
McIntosh, K
van Widenfelt, E
Zwerski, S
Mazhani, L
Makhema, J
Essex, M
AF Shapiro, Roger L.
Kitch, Douglas
Ogwu, Anthony
Hughes, Michael D.
Lockman, Shahin
Powis, Kathleen
Souda, Sajini
Moffat, Claire
Moyo, Sikhulile
McIntosh, Kenneth
van Widenfelt, Erik
Zwerski, Sheryl
Mazhani, Loeto
Makhema, Joseph
Essex, Max
TI HIV transmission and 24-month survival in a randomized trial of HAART to
prevent MTCT during pregnancy and breastfeeding in Botswana
SO AIDS
LA English
DT Article
DE Africa; antiretrovirals; Botswana; HIV; infant survival; maternal
health; mother-to-child HIV transmission
ID TO-CHILD TRANSMISSION; ANTIRETROVIRAL THERAPY; INFECTED WOMEN; INFANTS;
MALAWI; PROPHYLAXIS; MORTALITY; MOTHERS; BORN; ZIDOVUDINE
AB Objectives: HAART for prevention of mother-to-child HIV transmission (MTCT) may impact long-term survival of women and children.
Design: Randomized clinical trial.
Methods: HIV-infected pregnant women with CD4(+) cell count at least 200 cells/mu l were randomly assigned to abacavir, zidovudine, lamivudine (arm A) or lopinavir-ritonavir, zidovudine-lamivudine (arm B) from week 26 to 34 gestation through planned weaning by 6 months postpartum. Women with baseline CD4(+) cell count less than 200 cells/mu l received nevirapine-zidovudine-lamivudine indefinitely (Obs arm), as did randomized women later qualifying for treatment.
Results: Among 560 randomized and 170 observational women enrolled, there were 14 deaths (1.9%) - one antenatally (Obs), three from delivery to 6 months postpartum (1 arm A, 2 Obs), and 10 from 6 to 24 months postpartum (5 arm A, 3 arm B, 2 Obs). Time to death or CD4(+) cell count below 200 cells/mu l was shorter in arm A vs. B (P=0.03). Of the 709 live-born children, 97% breastfed for a median of 5.8 months. Of 37 (5.2%) deaths by 24 months, nine were before breastfeeding initiated (3 arm A, 2 arm B, 4 Obs); six while breastfeeding (1 arm A, 2 arm B, 3 Obs); and 22 after weaning (9 arm A, 11 arm B, 2 Obs). Only eight children (1.1%) were HIV-infected at 24 months (6 arm A, 1 arm B, 1 Obs), all before 6 months.
Conclusion: Low MTCT was maintained through extended follow-up in all arms. Disease progression appeared slower after discontinuing protease inhibitor-based HAART, but a concerning number of maternal deaths occurred after stopping either regimen. Strategies to improve maternal and child survival in the postintervention period are required. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Shapiro, Roger L.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA.
[Shapiro, Roger L.; Lockman, Shahin; Powis, Kathleen; Makhema, Joseph; Essex, Max] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Shapiro, Roger L.; Ogwu, Anthony; Lockman, Shahin; Powis, Kathleen; Souda, Sajini; Moffat, Claire; Moyo, Sikhulile; van Widenfelt, Erik; Makhema, Joseph; Essex, Max] Botswana Harvard AIDS Inst Partnership HIV Res &, Gaborone, Botswana.
[Kitch, Douglas; Hughes, Michael D.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Lockman, Shahin] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA.
[Powis, Kathleen] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Powis, Kathleen] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
[McIntosh, Kenneth] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Zwerski, Sheryl] NIAID, NIH, Bethesda, MD 20892 USA.
[Mazhani, Loeto] Univ Botswana, Sch Med, Gaborone, Botswana.
RP Shapiro, RL (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, 110 Francis St,Suite GB, Boston, MA 02215 USA.
EM rshapiro@hsph.harvard.edu
RI Moyo, Sikhulile/E-1464-2015
OI Moyo, Sikhulile/0000-0003-3821-4592
FU National Institute of Allergy and Infectious Diseases [U01-AI066454]
FX National Institute of Allergy and Infectious Diseases (U01-AI066454) /
clinicaltrials.-gov Identifier: NCT00270296.
NR 29
TC 11
Z9 11
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD JUL 31
PY 2013
VL 27
IS 12
BP 1911
EP 1920
DI 10.1097/QAD.0b013e32836158b0
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 301IK
UT WOS:000330525800008
PM 24180000
ER
PT J
AU Williams, PL
Abzug, MJ
Jacobson, DL
Wang, JJ
Van Dyke, RB
Hazra, R
Patel, K
Dimeglio, LA
Mcfarland, EJ
Silio, M
Borkowsky, W
Seage, GR
Oleske, JM
Geffner, ME
AF Williams, Paige L.
Abzug, Mark J.
Jacobson, Denise L.
Wang, Jiajia
Van Dyke, Russell B.
Hazra, Rohan
Patel, Kunjal
Dimeglio, Linda A.
Mcfarland, Elizabeth J.
Silio, Margarita
Borkowsky, William
Seage, George R., III
Oleske, James M.
Geffner, Mitchell E.
CA Int Maternal Pediat Adolescent
Pediat HIV AIDS Cohort Study
TI Pubertal onset in children with perinatal HIV infection in the era of
combination antiretroviral treatment
SO AIDS
LA English
DT Article
DE antiretroviral treatment; BMI; CD4; interval-censored; pediatrics;
protease inhibitors; puberty; statistics; Tanner stage; viral load
ID HUMAN-IMMUNODEFICIENCY-VIRUS; NUTRITION EXAMINATION SURVEY; SECONDARY
SEXUAL CHARACTERISTICS; PEDIATRIC HIV/AIDS COHORT; 3RD NATIONAL-HEALTH;
BODY-MASS INDEX; US CHILDREN; PROTEASE INHIBITORS; DISEASE PROGRESSION;
INSULIN-RESISTANCE
AB Objective: To evaluate associations of perinatal HIV infection, HIV disease severity, and combination antiretroviral treatment with age at pubertal onset.
Design: Analysis of data from two US longitudinal cohort studies (IMPAACT 219C and PHACS AMP), conducted during 2000-2012, including perinatally HIV-infected (PHIV) and HIV-exposed but uninfected (HEU) youth. Tanner stage assessments of pubertal status (breast and pubic hair in girls; genitalia and pubic hair in boys) were conducted annually.
Methods: We compared the timing of pubertal onset (Tanner stage >= 2) between PHIV and HEU youth using interval-censored models. For PHIV youth, we evaluated associations of HIV disease severity and combination antiretroviral treatment with age at pubertal onset, adjusting for race/ethnicity and birth cohort.
Results: The mean age at pubertal onset was significantly later for the 2086 PHIV youth compared to the 453 HEU children (10.3 vs. 9.6, 10.5 vs. 10.0, 11.3 vs. 10.4, and 11.5 vs. 10.7 years according to female breast, female pubic hair, male genitalia, and male pubic hair staging, respectively, all P<0.001). PHIV youth with HIV-1 RNA viral load above 10 000 copies/ml (vs. <= 10 000 copies/ml) or CD4% below 15% (vs. >= 15%) had significantly later pubertal onset (by 4-13 months). Each additional year of combination antiretroviral treatment was associated with a 0.6-1.2-month earlier mean age at pubertal onset, but this trend did not persist after adjustment for birth cohort.
Conclusion: Pubertal onset occurs significantly later in PHIV than in HEU youth, especially among those with more severe HIV disease. However, in the current era, combination antiretroviral treatment may result in more normal timing of pubertal onset. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Williams, Paige L.; Jacobson, Denise L.; Wang, Jiajia; Patel, Kunjal; Seage, George R., III] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Abzug, Mark J.] Univ Colorado, Sch Med, Dept Pediat Infect Dis, Aurora, CO USA.
[Abzug, Mark J.] Childrens Hosp Colorado, Aurora, CO USA.
[Van Dyke, Russell B.; Silio, Margarita] Tulane Univ, Sch Med, New Orleans, LA 70112 USA.
[Hazra, Rohan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Patel, Kunjal; Seage, George R., III] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Dimeglio, Linda A.] Indiana Univ Sch Med, Sect Pediat Endocrinol, Indianapolis, IN 46202 USA.
[Mcfarland, Elizabeth J.] Univ Colorado, Sch Med, Dept Pediat, Denver, CO USA.
[Borkowsky, William] NYU, Sch Med, New York, NY USA.
[Oleske, James M.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pediat, Newark, NJ 07103 USA.
[Geffner, Mitchell E.] Childrens Hosp Los Angeles, Saban Res Inst, Los Angeles, CA 90027 USA.
RP Williams, PL (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, 655 Huntington Ave,FXB 607, Boston, MA 02115 USA.
EM paige@sdac.harvard.edu
RI Oleske, James/C-1951-2016;
OI Oleske, James/0000-0003-2305-5605; DiMeglio, Linda/0000-0002-8033-6078
FU National Institute of Allergy and Infectious Diseases [U01 AI068632];
Eunice Kennedy Shriver National Institute of Child Health and Human
Development [N01-3-3345, HHSN267200800001C]; Statistical and Data
Analysis Center at Harvard School of Public Health, under the National
Institute of Allergy and Infectious Diseases [5 U01 AI41110]; Pediatric
AIDS Clinical Trials Group (PACTG); IMPAACT Group [1 U01 AI068616];
Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institute of Allergy and Infectious Diseases;
National Institute on Drug Abuse; National Institute of Mental Health;
National Institute of Deafness and Other Communication Disorders;
National Heart Lung and Blood Institute; National Institute of
Neurological Disorders and Stroke; National Institute on Alcohol Abuse
and Alcoholism; Harvard University School of Public Health [U01
HD052102-04]; Tulane University School of Medicine [U01 HD052104-01]
FX Funding: Support for the International Maternal Pediatric Adolescent
AIDS Clinical Trials Group (IMPAACT) was provided by the National
Institute of Allergy and Infectious Diseases (U01 AI068632) and the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (contract N01-3-3345 and HHSN267200800001C). This work was
also supported by the Statistical and Data Analysis Center at Harvard
School of Public Health, under the National Institute of Allergy and
Infectious Diseases cooperative agreement #5 U01 AI41110 with the
Pediatric AIDS Clinical Trials Group (PACTG) and #1 U01 AI068616 with
the IMPAACT Group. The Pediatric HIV/AIDS Cohort Study (PHACS) was
supported by the Eunice Kennedy Shriver National Institute of Child
Health and Human Development with co-funding from the National Institute
of Allergy and Infectious Diseases, the National Institute on Drug
Abuse, the National Institute of Mental Health, the National Institute
of Deafness and Other Communication Disorders, the National Heart Lung
and Blood Institute, the National Institute of Neurological Disorders
and Stroke, and the National Institute on Alcohol Abuse and Alcoholism,
through cooperative agreements with the Harvard University School of
Public Health (U01 HD052102-04) and the Tulane University School of
Medicine (U01 HD052104-01). Data management services were provided by
Frontier Science and Technology Research Foundation, and regulatory
services and logistical support were provided by Westat, Inc. NIH
representatives were part of the study team and therefore the sponsor
was involved in study design, coordination, data collection, data
analysis, data interpretation, and writing of the report. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.
NR 48
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U1 2
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD JUL 31
PY 2013
VL 27
IS 12
BP 1959
EP 1970
DI 10.1097/QAD.0b013e328361195b
PG 12
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 301IK
UT WOS:000330525800013
PM 24145244
ER
PT J
AU Kopp, JB
AF Kopp, Jeffrey B.
TI An Expanding Universe of FSGS Genes and Phenotypes: LMX1B Mutations
Cause Familial Autosomal Dominant FSGS Lacking Extrarenal Manifestations
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Editorial Material
ID NAIL-PATELLA SYNDROME
C1 [Kopp, Jeffrey B.] NIDDK, NIH, Kidney Dis Sect, Bethesda, MD USA.
RP Kopp, JB (reprint author), NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM jbkopp@nih.gov
OI Kopp, Jeffrey/0000-0001-9052-186X
FU Intramural NIH HHS
NR 12
TC 5
Z9 6
U1 0
U2 5
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD JUL 31
PY 2013
VL 24
IS 8
BP 1183
EP 1185
DI 10.1681/ASN.2013060661
PG 3
WC Urology & Nephrology
SC Urology & Nephrology
GA 198GD
UT WOS:000322909400002
PM 23868926
ER
PT J
AU Gbadegesin, RA
Brophy, PD
Adeyemo, A
Hall, G
Gupta, IR
Hains, D
Bartkowiak, B
Rabinovich, CE
Chandrasekharappa, S
Homstad, A
Westreich, K
Wu, GH
Liu, YT
Holanda, D
Clarke, J
Lavin, P
Selim, A
Miller, S
Wiener, JS
Ross, SS
Foreman, J
Rotimi, C
Winn, MP
AF Gbadegesin, Rasheed A.
Brophy, Patrick D.
Adeyemo, Adebowale
Hall, Gentzon
Gupta, Indra R.
Hains, David
Bartkowiak, Bartlomeij
Rabinovich, C. Egla
Chandrasekharappa, Settara
Homstad, Alison
Westreich, Katherine
Wu, Guanghong
Liu, Yutao
Holanda, Danniele
Clarke, Jason
Lavin, Peter
Selim, Angelica
Miller, Sara
Wiener, John S.
Ross, Sherry S.
Foreman, John
Rotimi, Charles
Winn, Michelle P.
TI TNXB Mutations Can Cause Vesicoureteral Reflux
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID EHLERS-DANLOS-SYNDROME; FOCAL ADHESION KINASE; TENASCIN-X DEFICIENCY;
URINARY-TRACT; VITAMIN-A; HYPERMOBILITY TYPE; MOUSE MODELS; UNDERSTAND;
EXPRESSION; PREDICTION
AB Primary vesicoureteral reflux (VUR) is the most common congenital anomaly of the kidney and the urinary tract, and it is a major risk factor for pyelonephritic scarring and CKD in children. Although twin studies support the heritability of VUR, specific genetic causes remain elusive. We performed a sequential genome-wide linkage study and whole-exome sequencing in a family with hereditary VUR. We obtained a significant multipoint parametric logarithm of odds score of 3.3 on chromosome 6p, and whole-exome sequencing identified a deleterious heterozygous mutation (T3257I) in the gene encoding tenascin XB (TNXB in 6p21.3). This mutation segregated with disease in the affected family as well as with a pathogenic G1331R change in another family. Fibroblast cell lines carrying the T3257I mutation exhibited a reduction in both cell motility and phosphorylated focal adhesion kinase expression, suggesting a defect in the focal adhesions that link the cell cytoplasm to the extracellular matrix. Immunohistochemical studies revealed that the human uroepithelial lining of the ureterovesical junction expresses TNXB, suggesting that TNXB may be important for generating tensile forces that close the ureterovesical junction during voiding. Taken together, these results suggest that mutations in TNXB can cause hereditary VUR.
C1 [Gbadegesin, Rasheed A.; Bartkowiak, Bartlomeij; Homstad, Alison; Westreich, Katherine; Foreman, John] Duke Univ, Med Ctr, Dept Pediat, Div Nephrol, Durham, NC 27710 USA.
[Rabinovich, C. Egla] Duke Univ, Med Ctr, Dept Pediat, Div Rheumatol, Durham, NC 27710 USA.
[Gbadegesin, Rasheed A.; Hall, Gentzon; Homstad, Alison; Wu, Guanghong; Liu, Yutao; Lavin, Peter; Winn, Michelle P.] Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC 27710 USA.
[Brophy, Patrick D.] Univ Iowa, Dept Pediat, Carver Coll Med, Iowa City, IA 52242 USA.
[Adeyemo, Adebowale; Chandrasekharappa, Settara; Rotimi, Charles] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
[Hall, Gentzon; Wu, Guanghong; Liu, Yutao; Lavin, Peter; Winn, Michelle P.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Selim, Angelica; Miller, Sara] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
[Gupta, Indra R.] McGill Univ, Dept Pediat & Human Genet, Montreal, PQ, Canada.
[Hains, David] Nationwide Childrens Hosp, Res Inst, Dept Pediat, Columbus, OH USA.
[Holanda, Danniele] Univ Iowa, Coll Med, Dept Pathol, Iowa City, IA 52242 USA.
[Lavin, Peter] Trinity Coll Dublin, Tallaght Hosp, Trinity Hlth Kidney Ctr, Dublin, Ireland.
[Wiener, John S.; Ross, Sherry S.] Duke Univ, Med Ctr, Dept Surg & Pediat, Div Urol Surg, Durham, NC 27710 USA.
RP Gbadegesin, RA (reprint author), Duke Univ, Med Ctr, Dept Pediat, Div Nephrol, Box 3352, Durham, NC 27710 USA.
EM rasheed.gbadegesin@duke.edu
OI Hains, David/0000-0001-6511-9561; Adeyemo, Adebowale/0000-0002-3105-3231
FU National Institutes of Health (NIH) National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK) [K08DK082495-03]; American
Recovery and Reinvestment Act (ARRA) [RC4DK090937]; Nephcure foundation;
Doris Duke Clinical Scientist Development Award; Bayden Collins
Pediatric Kidney Disease Research Fund; Duke University Medical Center;
Duke University School of Medicine core voucher program; University of
Iowa Pediatric Renal Biobank and sequencing core; Intramural Research
Program of the Center for Research on Genomics and Global Health
(CRGGH); Office of the Director; NIDDK; National Human Genome Research
Institute [Z01HG200362]; ARRA [1RC2NS070342-01]; Bryan Alzheimer's
Disease Research Centers of the National Institute on Aging
[P30AG028377]; National Institutes of Mental Health [RC2MH089915];
National Institute of Allergy and Infectious Diseases (NIAID)
[1R56AI098588-01A1]; Division of Intramural Research of the NIAID
FX This study was supported by grants from the National Institutes of
Health (NIH) National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) (K08DK082495-03 to R. G.) and the American Recovery and
Reinvestment Act (ARRA) (RC4DK090937 to P. D. B. and D.H.) and grants
from Nephcure foundation (to R. G.). R. G. is the recipient of a Doris
Duke Clinical Scientist Development Award. This work was also supported
by grants from the Bayden Collins Pediatric Kidney Disease Research
Fund, Duke University Medical Center, Duke University School of Medicine
core voucher program, and the University of Iowa Pediatric Renal Biobank
and sequencing core. In addition, this study was supported in part by
the Intramural Research Program of the Center for Research on Genomics
and Global Health (CRGGH). The CRGGH is supported by funds from the
Office of the Director, the NIDDK, and the National Human Genome
Research Institute (Z01HG200362). The sequenced controls used for this
study were funded in part by the ARRA (1RC2NS070342-01), the Bryan
Alzheimer's Disease Research Centers of the National Institute on Aging
(P30AG028377), the National Institutes of Mental Health (RC2MH089915),
and the National Institute of Allergy and Infectious Diseases (NIAID)
(1R56AI098588-01A1). This research was supported in part by funding from
the Division of Intramural Research of the NIAID.
NR 45
TC 13
Z9 14
U1 0
U2 6
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD JUL 31
PY 2013
VL 24
IS 8
BP 1313
EP 1322
DI 10.1681/ASN.2012121148
PG 10
WC Urology & Nephrology
SC Urology & Nephrology
GA 198GD
UT WOS:000322909400019
PM 23620400
ER
PT J
AU Rhee, EP
Clish, CB
Ghorbani, A
Larson, MG
Elmariah, S
McCabe, E
Yang, Q
Cheng, S
Pierce, K
Deik, A
Souza, AL
Farrell, L
Domos, C
Yeh, RW
Palacios, I
Rosenfield, K
Vasan, RS
Florez, JC
Wang, TJ
Fox, CS
Gerszten, RE
AF Rhee, Eugene P.
Clish, Clary B.
Ghorbani, Anahita
Larson, Martin G.
Elmariah, Sammy
McCabe, Elizabeth
Yang, Qiong
Cheng, Susan
Pierce, Kerry
Deik, Amy
Souza, Amanda L.
Farrell, Laurie
Domos, Carly
Yeh, Robert W.
Palacios, Igor
Rosenfield, Kenneth
Vasan, Ramachandran S.
Florez, Jose C.
Wang, Thomas J.
Fox, Caroline S.
Gerszten, Robert E.
TI A Combined Epidemiologic and Metabolomic Approach Improves CKD
Prediction
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID GLOMERULAR-FILTRATION-RATE; SERUM CREATININE; GENERAL-POPULATION;
ARGININE SYNTHESIS; RENAL METABOLISM; KYNURENIC ACID; AMINO-ACIDS; RAT
NEPHRON; DISEASE; PHOSPHATIDYLCHOLINE
AB Metabolomic approaches have begun to catalog the metabolic disturbances that accompany CKD, but whether metabolite alterations can predict future CKD is unknown. We performed liquid chromatography/mass spectrometry-based metabolite profiling on plasma from 1434 participants in the Framingham Heart Study (FHS) who did not have CKD at baseline. During the following 8 years, 123 individuals developed CKD, defined by an estimated GFR of <60 ml/min per 1.73 m(2). Numerous metabolites were associated with incident CKD, including 16 that achieved the Bonferroni-adjusted significance threshold of P0.00023. To explore how the human kidney modulates these metabolites, we profiled arterial and renal venous plasma from nine individuals. Nine metabolites that predicted CKD in the FHS cohort decreased more than creatinine across the renal circulation, suggesting that they may reflect non-GFR-dependent functions, such as renal metabolism and secretion. Urine isotope dilution studies identified citrulline and choline as markers of renal metabolism and kynurenic acid as a marker of renal secretion. In turn, these analytes remained associated with incident CKD in the FHS cohort, even after adjustment for eGFR, age, sex, diabetes, hypertension, and proteinuria at baseline. Addition of a multimarker metabolite panel to clinical variables significantly increased the c-statistic (0.77-0.83, P<0.0001); net reclassification improvement was 0.78 (95% confidence interval, 0.60 to 0.95; P<0.0001). Thus, the addition of metabolite profiling to clinical data may significantly improve the ability to predict whether an individual will develop CKD by identifying predictors of renal risk that are independent of estimated GFR.
C1 [Rhee, Eugene P.] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA 02129 USA.
[Ghorbani, Anahita; Elmariah, Sammy; Cheng, Susan; Farrell, Laurie; Domos, Carly; Yeh, Robert W.; Palacios, Igor; Rosenfield, Kenneth; Gerszten, Robert E.] Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA 02129 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Charlestown, MA 02129 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Charlestown, MA 02129 USA.
[Gerszten, Robert E.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA.
[Rhee, Eugene P.; Clish, Clary B.; Pierce, Kerry; Deik, Amy; Souza, Amanda L.; Gerszten, Robert E.] Broad Inst, Cambridge, MA USA.
[Ghorbani, Anahita; Larson, Martin G.; Cheng, Susan; Vasan, Ramachandran S.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Ghorbani, Anahita; Larson, Martin G.; Cheng, Susan; Vasan, Ramachandran S.; Fox, Caroline S.] Boston Univ, Sch Med, Framingham, MA USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[McCabe, Elizabeth; Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Cheng, Susan] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Boston Med Ctr, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Boston Med Ctr, Cardiol Sect, Boston, MA 02118 USA.
[Wang, Thomas J.] Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, Nashville, TN USA.
[Wang, Thomas J.] Vanderbilt Heart & Vasc Inst, Nashville, TN USA.
[Fox, Caroline S.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
RP Rhee, EP (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, 149 13th St,8th Floor,8401, Charlestown, MA 02129 USA.
EM eprhee@partners.org; rgerszten@partners.org
RI Yang, Qiong/G-5438-2014;
OI Larson, Martin/0000-0002-9631-1254; Ramachandran,
Vasan/0000-0001-7357-5970
FU National Institutes of Health (NIH) [N01-HC-25195, R01-DK-HL081572];
Leducq Foundation; American Heart Association; NIH [K08-DK-090142]
FX This work was supported by National Institutes of Health (NIH) contract
N01-HC-25195 to the Framingham Heart Study, R01-DK-HL081572 (R. E. G.
and T.J.W.), the Leducq Foundation (R. E. G.), and an Established
Investigator Award from the American Heart Association (R. E. G.). E. P.
R. received support from NIH award K08-DK-090142.
NR 35
TC 47
Z9 47
U1 5
U2 20
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD JUL 31
PY 2013
VL 24
IS 8
BP 1330
EP 1338
DI 10.1681/ASN.2012101006
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 198GD
UT WOS:000322909400021
PM 23687356
ER
PT J
AU Murima, P
de Sessions, PF
Lim, V
Naim, ANM
Bifani, P
Boshoff, HIM
Sambandamurthy, VK
Dick, T
Hibberd, ML
Schreiber, M
Rao, SPS
AF Murima, Paul
de Sessions, Paola Florez
Lim, Vivian
Naim, Ahmad Nazri Mohamed
Bifani, Pablo
Boshoff, Helena I. M.
Sambandamurthy, Vasan K.
Dick, Thomas
Hibberd, Martin L.
Schreiber, Mark
Rao, Srinivasa P. S.
TI Exploring the Mode of Action of Bioactive Compounds by Microfluidic
Transcriptional Profiling in Mycobacteria
SO PLOS ONE
LA English
DT Article
ID DRUG DISCOVERY; TUBERCULOSIS; SCREEN; ARRAY; MICROARRAYS; MECHANISMS;
PREDICTION; INHIBITORS; BIOLOGY; AGENTS
AB Most candidate anti-bacterials are identified on the basis of their whole cell anti-bacterial activity. A critical bottleneck in the early discovery of novel anti-bacterials is tracking the structure activity relationship (SAR) of the novel compounds synthesized during the hit to lead and lead optimization stage. It is often very difficult for medicinal chemists to visualize if the novel compounds synthesized for understanding SAR of a particular scaffold have similar molecular mechanism of action (MoA) as that of the initial hit. The elucidation of the molecular MoA of bioactive inhibitors is critical. Here, a new strategy and routine assay for MoA de-convolution, using a microfluidic platform for transcriptional profiling of bacterial response to inhibitors with whole cell activity has been presented. First a reference transcriptome compendium of Mycobacterial response to various clinical and investigational drugs was built. Using feature reduction, it was demonstrated that subsets of biomarker genes representative of the whole genome are sufficient for MoA classification and deconvolution in a medium-throughput microfluidic format ultimately leading to a cost effective and rapid tool for routine antibacterial drug-discovery programs.
C1 [Murima, Paul; Lim, Vivian; Bifani, Pablo; Sambandamurthy, Vasan K.; Dick, Thomas; Schreiber, Mark; Rao, Srinivasa P. S.] Novartis Inst Trop Dis, Singapore, Singapore.
[de Sessions, Paola Florez; Naim, Ahmad Nazri Mohamed; Hibberd, Martin L.] ASTAR, Genome Inst Singapore, Singapore, Singapore.
[Boshoff, Helena I. M.] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Dick, Thomas] Natl Univ Singapore, Dept Microbiol, Singapore 117548, Singapore.
[Schreiber, Mark] Novartis Inst Biomed Res, Cambridge, MA USA.
RP Schreiber, M (reprint author), Novartis Inst Trop Dis, Singapore, Singapore.
EM mark.schrieber@novartis.com; srinivasa.rao@novartis.com
OI Hibberd, Martin/0000-0001-8587-1849
FU Novartis Institute for Tropical Diseases (NITD); Genome Institute of
Singapore (GIS); Intramural Research Program of NIAID, National
Institutes of Health
FX This work was funded, in part, by Novartis Institute for Tropical
Diseases (NITD), Genome Institute of Singapore (GIS) and the Intramural
Research Program of NIAID, National Institutes of Health. No additional
external funding received for this study. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 33
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Z9 7
U1 1
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 31
PY 2013
VL 8
IS 7
AR e69191
DI 10.1371/journal.pone.0069191
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 194LB
UT WOS:000322633700019
PM 23935951
ER
PT J
AU Thomassen, HA
Fuller, T
Asefi-Najafabady, S
Shiplacoff, JAG
Mulembakani, PM
Blumberg, S
Johnston, SC
Kisalu, NK
Kinkela, TL
Fair, JN
Wolfe, ND
Shongo, RL
LeBreton, M
Meyer, H
Wright, LL
Muyembe, JJ
Buermann, W
Okitolonda, E
Hensley, LE
Lloyd-Smith, JO
Smith, TB
Rimoin, AW
AF Thomassen, Henri A.
Fuller, Trevon
Asefi-Najafabady, Salvi
Shiplacoff, Julia A. G.
Mulembakani, Prime M.
Blumberg, Seth
Johnston, Sara C.
Kisalu, Neville K.
Kinkela, Timothee L.
Fair, Joseph N.
Wolfe, Nathan D.
Shongo, Robert L.
LeBreton, Matthew
Meyer, Hermann
Wright, Linda L.
Muyembe, Jean-Jacques
Buermann, Wolfgang
Okitolonda, Emile
Hensley, Lisa E.
Lloyd-Smith, James O.
Smith, Thomas B.
Rimoin, Anne W.
TI Pathogen-Host Associations and Predicted Range Shifts of Human Monkeypox
in Response to Climate Change in Central Africa
SO PLOS ONE
LA English
DT Article
ID SPECIES DISTRIBUTION MODELS; INFECTIOUS-DISEASES; ECOLOGICAL NICHE;
UNITED-STATES; PUBLIC-HEALTH; RISK-FACTORS; SAMPLE-SIZE; MODIS DATA;
VIRUS; DISTRIBUTIONS
AB Climate change is predicted to result in changes in the geographic ranges and local prevalence of infectious diseases, either through direct effects on the pathogen, or indirectly through range shifts in vector and reservoir species. To better understand the occurrence of monkeypox virus (MPXV), an emerging Orthopoxvirus in humans, under contemporary and future climate conditions, we used ecological niche modeling techniques in conjunction with climate and remote-sensing variables. We first created spatially explicit probability distributions of its candidate reservoir species in Africa's Congo Basin. Reservoir species distributions were subsequently used to model current and projected future distributions of human monkeypox (MPX). Results indicate that forest clearing and climate are significant driving factors of the transmission of MPX from wildlife to humans under current climate conditions. Models under contemporary climate conditions performed well, as indicated by high values for the area under the receiver operator curve (AUC), and tests on spatially randomly and non-randomly omitted test data. Future projections were made on IPCC 4th Assessment climate change scenarios for 2050 and 2080, ranging from more conservative to more aggressive, and representing the potential variation within which range shifts can be expected to occur. Future projections showed range shifts into regions where MPX has not been recorded previously. Increased suitability for MPX was predicted in eastern Democratic Republic of Congo. Models developed here are useful for identifying areas where environmental conditions may become more suitable for human MPX; targeting candidate reservoir species for future screening efforts; and prioritizing regions for future MPX surveillance efforts.
C1 [Thomassen, Henri A.; Fuller, Trevon; Shiplacoff, Julia A. G.; Buermann, Wolfgang; Smith, Thomas B.] Univ Calif Los Angeles, Ctr Trop Res, Los Angeles, CA USA.
[Thomassen, Henri A.] Univ Tubingen, Dept Comparat Zool, Tubingen, Germany.
[Asefi-Najafabady, Salvi] Arizona State Univ, Sch Life Sci, Tempe, AZ USA.
[Asefi-Najafabady, Salvi] Univ Calif Los Angeles, Inst Environm & Sustainabil, Los Angeles, CA USA.
[Mulembakani, Prime M.; Kinkela, Timothee L.; Okitolonda, Emile] Kinshasa Sch Publ Hlth, Kinshasa, Zaire.
[Blumberg, Seth; Lloyd-Smith, James O.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Blumberg, Seth; Lloyd-Smith, James O.; Smith, Thomas B.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA USA.
[Johnston, Sara C.] US Army Med Res Inst Infect Dis, Frederick, MD USA.
[Kisalu, Neville K.; Rimoin, Anne W.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90024 USA.
[Fair, Joseph N.; Wolfe, Nathan D.; LeBreton, Matthew] Global Viral Forecasting, San Francisco, CA USA.
[Wolfe, Nathan D.] Stanford Univ, Program Human Biol, Stanford, CA 94305 USA.
[Shongo, Robert L.] Minist Hlth, Kinshasa, Zaire.
[Meyer, Hermann] Bundeswehr Inst Microbiol, Munich, Germany.
[Wright, Linda L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Muyembe, Jean-Jacques] Natl Inst Biomed Res, Kinshasa, Zaire.
[Buermann, Wolfgang] Univ Calif Los Angeles, Dept Atmospher & Ocean Sci, Los Angeles, CA USA.
[Hensley, Lisa E.] Med Countermeasures Initiat, Silver Spring, MD USA.
[Rimoin, Anne W.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA.
RP Rimoin, AW (reprint author), Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90024 USA.
EM arimoin@ucla.edu
RI Lloyd-Smith, James/K-4080-2012
OI Lloyd-Smith, James/0000-0001-7941-502X
FU Faucett Family Foundation; National Institutes of Health, the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, Bethesda, Maryland, United States of America; National
Science Foundation-National Institutes of Health Ecology of Infectious
Diseases Program [EF-0430146]; RAPIDD program of the Science &
Technology Directorate, Department of Homeland Security; Fogarty
International Center, National Institutes of Health; National Institute
of Allergy and Infectious Diseases [EID-1R01AI074059-01]; NIH
[DP1-OD00370]; Google.org; Skoll Foundation; Henry M. Jackson Foundation
for the Advancement of Military Medicine; US Armed Forces Health
Surveillance Center Division of GEIS Operations; United States Agency
for International Development (USAID) Emerging Pandemic Threats Program;
PREDICT project [GHN-A-OO-09-00010-00]; Department of Homeland
Security/National Biodefense Analysis and Countermeasures Center
[HSQDC-05-X-000-35/P400006]
FX This work was made possible by the support of the Faucett Family
Foundation. The authors thank the DRC Ministry of Health and local
health workers who were responsible for specimen collection and case
investigation. Additional support for this study was provided by the
National Institutes of Health, the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, Bethesda, Maryland,
United States of America, by the joint National Science
Foundation-National Institutes of Health Ecology of Infectious Diseases
Program (grant number EF-0430146), and the RAPIDD program of the Science
& Technology Directorate, Department of Homeland Security, by the
Fogarty International Center, National Institutes of Health, and by the
National Institute of Allergy and Infectious Diseases (grant number
EID-1R01AI074059-01). NDW is supported by the NIH Director's Pioneer
Award (DP1-OD00370). Global Viral Forecasting is supported by
Google.org, the Skoll Foundation, the Henry M. Jackson Foundation for
the Advancement of Military Medicine, the US Armed Forces Health
Surveillance Center Division of GEIS Operations, and the United States
Agency for International Development (USAID) Emerging Pandemic Threats
Program, PREDICT project, under the terms of Cooperative Agreement
Number GHN-A-OO-09-00010-00. This study is made possible by the generous
support of the American people through the United States Agency for
International Development (USAID). The contents are the responsibility
of the authors and do not necessarily reflect the views of USAID or the
United States Government. Further support came from the Department of
Homeland Security/National Biodefense Analysis and Countermeasures
Center Project #HSQDC-05-X-000-35/P400006 (RSCB-09-00343). Opinions,
interpretations, conclusions, and recommendations are those of the
authors and are not necessarily endorsed by the U.S. Army. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 90
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U1 2
U2 32
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 31
PY 2013
VL 8
IS 7
AR e66071
DI 10.1371/journal.pone.0066071
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 194LB
UT WOS:000322633700002
PM 23935820
ER
PT J
AU Valcour, VG
Ananworanich, J
Agsalda, M
Sailasuta, N
Chalermchai, T
Schuetz, A
Shikuma, C
Liang, CY
Jirajariyavej, S
Sithinamsuwan, P
Tipsuk, S
Clifford, DB
Paul, R
Fletcher, JLK
Marovich, MA
Slike, BM
DeGruttola, V
Shiramizu, B
AF Valcour, Victor G.
Ananworanich, Jintanat
Agsalda, Melissa
Sailasuta, Napapon
Chalermchai, Thep
Schuetz, Alexandra
Shikuma, Cecilia
Liang, Chin-Yuan
Jirajariyavej, Supunee
Sithinamsuwan, Pasiri
Tipsuk, Somporn
Clifford, David B.
Paul, Robert
Fletcher, James L. K.
Marovich, Mary A.
Slike, Bonnie M.
DeGruttola, Victor
Shiramizu, Bruce
CA SEARCH 011 Protocol Team
TI HIV DNA Reservoir Increases Risk for Cognitive Disorders in cART-Naive
Patients
SO PLOS ONE
LA English
DT Article
ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS;
NEUROCOGNITIVE DISORDERS; CIRCULATING MONOCYTES; DISEASE PROGRESSION;
DEMENTIA; INFECTION; AIDS; SPECTROSCOPY; PERSISTENCE
AB Objectives: Cognitive impairment remains frequent in HIV, despite combination antiretroviral therapy (cART). Leading theories implicate peripheral monocyte HIV DNA reservoirs as a mechanism for spread of the virus to the brain. These reservoirs remain present despite cART. The objective of this study was to determine if the level of HIV DNA in CD14(+) enriched monocytes predicted cognitive impairment and brain injury.
Methods: We enrolled 61 cART-naive HIV-infected Thais in a prospective study and measured HIV DNA in CD14+ enriched monocyte samples in a blinded fashion. We determined HAND diagnoses by consensus panel and all participants underwent magnetic resonance spectroscopy (MRS) to measure markers of brain injury. Immune activation was measured via cytokines in cerebrospinal fluid (CSF).
Results: The mean (SD) age was 35 (6.9) years, CD4 T-lymphocyte count was 236 (139) and log(10) plasma HIV RNA was 4.8 (0.73). Twenty-eight of 61 met HAND criteria. The log(10) CD14(+) HIV DNA was associated with HAND in unadjusted and adjusted models (p=0.001). There was a 14.5 increased odds ratio for HAND per 1 log-value of HIV DNA (10-fold increase in copy number). Plasma CD14(+) HIV DNA was associated with plasma and CSF neopterin (p = 0.023) and with MRS markers of neuronal injury (lower N-acetyl aspartate) and glial dysfunction (higher myoinositol) in multiple brain regions.
Interpretation: Reservoir burden of HIV DNA in monocyte-enriched (CD14(+)) peripheral blood cells increases risk for HAND in treatment-naive HIV+ subjects and is directly associated with CSF immune activation and both brain injury and glial dysfunction by MRS.
C1 [Valcour, Victor G.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA.
[Valcour, Victor G.] Univ Calif San Francisco, Dept Med, Div Geriatr Med, San Francisco, CA USA.
[Ananworanich, Jintanat; Chalermchai, Thep; Tipsuk, Somporn; Fletcher, James L. K.] Thai Red Cross AIDS Res Ctr, SEARCH, Bangkok, Thailand.
[Ananworanich, Jintanat] Thai Red Cross AIDS Res Ctr, HIV NAT, Bangkok, Thailand.
[Ananworanich, Jintanat] Chulalongkorn Univ, Fac Med, Bangkok 10330, Thailand.
[Ananworanich, Jintanat; Agsalda, Melissa; Shikuma, Cecilia; Liang, Chin-Yuan; Shiramizu, Bruce] Univ Hawaii, Hawaii Ctr AIDS, Honolulu, HI 96822 USA.
[Sailasuta, Napapon] Huntington Med Res Inst, Pasadena, CA USA.
[Schuetz, Alexandra] Armed Forces Res Inst Med Sci, Dept Retrovirol, Bangkok 10400, Thailand.
[Jirajariyavej, Supunee] Taksin Hosp, Bangkok, Thailand.
[Sithinamsuwan, Pasiri] Phramongkutklao Hosp, Dept Med, Div Neurol, Bangkok, Thailand.
[Clifford, David B.] Washington Univ, Dept Neurol, St Louis, MO USA.
[Paul, Robert] Univ Missouri, Dept Psychol, St Louis, MO 63121 USA.
[Marovich, Mary A.] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
[Marovich, Mary A.; Slike, Bonnie M.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Slike, Bonnie M.] Queen Savang Vadhana Mem Hosp, Si Racha, Thailand.
[DeGruttola, Victor] Thai Red Cross AIDS Res Ctr, Bangkok, Thailand.
RP Valcour, VG (reprint author), Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA.
EM vvalcour@memory.ucsf.edu
FU NINDS/NIH [R01-NS053359, R01-NS061696, R01-NS053345]; NIMH/NIH
[R21-MH072388]; NIMHD/NIH [MD007584]; National Center for Advancing
Translational Sciences, National Institutes of Health (NIH), through
UCSF-CTSI [UL1 TR000004]; Henry M. Jackson Foundation for the
Advancement of Military Medicine, Inc [W81XWH-11-2-0174]; U.S.
Department of Defense [W81XWH-11-2-0174]
FX This work was supported by R01-NS053359 (NINDS/NIH - SRK), R01-NS061696
(NINDS/NIH - VV), R21-MH072388 (NIMH/NIH - VV), R01-NS053345 (NINDS/NIH
- BS), and MD007584 (NIMHD/NIH - BS, CS). Added statistical assistance
was supported by the National Center for Advancing Translational
Sciences, National Institutes of Health (NIH), through UCSF-CTSI Grant
Number UL1 TR000004. Its contents are solely the responsibility of the
authors and do not necessarily represent the official views of the NIH.
This work was supported in part by a cooperative agreement
(W81XWH-11-2-0174) between the Henry M. Jackson Foundation for the
Advancement of Military Medicine, Inc, and the U.S. Department of
Defense. The views expressed are those of the authors and should not be
construed to represent the positions of the US Army 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 29
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U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 31
PY 2013
VL 8
IS 7
AR e70164
DI 10.1371/journal.pone.0070164
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 194LB
UT WOS:000322633700058
PM 23936155
ER
PT J
AU Byrd, RA
Weissman, AM
AF Byrd, R. Andrew
Weissman, Allan M.
TI Compact Parkin only: insights into the structure of an autoinhibited
ubiquitin ligase
SO EMBO JOURNAL
LA English
DT Editorial Material
ID MECHANISMS; DOMAIN; HHARI; E3
AB Mutations in Parkin represent similar to 50% of disease-causing defects in autosomal recessive-juvenile onset Parkinson's disease (AR-JP). Recently, there have been four structural reports of autoinhibited forms of this RING-IBR-RING (RBR) ubiquitin ligase (E3) by the Gehring, Komander, Johnston and Shaw groups. The important advances from these studies set the stage for the next steps in understanding the molecular basis for Parkinson's disease (PD).
C1 [Byrd, R. Andrew] Natl Canc Inst, Ctr Canc Res, Struct Biophys Lab, Frederick, MD USA.
[Weissman, Allan M.] Natl Canc Inst, Ctr Canc Res, Lab Prot Dynam & Signaling, Frederick, MD USA.
RP Byrd, RA (reprint author), Natl Canc Inst, Ctr Canc Res, Struct Biophys Lab, Frederick, MD USA.
EM byrdra@mail.nih.gov; weissmaa@mail.nih.gov
RI Byrd, R. Andrew/F-8042-2015
OI Byrd, R. Andrew/0000-0003-3625-4232
NR 16
TC 11
Z9 12
U1 0
U2 11
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0261-4189
J9 EMBO J
JI Embo J.
PD JUL 31
PY 2013
VL 32
IS 15
BP 2087
EP 2089
DI 10.1038/emboj.2013.158
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 192WI
UT WOS:000322517900001
PM 23852447
ER
PT J
AU Timmes, AG
Moore, RA
Fischer, ER
Priola, SA
AF Timmes, Andrew G.
Moore, Roger A.
Fischer, Elizabeth R.
Priola, Suzette A.
TI Recombinant Prion Protein Refolded with Lipid and RNA Has the
Biochemical Hallmarks of a Prion but Lacks In Vivo Infectivity
SO PLOS ONE
LA English
DT Article
ID CREUTZFELDT-JAKOB-DISEASE; SCRAPIE INFECTION; METHIONINE OXIDATION;
MAMMALIAN PRIONS; MASS-SPECTROMETRY; VITRO GENERATION; TRANSGENIC MICE;
WILD-TYPE; RESISTANT; CONVERSION
AB During prion infection, the normal, protease-sensitive conformation of prion protein (PrPC) is converted via seeded polymerization to an abnormal, infectious conformation with greatly increased protease-resistance (PrPSc). In vitro, protein misfolding cyclic amplification (PMCA) uses PrPSc in prion-infected brain homogenates as an initiating seed to convert PrPC and trigger the self-propagation of PrPSc over many cycles of amplification. While PMCA reactions produce high levels of protease-resistant PrP, the infectious titer is often lower than that of brain-derived PrPSc. More recently, PMCA techniques using bacterially derived recombinant PrP (rPrP) in the presence of lipid and RNA but in the absence of any starting PrPSc seed have been used to generate infectious prions that cause disease in wild-type mice with relatively short incubation times. These data suggest that lipid and/or RNA act as cofactors to facilitate the de novo formation of high levels of prion infectivity. Using rPrP purified by two different techniques, we generated a self-propagating protease-resistant rPrP molecule that, regardless of the amount of RNA and lipid used, had a molecular mass, protease resistance and insolubility similar to that of PrPSc. However, we were unable to detect prion infectivity in any of our reactions using either cell-culture or animal bioassays. These results demonstrate that the ability to self-propagate into a protease-resistant insoluble conformer is not unique to infectious PrP molecules. They suggest that the presence of RNA and lipid cofactors may facilitate the spontaneous refolding of PrP into an infectious form while also allowing the de novo formation of self-propagating, but non-infectious, rPrP-res.
C1 [Timmes, Andrew G.; Moore, Roger A.; Priola, Suzette A.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Fischer, Elizabeth R.] NIAID, Electron Microscopy Unit, Res Technol Branch, Rocky Mt Labs,NIH, Hamilton, MT USA.
RP Priola, SA (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
EM spriola@niaid.nih.gov
FU National Institute of Allergy and Infectious Disease, National
Institutes of Health [AI000752-17]
FX This research was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Disease, National
Institutes of Health (AI000752-17). The funders had no role in study
design, data collection and analysis, or preparation of the manuscript.
Prior to submission, approval had to be obtained to publish from NIH.
NR 68
TC 15
Z9 15
U1 0
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 30
PY 2013
VL 8
IS 7
AR e71081
DI 10.1371/journal.pone.0071081
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 201AX
UT WOS:000323114200110
PM 23936256
ER
PT J
AU Mahony, C
Erskine, L
Niven, J
Greig, NH
Figg, WD
Vargesson, N
AF Mahony, Chris
Erskine, Lynda
Niven, Jennifer
Greig, Nigel H.
Figg, William Douglas
Vargesson, Neil
TI Pomalidomide is nonteratogenic in chicken and zebrafish embryos and
nonneurotoxic in vitro
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cytoskeleton; Cox2; CPS49; drug screening
ID REFRACTORY MULTIPLE-MYELOMA; PERIPHERAL NEUROPATHY; THALIDOMIDE
EMBRYOPATHY; TRANSGENIC ZEBRAFISH; LENALIDOMIDE; ANALOGS; ALPHA;
CYCLOOXYGENASE-2; TERATOGENICITY; ANGIOGENESIS
AB Thalidomide and its analog, Lenalidomide, are in current use clinically for treatment of multiple myeloma, complications of leprosy and cancers. An additional analog, Pomalidomide, has recently been licensed for treatment of multiple myeloma, and is purported to be clinically more potent than either Thalidomide or Lenalidomide. Using a combination of zebrafish and chicken embryos together with in vitro assays we have determined the relative anti-inflammatory activity of each compound. We demonstrate that in vivo embryonic assays Pomalidomide is a significantly more potent anti-inflammatory agent than either Thalidomide or Lenalidomide. We tested the effect of Pomalidomide and Lenalidomide on angiogenesis, teratogenesis, and neurite outgrowth, known detrimental effects of Thalidomide. We found that Pomalidomide, displays a high degree of cell specificity, and has no detectable teratogenic, antiangiogenic or neurotoxic effects at potent anti-inflammatory concentrations. This is in marked contrast to Thalidomide and Lenalidomide, which had detrimental effects on blood vessels, nerves, and embryonic development at anti-inflammatory concentrations. This work has implications for Pomalidomide as a treatment for conditions Thalidomide and Lenalidomide treat currently.
C1 [Mahony, Chris; Erskine, Lynda; Vargesson, Neil] Univ Aberdeen, Inst Med Sci, Sch Med Sci, Aberdeen AB25 2ZD, Scotland.
[Niven, Jennifer] Univ Aberdeen, Inst Med Sci, Sch Med, Aberdeen AB25 2ZD, Scotland.
[Greig, Nigel H.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Figg, William Douglas] NCI, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Vargesson, N (reprint author), Univ Aberdeen, Inst Med Sci, Sch Med Sci, Aberdeen AB25 2ZD, Scotland.
EM n.vargesson@abdn.ac.uk
RI Figg Sr, William/M-2411-2016;
OI Erskine, Lynda/0000-0001-6538-9406; Vargesson, Neil/0000-0001-8027-114X
FU Kosterlitz Centre of Therapeutics; Cell, Developmental Biology, and
Cancer Theme of the University of Aberdeen; University of Aberdeen PhD
studentship
FX We thank past and current members of the N. V. laboratory for
discussions on this project; Dr. J. Martin Collinson for statistics
advice and comments on the manuscript; Dr. Isobel Crane for RAW cells;
Prof. Ruth Ross and Dr. Cindy Chau for helpful discussions and feedback
on this project; Dr. Stephen Renshaw (University of Sheffield) for the
kind gift of Tg(MPO::EGFP)114 fish. Fli1-EGFP fish were
obtained from the Zebrafish International Resources Center. C. M. was
funded by a University of Aberdeen PhD studentship. This work was funded
in part by small grants from the Kosterlitz Centre of Therapeutics; and
the Cell, Developmental Biology, and Cancer Theme of the University of
Aberdeen (to N.V.).
NR 40
TC 20
Z9 21
U1 0
U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 30
PY 2013
VL 110
IS 31
BP 12703
EP 12708
DI 10.1073/pnas.1307684110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 191VH
UT WOS:000322441500052
PM 23858438
ER
PT J
AU Ma, WJ
Westmoreland, JW
Resnick, MA
AF Ma, Wenjian
Westmoreland, James W.
Resnick, Michael A.
TI Homologous recombination rescues ssDNA gaps generated by nucleotide
excision repair and reduced translesion DNA synthesis in yeast G2 cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID DOUBLE-STRAND BREAKS; MAMMALIAN-CELLS; SACCHAROMYCES-CEREVISIAE; DAMAGE
RECOGNITION; PYRIMIDINE DIMERS; ESCHERICHIA-COLI; REPLICATION FORK; S1
NUCLEASE; GENE; NER
AB Repair of DNA bulky lesions often involves multiple repair pathways such as nucleotide-excision repair, translesion DNA synthesis (TLS), and homologous recombination (HR). Although there is considerable information about individual pathways, little is known about the complex interactions or extent to which damage in single strands, such as the damage generated by UV, can result in double-strand breaks (DSBs) and/or generate HR. We investigated the consequences of UV-induced lesions in nonreplicating G2 cells of budding yeast. In contrast to WT cells, there was a dramatic increase in ssDNA gaps for cells deficient in the TLS polymerases eta (Rad30) and zeta (Rev3). Surprisingly, repair in TLS-deficient G2 cells required HR repair genes RAD51 and RAD52, directly revealing a redundancy of TLS and HR functions in repair of ssDNAs. Using a physical assay that detects recombination between circular sister chromatids within a few hours after UV, we show an approximate three-fold increase in recombinants in the TLS mutants over that in WT cells. The recombination, which required RAD51 and RAD52, does not appear to be caused by DSBs, because a dose of ionizing radiation producing 20 times more DSBs was much less efficient than UV in producing recombinants. Thus, in addition to revealing TLS and HR functional redundancy, we establish that UV-induced recombination in TLS mutants is not attributable to DSBs. These findings suggest that ssDNA that might originate during the repair of closely opposed lesions or of ssDNA-containing lesions or from uncoupled replication may drive recombination directly in various species, including humans.
C1 [Ma, Wenjian; Westmoreland, James W.; Resnick, Michael A.] NIEHS, Chromosome Stabil Grp, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Resnick, MA (reprint author), NIEHS, Chromosome Stabil Grp, Mol Genet Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM Resnick@niehs.nih.gov
FU National Institute of Environmental Health Sciences (National Institutes
of Health, Department of Health and Human Services) [1 Z01 ES065073]
FX We thank Drs. Julie Horton, Dmitry Gordenin, Shay Covo, and Kin Chan for
critical reading of the manuscript and suggestions. This work was
supported by the Intramural Research Program of the National Institute
of Environmental Health Sciences (National Institutes of Health,
Department of Health and Human Services) under Project 1 Z01 ES065073
(to M.A.R.).
NR 55
TC 9
Z9 9
U1 1
U2 13
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 30
PY 2013
VL 110
IS 31
BP E2895
EP E2904
DI 10.1073/pnas.1301676110
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 191VH
UT WOS:000322441500010
PM 23858457
ER
PT J
AU Boudes, M
Uvin, P
Pinto, S
Freichel, M
Birnbaumer, L
Voets, T
De Ridder, D
Vennekens, R
AF Boudes, Mathieu
Uvin, Pieter
Pinto, Silvia
Freichel, Marc
Birnbaumer, Lutz
Voets, Thomas
De Ridder, Dirk
Vennekens, Rudi
TI Crucial Role of TRPC1 and TRPC4 in Cystitis-Induced Neuronal Sprouting
and Bladder Overactivity
SO PLOS ONE
LA English
DT Article
ID DORSAL-ROOT GANGLION; INTERSTITIAL CYSTITIS; RAT BLADDER; NEUROTROPHIC
FACTOR; URINARY-BLADDER; SENSORY NEURONS; GROWTH CONES; NERVE INJURY;
RECEPTOR; EXPRESSION
AB Purpose: During cystitis, increased innervation of the bladder by sensory nerves may contribute to bladder overactivity and pain. The mechanisms whereby cystitis leads to hyperinnervation of the bladder are, however, poorly understood. Since TRP channels have been implicated in the guidance of growth cones and survival of neurons, we investigated their involvement in the increases in bladder innervation and bladder activity in rodent models of cystitis.
Materials and Methods: To induce bladder hyperactivity, we chronically injected cyclophosphamide in rats and mice. All experiments were performed a week later. We used quantitative transcriptional analysis and immunohistochemistry to determine TRP channel expression on retrolabelled bladder sensory neurons. To assess bladder function and referred hyperalgesia, urodynamic analysis, detrusor strip contractility and Von Frey filament experiments were done in wild type and knock-out mice.
Results: Repeated cyclophosphamide injections induce a specific increase in the expression of TRPC1 and TRPC4 in bladder-innervating sensory neurons and the sprouting of sensory fibers in the bladder mucosa. Interestingly, cyclophosphamide-treated Trpc1/c4(-/-) mice no longer exhibited increased bladder innervations, and, concomitantly, the development of bladder overactivity was diminished in these mice. We did not observe a difference neither in bladder contraction features of double knock-out animals nor in cyclophosphamide-induced referred pain behavior.
Conclusions: Collectively, our data suggest that TRPC1 and TRPC4 are involved in the sprouting of sensory neurons following bladder cystitis, which leads to overactive bladder disease.
C1 [Boudes, Mathieu; Uvin, Pieter; De Ridder, Dirk] Katholieke Univ Leuven, Dept Dev & Regenerat, Lab Expt Urol, Louvain, Belgium.
[Boudes, Mathieu; Uvin, Pieter; Pinto, Silvia; Voets, Thomas; Vennekens, Rudi] Katholieke Univ Leuven, Dept Cellular & Mol Med, Lab Ion Channel Res, Louvain, Belgium.
[Boudes, Mathieu; Uvin, Pieter; Pinto, Silvia; Voets, Thomas; De Ridder, Dirk; Vennekens, Rudi] TRP Res Platform Leuven, Louvain, Belgium.
[Freichel, Marc] Univ Saarland, Homburg, Germany.
[Freichel, Marc] Heidelberg Univ, Inst Pharmakol, Heidelberg, Germany.
[Birnbaumer, Lutz] Natl Inst Environm Hlth Sci, Lab Neurobiol Signal Transduct, NIH, Res Triangle Pk, NC USA.
RP Boudes, M (reprint author), Katholieke Univ Leuven, Dept Dev & Regenerat, Lab Expt Urol, Louvain, Belgium.
EM mathieu.boudes@med.kuleuven.be; rudi.vennekens@med.kuleuven.be
RI De Ridder, Dirk /G-2481-2010; Voets, Thomas/E-2466-2012; Uvin,
Pieter/A-9221-2016;
OI De Ridder, Dirk /0000-0001-6914-0077; Voets, Thomas/0000-0001-5526-5821;
Uvin, Pieter/0000-0003-1264-2417; Vennekens, Rudi/0000-0002-2564-5150
FU Research Foundation Flanders (FWO) [G0565.07, G0686.09]; Research
Council of the KU Leuven [GOA 2009/07, EF/ 95/010]; TRPLe; Astellas;
National Institutes of Health [ZO1-ES-101684]
FX This research was supported by Research Foundation Flanders (FWO) Grants
G0565.07 and G0686.09 and Research Council of the KU Leuven Grants GOA
2009/07, EF/ 95/010 and TRPLe, an unrestricted educational grant by
Astellas, and in part by the Intramural Research Program of the National
Institutes of Health (project ZO1-ES-101684 to LB). MB is Marie Curie
Fellow and PU is a PhD student of the FWO. DDR is a senior clinical
researcher of the FWO Vlaanderen. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 47
TC 7
Z9 7
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 29
PY 2013
VL 8
IS 7
AR e69550
DI 10.1371/journal.pone.0069550
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 204MP
UT WOS:000323369700040
PM 23922735
ER
PT J
AU Kirkali, G
Jaruga, P
Reddy, PT
Tona, A
Nelson, BC
Li, MX
Wilson, DM
Dizdaroglu, M
AF Kirkali, Gueldal
Jaruga, Pawel
Reddy, Prasad T.
Tona, Alessandro
Nelson, Bryant C.
Li, Mengxia
Wilson, David M., III
Dizdaroglu, Miral
TI Identification and Quantification of DNA Repair Protein
Apurinic/Apyrimidinic Endonuclease 1 (APE1) in Human Cells by Liquid
Chromatography/Isotope-Dilution Tandem Mass Spectrometry
SO PLOS ONE
LA English
DT Article
ID BASE EXCISION-REPAIR; AMYOTROPHIC-LATERAL-SCLEROSIS; HUMAN APURINIC
ENDONUCLEASE; ACID SUBSTITUTION VARIANTS; MAJOR HUMAN; ABASIC
ENDONUCLEASE; OXIDATIVE STRESS; ENZYME HAP1; APE1/REF-1; GENES
AB Unless repaired, DNA damage can drive mutagenesis or cell death. DNA repair proteins may therefore be used as biomarkers in disease etiology or therapeutic response prediction. Thus, the accurate determination of DNA repair protein expression and genotype is of fundamental importance. Among DNA repair proteins involved in base excision repair, apurinic/apyrimidinic endonuclease 1 (APE1) is the major endonuclease in mammals and plays important roles in transcriptional regulation and modulating stress responses. Here, we present a novel approach involving LC-MS/MS with isotope-dilution to positively identify and accurately quantify APE1 in human cells and mouse tissue. A completely N-15-labeled full-length human APE1 was produced and used as an internal standard. Fourteen tryptic peptides of both human APE1 (hAPE1) and N-15-labeled hAPE1 were identified following trypsin digestion. These peptides matched the theoretical peptides expected from trypsin digestion and provided a statistically significant protein score that would unequivocally identify hAPE1. Using the developed methodology, APE1 was positively identified and quantified in nuclear and cytoplasmic extracts of multiple human cell lines and mouse liver using selected-reaction monitoring of typical mass transitions of the tryptic peptides. We also show that the methodology can be applied to the identification of hAPE1 variants found in the human population. The results describe a novel approach for the accurate measurement of wild-type and variant forms of hAPE1 in vivo, and ultimately for defining the role of this protein in disease development and treatment responses.
C1 [Kirkali, Gueldal; Jaruga, Pawel; Reddy, Prasad T.; Dizdaroglu, Miral] Natl Inst Stand & Technol, Biomol Measurement Div, Gaithersburg, MD 20899 USA.
[Tona, Alessandro; Nelson, Bryant C.] Natl Inst Stand & Technol, Biosyst & Biomat Div, Gaithersburg, MD 20899 USA.
[Li, Mengxia; Wilson, David M., III] NIA, NIH, Lab Mol Gerontol, Baltimore, MD 21224 USA.
RP Dizdaroglu, M (reprint author), Natl Inst Stand & Technol, Biomol Measurement Div, Gaithersburg, MD 20899 USA.
EM miral@nist.gov
RI Jaruga, Pawel/M-4378-2015
FU Intramural Research Program at the National Institutes of Health,
National Institute on Aging
FX This work was supported in part by the Intramural Research Program at
the National Institutes of Health, National Institute on Aging. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 47
TC 4
Z9 4
U1 1
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 29
PY 2013
VL 8
IS 7
AR e69894
DI 10.1371/journal.pone.0069894
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 204MP
UT WOS:000323369700098
PM 23922845
ER
PT J
AU Sette, P
Nagashima, K
Piper, RC
Bouamr, F
AF Sette, Paola
Nagashima, Kunio
Piper, Robert C.
Bouamr, Fadila
TI Ubiquitin conjugation to Gag is essential for ESCRT-mediated HIV-1
budding
SO RETROVIROLOGY
LA English
DT Article
DE Ubiquitin; HIV budding; ESCRT; Deubiquitination; Gag
ID IMMUNODEFICIENCY-VIRUS TYPE-1; INFECTIOUS-ANEMIA VIRUS; PROTEIN-SORTING
PATHWAY; MURINE LEUKEMIA-VIRUS; TSG101 UEV DOMAIN; MULTIVESICULAR
ENDOSOMES; FUNCTIONAL REPLACEMENT; RETROVIRUS; ALIX; RELEASE
AB Background: HIV-1 relies on the host ESCRTs for release from cells. HIV-1 Gag engages ESCRTs by directly binding TSG101 or Alix. ESCRTs also sort ubiquitinated membrane proteins through endosomes to facilitate their lysosomal degradation. The ability of ESCRTs to recognize and process ubiquitinated proteins suggests that ESCRT-dependent viral release may also be controlled by ubiquitination. Although both Gag and ESCRTs undergo some level of ubiquitination, definitive demonstration that ubiquitin is required for viral release is lacking. Here we suppress ubiquitination at viral budding sites by fusing the catalytic domain of the Herpes Simplex UL36 deubiquitinating enzyme (DUb) onto TSG101, Alix, or Gag.
Results: Expressing DUb-TSG101 suppressed Alix-independent HIV-1 release and viral particles remained tethered to the cell surface. DUb-TSG101 had no effect on budding of MoMLV or EIAV, two retroviruses that rely on the ESCRT machinery for exit. Alix-dependent virus release such as EIAV's, and HIV-1 lacking access to TSG101, was instead dramatically blocked by co-expressing DUb-Alix. Finally, Gag-DUb was unable to support virus release and dominantly interfered with release of wild type HIV-1. Fusion of UL36 did not effect interactions with Alix, TSG101, or Gag and all of the inhibitory effects of UL36 fusion were abolished when its catalytic activity was ablated. Accordingly, Alix, TSG101 and Gag fused to inactive UL36 functionally replaced their unfused counterparts. Interestingly, coexpression of the Nedd4-2s ubiquitin ligase suppressed the ability of DUb-TSG101 to inhibit HIV-1 release while also restoring detectable Gag ubiquitination at the membrane. Similarly, incorporation of Gag-Ub fusion proteins into virions lifted DUb-ESCRT inhibitory effect. In contrast, Nedd4-2s did not suppress the inhibition mediated by Gag-DUb despite restoring robust ubiquitination of TSG101/ESCRT-I at virus budding sites.
Conclusions: These studies demonstrate a necessary and natural role for ubiquitin in ESCRT-dependent viral release and indicate a critical role for ubiquitination of Gag rather than ubiquitination of ESCRTs themselves.
C1 [Sette, Paola; Bouamr, Fadila] NIAID, Viral Budding Unit, Mol Microbiol Lab, NIH, Bethesda, MD 20894 USA.
[Nagashima, Kunio] NCI Frederick, SAIC Frederick, Image Anal Lab, Adv Technol Program, Frederick, MD 21702 USA.
[Piper, Robert C.] Univ Iowa, Iowa City, IA 52246 USA.
RP Bouamr, F (reprint author), NIAID, Viral Budding Unit, Mol Microbiol Lab, NIH, 4 Ctr Dr, Bethesda, MD 20894 USA.
EM bouamrf@mail.nih.gov
FU Intramural Research Program of the NIAID, NIH
FX We are very grateful to Adam Harned (SAIC, NCI-Frederick) for assistance
with EM processing and imaging, to Vincent Dussupt for ESCRT-I
expression constructs (VBU, NIAID) and Melodi P. Javid (VBU, NIAID) for
CHMP4B expression vector, to Eric Freed (DRP, NCI-Frederick) for the
Gag-Ub expression plasmid and Ronald Montelaro (University of
Pittsburgh) for EIAV constructs as well as the anti-EIAV antibody. This
work was supported by the Intramural Research Program of the NIAID, NIH.
NR 60
TC 20
Z9 21
U1 2
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD JUL 29
PY 2013
VL 10
AR 79
DI 10.1186/1742-4690-10-79
PG 18
WC Virology
SC Virology
GA 204MN
UT WOS:000323369500001
PM 23895345
ER
PT J
AU Martinez-Llordella, M
Esensten, JH
Bailey-Bucktrout, SL
Lipsky, RH
Marini, A
Chen, J
Mughal, M
Mattson, MP
Taub, DD
Bluestone, JA
AF Martinez-Llordella, Marc
Esensten, Jonathan H.
Bailey-Bucktrout, Samantha L.
Lipsky, Robert H.
Marini, Ann
Chen, Jun
Mughal, Mohamed
Mattson, Mark P.
Taub, Dennis D.
Bluestone, Jeffrey A.
TI CD28-inducible transcription factor DEC1 is required for efficient
autoreactive CD4(+) T cell response
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID NF-KAPPA-B; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CD28
COSTIMULATION; C-REL; LYMPHOCYTE-ACTIVATION; SIGNALING PATHWAYS;
PROXIMAL PROMOTER; ANTIGEN RECEPTOR; GENE-EXPRESSION; BINDING-SITES
AB During the initial hours after activation, CD4(+) T cells experience profound changes in gene expression. Co-stimulation via the CD28 receptor is required for efficient activation of naive T cells. However, the transcriptional consequences of CD28 co-stimulation are not completely understood. We performed expression microarray analysis to elucidate the effects of CD28 signals on the transcriptome of activated T cells. We show that the transcription factor DEC1 is highly induced in a CD28-dependent manner upon T cell activation, is involved in essential CD4(+) effector T cell functions, and participates in the transcriptional regulation of several T cell activation pathways, including a large group of CD28-regulated genes. Antigen-specific, DEC1-deficient CD4(+) T cells have cell-intrinsic defects in survival and proliferation. Furthermore, we found that DEC1 is required for the development of experimental autoimmune encephalomyelitis because of its critical role in the production of the proinflammatory cytokines GM-CSF, IFN-gamma, and IL-2. Thus, we identify DEC1 as a critical transcriptional mediator in the activation of naive CD4(+) T cells that is required for the development of a T cell-mediated autoimmune disease.
C1 [Martinez-Llordella, Marc; Esensten, Jonathan H.; Bailey-Bucktrout, Samantha L.; Bluestone, Jeffrey A.] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA.
[Esensten, Jonathan H.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Martinez-Llordella, Marc] Kings Coll London, Med Res Council Ctr Transplantat, Inst Liver Studies, Div Transplantat Immunol & Mucosal Biol, London WC2R 2LS, England.
[Lipsky, Robert H.] George Mason Univ, Inova Fairfax Hosp, Dept Neurosci, Fairfax, VA 22030 USA.
[Lipsky, Robert H.] George Mason Univ, Krasnow Inst Adv Study, Dept Mol Neurosci, Fairfax, VA USA.
[Marini, Ann; Chen, Jun] Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA.
[Marini, Ann; Chen, Jun] Uniformed Serv Univ Hlth Sci, Neurosci Program, Bethesda, MD 20814 USA.
[Mughal, Mohamed; Mattson, Mark P.] NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA.
[Taub, Dennis D.] NIA, Lab Mol Biol & Immunol, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Bluestone, JA (reprint author), Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA.
EM Jeff.Bluestone@ucsf.edu
OI Lipsky, Robert/0000-0001-7753-1473
FU US National Institutes of Health (NIH) [P01 AI35297, R37 AI46643];
National Institute on Aging (NIH); Spanish Ministry of Science and
Education [EX2009-0538]; University of California, San Francisco Medical
Scientist Training Program
FX This research was supported by US National Institutes of Health (NIH)
grants P01 AI35297 and R37 AI46643 to J.A. Bluestone and P30 DK63720 for
core support. This research was also supported, in part, by the
Intramural Research Program of the National Institute on Aging (NIH),
the Spanish Ministry of Science and Education EX2009-0538, and the
University of California, San Francisco Medical Scientist Training
Program.
NR 70
TC 15
Z9 16
U1 1
U2 7
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD JUL 29
PY 2013
VL 210
IS 8
BP 1603
EP 1619
DI 10.1084/jem.20122387
PG 17
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 190WG
UT WOS:000322372800009
PM 23878307
ER
PT J
AU Rotimi, C
Shriner, D
Adeyemo, A
AF Rotimi, Charles
Shriner, Daniel
Adeyemo, Adebowale
TI Genome science and health disparities: a growing success story?
SO GENOME MEDICINE
LA English
DT Editorial Material
C1 [Rotimi, Charles; Shriner, Daniel; Adeyemo, Adebowale] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
RP Rotimi, C (reprint author), NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
EM rotimic@mail.nih.gov
OI Adeyemo, Adebowale/0000-0002-3105-3231
FU NIMHD NIH HHS [P20 MD006899]
NR 10
TC 2
Z9 2
U1 1
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-994X
J9 GENOME MED
JI Genome Med.
PD JUL 29
PY 2013
VL 5
AR 61
DI 10.1186/gm465
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA 192CA
UT WOS:000322460400001
PM 23899246
ER
PT J
AU Klett, EL
Chen, SF
Edin, ML
Li, LO
Ilkayeva, O
Zeldin, DC
Newgard, CB
Coleman, RA
AF Klett, Eric L.
Chen, Shufen
Edin, Matthew L.
Li, Lei O.
Ilkayeva, Olga
Zeldin, Darryl C.
Newgard, Christopher B.
Coleman, Rosalind A.
TI Diminished Acyl-CoA Synthetase Isoform 4 Activity in INS 832/13 Cells
Reduces Cellular Epoxyeicosatrienoic Acid Levels and Results in Impaired
Glucose-stimulated Insulin Secretion
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Arachidonic Acid; Beta-Cell; Eicosanoid; Insulin Secretion;
Polyunsaturated Fatty Acids; Acyl-CoA Synthetase; Epoxyeicosatrienoic
Acids
ID ISOLATED PANCREATIC-ISLETS; COENZYME-A ESTERS; FATTY-ACID;
ARACHIDONIC-ACID; BETA-CELLS; RAT PANCREAS; MALONYL-COA; TRIACSIN-C;
CHAIN; METABOLISM
AB Glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells is potentiated by fatty acids (FA). The initial step in the metabolism of intracellular FA is the conversion to acyl-CoA by long chain acyl-CoA synthetases (Acsls). Because the predominantly expressed Acsl isoforms in INS 832/13 cells are Acsl4 and -5, we characterized the role of these Acsls in beta-cell function by using siRNA to knock down Acsl4 or Acsl5. Compared with control cells, an 80% suppression of Acsl4 decreased GSIS and FA-potentiated GSIS by 32 and 54%, respectively. Knockdown of Acsl5 did not alter GSIS. Acsl4 knockdown did not alter FA oxidation or long chain acyl-CoA levels. With Acsl4 knockdown, incubation with 17 mm glucose increased media epoxyeicosatrienoic acids (EETs) and reduced cell membrane levels of EETs. Further, exogenous EETs reduced GSIS in INS 832/13 cells, and in Acsl4 knockdown cells, an EET receptor antagonist partially rescued GSIS. These results strongly suggest that Acsl4 activates EETs to form EET-CoAs that are incorporated into glycerophospholipids, thereby sequestering EETs. Exposing INS 832/13 cells to arachidonate or linoleate reduced Acsl4 mRNA and protein expression and reduced GSIS. These data indicate that Acsl4 modulates GSIS by regulating the levels of unesterified EETs and that arachidonate controls the expression of its activator Acsl4.
C1 [Klett, Eric L.; Chen, Shufen] Univ N Carolina, Sch Med, Dept Med, Div Endocrinol, Chapel Hill, NC 27599 USA.
[Edin, Matthew L.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
[Ilkayeva, Olga; Newgard, Christopher B.] Duke Univ, Sarah W Stedman Nutr & Metab Ctr, Dept Pharmacol & Canc Biol, Med Ctr, Durham, NC 27704 USA.
[Ilkayeva, Olga; Newgard, Christopher B.] Duke Univ, Dept Med, Med Ctr, Durham, NC 27704 USA.
[Li, Lei O.; Coleman, Rosalind A.] Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA.
RP Klett, EL (reprint author), Univ N Carolina, Sch Med, Dept Med, 8018 Burnett Womack,CB 7172, Chapel Hill, NC 27599 USA.
EM eklett@med.unc.edu
OI Edin, Matthew/0000-0002-7042-500X
FU National Institutes of Health [K08DK090141, DK59935, DK058398];
University of North Carolina Nutrition Obesity Research Center (NORC)
[DK056350]; National Institutes of Health, NIEHS [Z01 ES025034]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants K08DK090141 (to E. L. K.), DK59935 (to R. A. C.), and
DK058398 (to C. B. N.). This work was also supported by University of
North Carolina Nutrition Obesity Research Center (NORC) Grant DK056350
and by Grant Z01 ES025034 from the Intramural Research Program of the
National Institutes of Health, NIEHS (to D. C. Z.).
NR 47
TC 16
Z9 16
U1 1
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 26
PY 2013
VL 288
IS 30
BP 21618
EP 21629
DI 10.1074/jbc.M113.481077
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 277TJ
UT WOS:000328841900014
PM 23766516
ER
PT J
AU Wang, XC
Jin, CY
Tang, Y
Tang, LY
Zhang, YE
AF Wang, Xiangchun
Jin, Chaoyang
Tang, Yi
Tang, Liu-Ya
Zhang, Ying E.
TI Ubiquitination of Tumor Necrosis Factor Receptor-associated Factor 4
(TRAF4) by Smad Ubiquitination Regulatory Factor 1 (Smurf1) Regulates
Motility of Breast Epithelial and Cancer Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Breast Cancer; Cell Migration; E3 Ubiquitin Ligase; Rac1; Tight
Junctions; TRAF; Ubiquitination; Smurf1; TRAF4; Monoubiquitination
ID LIGASE SMURF2; TRAF4-DEFICIENT MICE; TGF-BETA; DEGRADATION; POLARITY;
PATHWAY; MIGRATION; TARGETS; PROTEIN; DIFFERENTIATION
AB Smad ubiquitin regulatory factors (Smurfs) are HECT-domain ubiquitin E3 ligases that regulate diverse cellular processes, including normal and tumor cell migration. However, the underlying mechanism of the Smurfs' role in cell migration is not fully understood. Here we show that Smurf1 induces ubiquitination of tumor necrosis factor receptor-associated factor 4 (TRAF4) at K190. Using the K190R mutant of TRAF4, we demonstrate that Smurf1-induced ubiquitination is required for proper localization of TRAF4 to tight junctions in confluent epithelial cells. We further show that TRAF4 is essential for the migration of both normal mammary epithelial and breast cancer cells. The ability of TRAF4 to promote cell migration is also dependent on Smurf1-mediated ubiquitination, which is associated with Rac1 activation by TRAF4. These results reveal a new regulatory circuit for cell migration, consisting of Smurf1-mediated ubiquitination of TRAF4 and Rac1 activation.
C1 [Wang, Xiangchun; Jin, Chaoyang; Tang, Yi; Tang, Liu-Ya; Zhang, Ying E.] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Zhang, YE (reprint author), NCI, Lab Cellular & Mol Biol, Ctr Canc Res, 37 Convent Dr,Bldg 37,Room 2056B, Bethesda, MD 20892 USA.
EM zhangyin@mail.nih.gov
RI Zhang, Ying/G-3657-2015
OI Zhang, Ying/0000-0003-2753-7601
FU National Institutes of Health, NCI, Center for Cancer Research [ZIA BC
011168]
FX This work was supported by the intramural research program of the
National Institutes of Health, NCI, Center for Cancer Research (ZIA BC
011168).
NR 44
TC 12
Z9 15
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 26
PY 2013
VL 288
IS 30
AR 21784
DI 10.1074/jbc.M113.472704
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 277TJ
UT WOS:000328841900028
PM 23760265
ER
PT J
AU Liu, ZG
Yedidi, RS
Wang, Y
Dewdney, TG
Reiter, SJ
Brunzelle, JS
Kovari, IA
Kovari, LC
AF Liu, Zhigang
Yedidi, Ravikiran S.
Wang, Yong
Dewdney, Tamaria G.
Reiter, Samuel J.
Brunzelle, Joseph S.
Kovari, Iulia A.
Kovari, Ladislau C.
TI Crystallographic study of multi-drug resistant HIV-1 protease lopinavir
complex: Mechanism of drug recognition and resistance
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE HIV-1 protease; Multi-drug resistance; X-ray crystallography; IC50;
Lopinavir
ID HUMAN-IMMUNODEFICIENCY-VIRUS; INHIBITOR; REFINEMENT; SELECTION; MODEL
AB Lopinavir (LPV) is a second generation HIV-1 protease inhibitor. Drug resistance has rapidly emerged against LPV since its US FDA approval on September 15, 2000. Mutations at residues 321, L33F, 461, 47A, I54V, V82A, I84V, and L90M render the protease drug resistant against LPV. We report the crystal structure of a clinical isolate multi-drug resistant (MDR) 769 HIV-1 protease (resistant mutations at residues 10, 36, 46, 54, 62, 63, 71, 82, 84, and 90) complexed with LPV and the in vitro enzymatic IC50 of LPV against MDR 769. The structural and functional studies demonstrate significant drug resistance of MDR 769 against LPV, arising from reduced interactions between LPV and the protease target. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Liu, Zhigang; Yedidi, Ravikiran S.; Wang, Yong; Dewdney, Tamaria G.; Reiter, Samuel J.; Kovari, Iulia A.; Kovari, Ladislau C.] Wayne State Univ, Sch Med, Dept Biochem & Mol Biol, Detroit, MI 48201 USA.
[Liu, Zhigang] Harbor Hosp, Div Internal Med, Baltimore, MD 21225 USA.
[Yedidi, Ravikiran S.] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
[Brunzelle, Joseph S.] Northwestern Univ, Feinberg Sch Med, Life Sci Collaborat Access Team, Chicago, IL 60611 USA.
[Brunzelle, Joseph S.] Northwestern Univ, Feinberg Sch Med, Dept Mol Pharmacol & Biol Chem, Chicago, IL 60611 USA.
RP Kovari, LC (reprint author), 540 E Canfield Ave,4263 Scott Hall, Detroit, MI 48201 USA.
EM kovari@med.wayne.edu
RI Liu, Zhigang/A-2003-2014;
OI Yedidi, Ravikiran/0000-0003-2755-1307
FU National Institutes of Health [AI65294]; American Foundation for AIDS
Research [106457-34-RGGN]
FX This research was supported by the National Institutes of Health Grant
AI65294 and the American Foundation for AIDS Research (106457-34-RGGN).
NR 22
TC 1
Z9 1
U1 1
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD JUL 26
PY 2013
VL 437
IS 2
BP 199
EP 204
DI 10.1016/j.bbrc.2013.06.027
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 199TJ
UT WOS:000323018100003
PM 23792096
ER
PT J
AU Busser, BW
Gisselbrecht, SS
Shokri, L
Tansey, TR
Gamble, CE
Bulyk, ML
Michelson, AM
AF Busser, Brian W.
Gisselbrecht, Stephen S.
Shokri, Leila
Tansey, Terese R.
Gamble, Caitlin E.
Bulyk, Martha L.
Michelson, Alan M.
TI Contribution of Distinct Homeodomain DNA Binding Specificities to
Drosophila Embryonic Mesodermal Cell-Specific Gene Expression Programs
SO PLOS ONE
LA English
DT Article
ID HOX PROTEINS; TRANSCRIPTION FACTORS; REGULATORY ELEMENTS; IDENTITY
GENES; MUSCLE; DIVERSITY; NETWORK; DIVERSIFICATION; COFACTORS; TINMAN
AB Homeodomain (HD) proteins are a large family of evolutionarily conserved transcription factors (TFs) having diverse developmental functions, often acting within the same cell types, yet many members of this family paradoxically recognize similar DNA sequences. Thus, with multiple family members having the potential to recognize the same DNA sequences in cis-regulatory elements, it is difficult to ascertain the role of an individual HD or a subclass of HDs in mediating a particular developmental function. To investigate this problem, we focused our studies on the Drosophila embryonic mesoderm where HD TFs are required to establish not only segmental identities (such as the Hox TFs), but also tissue and cell fate specification and differentiation (such as the NK-2 HDs, Six HDs and identity HDs (I-HDs)). Here we utilized the complete spectrum of DNA binding specificities determined by protein binding microarrays (PBMs) for a diverse collection of HDs to modify the nucleotide sequences of numerous mesodermal enhancers to be recognized by either no or a single subclass of HDs, and subsequently assayed the consequences of these changes on enhancer function in transgenic reporter assays. These studies show that individual mesodermal enhancers receive separate transcriptional input from both I-HD and Hox subclasses of HDs. In addition, we demonstrate that enhancers regulating upstream components of the mesodermal regulatory network are targeted by the Six class of HDs. Finally, we establish the necessity of NK-2 HD binding sequences to activate gene expression in multiple mesodermal tissues, supporting a potential role for the NK-2 HD TF Tinman (Tin) as a pioneer factor that cooperates with other factors to regulate cell-specific gene expression programs. Collectively, these results underscore the critical role played by HDs of multiple subclasses in inducing the unique genetic programs of individual mesodermal cells, and in coordinating the gene regulatory networks directing mesoderm development.
C1 [Busser, Brian W.; Tansey, Terese R.; Gamble, Caitlin E.; Michelson, Alan M.] NHLBI, Lab Dev Syst Biol, NIH, Bethesda, MD 20892 USA.
[Gisselbrecht, Stephen S.; Shokri, Leila; Bulyk, Martha L.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
[Gisselbrecht, Stephen S.; Shokri, Leila; Bulyk, Martha L.] Harvard Univ, Sch Med, Boston, MA USA.
[Bulyk, Martha L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Bulyk, Martha L.] Harvard Univ, Sch Med, Harvard MIT Div Hlth Sci & Technol HST, Boston, MA USA.
RP Michelson, AM (reprint author), NHLBI, Lab Dev Syst Biol, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM michelsonam@nhlbi.nih.gov
OI Gisselbrecht, Stephen/0000-0001-8723-902X
FU NHLBI Division of Intramural Research; NIH [R01 HG005287]; NIH NRSA [F32
GM090645]
FX This work was funded by the NHLBI Division of Intramural Research (AMM),
NIH grant R01 HG005287 (MLB) and NIH NRSA F32 GM090645 (LS). The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 62
TC 7
Z9 7
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 26
PY 2013
VL 8
IS 7
AR e69385
DI 10.1371/journal.pone.0069385
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 197GU
UT WOS:000322838900040
PM 23922708
ER
PT J
AU Koblin, BA
Mayer, KH
Eshleman, SH
Wang, L
Mannheimer, S
del Rio, C
Shoptaw, S
Magnus, M
Buchbinder, S
Wilton, L
Liu, TY
Cummings, V
Piwowar-Manning, E
Fields, SD
Griffith, S
Elharrar, V
Wheeler, D
AF Koblin, Beryl A.
Mayer, Kenneth H.
Eshleman, Susan H.
Wang, Lei
Mannheimer, Sharon
del Rio, Carlos
Shoptaw, Steven
Magnus, Manya
Buchbinder, Susan
Wilton, Leo
Liu, Ting-Yuan
Cummings, Vanessa
Piwowar-Manning, Estelle
Fields, Sheldon D.
Griffith, Sam
Elharrar, Vanessa
Wheeler, Darrell
CA HPTN 061 Protocol Team
TI Correlates of HIV Acquisition in a Cohort of Black Men Who Have Sex with
Men in the United States: HIV Prevention Trials Network (HPTN) 061
SO PLOS ONE
LA English
DT Article
ID INFECTION; DISPARITIES; MORTALITY; SYPHILIS; RISK
AB Background: Black men who have sex with men (MSM) in the United States (US) are affected by HIV at disproportionate rates compared to MSM of other race/ethnicities. Current HIV incidence estimates in this group are needed to appropriately target prevention efforts.
Methods: From July 2009 to October 2010, Black MSM reporting unprotected anal intercourse with a man in the past six months were enrolled and followed for one year in six US cities for a feasibility study of a multi-component intervention to reduce HIV infection. HIV incidence based on HIV seroconversion was calculated as number of events/100 person-years. Multivariate proportional hazards modeling with time-dependent covariates was used to identify correlates of HIV acquisition.
Results: Of 1,553 Black MSM enrolled, 1,164 were HIV-uninfected at baseline and included in follow-up. Overall annual HIV incidence was 3.0% (95% confidence interval (CI): 2.0, 4.4%) and 5.9% among men <= 30 years old (95% CI: 3.6, 9.1%). Men <= 30 years old reported significantly higher levels of sexual risk and were more likely to have a sexually transmitted infection diagnosed during follow-up. Younger men also were more likely to not have a usual place for health care, not have visited a health care provider recently, and to have unmet health care needs. In multivariate analysis, age <= 30 years (hazard ratio (HR): 3.4; 95% CI: 1.4, 8.3) and unprotected receptive anal intercourse with HIV-positive or unknown status partners (HR: 4.1; 95% CI: 1.9, 9.1) were significantly associated with HIV acquisition.
Conclusion: In the largest cohort of prospectively-followed Black MSM in the US, HIV incidence was high, particularly among young men. Targeted, tailored and culturally appropriate HIV prevention strategies incorporating behavioral, social and biomedical based interventions are urgently needed to lower these rates.
C1 [Koblin, Beryl A.] New York Blood Ctr, Lab Infect Dis Prevent, New York, NY 10021 USA.
[Mayer, Kenneth H.] Fenway Hlth, Boston, MA USA.
[Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Boston, MA USA.
[Eshleman, Susan H.; Cummings, Vanessa; Piwowar-Manning, Estelle] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Wang, Lei; Liu, Ting-Yuan] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[Mannheimer, Sharon] Columbia Univ, Dept Med, Harlem Hosp, New York, NY USA.
[Mannheimer, Sharon] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
[del Rio, Carlos] Emory Univ, Rollins Sch Publ Hlth, Dept Global Hlth, Atlanta, GA 30322 USA.
[del Rio, Carlos] Emory Univ, Sch Med, Dept Med, Atlanta, GA USA.
[Shoptaw, Steven] Univ Calif Los Angeles, Dept Family Med, Los Angeles, CA USA.
[Magnus, Manya] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Epidemiol & Biostat, Washington, DC USA.
[Buchbinder, Susan] San Francisco Dept Publ Hlth, San Francisco, CA USA.
[Wilton, Leo] Binghamton Univ, Coll Community & Publ Affairs, Dept Human Dev, New York, NY USA.
[Fields, Sheldon D.] Florida Int Univ, Coll Nursing & Hlth Sci, Miami, FL 33199 USA.
[Griffith, Sam] FHI 360, Res Triangle Pk, NC USA.
[Elharrar, Vanessa] NIAID, Clin Prevent Res Branch, PSP, DAIDS,NIH, Bethesda, MD 20892 USA.
[Wheeler, Darrell] Loyola Univ, Grad Sch Social Work, Chicago, IL 60611 USA.
RP Koblin, BA (reprint author), New York Blood Ctr, Lab Infect Dis Prevent, New York, NY 10021 USA.
EM bkoblin@nybloodcenter.org
RI del Rio, Carlos/B-3763-2012
OI del Rio, Carlos/0000-0002-0153-3517
FU National Institute of Allergy and Infectious Disease (NIAID) [HPTN 061];
National Institute on Drug Abuse (NIDA); National Institute of Mental
Health (NIMH) [UM1 AI068619, UM1 AI068617, UM1 AI068613]; Fenway
Institute Clinical Research Site (CRS): Harvard University CFAR [P30
AI060354]; CTU for HIV Prevention and Microbicide Research [UM1
AI069480]; George Washington University CRS: District of Columbia
Developmental CFAR [P30 AI087714]; Harlem Prevention Center CRS and NY
Blood Center/Union Square CRS: Columbia University CTU [5U01 AI069466];
ARRA [3U01 AI069466-03S1]; Hope Clinic of the Emory Vaccine Center CRS;
The Ponce de Leon Center CRS: Emory University HIV/AIDS CTU [5U01
AI069418]; CFAR [P30 AI050409]; CTSA [UL1 RR025008]; San Francisco
Vaccine and Prevention CRS: ARRA [3U01 AI069496-03S1, 3U01
AI069496-03S2]; UCLA Vine Street CRS: UCLA Department of Medicine,
Division of Infectious Diseases CTU [U01 AI069424]
FX HPTN 061 grant support provided by the National Institute of Allergy and
Infectious Disease (NIAID), National Institute on Drug Abuse (NIDA) and
National Institute of Mental Health (NIMH): Cooperative Agreements UM1
AI068619, UM1 AI068617, and UM1 AI068613. Additional site funding
-Fenway Institute Clinical Research Site (CRS): Harvard University CFAR
(P30 AI060354) and CTU for HIV Prevention and Microbicide Research (UM1
AI069480); George Washington University CRS: District of Columbia
Developmental CFAR (P30 AI087714); Harlem Prevention Center CRS and NY
Blood Center/Union Square CRS: Columbia University CTU (5U01 AI069466)
and ARRA funding (3U01 AI069466-03S1); Hope Clinic of the Emory Vaccine
Center CRS and The Ponce de Leon Center CRS: Emory University HIV/AIDS
CTU (5U01 AI069418), CFAR (P30 AI050409) and CTSA (UL1 RR025008); San
Francisco Vaccine and Prevention CRS: ARRA funding (3U01 AI069496-03S1,
3U01 AI069496-03S2); UCLA Vine Street CRS: UCLA Department of Medicine,
Division of Infectious Diseases CTU (U01 AI069424). The funder had a
role in the design of the study by providing input into the design. The
funder did not have a role in the data collection and analysis, decision
to publish, or preparation of the manuscript.
NR 24
TC 62
Z9 62
U1 2
U2 17
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 26
PY 2013
VL 8
IS 7
AR e70413
DI 10.1371/journal.pone.0070413
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 197GU
UT WOS:000322838900168
PM 23922989
ER
PT J
AU Kim, J
Stirling, KJ
Cooper, ME
Ascoli, M
Momany, AM
McDonald, EL
Ryckman, KK
Rhea, L
Schaa, KL
Cosentino, V
Gadow, E
Saleme, C
Shi, M
Hallman, M
Plunkett, J
Teramo, KA
Muglia, LJ
Feenstra, B
Geller, F
Boyd, HA
Melbye, M
Marazita, ML
Dagle, JM
Murray, JC
AF Kim, Jinsil
Stirling, Kara J.
Cooper, Margaret E.
Ascoli, Mario
Momany, Allison M.
McDonald, Erin L.
Ryckman, Kelli K.
Rhea, Lindsey
Schaa, Kendra L.
Cosentino, Viviana
Gadow, Enrique
Saleme, Cesar
Shi, Min
Hallman, Mikko
Plunkett, Jevon
Teramo, Kari A.
Muglia, Louis J.
Feenstra, Bjarke
Geller, Frank
Boyd, Heather A.
Melbye, Mads
Marazita, Mary L.
Dagle, John M.
Murray, Jeffrey C.
TI Sequence variants in oxytocin pathway genes and preterm birth: a
candidate gene association study
SO BMC MEDICAL GENETICS
LA English
DT Article
DE Preterm birth; Genetic association analysis; Oxytocin pathway; Single
nucleotide polymorphism; Rare variant
ID CASE-PARENT TRIADS; ARGININE-VASOPRESSIN; UNIFIED APPROACH; RECEPTOR;
PROGESTERONE; BINDING; PARTURITION; INHIBITION; PREGNANCY; DELIVERY
AB Background: Preterm birth (PTB) is a complex disorder associated with significant neonatal mortality and morbidity and long-term adverse health consequences. Multiple lines of evidence suggest that genetic factors play an important role in its etiology. This study was designed to identify genetic variation associated with PTB in oxytocin pathway genes whose role in parturition is well known.
Methods: To identify common genetic variants predisposing to PTB, we genotyped 16 single nucleotide polymorphisms (SNPs) in the oxytocin (OXT), oxytocin receptor (OXTR), and leucyl/cystinyl aminopeptidase (LNPEP) genes in 651 case infants from the U. S. and one or both of their parents. In addition, we examined the role of rare genetic variation in susceptibility to PTB by conducting direct sequence analysis of OXTR in 1394 cases and 1112 controls from the U. S., Argentina, Denmark, and Finland. This study was further extended to maternal triads (maternal grandparents- mother of a case infant, N=309). We also performed in vitro analysis of selected rare OXTR missense variants to evaluate their functional importance.
Results: Maternal genetic effect analysis of the SNP genotype data revealed four SNPs in LNPEP that show significant association with prematurity. In our case-control sequence analysis, we detected fourteen coding variants in exon 3 of OXTR, all but four of which were found in cases only. Of the fourteen variants, three were previously unreported novel rare variants. When the sequence data from the maternal triads were analyzed using the transmission disequilibrium test, two common missense SNPs (rs4686302 and rs237902) in OXTR showed suggestive association for three gestational age subgroups. In vitro functional assays showed a significant difference in ligand binding between wild-type and two mutant receptors.
Conclusions: Our study suggests an association between maternal common polymorphisms in LNPEP and susceptibility to PTB. Maternal OXTR missense SNPs rs4686302 and rs237902 may have gestational age-dependent effects on prematurity. Most of the OXTR rare variants identified do not appear to significantly contribute to the risk of PTB, but those shown to affect receptor function in our in vitro study warrant further investigation. Future studies with larger sample sizes are needed to confirm the findings of this study.
C1 [Kim, Jinsil; Murray, Jeffrey C.] Univ Iowa, Dept Anat & Cell Biol, Iowa City, IA 52242 USA.
[Stirling, Kara J.; Momany, Allison M.; McDonald, Erin L.; Ryckman, Kelli K.; Rhea, Lindsey; Schaa, Kendra L.; Dagle, John M.; Murray, Jeffrey C.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[Cooper, Margaret E.; Marazita, Mary L.] Univ Pittsburgh, Sch Dent Med, Ctr Craniofacial & Dent Genet, Dept Oral Biol, Pittsburgh, PA 15219 USA.
[Ascoli, Mario] Univ Iowa, Dept Pharmacol, Iowa City, IA 52242 USA.
[Cosentino, Viviana; Gadow, Enrique] Ctr Edu Med Inverst Clin, RA-1431 Buenos Aires, DF, Argentina.
[Saleme, Cesar] Inst Maternidad & Ginecol Nuestra Senora Mercedes, RA-4000 San Miguel De Tucuman, Argentina.
[Shi, Min] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
[Hallman, Mikko] Univ Oulu, Dept Pediat, Inst Clin Med, Oulu 90014, Finland.
[Plunkett, Jevon] Washington Univ, Human & Stat Genet Program, St Louis, MO 63110 USA.
[Teramo, Kari A.] Univ Helsinki, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland.
[Muglia, Louis J.] Univ Cincinnati, Coll Med, Perinatal Inst, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Muglia, Louis J.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH 45229 USA.
[Feenstra, Bjarke; Geller, Frank; Boyd, Heather A.; Melbye, Mads] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen S, Denmark.
[Marazita, Mary L.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15219 USA.
RP Murray, JC (reprint author), Univ Iowa, Dept Anat & Cell Biol, Iowa City, IA 52242 USA.
EM jeff-murray@uiowa.edu
OI Feenstra, Bjarke/0000-0003-1478-649X
FU National Institutes of Health [R01 HD052953, HD57192, Z01 ES040007, Z01
ES045002]; March of Dimes Foundation [FY2006-575, FY2008-260,
21-FY07-597]
FX We thank, in particular, the families that participated in this study
and we are ever grateful for the clinical care provided by our
colleagues that allowed those families to be enrolled. The research
nurses Susan Berends, Gretchen Cress, Karen Johnson, Laura Knosp, Nancy
Krutzfield, Silvina Arganaraz, Mirta Gladys Leguizamon, Mercedes Lopez,
Marta Padilla, and Azucena Singh were essential in contacting, enrolling
and sampling families. Kristin Orr, Cara Zimmerman, Keegan Kelsey, Marla
K. Johnson, and Tamara Busch were integral in sample organization or
testing. We acknowledge Elizabeth Leslie for her help in obtaining the
1000GP data as well as her input on the analysis of the reference
sequence data. Susie McConnell, Dan Benton, Erin Brothers-Smith, and
Nancy Davin were essential in administration. The authors would like to
thank the NHLBI GO Exome Sequencing Project and its ongoing studies
which produced and provided exome variant calls for comparison: the Lung
GO Sequencing Project (HL-102923), the WHI Sequencing Project
(HL-102924), the Broad GO Sequencing Project (HL-102925), the Seattle GO
Sequencing Project (HL-102926) and the Heart GO Sequencing Project
(HL-103010). This work was supported by the National Institutes of
Health [R01 HD052953 and HD57192 to J.C.M., Z01 ES040007 and Z01
ES045002 to M.S.]; and the March of Dimes Foundation [FY2006-575 and
FY2008-260 to J.C.M., 21-FY07-597 to L.J.M.].
NR 41
TC 11
Z9 11
U1 0
U2 11
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2350
J9 BMC MED GENET
JI BMC Med. Genet.
PD JUL 26
PY 2013
VL 14
AR 77
DI 10.1186/1471-2350-14-77
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 196RU
UT WOS:000322794400001
PM 23889750
ER
PT J
AU Raman, FS
Kawel-Boehm, N
Gai, N
Freed, M
Han, J
Liu, CY
Lima, JAC
Bluemke, DA
Liu, ST
AF Raman, Fabio S.
Kawel-Boehm, Nadine
Gai, Neville
Freed, Melanie
Han, Jing
Liu, Chia-Ying
Lima, Joao A. C.
Bluemke, David A.
Liu, Songtao
TI Modified look-locker inversion recovery T1 mapping indices: assessment
of accuracy and reproducibility between magnetic resonance scanners
SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
LA English
DT Article
DE T1 mapping; Partition coefficient (lambda); Extracellular volume
fraction (ECV); Diffuse myocardial fibrosis; Modified look-locker with
inversion recovery (MOLLI)
ID DIFFUSE MYOCARDIAL FIBROSIS; EXTRACELLULAR VOLUME FRACTION;
INTRAINDIVIDUAL ASSESSMENT; GD-DTPA; VALIDATION; HEART; CMR;
QUANTIFICATION; ASSOCIATION; RELAXATION
AB Background: Cardiovascular magnetic resonance (CMR) T1 mapping indices, such as T1 time and partition coefficient (lambda), have shown potential to assess diffuse myocardial fibrosis. The purpose of this study was to investigate how scanner and field strength variation affect the accuracy and precision/reproducibility of T1 mapping indices.
Methods: CMR studies were performed on two 1.5T and three 3T scanners. Eight phantoms were made to mimic the T1/T2 of pre- and post-contrast myocardium and blood at 1.5T and 3T. T1 mapping using MOLLI was performed with simulated heart rate of 40-100 bpm. Inversion recovery spin echo (IR-SE) was the reference standard for T1 determination. Accuracy was defined as the percent error between MOLLI and IR-SE, and scan/re-scan reproducibility was defined as the relative percent mean difference between repeat MOLLI scans. Partition coefficient was estimated by Delta R1myocardium phantom/Delta R1blood phantom. Generalized linear mixed model was used to compare the accuracy and precision/reproducibility of T1 and lambda across field strength, scanners, and protocols.
Results: Field strength significantly affected MOLLI T1 accuracy (6.3% error for 1.5T vs. 10.8% error for 3T, p<0.001) but not lambda accuracy (8.8% error for 1.5T vs. 8.0% error for 3T, p=0.11). Partition coefficients of MOLLI were not different between two 1.5T scanners (47.2% vs. 47.9%, p=0.13), and showed only slight variation across three 3T scanners (49.2% vs. 49.8% vs. 49.9%, p=0.016). Partition coefficient also had significantly lower percent error for precision (better scan/re-scan reproducibility) than measurement of individual T1 values (3.6% for lambda vs. 4.3%-4.8% for T1 values, approximately, for pre/post blood and myocardium values).
Conclusion: Based on phantom studies, T1 errors using MOLLI ranged from 6-14% across various MR scanners while errors for partition coefficient were less (6-10%). Compared with absolute T1 times, partition coefficient showed less variability across platforms and field strengths as well as higher precision.
C1 [Raman, Fabio S.; Kawel-Boehm, Nadine; Gai, Neville; Liu, Chia-Ying; Bluemke, David A.; Liu, Songtao] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Kawel-Boehm, Nadine] Univ Basel Hosp, Clin Radiol & Nucl Med, CH-4031 Basel, Switzerland.
[Freed, Melanie] NYU, Sch Med, New York, NY USA.
[Han, Jing] US FDA, Rockville, MD 20857 USA.
[Lima, Joao A. C.] Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD USA.
[Bluemke, David A.; Liu, Songtao] Natl Inst Biomed Imaging & Bioengn, Mol Biomed Imaging Lab, Bethesda, MD USA.
RP Liu, ST (reprint author), NIH, Ctr Clin, 10 Ctr Dr,MSC 1182, Bethesda, MD 20892 USA.
EM songtao.liu@nih.gov
OI Bluemke, David/0000-0002-8323-8086
FU National Institutes of Health (NIH) Intramural program
FX Funded by the National Institutes of Health (NIH) Intramural program.
NR 38
TC 25
Z9 25
U1 0
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1097-6647
J9 J CARDIOVASC MAGN R
JI J. Cardiov. Magn. Reson.
PD JUL 26
PY 2013
VL 15
AR 64
DI 10.1186/1532-429X-15-64
PG 10
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 193QA
UT WOS:000322574500001
PM 23890156
ER
PT J
AU Galon, J
Angell, HK
Bedognetti, D
Marincola, FM
AF Galon, Jerome
Angell, Helen K.
Bedognetti, Davide
Marincola, Francesco M.
TI The Continuum of Cancer Immunosurveillance: Prognostic, Predictive, and
Mechanistic Signatures
SO IMMUNITY
LA English
DT Review
ID CHRONIC HEPATITIS-C; COMPREHENSIVE GENOMIC CHARACTERIZATION;
TUMOR-INFILTRATING LYMPHOCYTES; ACUTE ALLOGRAFT-REJECTION; SEROUS
OVARIAN-CANCER; VERSUS-HOST-DISEASE; GENE-EXPRESSION; COLORECTAL-CANCER;
BREAST-CANCER; METASTATIC MELANOMA
AB Numerous analyses of large patient cohorts identified specific patterns of immune activation associated with patient survival. We established these as the immune contexture, encompassing the type, functional orientation, density, and location of adaptive immune cells within distinct tumor regions. Based on the immune contexture, a standardized, powerful immune stratification system, the Immunoscore, was delineated. The immune contexture is characterized by immune signatures also observed in association with the broader phenomenon of immune-mediated, tissue-specific destruction. We defined these as the immunologic constant of rejection. Predictive, prognostic, and mechanistic immune signatures overlap, and a continuum of intratumor immune reactions exists. The balance between tumor cell growth and elimination may be tipped upon a crescendo induced by immune manipulations aimed at enhancing naturally occurring immunosurveillance. Here, we propose a broader immunological interpretation of these three concepts-immune contexture, Immunoscore, and immunologic constant of rejection-that segregates oncogenic processes independently of their tissue origin.
C1 [Galon, Jerome; Angell, Helen K.] INSERM, Lab Integrat Canc Immunol, U872, F-75006 Paris, France.
[Galon, Jerome; Angell, Helen K.] Univ Paris 05, F-75006 Paris, France.
[Galon, Jerome; Angell, Helen K.] Univ Paris 06, Ctr Rech Cordeliers, F-75006 Paris, France.
[Bedognetti, Davide; Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Bedognetti, Davide; Marincola, Francesco M.] NIH, Trans NIH Ctr Human Immunol, Bethesda, MD 20892 USA.
[Marincola, Francesco M.] Sidra Med & Res Ctr, Res Branch, Doha, Qatar.
RP Galon, J (reprint author), INSERM, Lab Integrat Canc Immunol, U872, F-75006 Paris, France.
EM jerome.galon@crc.jussieu.fr; fmarincola@sidra.org
OI Bedognetti, Davide/0000-0002-5857-773X
FU Institut National du Cancer (INCa); INSERM; MedImmune; Qatar National
Research Fund under its National Priorities Research Program
[NPRP09-1174-3-291]; European Commission (7FP, Geninca Consortium)
[202230]; Cancer Research for Personalized Medicine (CARPEM);
Canceropole Ile-de-France; Paris Alliance of Cancer Research Institutes
(PACRI); LabEx Immuno-Oncology; Intramural Research Program of the
National Institutes of Health; Conquer Cancer Foundation of the American
Society of Clinical Oncology
FX We acknowledge all the scientists who made contributions to the area of
research reviewed here that were not cited due to space constraints.
J.G. and H. A. thank the members of the Laboratory of Integrative Cancer
Immunology for their invaluable contribution. The work performed in the
Laboratory of Integrative Cancer Immunology was supported by grants from
the Institut National du Cancer (INCa), INSERM, MedImmune, the Qatar
National Research Fund under its National Priorities Research Program
award number NPRP09-1174-3-291, the European Commission (7FP, Geninca
Consortium, grant 202230), Cancer Research for Personalized Medicine
(CARPEM), Canceropole Ile-de-France, the Paris Alliance of Cancer
Research Institutes (PACRI), and the LabEx Immuno-Oncology. D. B. and F.
M. M thank Ena Wang (Infectious Diseases and Immunogenetics Section) for
her outstanding contribution in the field. The work performed in the
Infectious Diseases and Immunogenetics Section was supported by the
Intramural Research Program of the National Institutes of Health. D.B.'s
research was supported by the Conquer Cancer Foundation of the American
Society of Clinical Oncology (2011 Young Investigator Award).
NR 145
TC 180
Z9 181
U1 6
U2 51
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
EI 1097-4180
J9 IMMUNITY
JI Immunity
PD JUL 25
PY 2013
VL 39
IS 1
BP 11
EP 26
DI 10.1016/j.immuni.2013.07.008
PG 16
WC Immunology
SC Immunology
GA AA2TZ
UT WOS:000330948300002
PM 23890060
ER
PT J
AU Roschewski, M
Korde, N
Wu, SP
Landgren, O
AF Roschewski, Mark
Korde, Neha
Wu, S. Peter
Landgren, Ola
TI Pursuing the curative blueprint for early myeloma
SO BLOOD
LA English
DT Article
ID UNDETERMINED SIGNIFICANCE MGUS; ASYMPTOMATIC MULTIPLE-MYELOMA; STEM-CELL
TRANSPLANTATION; FREE LIGHT-CHAIN; MONOCLONAL GAMMOPATHY;
FLOW-CYTOMETRY; RISK-FACTORS; PROGRESSION; SURVIVAL; THERAPY
AB Treatment philosophies in multiple myeloma (MM) debate the relative merits of achieving the deepest possible remissions ("curative" doctrine) vs sequential delivery of antimyeloma agents ("control" doctrine). In this paper, we highlight the relevant strengths of each doctrine in the context of modern patient selection strategies, fresh biological insights on MM pathogenesis, agents with improved safety profiles, and emerging molecular and imaging tools. Paramount fundamental questions remain unanswered that require an intense research focus as we pursue a cure for this devastating disease.
C1 [Roschewski, Mark; Korde, Neha; Wu, S. Peter; Landgren, Ola] NCI, Multiple Myeloma Sect, Ctr Canc Res, Metab Branch,NIH, Bethesda, MD 20892 USA.
RP Landgren, O (reprint author), NCI, Multiple Myeloma Sect, Ctr Canc Res, Metab Branch,NIH, 9000 Rockville Pike,Bldg 10,Room 13N240, Bethesda, MD 20892 USA.
EM landgreo@mail.nih.gov
OI Roschewski, Mark/0000-0003-0278-2635
FU National Institutes of Health
FX This work was supported by the intramural research program of the
National Institutes of Health.
NR 30
TC 10
Z9 10
U1 0
U2 2
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 JUL 25
PY 2013
VL 122
IS 4
BP 486
EP 490
DI 10.1182/blood-2013-01-481291
PG 5
WC Hematology
SC Hematology
GA 196RD
UT WOS:000322792300008
PM 23782936
ER
PT J
AU Xiao, TS
Fitzgerald, KA
AF Xiao, T. Sam
Fitzgerald, Katherine A.
TI The cGAS-STING Pathway for DNA Sensing
SO MOLECULAR CELL
LA English
DT Review
ID CYCLIC DI-GMP; CYTOSOLIC DNA; IMMUNE-RESPONSE; AMP SYNTHASE;
2ND-MESSENGER; RECOGNITION; ADAPTER; DINUCLEOTIDE; REVEALS; SENSOR
AB The nucleotidyl transferase cGAS, its second-messenger product cGAMP, and the cGAMP sensor STING form the basic mechanism of DNA sensing in the cytoplasm of mammalian cells. Several new reports now uncover key structural features associated with DNA recognition by cGAS and the catalytic mechanisms of cGAMP generation. Concurrent studies also reveal unique phosphodiester linkages in endogenous cGAMP that distinguish it from microbial cGAMP and other cyclic dinucleotides. Together, these studies provide a new perspective on DNA recognition in the innate immune system.
C1 [Xiao, T. Sam] NIAID, Struct Immunobiol Unit, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Fitzgerald, Katherine A.] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01655 USA.
RP Fitzgerald, KA (reprint author), Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01655 USA.
EM kate.fitzgerald@umassmed.edu
RI Xiao, Tsan/I-7616-2013; Xiao, Tsan/A-8590-2010
OI Xiao, Tsan/0000-0001-9688-475X;
FU Intramural NIH HHS [ZIA AI000960-07]; NIAID NIH HHS [R56 AI067497, R01
AI093752]
NR 28
TC 44
Z9 47
U1 4
U2 37
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD JUL 25
PY 2013
VL 51
IS 2
BP 135
EP 139
DI 10.1016/j.molcel.2013.07.004
PG 5
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 191PD
UT WOS:000322424200003
PM 23870141
ER
PT J
AU Paoletta, S
Tosh, DK
Finley, A
Gizewski, ET
Moss, SM
Gao, ZG
Auchampach, JA
Salvemini, D
Jacobson, KA
AF Paoletta, Silvia
Tosh, Dilip K.
Finley, Amanda
Gizewski, Elizabeth T.
Moss, Steven M.
Gao, Zhan-Guo
Auchampach, John A.
Salvemini, Daniela
Jacobson, Kenneth A.
TI Rational Design of Sulfonated A(3) Adenosine Receptor-Selective
Nucleosides as Pharmacological Tools To Study Chronic Neuropathic Pain
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID CRYSTAL-STRUCTURE; A3 RECEPTOR; AGONISTS; A(2A); DERIVATIVES;
ANTAGONISTS; POTENT; LIGANDS; BINDING; RAT
AB (N)-Methanocarba(bicyclo[3.1.0]hexane)adenosine derivatives were probed for sites of charged sulfonate substitution, which precludes diffusion across biological membranes, e.g., blood-brain barrier. Molecular modeling predicted that sulfonate groups on C2-phenylethynyl substituents would provide high affinity at both mouse (m) and human (h) A(3) adenosine receptors (ARs), while a N-6-p-sulfophenylethyl substituent would determine higher hA(3)AR vs mA(3)AR affinity. These modeling predictions, based on steric fitting of the binding cavity and crucial interactions with key residues, were confirmed by binding/efficacy studies of synthesized sulfonates. N-6-3-Chlorobenzyl-2-(3-sulfophenylethynyl) derivative 7 (MRS5841) bound selectively to h/m A(3)ARs (K-i(hA(3)AR) = 1.9 nM) as agonist, while corresponding p-sulfo isomer 6 (MRS5701) displayed mixed A(1)/A(3)AR agonism. Both nucleosides administered ip reduced mouse chronic neuropathic pain that was ascribed to either A(3)AR or A(1)/A(3)AR using A(3)AR genetic deletion. Thus, rational design methods based on A(3)AR homology models successfully predicted sites for sulfonate incorporation, for delineating adenosine's CNS vs peripheral actions.
C1 [Paoletta, Silvia; Tosh, Dilip K.; Moss, Steven M.; Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Finley, Amanda; Salvemini, Daniela] St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, St Louis, MO 63104 USA.
[Gizewski, Elizabeth T.; Auchampach, John A.] Med Coll Wisconsin, Dept Pharmacol, Milwaukee, WI 53226 USA.
RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU National Institutes of Health (Intramural Research Program of the
NIDDK); National Institutes of Health [R01HL077707]
FX We thank Dr. John Lloyd and Dr. Noel Whittaker (NIDDK) for mass spectral
determinations. This research was supported by the National Institutes
of Health (Intramural Research Program of the NIDDK and Grant
R01HL077707).
NR 59
TC 17
Z9 17
U1 0
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD JUL 25
PY 2013
VL 56
IS 14
BP 5949
EP 5963
DI 10.1021/jm4007966
PG 15
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 192RM
UT WOS:000322503000025
PM 23789857
ER
PT J
AU Prado-Martinez, J
Sudmant, PH
Kidd, JM
Li, H
Kelley, JL
Lorente-Galdos, B
Veeramah, KR
Woerner, AE
O'Connor, TD
Santpere, G
Cagan, A
Theunert, C
Casals, F
Laayouni, H
Munch, K
Hobolth, A
Halager, AE
Malig, M
Hernandez-Rodriguez, J
Hernando-Herraez, I
Prufer, K
Pybus, M
Johnstone, L
Lachmann, M
Alkan, C
Twigg, D
Petit, N
Baker, C
Hormozdiari, F
Fernandez-Callejo, M
Dabad, M
Wilson, ML
Stevison, L
Camprubi, C
Carvalho, T
Ruiz-Herrera, A
Vives, L
Mele, M
Abello, T
Kondova, I
Bontrop, RE
Pusey, A
Lankester, F
Kiyang, JA
Bergl, RA
Lonsdorf, E
Myers, S
Ventura, M
Gagneux, P
Comas, D
Siegismund, H
Blanc, J
Agueda-Calpena, L
Gut, M
Fulton, L
Tishkoff, SA
Mullikin, JC
Wilson, RK
Gut, IG
Gonder, MK
Ryder, OA
Hahn, BH
Navarro, A
Akey, JM
Bertranpetit, J
Reich, D
Mailund, T
Schierup, MH
Hvilsom, C
Andres, AM
Wall, JD
Bustamante, CD
Hammer, MF
Eichler, EE
Marques-Bonet, T
AF Prado-Martinez, Javier
Sudmant, Peter H.
Kidd, Jeffrey M.
Li, Heng
Kelley, Joanna L.
Lorente-Galdos, Belen
Veeramah, Krishna R.
Woerner, August E.
O'Connor, Timothy D.
Santpere, Gabriel
Cagan, Alexander
Theunert, Christoph
Casals, Ferran
Laayouni, Hafid
Munch, Kasper
Hobolth, Asger
Halager, Anders E.
Malig, Maika
Hernandez-Rodriguez, Jessica
Hernando-Herraez, Irene
Pruefer, Kay
Pybus, Marc
Johnstone, Laurel
Lachmann, Michael
Alkan, Can
Twigg, Dorina
Petit, Natalia
Baker, Carl
Hormozdiari, Fereydoun
Fernandez-Callejo, Marcos
Dabad, Marc
Wilson, Michael L.
Stevison, Laurie
Camprubi, Cristina
Carvalho, Tiago
Ruiz-Herrera, Aurora
Vives, Laura
Mele, Marta
Abello, Teresa
Kondova, Ivanela
Bontrop, Ronald E.
Pusey, Anne
Lankester, Felix
Kiyang, John A.
Bergl, Richard A.
Lonsdorf, Elizabeth
Myers, Simon
Ventura, Mario
Gagneux, Pascal
Comas, David
Siegismund, Hans
Blanc, Julie
Agueda-Calpena, Lidia
Gut, Marta
Fulton, Lucinda
Tishkoff, Sarah A.
Mullikin, James C.
Wilson, Richard K.
Gut, Ivo G.
Gonder, Mary Katherine
Ryder, Oliver A.
Hahn, Beatrice H.
Navarro, Arcadi
Akey, Joshua M.
Bertranpetit, Jaume
Reich, David
Mailund, Thomas
Schierup, Mikkel H.
Hvilsom, Christina
Andres, Aida M.
Wall, Jeffrey D.
Bustamante, Carlos D.
Hammer, Michael F.
Eichler, Evan E.
Marques-Bonet, Tomas
TI Great ape genetic diversity and population history
SO NATURE
LA English
DT Article
ID HUMAN GENOME; CHIMPANZEE GENOME; SEQUENCE; EVOLUTION; SELECTION;
PATTERNS; DECLINE
AB Most great ape genetic variation remains uncharacterized(1,2); however, its study is critical for understanding population history(3-6), recombination(7), selection(8) and susceptibility to disease(9,10). Here we sequence to high coverage a total of 79 wild-and captive-born individuals representing all six great ape species and seven subspecies and report 88.8 million single nucleotide polymorphisms. Our analysis provides support for genetically distinct populations within each species, signals of gene flow, and the split of common chimpanzees into two distinct groups: Nigeria-Cameroon/western and central/eastern populations. We find extensive inbreeding in almost all wild populations, with eastern gorillas being the most extreme. Inferred effective population sizes have varied radically over time in different lineages and this appears to have a profound effect on the genetic diversity at, or close to, genes in almost all species. We discover and assign 1,982 loss-of-function variants throughout the human and great ape lineages, determining that the rate of gene loss has not been different in the human branch compared to other internal branches in the great ape phylogeny. This comprehensive catalogue of great ape genome diversity provides a framework for understanding evolution and a resource for more effective management of wild and captive great ape populations.
C1 [Prado-Martinez, Javier; Lorente-Galdos, Belen; Santpere, Gabriel; Casals, Ferran; Laayouni, Hafid; Hernandez-Rodriguez, Jessica; Hernando-Herraez, Irene; Pybus, Marc; Petit, Natalia; Fernandez-Callejo, Marcos; Dabad, Marc; Carvalho, Tiago; Mele, Marta; Comas, David; Navarro, Arcadi; Bertranpetit, Jaume; Marques-Bonet, Tomas] Univ Pompeu Fabra, Inst Biol Evolut, CSIC, PRBB, Barcelona 08003, Catalonia, Spain.
[Sudmant, Peter H.; O'Connor, Timothy D.; Malig, Maika; Baker, Carl; Hormozdiari, Fereydoun; Vives, Laura; Akey, Joshua M.; Eichler, Evan E.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Kidd, Jeffrey M.; Twigg, Dorina] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Kidd, Jeffrey M.; Kelley, Joanna L.; Bustamante, Carlos D.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
[Li, Heng; Reich, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Veeramah, Krishna R.; Woerner, August E.; Johnstone, Laurel; Hammer, Michael F.] Univ Arizona, Div Biotechnol, Arizona Res Labs, Tucson, AZ 85721 USA.
[Cagan, Alexander; Theunert, Christoph; Pruefer, Kay; Lachmann, Michael; Andres, Aida M.] Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, D-04103 Leipzig, Germany.
[Munch, Kasper; Hobolth, Asger; Halager, Anders E.; Mailund, Thomas; Schierup, Mikkel H.] Aarhus Univ, Bioinformat Res Ctr, DK-8000 Aarhus C, Denmark.
[Alkan, Can] Bilkent Univ, Fac Engn, TR-06800 Ankara, Turkey.
[Wilson, Michael L.] Univ Minnesota, Dept Anthropol, Minneapolis, MN 55455 USA.
[Stevison, Laurie; Wall, Jeffrey D.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
[Camprubi, Cristina; Ruiz-Herrera, Aurora] Univ Autonoma Barcelona, Dept Biol Cellular Fisiol & Immunol, Cerdanyola Del Valles 08193, Catalonia, Spain.
[Ruiz-Herrera, Aurora] Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Cerdanyola Del Valles 08193, Catalonia, Spain.
[Abello, Teresa] Parc Zool Barcelona, Barcelona 08003, Catalonia, Spain.
[Kondova, Ivanela; Bontrop, Ronald E.] Biomed Primate Res Ctr, NL-2280 GH Rijswijk, Netherlands.
[Pusey, Anne] Duke Univ, Dept Evolutionary Anthropol, Durham, NC 27708 USA.
[Lankester, Felix; Kiyang, John A.] Limbe Wildlife Ctr, Limbe, Cameroon.
[Lankester, Felix] Washington State Univ, Paul G Allen Sch Global Anim Hlth, Pullman, WA 99164 USA.
[Bergl, Richard A.] North Carolina Zool Pk, Asheboro, NC 27205 USA.
[Lonsdorf, Elizabeth] Franklin & Marshall Coll, Dept Psychol, Lancaster, PA 17604 USA.
[Myers, Simon] Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
[Ventura, Mario] Univ Bari, Dept Genet & Microbiol, I-70126 Bari, Italy.
[Gagneux, Pascal] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
[Siegismund, Hans; Hvilsom, Christina] Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark.
[Blanc, Julie; Agueda-Calpena, Lidia; Gut, Marta; Gut, Ivo G.] PCB, Ctr Nacl Anal Genom CNAG, Barcelona 08028, Catalonia, Spain.
[Fulton, Lucinda; Wilson, Richard K.] Washington Univ, Sch Med, Genome Sequencing Ctr, St Louis, MO 63108 USA.
[Tishkoff, Sarah A.] Univ Penn, Dept Biol & Genet, Philadelphia, PA 19104 USA.
[Mullikin, James C.] NIH, Intramural Sequencing Ctr NISC, Bethesda, MD 20892 USA.
[Gonder, Mary Katherine] SUNY Albany, Albany, NY 12222 USA.
[Ryder, Oliver A.] San Diego Zoo, Genet Div, Inst Conservat Res, Escondido, CA 92027 USA.
[Hahn, Beatrice H.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Hahn, Beatrice H.] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Navarro, Arcadi] UPF, Inst Nacl Bioinformat, Barcelona 08003, Catalonia, Spain.
[Navarro, Arcadi; Marques-Bonet, Tomas] ICREA, Barcelona 08010, Catalonia, Spain.
[Schierup, Mikkel H.] Aarhus Univ, Dept Biosci, DK-8000 Aarhus C, Denmark.
[Hvilsom, Christina] Copenhagen Zoo, DK-2000 Frederiksberg, Denmark.
[Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
RP Marques-Bonet, T (reprint author), Univ Pompeu Fabra, Inst Biol Evolut, CSIC, PRBB, Doctor Aiguader 88, Barcelona 08003, Catalonia, Spain.
EM eee@gs.washington.edu; tomas.marques@upf.edu
RI Dabad, Marc/M-9522-2015; Ruiz-Herrera, Aurora/K-3728-2012; Munch,
Kasper/A-1434-2010; Myers, Simon/A-6792-2015; Casals,
Ferran/H-4347-2015; Bontrop, Ronald/J-3628-2012; Alkan, Can/D-2982-2009;
Andres, Aida/B-4088-2014; Comas, David/D-5382-2014; Bertranpetit,
Jaume/F-8550-2012; Navarro, Arcadi/F-1592-2011; Marques-Bonet,
Tomas/I-4618-2014; Santpere, Gabriel/I-9437-2014; Siegismund, Hans
R./K-4332-2014; Schierup, Mikkel/F-1675-2010
OI Carvalho, Tiago/0000-0002-8943-8732; Hernandez-Rodriguez,
Jessica/0000-0002-0402-286X; Kelley, Joanna/0000-0002-7731-605X;
Laayouni, Hafid/0000-0003-1297-5078; Ventura, Mario/0000-0001-7762-8777;
Hobolth, Asger/0000-0003-4056-1286; Dabad, Marc/0000-0002-6094-747X;
Ruiz-Herrera, Aurora/0000-0003-3868-6151; Kidd,
Jeffrey/0000-0002-9631-1465; Lorente-Galdos, Belen/0000-0001-5390-2452;
Prado-Martinez, Javier/0000-0001-5402-2721; Cagan,
Alex/0000-0002-7857-4771; Sudmant, Peter/0000-0002-9573-8248; Mailund,
Thomas/0000-0001-6206-9239; Munch, Kasper/0000-0003-2880-6252; Myers,
Simon/0000-0002-2585-9626; Casals, Ferran/0000-0002-8941-0369; Bontrop,
Ronald/0000-0003-0874-6467; Alkan, Can/0000-0002-5443-0706; Andres,
Aida/0000-0002-8590-9672; Comas, David/0000-0002-5075-0956;
Bertranpetit, Jaume/0000-0003-0100-0590; Navarro,
Arcadi/0000-0003-2162-8246; Marques-Bonet, Tomas/0000-0002-5597-3075;
Santpere, Gabriel/0000-0001-5909-8637; Siegismund, Hans
R./0000-0001-5757-3131; Schierup, Mikkel/0000-0002-5028-1790
FU ERC [260372]; NIH [HG002385, R01_HG005226, GM100233]; NSF HOMINID
[1032255]; MICINN(Spain) [BFU2011-28549, BFU2010-19443]; Spanish
Government; FEDER [BFU2009-13409-C02-02, BFU2012-38236]; Direccio
General de Recerca, Generalitat de Catalunya [2009 SGR 1101]; ERC
Advanced Grant [233297]; Max Planck Society; Danish Council for
Independent Research Natural Sciences; Zoo de Barcelona (Beca PRIC);
EUPRIM-Net; NSF [0755823]; G. Harold and Leila Y. Mathers Foundation;
HHMI; [CGL-2010-20170]; [DP1ES022577-04 NIH]
FX We thank the following funding agencies: ERC Starting Grant (260372) to
T.M.-B.; NIH grants HG002385 to E. E. E., R01_HG005226 to K. R. V., A.
E. W., M. F. H., L. S. and J.D.W., GM100233 and NSF HOMINID grant
1032255 to D. R. and He.Li.; MICINN(Spain) BFU2011-28549to T.M.-B.,
BFU2010-19443to Ja.Be., Spanish Government and FEDER for grants
BFU2009-13409-C02-02 and BFU2012-38236 to A.N. and J.P.-M., Direccio
General de Recerca, Generalitat de Catalunya (Grup de Recerca Consolidat
2009 SGR 1101) to Ja.Be., D. C., A.N. and T.M.-B.; ERC Advanced Grant
(233297) and Max Planck Society to S. Paabo; Danish Council for
Independent Research Natural Sciences to H. S.; Spanish Grant
(CGL-2010-20170) and Zoo de Barcelona (Beca PRIC) to A. R.-H.;
EUPRIM-Net to BPRC; DP1ES022577-04 NIH grant to S. A. T.; NSF Grant
0755823 to M. K. G.; P. G. is supported by the G. Harold and Leila Y.
Mathers Foundation. A. N. and T. M.-B. are ICREA Research Investigators
(Institut Catala d'Estudis i RecercaAvancats delaGeneralitat de
Catalunya). J. P.-M. is supported by the Zoo de Barcelona and
l'Ajuntament de Barcelona. P. H. S. is supported by an HHMI
International Student Fellowship. E. E. E. is an investigator with the
Howard Hughes Medical Institute. We are especially grateful to all those
who generously provided the samples for the project: O. Thalmann and H.
Siedel from Limbe Sanctuary; R. Garriga from Tacugama Sanctuary; W.
Schempp (University of Freiburg), Burgers' Zoo; Zoo of Antwerp; Wilhelma
Zoo; Givskud Zoo; Ngamba Island Chimpanzee Sanctuary and Centre de
Primatologie; Centre International de Recherches Medicales de
Franceville; North Carolina Zoological Park; Zoo Atlanta; the Lincoln
Park Zoo (Chicago); the Antwerp Zoo and the Limbe Wildlife Centre
(Cameroon); D. Travis from University of Minnesota and M. Kinsel from
University of Illinois Urbana-Champaign and S. Paabo and L. Vigilant,
Max Planck Institute for Evolutionary Anthropology. We thank T. Brown
for revising the manuscript, L. Capilla and E. Eyras for technical
support, and M. Dierssen for comments on genes expressed in the brain.
NR 30
TC 189
Z9 190
U1 29
U2 236
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 25
PY 2013
VL 499
IS 7459
BP 471
EP 475
DI 10.1038/nature12228
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187YP
UT WOS:000322157900039
PM 23823723
ER
PT J
AU Gameiro, SR
Higgins, JP
Dreher, MR
Woods, DL
Reddy, G
Wood, BJ
Guha, C
Hodge, JW
AF Gameiro, Sofia R.
Higgins, Jack P.
Dreher, Matthew R.
Woods, David L.
Reddy, Goutham
Wood, Bradford J.
Guha, Chandan
Hodge, James W.
TI Combination Therapy with Local Radiofrequency Ablation and Systemic
Vaccine Enhances Antitumor Immunity and Mediates Local and Distal Tumor
Regression
SO PLOS ONE
LA English
DT Article
ID HUMAN CARCINOEMBRYONIC ANTIGEN; COLORECTAL LIVER METASTASES; CYTOTOXIC
T-LYMPHOCYTES; HEPATOCELLULAR-CARCINOMA; CANCER CELLS; FOCUSED
ULTRASOUND; RANDOMIZED-TRIAL; PROSTATE-CANCER; KILLER-CELLS; RADIATION
AB Purpose: Radiofrequency ablation (RFA) is a minimally invasive energy delivery technique increasingly used for focal therapy to eradicate localized disease. RFA-induced tumor-cell necrosis generates an immunogenic source of tumor antigens known to induce antitumor immune responses. However, RFA-induced antitumor immunity is insufficient to control metastatic progression. We sought to characterize (a) the role of RFA dose on immunogenic modulation of tumor and generation of immune responses and (b) the potential synergy between vaccine immunotherapy and RFA aimed at local tumor control and decreased systemic progression.
Experimental Design: Murine colon carcinoma cells expressing the tumor-associated (TAA) carcinoembryonic antigen (CEA) (MC38-CEA(+)) were studied to examine the effect of sublethal hyperthermia in vitro on the cells' phenotype and sensitivity to CTL-mediated killing. The effect of RFA dose was investigated in vivo impacting (a) the phenotype and growth of MC38-CEA(+) tumors and (b) the induction of tumor-specific immune responses. Finally, the molecular signature was evaluated as well as the potential synergy between RFA and poxviral vaccines expressing CEA and a TRIad of COstimulatory Molecules (CEA/TRICOM).
Results: In vitro, sublethal hyperthermia of MC38-CEA(+) cells (a) increased cell-surface expression of CEA, Fas, and MHC class I molecules and (b) rendered tumor cells more susceptible to CTL-mediated lysis. In vivo, RFA induced (a) immunogenic modulation on the surface of tumor cells and (b) increased T-cell responses to CEA and additional TAAs. Combination therapy with RFA and vaccine in CEA-transgenic mice induced a synergistic increase in CD4(+) T-cell immune responses to CEA and eradicated both primary CEA(+) and distal CEA(-) s.c. tumors. Sequential administration of low-dose and high-dose RFA with vaccine decreased tumor recurrence compared to RFA alone. These studies suggest a potential clinical benefit in combining RFA with vaccine in cancer patients, and augment support for this novel translational paradigm.
C1 [Gameiro, Sofia R.; Higgins, Jack P.; Hodge, James W.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Dreher, Matthew R.; Woods, David L.; Reddy, Goutham; Wood, Bradford J.] NIH, Ctr Intervent Oncol Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Guha, Chandan] Albert Einstein Coll Med, Dept Radiat Oncol, Montefiore Med Ctr, New York, NY USA.
RP Hodge, JW (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM jh241d@nih.gov
RI Hodge, James/D-5518-2015
OI Hodge, James/0000-0001-5282-3154
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX This research was supported by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 64
TC 26
Z9 27
U1 0
U2 17
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 24
PY 2013
VL 8
IS 7
AR e70417
DI 10.1371/journal.pone.0070417
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 188BY
UT WOS:000322167900127
PM 23894654
ER
PT J
AU Humerick, M
Hanson, J
Rodriguez-Canales, J
Lubelski, D
Rashid, OM
Salinas, YD
Shi, YJ
Ponzio, T
Fields, R
Emmert-Buck, MR
Gainer, H
AF Humerick, Madison
Hanson, Jeffrey
Rodriguez-Canales, Jaime
Lubelski, Daniel
Rashid, Omar M.
Salinas, Yasmmyn D.
Shi, YiJun
Ponzio, Todd
Fields, Raymond
Emmert-Buck, Michael R.
Gainer, Harold
TI Analysis of Transcription Factor mRNAs in Identified Oxytocin and
Vasopressin Magnocellular Neurons Isolated by Laser Capture
Microdissection
SO PLOS ONE
LA English
DT Article
ID GENE-EXPRESSION ANALYSIS; RAT SUPRAOPTIC NUCLEUS; REAL-TIME PCR;
HYPOTHALAMONEUROHYPOPHYSEAL SYSTEM; RIBONUCLEIC-ACIDS; TISSUE SAMPLES;
CELL-TYPES; BRAIN; NEUROPEPTIDE; HYBRIDIZATION
AB The oxytocin (Oxt) and vasopressin (Avp) magnocellular neurons (MCNs) in the hypothalamus are the only neuronal phenotypes that are present in the supraoptic nucleus (SON), and are characterized by their robust and selective expression of either the Oxt or Avp genes. In this paper, we take advantage of the differential expression of these neuropeptide genes to identify and isolate these two individual phenotypes from the rat SON by laser capture microdissection (LCM), and to analyze the differential expression of several of their transcription factor mRNAs by qRT-PCR. We identify these neuronal phenotypes by stereotaxically injecting recombinant Adeno-Associated Viral (rAAV) vectors which contain cell-type specific Oxt or Avp promoters that drive expression of EGFP selectively in either the Oxt or Avp MCNs into the SON. The fluorescent MCNs are then dissected by LCM using a novel Cap Road Map protocol described in this paper, and the purified MCNs are extracted for their RNAs. qRT-PCR of these RNAs show that some transcription factors (RORA and c-jun) are differentially expressed in the Oxt and Avp MCNs.
C1 [Humerick, Madison; Lubelski, Daniel; Rashid, Omar M.; Salinas, Yasmmyn D.; Shi, YiJun; Ponzio, Todd; Fields, Raymond; Gainer, Harold] NINDS, Lab Neurochem, NIH, Bethesda, MD 20892 USA.
[Hanson, Jeffrey; Rodriguez-Canales, Jaime; Emmert-Buck, Michael R.] NCI, Laser Microdissect Core, NIH, Bethesda, MD 20892 USA.
RP Gainer, H (reprint author), NINDS, Lab Neurochem, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM gainerh@ninds.nih.gov
OI Rodriguez-Canales, Jaime/0000-0002-0885-2377; Lubelski,
Daniel/0000-0002-9403-9509
FU NIH, NINDS
FX This research was supported by the Intramural Research Program of the
NIH, NINDS. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 57
TC 5
Z9 5
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 24
PY 2013
VL 8
IS 7
AR e69407
DI 10.1371/journal.pone.0069407
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 188BY
UT WOS:000322167900066
PM 23894472
ER
PT J
AU Zelner, JL
Lopman, BA
Hall, AJ
Ballesteros, S
Grenfell, BT
AF Zelner, Jonathan L.
Lopman, Benjamin A.
Hall, Aron J.
Ballesteros, Sebastien
Grenfell, Bryan T.
TI Linking Time-Varying Symptomatology and Intensity of Infectiousness to
Patterns of Norovirus Transmission
SO PLOS ONE
LA English
DT Article
AB Background: Norovirus (NoV) transmission may be impacted by changes in symptom intensity. Sudden onset of vomiting, which may cause an initial period of hyper-infectiousness, often marks the beginning of symptoms. This is often followed by: a 1-3 day period of milder symptoms, environmental contamination following vomiting, and post-symptomatic shedding that may result in transmission at progressively lower rates. Existing models have not included time-varying infectiousness, though representing these features could add utility to models of NoV transmission.
Methods: We address this by comparing the fit of three models (Models 1-3) of NoV infection to household transmission data from a 2009 point-source outbreak of GII. 12 norovirus in North Carolina. Model 1 is an SEIR compartmental model, modified to allow Gamma-distributed sojourn times in the latent and infectious classes, where symptomatic cases are uniformly infectious over time. Model 2 assumes infectiousness decays exponentially as a function of time since onset, while Model 3 is discontinuous, with a spike concentrating 50% of transmissibility at onset. We use Bayesian data augmentation techniques to estimate transmission parameters for each model, and compare their goodness of fit using qualitative and quantitative model comparison. We also assess the robustness of our findings to asymptomatic infections.
Results: We find that Model 3 (initial spike in shedding) best explains the household transmission data, using both quantitative and qualitative model comparisons. We also show that these results are robust to the presence of asymptomatic infections.
Conclusions: Explicitly representing explosive NoV infectiousness at onset should be considered when developing models and interventions to interrupt and prevent outbreaks of norovirus in the community. The methods presented here are generally applicable to the transmission of pathogens that exhibit large variation in transmissibility over an infection.
C1 [Zelner, Jonathan L.; Ballesteros, Sebastien; Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Lopman, Benjamin A.; Hall, Aron J.] Ctr Dis Control & Prevent, Epidemiol Branch, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA.
[Zelner, Jonathan L.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Zelner, JL (reprint author), Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
EM jzelner@princeton.edu
FU Fogarty International Center, National Institutes of Health; RAPIDD
program of the Science & Technology Directorate, Department of Homeland
Security; Bill and Melinda Gates Foundation
FX J. Zelner and B. Grenfell were supported by the RAPIDD program of the
Science & Technology Directorate, Department of Homeland Security and
the Fogarty International Center, National Institutes of Health. B
Grenfell and S. Ballesteros were supported by the Bill and Melinda Gates
Foundation. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 2
TC 5
Z9 5
U1 0
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 24
PY 2013
VL 8
IS 7
AR e68413
DI 10.1371/journal.pone.0068413
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 188BY
UT WOS:000322167900011
PM 23894302
ER
PT J
AU Malley, JD
Moore, JH
AF Malley, James D.
Moore, Jason H.
TI The disconnect between classical biostatistics and the biological data
mining community
SO BIODATA MINING
LA English
DT Editorial Material
C1 [Malley, James D.] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Moore, Jason H.] Dartmouth Coll, Dept Genet, Inst Quantitat Biomed Sci, Geisel Sch Med, Lebanon, NH 03756 USA.
[Moore, Jason H.] Dartmouth Coll, Dept Community & Family Med, Inst Quantitat Biomed Sci, Geisel Sch Med, Lebanon, NH 03756 USA.
RP Moore, JH (reprint author), Dartmouth Coll, Dept Genet, Inst Quantitat Biomed Sci, Geisel Sch Med, 1 Med Ctr Dr, Lebanon, NH 03756 USA.
EM jason.h.moore@dartmouth.edu
NR 4
TC 2
Z9 2
U1 0
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-0381
J9 BIODATA MIN
JI BioData Min.
PD JUL 24
PY 2013
VL 6
AR UNSP 12
DI 10.1186/1756-0381-6-12
PG 2
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA 209XC
UT WOS:000323792900001
PM 23880104
ER
PT J
AU Szyk, A
Piszczek, G
Roll-Mecak, A
AF Szyk, Agnieszka
Piszczek, Grzegorz
Roll-Mecak, Antonina
TI Tubulin Tyrosine Ligase and Stathmin Compete for Tubulin Binding In
Vitro
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE tubulin; microtubule dynamics; polymerization; tubulin tyrosine ligase;
stathmin
ID MICROTUBULES
AB Tubulin partition between soluble and polymeric forms is tightly regulated in cells. Stathmin and tubulin tyrosine ligase (TTL) each form stable complexes with tubulin and inhibit tubulin polymerization. Here we explore the mutual relationship between these proteins in vitro and demonstrate that full-length stathmin and TTL compete for binding to tubulin and fail to make a stable tubulin:stathmin TTL triple complex in solution. Moreover, stathmin depresses TTL tubulin tyrosination activity in vitro. These results suggest either that TTL and stathmin have a partially overlapping footprint on the tubulin dimer or that stathmin induces a tubulin conformation incompatible with stable TTL binding. Published by Elsevier Ltd.
C1 [Szyk, Agnieszka; Roll-Mecak, Antonina] NINDS, Cell Biol & Biophys Unit, Bethesda, MD 20892 USA.
[Piszczek, Grzegorz; Roll-Mecak, Antonina] NHLBI, Bethesda, MD 20892 USA.
RP Roll-Mecak, A (reprint author), NIH, Cell Biol & Biophys Unit, Porter Neurosci Res Ctr, Bldg 35,Room 3B-203,35 Convent Dr,MSC 3700, Bethesda, MD 20892 USA.
EM Antonina@mail.nih.gov
FU National Institutes of Health; Searle Scholars Program
FX We thank V. Kormendi (National Institutes of Health) for purifying
stathmin, M. Sirajuddin and R. Vale (University of California, San
Francisco) for the stathmin expression plasmid and A. Ferre-D'Amare and
S. Gottesman for useful discussions. This work was supported by the
intramural program of the National Institutes of Health and a grant to
A.R.-M. from the Searle Scholars Program.
NR 11
TC 6
Z9 8
U1 0
U2 11
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD JUL 24
PY 2013
VL 425
IS 14
BP 2412
EP 2414
DI 10.1016/j.jmb.2013.04.017
PG 3
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 182DV
UT WOS:000321722800003
PM 23624152
ER
PT J
AU Martin, KR
Kuh, D
Harris, TB
Guralnik, JM
Coggon, D
Wills, AK
AF Martin, Kathryn R.
Kuh, Diana
Harris, Tamara B.
Guralnik, Jack M.
Coggon, David
Wills, Andrew K.
TI Body mass index, occupational activity, and leisure-time physical
activity: an exploration of risk factors and modifiers for knee
osteoarthritis in the 1946 British birth cohort
SO BMC MUSCULOSKELETAL DISORDERS
LA English
DT Article
DE Knee osteoarthritis; Body mass index; Physical activity; Occupational
activity
ID HIP OSTEOARTHRITIS; NATIONAL-HEALTH; OLDER-ADULTS; WOMEN; JOINT;
POPULATION; OVERWEIGHT; ASSOCIATION; PREVALENCE; OBESITY
AB Background: Knee osteoarthritis (kOA) risk is increased by obesity and physical activities (PA) which mechanically stress the joint. We examined the associations of midlife kOA with body mass index (BMI) and activity exposure across adult life and their interaction.
Methods: Data are from a UK birth cohort of 2597 participants with a clinical assessment for kOA at age 53. At ages 36, 43 and 53 BMI (kg/m(2)), self-reported leisure-time PA, and occupational activity (kneeling/squatting; lifting; climbing; sitting; assigned using a job-exposure matrix) were ascertained. Associations were explored using the multiplicative logistic model.
Results: BMI was strongly and positively associated with kOA in men and women. Men and women in manual occupations also had greater odds of kOA; there was a weak suggestion that kOA risk was higher among men exposed to lifting or kneeling at work. For men, the only evidence of a multiplicative interaction between BMI and activities was for lifting (p = 0.01) at age 43; BMI conferred higher kOA risk among those most-likely to lift at work (OR per increase in BMI z-score: 3.55, 95% CI: 1.72-7.33). For women, the only evidence of an interaction was between BMI and leisure-time PA (p = 0.005) at age 43; BMI conferred higher kOA risk among those at higher PA levels (OR per increase in BMI z-score: 1.59, 95% CI: 1.26-2.00 in inactive; 1.70, 95% CI: 1.14-2.55 (less-active); and 4.44; 95% CI: 2.26-8.36 (most-active).
Conclusions: At the very least, our study suggests that more active individuals (at work and in leisure) may see a greater reduction in risk of kOA from avoiding a high BMI than those less active.
C1 [Martin, Kathryn R.; Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20814 USA.
[Martin, Kathryn R.; Kuh, Diana] UCL, MRC Unit Lifelong Hlth & Ageing, London, England.
[Guralnik, Jack M.] Univ Maryland, Div Gerontol, Dept Epidemiol & Publ Hlth, College Pk, MD 20742 USA.
[Coggon, David] Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England.
[Wills, Andrew K.] Univ Bristol, Sch Social & Community Med, MRC CAiTE, Bristol, Avon, England.
RP Martin, KR (reprint author), NIA, Lab Epidemiol & Populat Sci, NIH, 7201 Wisconsin Ave,Room 3C309, Bethesda, MD 20814 USA.
EM kathryn.martin@nih.gov
FU Intramural Research Program of the National Institute on Aging, NIH
FX This research was supported in part by the Intramural Research Program
of the National Institute on Aging, NIH.
NR 42
TC 31
Z9 31
U1 3
U2 14
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2474
J9 BMC MUSCULOSKEL DIS
JI BMC Musculoskelet. Disord.
PD JUL 24
PY 2013
VL 14
AR 219
DI 10.1186/1471-2474-14-219
PG 11
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA 190ZN
UT WOS:000322382500001
PM 23883324
ER
PT J
AU Cheng, N
Bai, L
Steuer, E
Belluscio, L
AF Cheng, Ning
Bai, Li
Steuer, Elizabeth
Belluscio, Leonardo
TI Olfactory Functions Scale with Circuit Restoration in a Rapidly
Reversible Alzheimer's Disease Model
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID BROMIDE-INDUCED LESIONS; MOUSE MODEL; AMYLOID-BETA; TRANSGENIC MICE;
METHYL-BROMIDE; AXON GUIDANCE; IN-VIVO; NEURAL PLASTICITY; ISOVALERIC
ACID; MEMORY DEFICITS
AB Neural circuits maintain a precise organization that is vital for normal brain functions and behaviors, but become disrupted during neurological disease. Understanding the connection between wiring accuracy and function to measure disease progression or recovery has been difficult because of the complexity of behavioral circuits. The olfactory system maintains well-defined neural connections that regenerate throughout life. We previously established a reversible in vivo model of Alzheimer's disease by overexpressing a humanized mutated amyloid precursor protein (hAPP) in olfactory sensory neurons (OSNs). Using this model, we currently show that hAPP is present in the OSN axons of mutant mice, which exhibit strong caspase3 signal and reduced synaptic protein expression by 3 weeks of age. In the olfactory bulb, we show that glomerular structure is distorted and OSN axonal convergence is lost. In vivo functional imaging experiments further demonstrate disruption of the glomerular circuitry, and behavioral assays reveal that olfactory function is significantly impaired. Because OSNs regenerate, we also tested if the system could recover from hAPP-induced disruption. We found that after 1 or 3 weeks of shutting-off hAPP expression, the glomerular circuit was partially restored both anatomically and functionally, with behavioral deficits similarly reversed. Interestingly, the degree of functional recovery tracked directly with circuit restoration. Together, these data demonstrate that hAPP-induced circuit disruption and subsequent recovery can occur rapidly and that behavior can provide a measure of circuit organization. Thus, olfaction may serve as a useful biomarker to both follow disease progression and gauge potential recovery.
C1 [Cheng, Ning; Bai, Li; Steuer, Elizabeth; Belluscio, Leonardo] NINDS, Dev Neural Plast Sect, NIH, Bethesda, MD 20892 USA.
RP Belluscio, L (reprint author), NIH, 35 Convent Dr, Bethesda, MD 20892 USA.
EM belluscl@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke intramural
program [1ZIANS003116-02]
FX This work was supported by the National Institute of Neurological
Disorders and Stroke intramural program, project 1ZIANS003116-02. We
thank Rini Singh and Amit Sethi for assistance and Dr. Susan Wray and
members of the Belluscio laboratory for constructive comments.
NR 80
TC 16
Z9 16
U1 0
U2 11
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUL 24
PY 2013
VL 33
IS 30
BP 12208
EP 12217
DI 10.1523/JNEUROSCI.0291-13.2013
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 188CF
UT WOS:000322168600008
PM 23884929
ER
PT J
AU Sallet, J
Mars, RB
Noonan, MP
Neubert, FX
Jbabdi, S
O'Reilly, JX
Filippini, N
Thomas, AG
Rushworth, MF
AF Sallet, Jerome
Mars, Rogier B.
Noonan, MaryAnn P.
Neubert, Franz-Xaver
Jbabdi, Saad
O'Reilly, Jill X.
Filippini, Nicola
Thomas, Adam G.
Rushworth, Matthew F.
TI The Organization of Dorsal Frontal Cortex in Humans and Macaques
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID CONNECTIVITY-BASED PARCELLATION; DORSOLATERAL PREFRONTAL CORTEX;
COMPARATIVE CYTOARCHITECTONIC ANALYSIS; INTRINSIC FUNCTIONAL
ARCHITECTURE; TRACTOGRAPHY-BASED PARCELLATION; POSTERIOR PARIETAL
CORTEX; PRIMARY MOTOR CORTEX; RESTING-STATE FMRI; WORKING-MEMORY;
RHESUS-MONKEY
AB The human dorsal frontal cortex has been associated with the most sophisticated aspects of cognition, including those that are thought to be especially refined in humans. Here we used diffusion-weighted magnetic resonance imaging (DW-MRI) and functional MRI (fMRI) in humans and macaques to infer and compare the organization of dorsal frontal cortex in the two species. Using DW-MRI tractography-based parcellation, we identified 10 dorsal frontal regions lying between the human inferior frontal sulcus and cingulate cortex. Patterns of functional coupling between each area and the rest of the brain were then estimated with fMRI and compared with functional coupling patterns in macaques. Areas in human medial frontal cortex, including areas associated with high-level social cognitive processes such as theory of mind, showed a surprising degree of similarity in their functional coupling patterns with the frontal pole, medial prefrontal, and dorsal prefrontal convexity in the macaque. We failed to find evidence for "new" regions in human medial frontal cortex. On the lateral surface, comparison of functional coupling patterns suggested correspondences in anatomical organization distinct from those that are widely assumed. A human region sometimes referred to as lateral frontal pole more closely resembled area 46, rather than the frontal pole, of the macaque. Overall the pattern of results suggest important similarities in frontal cortex organization in humans and other primates, even in the case of regions thought to carry out uniquely human functions. The patterns of interspecies correspondences are not, however, always those that are widely assumed.
C1 [Sallet, Jerome; Mars, Rogier B.; Noonan, MaryAnn P.; Neubert, Franz-Xaver; Rushworth, Matthew F.] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England.
[Mars, Rogier B.; Jbabdi, Saad; O'Reilly, Jill X.; Filippini, Nicola; Thomas, Adam G.; Rushworth, Matthew F.] Univ Oxford, John Radcliffe Hosp, Ctr Funct Magnet Resonance Imaging Brain, Oxford OX3 9DU, England.
[Filippini, Nicola] Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England.
[Thomas, Adam G.] NIMH, Funct MRI Facil, NIH, Bethesda, MD 20892 USA.
RP Sallet, J (reprint author), Univ Oxford, Dept Expt Psychol, S Parks Rd, Oxford OX1 3UD, England.
EM Jerome.sallet@psy.ox.ac.uk
OI Jbabdi, Saad/0000-0003-3234-5639; Thomas, Adam/0000-0002-2850-1419
FU MRC
FX This research is supported by the MRC (J.S., R.B.M., M.F.R.).
NR 133
TC 73
Z9 73
U1 8
U2 46
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUL 24
PY 2013
VL 33
IS 30
BP 12255
EP 12274
DI 10.1523/JNEUROSCI.5108-12.2013
PG 20
WC Neurosciences
SC Neurosciences & Neurology
GA 188CF
UT WOS:000322168600012
PM 23884933
ER
PT J
AU Madhavan, A
Argilli, E
Bonci, A
Whistler, JL
AF Madhavan, Anuradha
Argilli, Emanuela
Bonci, Antonello
Whistler, Jennifer L.
TI Loss of D2 Dopamine Receptor Function Modulates Cocaine-Induced
Glutamatergic Synaptic Potentiation in the Ventral Tegmental Area
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID LONG-TERM POTENTIATION; NMDA-RECEPTORS; NEURONS; ARIPIPRAZOLE; MICE;
RAT; TRANSPORTER; PLASTICITY; RELEASE; BRAIN
AB Potentiation of glutamate responses is a critical synaptic response to cocaine exposure in ventral tegmental area (VTA) neurons. However, the mechanism by which cocaine exposure promotes potentiation of NMDA receptors (NMDARs) and subsequently AMPA receptors (AMPARs) is not fully understood. In this study we demonstrate that repeated cocaine treatment causes loss of D2 dopamine receptor functional responses via interaction with lysosome-targeting G-protein-associated sorting protein1 (GASP1). We also show that the absence of D2 downregulation in GASP1-KO mice prevents cocaine-induced potentiation of NMDAR currents, elevation of the AMPA/NMDA ratio, and redistribution of NMDAR and AMPAR subunits to the membrane. As a pharmacological parallel, coadministration of the high-affinity D2 agonist, aripiprazole, reduces not only functional downregulation of D2s in response to cocaine but also potentiation of NMDAR and AMPAR responses in wild-type mice. Together these data suggest that functional loss of D2 receptors is a critical mechanism mediating cocaine-induced glutamate plasticity in VTA neurons.
C1 [Madhavan, Anuradha; Whistler, Jennifer L.] Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, Emeryville, CA 94608 USA.
[Madhavan, Anuradha; Argilli, Emanuela; Bonci, Antonello; Whistler, Jennifer L.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Bonci, Antonello] NIDA, Intramural Res Program, Bethesda, MD 20892 USA.
[Bonci, Antonello] Johns Hopkins Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21287 USA.
RP Whistler, JL (reprint author), Ernest Gallo Clin & Res Ctr, 5858 Horton St,Suite 200, Emeryville, CA 94608 USA.
EM Jennifer.Whistler@ucsf.edu
FU National Alliance for Research on Schizophrenia and Depression Young
Investigator Award; National Institutes of Health National Research
Service Award F32 post-doctoral Fellowship [5F32DA027286-02]; National
Institute of Drug Abuse [R01 DA019958-05, R21 MH096058-01]; State of
California for medical research on alcohol and substance abuse through
the University of California San Francisco
FX A.M. was supported by a National Alliance for Research on Schizophrenia
and Depression Young Investigator Award and received salary support from
a National Institutes of Health National Research Service Award F32
post-doctoral Fellowship (5F32DA027286-02). J.L.W. was supported by
grants from the National Institute of Drug Abuse (R01 DA019958-05 and
R21 MH096058-01) and by funds provided by the State of California for
medical research on alcohol and substance abuse through the University
of California San Francisco. We thank Madeline Ferwerda for maintenance
and genotyping of mouse colonies and Dawn Thompson for assisting with
cocaine injections in preliminary experiments.
NR 42
TC 11
Z9 11
U1 0
U2 13
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUL 24
PY 2013
VL 33
IS 30
BP 12329
EP 12336
DI 10.1523/JNEUROSCI.0809-13.2013
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 188CF
UT WOS:000322168600018
PM 23884939
ER
PT J
AU Arce, SH
Wu, PH
Tseng, Y
AF Arce, Stephen Hugo
Wu, Pei-Hsun
Tseng, Yiider
TI Fast and accurate automated cell boundary determination for fluorescence
microscopy
SO SCIENTIFIC REPORTS
LA English
DT Article
ID IMAGE SEGMENTATION; EDGE-DETECTION
AB Detailed measurement of cell phenotype information from digital fluorescence images has the potential to greatly advance biomedicine in various disciplines such as patient diagnostics or drug screening. Yet, the complexity of cell conformations presents a major barrier preventing effective determination of cell boundaries, and introduces measurement error that propagates throughout subsequent assessment of cellular parameters and statistical analysis. State-of-the-art image segmentation techniques that require user-interaction, prolonged computation time and specialized training cannot adequately provide the support for high content platforms, which often sacrifice resolution to foster the speedy collection of massive amounts of cellular data. This work introduces a strategy that allows us to rapidly obtain accurate cell boundaries from digital fluorescent images in an automated format. Hence, this new method has broad applicability to promote biotechnology.
C1 [Arce, Stephen Hugo; Wu, Pei-Hsun; Tseng, Yiider] Univ Florida, Dept Chem Engn, Gainesville, FL 32611 USA.
[Tseng, Yiider] Univ Florida, Inst Cell Engn & Regenerat Med, Gainesville, FL 32611 USA.
[Wu, Pei-Hsun; Tseng, Yiider] NCI, Phys Sci Oncol Ctr, Gainesville, FL 32611 USA.
RP Tseng, Y (reprint author), Univ Florida, Dept Chem Engn, Gainesville, FL 32611 USA.
EM ytseng@che.ufl.edu
FU NIH/NCI [U54CA143868]; McKnight Doctoral Fellowship
FX This study was supported in part by grants from NIH/NCI U54CA143868.
Stephen H. Arce was partially supported by the McKnight Doctoral
Fellowship during the study. The authors are grateful for the great help
from Dr. Michael Kesler for vpSEM experiments.
NR 28
TC 3
Z9 3
U1 3
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUL 24
PY 2013
VL 3
AR 2266
DI 10.1038/srep02266
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187XB
UT WOS:000322153700001
PM 23881180
ER
PT J
AU Zhou, ZH
Wild, T
Xiong, Y
Sylvers, P
Zhang, YH
Zhang, LX
Wahl, L
Wahl, SM
Kozlowski, S
Notkins, AL
AF Zhou, Zhao-hua
Wild, Teresa
Xiong, Ying
Sylvers, Peter
Zhang, Yahong
Zhang, Luxia
Wahl, Larry
Wahl, Sharon M.
Kozlowski, Steven
Notkins, Abner L.
TI Polyreactive Antibodies Plus Complement Enhance the Phagocytosis of
Cells Made Apoptotic by UV-Light or HIV
SO SCIENTIFIC REPORTS
LA English
DT Article
ID NATURAL IGM ANTIBODY; BINDING B-CELLS; MONOCLONAL AUTOANTIBODIES;
INTRAVENOUS IMMUNOGLOBULIN; PROMOTES PHAGOCYTOSIS; CLEARANCE;
REPERTOIRE; IDENTIFICATION; AUTOIMMUNITY; LYMPHOCYTES
AB Polyreactive antibodies are a major component of the natural antibody repertoire and are capable of binding a variety of structurally unrelated antigens. Many of the properties attributed to natural antibodies, in fact, are turning out to be due to polyreactive antibodies. In humans, each day, billions of cells undergo apoptosis. In the present experiments, we show by ImageStream technology that although polyreactive antibodies do not bind to live T cells they bind to both the plasma membrane and cytoplasm of late apoptotic cells, fix complement, generate the anaphylatoxin C5a and increase by as much as 5 fold complement-mediated phagocytosis by macrophages. Of particular importance, T cells undergoing apoptosis following infection with HIV also bind polyreactive antibodies and are phagocytosed. We conclude that the polyreactive antibodies in the natural antibody repertoire contribute in a major way to the clearance of cells made apoptotic by a variety of natural and infectious processes.
C1 [Zhou, Zhao-hua; Sylvers, Peter; Kozlowski, Steven] US FDA, CDER, OPS, OBP,Div Monoclonal Antibodies, Rockville, MD 20857 USA.
[Wild, Teresa; Xiong, Ying; Wahl, Sharon M.; Notkins, Abner L.] NIDCR, NIH, Oral Infect & Immun Branch, Bethesda, MD USA.
[Zhang, Yahong; Wahl, Larry] NIDCR, Immunopathol Sect, Bethesda, MD USA.
RP Kozlowski, S (reprint author), US FDA, CDER, OPS, OBP,Div Monoclonal Antibodies, Rockville, MD 20857 USA.
EM Kozlowski@fda.hhs.gov; anotkins@mail.nih.gov
FU Intramural Research Programs of the US National Institutes of Health;
Food and Drug Administration
FX The authors thank Richard A. DeMarco of Amnis Corp for comments on
ImageStream analysis. This research was supported by the Intramural
Research Programs of the US National Institutes of Health and Food and
Drug Administration. The views expressed in this manuscript represent
the opinions of the authors, and do not necessarily represent the
official views of the NIH or FDA.
NR 44
TC 9
Z9 9
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUL 24
PY 2013
VL 3
AR 2271
DI 10.1038/srep02271
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187XB
UT WOS:000322153700006
PM 23881356
ER
PT J
AU Green, RC
Lupski, JR
Biesecker, LG
AF Green, Robert C.
Lupski, James R.
Biesecker, Leslie G.
TI Reporting Genomic Sequencing Results to Ordering Clinicians Incidental,
but Not Exceptional
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Green, Robert C.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
[Green, Robert C.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Lupski, James R.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Lupski, James R.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Lupski, James R.] Texas Childrens Hosp, Houston, TX 77030 USA.
[Biesecker, Leslie G.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
RP Green, RC (reprint author), Harvard Univ, Sch Med, 41 Ave Louis Pasteur,EC Alumnae Bldg,Ste 301, Boston, MA 02115 USA.
EM rcgreen@genetics.med.harvard.edu
FU Intramural NIH HHS; NCI NIH HHS [CA154517, R01 CA154517]; NHGRI NIH HHS
[HG003178, HG005092, HG006542, HG006615, HG02213, R01 HG002213, R01
HG003178, R01 HG005092, R01 HG006615, U54 HG003273, U54 HG006542, UM1
HG006542]; NINDS NIH HHS [NS058529, R01 NS058529]
NR 9
TC 42
Z9 43
U1 1
U2 5
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 24
PY 2013
VL 310
IS 4
BP 365
EP 366
DI 10.1001/jama.2013.41703
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 187LV
UT WOS:000322121500007
PM 23917280
ER
PT J
AU Tilburt, JC
Wynia, MK
Sheeler, RD
Thorsteinsdottir, B
James, KM
Egginton, JS
Liebow, M
Hurst, S
Danis, M
Goold, SD
AF Tilburt, Jon C.
Wynia, Matthew K.
Sheeler, Robert D.
Thorsteinsdottir, Bjorg
James, Katherine M.
Egginton, Jason S.
Liebow, Mark
Hurst, Samia
Danis, Marion
Goold, Susan Dorr
TI Views of US Physicians About Controlling Health Care Costs
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID NATIONAL-SURVEY; ATTITUDES; MEDICINE
AB IMPORTANCE Physicians' views about health care costs are germane to pending policy reforms.
OBJECTIVE To assess physicians' attitudes toward and perceived role in addressing health care costs.
DESIGN, SETTING, AND PARTICIPANTS A cross-sectional survey mailed in 2012 to 3897 US physicians randomly selected from the AMA Masterfile.
MAIN OUTCOMES AND MEASURES Enthusiasm for 17 cost-containment strategies and agreement with an 11-measure cost-consciousness scale.
RESULTS A total of 2556 physicians responded (response rate = 65%). Most believed that trial lawyers (60%), health insurance companies (59%), hospitals and health systems (56%), pharmaceutical and device manufacturers (56%), and patients (52%) have a "major responsibility" for reducing health care costs, whereas only 36% reported that practicing physicians have "major responsibility." Most were "very enthusiastic" for "promoting continuity of care" (75%), "expanding access to quality and safety data" (51%), and "limiting access to expensive treatments with little net benefit" (51%) as a means of reducing health care costs. Few expressed enthusiasm for "eliminating fee-for-service payment models" (7%). Most physicians reported being "aware of the costs of the tests/treatments [they] recommend" (76%), agreed they should adhere to clinical guidelines that discourage the use of marginally beneficial care (79%), and agreed that they "should be solely devoted to individual patients' best interests, even if that is expensive" (78%) and that "doctors need to take a more prominent role in limiting use of unnecessary tests" (89%). Most (85%) disagreed that they "should sometimes deny beneficial but costly services to certain patients because resources should go to other patients that need them more." In multivariable logistic regression models testing associations with enthusiasm for key cost-containment strategies, having a salary plus bonus or salary-only compensation type was independently associated with enthusiasm for "eliminating fee for service" (salary plus bonus: odds ratio [OR], 3.3, 99% CI, 1.8-6.1; salary only: OR, 4.3, 99% CI, 2.2-8.5). In multivariable linear regression models, group or government practice setting (beta = 0.87, 95% CI, 0.29 to 1.45, P = .004; and beta = 0.99, 95% CI, 0.20 to 1.79, P = .01, respectively) and having a salary plus bonus compensation type (beta = 0.82; 95% CI, 0.32 to 1.33; P = .002) were positively associated with cost-consciousness. Finding the "uncertainty involved in patient care disconcerting" was negatively associated with cost-consciousness (beta = -1.95; 95% CI, -2.71 to -1.18; P < .001).
CONCLUSION AND RELEVANCE In this survey about health care cost containment, US physicians reported having some responsibility to address health care costs in their practice and expressed general agreement about several quality initiatives to reduce cost but reported less enthusiasm for cost containment involving changes in payment models.
C1 [Tilburt, Jon C.; Liebow, Mark] Mayo Clin, Div Gen Internal Med, Rochester, MN 55905 USA.
[Tilburt, Jon C.; Thorsteinsdottir, Bjorg; James, Katherine M.] Mayo Clin, Biomed Eth Program, Rochester, MN 55905 USA.
[Tilburt, Jon C.] Mayo Clin, Knowledge & Evaluat Res Unit, Rochester, MN 55905 USA.
[Tilburt, Jon C.] Mayo Clin, Healthcare Delivery Res Program, Ctr Sci Healthcare Delivery, Rochester, MN 55905 USA.
[Tilburt, Jon C.; Egginton, Jason S.] Mayo Clin, Div Hlth Care Policy & Res, Rochester, MN 55905 USA.
[Wynia, Matthew K.] Amer Med Assoc, Inst Eth, Chicago, IL 60610 USA.
[Sheeler, Robert D.] Mayo Clin, Dept Family Med, Rochester, MN 55905 USA.
[Thorsteinsdottir, Bjorg] Mayo Clin, Div Primary Care Internal Med, Rochester, MN 55905 USA.
[Hurst, Samia] Univ Geneva, Inst Biomed Eth, CH-1211 Geneva 4, Switzerland.
[Danis, Marion] NIH, Dept Bioeth, Bethesda, MD 20892 USA.
[Goold, Susan Dorr] Univ Michigan, Med Ctr, Dept Gen Internal Med, Ann Arbor, MI USA.
[Wynia, Matthew K.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
RP Tilburt, JC (reprint author), Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA.
EM tilburt.jon@mayo.edu
RI Hurst, Samia/A-9661-2008;
OI Hurst, Samia/0000-0002-1980-5226; Goold, Susan Dorr/0000-0002-0258-9774
FU Greenwall Foundation; Mayo Clinic Program in Professionalism and Ethics;
Mayo Clinic Foundation; Swiss National Science Foundation
[PP00P3_123340]
FX Dr Tilburt's research was funded by the Faculty Scholars Program of the
Greenwall Foundation, Mayo Clinic Program in Professionalism and Ethics,
and an Early Career Development Award from the Mayo Clinic Foundation.
Dr Hurst is funded by a grant from the Swiss National Science Foundation
(PP00P3_123340).
NR 23
TC 83
Z9 83
U1 2
U2 20
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 24
PY 2013
VL 310
IS 4
BP 380
EP 388
DI 10.1001/jama.2013.8278
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 187LV
UT WOS:000322121500015
PM 23917288
ER
PT J
AU Golden, A
Steel, C
Yokobe, L
Jackson, E
Barney, R
Kubofcik, J
Peck, R
Unnasch, TR
Nutman, TB
de los Santos, T
Domingo, GJ
AF Golden, Allison
Steel, Cathy
Yokobe, Lindsay
Jackson, Emily
Barney, Rebecca
Kubofcik, Joseph
Peck, Roger
Unnasch, Thomas R.
Nutman, Thomas B.
de los Santos, Tala
Domingo, Gonzalo J.
TI Extended Result Reading Window in Lateral Flow Tests Detecting Exposure
to Onchocerca volvulus: A New Technology to Improve Epidemiological
Surveillance Tools
SO PLOS ONE
LA English
DT Article
ID IVERMECTIN TREATMENT; ENDEMIC FOCI; 1ST EVIDENCE; ELIMINATION;
INFECTION; SENEGAL; PROGRAM; MALI
AB Onchocerciasis is a neglected tropical disease caused by infection with the parasite Onchocerca volvulus (Ov). An estimated 180 million people are at risk for Ov infection, and 37 million people are infected, mostly in Africa. A lateral flow-based assay to detect human IgG4 antibodies to the Ov-specific antigen Ov-16 was developed as a rapid tool to detect exposure to Ov. The test, when performed on 449 sera specimens from patients with microfiladermia and Ov-negative patients, has a sensitivity of 89.1% (95% confidence interval: 86.2%-92.0%), and specificity of 97% (95% confidence interval: 95.4%-98.6%). Because the intended use of the test is for surveillance, it is highly desirable to have a stable, long-lasting result. An extended read window is thus desirable for a high-volume, busy workflow and facilitates post-surveillance quality assurance. The main restriction on achieving an extended read window for this assay was the erythrocyte lysis that can alter the signal-to-noise ratio, especially in those with low IgG4 levels (weak positives). We describe a test housing that incorporates a user-independent feature driven by assay fluid and an expanding wick that detaches the blood separation membrane from the nitrocellulose used in the assay, but before hemolysis occurs. We demonstrated material functionality at extreme operational conditions (37 degrees C, 80% relative humidity) and a read window of a minimum of 70 days. The fluid-driven assay device performs equally as well with whole blood as with plasma, as demonstrated with 100 spiked clinical specimens (with a correlation coefficient of 0.96). We show a novel, inexpensive, and simple approach to actuating the detachment of the blood separation membrane from the nitrocellulose test with no impact on the performance characteristics of the test.
C1 [Golden, Allison; Yokobe, Lindsay; Jackson, Emily; Barney, Rebecca; Peck, Roger; de los Santos, Tala; Domingo, Gonzalo J.] PATH, Diagnost Grp, Seattle, WA USA.
[Steel, Cathy; Kubofcik, Joseph; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Unnasch, Thomas R.] Univ S Florida, Dept Global Hlth, Global Hlth Infect Dis Res Program, Tampa, FL USA.
RP Domingo, GJ (reprint author), PATH, Diagnost Grp, Seattle, WA USA.
EM gdomingo@path.org
FU Bill & Melinda Gates Foundation
FX This publication is based on research funded by the Bill & Melinda Gates
Foundation. The findings and conclusions contained within are those of
the authors and do not necessarily reflect positions or policies of the
Bill & Melinda Gates Foundation. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 17
TC 14
Z9 14
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 23
PY 2013
VL 8
IS 7
AR e69231
DI 10.1371/journal.pone.0069231
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 228SX
UT WOS:000325211000090
PM 23935960
ER
PT J
AU Ma, N
Xing, C
Xiao, H
Wang, Y
Wang, K
Hou, CM
Han, GC
Chen, GJ
Marrero, B
Wang, YJ
Shen, BF
Li, Y
Wang, RX
AF Ma, Ning
Xing, Chen
Xiao, He
Wang, Yi
Wang, Ke
Hou, Chunmei
Han, Gencheng
Chen, Guojiang
Marrero, Bernadette
Wang, Yujuan
Shen, Beifen
Li, Yan
Wang, Renxi
TI C5a Regulates IL-12(+)DC Migration to Induce Pathogenic Th1 and Th17
Cells in Sepsis
SO PLOS ONE
LA English
DT Article
ID THYMOCYTE APOPTOSIS; DENDRITIC CELLS; RECEPTOR; MODEL; INFLAMMATION;
DEFINITIONS; EXPRESSION; CYTOKINE; ANTI-C5A; IMMUNITY
AB Objective: It is well known that complement system C5a is excessively activated during the onset of sepsis. However, it is unclear whether C5a can regulate dentritic cells (DCs) to stimulate adaptive immune cells such as Th1 and Th17 in sepsis.
Methods: Sepsis was induced by cecal ligation and puncture (CLP). CLP-induced sepsis was treated with anti-C5a or IL-12. IL-12(+)DC, IFN gamma(+)Th1, and IL-17(+)Th17 cells were analyzed by flow cytometry. IL-12 was measured by ELISA.
Results: Our studies here showed that C5a induced IL-12(+)DC cell migration from the peritoneal cavity to peripheral blood and lymph nodes. Furthermore, IL-12(+)DC cells induced the expansion of pathogenic IFN gamma(+)Th1 and IL-17(+)Th17 cells in peripheral blood and lymph nodes. Moreover, IL-12, secreted by DC cells in the peritoneal cavity, is an important factor that prevents the development of sepsis.
Conclusion: Our data suggests that C5a regulates IL-12(+)DC cell migration to induce pathogenic Th1 and Th17 cells in sepsis.
C1 [Ma, Ning; Xing, Chen; Xiao, He; Wang, Yi; Wang, Ke; Hou, Chunmei; Han, Gencheng; Chen, Guojiang; Shen, Beifen; Li, Yan; Wang, Renxi] Chinese Acad Med Sci, Inst Basic Med Sci, Immunol Lab, Beijing 100730, Peoples R China.
[Ma, Ning] Jilin Univ, Dept Rheumatol, Hosp 1, Changchun 130023, Peoples R China.
[Marrero, Bernadette] NEI, Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Wang, Yujuan] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Li, Y (reprint author), Chinese Acad Med Sci, Inst Basic Med Sci, Immunol Lab, Beijing 100730, Peoples R China.
EM liyan62033@yahoo.com.cn; wang_renxi@yahoo.com
RI wang, yujuan/C-8428-2016
FU National Basic Research Program 973 Grants [2013CB530506]; Beijing
Natural Science Foundation [7132139]
FX This study was supported by National Basic Research Program 973 Grants
(2013CB530506) and Beijing Natural Science Foundation (7132139). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 29
TC 9
Z9 11
U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 23
PY 2013
VL 8
IS 7
AR e69779
DI 10.1371/journal.pone.0069779
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 228SX
UT WOS:000325211000154
PM 23936099
ER
PT J
AU Springer, DJ
Saini, D
Byrnes, EJ
Heitman, J
Frothingham, R
AF Springer, Deborah J.
Saini, Divey
Byrnes, Edmond J.
Heitman, Joseph
Frothingham, Richard
TI Development of an Aerosol Model of Cryptococcus Reveals Humidity as an
Important Factor Affecting the Viability of Cryptococcus during
Aerosolization
SO PLOS ONE
LA English
DT Article
ID FUNGAL PATHOGEN CRYPTOCOCCUS; YERSINIA-PESTIS CO92; GATTII SEROTYPE-C;
ALVEOLAR MACROPHAGES; MURINE MODEL; PULMONARY CRYPTOCOCCOSIS;
ENVIRONMENTAL SOURCES; DENDRITIC CELLS; INFLUENZA-VIRUS; VAR. NEOFORMANS
AB Cryptococcus is an emerging global health threat that is annually responsible for over 1,000,000 infections and one third of all AIDS patient deaths. There is an ongoing outbreak of cryptococcosis in the western United States and Canada. Cryptococcosis is a disease resulting from the inhalation of the infectious propagules from the environment. The current and most frequently used animal infection models initiate infection via liquid suspension through intranasal instillation or intravenous injection. These models do not replicate the typically dry nature of aerosol exposure and may hinder our ability to decipher the initial events that lead to clearance or the establishment of infection. We have established a standardized aerosol model of murine infection for the human fungal pathogen Cryptococcus. Aerosolized cells were generated utilizing a Collison nebulizer in a whole-body Madison Chamber at different humidity conditions. The aerosols inside the chamber were sampled using a BioSampler to determine viable aerosol concentration and spray factor (ratio of viable aerosol concentration to total inoculum concentration). We have effectively delivered yeast and yeast-spore mixtures to the lungs of mice and observed the establishment of disease. We observed that growth conditions prior to exposure and humidity within the Madison Chamber during exposure can alter Cryptococcus survival and dose retained in mice.
C1 [Springer, Deborah J.; Heitman, Joseph; Frothingham, Richard] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
[Saini, Divey; Frothingham, Richard] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA.
[Byrnes, Edmond J.] NIH, Off Director, Baltimore, MD USA.
RP Springer, DJ (reprint author), Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
EM deborah.springer@duke.edu
FU Dean Voucher Program; Regional Biocontainment Laboratory at Duke [UC6
AI058607]; NIH/NAID [R37 AIO39115-15]
FX The work was support by the 2010-11 Dean Voucher Program, UC6 AI058607
(Regional Biocontainment Laboratory at Duke), and NIH/NAID R37
AIO39115-15 to JH. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 85
TC 4
Z9 4
U1 0
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 23
PY 2013
VL 8
IS 7
AR e69804
DI 10.1371/journal.pone.0069804
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 228SX
UT WOS:000325211000157
PM 23894542
ER
PT J
AU Lin, DY
Zeng, DL
Tang, ZZ
AF Lin, Dan-Yu
Zeng, Donglin
Tang, Zheng-Zheng
TI Quantitative trait analysis in sequencing studies under trait-dependent
sampling
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID GENETIC ASSOCIATION; RARE VARIANTS; LOCI; POWER
AB It is not economically feasible to sequence all study subjects in a large cohort. A cost-effective strategy is to sequence only the subjects with the extreme values of a quantitative trait. In the National Heart, Lung, and Blood Institute Exome Sequencing Project, subjects with the highest or lowest values of body mass index, LDL, or blood pressure were selected for whole-exome sequencing. Failure to account for such trait-dependent sampling can cause severe inflation of type I error and substantial loss of power in quantitative trait analysis, especially when combining results from multiple studies with different selection criteria. We present valid and efficient statistical methods for association analysis of sequencing data under trait-dependent sampling. We pay special attention to gene-based analysis of rare variants. Our methods can be used to perform quantitative trait analysis not only for the trait that is used to select subjects for sequencing but for any other traits that are measured. For a particular trait of interest, our approach properly combines the association results from all studies with measurements of that trait. This meta-analysis is substantially more powerful than the analysis of any single study. By contrast, meta-analysis of standard linear regression results (ignoring trait-dependent sampling) can be less powerful than the analysis of a single study. The advantages of the proposed methods are demonstrated through simulation studies and the National Heart, Lung, and Blood Institute Exome Sequencing Project data. The methods are applicable to other types of genetic association studies and nongenetic studies.
C1 [Lin, Dan-Yu; Zeng, Donglin; Tang, Zheng-Zheng] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA.
[Lin, Dan-Yu; Zeng, Donglin; Tang, Zheng-Zheng] NHLBI, GO Exome Sequencing Project, Bethesda, MD 20892 USA.
RP Lin, DY (reprint author), Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA.
EM lin@bios.unc.edu
RI Tang, Zheng-Zheng/F-6642-2014
OI Tang, Zheng-Zheng/0000-0003-3802-8087
FU NIH [R01 CA082659, R37 GM047845, P01 CA142538]; NHLBI [RC2 HL-103010,
RC2 HL-102923, RC2 HL-102924, RC2 HL-102925, RC2 HL-102926]
FX We thank G. R. Abecasis, P. L. Auer, C. Bizon, N. Franceschini, Y. Hu,
E. M. Lange, L. A. Lange, K. North, S. S. Rich, R. Tao, R. P. Tracy, and
C. J. Willer for discussions/comments. We thank K.-P. Li for programming
assistance and two referees for helpful suggestions. We acknowledge the
support of the NHLBI and the contributions of the research institutions,
study investigators, field staff, and study participants in creating the
ESP data for biomedical research. Additional acknowledgments are
provided in SI Appendix. This research was supported by the NIH Grants
R01 CA082659, R37 GM047845, and P01 CA142538. Funding for ESP was
provided by NHLBI Grants RC2 HL-103010 (Heart), RC2 HL-102923 (Lung),
and RC2 HL-102924 (WHI Sequencing Project). The exome sequencing was
performed through NHLBI Grants RC2 HL-102925 (Broad) and RC2 HL-102926
(Seattle).
NR 21
TC 20
Z9 21
U1 0
U2 8
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 23
PY 2013
VL 110
IS 30
BP 12247
EP 12252
DI 10.1073/pnas.1221713110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187JA
UT WOS:000322112300035
PM 23847208
ER
PT J
AU Maoz, K
Abend, R
Fox, NA
Pine, DS
Ar-Haim, Y
AF Maoz, Keren
Abend, Rany
Fox, Nathan A.
Pine, Daniel S.
Bar-Haim, Yair
TI Subliminal attention bias modification training in socially anxious
individuals
SO FRONTIERS IN HUMAN NEUROSCIENCE
LA English
DT Article
DE social anxiety; stress vulnerability; attention bias modification;
masking; subliminal
ID RANDOMIZED CONTROLLED-TRIAL; SELF-REPORT VERSION; ANXIETY DISORDER;
TRAIT ANXIETY; EMOTIONAL VULNERABILITY; PSYCHOMETRIC PROPERTIES;
MODIFICATION PROGRAM; SELECTIVE ATTENTION; PROCESSING BIASES; THREAT
CUES
AB Anxious individuals demonstrate threat-related attention biases both when threat stimuli are presented within conscious awareness and when presented below awareness threshold. Nevertheless, attention bias modification (ABM) research has rarely utilized sub-awareness protocols in an attempt to modify attention patterns and reduce anxiety. Exploring the potential of subliminal ABM is of interest, as it may target attention processes related to anxiety that are distinct from those engaged by supraliminal ABM. Here we examined the effect of a subliminal ABM training protocol on levels of social anxiety and stress vulnerability. Fifty-one socially anxious students were randomly assigned to either ABM or placebo condition, and completed a pre-training assessment, four training sessions, a social stressor task, and a post-training assessment. Results indicate that the subliminal ABM used here did not induce detectable changes in threa-trelated attention from pre- to post-training as measured by two independent attention tasks. Furthermore, the ABM and placebo groups did not differ on either self-reported social anxiety post-training or state anxiety following stress induction. Post-hoc auxiliary analyses suggest that ABM may be associated with smaller elevations in state anxiety during the stressor task only for participants who demonstrate attention bias toward threat at baseline. Implications and future research directions are discussed.
C1 [Maoz, Keren; Abend, Rany; Bar-Haim, Yair] Tel Aviv Univ, Sch Psychol Sci, IL-69978 Tel Aviv, Israel.
[Fox, Nathan A.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA.
[Pine, Daniel S.] NIMH, Bethesda, MD 20892 USA.
[Bar-Haim, Yair] Tel Aviv Univ, Sagol Sch Neurosci, IL-69978 Tel Aviv, Israel.
RP Maoz, K (reprint author), Tel Aviv Univ, Sch Psychol Sci, IL-69978 Tel Aviv, Israel.
EM kerenmao@mail.tau.ac.il
NR 58
TC 9
Z9 11
U1 7
U2 34
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5161
J9 FRONT HUM NEUROSCI
JI Front. Hum. Neurosci.
PD JUL 23
PY 2013
VL 7
AR 389
DI 10.3389/fnhum.2013.00389
PG 12
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA 187HG
UT WOS:000322106900001
PM 23888138
ER
PT J
AU Tatem, AJ
Garcia, AJ
Snow, RW
Noor, AM
Gaughan, AE
Gilbert, M
Linard, C
AF Tatem, Andrew J.
Garcia, Andres J.
Snow, Robert W.
Noor, Abdisalan M.
Gaughan, Andrea E.
Gilbert, Marius
Linard, Catherine
TI Millennium development health metrics: where do Africa's children and
women of childbearing age live?
SO POPULATION HEALTH METRICS
LA English
DT Article
DE Population; Demography; Mapping; Millenium development goals
ID GEOGRAPHICAL ACCESSIBILITY; GLOBAL DISTRIBUTION; UPDATED ATLAS;
EAST-AFRICA; MALARIA; RISK; TRANSMISSION; SCHISTOSOMIASIS; ENDEMICITY;
MORTALITY
AB The Millennium Development Goals (MDGs) have prompted an expansion in approaches to deriving health metrics to measure progress toward their achievement. Accurate measurements should take into account the high degrees of spatial heterogeneity in health risks across countries, and this has prompted the development of sophisticated cartographic techniques for mapping and modeling risks. Conversion of these risks to relevant population-based metrics requires equally detailed information on the spatial distribution and attributes of the denominator populations. However, spatial information on age and sex composition over large areas is lacking, prompting many influential studies that have rigorously accounted for health risk heterogeneities to overlook the substantial demographic variations that exist subnationally and merely apply national-level adjustments.
Here we outline the development of high resolution age- and sex-structured spatial population datasets for Africa in 2000-2015 built from over a million measurements from more than 20,000 subnational units, increasing input data detail from previous studies by over 400-fold. We analyze the large spatial variations seen within countries and across the continent for key MDG indicator groups, focusing on children under 5 and women of childbearing age, and find that substantial differences in health and development indicators can result through using only national level statistics, compared to accounting for subnational variation.
Progress toward meeting the MDGs will be measured through national-level indicators that mask substantial inequalities and heterogeneities across nations. Cartographic approaches are providing opportunities for quantitative assessments of these inequalities and the targeting of interventions, but demographic spatial datasets to support such efforts remain reliant on coarse and outdated input data for accurately locating risk groups. We have shown here that sufficient data exist to map the distribution of key vulnerable groups, and that doing so has substantial impacts on derived metrics through accounting for spatial demographic heterogeneities that exist within nations across Africa.
C1 [Tatem, Andrew J.] Univ Southampton, Dept Geog & Environm, Southampton, Hants, England.
[Tatem, Andrew J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Garcia, Andres J.; Gaughan, Andrea E.] Univ Florida, Dept Geog, Gainesville, FL 32611 USA.
[Garcia, Andres J.; Gaughan, Andrea E.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL USA.
[Snow, Robert W.; Noor, Abdisalan M.] Univ Oxford, Wellcome Trust Collaborat Programme, KEMRI, Malaria Publ Hlth & Epidemiol Grp,Ctr Geog Med, Nairobi, Kenya.
[Snow, Robert W.; Noor, Abdisalan M.] Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, CCVTM, Oxford, England.
[Gilbert, Marius; Linard, Catherine] Univ Libre Brussels, Brussels, Belgium.
[Gilbert, Marius; Linard, Catherine] Fonds Natl Rech Sci FRS FNRS, Brussels, Belgium.
RP Tatem, AJ (reprint author), Univ Southampton, Dept Geog & Environm, Southampton, Hants, England.
EM Andy.Tatem@gmail.com
OI Snow, Robert/0000-0003-3725-6088; Gilbert, Marius/0000-0003-3708-3359
FU Wellcome Trust [079080, 092654]
NR 59
TC 12
Z9 12
U1 4
U2 20
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1478-7954
J9 POPUL HEALTH METR
JI Popul. Health Metr.
PD JUL 23
PY 2013
VL 11
AR 11
DI 10.1186/1478-7954-11-11
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 191KU
UT WOS:000322412700001
PM 23875684
ER
PT J
AU Magnani, JW
Hylek, EM
Apovian, CM
AF Magnani, Jared W.
Hylek, Elaine M.
Apovian, Caroline M.
TI Obesity Begets Atrial Fibrillation: A Contemporary Summary
SO CIRCULATION
LA English
DT Article
DE atrial fibrillation; epidemiology; obesity; risk
ID ATHEROSCLEROSIS RISK; METABOLIC SYNDROME; COMMUNITIES; SURGERY; COHORT;
WHITES; SCORE
C1 [Magnani, Jared W.] NHLBI, Framingham, MA USA.
[Magnani, Jared W.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Magnani, Jared W.] Boston Univ, Sch Med, Sect Cardiovasc Med, Boston, MA 02118 USA.
[Hylek, Elaine M.] Boston Univ, Sch Med, Gen Internal Med Sect, Dept Med, Boston, MA 02118 USA.
[Apovian, Caroline M.] Boston Univ, Sch Med, Dept Endocrinol Diabet & Nutr, Boston, MA 02118 USA.
RP Magnani, JW (reprint author), Boston Univ, Sch Med, Sect Cardiovasc Med, 88 E Newton St, Boston, MA 02118 USA.
EM jmagnani@bu.edu
OI Apovian, Caroline/0000-0002-8029-1922
FU American Heart Association [09FTF2190028]; National Institutes of Health
(NIH) [R01NS070307, P30DK046200]
FX Dr Magnani is supported by American Heart Association award
09FTF2190028. Dr Hylek is supported by National Institutes of Health
(NIH) grant R01NS070307. Dr Apovian is supported by NIH grant
P30DK046200.
NR 15
TC 18
Z9 18
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JUL 23
PY 2013
VL 128
IS 4
BP 401
EP 405
DI 10.1161/CIRCULATIONAHA.113.001840
PG 5
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 187MP
UT WOS:000322123500023
PM 23877062
ER
PT J
AU Saint-Preux, F
Bores, LR
Tulloch, I
Ladenheim, B
Kim, R
Thanos, PK
Volkow, ND
Cadet, JL
AF Saint-Preux, F.
Bores, L. R.
Tulloch, I.
Ladenheim, B.
Kim, R.
Thanos, P. K.
Volkow, N. D.
Cadet, J. L.
TI CHRONIC CO-ADMINISTRATION OF NICOTINE AND METHAMPHETAMINE CAUSES
DIFFERENTIAL EXPRESSION OF IMMEDIATE EARLY GENES IN THE DORSAL STRIATUM
AND NUCLEUS ACCUMBENS OF RATS
SO NEUROSCIENCE
LA English
DT Article
DE nicotine; methamphetamine; striatum; nucleus accumbens; immediate early
genes
ID NEOSTRIATAL NEURONS; DOPAMINE RELEASE; MOLECULAR SWITCH; NERVOUS-SYSTEM;
DELTA-FOSB; ADDICTION; BRAIN; RECEPTORS; COCAINE; NEUROBIOLOGY
AB Nicotine and methamphetamine (METH) cause addiction by triggering neuroplastic changes in brain reward pathways though they each engage distinct molecular targets (nicotine receptors and dopamine transporters respectively). Addiction to both drugs is very prevalent, with the vast majority of METH users also being smokers of cigarettes. This co-morbid occurrence thus raised questions about potential synergistic rewarding effects of the drugs. However, few studies have investigated the chronic neurobiological changes associated with co-morbid nicotine and METH addiction. Here we investigated the effects of these two drugs alone and in combination on the expression of several immediate early genes (IEGs) that are sensitive to drug exposures. Chronic exposure to either nicotine or METH caused significant decreases in the expression of fosb, fra1, and fra2 in the nucleus accumbens (NAc) but not in the dorsal striatum whereas the drug combination increased fra2 expression in both structures. Except for junB mRNA levels that were decreased by the three drug treatments in the NAc, there were no significant changes in the Jun family members. Of the Egr family members, NAc egr2 expression was decreased after nicotine and the drug combination whereas NAc egr3 was decreased after METH and the drug combination. The drug combination also increased striatal egr3 expression. The Nr4a family member, nr4a2/nurr1, showed increased striatal expression after all three drug treatments, while striatal nr4a3/nor-1 expression was increased by the drug combination whereas NAc nr4a1/ nurr77 was decreased by nicotine and the drug combination. These observations suggest that, when given in combination, the two drugs exert distinct effects on the expression of IEGs in dopaminergic projection areas from those elicited by each drug alone. The significance of these changes in IEG expression and in other molecular markers in fostering co-morbid METH and nicotine abuse needs to be further evaluated. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
C1 [Saint-Preux, F.; Bores, L. R.; Tulloch, I.; Ladenheim, B.; Cadet, J. L.] NIDA IRP, Mol Neuropsychiat Res Branch, Baltimore, MD 21224 USA.
[Kim, R.; Thanos, P. K.; Volkow, N. D.] NIAAA, Behav Neuropharmacol & Neuroimaging Lab, Intramural NIAAA Program, Brookhaven Natl Lab, Upton, NY 11973 USA.
[Volkow, N. D.] NIDA, Bethesda, MD 20892 USA.
RP Cadet, JL (reprint author), NIDA IRP, Mol Neuropsychiat Res Branch, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM Jcadet@intra.nida.nih.gov
FU Intramural Research Program of the DHHS/NIH/NIDA
FX This research was supported by funds of the Intramural Research Program
of the DHHS/NIH/NIDA.
NR 40
TC 3
Z9 3
U1 0
U2 17
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
J9 NEUROSCIENCE
JI Neuroscience
PD JUL 23
PY 2013
VL 243
BP 89
EP 96
DI 10.1016/j.neuroscience.2013.03.052
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 156UK
UT WOS:000319849200011
PM 23562942
ER
PT J
AU Ioannidis, JPA
Prasad, V
AF Ioannidis, John P. A.
Prasad, Vinay
TI Evaluating Health System Processes With Randomized Controlled Trials
SO JAMA INTERNAL MEDICINE
LA English
DT Editorial Material
ID MEDICAL EMERGENCY TEAM; MORTALITY; MORBIDITY; CARE
C1 [Ioannidis, John P. A.] Stanford Univ, Stanford Prevent Res Ctr, Dept Med, Sch Med, Stanford, CA 94305 USA.
[Ioannidis, John P. A.] Stanford Univ, Stanford Prevent Res Ctr, Dept Hlth Res & Policy, Sch Med, Stanford, CA 94305 USA.
[Ioannidis, John P. A.] Stanford Univ, Dept Stat, Sch Humanities & Sci, Stanford, CA 94305 USA.
[Prasad, Vinay] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Ioannidis, JPA (reprint author), Stanford Prevent Res Ctr, 1265Welch Rd,MSOB X306, Stanford, CA 94305 USA.
EM jioannid@stanford.edu
NR 10
TC 3
Z9 3
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6106
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD JUL 22
PY 2013
VL 173
IS 14
BP 1279
EP 1280
DI 10.1001/jamainternmed.2013.1044
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 214TX
UT WOS:000324160100002
PM 23689271
ER
PT J
AU Yaffe, K
Falvey, CM
Hamilton, N
Harris, TB
Simonsick, EM
Strotmeyer, ES
Shorr, RI
Metti, A
Schwartz, AV
AF Yaffe, Kristine
Falvey, Cherie M.
Hamilton, Nathan
Harris, Tamara B.
Simonsick, Eleanor M.
Strotmeyer, Elsa S.
Shorr, Ronald I.
Metti, Andrea
Schwartz, Ann V.
CA Hlth ABC Study
TI Association Between Hypoglycemia and Dementia in a Biracial Cohort of
Older Adults With Diabetes Mellitus
SO JAMA INTERNAL MEDICINE
LA English
DT Article
ID COGNITIVE FUNCTION; ALZHEIMERS-DISEASE; RISK; DYSFUNCTION; IMPAIRMENT;
VETERANS; TRIAL
AB IMPORTANCE Hypoglycemia commonly occurs in patients with diabetes mellitus (DM) and may negatively influence cognitive performance. Cognitive impairment in turn can compromise DM management and lead to hypoglycemia.
OBJECTIVE To prospectively evaluate the association between hypoglycemia and dementia in a biracial cohort of older adults with DM.
DESIGN AND SETTING Prospective population-based study.
PARTICIPANTS We studied 783 older adults with DM (mean age, 74.0 years; 47.0% of black race/ethnicity; and 47.6% female) who were participating in the prospective population-based Health, Aging, and Body Composition Study beginning in 1997 and who had baseline Modified Mini-Mental State Examination scores of 80 or higher.
MAIN OUTCOME MEASURES Dementia diagnosis was determined during the follow-up period from hospital records indicating an admission associated with dementia or the use of prescribed dementia medications. Hypoglycemic events were determined during the follow-up period by hospital records.
RESULTS During the 12-year follow-up period, 61 participants (7.8%) had a reported hypoglycemic event, and 148 (18.9%) developed dementia. Those who experienced a hypoglycemic event had a 2-fold increased risk for developing dementia compared with those who did not have a hypoglycemic event (34.4% vs 17.6%, P < .001; multivariate-adjusted hazard ratio, 2.1; 95% CI, 1.0-4.4). Similarly, older adults with DM who developed dementia had a greater risk for having a subsequent hypoglycemic event compared with participants who did not develop dementia (14.2% vs 6.3%, P < .001; multivariate-adjusted hazard ratio, 3.1; 95% CI, 1.5-6.6). Further adjustment for stroke, hypertension, myocardial infarction, and cognitive change scores produced similar results.
CONCLUSION AND RELEVANCE Among older adults with DM, there seems to be a bidirectional association between hypoglycemia and dementia.
C1 [Yaffe, Kristine; Falvey, Cherie M.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA.
[Yaffe, Kristine; Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA.
[Yaffe, Kristine; Falvey, Cherie M.; Hamilton, Nathan] San Francisco VA Med Ctr, San Francisco, CA USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Baltimore, MD 21224 USA.
[Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA.
[Strotmeyer, Elsa S.; Metti, Andrea] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Shorr, Ronald I.] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA.
RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, 4150 Clement St,POB 181, San Francisco, CA 94121 USA.
EM kristine.yaffe@ucsf.edu
RI Strotmeyer, Elsa/F-3015-2014; Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Strotmeyer, Elsa/0000-0002-4093-6036
FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106, K24AG031155]; National Institute of Nursing Research
[R01-AG028050, R01-NR012459]; Intramural Research Program of the
National Institutes of Health; American Health Assistance Foundation
[A201-0029]
FX This study was supported by grants N01-AG-6-2101, N01-AG-6-2103, and
N01-AG-6-2106 from the National Institute on Aging and by grants
R01-AG028050 and R01-NR012459 from the National Institute of Nursing
Research. This research was supported in part by the Intramural Research
Program of the National Institutes of Health, by the National Institute
on Aging, and by grant A201-0029 from the American Health Assistance
Foundation. Dr Yaffe is supported in part by grant K24AG031155 from the
National Institute on Aging.
NR 33
TC 76
Z9 79
U1 5
U2 15
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 2168-6106
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD JUL 22
PY 2013
VL 173
IS 14
BP 1300
EP +
DI 10.1001/jamainternmed.2013.6176
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 214TX
UT WOS:000324160100007
PM 23753199
ER
PT J
AU Smagulova, F
Brick, K
Pu, YM
Sengupta, U
Camerini-Otero, RD
Petukhova, GV
AF Smagulova, Fatima
Brick, Kevin
Pu, Yongmei
Sengupta, Uttara
Camerini-Otero, R. Daniel
Petukhova, Galina V.
TI Suppression of genetic recombination in the pseudoautosomal region and
at subtelomeres in mice with a hypomorphic Spo11 allele
SO BMC GENOMICS
LA English
DT Article
DE Homologous recombination; Recombination hotspots; SPO11; Subtelomeres;
Double stranded DNA breaks
ID DOUBLE-STRAND BREAKS; SEX-CHROMOSOME INACTIVATION; MEIOTIC
RECOMBINATION; SYNAPTONEMAL COMPLEX; SACCHAROMYCES-CEREVISIAE; MAMMALIAN
MEIOSIS; MALE-FERTILITY; CROSSING-OVER; HOT-SPOTS; MOUSE
AB Background: Homologous recombination is the key process that generates genetic diversity and drives evolution. SPO11 protein triggers recombination by introducing DNA double stranded breaks at discreet areas of the genome called recombination hotspots. The hotspot locations are largely determined by the DNA binding specificity of the PRDM9 protein in human, mice and most other mammals. In budding yeast Saccharomyces cerevisae, which lacks a Prdm9 gene, meiotic breaks are formed opportunistically in the regions of accessible chromatin, primarily at gene promoters. The genome-wide distribution of hotspots in this organism can be altered by tethering Spo11 protein to Gal4 recognition sequences in the strain expressing Spo11 attached to the DNA binding domain of the Gal4 transcription factor. To establish whether similar re-targeting of meiotic breaks can be achieved in PRDM9-containing organisms we have generated a Gal4BD-Spo11 mouse that expresses SPO11 protein joined to the DNA binding domain of yeast Gal4.
Results: We have mapped the genome-wide distribution of the recombination initiation sites in the Gal4BD-Spo11 mice. More than two hundred of the hotspots in these mice were novel and were likely defined by Gal4BD, as the Gal4 consensus motif was clustered around the centers in these hotspots. Surprisingly, meiotic DNA breaks in the Gal4BD-Spo11 mice were significantly depleted near the ends of chromosomes. The effect is particularly striking at the pseudoautosomal region of the X and Y chromosomes - normally the hottest region in the genome.
Conclusions: Our data suggest that specific, yet-unidentified factors influence the initiation of meiotic recombination at subtelomeric chromosomal regions.
C1 [Smagulova, Fatima; Pu, Yongmei; Sengupta, Uttara; Petukhova, Galina V.] Uniformed Serv Univ Hlth Sci, Dept Biochem & Mol Biol, Bethesda, MD 20814 USA.
[Brick, Kevin; Camerini-Otero, R. Daniel] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD USA.
RP Petukhova, GV (reprint author), Uniformed Serv Univ Hlth Sci, Dept Biochem & Mol Biol, Bethesda, MD 20814 USA.
EM Galina.Petukhova@usuhs.edu
RI Smagulova, Fatima/K-5459-2015
OI Brick, Kevin/0000-0002-9596-6400; Smagulova, Fatima/0000-0001-6883-1968
FU NIH; NIGMS [1R01GM084104-01A1]; USUHS [FS71HU, R071HU, CS71HU]; NIDDK
Intramural Research Program
FX The authors would like to thank Pavel Khil for helpful discussions. This
research was supported by the NIH grant 1R01GM084104-01A1 from NIGMS
(G.V.P.); grants FS71HU, R071HU and CS71HU from USUHS (G.V.P.) and by
the NIDDK Intramural Research Program (RDCO).
NR 58
TC 2
Z9 2
U1 0
U2 18
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD JUL 22
PY 2013
VL 14
AR 493
DI 10.1186/1471-2164-14-493
PG 13
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 192ZV
UT WOS:000322527400001
PM 23870400
ER
PT J
AU Kellman, P
Herzka, DA
Arai, AE
Hansen, MS
AF Kellman, Peter
Herzka, Daniel A.
Arai, Andrew E.
Hansen, Michael Schacht
TI Influence of Off-resonance in myocardial T1-mapping using SSFP based
MOLLI method
SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
LA English
DT Article
DE T1 map; Error; Off-resonance; MOLLI; Shim; SSFP
ID CARDIOVASCULAR MAGNETIC-RESONANCE; INVERSION-RECOVERY MOLLI; HEART; T1;
VALIDATION; HUMANS
AB Background: Myocardial T1-mapping methods such as MOLLI use SSFP readout and are prone to frequency-dependent error in T1-measurement. A significant error in T1 may result at relatively small off-resonance frequencies that are well within the region without banding artifacts.
Methods: The sensitivity of T1-estimates based on the SSFP based MOLLI sequence to errors in center frequency are calculated by means of a Bloch simulation and validated by phantom measurements. Typical off-resonance errors following local cardiac shimming are determined by field mapping at both 1.5 and 3.0T. In vivo examples demonstrate the artifactual appearance of T1-maps in the presence of off-resonance variation.
Results: Off-resonance varied 61.8 +/- 15.5 Hz (mean +/- SD, n = 18) across the heart at 1.5T and 125.0 +/- 40.6 Hz (mean +/- SD, n = 18) at 3.0T. For T1 = 1000 ms, the variation in T1 due to off-resonance variation was approximately 20 ms at 62 Hz, and > 50 ms at 125 Hz.
Conclusions: Regional variations due to the inability to completely shim the B0-field variation around the heart appear as regional variation in T1, which is artifactual.
C1 [Kellman, Peter; Arai, Andrew E.; Hansen, Michael Schacht] NHLBI, NIH, DHHS, Bethesda, MD 20892 USA.
[Herzka, Daniel A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
RP Kellman, P (reprint author), NHLBI, NIH, DHHS, 10 Ctr Dr MSC-1061, Bethesda, MD 20892 USA.
EM kellman@nih.gov
RI Hansen, Michael/J-5391-2015;
OI Hansen, Michael/0000-0002-8087-8731; Herzka, Daniel/0000-0002-9400-7814
FU National Heart, Lung and Blood Institute, National Institutes of Health
by the Division of Intramural Research, NHLBI, NIH, DHHS
[HL004607-14CPB]
FX Supported by the National Heart, Lung and Blood Institute, National
Institutes of Health by the Division of Intramural Research, NHLBI, NIH,
DHHS (HL004607-14CPB).
NR 21
TC 26
Z9 26
U1 1
U2 13
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1097-6647
J9 J CARDIOVASC MAGN R
JI J. Cardiov. Magn. Reson.
PD JUL 22
PY 2013
VL 15
AR 63
DI 10.1186/1532-429X-15-63
PG 8
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 193PZ
UT WOS:000322574400001
PM 23875774
ER
PT J
AU Chen, YM
Sheng, ZH
AF Chen, Yanmin
Sheng, Zu-Hang
TI Kinesin-1-syntaphilin coupling mediates activity-dependent regulation of
axonal mitochondrial transport
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID SYNAPTIC-TRANSMISSION; HIPPOCAMPAL-NEURONS; CORTICAL-NEURONS; PROTEIN;
DYNEIN; KINESIN; TRAFFICKING; SYNAPSES; SYNTAPHILIN; DYNAMICS
AB Axonal mitochondria are recruited to synaptic terminals in response to neuronal activity, but the mechanisms underlying activity-dependent regulation of mitochondrial transport are largely unknown. In this paper, using genetic mouse model combined with live imaging, we demonstrate that syntaphilin (SNPH) mediates the activity-dependent immobilization of axonal mitochondria through binding to KIF5. In vitro analysis showed that the KIF5-SNPH coupling inhibited the motor adenosine triphosphatase. Neuronal activity further recruited SNPH to axonal mitochondria. This motor-docking interplay was induced by Ca2+ and synaptic activity and was necessary to establish an appropriate balance between motile and stationary axonal mitochondria. Deleting snph abolished the activity-dependent immobilization of axonal mitochondria. We propose an "Engine-Switch and Brake" model, in which SNPH acts both as an engine off switch by sensing mitochondrial Rho guanosine triphosphatase-Ca2+ and as a brake by anchoring mitochondria to the microtubule track. Altogether, our study provides new mechanistic insight into the molecular interplay between motor and docking proteins, which arrests axonal mitochondrial transport in response to changes in neuronal activity.
C1 [Chen, Yanmin; Sheng, Zu-Hang] NINDS, Synapt Funct Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Sheng, ZH (reprint author), NINDS, Synapt Funct Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
EM shengz@ninds.nih.gov
FU Intramural Research Program of NINDS, National Institutes of Health;
NINDS Competitive Fellowship
FX This work was supported by the Intramural Research Program of NINDS,
National Institutes of Health (Z.-H. Sheng) and an NINDS Competitive
Fellowship (Y. Chen).
NR 44
TC 47
Z9 47
U1 0
U2 15
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD JUL 22
PY 2013
VL 202
IS 2
BP 351
EP 364
DI 10.1083/jcb.201302040
PG 14
WC Cell Biology
SC Cell Biology
GA 186RR
UT WOS:000322062300016
PM 23857772
ER
PT J
AU Parry, C
Kent, EE
Forsythe, LP
Alfano, CM
Rowland, JH
AF Parry, Carla
Kent, Erin E.
Forsythe, Laura P.
Alfano, Catherine M.
Rowland, Julia H.
TI Can't See the Forest for the Care Plan: A Call to Revisit the Context of
Care Planning
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID SURVIVORSHIP CARE; BREAST-CANCER; COMMON-SENSE; PROVIDERS; ARGUMENT
C1 [Parry, Carla; Kent, Erin E.; Forsythe, Laura P.; Alfano, Catherine M.; Rowland, Julia H.] NCI, Bethesda, MD 20892 USA.
[Forsythe, Laura P.] Ctr Canc Training, Bethesda, MD USA.
RP Parry, C (reprint author), NCI, Bethesda, MD 20892 USA.
NR 20
TC 37
Z9 37
U1 1
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 20
PY 2013
VL 31
IS 21
BP 2651
EP 2653
DI 10.1200/JCO.2012.48.4618
PG 3
WC Oncology
SC Oncology
GA 301NJ
UT WOS:000330538700011
PM 23796989
ER
PT J
AU Kreimer, AR
Johansson, M
Waterboer, T
Kaaks, R
Chang-Claude, J
Drogen, D
Tjonneland, A
Overvad, K
Quiros, JR
Gonzalez, CA
Sanchez, MJ
Larranaga, N
Navarro, C
Barricarte, A
Travis, RC
Khaw, KT
Wareham, N
Trichopoulou, A
Lagiou, P
Trichopoulos, D
Peeters, PHM
Panico, S
Masala, G
Grioni, S
Tumino, R
Vineis, P
Bueno-de-Mesquita, HB
Laurell, G
Hallmans, G
Manjer, J
Ekstrom, J
Skeie, G
Lund, E
Weiderpass, E
Ferrari, P
Byrnes, G
Romieu, I
Riboli, E
Hildesheim, A
Boeing, H
Pawlita, M
Brennan, P
AF Kreimer, Aimee R.
Johansson, Mattias
Waterboer, Tim
Kaaks, Rudolf
Chang-Claude, Jenny
Drogen, Dagmar
Tjonneland, Anne
Overvad, Kim
Ramon Quiros, J.
Gonzalez, Carlos A.
Jose Sanchez, Maria
Larranaga, Nerea
Navarro, Carmen
Barricarte, Aurelio
Travis, Ruth C.
Khaw, Kay-Tee
Wareham, Nick
Trichopoulou, Antonia
Lagiou, Pagona
Trichopoulos, Dimitrios
Peeters, Petra H. M.
Panico, Salvatore
Masala, Giovanna
Grioni, Sara
Tumino, Rosario
Vineis, Paolo
Bueno-de-Mesquita, H. Bas
Laurell, Goran
Hallmans, Goran
Manjer, Jonas
Ekstrom, Johanna
Skeie, Guri
Lund, Eiliv
Weiderpass, Elisabete
Ferrari, Pietro
Byrnes, Graham
Romieu, Isabelle
Riboli, Elio
Hildesheim, Allan
Boeing, Heiner
Pawlita, Michael
Brennan, Paul
TI Evaluation of Human Papillomavirus Antibodies and Risk of Subsequent
Head and Neck Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; OROPHARYNGEAL CANCER; CERVICAL-CANCER;
ONCOPROTEINS E6; EARLY PROTEINS; MARKERS; E7; SURVIVAL; WOMEN
AB Purpose
Human papillomavirus type 16 (HPV16) infection is causing an increasing number of oropharyngeal cancers in the United States and Europe. The aim of our study was to investigate whether HPV antibodies are associated with head and neck cancer risk when measured in prediagnostic sera.
Methods
We identified 638 participants with incident head and neck cancers (patients; 180 oral cancers, 135 oropharynx cancers, and 247 hypopharynx/larynx cancers) and 300 patients with esophageal cancers as well as 1,599 comparable controls from within the European Prospective Investigation Into Cancer and Nutrition cohort. Prediagnostic plasma samples from patients (collected, on average, 6 years before diagnosis) and control participants were analyzed for antibodies against multiple proteins of HPV16 as well as HPV6, HPV11, HPV18, HPV31, HPV33, HPV45, and HPV52. Odds ratios (ORs) of cancer and 95% CIs were calculated, adjusting for potential confounders. All-cause mortality was evaluated among patients using Cox proportional hazards regression.
Results
HPV16 E6 seropositivity was present in prediagnostic samples for 34.8% of patients with oropharyngeal cancer and 0.6% of controls (OR, 274; 95% CI, 110 to 681) but was not associated with other cancer sites. The increased risk of oropharyngeal cancer among HPV16 E6 seropositive participants was independent of time between blood collection and diagnosis and was observed more than 10 years before diagnosis. The all-cause mortality ratio among patients with oropharyngeal cancer was 0.30 (95% CI, 0.13 to 0.67), for patients who were HPV16 E6 seropositive compared with seronegative.
Conclusion
HPV16 E6 seropositivity was present more than 10 years before diagnosis of oropharyngeal cancers. (C) 2013 by American Society of Clinical Oncology
C1 [Kreimer, Aimee R.; Hildesheim, Allan] NCI, NIH, Rockville, MD USA.
[Lagiou, Pagona; Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Johansson, Mattias; Ferrari, Pietro; Byrnes, Graham; Romieu, Isabelle; Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon 08, France.
[Waterboer, Tim; Kaaks, Rudolf; Chang-Claude, Jenny; Pawlita, Michael] German Canc Res Ctr, Heidelberg, Germany.
[Drogen, Dagmar; Boeing, Heiner] German Inst Human Nutr Potsdam Rehbrucke, Nuthetal, Germany.
[Tjonneland, Anne] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark.
[Overvad, Kim] Inst Publ Hlth, Aarhus, Denmark.
[Ramon Quiros, J.] Publ Hlth Directorage, Oviedo, Spain.
[Gonzalez, Carlos A.] Catalan Inst Oncol, Canc Epidemiol Res Programme, Barcelona, Spain.
[Jose Sanchez, Maria] Andalusian Sch Publ Hlth, Granada, Spain.
[Jose Sanchez, Maria; Larranaga, Nerea; Navarro, Carmen; Barricarte, Aurelio] Ctr Invest Biomed Red CIBER Epidemiol & Salud Pub, Madrid, Spain.
[Larranaga, Nerea] Basque Govt, Publ Hlth Dept Gipuzkoa, San Sebastian, Spain.
[Navarro, Carmen] Murcia Reg Hlth Council, Murcia, Spain.
[Barricarte, Aurelio] Navarre Publ Hlth Inst, Pamplona, Spain.
[Travis, Ruth C.] Univ Oxford, Oxford, England.
[Khaw, Kay-Tee] Univ Cambridge, Sch Clin Med, Cambridge, England.
[Wareham, Nick] Univ Cambridge, MRC, Epidemiol Unit, Cambridge, England.
[Vineis, Paolo; Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, London, England.
[Trichopoulou, Antonia; Lagiou, Pagona] Univ Athens, Sch Med, WHO Collaborating Ctr Food & Nutr Policies, GR-11527 Athens, Greece.
[Trichopoulou, Antonia; Trichopoulos, Dimitrios] Hellen Hlth Fdn, Athens, Greece.
[Lagiou, Pagona; Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece.
[Peeters, Petra H. M.; Bueno-de-Mesquita, H. Bas] Univ Med Ctr Utrecht, Utrecht, Netherlands.
[Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands.
[Panico, Salvatore] Univ Naples Federico II, Naples, Italy.
[Masala, Giovanna] Canc Prevent & Res Inst ISPO, Florence, Italy.
[Grioni, Sara] Ist Nazl Tumori, Fdn Ist Ricovero & Cura Carattere Sci IRCCS, I-20133 Milan, Italy.
[Tumino, Rosario] Civile MP Arezzo Hosp, Ragusa, Italy.
[Vineis, Paolo] HuGeF Fdn, Turin, Italy.
[Laurell, Goran; Hallmans, Goran] Umea Univ, Umea, Sweden.
[Manjer, Jonas; Ekstrom, Johanna] Lund Univ, Malmo Univ Hosp, Malmo, Sweden.
[Weiderpass, Elisabete] Karolinska Inst, Stockholm, Sweden.
[Skeie, Guri; Lund, Eiliv; Weiderpass, Elisabete] Univ Tromso, Tromso, Norway.
[Weiderpass, Elisabete] Canc Registry Norway, Oslo, Norway.
[Weiderpass, Elisabete] Samfundet Folkhalsan, Helsinki, Finland.
RP Brennan, P (reprint author), Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon 08, France.
EM gep@iarc.fr
RI Gonzalez, Carlos A/O-4651-2014; SANCHEZ-PEREZ, MARIA JOSE/D-1087-2011;
Hildesheim, Allan/B-9760-2015; Kreimer, Aimee/H-1687-2015; Panico,
Salvatore/K-6506-2016; Weiderpass, Elisabete/M-4029-2016; Waterboer,
Tim/G-1252-2010; Grioni, Sara/K-5320-2016
OI Gonzalez, Carlos A/0000-0003-2822-9715; SANCHEZ-PEREZ, MARIA
JOSE/0000-0003-4817-0757; Hildesheim, Allan/0000-0003-0257-2363;
Laurell, Goran/0000-0002-7760-246X; Panico,
Salvatore/0000-0002-5498-8312; Skeie, Guri/0000-0003-2476-4251; Masala,
Giovanna/0000-0002-5758-9069; Pawlita, Michael/0000-0002-4720-8306;
Weiderpass, Elisabete/0000-0003-2237-0128; Grioni,
Sara/0000-0002-5891-8426
FU National Cancer Institute Intramural Research Program; International
Agency for Research on Cancer; Health General Directorate of the French
Social Affairs and Health Ministry; European Commission (HPV-AHEAD)
[FP7-HEALTH-2011-282562]
FX Supported by the National Cancer Institute Intramural Research Program
(A. R. K.), the International Agency for Research on Cancer, the Health
General Directorate of the French Social Affairs and Health Ministry (P.
B.), and Grant No. FP7-HEALTH-2011-282562 from the European Commission
(HPV-AHEAD: Massimo Tommasino).
NR 26
TC 73
Z9 73
U1 0
U2 17
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 20
PY 2013
VL 31
IS 21
BP 2708
EP +
DI 10.1200/JCO.2012.47.2738
PG 12
WC Oncology
SC Oncology
GA 301NJ
UT WOS:000330538700019
PM 23775966
ER
PT J
AU Lee, CR
Park, YH
Kim, YR
Peterkofsky, A
Seok, YJ
AF Lee, Chang-Ro
Park, Young-Ha
Kim, Yeon-Ran
Peterkofsky, Alan
Seok, Yeong-Jae
TI Phosphorylation-Dependent Mobility Shift of Proteins on SDS-PAGE is Due
to Decreased Binding of SDS
SO BULLETIN OF THE KOREAN CHEMICAL SOCIETY
LA English
DT Article
DE Electrophoretic mobility shift; Protein phosphorylation; SDS-PAGE;
Signal transduction
ID GLOBAL REPRESSOR MLC; ESCHERICHIA-COLI; PHOSPHOTRANSFERASE SYSTEM;
ENZYME IIA(NTR); GLUCOSE-TRANSPORTER; EXPRESSION; GROWTH; OPERON
AB While many eukaryotic and some prokaryotic proteins show a phosphorylation-dependent mobility shift (PDMS) on SDS-PAGE, the molecular mechanism for this phenomenon had not been elucidated. We have recently shown that the distribution of negatively charged amino acids around the phosphorylation site is important for the PDMS of some proteins. Here, we show that replacement of the phosphorylation site with a negatively charged amino acid results in a similar degree of the mobility shift of a protein as phosphorylation, indicating that the PDMS is due to the introduction of a negative charge by phosphorylation. Compared with a protein showing no shift, one showing a retarded mobility on SDS-PAGE had a decreased capacity for SDS binding. The elucidation of the consensus sequence (Theta X1-3 Theta X1-3 Theta, where Theta corresponds to an acidic function) for a PDMS suggests a general strategy for mutagenizing a phosphorylatable protein resulting in a PDMS.
C1 [Lee, Chang-Ro; Park, Young-Ha; Kim, Yeon-Ran; Seok, Yeong-Jae] Seoul Natl Univ, Dept Biol Sci, Seoul 151742, South Korea.
[Lee, Chang-Ro; Park, Young-Ha; Kim, Yeon-Ran; Seok, Yeong-Jae] Seoul Natl Univ, Inst Microbiol, Seoul 151742, South Korea.
[Peterkofsky, Alan] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Seok, Yeong-Jae] Seoul Natl Univ, Dept Biophys & Chem Biol, Seoul 151742, South Korea.
[Lee, Chang-Ro] Myongji Univ, Dept Biol Sci, Yongin 449728, South Korea.
RP Seok, YJ (reprint author), Seoul Natl Univ, Dept Biol Sci, Seoul 151742, South Korea.
EM yjseok@snu.ac.kr
FU Korea Research Foundation [NRF 2010-0017384]; Ministry of Education,
Science, and Technology, Republic of Korea [NRF 2012-044184,
R31-2009-000-10032-0]; NIMBI, National Institutes of Health
FX This work was supported by the Korea Research Foundation Grant (NRF
2010-0017384), the Basic Science Research Program (NRF 2012-044184), and
the WCU program (R31-2009-000-10032-0) from Ministry of Education,
Science, and Technology, Republic of Korea. A.P. was supported by the
Intramural Research Program of NIMBI, National Institutes of Health.
NR 28
TC 7
Z9 7
U1 0
U2 5
PU KOREAN CHEMICAL SOC
PI SEOUL
PA 635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL 135-703, SOUTH KOREA
SN 0253-2964
J9 B KOREAN CHEM SOC
JI Bull. Korean Chem. Soc.
PD JUL 20
PY 2013
VL 34
IS 7
BP 2063
EP 2066
DI 10.5012/bkcs.2013.34.7.2063
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA 194DY
UT WOS:000322612400024
ER
PT J
AU Halabi, M
Faranesh, AZ
Schenke, WH
Wright, VJ
Hansen, MS
Saikus, CE
Kocaturk, O
Lederman, RJ
Ratnayaka, K
AF Halabi, Majdi
Faranesh, Anthony Z.
Schenke, William H.
Wright, Victor J.
Hansen, Michael S.
Saikus, Christina E.
Kocaturk, Ozgur
Lederman, Robert J.
Ratnayaka, Kanishka
TI Real-time cardiovascular magnetic resonance subxiphoid pericardial
access and pericardiocentesis using off-the-shelf devices in swine
SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
LA English
DT Article
DE Pericardiocentesis; Catheterization; Image guided intervention;
Interventional magnetic resonance imaging; Cardiovascular magnetic
resonance; Pericardial disease
ID CARDIAC-TAMPONADE; ELECTROPHYSIOLOGY; MRI; CATHETERIZATION;
INTERVENTIONS; FEASIBILITY; ADULTS
AB Background: Needle access or drainage of pericardial effusion, especially when small, entails risk of bystander tissue injury or operator uncertainty about proposed trajectories. Cardiovascular magnetic resonance (CMR) might allow enhanced imaging guidance.
Methods and results: We used real-time CMR to guide subxiphoid pericardial access in naive swine using commercial 18G titanium puncture needles, which were exchanged for pericardial catheters. To test the value of CMR needle pericardiocentesis, we also created intentional pericardial effusions of a range of volumes, via a separate transvenous-transatrial catheter. We performed these procedures in 12 animals.
Pericardiocentesis was performed in 2:47 +/- 1:43 minutes; pericardial access was performed in 1:40 +/- 4:34 minutes. The procedure was successful in all animals. Moderate and large effusions required only one needle pass. There were no complications, including pleural, hepatic or myocardial transit.
Conclusions: CMR guided pericardiocentesis is attractive because the large field of view and soft tissue imaging depict global anatomic context in arbitrary planes, and allow the operator to plan trajectories that limit inadvertent bystander tissue injury. More important, CMR provides continuous visualization of the needle and target throughout the procedure. Using even passive needle devices, CMR enabled rapid pericardial needle access and drainage. We believe this experience supports clinical testing of real-time CMR guided needle access or drainage of the pericardial space. We suspect this would be especially helpful in "difficult" pericardial access, for example, in distorted thoracic anatomy or loculated effusion.
C1 [Halabi, Majdi; Faranesh, Anthony Z.; Schenke, William H.; Wright, Victor J.; Hansen, Michael S.; Saikus, Christina E.; Kocaturk, Ozgur; Lederman, Robert J.; Ratnayaka, Kanishka] NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, Bethesda, MD 20892 USA.
[Ratnayaka, Kanishka] Childrens Natl Med Ctr, Dept Cardiol, Washington, DC 20010 USA.
RP Lederman, RJ (reprint author), NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA.
EM lederman@nih.gov
RI Hansen, Michael/J-5391-2015; Kocaturk, Ozgur/A-1419-2016;
OI Hansen, Michael/0000-0002-8087-8731; lederman,
robert/0000-0003-1202-6673
FU Division of Intramural Research, National Heart Lung and Blood
Institute, National Institutes of Health [Z01-HL005062-08]
FX This work was supported by the Division of Intramural Research, National
Heart Lung and Blood Institute, National Institutes of Health
(Z01-HL005062-08, RJL).
NR 18
TC 7
Z9 7
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1097-6647
J9 J CARDIOVASC MAGN R
JI J. Cardiov. Magn. Reson.
PD JUL 20
PY 2013
VL 15
AR 61
DI 10.1186/1532-429X-15-61
PG 6
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 193PY
UT WOS:000322574200001
PM 23870697
ER
PT J
AU Wang, JCM
Felizardo, TC
Au, BCY
Fowler, DH
Dekaban, GA
Medin, JA
AF Wang, James C. M.
Felizardo, Tania C.
Au, Bryan C. Y.
Fowler, Daniel H.
Dekaban, Gregory A.
Medin, Jeffrey A.
TI Engineering lentiviral vectors for modulation of dendritic cell
apoptotic pathways
SO VIROLOGY JOURNAL
LA English
DT Article
DE HER-2/neu; Lentivirus; Dendritic cell vaccine; Dendritic cell
longevity/lifespan
ID IN-VIVO; LIFE-SPAN; CLINICAL-TRIALS; TRANSDUCED DCS; PROTEIN-KINASE;
GENE DELIVERY; CANCER; DEATH; SURVIVAL; IMMUNITY
AB Background: Dendritic cells (DCs) are promising mediators of anti-tumor immune responses due to their potent antigen-presentation capacity. Unfortunately, cancer cells can often disarm differentiated DCs by rendering them incapable of maturation or by promoting their apoptosis. DC vaccine regimens attempt to generate functional DCs and preload them with Tumor-Associated Antigens (TAAs) to target various malignancies. Despite these efforts, the efficacy of DC vaccines in clinical trials is still rather disappointing to date. In addition to undergoing cancer-induced apoptosis, it is well established that DCs are intrinsically short-lived cell types. It is likely that a significant portion of infused DCs undergo apoptosis prior to locating and activating naive TAA-reactive T cells.
Methods: In our current study, we constructed and investigated novel bicistronic lentivectors (LVs) encoding the cDNA for the xeno-TAA, rat HER-2/neu (rHER-2), along with five candidate mouse DC survival factors (c-FLIPS, c-FLIPL, Bcl-(XL), M11L, and AKT-1) that operate in both the extrinsic and intrinsic cycles of apoptosis. The murine DC cell line, DC2.4 was transduced separately with each novel LV construct. Infected cells were enriched via flow cytometric methods based on rHER-2 expression. Transduced DC2.4 cell lines were then exposed to Fetal Calf Serum (FCS) withdrawal and to specific pharmacological apoptosis-inducing agents. DC2.4 cell death was assayed based on Annexin V and PI double-positive staining via flow cytometry. The phenotype and function of transduced DC2.4 cells and primary bone marrow-derived DCs were then assessed via expression and secretion of DC markers and cytokines, respectively.
Results: DC2.4 cells transduced with LVs encoding cDNAs for c-FLIPS, c-FLIPL, Bcl-(XL), and M11L were protected from apoptosis when exposed to low FCS-containing culture media. When treated with an anti-CD95 antibody, only DC2.4 cells transduced with LVs encoding c-FLIPS and c-FLIPL were protected from apoptosis. In contrast, only DC2.4 cells transduced with LVs encoding Bcl-(XL) and M11L were protected from effects of staurosporine (STS) treatment. Also, LV-modified DCs maintained their original phenotype and function.
Conclusions: We present evidence that by employing novel recombinant bicistronic LVs we can simultaneously load DCs with a relevant TAA and block apoptosis; thereby confirming the usage of such LVs in the modulation of DC lifespan and function.
C1 [Wang, James C. M.; Au, Bryan C. Y.; Medin, Jeffrey A.] Univ Hlth Network, Toronto, ON M5G 2M1, Canada.
[Wang, James C. M.; Medin, Jeffrey A.] Univ Toronto, Fac Med, Toronto, ON M5S 1A8, Canada.
[Felizardo, Tania C.; Fowler, Daniel H.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Dekaban, Gregory A.] Univ Western Ontario, Dept Microbiol & Immunol, London, ON N6A 5C1, Canada.
[Dekaban, Gregory A.] Robarts Res Inst, BioTherapeut Res Lab, London, ON N6A 5K8, Canada.
[Medin, Jeffrey A.] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada.
[Medin, Jeffrey A.] Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A8, Canada.
RP Medin, JA (reprint author), Univ Hlth Network, Canadian Blood Serv Bldg,67 Coll St Room 406, Toronto, ON M5G 2M1, Canada.
EM jmedin@uhnres.utoronto.ca
RI Dekaban, Gregory/L-1987-2013
OI Dekaban, Gregory/0000-0002-3087-4660
FU Ontario Ministry of Health and Long Term Care; Terry Fox Foundation
Canada
FX The authors thank Orlay Lopez-Perez (UHN) for excellent technical
assistance. This research was funded in part by the Ontario Ministry of
Health and Long Term Care. The views expressed do not necessarily
reflect those of the OMOHLTC. Funding was also provided in part by a
Program Project Grant from The Terry Fox Foundation Canada to GAD and
JAM.
NR 34
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Z9 2
U1 1
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1743-422X
J9 VIROL J
JI Virol. J.
PD JUL 20
PY 2013
VL 10
AR 240
DI 10.1186/1743-422X-10-240
PG 12
WC Virology
SC Virology
GA 188LR
UT WOS:000322195000001
PM 23870437
ER
PT J
AU Arbuckle, JH
Pantry, SN
Medveczky, MM
Prichett, J
Loomis, KS
Ablashi, D
Medveczky, PG
AF Arbuckle, Jesse H.
Pantry, Shara N.
Medveczky, Maria M.
Prichett, Joshua
Loomis, Kristin S.
Ablashi, Dharam
Medveczky, Peter G.
TI Mapping the telomere integrated genome of human herpesvirus 6A and 6B
SO VIROLOGY
LA English
DT Article
DE HHV-6; Human herpesvirus 6; CIHHV-6: chromosomally integrated human
herpesvirus 6; PBMC; Peripheral blood mononuclear cells; Integration;
Telomere; Telomere integration; single telomere length analysis; STELA
ID HUMAN-HERPESVIRUS-6 INFECTION; CHROMOSOMAL INTEGRATION;
CLINICAL-FEATURES; EXANTHEM-SUBITUM; CODING CONTENT; HUMAN-CELLS;
VIRAL-DNA; VIRUS; HHV-6; LYMPHOMA
AB Human herpesvirus 6B (HHV-6B) is the causative agent of roseola infantum. HHV-6A and 6B can reactivate in immunosuppressed individuals and are linked with severe inflammatory response, organ rejection and central nervous system diseases. About 0.85% of the US and UK population carries an integrated HHV-6 genome in all nucleated cells through germline transmission. We have previously reported that the HHV-6A genome integrated in telomeres of patients suffering from neurological dysfunction and also in telomeres of tissue culture cells. We now report that HHV-6B also integrates in telomeres during latency. Detailed mapping of the integrated viral genomes demonstrates that a single HHV-6 genome integrates and telomere repeats join the left end of the integrated viral genome. When HEK-293 cells carrying integrated HHV-6A were exposed to the histone deacetylase inhibitor Trichostatin A, circularization and/or formation of concatamers were detected and this assay could be used to distinguish between lytic replication and latency. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Arbuckle, Jesse H.; Pantry, Shara N.; Medveczky, Maria M.; Medveczky, Peter G.] Univ S Florida, Coll Med, Dept Mol Med, Tampa, FL 33612 USA.
[Arbuckle, Jesse H.] NIH, Mol Genet Sect, Viral Dis Lab, Bethesda, MD 20892 USA.
[Prichett, Joshua; Loomis, Kristin S.; Ablashi, Dharam] HHV 6 Fdn, Santa Barbara, CA USA.
RP Medveczky, PG (reprint author), Univ S Florida, Coll Med, 12901 Bruce B Blvd,MDC Box 7, Tampa, FL 33612 USA.
EM pmedvecz@health.usf.edu
OI Medveczky, Peter/0000-0002-1798-2595
FU HHV-6 Foundation; National Institute of Health [5R01CA111196]
FX We thank Dr. Philip Pellett providing HHV-6A and 6B stocks. This work
was supported by a grant from the HHV-6 Foundation and the National
Institute of Health 5R01CA111196 for PGM.
NR 45
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U1 2
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD JUL 20
PY 2013
VL 442
IS 1
BP 3
EP 11
DI 10.1016/j.virol.2013.03.030
PG 9
WC Virology
SC Virology
GA 168DW
UT WOS:000320686900002
PM 23648233
ER
PT J
AU Kitanaka, J
Kitanaka, N
Hall, FS
Uhl, GR
Fukushima, Y
Sawai, T
Watabe, K
Kubo, H
Takahashi, H
Tanaka, K
Nishiyama, N
Tatsuta, T
Morita, Y
Takemura, M
AF Kitanaka, Junichi
Kitanaka, Nobue
Hall, F. Scott
Uhl, George R.
Fukushima, Yuko
Sawai, Tatsuo
Watabe, Kaname
Kubo, Hitoshi
Takahashi, Hitoshi
Tanaka, Koh-ichi
Nishiyama, Nobuyoshi
Tatsuta, Tomohiro
Morita, Yoshio
Takemura, Motohiko
TI The selective mu opioid receptor antagonist beta-funaltrexamine
attenuates methamphetamine-induced stereotypical biting in mice
SO BRAIN RESEARCH
LA English
DT Article
DE Methamphetamine; Stereotypical behavior; Endogenous opioid system; mu
Opioid receptor
ID INDUCED BEHAVIORAL SENSITIZATION; KNOCKOUT MICE; NUCLEUS-ACCUMBENS;
NALTREXONE; AMPHETAMINE; DEPENDENCE; STRIATUM; SYSTEM; ABUSE; RAT
AB We investigated whether pretreatment with opioid receptor antagonists affected methamphetamine (METH)-induced stereotypy in mice. Pretreatment of male ICR mice with naloxone, a relatively non-selective opioid receptor antagonist, significantly attenuated the total incidence of METH-induced stereotypical behavior compared with saline vehicle-pretreated subjects. Furthermore, the distribution of METH-induced stereotypical behavior was affected by naloxone administration. Thus, METH-induced stereotypical sniffing and persistent locomotion were significantly increased by naloxone treatment while stereotypical biting was reduced. One way to interpret this pattern of effects is that pretreatment with naloxone appeared to produce a shift in the dose-response curve for METH. Thus, while the more intense forms of oral-facial stereotypies were reduced, increased persistent locomotion was observed in mice given naloxone followed by METH. The selective mu opioid receptor antagonist beta-funaltrexamine, but not nor-binaltorphimine (a kappa-selective antagonist) nor naltrindole (a delta-selective antagonist), mimicked the effect of naloxone. These observations suggest that opioid receptor antagonists may attenuate METH-induced stereotypical biting in mice via mu opioid receptors, and suggest that antagonism of this system may be a potential therapeutic approach to reducing some deleterious effects of METH use and perhaps in the treatment of some forms of self-injurious behavior. (c) 2013 Elsevier B.V. All rights reserved.
C1 [Kitanaka, Junichi; Kitanaka, Nobue; Fukushima, Yuko; Sawai, Tatsuo; Takemura, Motohiko] Hyogo Coll Med, Dept Pharmacol, Nishinomiya, Hyogo 6638501, Japan.
[Hall, F. Scott; Uhl, George R.] Natl Inst Drug Abuse, Mol Neurobiol Branch, Intramural Res Program, Baltimore, MD 21224 USA.
[Watabe, Kaname; Kubo, Hitoshi; Takahashi, Hitoshi] Muromachi Kikai Co Ltd, Tokyo 1030022, Japan.
[Tanaka, Koh-ichi; Nishiyama, Nobuyoshi] Hyogo Univ Hlth Sci, Sch Pharm, Div Pharmacol, Dept Pharm, Hyogo 6508530, Japan.
[Tatsuta, Tomohiro] Ibogawa Hosp Furuhashikai Med Corp, Hyogo 6711688, Japan.
[Morita, Yoshio] Baika Womens Univ, Fac Nursing, Osaka 5678578, Japan.
RP Kitanaka, J (reprint author), Hyogo Coll Med, Dept Pharmacol, 1-1 Mukogawa Cho, Nishinomiya, Hyogo 6638501, Japan.
EM kitanaka-hyg@umin.net
RI Hall, Frank/C-3036-2013
OI Hall, Frank/0000-0002-0822-4063
FU Hyogo College of Medicine; National Institute on Drug Abuse, USA
FX The authors are grateful to Ms. A. Yoshioka of the Department of
Pharmacology, Hyogo College of Medicine, for preparing the animal study
proposal. We also thank Mr. T. Nakajima of Joint-Use Research
Facilities, Hyogo College of Medicine, for constructing the acrylic test
boxes. This research was supported, in part, by Grants-in-Aid for
Researchers, Hyogo College of Medicine (2011 to NK; 2012 to JK), and
intramural funding from the National Institute on Drug Abuse, USA (GRU
and FSH).
NR 38
TC 5
Z9 5
U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD JUL 19
PY 2013
VL 1522
BP 88
EP 98
DI 10.1016/j.brainres.2013.05.027
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 198NU
UT WOS:000322930400009
PM 23727404
ER
PT J
AU Arao, Y
Hamilton, KJ
Coons, LA
Korach, KS
AF Arao, Yukitomo
Hamilton, Katherine J.
Coons, Laurel A.
Korach, Kenneth S.
TI Estrogen Receptor alpha L543A,L544A Mutation Changes Antagonists to
Agonists, Correlating with the Ligand Binding Domain Dimerization
Associated with DNA Binding Activity
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID STRUCTURAL BASIS; ANTIESTROGEN; ACTIVATION; ESTRADIOL; MODE
AB Aligand-dependent nuclear transcription factor, ER alpha has two transactivating functional domains (AF), AF-1 and AF-2. AF-1 is localized in the N-terminal region, and AF-2 is distributed in the C-terminal ligand-binding domain (LBD) of the ER alpha protein. Helix 12 (H12) in the LBD is a component of the AF-2, and the configuration of H12 is ligand-inducible to an active or inactive form. We demonstrated previously that the ER alpha mutant (AF2ER) possessing L543A,L544A mutations in H12 disrupts AF-2 function and reverses antagonists such as fulvestrant/ICI182780 (ICI) or 4-hydoxytamoxifen (OHT) into agonists in the AF2ER knock-in mouse. Our previous in vitro studies suggested that the mode of AF2ER activation is similar to the partial agonist activity of OHT for WT-ER alpha. However, it is still unclear how antagonists activate ER alpha. To understand the molecular mechanism of antagonist reversal activity, we analyzed the correlation between the ICI-dependent estrogen-responsive element-mediated transcription activity of AF2ER and AF2ER-LBD dimerization activity. We report here that ICI-dependent AF2ER activation correlated with the activity of AF2ER-LBD homodimerization. Prevention of dimerization impaired the ICI-dependent ERE binding and transcription activity of AF2ER. The dislocation of H12 caused ICI-dependent LBD homodimerization involving the F-domain, the adjoining region of H12. Furthermore, F-domain truncation also strongly depressed the dimerization of WT-ER alpha-LBD with antagonists but not with E2. AF2ER activation levels with ICI, OHT, and raloxifene were parallel with the degree of AF2ER-LBD homodimerization, supporting a mechanism that antagonist-dependent LBD homodimerization involving the F-domain results in antagonist reversal activity of H12-mutated ER alpha.
C1 [Arao, Yukitomo; Hamilton, Katherine J.; Coons, Laurel A.; Korach, Kenneth S.] NIEHS, Receptor Biol Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA.
[Coons, Laurel A.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
RP Korach, KS (reprint author), 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM korach@niehs.nih.gov
OI Korach, Kenneth/0000-0002-7765-418X
FU National Institutes of Health, National Institute of Environmental
Health Sciences [Z01ES70065]
FX This work was supported by Intramural Research Program of the National
Institutes of Health, National Institute of Environmental Health
Sciences Grant Z01ES70065 (to K. S. K.).
NR 24
TC 6
Z9 7
U1 3
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 19
PY 2013
VL 288
IS 29
BP 21105
EP 21116
DI 10.1074/jbc.M113.463455
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 186AU
UT WOS:000322014400031
PM 23733188
ER
PT J
AU Chen, QR
Braun, R
Hu, Y
Yan, CH
Brunt, EM
Meerzaman, D
Sanyal, AJ
Buetow, K
AF Chen, Qing-Rong
Braun, Rosemary
Hu, Ying
Yan, Chunhua
Brunt, Elizabeth M.
Meerzaman, Daoud
Sanyal, Arun J.
Buetow, Kenneth
TI Multi-SNP Analysis of GWAS Data Identifies Pathways Associated with
Nonalcoholic Fatty Liver Disease
SO PLOS ONE
LA English
DT Article
ID STEATOHEPATITIS; DYSREGULATION; POPULATION; SEVERITY
AB Non-alcoholic fatty liver disease (NAFLD) is a common liver disease; the histological spectrum of which ranges from steatosis to steatohepatitis. Nonalcoholic steatohepatitis (NASH) often leads to cirrhosis and development of hepatocellular carcinoma. To better understand pathogenesis of NAFLD, we performed the pathway of distinction analysis (PoDA) on a genome-wide association study dataset of 250 non-Hispanic white female adult patients with NAFLD, who were enrolled in the NASH Clinical Research Network (CRN) Database Study, to investigate whether biologic process variation measured through genomic variation of genes within these pathways was related to the development of steatohepatitis or cirrhosis. Pathways such as Recycling of eIF2:GDP, biosynthesis of steroids, Terpenoid biosynthesis and Cholesterol biosynthesis were found to be significantly associated with NASH. SNP variants in Terpenoid synthesis, Cholesterol biosynthesis and biosynthesis of steroids were associated with lobular inflammation and cytologic ballooning while those in Terpenoid synthesis were also associated with fibrosis and cirrhosis. These were also related to the NAFLD activity score (NAS) which is derived from the histological severity of steatosis, inflammation and ballooning degeneration. Eukaryotic protein translation and recycling of eIF2:GDP related SNP variants were associated with ballooning, steatohepatitis and cirrhosis. Il2 signaling events mediated by PI3K, Mitotic metaphase/anaphase transition, and Prostanoid ligand receptors were also significantly associated with cirrhosis. Taken together, the results provide evidence for additional ways, beyond the effects of single SNPs, by which genetic factors might contribute to the susceptibility to develop a particular phenotype of NAFLD and then progress to cirrhosis. Further studies are warranted to explain potential important genetic roles of these biological processes in NAFLD.
C1 [Chen, Qing-Rong; Braun, Rosemary; Hu, Ying; Yan, Chunhua; Meerzaman, Daoud; Buetow, Kenneth] NCI, Ctr Biomed Informat & Informat Technol, NIH, Bethesda, MD 20892 USA.
[Braun, Rosemary] Northwestern Univ, Dept Prevent Med, Div Biostat, Evanston, IL USA.
[Braun, Rosemary] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL USA.
[Brunt, Elizabeth M.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA.
[Sanyal, Arun J.] Virginia Commonwealth Univ, Med Ctr, Dept Internal Med, Div Gastroenterol Hepatol & Nutr, Richmond, VA USA.
[Buetow, Kenneth] Arizona State Univ, Complex Adapt Syst Initiat, Computat Sci & Informat Program, Phoenix, AZ USA.
RP Chen, QR (reprint author), NCI, Ctr Biomed Informat & Informat Technol, NIH, Bethesda, MD 20892 USA.
EM chenqi@mail.nih.gov
OI Braun, Rosemary/0000-0001-9668-9866
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK) [U01DK061718, U01DK061728, U01DK061731,
U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730,
U01DK061713]; National Institute of Child Health and Human Development
(NICHD)
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. This study
utilized the high-performance computational capabilities of the Biowulf
Linux cluster at the National Institutes of Health, Bethesda, MD. The
Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) is
supported by the National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) (grants U01DK061718, U01DK061728, U01DK061731,
U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730,
U01DK061713), and the National Institute of Child Health and Human
Development (NICHD). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 22
TC 9
Z9 11
U1 0
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 19
PY 2013
VL 8
IS 7
AR e65982
DI 10.1371/journal.pone.0065982
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 191CY
UT WOS:000322391400001
PM 23894275
ER
PT J
AU Ha, J
Kuznetsov, A
AF Ha, Joon
Kuznetsov, Alexey
TI Interaction of NMDA Receptor and Pacemaking Mechanisms in the Midbrain
Dopaminergic Neuron
SO PLOS ONE
LA English
DT Article
ID COUPLED-OSCILLATOR MODEL; SUBSTANTIA-NIGRA; FIRING PATTERN;
COMPUTATIONAL MODEL; POTASSIUM CHANNELS; CALCIUM-CHANNELS; COMPACTA
NEURONS; IN-VITRO; RAT; CONDUCTANCES
AB Dopamine neurotransmission has been found to play a role in addictive behavior and is altered in psychiatric disorders. Dopaminergic (DA) neurons display two functionally distinct modes of electrophysiological activity: low- and high-frequency firing. A puzzling feature of the DA neuron is the following combination of its responses: N-methyl-D-aspartate receptor (NMDAR) activation evokes high-frequency firing, whereas other tonic excitatory stimuli (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate receptor (AMPAR) activation or applied depolarization) block firing instead. We suggest a new computational model that reproduces this combination of responses and explains recent experimental data. Namely, somatic NMDAR stimulation evokes high-frequency firing and is more effective than distal dendritic stimulation. We further reduce the model to a single compartment and analyze the mechanism of the distinct high-frequency response to NMDAR activation vs. other stimuli. Standard nullcline analysis shows that the mechanism is based on a decrease in the amplitude of calcium oscillations. The analysis confirms that the nonlinear voltage dependence provided by the magnesium block of the NMDAR determine its capacity to elevate the firing frequency. We further predict that the moderate slope of the voltage dependence plays the central role in the frequency elevation. Additionally, we suggest a repolarizing current that sustains calcium-independent firing or firing in the absence of calcium-dependent repolarizing currents. We predict that the ether-a-go-go current (ERG), which has been observed in the DA neuron, is the best fit for this critical role. We show that a calcium-dependent and a calcium-independent oscillatory mechanisms form a structure of interlocked negative feedback loops in the DA neuron. The structure connects research of DA neuron firing with circadian biology and determines common minimal models for investigation of robustness of oscillations, which is critical for normal function of both systems.
C1 [Ha, Joon] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
[Kuznetsov, Alexey] Purdue Univ Indianapolis, Indiana Univ, Dept Math Sci, Indianapolis, IN USA.
[Kuznetsov, Alexey] Purdue Univ Indianapolis, Indiana Univ, Ctr Math Biosci, Indianapolis, IN USA.
RP Kuznetsov, A (reprint author), Purdue Univ Indianapolis, Indiana Univ, Dept Math Sci, Indianapolis, IN USA.
EM alexey@math.iupui.edu
FU National Science Foundation [DMS-0817717]
FX The work was supported by the National Science Foundation grant
DMS-0817717. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 54
TC 4
Z9 4
U1 1
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 19
PY 2013
VL 8
IS 7
AR e69984
DI 10.1371/journal.pone.0069984
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 191CY
UT WOS:000322391400075
PM 23894569
ER
PT J
AU Wojczynski, MK
Li, MY
Bielak, LF
Kerr, KF
Reiner, AP
Wong, ND
Yanek, LR
Qu, LM
White, CC
Lange, LA
Ferguson, JF
He, J
Young, T
Mosley, TH
Smith, JA
Kral, BG
Guo, XQ
Wong, Q
Ganesh, SK
Heckbert, SR
Griswold, ME
O'Leary, DH
Budoff, M
Carr, JJ
Taylor, HA
Bluemke, DA
Demissie, S
Hwang, SJ
Paltoo, DN
Polak, JF
Psaty, BM
Becker, DM
Province, MA
Post, WS
O'Donnell, CJ
Wilson, JG
Harris, TB
Kavousi, M
Cupples, LA
Rotter, JI
Fornage, M
Becker, LC
Peyser, PA
Borecki, IB
Reilly, MP
AF Wojczynski, Mary K.
Li, Mingyao
Bielak, Lawrence F.
Kerr, Kathleen F.
Reiner, Alex P.
Wong, Nathan D.
Yanek, Lisa R.
Qu, Liming
White, Charles C.
Lange, Leslie A.
Ferguson, Jane F.
He, Jing
Young, Taylor
Mosley, Thomas H.
Smith, Jennifer A.
Kral, Brian G.
Guo, Xiuqing
Wong, Quenna
Ganesh, Santhi K.
Heckbert, Susan R.
Griswold, Michael E.
O'Leary, Daniel H.
Budoff, Matthew
Carr, J. Jeffrey
Taylor, Herman A., Jr.
Bluemke, David A.
Demissie, Serkalem
Hwang, Shih-Jen
Paltoo, Dina N.
Polak, Joseph F.
Psaty, Bruce M.
Becker, Diane M.
Province, Michael A.
Post, Wendy S.
O'Donnell, Christopher J.
Wilson, James G.
Harris, Tamara B.
Kavousi, Maryam
Cupples, L. Adrienne
Rotter, Jerome I.
Fornage, Myriam
Becker, Lewis C.
Peyser, Patricia A.
Borecki, Ingrid B.
Reilly, Muredach P.
TI Genetics of coronary artery calcification among African Americans, a
meta-analysis
SO BMC MEDICAL GENETICS
LA English
DT Article
DE Atherosclerosis; Coronary artery calcium; Genetics; Meta-analysis;
African-American
ID GENOME-WIDE ASSOCIATION; BEAM COMPUTED-TOMOGRAPHY; SINGLE NUCLEOTIDE
POLYMORPHISMS; MYOCARDIAL-INFARCTION; ATHEROSCLEROSIS MESA;
ETHNIC-DIFFERENCES; RISK-FACTORS; CARDIOVASCULAR-DISEASE; ASYMPTOMATIC
ADULTS; QUANTITATIVE-TRAIT
AB Background: Coronary heart disease (CHD) is the major cause of death in the United States. Coronary artery calcification (CAC) scores are independent predictors of CHD. African Americans (AA) have higher rates of CHD but are less well-studied in genomic studies. We assembled the largest AA data resource currently available with measured CAC to identify associated genetic variants.
Methods: We analyzed log transformed CAC quantity (ln(CAC + 1)), for association with similar to 2.5 million single nucleotide polymorphisms (SNPs) and performed an inverse-variance weighted meta-analysis on results for 5,823 AA from 8 studies. Heritability was calculated using family studies. The most significant SNPs among AAs were evaluated in European Ancestry (EA) CAC data; conversely, the significance of published SNPs for CAC/CHD in EA was queried within our AA meta-analysis.
Results: Heritability of CAC was lower in AA (similar to 30%) than previously reported for EA (similar to 50%). No SNP reached genome wide significance (p < 5E-08). Of 67 SNPs with p < 1E-05 in AA there was no evidence of association in EA CAC data. Four SNPs in regions previously implicated in CAC/CHD (at 9p21 and PHACTR1) in EA reached nominal significance for CAC in AA, with concordant direction. Among AA, rs16905644 (p = 4.08E-05) had the strongest association in the 9p21 region.
Conclusions: While we observed substantial heritability for CAC in AA, we failed to identify loci for CAC at genome-wide significant levels despite having adequate power to detect alleles with moderate to large effects. Although suggestive signals in AA were apparent at 9p21 and additional CAC and CAD EA loci, overall the data suggest that even larger samples and an ethnic specific focus will be required for GWAS discoveries for CAC in AA populations.
C1 [Wojczynski, Mary K.; Province, Michael A.; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
[Li, Mingyao; Qu, Liming] Univ Penn, Philadelphia, PA 19104 USA.
[Bielak, Lawrence F.; Smith, Jennifer A.; Peyser, Patricia A.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Kerr, Kathleen F.; Wong, Quenna] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Reiner, Alex P.; Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Wong, Nathan D.] Univ Calif Irvine, Heart Dis Prevent Program, Irvine, CA USA.
[Yanek, Lisa R.; Kral, Brian G.; Becker, Diane M.; Becker, Lewis C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[White, Charles C.; Demissie, Serkalem] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Lange, Leslie A.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Ferguson, Jane F.; Reilly, Muredach P.] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Ferguson, Jane F.; Reilly, Muredach P.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Young, Taylor] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
[Guo, Xiuqing; Rotter, Jerome I.] Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst Harbor, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
[Ganesh, Santhi K.] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
[Griswold, Michael E.] Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA.
[O'Leary, Daniel H.; Polak, Joseph F.] Tufts Univ, Sch Med, Dept Radiol, Boston, MA 02111 USA.
[Budoff, Matthew] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA.
[Carr, J. Jeffrey] Wake Forest Univ, Bowman Gray Sch Med, Dept Radiol, Winston Salem, NC USA.
[Taylor, Herman A., Jr.] Jackson State Univ, Tougaloo Coll, Jackson, MS USA.
[Taylor, Herman A., Jr.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Hwang, Shih-Jen; O'Donnell, Christopher J.; Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Hwang, Shih-Jen] Ctr Populat Studies, Framingham, MA USA.
[Paltoo, Dina N.] NHLBI, Adv Technol & Surg Branch, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA.
[Post, Wendy S.] Johns Hopkins Sch Med & Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Post, Wendy S.] Johns Hopkins Sch Med & Publ Hlth, Dept Med, Baltimore, MD USA.
[O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA USA.
[O'Donnell, Christopher J.] NHLBI, Bethesda, MD 20892 USA.
[Wilson, James G.] Univ Mississippi, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Kavousi, Maryam] Netherlands Genom Initiat Sponsored Netherlands C, Rotterdam, Netherlands.
[Kavousi, Maryam] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Fornage, Myriam] Univ Texas Houston, Houston Inst Mol Med, Houston, TX USA.
RP Wojczynski, MK (reprint author), Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
EM mwojczynski@wustl.edu; iborecki@wustl.edu; Muredach@mail.med.upenn.edu
RI Ferguson, Jane/C-7154-2011; Carr, John/A-1938-2012; Kerr,
Kathleen/A-2893-2013;
OI Ferguson, Jane/0000-0001-6896-1025; Carr, John/0000-0002-4398-8237;
Cupples, L. Adrienne/0000-0003-0273-7965; Bluemke,
David/0000-0002-8323-8086; Smith, Jennifer/0000-0002-3575-5468
FU NIH from NHLBI [R01-HL-087700, R01-HL-088215]; NIH from NIDDK
[R01-DK-8925601, R01-DK-075681]; National Heart, Lung, and Blood
Institute; University of Alabama at Birmingham [N01-HC-48047,
N01-HC-95095]; University of Minnesota [N01-HC-48048, N01-HC-95163];
Northwestern University [N01-HC-48049, N01-HC-95164]; Kaiser Foundation
Research Institute [N01-HC-48050]; Tufts-New England Medical Center
[N01-HC-45204]; Wake Forest University [N01-HC-45205, N01-HC-95165];
Harbor-UCLA Research and Education Institute [N01-HC-05187,
N01-HC-95169]; University of California, Irvine [N01-HC-45134,
N01-HC-95100]; Jackson Heart Study (JHS): Jackson State University
[N01-HC-95170]; University of Mississippi [N01-HC-95171]; Tougaloo
College [N01-HC-95172]; Multi-Ethnic Study of Atherosclerosis (MESA):
University of Washington [N01-HC-95159]; Regents of the University of
California [N01-HC-95160]; Columbia University [N01-HC-95161]; Johns
Hopkins University [N01-HC-95162, N01-HC-95168]; University of Vermont
[N01-HC-95166]; New England Medical Center [N01-HC-95167]; Cedars-Sinai
Medical Center [R01-HL-071205]; University of Virginia [R01-HL-071205];
National Heart, Lung, and Blood Institute [N01-HC-48047, N01-HC-95095,
N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-45204, N01-HC-45205,
N01-HC-05187, N01-HC-45134]; NHLBI's Candidate-gene Association REsource
(CARe) Study; National Heart, Lung, and Blood Institute (NHLBI); United
States Environmental Protection Agency (EPA); NHLBI [N02-HL-6-4278];
National Heart, Lung, and Blood Institute (NHLBI) through the STAMPEED
[R01 HL087698-01]; NIH/National Institute of Nursing Research
[NR008153-01]; NIH/National Center for Research Resources
[M01-RR000052]; National Institutes of Health from National Heart, Lung,
Blood Institute [HL085571, HL087660, HL100245]; AXA Research Fund;
[R01-HL084099]; [U01-HG004729]; [R01HL071051]; [R01HL071205];
[R01HL071250]; [R01HL071251]; [R01HL071252]; [R01HL071258];
[R01HL071259]; [RD83169701]; [HL58625-01A1]; [HL59684];
[HL071025-01A1]; [R01-DK071224]; [R01-DK-090505]; [U01-HL108636];
[K24-HL107643]; [R01-HL113147]
FX The National Heart, Lung, and Blood Institute's Family Heart Study
(FamHS) was supported by NIH grants R01-HL-087700 and R01-HL-088215
(Michael A. Province, PI) from NHLBI; and R01-DK-8925601 and
R01-DK-075681 (Ingrid B. Borecki, PI) from NIDDK.; The authors from the
CARe Consortium wish to acknowledge the support of the National Heart,
Lung, and Blood Institute and the contributions of the research
institutions, study investigators, field staff and study participants in
creating this resource for biomedical research. The following studies
have contributed parent study data, ancillary study data, and DNA
samples through the Broad Institute (N01-HC-65226).; Coronary Artery
Risk in Young Adults (CARDIA): University of Alabama at Birmingham
(N01-HC-48047), University of Minnesota (N01-HC-48048), Northwestern
University (N01-HC-48049), Kaiser Foundation Research Institute
(N01-HC-48050), University of Alabama at Birmingham (N01-HC-95095),
Tufts-New England Medical Center (N01-HC-45204), Wake Forest University
(N01-HC-45205), Harbor-UCLA Research and Education Institute
(N01-HC-05187), University of California, Irvine (N01-HC-45134,
N01-HC-95100); Jackson Heart Study (JHS): Jackson State University
(N01-HC-95170), University of Mississippi (N01-HC-95171), Tougaloo
College (N01-HC-95172); Multi-Ethnic Study of Atherosclerosis (MESA):
University of Washington (N01-HC-95159), Regents of the University of
California (N01-HC-95160), Columbia University (N01-HC-95161), Johns
Hopkins University (N01-HC-95162, N01-HC-95168), University of Minnesota
(N01-HC-95163), Northwestern University (N01-HC-95164), Wake Forest
University (N01-HC-95165), University of Vermont (N01-HC-95166), New
England Medical Center (N01-HC-95167), Harbor-UCLA Research and
Education Institute (N01-HC-95169), Cedars-Sinai Medical Center
(R01-HL-071205), University of Virginia (subcontract to R01-HL-071205).;
The Coronary Artery Risk Development in Young Adults (CARDIA) study is
funded by contracts N01-HC-95095, N01-HC-48047, N01-HC-48048,
N01-HC-48049, N01-HC-48050, N01-HC-45134, N01-HC-05187, N01-HC-45205,
and N01-HC-45204 from the National Heart, Lung, and Blood Institute to
the CARDIA investigators. GWAS genotyping and quality control for the
CARDIA African-Americans was supported by the NHLBI's Candidate-gene
Association REsource (CARe) Study. Statistical analysis of CARDIA data
was supported by grants R01-HL084099 and U01-HG004729 to MF. This
manuscript has been reviewed by CARDIA for scientific content and
consistency of data interpretation with previous CARDIA publications.;
The MESA Family/Air Studies were conducted and supported by the National
Heart, Lung, and Blood Institute (NHLBI) and the United States
Environmental Protection Agency (EPA) in collaboration with MESA Family
and MESA Air investigators, respectively. Support for MESA Family is
provided by grants and contracts R01HL071051, R01HL071205, R01HL071250,
R01HL071251, R01HL071252, R01HL071258, and R01HL071259. Support for MESA
Air is provided by grant RD83169701. Funding for genotyping was provided
by NHLBI Contract N02-HL-6-4278. Genotyping was performed at the Broad
Institute of Harvard and MIT (Boston, Massachusetts, USA) and at
Affymetrix (Santa Clara, California, USA) using the Affymetrix
Genome-Wide Human SNP Array 6.0.; The GeneSTAR Study was supported by
the National Heart, Lung, and Blood Institute (NHLBI) through the
STAMPEED (R01 HL087698-01) consortium as well as grants HL58625-01A1,
HL59684, and HL071025-01A1, and a grant from the NIH/National Institute
of Nursing Research (NR008153-01).; Additional support was provided by a
grant from the NIH/National Center for Research Resources (M01-RR000052)
to the Johns Hopkins General Clinical Research Center.; The Genetic
Epidemiology Network of Arteriopathy (GENOA) is supported by the
National Institutes of Health, grant numbers HL085571, HL087660, and
HL100245 from National Heart, Lung, Blood Institute. We thank Eric
Boerwinkle, PhD from the Human Genetics Center and Institute of
Molecular Medicine and Division of Epidemiology, University of Texas
Health Science Center, Houston, Texas, USA and Julie Cunningham, PhD
from the Department of Health Sciences Research, Mayo Clinic College of
Medicine, Rochester, MN, USA for their help with genotyping.; MPR is
supported by R01-DK071224, R01-DK-090505, U01-HL108636, K24-HL107643 and
R01-HL113147.; MK is supported by the AXA Research Fund.
NR 46
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Z9 18
U1 0
U2 11
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2350
J9 BMC MED GENET
JI BMC Med. Genet.
PD JUL 19
PY 2013
VL 14
AR 75
DI 10.1186/1471-2350-14-75
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 193ED
UT WOS:000322539700001
PM 23870195
ER
PT J
AU Robledo, C
Peck, JD
Stoner, JA
Carabin, H
Cowan, L
Koch, HM
Goodman, JR
AF Robledo, Candace
Peck, Jennifer D.
Stoner, Julie A.
Carabin, Helene
Cowan, Linda
Koch, Holger M.
Goodman, Jean R.
TI IS BISPHENOL-A EXPOSURE DURING PREGNANCY ASSOCIATED WITH BLOOD GLUCOSE
LEVELS OR DIAGNOSIS OF GESTATIONAL DIABETES?
SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES
LA English
DT Article
ID MEMBRANE ESTROGEN-RECEPTOR; INSULIN-RESISTANCE;
POLYCHLORINATED-BIPHENYLS; METABOLITE CONCENTRATIONS; PHTHALATE
METABOLITES; SEX STEROIDS; WOMEN; COHORT; URINE; VARIABILITY
AB Recent epidemiological studies indicate bisphenol A (BPA), an estrogenic chemical used in production of epoxy, polycarbonate, and plastic may increase risk of insulin resistance and type 2 diabetes. Exposure to BPA during pregnancy may contribute to development of gestational diabetes mellitus (GDM), a precursor to type 2 diabetes in women. This pilot study examined the association between BPA exposure, fasting blood glucose levels (FBG), and GDM diagnosis during pregnancy. Banked urine samples from 22 cases of GDM and 72 controls were analyzed for total (free BPA + conjugates) urinary BPA concentrations (g/L). FBG levels (mg/dl) were obtained from 1-h 50-g glucose tolerance tests (GTT) that women underwent for routine GDM screening (mean gestational age = 26.6 weeks, SD = 3.8). Those with an initial screening value 135 mg/dl underwent 3-h 100 g oral GTT. GDM diagnoses were made when the initial screening value was 200 mg/dl or when values at 2 time points exceeded 3-h oral GTT thresholds. Among controls, median FBG levels (mg/dL) did not differ across exposure tertiles, defined according to the distribution of total specific-gravity-adjusted urinary BPA concentrations. Logistic regression models controlling for race/ethnicity did not provide evidence of association between BPA exposure and case status across increasing tertiles of BPA exposure (number of GDM cases/controls in tertile1: 13/24; in tertile 2: 6/24; in tertile 3: 3/24). Findings do not support a relationship between total urinary BPA concentrations and altered glucose metabolism during pregnancy. However, due to study limitations, findings need to be interpreted with caution.
C1 [Robledo, Candace; Peck, Jennifer D.; Stoner, Julie A.; Carabin, Helene; Cowan, Linda] Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Dept Biostat & Epidemiol, Oklahoma City, OK USA.
[Koch, Holger M.] Inst Ruhr Univ Bochum IPA, German Social Accid Insurance, Inst Prevent & Occupat Med, Bochum, Germany.
[Goodman, Jean R.] Loyola Univ Hlth Syst, Stritch Sch Med, Dept Obstet & Gynecol, Maternal Fetal Med, Maywood, IL USA.
RP Robledo, C (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd,Room 7B13E, Rockville, MD 20892 USA.
EM robledoc@mail.nih.gov
RI Koch, Holger/B-3277-2011; Carabin, Helene/B-7600-2016
OI Koch, Holger/0000-0002-8328-2837;
FU National Institute for Occupational and Environmental Health
(NIOSH)/Centers for Disease Control and Prevention [T42OH008421];
Oklahoma Tobacco Research Center; Intramural Research Program of the
NIH, Eunice Kennedy Shriver National Institute of Child Health & Human
Development
FX This research was supported in part by the Oklahoma Tobacco Research
Center and the Intramural Research Program of the NIH, Eunice Kennedy
Shriver National Institute of Child Health & Human Development. Grant
funds for lab analyses were provided by grant T42OH008421 from the
National Institute for Occupational and Environmental Health
(NIOSH)/Centers for Disease Control and Prevention to the Southwest
Center for Occupational and Environmental Health (SWCOEH), a NIOSH
Education and Research Center.
NR 41
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U1 1
U2 20
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 520 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1528-7394
EI 1087-2620
J9 J TOXICOL ENV HEAL A
JI J. Toxicol. Env. Health Part A
PD JUL 18
PY 2013
VL 76
IS 14
BP 865
EP 873
DI 10.1080/15287394.2013.824395
PG 9
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 220TW
UT WOS:000324610800004
PM 24053363
ER
PT J
AU Li, WQ
Hu, N
Wang, ZM
Yu, K
Su, H
Wang, LM
Wang, CY
Chanock, SJ
Burdett, L
Ding, T
Qiao, YL
Fan, JH
Wang, Y
Xu, Y
Giffen, C
Xiong, XQ
Murphy, G
Tucker, MA
Dawsey, SM
Freedman, ND
Abnet, CC
Goldstein, AM
Taylor, PR
AF Li, Wen-Qing
Hu, Nan
Wang, Zhaoming
Yu, Kai
Su, Hua
Wang, Lemin
Wang, Chaoyu
Chanock, Stephen J.
Burdett, Laurie
Ding, Ti
Qiao, You-Lin
Fan, Jin-Hu
Wang, Yuan
Xu, Yi
Giffen, Carol
Xiong, Xiaoqin
Murphy, Gwen
Tucker, Margaret A.
Dawsey, Sanford M.
Freedman, Neal D.
Abnet, Christian C.
Goldstein, Alisa M.
Taylor, Philip R.
TI Genetic Variants in Epidermal Growth Factor Receptor Pathway Genes and
Risk of Esophageal Squamous Cell Carcinoma and Gastric Cancer in a
Chinese Population
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; SOMATIC MUTATIONS; KINASE
DOMAIN; HELICOBACTER-PYLORI; ADENOCARCINOMA; POLYMORPHISMS; TARGETS;
MDM2; P53
AB The epidermal growth factor receptor (EGFR) signaling pathway regulates cell proliferation, differentiation, and survival, and is frequently dysregulated in esophageal and gastric cancers. Few studies have comprehensively examined the association between germline genetic variants in the EGFR pathway and risk of esophageal and gastric cancers. Based on a genome-wide association study in a Han Chinese population, we examined 3443 SNPs in 127 genes in the EGFR pathway for 1942 esophageal squamous cell carcinomas (ESCCs), 1758 gastric cancers (GCs), and 2111 controls. SNP-level analyses were conducted using logistic regression models. We applied the resampling-based adaptive rank truncated product approach to determine the gene- and pathway-level associations. The EGFR pathway was significantly associated with GC risk (P = 2.16x10(-3)). Gene-level analyses found 10 genes to be associated with GC, including FYN, MAPK8, MAP2K4, GNAI3, MAP2K1, TLN1, PRLR, PLCG2, RPS6KB2, and PIK3R3 (P<0.05). For ESCC, we did not observe a significant pathway-level association (P = 0.72), but gene-level analyses suggested associations between GNAI3, CHRNE, PAK4, WASL, and ITCH, and ESCC (P<0.05). Our data suggest an association between specific genes in the EGFR signaling pathway and risk of GC and ESCC. Further studies are warranted to validate these associations and to investigate underlying mechanisms.
C1 [Li, Wen-Qing; Hu, Nan; Wang, Zhaoming; Yu, Kai; Su, Hua; Wang, Lemin; Wang, Chaoyu; Murphy, Gwen; Tucker, Margaret A.; Dawsey, Sanford M.; Freedman, Neal D.; Abnet, Christian C.; Goldstein, Alisa M.; Taylor, Philip R.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Wang, Zhaoming; Chanock, Stephen J.; Burdett, Laurie] SAIC Frederick Inc, NCI Frederick, Canc Genom Res Lab, Frederick, MD USA.
[Ding, Ti; Wang, Yuan; Xu, Yi] Shanxi Canc Hosp, Taiyuan, Shanxi, Peoples R China.
[Qiao, You-Lin; Fan, Jin-Hu] Chinese Acad Med Sci, Canc Inst Hosp, Dept Epidemiol, Beijing 100730, Peoples R China.
[Giffen, Carol; Xiong, Xiaoqin] Informat Management Serv Inc, Silver Spring, MD USA.
RP Li, WQ (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM liw9@mail.nih.gov
RI Li, Wenqing/N-2293-2014; Tucker, Margaret/B-4297-2015; Abnet,
Christian/C-4111-2015; Murphy, Gwen/G-7443-2015; Freedman,
Neal/B-9741-2015;
OI Li, Wenqing/0000-0002-1283-4091; Abnet, Christian/0000-0002-3008-7843;
Freedman, Neal/0000-0003-0074-1098; Qiao, You-Lin/0000-0001-6380-0871
FU National Cancer Institute (NCI) [NO2-SC-66211]; Shanxi Cancer Hospital;
Shanxi Cancer Institute; NCI [NO1-SC-91030, HHSN261200477001C]; Cancer
Institute of the Chinese Academy of Medical Sciences; Intramural
Research Program of the National Institutes of Health (NIH), NCI;
Division of Cancer Epidemiology and Genetics
FX The Shanxi Upper Gastrointestinal Cancer Genetics Project was supported
by the National Cancer Institute (NCI) contract NO2-SC-66211 with the
Shanxi Cancer Hospital and Institute. The Nutrition Intervention Trials
were supported by NCI contracts NO1-SC-91030 and HHSN261200477001C with
the Cancer Institute of the Chinese Academy of Medical Sciences. The
current analysis was supported by the Intramural Research Program of the
National Institutes of Health (NIH), NCI, and the Division of Cancer
Epidemiology and Genetics. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 41
TC 8
Z9 9
U1 0
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 18
PY 2013
VL 8
IS 7
AR e68999
DI 10.1371/journal.pone.0068999
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 214PM
UT WOS:000324146200050
PM 23874846
ER
PT J
AU Monteiro, AC
Leal, AC
Goncalves-Silva, T
Mercadante, ACT
Kestelman, F
Chaves, SB
Azevedo, RB
Monteiro, JP
Bonomo, A
AF Monteiro, Ana Carolina
Leal, Ana Carolina
Goncalves-Silva, Triciana
Mercadante, Ana Carolina T.
Kestelman, Fabiola
Chaves, Sacha Braun
Azevedo, Ricardo Bentes
Monteiro, Joao P.
Bonomo, Adriana
TI T Cells Induce Pre-Metastatic Osteolytic Disease and Help Bone
Metastases Establishment in a Mouse Model of Metastatic Breast Cancer
SO PLOS ONE
LA English
DT Article
ID OSTEOCLAST FORMATION; OSTEOPROTEGERIN-LIGAND; MAMMARY-CANCER;
IMMUNE-SYSTEM; FAMILY-MEMBER; IN-VIVO; TUMOR; MARROW; MICE; RANK
AB Bone metastases, present in 70% of patients with metastatic breast cancer, lead to skeletal disease, fractures and intense pain, which are all believed to be mediated by tumor cells. Engraftment of tumor cells is supposed to be preceded by changes in the target tissue to create a permissive microenvironment, the pre-metastatic niche, for the establishment of the metastatic foci. In bone metastatic niche, metastatic cells stimulate bone consumption resulting in the release of growth factors that feed the tumor, establishing a vicious cycle between the bone remodeling system and the tumor itself. Yet, how the pre-metastatic niches arise in the bone tissue remains unclear. Here we show that tumor-specific T cells induce osteolytic bone disease before bone colonization. T cells pro-metastatic activity correlate with a pro-osteoclastogenic cytokine profile, including RANKL, a master regulator of osteoclastogenesis. In vivo inhibition of RANKL from tumor-specific T cells completely blocks bone loss and metastasis. Our results unveil an unexpected role for RANKL-derived from T cells in setting the pre-metastatic niche and promoting tumor spread. We believe this information can bring new possibilities for the development of prognostic and therapeutic tools based on modulation of T cell activity for prevention and treatment of bone metastasis.
C1 [Monteiro, Ana Carolina; Leal, Ana Carolina; Goncalves-Silva, Triciana; Mercadante, Ana Carolina T.; Bonomo, Adriana] Brazilian Natl Canc Inst, Expt Med Program, Rio De Janeiro, Brazil.
[Kestelman, Fabiola] Brazilian Natl Canc Inst, HCIII, Rio De Janeiro, Brazil.
[Chaves, Sacha Braun; Azevedo, Ricardo Bentes] Univ Brasilia, Inst Biol, Brasilia, DF, Brazil.
[Monteiro, Joao P.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
[Monteiro, Ana Carolina; Goncalves-Silva, Triciana; Mercadante, Ana Carolina T.; Bonomo, Adriana] Fiocruz MS, Inst Oswaldo Cruz, Lab Thymus Res, BR-21045900 Rio De Janeiro, Brazil.
[Goncalves-Silva, Triciana; Bonomo, Adriana] Univ Fed Rio de Janeiro, Microbiol Inst Prof Paulo de Goes, Dept Immunol, Rio De Janeiro, Brazil.
RP Bonomo, A (reprint author), Brazilian Natl Canc Inst, Expt Med Program, Rio De Janeiro, Brazil.
EM abonomo@micro.ufrj.br
FU CNPq [57.3806/2008- INCT, 306624/2010-9]; FAPERJ [E-26/111.423/2010,
E-26/110.949/2008, E-26/110.323/2010]; Swiss Bridge Foundation [2301500]
FX This work was supported by CNPq grants 57.3806/2008- INCT,
306624/2010-9, FAPERJ grants #E-26/111.423/2010; E-26/110.949/2008;
E-26/110.323/2010 and Swiss Bridge Foundation # 2301500. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 47
TC 17
Z9 18
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 18
PY 2013
VL 8
IS 7
AR UNSP e68171
DI 10.1371/journal.pone.0068171
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 214PM
UT WOS:000324146200014
PM 23935856
ER
PT J
AU Movahedan, A
Afsharkhamseh, N
Sagha, HM
Shah, JR
Milani, BY
Milani, FY
Logothetis, HD
Chan, CC
Djalilian, AR
AF Movahedan, Asadolah
Afsharkhamseh, Neda
Sagha, Hossein M.
Shah, Jarna R.
Milani, Behrad Y.
Milani, Farnoud Y.
Logothetis, Hercules D.
Chan, Chi-Chao
Djalilian, Ali R.
TI Loss of Notch1 Disrupts the Barrier Repair in the Corneal Epithelium
SO PLOS ONE
LA English
DT Article
ID EPIDERMAL DIFFERENTIATION; CELL DIFFERENTIATION; DOWN-REGULATION; MOUSE
SKIN; FATE; PROLIFERATION; PROMOTES; PATHWAY; RESTORATION; JUNCTIONS
AB The corneal epithelium is the outermost layer of the cornea that directly faces the outside environment, hence it plays a critical barrier function. Previously, conditional loss of Notch1 on the ocular surface was found to cause inflammation and keratinization of the corneal epithelium. This was in part attributed to impaired vitamin A metabolism, loss of the meibomian glands and recurrent eyelid trauma. We hypothesized that Notch1 plays an essential role in the corneal epithelial barrier function and is a contributing factor in the pathologic changes in these mice. Notch1 was conditionally deleted in adult Notch1(flox/flox), K14-Cre-ERT+/- mice using hydroxy-tamoxifen. The results indicated that conditional deletion of Notch1 on the ocular surface leads to progressive impairment of the epithelial barrier function before the onset of corneal opacification and keratinization. Loss of the barrier was demonstrated both by an increase in in vivo corneal fluorescein staining and by enhanced penetration of a small molecule through the epithelium. Corneal epithelial wounding resulted in significant delay in recovery of the barrier function in conditional Notch1(-/-) mice compared to wild type. Mice with conditional deletion of Notch1 did not demonstrate any evidence of dry eyes based on aqueous tear production and had normal conjunctival goblet cells. In a calcium switch experiment in vitro, Notch1(-/-) cells demonstrated delayed membrane localization of the tight junction protein ZO-1 consistent with a defect in the epithelial tight junction formation. These findings highlight the role of Notch1 in epithelial differentiation and suggest that intrinsic defects in the corneal epithelial barrier recovery after wounding is an important contributing factor to the development of inflammatory keratinization in Notch1(-/-) mice.
C1 [Movahedan, Asadolah; Afsharkhamseh, Neda; Sagha, Hossein M.; Shah, Jarna R.; Milani, Behrad Y.; Milani, Farnoud Y.; Logothetis, Hercules D.; Djalilian, Ali R.] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60607 USA.
[Chan, Chi-Chao] NEI, NIH, Bethesda, MD 20892 USA.
RP Djalilian, AR (reprint author), Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60607 USA.
EM adjalili@uic.edu
OI Movahedan, Asadolah/0000-0001-5759-6579
FU National Institutes of Health [K08EY017561-A1, EY01792]; Cless Family
Foundation; Research to Prevent Blindness
FX This research was supported by a career development grant K08EY017561-A1
to ARD, a core grant EY01792 from the National Institutes of Health, and
by the Cless Family Foundation. ARD is the recipient of a Career
Development Award from Research to Prevent Blindness. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 43
TC 8
Z9 9
U1 0
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 18
PY 2013
VL 8
IS 7
AR e69113
DI 10.1371/journal.pone.0069113
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 214PM
UT WOS:000324146200057
PM 23874882
ER
PT J
AU Dunleavy, K
Bollard, CM
AF Dunleavy, Kieron
Bollard, Catherine M.
TI Scouting out the neighborhood in AIDS-related lymphoma
SO BLOOD
LA English
DT Editorial Material
ID B-CELL LYMPHOMA; ANGIOGENESIS
C1 [Dunleavy, Kieron] NCI, Bethesda, MD 20892 USA.
[Bollard, Catherine M.] Baylor Coll Med, Houston, TX 77030 USA.
RP Dunleavy, K (reprint author), NCI, Bethesda, MD 20892 USA.
FU NCI NIH HHS [P50 CA126752]
NR 10
TC 1
Z9 1
U1 0
U2 1
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 JUL 18
PY 2013
VL 122
IS 3
BP 306
EP 307
DI 10.1182/blood-2013-06-502591
PG 4
WC Hematology
SC Hematology
GA 196QM
UT WOS:000322790500003
PM 23869074
ER
PT J
AU Galarneau, G
Coady, S
Garrett, ME
Jeffries, N
Puggal, M
Paltoo, D
Soldano, K
Guasch, A
Ashley-Koch, AE
Telen, MJ
Kutlar, A
Lettre, G
Papanicolaou, GJ
AF Galarneau, Genevieve
Coady, Sean
Garrett, Melanie E.
Jeffries, Neal
Puggal, Mona
Paltoo, Dina
Soldano, Karen
Guasch, Antonio
Ashley-Koch, Allison E.
Telen, Marilyn J.
Kutlar, Abdullah
Lettre, Guillaume
Papanicolaou, George J.
TI Gene-centric association study of acute chest syndrome and painful
crisis in sickle cell disease patients
SO BLOOD
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SECRETORY PHOSPHOLIPASE A(2); RISK-FACTORS;
INFLAMMATORY HYPERALGESIA; HEMOGLOBIN DISORDERS; FETAL-HEMOGLOBIN;
POLYMORPHISMS; CHILDREN; ANEMIA; FAMILY
AB Patients with sickle cell disease (SCD) present with a wide range of clinical complications. Understanding this clinical heterogeneity offers the prospects to tailor the right treatments to the right patients and also guide the development of novel therapies. Several environmental (eg, nutrition) and nonenvironmental (eg, fetal hemoglobin levels, alpha-thalassemia status) factors are known to modify SCD severity. To find new genetic modifiers of SCD severity, we performed a gene-centric association study in 1514 African American participants from the Cooperative Study of Sickle Cell Disease (CSSCD) for acute chest syndrome (ACS) and painful crisis. From the initial results, we selected 36 single nucleotide polymorphism (SNPs) and genotyped them for replication in 387 independent patients from the CSSCD, 318 SCD patients recruited at Georgia Health Sciences University, and 449 patients from the Duke SCD cohort. In the combined analysis, an association between ACS and rs6141803 reached array-wide significance (P = 4.1 x 10(-7)). This SNP is located 8.2 kilobases upstream of COMMD7, a gene highly expressed in the lung that interacts with nuclear factor-kappa B signaling. Our results provide new leads to gaining a better understanding of clinical variability in SCD, a "simple" monogenic disease.
C1 [Galarneau, Genevieve; Lettre, Guillaume] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.
[Galarneau, Genevieve; Lettre, Guillaume] Univ Montreal, Montreal, PQ, Canada.
[Coady, Sean; Jeffries, Neal; Puggal, Mona; Paltoo, Dina; Papanicolaou, George J.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Garrett, Melanie E.; Soldano, Karen; Ashley-Koch, Allison E.] Duke Univ, Med Ctr, Dept Med, Ctr Human Genet, Durham, NC 27710 USA.
[Guasch, Antonio] Emory Univ, Atlanta, GA 30322 USA.
[Telen, Marilyn J.] Duke Univ, Med Ctr, Dept Med, Div Hematol, Durham, NC 27710 USA.
[Kutlar, Abdullah] Med Coll Georgia, Dept Med, Sickle Cell Ctr, Augusta, GA 30912 USA.
RP Lettre, G (reprint author), Montreal Heart Inst, 5000 Belanger St, Montreal, PQ H1T 1C8, Canada.
EM guillaume.lettre@umontreal.ca; gjp@mail.nih.gov
OI Ashley-Koch, Allison/0000-0001-5409-9155
FU National Institutes of Health, National Heart, Lung, and Blood Institute
[N01-HB-47110]; National Heart, Lung, and Blood Institute
[HHSN268200625226C, RO1 HL079915, RC2-HL101212]; Doris Duke Charitable
Foundation [2009089]; Canada Research Chair Program; Canadian Institute
of Health Research [123382]; Fonds de Recherche Sante Quebec
FX CSSCD is supported in part by the National Institutes of Health,
National Heart, Lung, and Blood Institute (N01-HB-47110). CARe is
supported by the National Heart, Lung, and Blood Institute
(HHSN268200625226C). A full listing of the grants and contracts that
have supported CARe is provided at
http://www.nhlbi.nih.gov/resources/geneticsgenomics/programs/care.htm.
The work in the Lettre Laboratory is supported by a Innovation in
Clinical Research Award grant from the Doris Duke Charitable Foundation
(2009089), the Canada Research Chair Program, the Canadian Institute of
Health Research (123382), and the Fonds de Recherche Sante Quebec. The
work at Duke University was funded in part by the National Heart, Lung,
and Blood Institute (RO1 HL079915 and RC2-HL101212).
NR 50
TC 9
Z9 9
U1 0
U2 8
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 JUL 18
PY 2013
VL 122
IS 3
BP 434
EP 442
DI 10.1182/blood-2013-01-478776
PG 9
WC Hematology
SC Hematology
GA 196QM
UT WOS:000322790500020
PM 23719301
ER
PT J
AU Bjorkholm, M
Kristinsson, SY
Landgren, O
Goldin, LR
AF Bjorkholm, Magnus
Kristinsson, Sigurdur Y.
Landgren, Ola
Goldin, Lynn R.
TI No familial aggregation in chronic myeloid leukemia
SO BLOOD
LA English
DT Letter
ID CHRONIC MYELOGENOUS LEUKEMIA
C1 [Bjorkholm, Magnus; Kristinsson, Sigurdur Y.] Karolinska Univ Hosp, Dept Med, Stockholm, Sweden.
[Bjorkholm, Magnus; Kristinsson, Sigurdur Y.] Karolinska Inst, Stockholm, Sweden.
[Kristinsson, Sigurdur Y.] Univ Iceland, Landspitali Natl Univ Hosp, Fac Med, Dept Hematol, Reykjavik, Iceland.
[Landgren, Ola] NCI, Multiple Myeloma Sect, Metab Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Goldin, Lynn R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Bjorkholm, M (reprint author), Karolinska Univ Hosp & Inst, Dept Med, SE-17176 Stockholm, Sweden.
EM magnus.bjorkholm@karolinska.se
RI Kristinsson, Sigurdur /M-2910-2015
OI Kristinsson, Sigurdur /0000-0002-4964-7476
FU Intramural NIH HHS
NR 8
TC 6
Z9 6
U1 0
U2 2
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 JUL 18
PY 2013
VL 122
IS 3
BP 460
EP 461
DI 10.1182/blood-2013-05-501312
PG 4
WC Hematology
SC Hematology
GA 196QM
UT WOS:000322790500025
PM 23869079
ER
PT J
AU Bruno, RD
Rosenfield, SM
Smith, GH
AF Bruno, Robert D.
Rosenfield, Sonia M.
Smith, Gilbert H.
TI Late developing mammary tumors and hyperplasia induced by a
low-oncogenic variant of mouse mammary tumor virus (MMTV) express genes
identical to those induced by canonical MMTV
SO MOLECULAR CANCER
LA English
DT Article
DE Mammary tumorigenesis; Mouse mammary tumor virus; Nodule inducing virus;
Mtv-1; Common integration sites
ID PROLACTIN; SECRETION; CANCER; STRAIN; MICE
AB Background: The canonical milk-transmitted mouse mammary tumor virus (MMTV) of C3H mice (C3H-MMTV) rapidly induces tumors in 90% of infected animals by 8 months of age. Pro-viral insertions of C3H-MMTV into genomic DNA results in the overexpression of common core insertion site (CIS) genes, including Wnt1/10b, Rspo2, and Fgf3. Conversely, infection by either the endogenous Mtv-1 virus (in C3Hf) or the exogenous nodule-inducing virus (NIV) (in Balb/c NIV) induces premalignant mammary lesions and tumors with reduced incidence and longer latency than C3H-MMTV. Here, we asked whether Mtv-1/NIV affected the expression of core CIS genes.
Findings: We confirmed the presence of active virus in Mtv-1/NIV infected tissues and using quantitative reverse transcription PCR (qRT-PCR) found that Mtv-1/NIV induced neoplasms (tumors and hyperplasia) commonly expressed the core CIS genes Wnt1, Wnt10b, Rspo2, Fgf3.
Conclusions: These results underscore the importance of core CIS gene expression in the early events leading to MMTV-induced mammary tumor initiation regardless of the viral variant.
C1 [Bruno, Robert D.; Rosenfield, Sonia M.; Smith, Gilbert H.] NCI, CCBB, CCR, Bethesda, MD 20892 USA.
RP Smith, GH (reprint author), NCI, CCBB, CCR, Bethesda, MD 20892 USA.
EM smithg@mail.nih.gov
OI Bruno, Robert/0000-0003-3329-9478
FU Center for Cancer Research at NCI
FX The authors wish to acknowledge the excellent technical help of Adam
Money during his summer internship. This manuscript is dedicated to the
memory of L. J.T. Young whose contributions to this field have been far
reaching and without whose steadfast interest in mammary tumorigenesis,
this work would not have been possible. The research reported here was
supported in its entirety by the intramural research program of the
Center for Cancer Research at NCI.
NR 18
TC 1
Z9 1
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-4598
J9 MOL CANCER
JI Mol. Cancer
PD JUL 18
PY 2013
VL 12
AR 79
DI 10.1186/1476-4598-12-79
PG 6
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 198JX
UT WOS:000322920100001
PM 23866257
ER
PT J
AU Kovalchik, SA
Tammemagi, M
Berg, CD
Caporaso, NE
Riley, TL
Korch, M
Silvestri, GA
Chaturvedi, AK
Katki, HA
AF Kovalchik, Stephanie A.
Tammemagi, Martin
Berg, Christine D.
Caporaso, Neil E.
Riley, Tom L.
Korch, Mary
Silvestri, Gerard A.
Chaturvedi, Anil K.
Katki, Hormuzd A.
TI Targeting of Low-Dose CT Screening According to the Risk of Lung-Cancer
Death
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID TRIAL; PREDICTION; MODEL; VALIDATION; BENEFITS; SELECTION; PROSTATE;
CRITERIA; SMOKERS; COHORT
AB Background
In the National Lung Screening Trial (NLST), screening with low-dose computed tomography (CT) resulted in a 20% reduction in lung-cancer mortality among participants between the ages of 55 and 74 years with a minimum of 30 pack-years of smoking and no more than 15 years since quitting. It is not known whether the benefits and potential harms of such screening vary according to lung-cancer risk.
Methods
We assessed the variation in efficacy, the number of false positive results, and the number of lung-cancer deaths prevented among 26,604 participants in the NLST who underwent low-dose CT screening, as compared with the 26,554 participants who underwent chest radiography, according to the quintile of 5-year risk of lung-cancer death (ranging from 0.15 to 0.55% in the lowest-risk group [quintile 1] to more than 2.00% in the highest-risk group [quintile 5]).
Results
The number of lung-cancer deaths per 10,000 person-years that were prevented in the CT-screening group, as compared with the radiography group, increased according to risk quintile (0.2 in quintile 1, 3.5 in quintile 2, 5.1 in quintile 3, 11.0 in quintile 4, and 12.0 in quintile 5; P=0.01 for trend). Across risk quintiles, there were significant decreasing trends in the number of participants with false positive results per screening-prevented lung-cancer death (1648 in quintile 1, 181 in quintile 2, 147 in quintile 3, 64 in quintile 4, and 65 in quintile 5). The 60% of participants at highest risk for lung-cancer death (quintiles 3 through 5) accounted for 88% of the screening-prevented lung-cancer deaths and for 64% of participants with false positive results. The 20% of participants at lowest risk (quintile 1) accounted for only 1% of prevented lung-cancer deaths.
Conclusions
Screening with low-dose CT prevented the greatest number of deaths from lung cancer among participants who were at highest risk and prevented very few deaths among those at lowest risk. These findings provide empirical support for risk-based targeting of smokers for such screening. (Funded by the National Cancer Institute.)
C1 [Kovalchik, Stephanie A.; Caporaso, Neil E.; Chaturvedi, Anil K.; Katki, Hormuzd A.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Berg, Christine D.] NCI, Canc Prevent Div, NIH, Rockville, MD USA.
[Riley, Tom L.; Korch, Mary] Informat Management Serv Inc, Rockville, MD USA.
[Tammemagi, Martin] Brock Univ, Dept Community Hlth Sci, St Catharines, ON L2S 3A1, Canada.
[Silvestri, Gerard A.] Med Univ S Carolina, Div Pulm & Crit Care Med, Charleston, SC 29425 USA.
RP Kovalchik, SA (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,Rm 7E-606 MSC 9780, Bethesda, MD 20892 USA.
EM kovalchiksa@mail.nih.gov; katkih@mail.nih.gov
RI Berg , Christine/K-1047-2014; Katki, Hormuzd/B-4003-2015; Chaturvedi,
Anil/J-2024-2015
OI Chaturvedi, Anil/0000-0003-2696-8899
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute
(NCI), National Institutes of Health, Department of Health and Human
Services; NCI; Cancer Imaging Program, Division of Cancer Treatment and
Diagnosis, NCI; Early Detection Research Group and Biometry Research
Group, Division of Cancer Prevention, NCI [N01-CN-25514, N01-CN-25522,
N01-CN-25515, N01-CN-25512, N01-CN-25513, N01-CN-25516, N01-CN-25511,
N01-CN-25524, N01-CN-25518, N01-CN-75022, N01-CN-25476, N02-CN-63300]
FX Supported by the Intramural Research Program of the Division of Cancer
Epidemiology and Genetics, National Cancer Institute (NCI), National
Institutes of Health, Department of Health and Human Services. The PLCO
trial was supported by the NCI. The American College of Radiology
Imaging Network component of the NLST was supported by grants
(U01-CA-80098 and U01-CA-79778) under a cooperative agreement with the
Cancer Imaging Program, Division of Cancer Treatment and Diagnosis, NCI.
The Lung Screening Study sites of the NLST were funded through contracts
with the Early Detection Research Group and Biometry Research Group,
Division of Cancer Prevention, NCI (N01-CN-25514, to University of
Colorado-Denver; N01-CN-25522, to Georgetown University; N01-CN-25515,
to Pacific Health Research and Education Institute; N01-CN-25512, to
Henry Ford Health System; N01-CN-25513, to University of Minnesota;
N01-CN-25516, to Washington University in St. Louis; N01-CN-25511, to
University of Pittsburgh; N01-CN-25524, to University of Utah;
N01-CN-25518, to Marshfield Clinic Research Foundation; N01-CN-75022, to
University of Alabama at Birmingham; N01-CN-25476, to Westat;
N02-CN-63300, to Information Management Services).
NR 33
TC 161
Z9 166
U1 2
U2 27
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 18
PY 2013
VL 369
IS 3
BP 245
EP 254
DI 10.1056/NEJMoa1301851
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 185DQ
UT WOS:000321945800010
PM 23863051
ER
PT J
AU Cohen, JI
AF Cohen, Jeffrey I.
TI Herpes Zoster
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID PLACEBO-CONTROLLED TRIAL; POSTHERPETIC NEURALGIA; DOUBLE-BLIND;
IMMUNOCOMPROMISED PATIENTS; IMMUNOCOMPETENT PATIENTS; NEUROPATHIC PAIN;
RANDOMIZED-TRIAL; IMPROVED THERAPY; ORAL ACYCLOVIR; VIRUS
AB A 65-year-old man presents with a rash of 2 days' duration over the right forehead with vesicles and pustules, a few lesions on the right side and tip of the nose, and slight blurring of vision in the right eye. The rash was preceded by tingling in the area and is now associated with aching pain. How should this patient be evaluated and treated?
C1 [Cohen, Jeffrey I.] NIH, Infect Dis Lab, Med Virol Sect, Bethesda, MD 20892 USA.
RP Cohen, JI (reprint author), NIH, Infect Dis Lab, Bldg 50,Rm 6134,50 South Dr,MSC1807, Bethesda, MD 20892 USA.
EM jcohen@niaid.nih.gov
FU Intramural NIH HHS [Z01 AI000430-23]
NR 42
TC 78
Z9 79
U1 0
U2 20
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 18
PY 2013
VL 369
IS 3
BP 255
EP 263
DI 10.1056/NEJMcp1302674
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 185DQ
UT WOS:000321945800011
PM 23863052
ER
PT J
AU Joseph, SK
Ramaswamy, K
AF Joseph, S. K.
Ramaswamy, K.
TI Single multivalent vaccination boosted by trickle larval infection
confers protection against experimental lymphatic filariasis
SO VACCINE
LA English
DT Article
DE Lymphatic filariasis; Brugia malayi; BmHAT multivalent vaccine; L3
trickle booster
ID WUCHERERIA-BANCROFTI MICROFILARIAE; BRUGIA-MALAYI; IMMUNE-RESPONSES;
MASTOMYS-COUCHA; DNA VACCINATION; ADULT WORM; PROTEIN; STAGE; ALT-2;
TETRASPANIN-2
AB The multivalent vaccine BmHAT, consisting of the Brugia malayi infective larval (L3) antigens heat shock protein12.6 (HSP12.6), abundant larval transcript-2 (ALT-2) and tetraspanin large extra cellular loop (TSP-LEL), was shown to be protective in rodent models from our laboratory. We hypothesize that since these antigens were identified using protective antibodies from immune endemic normal individuals, the multivalent vaccine can be augmented by natural L3 infections providing protection to the vaccinated host. This hypothesis was tested using single dose of DNA and protein or protein alone of the BmHAT vaccination in gerbils followed by live trickle L3 infection as booster dose. Vaccine-induced protection in gerbils was determined by worm establishment, micropore chamber assay and by antibody dependant cell cytotoxicity (ADCC) assay. Results were compared with the traditional prime-boost vaccination regimen. Gerbils vaccinated with BmHAT and boosted with L3 trickle infection were protected 51% (BmHAT DNA protein) and 48% (BmHAT protein) respectively. BmHAT vaccination plus L3 trickle booster generated significant titer of antigen-specific IgG antibodies comparable to the traditional prime boost vaccination approach. BmHAT vaccination plus L3 trickle booster also generated antigen-specific cells in the spleen of vaccinated animals and these cells secreted predominantly IFN-gamma and IL-4 in response to the vaccine antigens. These studies thus show that single dose of BmHAT multivalent vaccination followed by L3 trickle booster infection can confer significant protection against lymphatic filariasis. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Joseph, S. K.; Ramaswamy, K.] Univ Illinois, Coll Med Rockford, Dept Biomed Sci, Rockford, IL 61107 USA.
[Joseph, S. K.] NIH NIAID LMIV Twinbrook I, Rockville, MD 20852 USA.
RP Ramaswamy, K (reprint author), Univ Illinois, Coll Med, Dept Biomed Sci, 1601 Parkview Ave, Rockford, IL 61107 USA.
EM ramswamy@uic.edu
RI Joseph, Sujith/C-2835-2012
OI Joseph, Sujith/0000-0003-4596-1270
FU NIH [AI064745]
FX We would like to thank NIAID/NIH Filariasis Research Reagent Resource
Center (FR3) at the University of Georgia, Athens, GA, for providing us
with parasite materials for this study. This study was supported by NIH
Grant AI064745.
NR 32
TC 7
Z9 7
U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD JUL 18
PY 2013
VL 31
IS 33
BP 3320
EP 3326
DI 10.1016/j.vaccine.2013.05.077
PG 7
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 187FF
UT WOS:000322101600003
PM 23735679
ER
PT J
AU Lindow, JC
Durbin, AP
Whitehead, SS
Pierce, KK
Carmolli, MP
Kirkpatrick, BD
AF Lindow, Janet C.
Durbin, Anna P.
Whitehead, Stephen S.
Pierce, Kristen K.
Carmolli, Marya P.
Kirkpatrick, Beth D.
TI Vaccination of volunteers with low-dose, live-attenuated, dengue viruses
leads to serotype-specific immunologic and virologic profiles
SO VACCINE
LA English
DT Article
DE Dengue virus; Dengue vaccine; Low dose; Viremia; Neutralizing
antibodies; HID50
ID HEALTHY ADULT VOLUNTEERS; RHESUS-MONKEYS; NAIVE ADULTS; VACCINES;
IMMUNOGENICITY; CANDIDATE; SAFETY; TYPE-4; MOSQUITOS; CHILDREN
AB There are currently no vaccines or therapeutics to prevent dengue disease which ranges in severity from asymptomatic infections to life-threatening illness. The National Institute of Allergy and Infectious Diseases (NIAID) Division of Intramural Research has developed live, attenuated vaccines to each of the four dengue serotypes (DENV-1-DENV-4). Two doses (10 PFU and 1000 PFU) of three monovalent vaccines were tested in human clinical trials to compare safety and immunogenicity profiles. DEN4 Delta 30 had been tested previously at multiple doses. The three dengue vaccine candidates tested (DEN1 Delta 30, DEN2/4 Delta 30, and DEN3 Delta 30/31) were very infectious, each with a human infectious dose 50% <= 10 PFU. Further, infectivity rates ranged from 90 to 100% regardless of dose, excepting DEN2/4 Delta 30 which dropped from 100% at the 1000 PFU dose to 60% at the 10 PFU dose. Mean geometric peak antibody titers did not differ significantly between doses for DEN1 Delta 30 (92 +/- 19 vs. 214 +/- 97, p = 0.08); however, significant differences were observed between the 10 PFU and 1000 PFU doses for DEN2/4 Delta 30, 19 +/- 9 vs. 102 +/- 25 (p = 0.001), and DEN3 Delta 30/31, 119 +/- 135 vs. 50 +/- 50 (p = 0.046). No differences in the incidences of rash, neutropenia, or viremia were observed between doses for any vaccines, though the mean peak titer of viremia for DEN1 Delta 30 was higher at the 1000 PFU dose (0.5 +/- 0 vs. 1.1 +/- 0.1, p = 0.007). These data demonstrate that a target dose of 1000 PFU for inclusion of each dengue serotype into a tetravalent vaccine is likely to be safe and generate a balanced immune response for all serotypes. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Lindow, Janet C.; Pierce, Kristen K.; Carmolli, Marya P.; Kirkpatrick, Beth D.] Univ Vermont, Coll Med, Vaccine Testing Ctr, Burlington, VT USA.
[Lindow, Janet C.; Pierce, Kristen K.; Carmolli, Marya P.; Kirkpatrick, Beth D.] Infect Dis Unit, Burlington, VT USA.
[Durbin, Anna P.] Johns Hopkins Sch Publ Hlth, CIR, Baltimore, MD 21205 USA.
[Whitehead, Stephen S.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
RP Kirkpatrick, BD (reprint author), Univ Vermont, Coll Med, Vaccine Testing Ctr, 95 Carrigan Dr,Stafford Hall 110, Burlington, VT USA.
EM beth.kirkpatrick@uvm.edu
OI Lindow, Janet/0000-0003-3235-3698
FU Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Disease [HHSN272200900010C]
FX This work was supported by contract HHSN272200900010C from the
Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Disease. We are grateful
for the tireless efforts of the dengue vaccine teams. At the University
of Vermont's Vaccine Testing Center we thank: Caroline Lyon, Catherine
Larsson, Mary Claire Walsh, Ellen Fraser, Cassandra Ventrone, Elizabeth
Dill, Nathan Borochoff-Porte, Stacia Rymarchyk, GCRC Staff, Donna
Jacobs. At the Johns Hopkins Bloomberg School of Public Health, we
thank: Cecilia Tibery, Donna Shaffer, Kawsar Talaat, Noreen Hynes,
Beulah Sabundayo, Bridget McMahon, Janet Hurd, Kimberli Wanionek, and
Sabrina Drayton. Lastly we wish to thank our biostatistician, Janice Y.
Bunn, for her invaluable assistance.
NR 41
TC 17
Z9 17
U1 1
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD JUL 18
PY 2013
VL 31
IS 33
BP 3347
EP 3352
DI 10.1016/j.vaccine.2013.05.075
PG 6
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 187FF
UT WOS:000322101600007
PM 23735680
ER
PT J
AU Kim, JY
Zhao, H
Martinez, J
Doggett, TA
Kolesnikov, AV
Tang, PH
Ablonczy, Z
Chan, CC
Zhou, ZQ
Green, DR
Ferguson, TA
AF Kim, Ji-Young
Zhao, Hui
Martinez, Jennifer
Doggett, Teresa Ann
Kolesnikov, Alexander V.
Tang, Peter H.
Ablonczy, Zsolt
Chan, Chi-Chao
Zhou, Zhenqing
Green, Douglas R.
Ferguson, Thomas A.
TI Noncanonical Autophagy Promotes the Visual Cycle
SO CELL
LA English
DT Article
ID RETINAL-PIGMENT EPITHELIUM; LIPID-PEROXIDATION PRODUCTS; LEBER
CONGENITAL AMAUROSIS; AGE-RELATED MACULOPATHY; PHOTORECEPTOR
DEGENERATION; ALPHA-V-BETA-5 INTEGRIN; MACULAR DEGENERATION; TARGETED
DISRUPTION; BINDING PROTEIN; OUTER SEGMENTS
AB Phagocytosis and degradation of photoreceptor outer segments (POS) by retinal pigment epithelium (RPE) is fundamental to vision. Autophagy is also responsible for bulk degradation of cellular components, but its role in POS degradation is not well understood. We report that the morning burst of RPE phagocytosis coincided with the enzymatic conversion of autophagy protein LC3 to its lipidated form. LC3 associated with single-membrane phagosomes containing engulfed POS in an Atg5-dependent manner that required Beclin1, but not the autophagy preinitiation complex. The importance of this process was verified in mice with Atg5-deficient RPE cells that showed evidence of disrupted lysosomal processing. These mice also exhibited decreased photoreceptor responses to light stimuli and decreased chromophore levels that were restored with exogenous retinoid supplementation. These results establish that the interplay of phagocytosis and autophagy within the RPE is required for both POS degradation and the maintenance of retinoid levels to support vision.
C1 [Kim, Ji-Young; Zhao, Hui; Doggett, Teresa Ann; Kolesnikov, Alexander V.; Zhou, Zhenqing; Ferguson, Thomas A.] Washington Univ, St Louis Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA.
[Martinez, Jennifer; Green, Douglas R.] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA.
[Tang, Peter H.; Ablonczy, Zsolt] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA.
[Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Green, DR (reprint author), St Jude Childrens Res Hosp, Dept Immunol, 332 N Lauderdale St, Memphis, TN 38105 USA.
EM douglas.green@stjude.org; ferguson@vision.wustl.edu
RI Zhou, Zhenqing/I-7260-2016
FU National Institutes of Health [EY015570, AI40646]; Department of
Ophthalmology and Visual Sciences [EY02687]; Research to Prevent
Blindness (New York); BrightFocus Foundation (Clarksburg)
FX This work was supported by National Institutes of Health grants EY015570
(to T.A.F.) and AI40646 (to D.R.G.) and the Department of Ophthalmology
and Visual Sciences core grant (EY02687). Support was also received from
Research to Prevent Blindness (New York) and the BrightFocus Foundation
(Clarksburg). The authors would like to thank Wandy Beatty for
performing the TEM and Jayoung Choi for assistance with the figure
layouts.
NR 63
TC 77
Z9 77
U1 0
U2 22
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD JUL 18
PY 2013
VL 154
IS 2
BP 365
EP 376
DI 10.1016/j.cell.2013.06.012
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 185FF
UT WOS:000321950700013
PM 23870125
ER
PT J
AU Yewdell, JW
Ince, WL
AF Yewdell, Jonathan W.
Ince, William L.
TI Greasing the SCIDs for Universal Flu Antibodies
SO CELL HOST & MICROBE
LA English
DT Editorial Material
ID BINDING SITE; INFLUENZA; NEUTRALIZATION; H5N1
AB In this issue, Nakamura et al. (2013) describe a robust SCID mouse-based method for isolating human monoclonal antibodies of desired specificity from adoptively transferred human B cells. As proof of principle, they isolate human mAbs that could potentially be used to treat or prevent human infection with any influenza A virus strain.
C1 [Yewdell, Jonathan W.; Ince, William L.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
EM jyewdell@nih.gov
FU Intramural NIH HHS [Z01 AI001055-01, ZIA AI001055-05, ZIA AI001055-02,
ZIA AI001014-03]
NR 10
TC 0
Z9 0
U1 0
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
EI 1934-6069
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD JUL 17
PY 2013
VL 14
IS 1
BP 7
EP 8
DI 10.1016/j.chom.2013.07.002
PG 2
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AA1JB
UT WOS:000330851300004
PM 23870308
ER
PT J
AU Luthra, P
Ramanan, P
Mire, CE
Weisend, C
Tsuda, Y
Yen, BJM
Liu, G
Leung, DW
Geisbert, TW
Ebihara, H
Amarasinghe, GK
Basler, CF
AF Luthra, Priya
Ramanan, Parameshwaran
Mire, Chad E.
Weisend, Carla
Tsuda, Yoshimi
Yen, Benjamin
Liu, Gai
Leung, Daisy W.
Geisbert, Thomas W.
Ebihara, Hideki
Amarasinghe, Gaya K.
Basler, Christopher F.
TI Mutual Antagonism between the Ebola Virus VP35 Protein and the RIG-I
Activator PACT Determines Infection Outcome
SO CELL HOST & MICROBE
LA English
DT Article
ID DOUBLE-STRANDED-RNA; INTERFERON INHIBITORY DOMAIN; MARBURG-VIRUS;
CELLULAR ACTIVATOR; PKR ACTIVATION; NUCLEOCAPSID PROTEINS; IRF-3
ACTIVATION; STRUCTURAL BASIS; KINASE; TRBP
AB The cytoplasmic pattern recognition receptor RIG-I is activated by viral RNA and induces type I IFN responses to control viral replication. The cellular dsRNA binding protein PACT can also activate RIG-I. To counteract innate antiviral responses, some viruses, including Ebola virus (EBOV), encode proteins that antagonize RIG-I signaling. Here, we show that EBOV VP35 inhibits PACT-induced RIG-I ATPase activity in a dose-dependent manner. The interaction of PACT with RIG-I is disrupted by wild-type VP35, but not by VP35 mutants that are unable to bind PACT. In addition, PACT-VP35 interaction impairs the association between VP35 and the viral polymerase, thereby diminishing viral RNA synthesis and modulating EBOV replication. PACT-deficient cells are defective in IFN induction and are insensitive to VP35 function. These data support a model in which the VP35-PACT interaction is mutually antagonistic and plays a fundamental role in determining the outcome of EBOV infection.
C1 [Luthra, Priya; Yen, Benjamin; Basler, Christopher F.] Mt Sinai Sch, Icahn Sch Med, Dept Microbiol, New York, NY 10029 USA.
[Ramanan, Parameshwaran; Liu, Gai; Leung, Daisy W.; Amarasinghe, Gaya K.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Ramanan, Parameshwaran] Iowa State Univ, Roy J Carver Dept Biochem Biophys & Mol Biol, Biochem Grad Program, Ames, IA 50011 USA.
[Mire, Chad E.; Geisbert, Thomas W.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston Natl Lab, Galveston, TX 77555 USA.
[Weisend, Carla; Tsuda, Yoshimi; Ebihara, Hideki] NIAID, Div Intramural Res, Virol Lab, NIH, Hamilton, MT 59840 USA.
RP Basler, CF (reprint author), Mt Sinai Sch, Icahn Sch Med, Dept Microbiol, New York, NY 10029 USA.
EM chris.basler@mssm.edu
OI Amarasinghe, Gaya/0000-0002-0418-9707
FU NIH [AI059536, AI093786, AI081914]; Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, USA
FX The work was supported in part by NIH grants AI059536 and AI093786 to C.
F. B.; NIH grant AI081914 to G. K. A.; and the Division of Intramural
Research, National Institute of Allergy and Infectious Diseases,
National Institutes of Health, USA. Monoclonal antibodies against EBOV
VP35 and EBOV NP were generated in collaboration with the Mount Sinai
Hybridoma Shared Research Facility. We thank Ganes Sen (Lerner Research
Institute, Cleveland Clinic) for providing PACT knockout MEFs, Qinghua
Liu (UT Southwestern, Dallas) for PACT cDNA, and Adolfo Garcia-Sastre
(Mount Sinai School of Medicine) for providing the RIG-I expression
plasmid. We thank Reed S. Shabman for assistance in setting up the
minigenome assays and Juyoung Huh (WUSM), Krystle Agans (UTMB), and
Kwabena Bonsu (MSSM) for excellent technical support.
NR 47
TC 41
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U1 2
U2 24
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
EI 1934-6069
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD JUL 17
PY 2013
VL 14
IS 1
BP 74
EP 84
DI 10.1016/j.chom.2013.06.010
PG 11
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AA1JB
UT WOS:000330851300011
PM 23870315
ER
PT J
AU Liao, LJ
Xing, H
Su, B
Wang, Z
Ruan, YH
Wang, X
Liu, ZD
Lu, YN
Yang, SM
Zhao, QB
Vermund, SH
Chen, RY
Shao, YM
AF Liao, Lingjie
Xing, Hui
Su, Bin
Wang, Zhe
Ruan, Yuhua
Wang, Xia
Liu, Zhendong
Lu, Yanan
Yang, Shimei
Zhao, Quanbi
Vermund, Sten H.
Chen, Ray Y.
Shao, Yiming
TI Impact of HIV drug resistance on virologic and immunologic failure and
mortality in a cohort of patients on antiretroviral therapy in China
SO AIDS
LA English
DT Article
DE antiretroviral therapy; China; cohort; drug resistance; immunologic
failure; mortality; virologic failure
ID RESOURCE-LIMITED SETTINGS; REVERSE-TRANSCRIPTASE; INFECTED PATIENTS;
INDIVIDUALS; MUTATIONS; ADHERENCE; REGIMEN; AFRICA; VIRUS; PERSPECTIVES
AB Objectives:To study the dynamics of HIV drug resistance (HIVDR) and its association with virologic and immunologic failure as well as mortality among patients on combination antiretroviral therapy (cART) in China.Design:We recruited 365 patients on cART in two rural Chinese counties in 2003-2004 and followed them every 6 months until May 2010.Methods:Virologic failure, HIVDR, immunologic failure and death were documented. We used Kaplan-Meier and the proportional hazards models to identify the timing of the events, and risk factors for mortality.Results:At the end of study, patients had been followed for 1974.3 person-years, a median of 6.1 years. HIVDR mutations were found in 235 (64.4%) patients and 75 died (20.5%, 3.8/100 person-years). Median time from cART to detection of virologic failure was 17.5 months, to HIVDR 36.6 months and to immunologic failure 55.2 months (approximate to 18-month median interval between each adverse milestone). Being male, having a baseline CD4(+) cell count of less than 50cells/l and HIVDR were associated with higher mortality. Patients who developed HIVDR in the first year of treatment had higher mortality than those developing HIVDR later (adjusted hazard ratio 1.90, 95% confidence interval 1.01-3.48).Conclusion:HIVDR was common and was associated with higher mortality among Chinese patients on cART, particular when HIVDR was detected early in therapy. Our study reinforces the importance of improving patient adherence to cART in order to delay the emergence of HIVDR and obviate the need to switch to costly second-line drug regimens too early.
C1 [Liao, Lingjie; Xing, Hui; Ruan, Yuhua; Wang, Xia; Zhao, Quanbi; Shao, Yiming] Chinese Ctr Dis Control & Prevent, Collaborat Innovat Ctr Diag & Treatment Infect Di, State Key Lab Infect Dis Prevent & Control, Beijing 102206, Peoples R China.
[Liao, Lingjie; Xing, Hui; Ruan, Yuhua; Wang, Xia; Zhao, Quanbi; Shao, Yiming] Chinese Ctr Dis Control & Prevent, Natl Ctr AIDS STD Control & Prevent, Beijing 102206, Peoples R China.
[Su, Bin] Anhui Ctr Dis Control & Prevent, Hefei, Anhui, Peoples R China.
[Liu, Zhendong] Funan Ctr Dis Control & Prevent, Funan, Peoples R China.
[Lu, Yanan] Yingzhou Ctr Dis Control & Prevent, Yingzhou, Anhui, Peoples R China.
[Yang, Shimei] Queshan Ctr Dis Control & Prevent, Queshan, Henan, Peoples R China.
[Vermund, Sten H.] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA.
[Vermund, Sten H.] Vanderbilt Univ, Sch Med, Inst Global Hlth, Nashville, TN 37212 USA.
[Chen, Ray Y.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Shao, YM (reprint author), Chinese Ctr Dis Control & Prevent, Collaborat Innovat Ctr Diag & Treatment Infect Di, State Key Lab Infect Dis Prevent & Control, 155 Changbai Rd, Beijing 102206, Peoples R China.
EM yshao08@gmail.com
OI Chen, Ray/0000-0001-6344-1442; Vermund, Sten/0000-0001-7289-8698
FU Ministry of Science and Technology of China [2012ZX10001-002]; National
natural Science Foundation in China [81101281]; Chinese State Key
Laboratory for Infectious Disease Develop Grant [2011SKLID102]; Canadian
International Development Research Centre [104519-010]
FX We appreciate the contribution of all persons participating in this
study. We thank the staff from provincial and county CDCs for sample
collection and assistance. We thank Drs Xihong Lin, Peter Gilbert and
Haiqun Lin for statistical suggestions. This work was supported by
grants from the Ministry of Science and Technology of China
(2012ZX10001-002), National natural Science Foundation in China
(81101281), and Chinese State Key Laboratory for Infectious Disease
Develop Grant (2011SKLID102), and the Canadian International Development
Research Centre (104519-010).
NR 38
TC 22
Z9 25
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD JUL 17
PY 2013
VL 27
IS 11
BP 1815
EP 1824
DI 10.1097/QAD.0b013e3283611931
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 250HL
UT WOS:000326841200015
PM 23803794
ER
PT J
AU Sheikh, V
Caplan, M
Wilson, EMP
Papadi, B
Rosenberg, AZ
Higgins, J
Driscoll, B
Filie, AC
Sereti, I
AF Sheikh, Virginia
Caplan, Margaret
Wilson, Eleanor M. P.
Papadi, Bhavesh
Rosenberg, Avi Z.
Higgins, Jeannette
Driscoll, Brian
Filie, Armando C.
Sereti, Irini
TI Cytomegalovirus immune reconstitution inflammatory syndrome manifesting
as sialadenitis in an HIV-infected patient
SO AIDS
LA English
DT Letter
ID SUBMANDIBULAR-GLAND; AIDS; DISEASE
C1 [Sheikh, Virginia; Wilson, Eleanor M. P.; Sereti, Irini] NIAID, NIH, Immunoregulat Lab, Bethesda, MD 20892 USA.
[Caplan, Margaret; Higgins, Jeannette] Frederick Natl Lab, Sci Applicat Int Corp Frederick, Frederick, MD USA.
[Papadi, Bhavesh; Rosenberg, Avi Z.; Filie, Armando C.] NCI, NIH, Pathol Lab, Bethesda, MD 20892 USA.
[Driscoll, Brian] NIDCD, NIH, Head & Neck Surg Branch, Bethesda, MD USA.
RP Sheikh, V (reprint author), NIAID, NIH, Immunoregulat Lab, CRC, 10 Ctr Dr,Rm 8C408, Bethesda, MD 20892 USA.
EM sheikh@niaid.nih.gov
OI Rosenberg, Avi/0000-0003-2356-950X; Wilson, Eleanor/0000-0002-4855-514X
FU Intramural NIH HHS; PHS HHS [HHSN261200800001E]
NR 6
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD JUL 17
PY 2013
VL 27
IS 11
BP 1833
EP 1835
DI 10.1097/QAD.0b013e328362d8b0
PG 3
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 250HL
UT WOS:000326841200020
PM 23803796
ER
PT J
AU Herrero, R
Quint, W
Hildesheim, A
Gonzalez, P
Struijk, L
Katki, HA
Porras, C
Schiffman, M
Rodriguez, AC
Solomon, D
Jimenez, S
Schiller, JT
Lowy, DR
van Doorn, LJ
Wacholder, S
Kreimer, AR
AF Herrero, Rolando
Quint, Wim
Hildesheim, Allan
Gonzalez, Paula
Struijk, Linda
Katki, Hormuzd A.
Porras, Carolina
Schiffman, Mark
Cecilia Rodriguez, Ana
Solomon, Diane
Jimenez, Silvia
Schiller, John T.
Lowy, Douglas R.
van Doorn, Leen-Jan
Wacholder, Sholom
Kreimer, Aimee R.
CA CVT Vaccine Grp
TI Reduced Prevalence of Oral Human Papillomavirus (HPV) 4 Years after
Bivalent HPV Vaccination in a Randomized Clinical Trial in Costa Rica
SO PLOS ONE
LA English
DT Article
ID YOUNG-WOMEN; INTRAEPITHELIAL NEOPLASIA; CANCER INCIDENCE;
BROAD-SPECTRUM; UNITED-STATES; GENOMIC DNA; NECK-CANCER; INFECTION;
EFFICACY; ASSAY
AB Background: Human papillomavirus (HPV) infection, particularly with type 16, causes a growing fraction of oropharyngeal cancers, whose incidence is increasing, mainly in developed countries. In a double-blind controlled trial conducted to investigate vaccine efficacy (VE) of the bivalent HPV 16/18 vaccine against cervical infections and lesions, we estimated VE against prevalent oral HPV infections 4 years after vaccination.
Methods and Findings: A total of 7,466 women 18-25 years old were randomized (1: 1) to receive the HPV16/18 vaccine or hepatitis A vaccine as control. At the final blinded 4-year study visit, 5,840 participants provided oral specimens (91.9% of eligible women) to evaluate VE against oral infections. Our primary analysis evaluated prevalent oral HPV infection among all vaccinated women with oral and cervical HPV results. Corresponding VE against prevalent cervical HPV16/18 infection was calculated for comparison. Oral prevalence of identifiable mucosal HPV was relatively low (1.7%). Approximately four years after vaccination, there were 15 prevalent HPV16/18 infections in the control group and one in the vaccine group, for an estimated VE of 93.3% (95% CI = 63% to 100%). Corresponding efficacy against prevalent cervical HPV16/18 infection for the same cohort at the same visit was 72.0% (95% CI = 63% to 79%) (p versus oral VE = 0.04). There was no statistically significant protection against other oral HPV infections, though power was limited for these analyses.
Conclusions: HPV prevalence four years after vaccination with the ASO4-adjuvanted HPV16/18 vaccine was much lower among women in the vaccine arm compared to the control arm, suggesting that the vaccine affords strong protection against oral HPV16/18 infection, with potentially important implications for prevention of increasingly common HPV-associated oropharyngeal cancer.
C1 [Herrero, Rolando] Int Agcy Res Canc, Prevent & Implementat Grp, F-69372 Lyon, France.
[Quint, Wim; Struijk, Linda; van Doorn, Leen-Jan] DDL Diagnost Lab, Rijswijk, Netherlands.
[Hildesheim, Allan; Katki, Hormuzd A.; Schiffman, Mark; Wacholder, Sholom; Kreimer, Aimee R.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Gonzalez, Paula; Porras, Carolina; Cecilia Rodriguez, Ana; Jimenez, Silvia] Fdn INCIENSA, Proyecto Epidemiol Guanacaste, Guanacaste, Costa Rica.
[Solomon, Diane] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Schiller, John T.; Lowy, Douglas R.] NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA.
RP Herrero, R (reprint author), Int Agcy Res Canc, Prevent & Implementat Grp, 150 Cours Albert Thomas, F-69372 Lyon, France.
EM herreror@iarc.fr
RI Katki, Hormuzd/B-4003-2015; Hildesheim, Allan/B-9760-2015; Kreimer,
Aimee/H-1687-2015
OI Hildesheim, Allan/0000-0003-0257-2363;
FU NCI [N01-CP-11005]; National Institutes of Health Office of Research on
Women's Health; GSK [FDA BB-IND 7920]
FX The Costa Rica HPV Vaccine Trial is a long-standing collaboration
between investigators in Costa Rica and the National Cancer Institute
(NCI). The trial is sponsored and funded by the NCI (contract
N01-CP-11005), with funding support from the National Institutes of
Health Office of Research on Women's Health. Vaccine was provided for
our trial by GlaxoSmithKline Biologicals (GSK), under a Clinical Trials
Agreement with the NCI. GSK also provided support for aspects of the
trial associated with regulatory submission needs of the company under
FDA BB-IND 7920. NCI and Costa Rica investigators were responsible for
the study design, data collection, data management, data analysis,
interpretation, and preparation of the report. The corresponding author
had access to all summary-level data. The NCI and Costa Rica
investigators had final responsibility for the decision to submit for
publication. GSK had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript. GSK had
the right to review and comment on the report.
NR 34
TC 130
Z9 132
U1 5
U2 14
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 17
PY 2013
VL 8
IS 7
AR e68329
DI 10.1371/journal.pone.0068329
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 185WH
UT WOS:000322000600008
PM 23873171
ER
PT J
AU Loverdo, C
Lloyd-Smith, JO
AF Loverdo, Claude
Lloyd-Smith, James O.
TI Evolutionary Invasion and Escape in the Presence of Deleterious
Mutations
SO PLOS ONE
LA English
DT Article
ID ASEXUAL POPULATIONS; LETHAL MUTAGENESIS; EMERGENCE; ADAPTATION;
PATHOGENS; VIRUSES; RATES; RNA; CONSEQUENCES; EPIDEMIOLOGY
AB Replicators such as parasites invading a new host species, species invading a new ecological niche, or cancer cells invading a new tissue often must mutate to adapt to a new environment. It is often argued that a higher mutation rate will favor evolutionary invasion and escape from extinction. However, most mutations are deleterious, and even lethal. We study the probability that the lineage will survive and invade successfully as a function of the mutation rate when both the initial strain and an adaptive mutant strain are threatened by lethal mutations. We show that mutations are beneficial, i.e. a non-zero mutation rate increases survival compared to the limit of no mutations, if in the no-mutation limit the survival probability of the initial strain is smaller than the average survival probability of the strains which are one mutation away. The mutation rate that maximizes survival depends on the characteristics of both the initial strain and the adaptive mutant, but if one strain is closer to the threshold governing survival then its properties will have greater influence. These conclusions are robust for more realistic or mechanistic depictions of the fitness landscapes such as a more detailed viral life history, or non-lethal deleterious mutations.
C1 [Loverdo, Claude; Lloyd-Smith, James O.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90024 USA.
[Lloyd-Smith, James O.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Loverdo, C (reprint author), Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90024 USA.
EM loverdo@ucla.edu
RI Lloyd-Smith, James/K-4080-2012;
OI Lloyd-Smith, James/0000-0001-7941-502X; Loverdo,
Claude/0000-0002-0888-1717
FU NSF [EF-0928690]; De Logi Chair in Biological Sciences; RAPIDD program
of the Science & Technology Directorate, Department of Homeland
Security; Fogarty International Center, National Institutes of Health
FX Both authors are supported by the NSF grant EF-0928690. JLS is grateful
for the support of the De Logi Chair in Biological Sciences, and the
RAPIDD program of the Science & Technology Directorate, Department of
Homeland Security, and the Fogarty International Center, National
Institutes of Health. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 45
TC 2
Z9 2
U1 2
U2 20
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 17
PY 2013
VL 8
IS 7
AR e68179
DI 10.1371/journal.pone.0068179
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 185WH
UT WOS:000322000600004
PM 23874532
ER
PT J
AU Timmerman, C
Suppiah, S
Gurudatta, BV
Yang, JP
Banerjee, C
Sandstrom, DJ
Corces, VG
Sanyal, S
AF Timmerman, Christina
Suppiah, Somu
Gurudatta, Baraka V.
Yang, Jingping
Banerjee, Christopher
Sandstrom, David J.
Corces, Victor G.
Sanyal, Subhabrata
TI The Drosophila Transcription Factor Adf-1 (nalyot) Regulates Dendrite
Growth by Controlling FasII and Staufen Expression Downstream of CaMKII
and Neural Activity
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID LOCAL PROTEIN-SYNTHESIS; ACTIVITY-DEPENDENT REGULATION; CONFOCAL IMAGE
STACKS; ENHANCER TRAP LINES; STRUCTURE IN-VIVO; LONG-TERM-MEMORY;
SYNAPTIC PLASTICITY; GENE-EXPRESSION; FASCICLIN-II; FUNCTIONAL
COMPONENTS
AB Memory deficits in Drosophila nalyot mutants suggest that the Myb family transcription factor Adf-1 is an important regulator of developmental plasticity in the brain. However, the cellular functions for this transcription factor in neurons or molecular mechanisms by which it regulates plasticity remain unknown. Here, we use in vivo 3D reconstruction of identifiable larval motor neuron dendrites to show that Adf-1 is required cell autonomously for dendritic development and activity-dependent plasticity of motor neurons downstream of CaMKII. Adf-1 inhibition reduces dendrite growth and neuronal excitability, and results in motor deficits and altered transcriptional profiles. Surprisingly, analysis by comparative chromatin immunoprecipitation followed by sequencing (ChIP-Seq) of Adf-1, RNA Polymerase II (Pol II), and histone modifications in Kc cells shows that Adf-1 binding correlates positively with high Pol II-pausing indices and negatively with active chromatin marks such as H3K4me3 and H3K27ac. Consistently, the expression of Adf-1 targets Staufen and Fasciclin II (FasII), identified through larval brain ChIP-Seq for Adf-1, is negatively regulated by Adf-1, and manipulations of these genes predictably modify dendrite growth. Our results imply mechanistic interactions between transcriptional and local translational machinery in neurons as well as conserved neuronal growth mechanisms mediated by cell adhesion molecules, and suggest that CaMKII, Adf-1, FasII, and Staufen influence crucial aspects of dendrite development and plasticity with potential implications for memory formation. Further, our experiments reveal molecular details underlying transcriptional regulation by Adf-1, and indicate active interaction between Adf-1 and epigenetic regulators of gene expression during activity-dependent neuronal plasticity.
C1 [Timmerman, Christina; Suppiah, Somu; Banerjee, Christopher; Sanyal, Subhabrata] Emory Univ, Dept Cell Biol, Atlanta, GA 30322 USA.
[Sanyal, Subhabrata] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA.
[Gurudatta, Baraka V.; Yang, Jingping; Corces, Victor G.] Emory Univ, Dept Biol, Atlanta, GA 30322 USA.
[Sandstrom, David J.] NIMH, Mol Biol Lab, Bethesda, MD 20892 USA.
[Sandstrom, David J.] Univ Maryland, Dept Biol Sci, College Pk, MD 20742 USA.
[Sanyal, Subhabrata] Biogen Idec Inc, Cambridge, MA 02142 USA.
RP Sanyal, S (reprint author), Emory Univ, Dept Cell Biol, Room 444,615 Michael St, Atlanta, GA 30322 USA.
EM ssanya2@emory.edu
FU Brain and Behavior Research Foundation; National Institutes of Health
[1R03DA027979, 5R21MH091520, 2R01GM035463]; National Institute of Child
Health and Human Development at the University of Iowa; Department of
Biological Sciences, Iowa City, IA
FX This work was supported by grants from the Brain and Behavior Research
Foundation (formerly the National Alliance for Research on Schizophrenia
and Depression), and by National Institutes of Health Grants
1R03DA027979 and 5R21MH091520 to S. Sanyal, and 2R01GM035463 to V.G.C.
We thank Carsten Duch, Felix Evers, and Fernando Vonhoff for help with
AMIRA and 3D dendrite reconstruction; and Pearl Ryder and Victor Faundez
for help with Cytoscape. The anti-Elav (Gerald Rubin) antibodies were
obtained from the Developmental Studies Hybridoma Bank developed under
the auspices of the National Institute of Child Health and Human
Development at the University of Iowa, Department of Biological
Sciences, Iowa City, IA.
NR 118
TC 4
Z9 4
U1 0
U2 9
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUL 17
PY 2013
VL 33
IS 29
BP 11916
EP +
DI 10.1523/JNEUROSCI.1760-13.2013
PG 17
WC Neurosciences
SC Neurosciences & Neurology
GA 184MG
UT WOS:000321893500019
PM 23864680
ER
PT J
AU Reis, JP
Loria, CM
Lewis, CE
Powell-Wiley, TM
Wei, GS
Carr, JJ
Terry, JG
Liu, K
AF Reis, Jared P.
Loria, Catherine M.
Lewis, Cora E.
Powell-Wiley, Tiffany M.
Wei, Gina S.
Carr, J. Jeffrey
Terry, James G.
Liu, Kiang
TI Association Between Duration of Overall and Abdominal Obesity Beginning
in Young Adulthood and Coronary Artery Calcification in Middle Age
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID DEPENDENT DIABETES-MELLITUS; BODY-MASS INDEX; ATHEROSCLEROSIS MESA;
ASYMPTOMATIC SUBJECTS; COMPUTED-TOMOGRAPHY; RISK DEVELOPMENT;
ADIPOSE-TISSUE; WEIGHT CHANGE; CARDIA; TRENDS
AB IMPORTANCE Younger individuals are experiencing a greater cumulative exposure to excess adiposity over their lifetime. However, few studies have determined the consequences of long-term obesity.
OBJECTIVE To examine whether the duration of overall and abdominal obesity was associated with the presence and 10-year progression of coronary artery calcification (CAC), a subclinical predictor of coronary heart disease.
DESIGN, SETTING, AND PARTICIPANTS Prospective study of 3275 white and black adults aged 18 to 30 years at baseline in 1985-1986 who did not initially have overall obesity (body mass index [BMI] >= 30) or abdominal obesity (men: waist circumference [WC] >102 cm; women: >88 cm) in the multicenter, community-based Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants completed computed tomography scanning for the presence of CAC during the 15-, 20-, or 25-year follow-up examinations. Duration of overall and abdominal obesity was calculated using repeat measurements of BMI and WC, respectively, performed 2, 5, 7, 10, 15, 20, and 25 years after baseline.
MAIN OUTCOMES AND MEASURES Presence of CAC was measured by computed tomography at the year 15 (2000-2001), year 20 (2005-2006), or year 25 (2010-2011) follow-up examinations. Ten-year progression of CAC (2000-2001 to 2010-2011) was defined as incident CAC in 2010-2011 or an increase in CAC score of 20 Agatston units or greater.
RESULTS During follow-up, 40.4% and 41.0% developed overall and abdominal obesity, respectively. Rates of CAC per 1000 person-years were higher for those who experienced more than 20 years vs 0 years of overall obesity (16.0 vs 11.0, respectively) and abdominal obesity (16.7 vs 11.0). Approximately 25.2% and 27.7% of those with more than 20 years of overall and abdominal obesity, respectively, experienced progression of CAC vs 20.2% and 19.5% of those with 0 years. After adjustment for BMI or WC and potential confounders, the hazard ratios for CAC for each additional year of overall or abdominal obesity were 1.02 (95% CI, 1.01-1.03) and 1.03 (95% CI, 1.02-1.05), respectively. The adjusted odds ratios for CAC progression were 1.04 (95% CI, 1.01-1.06) and 1.04 (95% CI, 1.01-1.07), respectively. Associations were attenuated but largely persisted following additional adjustment for potential intermediate metabolic factors during follow-up.
CONCLUSIONS AND RELEVANCE Longer duration of overall and abdominal obesity was associated with subclinical coronary heart disease and its progression through midlife independent of the degree of adiposity. Preventing or at least delaying the onset of obesity in young adulthood may lower the risk of developing atherosclerosis through middle age.
C1 [Reis, Jared P.; Loria, Catherine M.; Wei, Gina S.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Lewis, Cora E.] Univ Alabama Birmingham, Dept Med, Div Prevent Med, Birmingham, AL USA.
[Powell-Wiley, Tiffany M.] NHLBI, Cardiovasc & Pulm Branch, Bethesda, MD 20892 USA.
[Powell-Wiley, Tiffany M.] NCI, Appl Res Program, Div Canc Control & Populat Studies, Bethesda, MD 20892 USA.
[Carr, J. Jeffrey; Terry, James G.] Wake Forest Sch Med, Dept Radiol, Winston Salem, NC USA.
[Liu, Kiang] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
RP Reis, JP (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Ste 10197, Bethesda, MD 20892 USA.
EM reisjp@mail.nih.gov
RI Carr, John/A-1938-2012
OI Carr, John/0000-0002-4398-8237
FU National Heart, Lung, and Blood Institute [N01-HC95095, N01-HC48047,
N01-HC48050, N01-HC48049, N01-HC48048, R01-HL098445]
FX The Coronary Risk Development in Young Adults Study (CARDIA) was
conducted and supported by grants from the National Heart, Lung, and
Blood Institute (N01-HC95095 and N01-HC48047 awarded to the University
of Alabama at Birmingham; grant N01-HC48050 awarded to the Kaiser
Foundation Research Institute; grant N01-HC48049 awarded to Northwestern
University; N01-HC48048 awarded to the University of Minnesota; and
grant R01-HL098445 awarded to Wake Forest School of Medicine). Dr
Powell-Wiley is supported by the intramural research program of the
National Heart, Lung, and Blood Institute.
NR 36
TC 43
Z9 46
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 17
PY 2013
VL 310
IS 3
BP 280
EP 288
DI 10.1001/jama.2013.7833
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 183RU
UT WOS:000321835700015
PM 23860986
ER
PT J
AU Fisher, E
Reich, DS
AF Fisher, Elizabeth
Reich, Daniel S.
TI Imaging new lesions Enhancing our understanding of multiple sclerosis
pathogenesis
SO NEUROLOGY
LA English
DT Editorial Material
ID CONTRAST
C1 [Fisher, Elizabeth] Cleveland Clin, Lerner Res Inst, Dept Biomed Engn, Cleveland, OH 44106 USA.
[Reich, Daniel S.] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
RP Fisher, E (reprint author), Cleveland Clin, Lerner Res Inst, Dept Biomed Engn, Cleveland, OH 44106 USA.
EM fishere@ccf.org
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
NR 10
TC 0
Z9 0
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD JUL 16
PY 2013
VL 81
IS 3
BP 202
EP 203
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 304JP
UT WOS:000330743200004
PM 23761620
ER
PT J
AU Albanese, E
Lombardo, FL
Prince, MJ
Stewart, R
AF Albanese, Emiliano
Lombardo, Flavia L.
Prince, Martin J.
Stewart, Robert
TI Dementia and lower blood pressure in Latin America, India, and China A
10/66 cross-cohort study
SO NEUROLOGY
LA English
DT Article
ID INCIDENT DEMENTIA; ALZHEIMERS-DISEASE; DEVELOPING-COUNTRIES;
WEIGHT-LOSS; DIAGNOSIS; COMMUNITY; AGE; ASSOCIATION; MORTALITY; DECLINE
AB Objective: To study the relationship between dementia and blood pressure (BP) in 8 low-and middle-income countries.
Methods: In identical cross-sectional surveys of older adults (aged 65 years and older) conducted in Cuba, Dominican Republic, Peru, Venezuela, Mexico, Puerto Rico, China, and India (n = 15,746), we measured systolic and diastolic BP and used the 10/66 prevalidated algorithms to adjudicate dementia diagnosis and quantify dementia severity (Clinical Dementia Rating [CDR]).
Results: BP levels, dementia prevalence, and participants' sociodemographic and health characteristics varied across sites. In fixed-effect meta-analyses of site-specific linear regression coefficients adjusted for potential confounders, dementia and CDR were cross-sectionally associated with lower systolic BP (beta = -1.7, 95% confidence interval [CI]: -2.8, -0.6; and beta = -1.1, 95% CI: -1.5, -0.7) and diastolic BP (beta = -0.4, 95% CI: -1.1, 0.2; and beta = -0.4, 95% CI: -0.7, -0.2). Associations were heterogeneous across sites for both dementia (I-2, 47%) and CDR (I-2, 75%), and were strongest in Cuba, where prevalence of hypertension was highest. Results were robust to alternative model specifications that accounted for hypertensive status, antihypertensive treatment, and leanness (i.e., smaller waist circumference).
Conclusion: The association between dementia and lower BP was heterogeneous across geographically diverse samples, strongest where prevalent hypertension was highest (in Cuba), and relatively small compared with that found in Western settings. Both the mechanisms and the extent to which different levels of lifetime hypertensive disease explain this heterogeneity remain uncertain. However, because rapid increments in both dementia and hypertension are predicted in low-and middle-income countries, closer monitoring is warranted.
C1 [Albanese, Emiliano] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
[Lombardo, Flavia L.] Italian Natl Inst Hlth, Natl Ctr Epidemiol, Rome, Italy.
[Prince, Martin J.; Stewart, Robert] Kings Coll London, Inst Psychiat, London WC2R 2LS, England.
RP Albanese, E (reprint author), NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
EM emiliano.albanese@gmail.com
RI Prince, Martin/A-9170-2010
OI Prince, Martin/0000-0003-1379-7146
FU Wellcome Trust (UK) [GR066133]; WHO; US Alzheimer's Association
[IIRG-04-1286]; Fondo Nacional de Ciencia Y Tecnologia, Consejo de
Desarollo Cientifico Y Humanistico, Universidad Central de Venezuela
(Venezuela); GlaxoSmithKline; Novartis; Lundbeck; Pfizer; Eisai;
National Institute on Aging, NIH; National Institute for Health Research
(NIHR) Biomedical Research Centre; Dementia Biomedical Research Unit at
South London; Maudsley NHS Foundation Trust; King's College London
FX The 10/66 Dementia Research Group population-based surveys were funded
by the Wellcome Trust (UK) (GR066133); WHO; the US Alzheimer's
Association (IIRG-04-1286); and the Fondo Nacional de Ciencia Y
Tecnologia, Consejo de Desarollo Cientifico Y Humanistico, Universidad
Central de Venezuela (Venezuela). The Rockefeller Foundation supported a
dissemination meeting in their Bellagio Center. Alzheimer's Disease
International (ADI) has provided support for networking and
infrastructure. The 10/66 Dementia Research Group works closely with
ADI, which is a nonprofit federation of 77 Alzheimer associations around
the world. ADI is committed to strengthening Alzheimer associations
worldwide, raising awareness regarding dementia and Alzheimer disease,
and advocating for more and better services for people with dementia and
their caregivers. ADI is supported in part by grants from
GlaxoSmithKline, Novartis, Lundbeck, Pfizer, and Eisai. E. A. is
supported by the Intramural Research Program of the National Institute
on Aging, NIH. R. S. is partly funded by the National Institute for
Health Research (NIHR) Biomedical Research Centre and Dementia
Biomedical Research Unit at South London and Maudsley NHS Foundation
Trust and King's College London. None of the funders had any role in the
design, data collection, manuscript writing, or decision to submit for
publication.
NR 37
TC 5
Z9 5
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD JUL 16
PY 2013
VL 81
IS 3
BP 228
EP 235
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 304JP
UT WOS:000330743200009
PM 23771488
ER
PT J
AU Defazio, G
Hallett, M
Jinnah, HA
Berardelli, A
AF Defazio, Giovanni
Hallett, Mark
Jinnah, Hyder A.
Berardelli, Alfredo
TI Development and validation of a clinical guideline for diagnosing
blepharospasm
SO NEUROLOGY
LA English
DT Article
ID ADULT-ONSET DYSTONIA; FAMILY
AB Objective: To design and validate a clinical diagnostic guideline for aiding physicians in confirming or refuting suspected blepharospasm.
Methods: The guideline was developed and validated in a 3-step procedure: 1) identification of clinical items related to the phenomenology of blepharospasm, 2) assessment of the relevance of each item to the diagnosis of blepharospasm, and 3) evaluation of the reliability and diagnostic sensitivity/specificity of the selected clinical items.
Results: Of 19 clinical items initially identified, 7 were admitted by content validity analysis to further assessment. Both neurologists and ophthalmologists achieved satisfactory interobserver agreement for all 7 items, including "involuntary eyelid narrowing/closure due to orbicularis oculi spasms," "bilateral spasms," " synchronous spasms," " stereotyped spasm pattern," " sensory trick," " inability to voluntarily suppress the spasms," and " blink count at rest." Each selected item yielded unsatisfactory accuracy in discriminating patients with blepharospasm from healthy subjects and patients with other eyelid disturbances. Combining the selected items, however, improved diagnostic sensitivity/specificity. The best combination, yielding 93% sensitivity and 90% specificity, was an algorithm starting with the item " stereotyped, bilateral, and synchronous orbicularis oculi spasms inducing eyelid narrowing/closure" and followed by recognition of "sensory trick" or, alternatively, "increased blinking."
Conclusion: This study provides an accurate and valid clinical guideline for diagnosing blepharospasm. Use of this guideline would make it easier for providers to recognize dystonia in clinical and research settings.
C1 [Defazio, Giovanni] Aldo Moro Univ Bari, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy.
[Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
[Jinnah, Hyder A.] Emory Univ, Dept Neurol, Atlanta, GA 30322 USA.
[Jinnah, Hyder A.] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA.
[Jinnah, Hyder A.] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA.
[Berardelli, Alfredo] Univ Roma La Sapienza, Dept Neurol & Psychiat, Rome, Italy.
IRCCS Neuromed Inst, Pozzilli, IS, Italy.
RP Defazio, G (reprint author), Aldo Moro Univ Bari, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy.
EM gdefazio@neurol.uniba.it
OI DEFAZIO, GIOVANNI/0000-0001-5950-3110
FU Benign Essential Blepharospasm Research Foundation; Dystonia Coalition
from the Office of Rare Diseases Research [NS065701]; Dystonia Coalition
from the National Institute of Neurological Disorders and Stroke at the
National Center for Clinical and Translational Sciences
FX Funded by the Benign Essential Blepharospasm Research Foundation and a
Pilot Project Grant from the Dystonia Coalition (NS065701 from the
Office of Rare Diseases Research and the National Institute of
Neurological Disorders and Stroke at the National Center for Clinical
and Translational Sciences).
NR 12
TC 15
Z9 15
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD JUL 16
PY 2013
VL 81
IS 3
BP 236
EP 240
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA 304JP
UT WOS:000330743200010
PM 23771487
ER
PT J
AU Farrell, BT
Hamilton, BE
Dosa, E
Rimely, E
Nasseri, M
Gahramanov, S
Lacy, CA
Frenkel, EP
Doolittle, ND
Jacobs, PM
Neuwelt, EA
AF Farrell, Brian T.
Hamilton, Bronwyn E.
Dosa, Edit
Rimely, Endre
Nasseri, Morad
Gahramanov, Seymur
Lacy, Cynthia A.
Frenkel, Eugene P.
Doolittle, Nancy D.
Jacobs, Paula M.
Neuwelt, Edward A.
TI Using iron oxide nanoparticles to diagnose CNS inflammatory diseases and
PCNSL
SO NEUROLOGY
LA English
DT Article
ID NERVOUS-SYSTEM LYMPHOMA; COLLABORATIVE GROUP-REPORT; MULTIPLE-SCLEROSIS;
FERUMOXYTOL; PERFUSION; BRAIN; GADOTERIDOL; THERAPY; PSEUDOPROGRESSION;
DIFFERENTIATION
AB Objective: The study goal was to assess the benefits and potential limitations in the use of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles in the MRI diagnosis of CNS inflammatory diseases and primary CNS lymphoma.
Methods: Twenty patients with presumptive or known CNS lesions underwent MRI study. Eighteen patients received both gadolinium-based contrast agents (GBCAs) and 1 of 2 USPIO contrast agents (ferumoxytol and ferumoxtran-10) 24 hours apart, which allowed direct comparative analysis. The remaining 2 patients had only USPIO-enhanced MRI because of a renal contraindication to GBCA. Conventional T1- and T2-weighted MRI were acquired before and after contrast administration in all patients, and perfusion MRI for relative cerebral blood volume (rCBV) assessment was obtained in all 9 patients receiving ferumoxytol.
Results: USPIO-enhanced MRI showed an equal number of enhancing brain lesions in 9 of 18 patients (50%), more enhancing lesions in 2 of 18 patients (11%), and fewer enhancing lesions in 3 of 18 patients (17%) compared with GBCA-enhanced MRI. Four of 18 patients (22%) showed no MRI enhancement. Dynamic susceptibility-weighted contrast-enhanced perfusion MRI using ferumoxytol showed low rCBV (ratio <1.0) in 3 cases of demyelination or inflammation, modestly elevated rCBV in 5 cases of CNS lymphoma or lymphoproliferative disorder (range: 1.3-4.1), and no measurable disease in one case.
Conclusions: This study showed that USPIO-enhanced brain MRI can be useful in the diagnosis of CNS inflammatory disorders and lymphoma, and is also useful for patients with renal compromise at risk of nephrogenic systemic fibrosis who are unable to receive GBCA.
C1 [Farrell, Brian T.; Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurosurg, Portland, OR 97201 USA.
[Hamilton, Bronwyn E.] Oregon Hlth & Sci Univ, Dept Radiol, Portland, OR 97201 USA.
[Dosa, Edit; Rimely, Endre; Nasseri, Morad; Gahramanov, Seymur; Lacy, Cynthia A.; Doolittle, Nancy D.; Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
[Frenkel, Eugene P.] Univ Texas SW Med Ctr Dallas, Harold C Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA.
[Jacobs, Paula M.] NCI, Canc Imaging Program, Rockville, MD USA.
[Neuwelt, Edward A.] Dept Vet Affairs Med Ctr, Portland, OR USA.
RP Neuwelt, EA (reprint author), Oregon Hlth & Sci Univ, Dept Neurosurg, Portland, OR 97201 USA.
EM neuwelte@ohsu.edu
FU Veterans Administration; NIH [NS53468, NS44687, CA137488]; National
Cancer Institute, NIH [HHSN261200800001E]; Walter S. and Lucienne
Driskill Foundation
FX This work was supported by a Veterans Administration merit review grant
and by NIH grants NS53468, NS44687, and CA137488, in part with federal
funds from the National Cancer Institute, NIH, under contract no.
HHSN261200800001E, and by the Walter S. and Lucienne Driskill Foundation
to E.A.N.
NR 30
TC 19
Z9 19
U1 2
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD JUL 16
PY 2013
VL 81
IS 3
BP 256
EP 263
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 304JP
UT WOS:000330743200013
PM 23771486
ER
PT J
AU Lehmann, ML
Geddes, CE
Lee, JL
Herkenham, M
AF Lehmann, Michael L.
Geddes, Claire E.
Lee, Jennifer L.
Herkenham, Miles
TI Urine Scent Marking (USM): A Novel Test for Depressive-Like Behavior and
a Predictor of Stress Resiliency in Mice
SO PLOS ONE
LA English
DT Article
ID MUS-DOMESTICUS RUTTY; CHRONIC MILD STRESS; CHRONIC RESTRAINT STRESS;
REPEATED SOCIAL DEFEAT; HOUSE MICE; ULTRASONIC VOCALIZATIONS;
PERIAQUEDUCTAL GRAY; SUCROSE CONSUMPTION; LOCOMOTOR-ACTIVITY;
SEXUAL-BEHAVIOR
AB Decreased interest in pleasurable stimuli including social withdrawal and reduced libido are some of the key symptomatic criteria for major depression, and thus assays that measure social and sexual behavior in rodents may be highly appropriate for modeling depressive states. Here we present a novel approach for validating rodent models of depression by assessing male urine scent marking (USM) made in consequence to a spot of urine from a proestrous female. USM is an ethologically important form of sexual communication expressed by males to attract females. The expression of this behavior is highly sensitive and adaptive to environmental cues and social status. We hypothesized that male USM behavior offers a naturalistic measure of social motivation that can be used to evaluate hedonic behaviors relevant to the study of mood disorders. We demonstrated that 1) adult male mice displayed a strong preference for marking proestrous female urine with a high degree of specificity, 2) exposure to chronic social defeat profoundly decreased USM whereas exposure to environmental enrichment increased USM, 3) the standard antidepressant fluoxetine reversed declines in USM induced by social defeat, 4) USM behavior closely correlated with other hedonic measures, and 5) USM scores in non-stressed mice predicted behavioral outcomes after defeat exposure such that mice displaying high preference for marking female urine prior to social defeat showed behavioral resiliency after social defeat. The findings indicate that the USM test is a sensitive, validated measure of psychosocial stress effects that has high predictive value for examination of stress resiliency and vulnerability and their neurobiological substrates.
C1 [Lehmann, Michael L.; Geddes, Claire E.; Lee, Jennifer L.; Herkenham, Miles] NIMH, Funct Neuroanat Sect, NIH, Bethesda, MD 20892 USA.
RP Lehmann, ML (reprint author), NIMH, Funct Neuroanat Sect, NIH, Bethesda, MD 20892 USA.
EM Michael.lehmann@nih.gov
OI Herkenham, Miles/0000-0003-2228-4238; Lehmann,
Michael/0000-0003-4476-8268
FU Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health
FX The research was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 83
TC 8
Z9 9
U1 4
U2 15
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 16
PY 2013
VL 8
IS 7
AR e69822
DI 10.1371/journal.pone.0069822
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 186SF
UT WOS:000322064300119
PM 23875001
ER
PT J
AU Loots, GG
Bergmann, A
Hum, NR
Oldenburg, CE
Wills, AE
Hu, N
Ovcharenko, I
Harland, RM
AF Loots, Gabriela G.
Bergmann, Anne
Hum, Nicholas R.
Oldenburg, Catherine E.
Wills, Andrea E.
Hu, Na
Ovcharenko, Ivan
Harland, Richard M.
TI Interrogating Transcriptional Regulatory Sequences in Tol2-Mediated
Xenopus Transgenics
SO PLOS ONE
LA English
DT Article
ID CONSERVED NONCODING SEQUENCES; TISSUE-SPECIFIC ENHANCERS; RED
FLUORESCENT PROTEIN; SKELETAL-MUSCLE; GENE-EXPRESSION; HUMAN GENOME;
IN-VIVO; TROPICALIS; ZEBRAFISH; PROMOTER
AB Identifying gene regulatory elements and their target genes in vertebrates remains a significant challenge. It is now recognized that transcriptional regulatory sequences are critical in orchestrating dynamic controls of tissue-specific gene expression during vertebrate development and in adult tissues, and that these elements can be positioned at great distances in relation to the promoters of the genes they control. While significant progress has been made in mapping DNA binding regions by combining chromatin immunoprecipitation and next generation sequencing, functional validation remains a limiting step in improving our ability to correlate in silico predictions with biological function. We recently developed a computational method that synergistically combines genome-wide gene-expression profiling, vertebrate genome comparisons, and transcription factor binding-site analysis to predict tissue-specific enhancers in the human genome. We applied this method to 270 genes highly expressed in skeletal muscle and predicted 190 putative cis-regulatory modules. Furthermore, we optimized Tol2 transgenic constructs in Xenopus laevis to interrogate 20 of these elements for their ability to function as skeletal muscle-specific transcriptional enhancers during embryonic development. We found 45% of these elements expressed only in the fast muscle fibers that are oriented in highly organized chevrons in the Xenopus laevis tadpole. Transcription factor binding site analysis identified >2 Mef2/MyoD sites within similar to 200 bp regions in 6 of the validated enhancers, and systematic mutagenesis of these sites revealed that they are critical for the enhancer function. The data described herein introduces a new reporter system suitable for interrogating tissue-specific cis-regulatory elements which allows monitoring of enhancer activity in real time, throughout early stages of embryonic development, in Xenopus.
C1 [Loots, Gabriela G.; Bergmann, Anne; Hum, Nicholas R.] Lawrence Livermore Natl Lab, Biol & Biotechnol Div, Livermore, CA 94550 USA.
[Loots, Gabriela G.] Univ Calif Merced, Sch Nat Sci, Merced, CA USA.
[Ovcharenko, Ivan] Natl Lib Med, Computat Biol Branch, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD USA.
[Oldenburg, Catherine E.; Wills, Andrea E.; Hu, Na; Harland, Richard M.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
RP Loots, GG (reprint author), Lawrence Livermore Natl Lab, Biol & Biotechnol Div, Livermore, CA 94550 USA.
EM loots1@llnl.gov
FU National Institutes of Health (NIH) [HG003963]; Intramural Research
Program of the NIH, National Library of Medicine; United States
Department of Energy by Lawrence Livermore National Laboratory
[DE-AC52-07NA27344]
FX GGL, NH, and AB were supported by National Institutes of Health (NIH)
grant HG003963. This research was supported in part by the Intramural
Research Program of the NIH, National Library of Medicine to I.O. This
work performed under the auspices of the United States Department of
Energy by Lawrence Livermore National Laboratory under contract
DE-AC52-07NA27344. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 46
TC 1
Z9 1
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 16
PY 2013
VL 8
IS 7
AR e68548
DI 10.1371/journal.pone.0068548
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 186SF
UT WOS:000322064300046
PM 23874664
ER
PT J
AU Yang, YZ
Jittayasothorn, Y
Chronis, D
Wang, XH
Cousins, P
Zhong, GY
AF Yang, Yingzhen
Jittayasothorn, Yingyos
Chronis, Demosthenis
Wang, Xiaohong
Cousins, Peter
Zhong, Gan-Yuan
TI Molecular Characteristics and Efficacy of 16D10 siRNAs in Inhibiting
Root-Knot Nematode Infection in Transgenic Grape Hairy Roots
SO PLOS ONE
LA English
DT Article
ID PLANT-PARASITIC NEMATODES; DICER-LIKE PROTEINS; RNA INTERFERENCE;
MAMMALIAN-CELLS; GC PREFERENCE; GENE; RESISTANCE; EXPRESSION; DESIGN;
SYSTEM
AB Root-knot nematodes (RKNs) infect many annual and perennial crops and are the most devastating soil-born pests in vineyards. To develop a biotech-based solution for controlling RKNs in grapes, we evaluated the efficacy of plant-derived RNA interference (RNAi) silencing of a conserved RKN effector gene, 16D10, for nematode resistance in transgenic grape hairy roots. Two hairpin-based silencing constructs, containing a stem sequence of 42 bp (pART27-42) or 271 bp (pART27-271) of the 16D10 gene, were transformed into grape hairy roots and compared for their small interfering RNA (siRNA) production and efficacy on suppression of nematode infection. Transgenic hairy root lines carrying either of the two RNAi constructs showed less susceptibility to nematode infection compared with control. Small RNA libraries from four pART27-42 and two pART27-271 hairy root lines were sequenced using an Illumina sequencing technology. The pART27-42 lines produced hundred times more 16D10-specific siRNAs than the pART27-271 lines. On average the 16D10 siRNA population had higher GC content than the 16D10 stem sequences in the RNAi constructs, supporting previous observation that plant dicer-like enzymes prefer GC-rich sequences as substrates for siRNA production. The stems of the 16D10 RNAi constructs were not equally processed into siRNAs. Several hot spots for siRNA production were found in similar positions of the hairpin stems in pART27-42 and pART27-271. Interestingly, stem sequences at the loop terminus produced more siRNAs than those at the stem base. Furthermore, the relative abundance of guide and passenger single-stranded RNAs from putative siRNA duplexes was largely correlated with their 59 end thermodynamic strength. This study demonstrated the feasibility of using a plant-derived RNAi approach for generation of novel nematode resistance in grapes and revealed several interesting molecular characteristics of transgene siRNAs important for optimizing plant RNAi constructs.
C1 [Yang, Yingzhen; Jittayasothorn, Yingyos; Cousins, Peter; Zhong, Gan-Yuan] USDA ARS, Grape Genet Res Unit, Geneva, NY USA.
[Jittayasothorn, Yingyos] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Chronis, Demosthenis; Wang, Xiaohong] USDA ARS, Robert W Holley Ctr Agr & Hlth, Ithaca, NY 14853 USA.
[Cousins, Peter] E&J Gallo Winery, Modesto, CA USA.
RP Zhong, GY (reprint author), USDA ARS, Grape Genet Res Unit, Geneva, NY USA.
EM ganyuan.zhong@ars.usda.gov
FU United States Department of Agriculture-Agricultural Research Service
Project [1910-21220-004-00D]
FX This project was supported by the United States Department of
Agriculture-Agricultural Research Service Project 1910-21220-004-00D.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 59
TC 17
Z9 17
U1 3
U2 37
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 16
PY 2013
VL 8
IS 7
AR e69463
DI 10.1371/journal.pone.0069463
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 186SF
UT WOS:000322064300102
PM 23874962
ER
PT J
AU Ma, WL
Yun, SH
Bell, EM
Druschel, CM
Caggana, M
Aldous, KM
Louis, GMB
Kannan, K
AF Ma, Wan-Li
Yun, Sehun
Bell, Erin M.
Druschel, Charlotte M.
Caggana, Michele
Aldous, Kenneth M.
Louis, Germaine M. Buck
Kannan, Kurunthachalam
TI Temporal Trends of Polybrominated Diphenyl Ethers (PBDEs) in the Blood
of Newborns from New York State during 1997 through 2011: Analysis of
Dried Blood Spots from the Newborn Screening Program
SO ENVIRONMENTAL SCIENCE & TECHNOLOGY
LA English
DT Article
ID BROMINATED FLAME RETARDANTS; EXPOSURE ASSESSMENT; BREAST-MILK; CHAMACOS
COHORT; PREGNANT-WOMEN; UNITED-STATES; FETAL BLOOD; CORD SERUM;
PHASE-OUT; ENVIRONMENT
AB Polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental pollutants, and on a global basis, North American populations are exposed to the highest doses of PBDEs. In response to the exponential increase in human exposure to PBDEs during the late 1990s, some PBDE formulations were phased out from production in the early 2000s. The effectiveness of the phase-out of commercial penta-BDE and octa-BDE mixtures in 2004 in the U.S. on human exposure levels is not known. Dried blood spots (DBSs), collected for the newborn screening program (NSP) in the U.S., are a valuable resource for the elucidation of trends in exposure to environmental pollutants in newborns. In this study, seven PBDE congeners were determined by gas chromatography-high resolution mass spectrometry (GC-HRMS) in archived DBS samples (in total, 51 blood spot composites from 1224 newborns) collected from newborns in New York State (NYS) from 1997 to 2011. The most frequently detected PBDE congener was BDE-47, with a detection rate (DR) of 86%, followed by BDE-99 (DR: 45%) and BDE-100 (DR: 43%). The mean concentrations determined during 1997 through 2011 in the whole blood of newborns were 0.128, 0.040, and 0.012 ng/mL for BDE-47, -99, and -100, respectively. A significant correlation was found among the concentrations of three major congeners (p < 0.001). PBDE concentrations were similar during 1997 through 2002 and, thereafter, decreased significantly, which was similar to the trends observed for perfluorinated compounds (PFCs) in DBS samples. Occurrence of PBDEs in the whole blood of newborns confirms that these compounds do cross the placental barrier.
C1 [Ma, Wan-Li; Yun, Sehun; Caggana, Michele; Aldous, Kenneth M.; Kannan, Kurunthachalam] New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA.
[Ma, Wan-Li; Yun, Sehun; Caggana, Michele; Aldous, Kenneth M.; Kannan, Kurunthachalam] SUNY Albany, Sch Publ Hlth, Dept Environm Hlth Sci, Albany, NY 12201 USA.
[Ma, Wan-Li; Kannan, Kurunthachalam] Harbin Inst Technol, State Key Lab Urban Water Resource & Environm, Int Joint Res Ctr Persistent Tox Subst, Harbin 150090, Peoples R China.
[Bell, Erin M.] SUNY Albany, Sch Publ Hlth, Dept Environm Hlth Sci, Albany, NY 12222 USA.
[Druschel, Charlotte M.] New York State Dept Hlth, Bur Environm & Occupat Epidemiol, Albany, NY 12237 USA.
[Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD USA.
RP Kannan, K (reprint author), New York State Dept Hlth, Wadsworth Ctr, Empire State Plaza,POB 509, Albany, NY 12201 USA.
EM kkannan@wadsworth.org
OI Buck Louis, Germaine/0000-0002-1774-4490
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD)
[HHSN275201200005C, HHSN267200700019C]
FX This study was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) contracts #HHSN275201200005C and #HHSN267200700019C
to New York State Department of Health.
NR 33
TC 17
Z9 17
U1 7
U2 70
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0013-936X
J9 ENVIRON SCI TECHNOL
JI Environ. Sci. Technol.
PD JUL 16
PY 2013
VL 47
IS 14
BP 8015
EP 8021
DI 10.1021/es401857v
PG 7
WC Engineering, Environmental; Environmental Sciences
SC Engineering; Environmental Sciences & Ecology
GA 186QS
UT WOS:000322059800056
PM 23755886
ER
PT J
AU Beans, EJ
Fournogerakis, D
Gauntlett, C
Heumann, LV
Kramer, R
Marsden, MD
Murray, D
Chun, TW
Zack, JA
Wender, PA
AF Beans, Elizabeth J.
Fournogerakis, Dennis
Gauntlett, Carolyn
Heumann, Lars V.
Kramer, Rainer
Marsden, Matthew D.
Murray, Danielle
Chun, Tae-Wook
Zack, Jerome A.
Wender, Paul A.
TI Highly potent, synthetically accessible prostratin analogs induce latent
HIV expression in vitro and ex vivo
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE HIV latency; NF-kappa B; PKC-delta; bryostatin
ID ACTIVE ANTIRETROVIRAL THERAPY; PROTEIN-KINASE-C; HOMALANTHUS-NUTANS;
PHORBOL ESTER; ACTIVATION; RESERVOIRS; HAART; 12-DEOXYPHORBOL;
ERADICATION; PROVIDES
AB Highly active antiretroviral therapy (HAART) decreases plasma viremia below the limits of detection in the majority of HIV-infected individuals, thus serving to slow disease progression. However, HAART targets only actively replicating virus and is unable to eliminate latently infected, resting CD4(+) T cells. Such infected cells are potentially capable of reinitiating virus replication upon cessation of HAART, thus leading to viral rebound. Agents that would eliminate these reservoirs, when used in combination with HAART, could thus provide a strategy for the eradication of HIV. Prostratin is a preclinical candidate that induces HIV expression from latently infected CD4(+) T cells, potentially leading to their elimination through a virus-induced cytopathic effect or host anti-HIV immunity. Here, we report the synthesis of a series of designed prostratin analogs and report in vitro and ex vivo studies of their activity relevant to induction of HIV expression. Members of this series are up to 100-fold more potent than the preclinical lead (prostratin) in binding to cell-free PKC, and in inducing HIV expression in a latently infected cell line and prostratin-like modulation of cell surface receptor expression in primary cells from HIV-negative donors. Significantly, selected members were also tested for HIV induction in resting CD4(+) T cells isolated from infected individuals receiving HAART and were found to exhibit potent induction activity. These more potent agents and by extension related tunable analogs now accessible through the studies described herein should facilitate research and preclinical advancement of this strategy for HIV/AIDS eradication.
C1 [Beans, Elizabeth J.; Fournogerakis, Dennis; Gauntlett, Carolyn; Heumann, Lars V.; Kramer, Rainer; Wender, Paul A.] Stanford Univ, Dept Chem, Stanford, CA 94305 USA.
[Beans, Elizabeth J.; Fournogerakis, Dennis; Gauntlett, Carolyn; Heumann, Lars V.; Kramer, Rainer; Wender, Paul A.] Stanford Univ, Dept Chem & Syst Biol, Stanford, CA 94305 USA.
[Marsden, Matthew D.; Zack, Jerome A.] Univ Calif Los Angeles, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA.
[Zack, Jerome A.] Univ Calif Los Angeles, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90095 USA.
[Murray, Danielle; Chun, Tae-Wook] NIAID, NIH, Bethesda, MD 20892 USA.
RP Zack, JA (reprint author), Univ Calif Los Angeles, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA.
EM jzack@ucla.edu; wenderp@stanford.edu
FU National Institutes of Health [AI70010, R01 CA031841, R01 CA031845];
University of California, Los Angeles, Center for AIDS Research Grant
[AI28697]; Intramural Research Program of the National Institute Allergy
and Infectious Diseases; Novartis; Fulbright Commission; American Cancer
Society; Alexander von Humboldt Foundation
FX We thank Prof. Lynette Cegelski for support with biological materials
and equipment. Support of this work through National Institutes of
Health Grants AI70010 (to J.A.Z.) and R01 CA031841 and R01 CA031845 (to
P.A.W.), and University of California, Los Angeles, Center for AIDS
Research Grant AI28697 is gratefully acknowledged. This research was
also supported in part by the Intramural Research Program of the
National Institute Allergy and Infectious Diseases. Further support
through fellowships by Novartis (to E.J.B.), Fulbright Commission (to
C.G.), American Cancer Society (to L.V.H.), and Alexander von Humboldt
Foundation (to R.K.) is gratefully acknowledged.
NR 32
TC 53
Z9 55
U1 3
U2 42
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 16
PY 2013
VL 110
IS 29
BP 11698
EP 11703
DI 10.1073/pnas.1302634110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187AB
UT WOS:000322086100023
PM 23812750
ER
PT J
AU Huang, H
Jiang, X
Li, ZJ
Li, YY
Song, CX
He, CJ
Sun, M
Chen, P
Gurbuxani, S
Wang, JP
Hong, GM
Elkahloun, AG
Arnovitz, S
Wang, JH
Szulwach, K
Lin, L
Street, C
Wunderlich, M
Dawlaty, M
Neilly, MB
Jaenisch, R
Yang, FC
Mulloy, JC
Jin, P
Liu, PP
Rowley, JD
Xu, MJ
He, C
Chen, JJ
AF Huang, Hao
Jiang, Xi
Li, Zejuan
Li, Yuanyuan
Song, Chun-Xiao
He, Chunjiang
Sun, Miao
Chen, Ping
Gurbuxani, Sandeep
Wang, Jiapeng
Hong, Gia-Ming
Elkahloun, Abdel G.
Arnovitz, Stephen
Wang, Jinhua
Szulwach, Keith
Lin, Li
Street, Craig
Wunderlich, Mark
Dawlaty, Meelad
Neilly, Mary Beth
Jaenisch, Rudolf
Yang, Feng-Chun
Mulloy, James C.
Jin, Peng
Liu, Paul P.
Rowley, Janet D.
Xu, Mingjiang
He, Chuan
Chen, Jianjun
TI TET1 plays an essential oncogenic role in MLL-rearranged leukemia
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; MIXED-LINEAGE LEUKEMIA; EMBRYONIC STEM-CELLS;
POSTNATAL-DEVELOPMENT; HEMATOPOIETIC-CELLS; GENE-EXPRESSION;
DOWN-REGULATION; MAMMALIAN DNA; SELF-RENEWAL; 5-HYDROXYMETHYLCYTOSINE
AB The ten-eleven translocation 1 (TET1) gene is the founding member of the TET family of enzymes (TET1/2/3) that convert 5-methylcytosine to 5-hydroxymethylcytosine. Although TET1 was first identified as a fusion partner of the mixed lineage leukemia (MLL) gene in acute myeloid leukemia carrying t(10,11), its definitive role in leukemia is unclear. In contrast to the frequent down-regulation (or loss-of-function mutations) and critical tumor-suppressor roles of the three TET genes observed in various types of cancers, here we show that TET1 is a direct target of MLL-fusion proteins and is significantly up-regulated in MLL-rearranged leukemia, leading to a global increase of 5-hydroxymethylcytosine level. Furthermore, our both in vitro and in vivo functional studies demonstrate that Tet1 plays an indispensable oncogenic role in the development of MLL-rearranged leukemia, through coordination with MLL-fusion proteins in regulating their critical cotargets, including homeobox A9 (Hoxa9)/myeloid ecotropic viral integration 1 (Meis1)/pre-B-cell leukemia homeobox 3 (Pbx3) genes. Collectively, our data delineate an MLL-fusion/Tet1/Hoxa9/Meis1/Pbx3 signaling axis in MLL-rearranged leukemia and highlight TET1 as a potential therapeutic target in treating this presently therapy-resistant disease.
C1 [Huang, Hao; Jiang, Xi; Li, Zejuan; Li, Yuanyuan; He, Chunjiang; Chen, Ping; Hong, Gia-Ming; Arnovitz, Stephen; Wang, Jinhua; Neilly, Mary Beth; Rowley, Janet D.; Chen, Jianjun] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Song, Chun-Xiao; He, Chuan] Univ Chicago, Dept Chem, Chicago, IL 60637 USA.
[Song, Chun-Xiao; He, Chuan] Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA.
[Gurbuxani, Sandeep] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA.
[Wang, Jiapeng; Yang, Feng-Chun; Xu, Mingjiang] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA.
[Elkahloun, Abdel G.; Liu, Paul P.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Szulwach, Keith; Street, Craig] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA.
[Wunderlich, Mark] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.
[Dawlaty, Meelad; Jaenisch, Rudolf] MIT, Whitehead Inst, Cambridge, MA 02142 USA.
[Dawlaty, Meelad; Jaenisch, Rudolf] MIT, Dept Biol, Cambridge, MA 02142 USA.
RP Rowley, JD (reprint author), Univ Chicago, Dept Med, Chicago, IL 60637 USA.
EM jrowley@bsd.uchicago.edu; jchen@medicine.bsd.uchicago.edu
OI He, Chunjiang/0000-0002-4868-331X
FU National Institutes of Health [CA127277, NS079625, HD073162, HG006827,
HL112294, CA118319]; National Human Genome Research Institute; American
Cancer Society Research Scholar grant; Emory Genetics Discovery Fund;
Winship Cancer Institute Kennedy Seed Grant; Winship Multi-Investigator
Pilot Grant; G. Harold and Leila Y. Mathers Charitable Foundation;
Gabrielle's Angel Foundation; Leukemia and Lymphoma Society;
Translational Research grant; LLS Special Fellowship; University of
Chicago Committee on Cancer Biology Fellowship Program; Department of
Defense Predoctoral Traineeship Award [W81XWH-10-1-0396]
FX We thank Drs. Robert K. Slany, Gregory Hannon, Scott Hammond, Lin He,
Scott Armstrong, and Michael Thirman for providing cell lines or
plasmids. This work was supported in part by National Institutes of
Health Grants CA127277 (to J.C.), NS079625 and HD073162 (to P.J.),
HG006827 (to Chuan He), HL112294 (to M.X.), and CA118319 (to J.C.M.),
the Intramural Program of the National Human Genome Research Institute
(A.G.E. and P.P.L.), the American Cancer Society Research Scholar grant
(J.C.), the Emory Genetics Discovery Fund (P.J.), a Winship Cancer
Institute Kennedy Seed Grant and a Winship Multi-Investigator Pilot
Grant (to P.J.), the G. Harold and Leila Y. Mathers Charitable
Foundation (J.C.), Gabrielle's Angel Foundation (J.C., Z.L., H.H., X.J.,
and G.-M.H.), a Leukemia and Lymphoma Society (LLS) Translational
Research grant (to J.D.R. and J.C.), an LLS Special Fellowship (to
Z.L.), and the University of Chicago Committee on Cancer Biology
Fellowship Program (X.J.). M.S. was supported by Department of Defense
Predoctoral Traineeship Award W81XWH-10-1-0396. J.C.M. is an LLS
Scholar.
NR 59
TC 61
Z9 63
U1 0
U2 15
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 16
PY 2013
VL 110
IS 29
BP 11994
EP 11999
DI 10.1073/pnas.1310656110
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 187AB
UT WOS:000322086100074
PM 23818607
ER
PT J
AU Tycko, R
Wickner, RB
AF Tycko, Robert
Wickner, Reed B.
TI Molecular Structures of Amyloid and Prion Fibrils: Consensus versus
Controversy
SO ACCOUNTS OF CHEMICAL RESEARCH
LA English
DT Review
ID SOLID-STATE NMR; BETA-SHEET STRUCTURE; IN-VITRO; PARALLEL; SPECTROSCOPY;
POLYMORPHISM; PEPTIDE; MODEL; URE2P; CORE
AB Many peptides and proteins self-assemble into amyloid fibrils. Examples include mammalian and fungal prion proteins, polypeptides associated with human amyloid diseases, and proteins that may have biologically functional amyloid states. To understand the propensity for polypeptides to form amyloid fibrils and to facilitate rational design of amyloid inhibitors and imaging agents, it is necessary to elucidate the molecular structures of these fibrils. Although fibril structures were largely mysterious 15 years ago, a considerable body of reliable structural information about amyloid fibril structures now exists, with essential contributions from solid state nuclear magnetic resonance (NMR) measurements. This Account reviews results from our laboratories and discusses several structural issues that have been controversial.
In many cases, the amino add sequences of amyloid fibrils do not uniquely determine their molecular structures. Self-propagating, molecular-level polymorphism complicates the structure determination problem and can lead to apparent disagreements between results from different laboratories, particularly when different laboratories study different polymorphs. For 40-residue beta-amyloid (A beta(1-40)) fibrils associated with Alzheimer's disease, we have developed detailed structural models from solid state NMR and electron microscopy data for two polymorphs. These polymorphs have similar peptide conformations, identical in-register parallel beta-sheet organizations, but different overall symmetry. Other polymorphs have also been partially characterized by solid state NMR and appear to have similar structures. In contrast, cryo-electron microscopy studies that use significantly different fibril growth conditions have identified structures that appear (at low resolution) to be different from those examined by solid state NMR.
Based on solid state NMR and electron paramagnetic resonance (EPR) measurements, the in-register parallel beta-sheet organization found in beta-amyloid fibrils also occurs in many other fibril-forming systems. We attribute this common structural motif to the stabilization of amyloid structures by intermolecular interactions among like amino adds, including hydrophobic interactions and polar zippers. Surprisingly, we have recently identified and characterized antiparallel beta-sheets in certain fibrils that are formed by the D23N mutant of A beta(1-40), a mutant that is associated with early-onset, familial neurodegenerative disease Antiparallel D23N-A beta(1-40) fibrils are metastable with respect to parallel structures and, therefore, represent an off-pathway Intermediate in the amyloid fibril formation process. Other methods have recently produced additional evidence for antiparallel beta-sheets in other amyloid-formation intermediates.
As an alternative to simple parallel and antiparallel beta-sheet structures, researchers have proposed beta-helical structural models for some fibrils, especially those formed by mammalian and fungal pion proteins. Solid state NMR and EPR data show that fibrils formed in vitro by recombinant PIP have In-register parallel beta-sheet structures. However, the structure of infectious PrP aggregates Is not yet known. Me fungal HET-s prion protein has been shown to contain a beta-helical structure. However, all yeast prions studied by solid state NMR (Sup35p, Ure2p, and Rnq1p) have in-register parallel beta-sheet structures, with their Gln- and Asn-rich N-terminal segments forming the fibril core.
C1 [Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Wickner, Reed B.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
RP Tycko, R (reprint author), NIH, Bldg 5,Room 112, Bethesda, MD 20892 USA.
EM robertty@mail.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 55
TC 116
Z9 117
U1 17
U2 192
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0001-4842
EI 1520-4898
J9 ACCOUNTS CHEM RES
JI Accounts Chem. Res.
PD JUL 16
PY 2013
VL 46
IS 7
BP 1487
EP 1496
DI 10.1021/ar300282r
PG 10
WC Chemistry, Multidisciplinary
SC Chemistry
GA 187AC
UT WOS:000322086600012
PM 23294335
ER
PT J
AU Liu, ZH
Rader, J
He, S
Phung, T
Thiele, CJ
AF Liu, Zhihui
Rader, JulieAnn
He, Stanley
Phung, Tanya
Thiele, Carol J.
TI CASZ1 inhibits cell cycle progression in neuroblastoma by restoring pRb
activity
SO CELL CYCLE
LA English
DT Article
DE CASZ1; tumor suppressor; neuroblastoma; cell cycle; Rb; Cyclin; Cdk;
Chk1
ID TUMOR-SUPPRESSOR GENES; NERVOUS-SYSTEM; CANCER; DIFFERENTIATION; KINASE;
CHECKPOINT; EXPRESSION; APOPTOSIS; PROTEIN; TARGET
AB Dysregulation of cell cycle genes such as Cyclin D1 and Chk1 contributes to the undifferentiated phenotype of neuroblastoma (NB). CASZ1 functions as a tumor suppressor in NB; here we sought to determine how loss of CASZ1 contributes to cell cycle dysregulation in NB. CASZ1 restoration in NB cells delays NB cell cycle progression. The earliest changes occur within 8 h of CASZ1 restoration in SY5Y cells with a 2.8-fold increase in the level of p21, an inhibitor of Cdk2/4. By 16 h, there is a 40% decrease in the steady-state levels of Cdk6. Restoration of CASZ1 decreases Cdk2-dependent cyclins A and E protein levels and Cdk4/6-dependent Cyclin D1 protein levels. The restoration of CASZ1 resulted in a decrease in pRb phosphorylation and a significant reduction of E2F transcriptional activity. Subsequent to the changes in the G(1)/S transition, induction of CASZ1 results in a decrease in Cyclin B levels and Cdc25c phosphatase levels, an upstream activator of the G(2)/M regulator CyclinB:Cdk1. In addition, induction of CASZ1 results in a decrease in the levels of phospho-Chk1, a key M-phase regulatory kinase. Similar results were found in a NB cell line with MYCN amplification. Taken together, this study indicates that restoration of CASZ1 activates pRb in G(1) and inhibits the G(2)/M regulators Cyclin B1 and Chk1, leading to a lengthening of NB cell cycle progression and a subsequent decrease in cell proliferation.
C1 [Liu, Zhihui; Rader, JulieAnn; He, Stanley; Phung, Tanya; Thiele, Carol J.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
RP Thiele, CJ (reprint author), NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
EM thielec@mail.nih.gov
FU NIH, National Cancer Institute, and Center for Cancer Research
FX This work was supported by the Intramural Research Program of the NIH,
National Cancer Institute, and Center for Cancer Research.
NR 34
TC 4
Z9 4
U1 0
U2 4
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
EI 1551-4005
J9 CELL CYCLE
JI Cell Cycle
PD JUL 15
PY 2013
VL 12
IS 14
BP 2210
EP 2218
DI 10.4161/cc.25265
PG 9
WC Cell Biology
SC Cell Biology
GA 260US
UT WOS:000327620600017
PM 23892435
ER
PT J
AU Zou, JQ
Rezvani, K
Wang, HM
Lee, KS
Zhang, D
AF Zou, Jianqiu
Rezvani, Khosrow
Wang, Hongmin
Lee, Kyung S.
Zhang, Dong
TI BRCA1 downregulates the kinase activity of Polo-like kinase 1 in
response to replication stress
SO CELL CYCLE
LA English
DT Article
DE BRCA1; PLK1; replication stress; DNA damage
ID DNA-DAMAGE RESPONSE; TRCP-DEPENDENT DEGRADATION; DOUBLE-STRAND BREAKS;
AURORA-A; MITOTIC ENTRY; CELL-CYCLE; HOMOLOGOUS RECOMBINATION;
CANCER-THERAPY; TARGETS BRCA1; CHECKPOINT
AB In response to DNA damage or replication stress, proliferating cells are arrested at different cell cycle stages for DNA repair by downregulating the activity of both the cyclin-dependent kinases (CDKs) and other important cell cycle kinases, including Polo-like kinase 1 (PLK1) . The signaling pathway to inhibit CDKs is relatively well understood, and breast cancer gene 1 (BRCA1) and other DNA damage response (DDR) factors play a key role in this process. However, the DNA damage-induced inhibition of PLK1 is still largely a mystery. Here we show that DNA damage and replication stress stimulate the association between BRCA1 and PLK1. Most importantly, we demonstrate that BRCA1 downregulates the kinase activity of PLK1 by modulating the dynamic interactions of Aurora A, hBora, and PLK1. Together with previous findings, we propose that in response to replication stress and DNA damage, BRCA1 plays a critical role in downregulating the kinase activity of both CDKs and PLK1.
C1 [Zou, Jianqiu; Rezvani, Khosrow; Wang, Hongmin; Zhang, Dong] Univ S Dakota, Basic Biomed Sci Div, Sanford Sch Med, Vermillion, SD 57069 USA.
[Lee, Kyung S.] Natl Canc Inst Hlth, Lab Metab, Ctr Canc Res, Bethesda, MD USA.
RP Zhang, D (reprint author), Univ S Dakota, Basic Biomed Sci Div, Sanford Sch Med, Vermillion, SD 57069 USA.
EM dong.zhang@usd.edu
FU Sanford School of Medicine
FX We are grateful to Drs Erich Nigg and Natsuko Chiba for reagents and
Christine Canmam and Robin Miskimins for critical reading of the
manuscript. This research was supported by the generous starting package
from the Sanford School of Medicine (to DZ).
NR 64
TC 7
Z9 7
U1 0
U2 2
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
EI 1551-4005
J9 CELL CYCLE
JI Cell Cycle
PD JUL 15
PY 2013
VL 12
IS 14
BP 2255
EP 2265
DI 10.4161/cc.25349
PG 11
WC Cell Biology
SC Cell Biology
GA 260US
UT WOS:000327620600022
PM 24067368
ER
PT J
AU Potischman, N
Linet, MS
AF Potischman, Nancy
Linet, Martha S.
TI Invited Commentary: Are Dietary Intakes and Other Exposures in Childhood
and Adolescence Important for Adult Cancers?
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Editorial Material
DE adolescence; diet; distant past; life course; methods; recall
ID LIFETIME PHYSICAL-ACTIVITY; 1944-1945 DUTCH FAMINE; RENAL-CELL CANCER;
NIH-AARP DIET; BREAST-CANCER; PROSTATE-CANCER; ENDOMETRIAL CANCER;
COLORECTAL-CANCER; RISK-FACTORS; EPIDEMIOLOGIC EVIDENCE
AB In this issue of the Journal, Nimptsch et al. (Am J Epidemiol. 2013; 178(2): 172-183) report significant associations between female adolescents' poultry consumption in high school and subsequent reduced risk of colorectal adenomas in adulthood. Consumption of red meat or fish was not related to risk, but replacement with poultry reduced the risk of later adenomas. Most epidemiologic studies of adult diseases lack exposure data from the distant past. By focusing on a cancer precursor lesion and using a variety of methods to assess data quality, the investigators address concerns about the quality of distant recall. These findings add to the growing evidence that links childhood and adolescent lifestyle and environmental exposures with subsequent risk of cancers arising in adulthood. Highlights of the literature on this topic and methodological challenges are summarized. Future studies would benefit from incorporating measures of lifestyle, diet, environmental exposures, and other risk factors from early in life and from validation and other data quality checks of such measurements. Sources of historical data on children's and adolescents' exposures should be sought and evaluated in conjunction with subsequent exposures in relationship to adult-onset cancers.
C1 [Potischman, Nancy] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Linet, Martha S.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Potischman, N (reprint author), NCI, Div Canc Control & Populat Sci, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM potischn@mail.nih.gov
NR 80
TC 7
Z9 7
U1 1
U2 8
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 JUL 15
PY 2013
VL 178
IS 2
BP 184
EP 189
DI 10.1093/aje/kwt101
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 186DD
UT WOS:000322021300003
PM 23792894
ER
PT J
AU Chatterjee, S
Santos, N
Holgate, J
Haass-Koffler, CL
Hopf, FW
Kharazia, V
Lester, H
Bonci, A
Bartlett, SE
AF Chatterjee, Susmita
Santos, Nathan
Holgate, Joan
Haass-Koffler, Carolina L.
Hopf, F. Woodward
Kharazia, Viktor
Lester, Henry
Bonci, Antonello
Bartlett, Selena E.
TI The alpha 5 Subunit Regulates the Expression and Function of alpha
4*-Containing Neuronal Nicotinic Acetylcholine Receptors in the
Ventral-Tegmental Area
SO PLOS ONE
LA English
DT Article
ID MIDBRAIN DOPAMINE NEURONS; CA2+ PERMEABILITY; PHYSIOLOGICAL DIVERSITY;
CHOLINERGIC-RECEPTOR; CORTICAL-NEURONS; MEDIAL HABENULA; UP-REGULATION;
MUTANT MICE; RAT-BRAIN; IN-VIVO
AB Human genetic association studies have shown gene variants in the alpha 5 subunit of the neuronal nicotinic receptor (nAChR) influence both ethanol and nicotine dependence. The alpha 5 subunit is an accessory subunit that facilitates alpha 4* nAChRs assembly in vitro. However, it is unknown whether this occurs in the brain, as there are few research tools to adequately address this question. As the alpha 4*-containing nAChRs are highly expressed in the ventral tegmental area (VTA) we assessed the molecular, functional and pharmacological roles of alpha 5 in alpha 4*-containing nAChRs in the VTA. We utilized transgenic mice alpha 5+/+(alpha 4YFP) and alpha 5-/-(alpha alpha 4YFP) that allow the direct visualization and measurement of alpha 4-YFP expression and the effect of the presence (alpha 5+/+) and absence of alpha 5 (-/-) subunit, as the antibodies for detecting the alpha 4* subunits of the nAChR are not specific. We performed voltage clamp electrophysiological experiments to study baseline nicotinic currents in VTA dopaminergic neurons. We show that in the presence of the alpha 5 subunit, the overall expression of alpha 4 subunit is increased significantly by 60% in the VTA. Furthermore, the alpha 5 subunit strengthens baseline nAChR currents, suggesting the increased expression of alpha 4* nAChRs to be likely on the cell surface. While the presence of the alpha 5 subunit blunts the desensitization of nAChRs following nicotine exposure, it does not alter the amount of ethanol potentiation of VTA dopaminergic neurons. Our data demonstrates a major regulatory role for the alpha 5 subunit in both the maintenance of alpha 4*-containing nAChRs expression and in modulating nicotinic currents in VTA dopaminergic neurons. Additionally, the alpha 5 alpha 4* nAChR in VTA dopaminergic neurons regulates the effect of nicotine but not ethanol on currents. Together, the data suggest that the alpha 5 subunit is critical for controlling the expression and functional role of a population of alpha 4*-containing nAChRs in the VTA.
C1 [Holgate, Joan; Bartlett, Selena E.] Queensland Univ Technol, Sch Clin Sci, Fac Hlth, Translat Res Inst,Inst Hlth & Biomed Sci, Brisbane, Qld 4001, Australia.
[Chatterjee, Susmita; Santos, Nathan; Haass-Koffler, Carolina L.; Hopf, F. Woodward; Kharazia, Viktor] Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, Emeryville, CA USA.
[Haass-Koffler, Carolina L.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA.
[Lester, Henry] CALTECH, Div Biol, Pasadena, CA 91125 USA.
[Bonci, Antonello] NIDA, Intramural Res Program, Baltimore, MD USA.
[Hopf, F. Woodward; Bonci, Antonello] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Bonci, Antonello] Johns Hopkins Univ, Solomon Snyder Dept Neurosci, Baltimore, MD USA.
RP Bartlett, SE (reprint author), Queensland Univ Technol, Sch Clin Sci, Fac Hlth, Translat Res Inst,Inst Hlth & Biomed Sci, Brisbane, Qld 4001, Australia.
EM selena.bartlett@qut.edu.au
RI Bartlett, Selena/J-1345-2012;
OI Bartlett, Selena/0000-0002-1741-3958; Holgate, Joan/0000-0002-7953-0180
FU National Institutes of Health (NIH) [1RC2AA019429-01, 1R01AA017924-01,
1R01DA17279]; State of California for Medical Research on Alcohol and
Substance Abuse through the University of California San Francisco;
California Tobacco-Related Disease Research Program
FX This work was supported by funding from the National Institutes of
Health (NIH) 1RC2AA019429-01 (to SEB), NIH 1R01AA017924-01 (to SEB), NIH
1R01DA17279 (to HL), and the State of California for Medical Research on
Alcohol and Substance Abuse through the University of California San
Francisco (to SEB), and the California Tobacco-Related Disease Research
Program (to HL). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 77
TC 14
Z9 15
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 15
PY 2013
VL 8
IS 7
AR e68300
DI 10.1371/journal.pone.0068300
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 200ZN
UT WOS:000323110600013
PM 23869214
ER
PT J
AU Singh, TR
Ali, AM
Paramasivam, M
Pradhan, A
Wahengbam, K
Seidman, MM
Meetei, AR
AF Singh, Thiyam Ramsing
Ali, Abdullah Mahmood
Paramasivam, Manikandan
Pradhan, Arun
Wahengbam, Kebola
Seidman, Michael M.
Meetei, Amom Ruhikanta
TI ATR-Dependent Phosphorylation of FANCM at Serine 1045 Is Essential for
FANCM Functions
SO CANCER RESEARCH
LA English
DT Article
ID DNA-DAMAGE RESPONSE; FOLD-CONTAINING PROTEIN; COMPLEMENTATION GROUP-M;
S-PHASE CHECKPOINT; CROSS-LINK REPAIR; ANEMIA PATHWAY; CORE-COMPLEX;
FORK; MONOUBIQUITINATION; ACTIVATION
AB Fanconi anemia (FA) is a genome instability syndrome that has been associated with both cancer predisposition and bone marrow failure. FA proteins are involved in cellular response to replication stress in which they coordinate DNA repair with DNA replication and cell-cycle progression. One regulator of the replication stress response is the ATP-dependent DNA translocase FANCM, which we have shown to be hyperphosphorylated in response to various genotoxic agents. However, the significance of this phosphorylation remained unclear. Here, we show that genotoxic stress-induced FANCM phosphorylation is ATR-dependent and that this modification is highly significant for the cellular response to replication stress. We identified serine (S1045) residue of FANCM that is phosphorylated in response to genotoxic stress and this effect is ATR-dependent. We show that S1045 is required for FANCM functions including its role in FA pathway integrity, recruiting FANCM to the site of interstrand cross links, preventing the cells from entering mitosis prematurely, and efficient activation of the CHK1 and G(2)-M checkpoints. Overall, our data suggest that an ATR-FANCM feedback loop is present in the FA and replication stress response pathways and that it is required for both efficient ATR/CHK1 checkpoint activation and FANCM function. (C) 2013 AACR.
C1 [Singh, Thiyam Ramsing; Ali, Abdullah Mahmood; Pradhan, Arun; Wahengbam, Kebola; Meetei, Amom Ruhikanta] Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.
[Singh, Thiyam Ramsing; Ali, Abdullah Mahmood; Pradhan, Arun; Wahengbam, Kebola; Meetei, Amom Ruhikanta] Cincinnati Childrens Hosp Med Ctr, Canc & Blood Dis Inst, Cincinnati, OH 45229 USA.
[Meetei, Amom Ruhikanta] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA.
[Paramasivam, Manikandan; Seidman, Michael M.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Singh, Thiyam Ramsing] Manipur Univ, Dept Biotechnol, Imphal, Manipur, India.
RP Meetei, AR (reprint author), Cincinnati Childrens Hosp Med Ctr, 240 Albert Sabin Way, Cincinnati, OH 45229 USA.
EM Ruhikanta.Meetei@cchmc.org
FU NIH [HL084082, HL084082-03S1]; Ohio Cancer Research Associates; Fanconi
Anemia Research Fund; Intramural Research Program of the NIH, National
Institute on Aging; Ramalingaswami re-entry fellowship, DBT-INDIA
FX This work was supported by NIH research grants HL084082 and
HL084082-03S1 and grants from the Ohio Cancer Research Associates and
the Fanconi Anemia Research Fund to A.R. Meetei. This work was also
supported, in part, by the Intramural Research Program of the NIH,
National Institute on Aging to M.M. Seidman. T.R. Singh is supported by
the Ramalingaswami re-entry fellowship, DBT-INDIA.
NR 30
TC 16
Z9 17
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 JUL 15
PY 2013
VL 73
IS 14
BP 4300
EP 4310
DI 10.1158/0008-5472.CAN-12-3976
PG 11
WC Oncology
SC Oncology
GA 183NR
UT WOS:000321823600014
PM 23698467
ER
PT J
AU Yuan, HY
Lu, J
Xiao, JF
Upadhyay, G
Umans, R
Kallakury, B
Yin, YZ
Fant, ME
Kopelovich, L
Glazer, RI
AF Yuan, Hongyan
Lu, Jin
Xiao, Junfeng
Upadhyay, Geeta
Umans, Rachel
Kallakury, Bhaskar
Yin, Yuhzi
Fant, Michael E.
Kopelovich, Levy
Glazer, Robert I.
TI PPAR delta Induces Estrogen Receptor-Positive Mammary Neoplasia through
an Inflammatory and Metabolic Phenotype Linked to mTOR Activation
SO CANCER RESEARCH
LA English
DT Article
ID BINDING PROTEIN-BETA; CANCER-CELL-LINES; GENE-EXPRESSION; TRANSGENIC
MICE; FATTY-ACIDS; BETA/DELTA AGONIST; SIGNALING PATHWAY; BREAST-CANCER;
COLORECTAL-CANCER; MAMMALIAN TARGET
AB The peroxisome proliferator-activated receptor-delta (PPAR delta) regulates a multitude of physiological processes associated with glucose and lipid metabolism, inflammation, and proliferation. One or more of these processes are potential risk factors for the ability of PPAR delta agonists to promote tumorigenesis in the mammary gland. In this study, we describe a new transgenic mouse model in which activation of PPAR delta in the mammary epithelium by endogenous or synthetic ligands resulted in progressive histopathologic changes that culminated in the appearance of estrogen receptor-and progesterone receptor-positive and ErbB2-negative infiltrating ductal carcinomas. Multiparous mice presented with mammary carcinomas after a latency of 12 months, and administration of the PPAR delta ligand GW501516 reduced tumor latency to 5 months. Histopathologic changes occurred concurrently with an increase in an inflammatory, invasive, metabolic, and proliferative gene signature, including expression of the trophoblast gene, Plac1, beginning 1 week after GW501516 treatment, and remained elevated throughout tumorigenesis. The appearance of malignant changes correlated with a pronounced increase in phosphatidylcholine and lysophosphatidic acid metabolites, which coincided with activation of Akt and mTOR signaling that were attenuated by treatment with the mTOR inhibitor everolimus. Our findings are the first to show a direct role of PPARd in the pathogenesis of mammary tumorigenesis, and suggest a rationale for therapeutic approaches to prevent and treat this disease. (C) 2013 AACR.
C1 [Yuan, Hongyan; Lu, Jin; Xiao, Junfeng; Upadhyay, Geeta; Glazer, Robert I.] Georgetown Univ, Dept Oncol, Washington, DC 20007 USA.
[Yuan, Hongyan; Lu, Jin; Xiao, Junfeng; Upadhyay, Geeta; Glazer, Robert I.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
[Kallakury, Bhaskar] Georgetown Univ, Dept Pathol, Washington, DC 20007 USA.
[Yin, Yuhzi] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Kopelovich, Levy] NCI, Chemoprevent Agent Dev & Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Fant, Michael E.] Univ S Florida, Dept Pediat, Tampa, FL 33620 USA.
[Umans, Rachel] Univ Chicago, Chicago, IL 60637 USA.
RP Glazer, RI (reprint author), Georgetown Univ, 3970 Reservoir Rd NW, Washington, DC 20007 USA.
EM glazerr@georgetown.edu
FU National Cancer Institute, NIH [1R01 CA111482, 1NO1 CN43302-WA19, 1P30
CA051008]; NIH
FX This work was supported by grant 1R01 CA111482 and contract 1NO1
CN43302-WA19 from the National Cancer Institute, NIH, and award 1P30
CA051008 from the National Cancer Institute, NIH to the Lombardi
Comprehensive Cancer Center. This investigation was conducted using the
Animal Research, Genomics and Epigenomics, and Microscopy and Imaging
Shared Resources of the LCCC, and by an animal facilities construction
grant from the NIH.
NR 87
TC 10
Z9 10
U1 0
U2 10
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 JUL 15
PY 2013
VL 73
IS 14
BP 4349
EP 4361
DI 10.1158/0008-5472.CAN-13-0322
PG 13
WC Oncology
SC Oncology
GA 183NR
UT WOS:000321823600018
PM 23811944
ER
PT J
AU Abaan, OD
Polley, EC
Davis, SR
Zhu, YJ
Bilke, S
Walker, RL
Pineda, M
Gindin, Y
Jiang, Y
Reinhold, WC
Holbeck, SL
Simon, RM
Doroshow, JH
Pommier, Y
Meltzer, PS
AF Abaan, Ogan D.
Polley, Eric C.
Davis, Sean R.
Zhu, Yuelin J.
Bilke, Sven
Walker, Robert L.
Pineda, Marbin
Gindin, Yevgeniy
Jiang, Yuan
Reinhold, William C.
Holbeck, Susan L.
Simon, Richard M.
Doroshow, James H.
Pommier, Yves
Meltzer, Paul S.
TI The Exomes of the NCI-60 Panel: A Genomic Resource for Cancer Biology
and Systems Pharmacology
SO CANCER RESEARCH
LA English
DT Article
ID CELL-LINE SET; DRUG-SENSITIVITY; RENAL-CARCINOMA; SEQUENCING DATA;
MUTATIONS; GENES; INACTIVATION; RESISTANCE; INHIBITORS; DISCOVERY
AB The NCI-60 cell lines are the most frequently studied human tumor cell lines in cancer research. This panel has generated the most extensive cancer pharmacology database worldwide. In addition, these cell lines have been intensely investigated, providing a unique platform for hypothesis-driven research focused on enhancing our understanding of tumor biology. Here, we report a comprehensive analysis of coding variants in the NCI-60 panel of cell lines identified by whole exome sequencing, providing a list of possible cancer specific variants for the community. Furthermore, we identify pharmacogenomic correlations between specific variants in genes such as TP53, BRAF, ERBBs, and ATAD5 and anticancer agents such as nutlin, vemurafenib, erlotinib, and bleomycin showing one of many ways the data could be used to validate and generate novel hypotheses for further investigation. As new cancer genes are identified through large-scale sequencing studies, the data presented here for the NCI-60 will be an invaluable resource for identifying cell lines with mutations in such genes for hypothesis-driven research. To enhance the utility of the data for the greater research community, the genomic variants are freely available in different formats and from multiple sources including the CellMiner and Ingenuity websites. (C) 2013 AACR.
C1 [Abaan, Ogan D.; Davis, Sean R.; Zhu, Yuelin J.; Bilke, Sven; Walker, Robert L.; Pineda, Marbin; Gindin, Yevgeniy; Jiang, Yuan; Meltzer, Paul S.] NCI, Genet Branch, NIH, Bethesda, MD 20982 USA.
[Reinhold, William C.; Doroshow, James H.; Pommier, Yves] NCI, Lab Mol Pharmacol, Ctr Canc Res, NIH, Bethesda, MD 20982 USA.
[Polley, Eric C.; Holbeck, Susan L.; Simon, Richard M.; Doroshow, James H.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20982 USA.
RP Pommier, Y (reprint author), NCI, Lab Mol Pharmacol, Ctr Canc Res, 37 Convent Dr, Bethesda, MD 20982 USA.
EM pommier@nih.gov; pmeltzer@mail.nih.gov
OI Davis, Sean/0000-0002-8991-6458
FU Division of Cancer Treatment and Diagnosis (DCTD); Center for Cancer
Research (CCR) of the National Cancer Institute, NIH
FX This study was supported by the Division of Cancer Treatment and
Diagnosis (DCTD), and the Center for Cancer Research (CCR) of the
National Cancer Institute, NIH.
NR 50
TC 102
Z9 104
U1 0
U2 20
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 JUL 15
PY 2013
VL 73
IS 14
BP 4372
EP 4382
DI 10.1158/0008-5472.CAN-12-3342
PG 11
WC Oncology
SC Oncology
GA 183NR
UT WOS:000321823600020
PM 23856246
ER
PT J
AU Santos, AJM
Meinecke, M
Fessler, MB
Holden, DW
Boucrot, E
AF Santos, Antonio J. M.
Meinecke, Michael
Fessler, Michael B.
Holden, David W.
Boucrot, Emmanuel
TI Preferential invasion of mitotic cells by Salmonella reveals that cell
surface cholesterol is maximal during metaphase
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Mitosis; Cholesterol; Plasma membrane; Bacterial pathogenesis;
Salmonella
ID BACTERIAL PATHOGENS; MAMMALIAN-CELLS; STEM-CELLS; TRANSPORT; MITOSIS;
REDISTRIBUTION; SECRETION; MEMBRANES; RIGIDITY; ENTRY
AB Cell surface-exposed cholesterol is crucial for cell attachment and invasion of many viruses and bacteria, including the bacterium Salmonella, which causes typhoid fever and gastroenteritis. Using flow cytometry and 3D confocal fluorescence microscopy, we found that mitotic cells, although representing only 1-4% of an exponentially growing population, were much more efficiently targeted for invasion by Salmonella. This targeting was not dependent on the spherical shape of mitotic cells, but was instead SipB and cholesterol dependent. Thus, we measured the levels of plasma membrane and cell surface cholesterol throughout the cell cycle using, respectively, brief staining with filipin and a fluorescent ester of polyethylene glycol-cholesterol that cannot flip through the plasma membrane, and found that both were maximal during mitosis. This increase was due not only to the rise in global cell cholesterol levels along the cell cycle but also to a transient loss in cholesterol asymmetry at the plasma membrane during mitosis. We measured that cholesterol, but not phosphatidylserine, changed from a,20: 80 outer: inner leaflet repartition during interphase to,50: 50 during metaphase, suggesting this was specific to cholesterol and not due to a broad change of lipid asymmetry during metaphase. This explains the increase in outer surface levels that make dividing cells more susceptible to Salmonella invasion and perhaps to other viruses and bacteria entering cells in a cholesterol-dependent manner. The change in cholesterol partitioning also favoured the recruitment of activated ERM (Ezrin, Radixin, Moesin) proteins at the plasma membrane and thus supported mitotic cell rounding.
C1 [Santos, Antonio J. M.; Holden, David W.] Univ London Imperial Coll Sci Technol & Med, Microbiol Sect, MRC Ctr Mol Bacteriol & Infect, London SW7 2AZ, England.
[Santos, Antonio J. M.] Univ Porto, Grad Program Areas Basic & Appl Biol GABBA, P-4100 Oporto, Portugal.
[Meinecke, Michael] Univ Gottingen, Dept Biochem 2, D-37073 Gottingen, Germany.
[Fessler, Michael B.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
[Boucrot, Emmanuel] UCL, Inst Struct & Mol Biol, Div Biosci, London WC1E 6BT, England.
RP Boucrot, E (reprint author), UCL, Inst Struct & Mol Biol, Div Biosci, Mortimer St, London WC1E 6BT, England.
EM e.boucrot@ucl.ac.uk
RI Meinecke, Michael/C-4833-2013;
OI Meinecke, Michael/0000-0003-1414-6951; Santos,
Antonio/0000-0001-6514-7423
FU Fundacao para a Ciencia e Tecnologia; Human Frontier Science Program;
Deutsche Forschungsgemeinschaft [803]; Intramural Research Program of
the National Institutes of Health National Institute of Environmental
Health Sciences [Z01 ES102005]; Medical Research Council; Wellcome
Trust; Biotechnology and Biological Sciences Research Council David
Phillips Research Fellowship
FX This work was supported in part by Fundacao para a Ciencia e Tecnologia
(to A.J.M.S.); the Human Frontier Science Program; Deutsche
Forschungsgemeinschaft [grant number SFB 803 to M.M.]; the Intramural
Research Program of the National Institutes of Health National Institute
of Environmental Health Sciences [grant number Z01 ES102005 to M.B.F.];
the Medical Research Council and the Wellcome Trust [to D.W.H.]; and a
Biotechnology and Biological Sciences Research Council David Phillips
Research Fellowship [to E.B.]. Deposited in PMC for release after 6
months.
NR 26
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PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
J9 J CELL SCI
JI J. Cell Sci.
PD JUL 15
PY 2013
VL 126
IS 14
BP 2990
EP 2996
DI 10.1242/jcs.115253
PG 7
WC Cell Biology
SC Cell Biology
GA 182MQ
UT WOS:000321747400003
PM 23687374
ER
PT J
AU Fu, CH
Jin, GX
Gao, JF
Zhu, R
Ballesteros-villagrana, E
Wong, STC
AF Fu, Changhe
Jin, Guangxu
Gao, Junfeng
Zhu, Rui
Ballesteros-villagrana, Efren
Wong, Stephen T. C.
TI DrugMap Central: an on-line query and visualization tool to facilitate
drug repositioning studies
SO BIOINFORMATICS
LA English
DT Article
ID DATABASE
AB Systematic studies of drug repositioning require the integration of multi-level drug data, including basic chemical information (such as SMILES), drug targets, target-related signaling pathways, clinical trial information and Food and Drug Administration (FDA)-approval information, to predict new potential indications of existing drugs. Currently available databases, however, lack query support for multi-level drug information and thus are not designed to support drug repositioning studies. DrugMap Central (DMC), an online tool, is developed to help fill the gap. DMC enables the users to integrate, query, visualize, interrogate, and download multi-level data of known drugs or compounds quickly for drug repositioning studies all within one system.
C1 [Fu, Changhe; Jin, Guangxu; Gao, Junfeng; Zhu, Rui; Ballesteros-villagrana, Efren; Wong, Stephen T. C.] Methodist Hosp, Res Inst, Weill Cornell Med Coll, Dept Syst Med & Bioengn, Houston, TX 77030 USA.
[Jin, Guangxu; Wong, Stephen T. C.] Methodist Hosp, Res Inst, NCI Ctr Modeling Canc Dev, Houston, TX 77030 USA.
RP Wong, STC (reprint author), Methodist Hosp, Res Inst, Weill Cornell Med Coll, Dept Syst Med & Bioengn, Houston, TX 77030 USA.
EM STWong@tmhs.org
FU NIH [U54CA149196]; TT & WF Chao Foundation
FX Funding: NIH [U54CA149196]; TT & WF Chao Foundation (to S.T.C.W.).
NR 11
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U1 0
U2 14
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD JUL 15
PY 2013
VL 29
IS 14
BP 1834
EP 1836
DI 10.1093/bioinformatics/btt279
PG 3
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 182MS
UT WOS:000321747800027
PM 23681121
ER
PT J
AU Qian, WJ
Park, JE
Liu, F
Lee, KS
Burke, TR
AF Qian, Wenjian
Park, Jung-Eun
Liu, Fa
Lee, Kyung S.
Burke, Terrence R., Jr.
TI Effects on polo-like kinase 1 polo-box domain binding affinities of
peptides incurred by structural variation at the phosphoamino acid
position
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Plk1; Polo-like kinase; Polo-box domain; Phosphoamino acid mimetic
ID PROTEIN-PROTEIN INTERACTIONS; SMALL-MOLECULE INHIBITOR;
SIGNAL-TRANSDUCTION; CANCER-THERAPY; HOT-SPOT; PHOSPHORYLATION;
DISCOVERY; POLO-LIKE-KINASE-1; DERIVATIVES; SERINE
AB Protein-protein interactions (PPIs) mediated by the polo-box domain (PBD) of polo-like kinase 1 (Plk1) serve important roles in cell proliferation. Critical elements in the high affinity recognition of peptides and proteins by PBD are derived from pThr/pSer-residues in the binding ligands. However, there has been little examination of pThr/pSer mimetics within a PBD context. Our current paper compares the abilities of a variety of amino acid residues and derivatives to serve as pThr/pSer replacements by exploring the role of methyl functionality at the pThr beta-position and by replacing the phosphoryl group by phosphonic acid, sulfonic acid and carboxylic acids. This work sheds new light on structure activity relationships for PBD recognition of phosphoamino acid mimetics. Published by Elsevier Ltd.
C1 [Qian, Wenjian; Liu, Fa; Burke, Terrence R., Jr.] NCI, Biol Chem Lab, Frederick Natl Lab Canc Res, NIH, Frederick, MD 21702 USA.
[Park, Jung-Eun; Lee, Kyung S.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Lee, KS (reprint author), NCI, NIH, 9000 Rockville Pike,Bldg 37,Room 3118, Bethesda, MD 20892 USA.
EM kyunglee@mail.nih.gov; tburke@helix.nih.gov
RI Burke, Terrence/N-2601-2014
FU Intramural Research Program of the NIH; Center for Cancer Research;
NCI-Frederick; National Cancer Institute, National Institutes of Health
FX This work was supported in part by the Intramural Research Program of
the NIH, Center for Cancer Research, NCI-Frederick and the National
Cancer Institute, National Institutes of Health. We thank Drs.
Christpher C. Lai and James A. Kelley of the CBL for obtaining the
high-resolution mass spectra and for assistance in the interpretation of
the data. The content of this publication does not necessarily reflect
the views or policies of the Department of Health and Human Services,
nor does mention of trade names, commercial products, or organizations
imply endorsement by the U.S. Government.
NR 71
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PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD JUL 15
PY 2013
VL 21
IS 14
BP 3996
EP 4003
DI 10.1016/j.bmc.2012.05.036
PG 8
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 170GK
UT WOS:000320838200003
PM 22743087
ER
PT J
AU Simister, PC
Luccarelli, J
Thompson, S
Appella, DH
Feller, SM
Hamilton, AD
AF Simister, Philip C.
Luccarelli, James
Thompson, Sam
Appella, Daniel H.
Feller, Stephan M.
Hamilton, Andrew D.
TI Novel inhibitors of a Grb2 SH3C domain interaction identified by a
virtual screen
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE SH3 Domain; Grb2; Gab2; Virtual screening; Protein-protein interaction;
Inhibitors
ID HUMAN-BREAST-CANCER; HIGH-AFFINITY; BINDING; PROTEIN; PLUS;
OVEREXPRESSION; TRASTUZUMAB; DOCETAXEL; MONA/GADS; DOCKING
AB The adaptor protein Grb2 links cell-surface receptors, such as Her2, to the multisite docking proteins Gab1 and 2, leading to cell growth and proliferation in breast and other cancers. Gab2 interacts with the C-terminal SH3 domain (SH3C) of Grb2 through atypical RxxK motifs within polyproline II or 3(10) helices. A virtual screen was conducted for putative binders of the Grb2 SH3C domain. Of the top hits, 34 were validated experimentally by surface plasmon resonance spectroscopy and isothermal titration calorimetry. A subset of these molecules was found to inhibit the Grb2-Gab2 interaction in a competition assay, with moderate to low affinities (5: IC50 320 mu M). The most promising binders were based on a dihydro-s-triazine scaffold, and are the first small molecules reported to target the Grb2 SH3C protein-interaction surface. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Luccarelli, James; Thompson, Sam; Hamilton, Andrew D.] Univ Oxford, Dept Chem, Chem Res Lab, Oxford OX1 3TA, England.
[Simister, Philip C.; Feller, Stephan M.] Univ Oxford, Weatherall Inst Mol Med, Biol Syst Architecture Grp, Oxford OX3 9DS, England.
[Luccarelli, James; Appella, Daniel H.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Feller, SM (reprint author), Univ Oxford, Weatherall Inst Mol Med, Biol Syst Architecture Grp, Oxford OX3 9DS, England.
EM stephan.feller@imm.ox.ac.uk; andrew.hamil-ton@chem.ox.ac.uk
RI Thompson, Sam/I-5599-2013
OI Thompson, Sam/0000-0001-6267-5693
FU Oxford Cancer Research Centre Development Fund; Rosetrees Trust; Breast
Cancer Campaign and Cancer Research UK; Cancer Research UK; University
of Oxford; Marshall Aid Commemoration Commission; Oriel College, Oxford
FX We thank the Oxford Cancer Research Centre Development Fund and the
Rosetrees Trust (PCS and SF), Breast Cancer Campaign and Cancer Research
UK (SF) Cancer Research UK (SF), the University of Oxford (JL and ST),
the Marshall Aid Commemoration Commission and Oriel College, Oxford (JL)
for funding. This study utilized the high-performance computational
capabilities of the Biowulf Linux cluster at the National Institutes of
Health, Bethesda, Md. (http://biowulf.nih.gov).
NR 32
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PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD JUL 15
PY 2013
VL 21
IS 14
BP 4027
EP 4033
DI 10.1016/j.bmc.2012.10.023
PG 7
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 170GK
UT WOS:000320838200007
PM 23182216
ER
PT J
AU Rao, JU
Engelke, UFH
Rodenburg, RJT
Wevers, RA
Pacak, K
Eisenhofer, G
Qin, N
Kusters, B
Goudswaard, AG
Lenders, JWM
Hermus, ARMM
Mensenkamp, AR
Kunst, HPM
Sweep, FCGJ
Timmers, HJLM
AF Rao, Jyotsna U.
Engelke, Udo F. H.
Rodenburg, Richard J. T.
Wevers, Ron A.
Pacak, Karel
Eisenhofer, Graeme
Qin, Nan
Kusters, Benno
Goudswaard, Angelina G.
Lenders, Jacques W. M.
Hermus, Ad R. M. M.
Mensenkamp, Arjen R.
Kunst, Henricus P. M.
Sweep, Fred C. G. J.
Timmers, Henri J. L. M.
TI Genotype-Specific Abnormalities in Mitochondrial Function Associate with
Distinct Profiles of Energy Metabolism and Catecholamine Content in
Pheochromocytoma and Paraganglioma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; SPORADIC PHEOCHROMOCYTOMA; CHROMAFFIN
GRANULES; PROLYL HYDROXYLASE; ENZYMATIC-ACTIVITY; RESPIRATORY-CHAIN; SDH
MUTATIONS; COMPLEX-II; TRANSPORTER; GENE
AB Purpose: Pheochromocytomas and paragangliomas (PGL) are neuroendocrine tumors of sympathetic and parasympathetic paraganglia. This study investigated the relationships between genotype-specific differences in mitochondrial function and catecholamine content in PGL tumors.
Experimental Design: Respiratory chain enzyme assays and 1 H-nuclear magnetic resonance (NMR) spectroscopy at 500 MHz were conducted on homogenates of 35 sporadic PGLs and 59 PGLs from patients with hereditary mutations in succinate dehydrogenase subunits B and D (SDHB, SDHD), succinate dehydrogenase assembly factor 2, von Hippel-Lindau (VHL), rearranged during transfection (RET), neurofibromatosis type 1 (NF1), and myc-associated factor X.
Results: In SDHx-related PGLs, a significant decrease in complex II activity (P < 0.0001) and a significant increase in complex I, III, and IV enzyme activities were observed when compared to sporadic, RET, and NF1 tumors. Also, a significant increase in citrate synthase (P < 0.0001) enzyme activity was observed in SDHx-related PGLs when compared to sporadic-, VHL-, RET-, and NF1-related tumors. An increase in succinate accumulation (P < 0.001) and decrease in ATP/ADP/AMP accumulation (P < 0.001) was observed when compared to sporadic PGLs and PGLs of other genotypes. Positive correlations (P < 0.01) were observed between respiratory chain complex II activity and total catecholamine content and ATP/ADP/AMP and total catecholamine contents in tumor tissues.
Conclusions: This study for the first time establishes a relationship between determinants of energy metabolism, like activity of respiratory chain enzyme complex II, ATP/ADP/AMP content, and catecholamine content in PGL tumors. Also, this study for the first time successfully uses NMR spectroscopy to detect catecholamines in PGL tumors and provides ex vivo evidence for the accumulation of succinate in PGL tumors with an SDHx mutation. (C) 2013 AACR.
C1 [Rao, Jyotsna U.; Engelke, Udo F. H.; Rodenburg, Richard J. T.; Wevers, Ron A.; Goudswaard, Angelina G.; Sweep, Fred C. G. J.] Radboud Univ Nijmegen, Med Ctr, Dept Lab Med, Lab Genet Endocrine & Metab Dis, NL-6525 ED Nijmegen, Netherlands.
[Rao, Jyotsna U.; Hermus, Ad R. M. M.; Timmers, Henri J. L. M.] Radboud Univ Nijmegen, Med Ctr, Dept Med, Div Endocrinol, NL-6525 ED Nijmegen, Netherlands.
[Rodenburg, Richard J. T.] Radboud Univ Nijmegen, Med Ctr, Dept Pediat, NL-6525 ED Nijmegen, Netherlands.
[Kusters, Benno] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6525 ED Nijmegen, Netherlands.
[Lenders, Jacques W. M.] Radboud Univ Nijmegen, Med Ctr, Dept Med, Div Vasc Med, NL-6525 ED Nijmegen, Netherlands.
[Mensenkamp, Arjen R.] Radboud Univ Nijmegen, Med Ctr, Dept Genet, NL-6525 ED Nijmegen, Netherlands.
[Kunst, Henricus P. M.] Radboud Univ Nijmegen, Med Ctr, Dept Otolaryngol, NL-6525 ED Nijmegen, Netherlands.
[Kusters, Benno] Maastricht Univ, Med Ctr, Dept Pathol, Maastricht, Netherlands.
[Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Eisenhofer, Graeme; Qin, Nan; Lenders, Jacques W. M.] Univ Hosp Carl Gustav Carus, Dept Med, Dresden, Germany.
[Eisenhofer, Graeme; Qin, Nan; Lenders, Jacques W. M.] Univ Hosp Carl Gustav Carus, Inst Clin Chem & Lab Med, Dresden, Germany.
RP Timmers, HJLM (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Med, Div Endocrinol, NL-6525 ED Nijmegen, Netherlands.
EM H.Timmers@endo.umcn.nl
RI Mensenkamp, A.R./L-4520-2015; Kunst, Henricus/J-6456-2012; Sweep,
C.G.J./H-8096-2014; Wevers, Ron/H-8116-2014; Hermus,
A.R.M.M./H-8043-2014; Engelke, U.F.H./L-4293-2015; Kusters,
B./L-4465-2015; Lenders, J.W.M./L-4487-2015; Rodenburg,
Richard/N-3579-2014
OI Wevers, Ron/0000-0003-2278-9746; Rodenburg, Richard/0000-0001-5227-3527
FU European Union Seventh Framework Programme [259735]
FX The work leading to these results has received funding from the European
Union Seventh Framework Programme (FP7/2007-2013) under grant agreement
no. 259735 (ENSAT CANCER).
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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 JUL 15
PY 2013
VL 19
IS 14
BP 3787
EP 3795
DI 10.1158/1078-0432.CCR-12-3922
PG 9
WC Oncology
SC Oncology
GA 183NE
UT WOS:000321822000009
PM 23723300
ER
PT J
AU Herzog, A
Bian, YS
Vander Broek, R
Hall, B
Coupar, J
Cheng, H
Sowers, AL
Cook, JD
Mitchell, JB
Chen, Z
Kulkarni, AB
Van Waes, C
AF Herzog, Amanda
Bian, Yansong
Vander Broek, Robert
Hall, Bradford
Coupar, Jamie
Cheng, Hui
Sowers, Anastasia L.
Cook, John D.
Mitchell, James B.
Chen, Zhong
Kulkarni, Ashok B.
Van Waes, Carter
TI PI3K/mTOR Inhibitor PF-04691502 Antitumor Activity Is Enhanced with
Induction of Wild-Type TP53 in Human Xenograft and Murine Knockout
Models of Head and Neck Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; NF-KAPPA-B; MAMMALIAN TARGET; GROWTH-FACTOR;
AKT/MAMMALIAN TARGET; MOLECULAR TARGET; SURGICAL MARGINS; MTOR
INHIBITION; RAPAMYCIN; ACTIVATION
AB Purpose: Phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway activation is often associated with altered expression or mutations of PIK3CA, TP53/p73, PTEN, and TGF-beta receptors (TGFBR) in head and neck squamous cell carcinomas (HNSCC). However, little is known about how these alterations affect response to PI3K/mTOR-targeted agents.
Experimental Design: In this preclinical study, PI3K/Akt/mTOR signaling was characterized in nine HNSCC (UM-SCC) cell lines and human oral keratinocytes. We investigated the molecular and anticancer effects of dual PI3K/mTOR inhibitor PF-04691502(PF-502) in UM-SCC expressing PIK3CA with decreased wild-type TP53, mutant TP53-/+ mutantTGFBR2, and in HNSCC of a conditional Pten/Tgfbr1 double knockout mouse model displaying PI3K/Akt/mTOR activation.
Results: UM-SCC showed increased PIK3CA expression and Akt/mTOR activation, and PF-502 inhibited PI3K/mTORC1/2 targets. In human HNSCC expressing PIK3CA and decreased wtTP53 and p73, PF-502 reciprocally enhanced TP53/p73 expression and growth inhibition, which was partially reversible by p53 inhibitor pifithrin-alpha. Most UM-SCC with wtTP53 exhibited a lower IC50 than those with mtTP53 status. PF-502 blocked growth in G(0)-G(1) and increased apoptotic sub-G(0) DNA. PF-502 suppressed tumorigenesis and showed combinatorial activity with radiation in a wild-type TP53 UM-SCC xenograft model. PF-502 also significantly delayed HNSCC tumorigenesis and prolonged survival of Pten/Tgfbr1-deficient mice. Significant inhibition of p-Akt, p-4EBP1, p-S6, and Ki67, as well as increased p53 and TUNEL were observed in tumor specimens.
Conclusions: PI3K-mTOR inhibition can enhance TP53/p73 expression and significantly inhibit tumor growth alone or when combined with radiation in HNSCC with wild-type TP53. PIK3CA, TP53/p73, PTEN, and TGF-beta alterations are potential modifiers of response and merit investigation in future clinical trials with PI3K-mTOR inhibitors. (C)2013 AACR
C1 [Herzog, Amanda; Bian, Yansong; Vander Broek, Robert; Coupar, Jamie; Cheng, Hui; Chen, Zhong; Van Waes, Carter] NIDCD, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA.
[Herzog, Amanda; Vander Broek, Robert] NIH Med Res Scholars Program, HHMI NIH Res Scholars Program, Bethesda, MD USA.
[Hall, Bradford; Kulkarni, Ashok B.] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Bethesda, MD USA.
[Sowers, Anastasia L.; Cook, John D.; Mitchell, James B.] NCI, Radiat Biol Branch, Bethesda, MD 20892 USA.
RP Van Waes, C (reprint author), NIDCD, NIH, Bldg 10-CRC,4-2732,10 Ctr Dr, Bethesda, MD 20892 USA.
EM vanwaesc@nidcd.nih.gov
FU NIDCD [ZIA-DC-000073, ZIA-DC-000074]; NIDCR [ZIA-DE-000698,
ZIA-SC-006321]
FX This work is supported by NIDCD intramural projects ZIA-DC-000073 and
ZIA-DC-000074 (C. Van Waes), NIDCR intramural project ZIA-DE-000698
(A.B. Kulkarni), and ZIA-SC-006321 (J.B. Mitchell).
NR 45
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U2 6
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 JUL 15
PY 2013
VL 19
IS 14
BP 3808
EP 3819
DI 10.1158/1078-0432.CCR-12-2716
PG 12
WC Oncology
SC Oncology
GA 183NE
UT WOS:000321822000011
PM 23640975
ER
PT J
AU Zhu, WW
Guo, JJ
Guo, L
Jia, HL
Zhu, M
Zhang, JB
Loffredo, CA
Forgues, M
Huang, H
Xing, XJ
Ren, N
Dong, QZ
Zhou, HJ
Ren, ZG
Zhao, NQ
Wang, XW
Tang, ZY
Qin, LX
Ye, QH
AF Zhu, Wen-Wei
Guo, Jia-Jian
Guo, Lei
Jia, Hu-Liang
Zhu, Ming
Zhang, Ju-Bo
Loffredo, Christopher A.
Forgues, Marshonna
Huang, Hua
Xing, Xu-Jian
Ren, Ning
Dong, Qiong-Zhu
Zhou, Hai-Jun
Ren, Zheng-Gang
Zhao, Nai-Qing
Wang, Xin Wei
Tang, Zhao-You
Qin, Lun-Xiu
Ye, Qing-Hai
TI Evaluation of Midkine as a Diagnostic Serum Biomarker in Hepatocellular
Carcinoma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ALPHA-FETOPROTEIN; TUMOR-MARKERS; UNITED-STATES; EXPRESSION; SURVIVAL;
CANCER; RESECTION; TUMORIGENESIS; PLEIOTROPHIN; MANAGEMENT
AB Purpose: To evaluate the value of serum midkine (MDK) as a diagnostic biomarker in hepatocellular carcinoma, particularly for those with negative alpha-fetoprotein (AFP) and at an early stage.
Experimental Design: MDK expression in tumors was assessed by immunohistochemistry from 105 patients with hepatocellular carcinomas or liver cirrhosis. Serum MDK levels were detected by ELISA in 933 participants including hepatocellular carcinomas and hospital controls from different medical centers. Sensitivities and specificities of serum MDK in diagnosing hepatocellular carcinoma according to AFP level and Barcelona Clinic Liver Cancer (BCLC) stage were analyzed.
Results: MDK levels were significantly elevated in hepatocellular carcinoma tissues as well as serum samples. The sensitivity of serum MDK for hepatocellular carcinoma diagnosis was much higher than that of AFP (86.9% vs. 51.9%) with similar specificities (83.9% vs. 86.3%). Notably, serum MDK had an outstanding performance in distinguishing AFP-negative hepatocellular carcinomas from different controls: In those AFP-negative hepatocellular carcinomas, the sensitivity could reach as high as 89.2%. Moreover, receiver operating characteristic (ROC) curve analysis also showed that serum MDK had a better performance compared with AFP in distinguishing early-stage hepatocellular carcinomas as well as small hepatocellular carcinomas. Even in very early-stage hepatocellular carcinomas, MDK showed an obviously higher sensitivity compared with AFP (80% vs. 40%). Furthermore, serum MDK level was significantly decreased in patients with hepatocellular carcinomas after curative resection and re-elevated when tumor relapse occurred.
Conclusions: Serum MDK is significantly elevated in most hepatocellular carcinomas, including those with negative AFP and at an early stage, which may serve as a novel diagnostic marker in early diagnosis and postoperative monitoring of hepatocellular carcinomas. (C) 2013 AACR.
C1 [Zhu, Wen-Wei; Guo, Jia-Jian; Guo, Lei; Jia, Hu-Liang; Zhang, Ju-Bo; Xing, Xu-Jian; Ren, Ning; Dong, Qiong-Zhu; Zhou, Hai-Jun; Ren, Zheng-Gang; Tang, Zhao-You; Qin, Lun-Xiu; Ye, Qing-Hai] Fudan Univ, Liver Canc Inst, Sch Publ Hlth, Shanghai 200032, Peoples R China.
[Zhu, Wen-Wei; Guo, Jia-Jian; Guo, Lei; Jia, Hu-Liang; Zhang, Ju-Bo; Xing, Xu-Jian; Ren, Ning; Dong, Qiong-Zhu; Zhou, Hai-Jun; Ren, Zheng-Gang; Tang, Zhao-You; Qin, Lun-Xiu; Ye, Qing-Hai] Fudan Univ, Sch Publ Hlth, Zhongshan Hosp, Inst Biomed Sci, Shanghai 200032, Peoples R China.
[Zhu, Ming; Zhao, Nai-Qing] Fudan Univ, Sch Publ Hlth, Dept Biostat, Shanghai 200032, Peoples R China.
[Zhu, Wen-Wei; Guo, Jia-Jian; Guo, Lei; Jia, Hu-Liang; Zhang, Ju-Bo; Xing, Xu-Jian; Ren, Ning; Dong, Qiong-Zhu; Zhou, Hai-Jun; Ren, Zheng-Gang; Tang, Zhao-You; Qin, Lun-Xiu; Ye, Qing-Hai] Fudan Univ, Minist Educ, Key Lab Carcinogenesis & Canc Invas, Shanghai 200032, Peoples R China.
[Huang, Hua] Fudan Univ, Shanghai Canc Ctr, Dept Abdominal Surg, Shanghai 200032, Peoples R China.
[Loffredo, Christopher A.] Georgetown Univ, Lombardi Canc Ctr, Washington, DC USA.
[Forgues, Marshonna; Wang, Xin Wei] NCI, Lab Human Carcinogenesis, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Ye, QH (reprint author), Fudan Univ, Liver Canc Inst, 180 Feng Lin Rd, Shanghai 200032, Peoples R China.
EM qin.lunxiu@zs-hospital.sh.cn; ye.qinghai@zs-hospital.sh.cn
RI Wang, Xin/B-6162-2009
FU National Key Project for Infectious Disease of China
[2012ZX10002012-003]; State Key Basic Research Program of China
[2009CB521701]; National Natural Science Foundation of China [81071993,
30672037, 30300400, 30700991]; Intramural Research Program of the Center
for Cancer Research of the National Cancer Institute [Z01 BC 010313, Z01
BC 010876]; U.S. NIH [R01CA85888]; Clinical and Molecular Epidemiology
Shared Resource of the Lombardi Cancer Center at Georgetown University
[P30CA51008]
FX This work was supported in part by the Grants of the National Key
Project for Infectious Disease of China (2012ZX10002012-003), the State
Key Basic Research Program of China (2009CB521701), and the National
Natural Science Foundation of China (No. 81071993, 30672037, 30300400
and 30700991). X.W. Wang was supported by grants (Z01 BC 010313 and Z01
BC 010876) from the Intramural Research Program of the Center for Cancer
Research of the National Cancer Institute. The study in Egypt was funded
by the U.S. NIH (grant R01CA85888) and supported by the Clinical and
Molecular Epidemiology Shared Resource of the Lombardi Cancer Center at
Georgetown University (grant P30CA51008).
NR 41
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PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 15
PY 2013
VL 19
IS 14
BP 3944
EP 3954
DI 10.1158/1078-0432.CCR-12-3363
PG 11
WC Oncology
SC Oncology
GA 183NE
UT WOS:000321822000023
PM 23719264
ER
PT J
AU Stearns, V
Jacobs, LK
Fackler, M
Tsangaris, TN
Rudek, MA
Higgins, M
Lange, J
Cheng, Z
Slater, SA
Jeter, SC
Powers, P
Briest, S
Chao, C
Yoshizawa, C
Sugar, E
Espinoza-Delgado, I
Sukumar, S
Gabrielson, E
Davidson, NE
AF Stearns, Vered
Jacobs, Lisa K.
Fackler, MaryJo
Tsangaris, Theodore N.
Rudek, Michelle A.
Higgins, Michaela
Lange, Julie
Cheng, Zandra
Slater, Shannon A.
Jeter, Stacie C.
Powers, Penny
Briest, Susanne
Chao, Calvin
Yoshizawa, Carl
Sugar, Elizabeth
Espinoza-Delgado, Igor
Sukumar, Saraswati
Gabrielson, Edward
Davidson, Nancy E.
TI Biomarker Modulation following Short-Term Vorinostat in Women with Newly
Diagnosed Primary Breast Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID SUBEROYLANILIDE HYDROXAMIC ACID; HISTONE DEACETYLASE INHIBITOR;
METHYLATION-SPECIFIC PCR; PROMOTER HYPERMETHYLATION; PHASE-II; CELLS;
TAMOXIFEN; ASSAY; THERAPY; TARGET
AB Purpose: Agents that target the epigenome show activity in breast cancer models. In preclinical studies, the histone deacetylase inhibitor vorinostat induces cell-cycle arrest, apoptosis, and differentiation. We evaluated biomarker modulation in breast cancer tissues obtained from women with newly diagnosed invasive disease who received vorinostat and those who did not.
Experimental Design: Tumor specimens were collected from 25 women who received up to 6 doses of oral vorinostat 300 mg twice daily and from 25 untreated controls in a nonrandomized study. Candidate gene expression was analyzed by reverse transcription PCR (RT-PCR) using the Oncotype DX 21-gene assay, and by immunohistochemistry for Ki-67 and cleaved caspase-3. Matched samples from treated women were analyzed for gene methylation by quantitative multiplex methylation-specific PCR (QM-MSP). Wilcoxon nonparametric tests were used to compare changes in quantitative gene expression levels pre- and post-vorinostat with changes in expression in untreated controls, and changes in gene methylation between pre- and post-vorinostat samples.
Results: Vorinostat was well tolerated and there were no study-related delays in treatment. Compared with untreated controls, there were statistically significant decreases in the expression of proliferation-associated genes Ki-67 (P = 0.003), STK15 (P = 0.005), and Cyclin B1 (P = 0.03) following vorinostat, but not in other genes by the Oncotype DX assay, or in expression of Ki-67 or cleaved caspase-3 by immunohistochemistry. Changes in methylation were not observed.
Conclusions: Short-term vorinostat administration is associated with a significant decrease in expression of proliferation-associated genes in untreated breast cancers. This demonstration of biologic activity supports investigation of vorinostat in combination with other agents for the management of breast cancer. (C) 2013 AACR.
C1 [Stearns, Vered; Fackler, MaryJo; Rudek, Michelle A.; Higgins, Michaela; Slater, Shannon A.; Jeter, Stacie C.; Powers, Penny; Briest, Susanne; Sugar, Elizabeth; Sukumar, Saraswati; Davidson, Nancy E.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
[Jacobs, Lisa K.; Tsangaris, Theodore N.; Lange, Julie] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA.
[Gabrielson, Edward] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Sugar, Elizabeth] Johns Hopkins Bloomberg, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Sugar, Elizabeth] Johns Hopkins Bloomberg, Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
[Cheng, Zandra] Anne Arundel Med Ctr, Annapolis, MD USA.
[Espinoza-Delgado, Igor] NCI, NIH, Bethesda, MD 20892 USA.
[Chao, Calvin; Yoshizawa, Carl] Genom Hlth Inc, Redwood City, CA USA.
RP Higgins, M (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
EM theodore.tsangaris@yale.edu; mjhiggins@partners.org
FU CTEP; NIH [U01 CA 70095]; SAIC [P6914, P30CA47904, U01-CA099168];
American Society of Clinical Oncology Advanced Clinical Research Award;
Young Investigator Award; Specialized Program of Research Excellence in
Breast Cancer [P50 CA88843]; Avon Foundation; Merck
FX This work was supported by the CTEP, NIH U01 CA 70095 (to V. Stearns VS
and M.A. Rudek) and SAIC (P6914 to V. Stearns), P30CA47904 (to M.
Egorin) and U01-CA099168 (to M. Egorin), American Society of Clinical
Oncology Advanced Clinical Research Award (to V. Stearns), Young
Investigator Award (to M.J. Higgins), Specialized Program of Research
Excellence in Breast Cancer (P50 CA88843 to S. Sukumar and N.E.
Davidson), and by the Avon Foundation. Vorinostat for the vorinostat and
tamoxifen study was supplied by Merck. The Oncotype DX 21-gene assays
were conducted by Genomic Health, Inc.
NR 23
TC 14
Z9 14
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 15
PY 2013
VL 19
IS 14
BP 4008
EP 4016
DI 10.1158/1078-0432.CCR-13-0033
PG 9
WC Oncology
SC Oncology
GA 183NE
UT WOS:000321822000029
PM 23719261
ER
PT J
AU Alvarez, M
Sungur, CM
Ames, E
Anderson, SK
Pomeroy, C
Murphy, WJ
AF Alvarez, Maite
Sungur, Can M.
Ames, Erik
Anderson, Stephen K.
Pomeroy, Claire
Murphy, William J.
TI Contrasting Effects of Anti-Ly49A Due to MHC Class I cis Binding on NK
Cell-Mediated Allogeneic Bone Marrow Cell Resistance
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NATURAL-KILLER-CELLS; H-2-DEFICIENT LYMPHOMA VARIANTS; RECEPTOR LY49A;
INHIBITORY RECEPTORS; CRYSTAL-STRUCTURE; REJECTION; MOLECULES; LIGAND;
RECOGNITION; SPECIFICITY
AB NK subsets have activating and inhibitory receptors that bind MHC-I. Ly49A is a mouse inhibitory receptor that binds with high affinity to H2(d) in both a cis- and trans-manner. Ly49A cis-associations limit trans-interactions with H2(d)-expressing targets as well as mAb binding. We demonstrate that cis-interactions affect mAb effector functions. In vivo administration of anti-Ly49A depleted NK cells in H2(b) but not H2(d) mice. Despite lack of depletion, in vivo treatment with anti-Ly49A reduced NK killing capabilities and inhibited activation, partially due to its agonistic effect. These data explain the previously described in vivo effects on bone marrow allograft rejection observed with anti-Ly49A treatment in H2(d)-haplotype mice. However, prior treatment of mice with poly(I:C) or mouse CMV infection resulted in increased Ly49A expression and Ly49A(+) NK cell depletion in H2(d) mice. These data indicate that, although Ly49 mAbs can exert similar in vivo effects in mice with different MHC haplotypes, these effects are mediated via different mechanisms of action correlating with Ly49A expression levels and can be altered within the same strain contingent on stimuli. This illustrates the marked diversity of mAb effector functions due to the regulation of the level of expression of target Ags and responses by stimulatory incidents such as infection. The Journal of Immunology, 2013, 191: 688-698.
C1 [Alvarez, Maite; Sungur, Can M.; Ames, Erik; Murphy, William J.] Univ Calif Davis, Dept Dermatol, Sacramento, CA 95817 USA.
[Anderson, Stephen K.] NCI, Expt Immunol Lab, Canc & Inflammat Program, SAIC Frederick, Frederick, MD 21702 USA.
[Pomeroy, Claire; Murphy, William J.] Univ Calif Davis, Dept Internal Med, Sacramento, CA 95817 USA.
RP Murphy, WJ (reprint author), Univ Calif Davis, Clin & Translat Sci Ctr, Inst Regenerat Cures Bldg CTSC IRC, Dept Dermatol,Sch Med, Suite 1630,2921 Stockton Blvd, Sacramento, CA 95817 USA.
EM wmjmurphy@ucdavis.edu
RI Anderson, Stephen/B-1727-2012
OI Anderson, Stephen/0000-0002-7856-4266
FU National Institutes of Health [R01-HL089905]
FX This work was supported by National Institutes of Health Grant
R01-HL089905.
NR 55
TC 3
Z9 4
U1 0
U2 5
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUL 15
PY 2013
VL 191
IS 2
BP 688
EP 698
DI 10.4049/jimmunol.1300202
PG 11
WC Immunology
SC Immunology
GA 175UW
UT WOS:000321260100021
PM 23752612
ER
PT J
AU Mattila, JT
Ojo, OO
Kepka-Lenhart, D
Marino, S
Kim, JH
Eum, SY
Via, LE
Barry, CE
Klein, E
Kirschner, DE
Morris, SM
Lin, PL
Flynn, JL
AF Mattila, Joshua T.
Ojo, Olabisi O.
Kepka-Lenhart, Diane
Marino, Simeone
Kim, Jin Hee
Eum, Seok Yong
Via, Laura E.
Barry, Clifton E., III
Klein, Edwin
Kirschner, Denise E.
Morris, Sidney M., Jr.
Lin, Philana Ling
Flynn, JoAnne L.
TI Microenvironments in Tuberculous Granulomas Are Delineated by Distinct
Populations of Macrophage Subsets and Expression of Nitric Oxide
Synthase and Arginase Isoforms
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID HUMAN HOST-DEFENSE; MYCOBACTERIUM-TUBERCULOSIS; ALTERNATIVE ACTIVATION;
ARGININE METABOLISM; DIFFERENTIAL REGULATION; PULMONARY TUBERCULOSIS;
CYNOMOLGUS MACAQUES; GENE-EXPRESSION; REACTIVE OXYGEN; T-LYMPHOCYTES
AB Macrophages in granulomas are both antimycobacterial effector and host cell for Mycobacterium tuberculosis, yet basic aspects of macrophage diversity and function within the complex structures of granulomas remain poorly understood. To address this, we examined myeloid cell phenotypes and expression of enzymes correlated with host defense in macaque and human granulomas. Macaque granulomas had upregulated inducible and endothelial NO synthase (iNOS and eNOS) and arginase (Arg1 and Arg2) expression and enzyme activity compared with nongranulomatous tissue. Immunohistochemical analysis indicated macrophages adjacent to uninvolved normal tissue were more likely to express CD163, whereas epithelioid macrophages in regions where bacteria reside strongly expressed CD11c, CD68, and HAM56. Calprotectin-positive neutrophils were abundant in regions adjacent to caseum. iNOS, eNOS, Arg1, and Arg2 proteins were identified in macrophages and localized similarly in granulomas across species, with greater eNOS expression and ratio of iNOS/Arg1 expression in epithelioid macrophages as compared with cells in the lymphocyte cuff. iNOS, Arg1, and Arg2 expression in neutrophils was also identified. The combination of phenotypic and functional markers support that macrophages with anti-inflammatory phenotypes localized to outer regions of granulomas, whereas the inner regions were more likely to contain macrophages with proinflammatory, presumably bactericidal, phenotypes. Together, these data support the concept that granulomas have organized microenvironments that balance antimicrobial anti-inflammatory responses to limit pathology in the lungs. The Journal of Immunology, 2013, 191: 773-784.
C1 [Mattila, Joshua T.; Ojo, Olabisi O.; Kepka-Lenhart, Diane; Morris, Sidney M., Jr.; Flynn, JoAnne L.] Univ Pittsburgh, Dept Microbiol & Mol Genet, Pittsburgh, PA 15261 USA.
[Marino, Simeone; Kirschner, Denise E.] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA.
[Kim, Jin Hee] Natl Masan TB Hosp, Chang Won 631710, South Korea.
[Eum, Seok Yong] Int TB Res Inst, Chang Won 631710, South Korea.
[Via, Laura E.; Barry, Clifton E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Klein, Edwin] Univ Pittsburgh, Div Lab Anim Resources, Pittsburgh, PA 15261 USA.
[Lin, Philana Ling] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Dept Pediat, Pittsburgh, PA 15224 USA.
[Flynn, JoAnne L.] Univ Pittsburgh, Sch Med, Ctr Vaccine Res, Pittsburgh, PA 15261 USA.
RP Flynn, JL (reprint author), Univ Pittsburgh, Sch Med, Ctr Vaccine Res, W1144 Biomed Sci Tower,200 Lothrop St, Pittsburgh, PA 15261 USA.
EM joanne@pitt.edu
RI Barry, III, Clifton/H-3839-2012; Morris, Sidney/I-3440-2015;
OI Via, Laura/0000-0001-6074-9521; , Joshua/0000-0002-6384-1291
FU National Institutes of Health (NIH) [HL074845, HL106804, HL092883,
EB012579, GM057384-11]; Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, NIH; Korean Ministry of
Health, Welfare and Family Affairs; NIH [AI060525-05, AI077183, K08
AI063101]; Bill and Melinda Gates Foundation; Otis Foundation; Heiser
Program for Research in Tuberculosis and Leprosy
FX This work was supported by National Institutes of Health (NIH) Grants
HL074845 (to J.L.F.), HL106804 (to J.L.F. and D. E. K.), HL092883 (to
J.L.F. and D. E. K.), EB012579 (to D. E. K. and J.L.F.), GM057384-11 (to
S. M. M.); the Division of Intramural Research, National Institute of
Allergy and Infectious Diseases, NIH and the Korean Ministry of Health,
Welfare and Family Affairs (to C. E. B.); NIH Grant AI060525-05 (to
J.L.F., supporting J.T.M.); NIH Grant AI077183 (to J.T.M.); the Bill and
Melinda Gates Foundation (to J.L.F., P. L. L., and C. E. B.); NIH Grant
K08 AI063101 (to P. L. L.); the Otis Foundation (to P. L. L.); and the
Heiser Program for Research in Tuberculosis and Leprosy (to J.T.M.).
NR 70
TC 92
Z9 94
U1 2
U2 20
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUL 15
PY 2013
VL 191
IS 2
BP 773
EP 784
DI 10.4049/jimmunol.1300113
PG 12
WC Immunology
SC Immunology
GA 175UW
UT WOS:000321260100030
PM 23749634
ER
PT J
AU Richards, JS
Arumugam, TU
Reiling, L
Healer, J
Hodder, AN
Fowkes, FJI
Cross, N
Langer, C
Takeo, S
Uboldi, AD
Thompson, JK
Gilson, PR
Coppel, RL
Siba, PM
King, CL
Torii, M
Chitnis, CE
Narum, DL
Mueller, I
Crabb, BS
Cowman, AF
Tsuboi, T
Beeson, JG
AF Richards, Jack S.
Arumugam, Thangavelu U.
Reiling, Linda
Healer, Julie
Hodder, Anthony N.
Fowkes, Freya J. I.
Cross, Nadia
Langer, Christine
Takeo, Satoru
Uboldi, Alex D.
Thompson, Jennifer K.
Gilson, Paul R.
Coppel, Ross L.
Siba, Peter M.
King, Christopher L.
Torii, Motomi
Chitnis, Chetan E.
Narum, David L.
Mueller, Ivo
Crabb, Brendan S.
Cowman, Alan F.
Tsuboi, Takafumi
Beeson, James G.
TI Identification and Prioritization of Merozoite Antigens as Targets of
Protective Human Immunity to Plasmodium falciparum Malaria for Vaccine
and Biomarker Development
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID APICAL MEMBRANE ANTIGEN-1; RECEPTOR-BINDING DOMAIN; INHIBIT PARASITE
GROWTH; HUMAN ERYTHROCYTES; IN-VITRO; ACQUIRED-IMMUNITY; ARTEMISININ
RESISTANCE; INVASION PATHWAYS; ANTIBODY-RESPONSE; CLINICAL MALARIA
AB The development of effective malaria vaccines and immune biomarkers of malaria is a high priority for malaria control and elimination. Ags expressed by merozoites of Plasmodium falciparum are likely to be important targets of human immunity and are promising vaccine candidates, but very few Ags have been studied. We developed an approach to assess Ab responses to a comprehensive repertoire of merozoite proteins and investigate whether they are targets of protective Abs. We expressed 91 recombinant proteins, located on the merozoite surface or within invasion organelles, and screened them for quality and reactivity to human Abs. Subsequently, Abs to 46 proteins were studied in a longitudinal cohort of 206 Papua New Guinean children to define Ab acquisition and associations with protective immunity. Ab responses were higher among older children and those with active parasitemia. High-level Ab responses to rhoptry and microneme proteins that function in erythrocyte invasion were identified as being most strongly associated with protective immunity compared with other Ags. Additionally, Abs to new or understudied Ags were more strongly associated with protection than were Abs to current vaccine candidates that have progressed to phase 1 or 2 vaccine trials. Combinations of Ab responses were identified that were more strongly associated with protective immunity than responses to their single-Ag components. This study identifies Ags that are likely to be key targets of protective human immunity and facilitates the prioritization of Ags for further evaluation as vaccine candidates and/or for use as biomarkers of immunity in malaria surveillance and control. The Journal of Immunology, 2013, 191: 795-809.
C1 [Richards, Jack S.; Reiling, Linda; Fowkes, Freya J. I.; Cross, Nadia; Langer, Christine; Gilson, Paul R.; Crabb, Brendan S.; Beeson, James G.] Burnet Inst, Dept Immunol, Melbourne, Vic 3001, Australia.
[Richards, Jack S.; Healer, Julie; Hodder, Anthony N.; Uboldi, Alex D.; Thompson, Jennifer K.; Mueller, Ivo; Cowman, Alan F.; Beeson, James G.] Walter & Eliza Hall Inst Med Res, Infect & Immun Div, Parkville, Vic 3052, Australia.
[Richards, Jack S.; Coppel, Ross L.; Beeson, James G.] Monash Univ, Dept Microbiol, Clayton, Vic 3800, Australia.
[Richards, Jack S.; Cowman, Alan F.] Univ Melbourne, Dept Med Biol, Parkville, Vic 3052, Australia.
[Arumugam, Thangavelu U.; Takeo, Satoru; Tsuboi, Takafumi] Ehime Univ, Cell Free Sci & Technol Res Ctr, Matsuyama, Ehime 7908577, Japan.
[Fowkes, Freya J. I.] Univ Melbourne, Melbourne Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Parkville, Vic 3010, Australia.
[Fowkes, Freya J. I.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia.
[Siba, Peter M.; Mueller, Ivo] Papua New Guinea Inst Med Res, Goroka 441, Papua N Guinea.
[King, Christopher L.] Case Western Reserve Univ, Ctr Global Hlth & Dis, Cleveland, OH 44106 USA.
[Torii, Motomi] Ehime Univ, Dept Mol Parasitol, Grad Sch Med, Toon, Ehime 7910925, Japan.
[Chitnis, Chetan E.] Int Ctr Genet Engn & Biotechnol, New Delhi 110067, India.
[Narum, David L.] NIAID, Malaria Vaccine Dev Branch, Bethesda, MD 20892 USA.
RP Beeson, JG (reprint author), Burnet Inst Med Res & Publ Hlth, 85 Commercial Rd,GPO Box 2284, Melbourne, Vic 3004, Australia.
EM beeson@burnet.edu.au
RI Coppel, Ross/A-6626-2008;
OI Coppel, Ross/0000-0002-4476-9124; Richards, Jack/0000-0001-5786-6989;
Fowkes, Freya/0000-0001-5832-9464
FU National Health and Medical Research Council of Australia; Bill and
Melinda Gates Foundation; Australian Research Council; Australia-India
Strategic Research Fund of the Department of Innovation Industry Science
and Research, Australia and Department of Biotechnology, India; Ministry
of Education, Culture, Sports, Science and Technology (KAKENHI)
[23117008]; Japan Society for the Promotion of Science (KAKENHI)
[23406007]; Ministry of Health, Labour, and Welfare, Japan
[H21-Chikyukibo-ippan-005]; Victorian State Government Operational
Infrastructure Support; National Institutes of Health
FX This work was supported by the National Health and Medical Research
Council of Australia (a project grant and program grant, postgraduate
research fellowship to J.S.R., a Training Award to F.J.I.F., and an
Infrastructure for Research Institutes Support Scheme Grant); the Bill
and Melinda Gates Foundation; the Australian Research Council (a Future
Fellowship to J.G.B.); the Australia-India Strategic Research Fund of
the Department of Innovation Industry Science and Research, Australia
and Department of Biotechnology, India; Ministry of Education, Culture,
Sports, Science and Technology Grants-in-Aid for Scientific Research
(KAKENHI) (23117008); Japan Society for the Promotion of Science
Grants-in-Aid for Scientific Research (KAKENHI) (23406007); the Ministry
of Health, Labour, and Welfare, Japan (Grant H21-Chikyukibo-ippan-005);
the Victorian State Government Operational Infrastructure Support; and
the National Institutes of Health (to D.L.N.).
NR 69
TC 71
Z9 72
U1 1
U2 19
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUL 15
PY 2013
VL 191
IS 2
BP 795
EP 809
DI 10.4049/jimmunol.1300778
PG 15
WC Immunology
SC Immunology
GA 175UW
UT WOS:000321260100032
PM 23776179
ER
PT J
AU Tewary, P
de la Rosa, G
Sharma, N
Rodriguez, LG
Tarasov, SG
Howard, OMZ
Shirota, H
Steinhagen, F
Klinman, DM
Yang, D
Oppenheim, JJ
AF Tewary, Poonam
de la Rosa, Gonzalo
Sharma, Neeraj
Rodriguez, Luis G.
Tarasov, Sergey G.
Howard, O. M. Zack
Shirota, Hidekazu
Steinhagen, Folkert
Klinman, Dennis M.
Yang, De
Oppenheim, Joost J.
TI beta-Defensin 2 and 3 Promote the Uptake of Self or CpG DNA, Enhance
IFN-alpha Production by Human Plasmacytoid Dendritic Cells, and Promote
Inflammation
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID ANTIGEN-PRESENTING CELLS; ADAPTIVE IMMUNITY; LINKING INNATE; ACTIVATION;
RECOGNITION; PEPTIDES; ALARMIN; ROLES; ACTS
AB Alarmins are a group of structurally diverse host defense antimicrobial peptides that are important immune activators. In this article, we present a novel role for two potent alarmins, human beta-defensin 2 and 3 (HBD2 and 3), in promoting IFN-alpha production by human plasmacytoid dendritic cells. We demonstrate that HBD2 and 3 activate pDCs by enhancing the intracellular uptake of CpG and self DNA and promote DNA-induced IFN-alpha production in a TLR9-dependent manner. Both CpG and host DNA form aggregates that resemble DNA nets when combined with HBD2 and 3. Isothermal titration calorimetry studies to elucidate the nature of HBD3/CpG complexes demonstrate involvement of enthalpy-driven interactions, in addition to hydrophobic interactions, with the formation of complexes at a molar ratio of 2: 1 defensin/CpG. The i.v. administration of HBD3/CpG complexes induced proinflammatory cytokines like IL-12, IFN-gamma, IL-6, IFN-alpha, and IL-10 in serum, associated with an increased recruitment of APCs in the spleen. Subcutaneous injections of these complexes showed enhanced infiltration of inflammatory cells at the injection site, indicating a potential pathophysiological role for alarmin/DNA complexes in contributing to inflammation. Intraperitoneal immunization of HBD3/CpG complexes with OVA enhanced both cellular and humoral responses to OVA, compared with OVA/HBD3 or OVA/CPG alone, indicative of a much more potent adjuvant effect of the HBD3/CpG complexes. Thus, the ability of defensins to enhance cellular uptake of nucleic acids can lead to improved vaccine formulations by promoting their uptake by various cells, resulting in an enhanced immune response. The Journal of Immunology, 2013, 191: 865-874.
C1 [Tewary, Poonam; de la Rosa, Gonzalo; Howard, O. M. Zack; Yang, De; Oppenheim, Joost J.] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res,Lab Canc Res, Frederick, MD 21702 USA.
[Sharma, Neeraj; Shirota, Hidekazu; Steinhagen, Folkert; Klinman, Dennis M.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res,SAIC Frederick,Frederick Natl Lab Ca, Frederick, MD 21702 USA.
[Rodriguez, Luis G.] Frederick Natl Lab Canc Res, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick, Frederick, MD 21702 USA.
[Tarasov, Sergey G.] NCI, Struct Biophys Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Yang, De] Frederick Natl Lab Canc Res, SAIC Frederick, Basic Sci Program, Frederick, MD 21702 USA.
RP Tewary, P (reprint author), NCI, 1050 Boyles St,560 Room 31-19, Frederick, MD 21702 USA.
EM tewaryp@mail.nih.gov
RI Howard, O M Zack/B-6117-2012
OI Howard, O M Zack/0000-0002-0505-7052
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; National Institutes of Health, National Cancer
Institute, Center for Cancer Research
FX This work was supported by National Cancer Institute, National
Institutes of Health Contract HHSN261200800001E. This work was also
supported by the Intramural Research Program of the National Institutes
of Health, National Cancer Institute, Center for Cancer Research.
NR 27
TC 28
Z9 30
U1 0
U2 13
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUL 15
PY 2013
VL 191
IS 2
BP 865
EP 874
DI 10.4049/jimmunol.1201648
PG 10
WC Immunology
SC Immunology
GA 175UW
UT WOS:000321260100039
PM 23776172
ER
PT J
AU Lin, J
Cheng, NQ
Hogle, JM
Steven, AC
Belnap, DM
AF Lin, Jun
Cheng, Naiqian
Hogle, James M.
Steven, Alasdair C.
Belnap, David M.
TI Conformational Shift of a Major Poliovirus Antigen Confirmed by
Immuno-Cryogenic Electron Microscopy
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID TYPE-1 NEUTRALIZATION EPITOPE; VIRAL CAPSID POLYPEPTIDE-VP1;
CRYOELECTRON MICROSCOPY; CELL ENTRY; EXTERNALIZED POLYPEPTIDE;
3-DIMENSIONAL STRUCTURE; HUMAN RHINOVIRUS-14; SYNTHETIC PEPTIDES;
STRUCTURAL-CHANGES; DENSITY MAPS
AB Small, interfacial conformational changes occur in some Ag-Ab interactions. Using cryogenic electron microscopy (cryo-EM), we have demonstrated such changes in a major antigenic site of a poliovirus capsid protein. During cell entry, native human poliovirus (160S particle) converts to a cell entry intermediate (135S particle) and later to an RNA-released (80S) particle. By mixing particles with Fabs of the neutralizing C3 mAb, we labeled the external loop connecting the B and C beta-strands (BC loop) of the capsid protein VP1 (residues 95-105) in the 160S and 135S states. We then determined three-dimensional structures by cryo-EM and enhanced their interpretability by fitting high-resolution coordinates of C3 Fab and the capsid proteins into the density maps. Binding of C3 to either 160S or 135S particles caused residues of the BC loop, located on the tip of a prominent peak known as the "mesa," to move by an estimated 5 angstrom. C3 Abs are neutralizing and can bind bivalently. The orientation of the bound Fabs in our reconstructions suggests that C3 neutralizes poliovirus by binding two adjacent BC loops on the same mesa and inhibiting conformational changes in the viral capsid. The Journal of Immunology, 2013, 191: 884-891.
C1 [Lin, Jun; Belnap, David M.] Brigham Young Univ, Dept Chem & Biochem, Provo, UT 84602 USA.
[Cheng, Naiqian; Steven, Alasdair C.; Belnap, David M.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA.
[Hogle, James M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Belnap, David M.] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA.
[Belnap, David M.] Univ Utah, Dept Biochem, Salt Lake City, UT 84112 USA.
RP Belnap, DM (reprint author), Univ Utah, Sch Med, Room 5C124, Salt Lake City, UT 84132 USA.
EM David.Belnap@utah.edu
OI Hogle, James/0000-0002-3655-1504
FU National Institute of Allergy and Infectious Diseases [R15AI084085,
R01AI020566]; Brigham Young University; National Institute of Arthritis
and Musculoskeletal and Skin Diseases of the National Institutes of
Health; Health Sciences Center and the Department of Biology at the
University of Utah; Brigham Young University Department of Chemistry and
Biochemistry
FX This work was partially supported by National Institute of Allergy and
Infectious Diseases Grants R15AI084085 (to D. M. B.) and R01AI020566 (to
J.M.H.). This work was also supported by Brigham Young University
institutional funds (to D. M. B.), by the Intramural Research Program of
the National Institute of Arthritis and Musculoskeletal and Skin
Diseases of the National Institutes of Health (to D. M. B., N.C., and A.
C. S.), and by the Health Sciences Center and the Department of Biology
at the University of Utah (D. M. B.). J.L. was partially supported by a
fellowship from the Brigham Young University Department of Chemistry and
Biochemistry.
NR 47
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U1 0
U2 10
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUL 15
PY 2013
VL 191
IS 2
BP 884
EP 891
DI 10.4049/jimmunol.1202014
PG 8
WC Immunology
SC Immunology
GA 175UW
UT WOS:000321260100041
PM 23772035
ER
PT J
AU Dauphinee, SM
Clayton, A
Hussainkhel, A
Yang, C
Park, YJ
Fuller, ME
Blonder, J
Veenstra, TD
Karsan, A
AF Dauphinee, Shauna M.
Clayton, Ashley
Hussainkhel, Angela
Yang, Cindy
Park, Yoo-Jin
Fuller, Megan E.
Blonder, Josip
Veenstra, Timothy D.
Karsan, Aly
TI SASH1 Is a Scaffold Molecule in Endothelial TLR4 Signaling
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NF-KAPPA-B; TUMOR-SUPPRESSOR GENE; BACTERIAL LIPOPOLYSACCHARIDE;
PROTEOMIC ANALYSIS; CELL ACTIVATION; ADAPTER HACS1; KINASE; TRAF6;
TRANSDUCTION; PROTEINS
AB Recognition of microbial products by TLRs is critical for mediating innate immune responses to invading pathogens. In this study, we identify a novel scaffold protein in TLR4 signaling called SAM and SH3 domain containing protein 1 (SASH1). Sash1 is expressed across all microvascular beds and functions as a scaffold molecule to independently bind TRAF6, TAK1, I kappa B kinase alpha, and I kappa B kinase beta. This interaction fosters ubiquitination of TRAF6 and TAK1 and promotes LPS-induced NF-kappa B, JNK, and p38 activation, culminating in increased production of proinflammatory cytokines and increased LPS-induced endothelial migration. Our findings suggest that SASH1 acts to assemble a signaling complex downstream of TLR4 to activate early endothelial responses to receptor activation. The Journal of Immunology, 2013, 191: 892-901.
C1 [Dauphinee, Shauna M.; Clayton, Ashley; Hussainkhel, Angela; Fuller, Megan E.; Karsan, Aly] British Columbia Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada.
[Dauphinee, Shauna M.; Clayton, Ashley; Karsan, Aly] Univ British Columbia, Expt Med Program, Vancouver, BC V6T 2B5, Canada.
[Hussainkhel, Angela; Karsan, Aly] Univ British Columbia, Dept Interdisciplinary Oncol, Vancouver, BC V6T 2B5, Canada.
[Yang, Cindy; Park, Yoo-Jin; Karsan, Aly] British Columbia Canc Agcy, Dept Pathol & Lab Med, Vancouver, BC V5Z 1L3, Canada.
[Fuller, Megan E.; Karsan, Aly] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6T 2B5, Canada.
[Blonder, Josip; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA.
RP Karsan, A (reprint author), British Columbia Canc Agcy, Genome Sci Ctr, 675 West 10th Ave, Vancouver, BC V5Z 1L3, Canada.
EM akarsan@bcgsc.ca
RI Tang, Macy/B-9798-2014; Karsan, Aly/K-2067-2015
FU Canadian Institutes for Health Research [MOP 97744]; Canadian Institutes
for Health Research; Michael Smith Foundation for Health Research;
University of British Columbia
FX This work was supported by Canadian Institutes for Health Research Grant
MOP 97744 (to A. K.). S. M. D. was supported by studentships from the
Canadian Institutes for Health Research and the Michael Smith Foundation
for Health Research. A. H. was supported by a Canadian Institutes for
Health Research studentship and a University of British Columbia
doctoral fellowship. A. K. is a Senior Scholar of the Michael Smith
Foundation for Health Research.
NR 46
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U1 2
U2 13
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUL 15
PY 2013
VL 191
IS 2
BP 892
EP 901
DI 10.4049/jimmunol.1200583
PG 10
WC Immunology
SC Immunology
GA 175UW
UT WOS:000321260100042
PM 23776175
ER
PT J
AU Racicot, K
Cardenas, I
Wunsche, V
Aldo, P
Guller, S
Means, RE
Romero, R
Mor, G
AF Racicot, Karen
Cardenas, Ingrid
Wuensche, Vera
Aldo, Paulomi
Guller, Seth
Means, Robert E.
Romero, Roberto
Mor, Gil
TI Viral Infection of the Pregnant Cervix Predisposes to Ascending
Bacterial Infection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID FEMALE REPRODUCTIVE-TRACT; TOLL-LIKE RECEPTORS; INFLAMMATORY RESPONSE
SYNDROME; PRETERM PREMATURE RUPTURE; EPITHELIAL-CELLS; MURINE
GAMMAHERPESVIRUS-68; INTRAUTERINE INFECTION; HUMAN-PAPILLOMAVIRUS;
UNITED-STATES; MUCUS PLUG
AB Preterm birth is the major cause of neonatal mortality and morbidity, and bacterial infections that ascend from the lower female reproductive tract are the most common route of uterine infection leading to preterm birth. The uterus and growing fetus are protected from ascending infection by the cervix, which controls and limits microbial access by the production of mucus, cytokines, and antimicrobial peptides. If this barrier is compromised, bacteria may enter the uterine cavity, leading to preterm birth. Using a mouse model, we demonstrate, to our knowledge for the first time, that viral infection of the cervix during pregnancy reduces the capacity of the female reproductive tract to prevent bacterial infection of the uterus. This is due to differences in susceptibility of the cervix to infection by virus during pregnancy and the associated changes in TLR and antimicrobial peptide expression and function. We suggest that preterm labor is a polymicrobial disease, which requires a multifactorial approach for its prevention and treatment.
C1 [Racicot, Karen; Wuensche, Vera; Aldo, Paulomi; Guller, Seth; Mor, Gil] Yale Univ, Sch Med, Dept Obstet & Gynecol, New Haven, CT 06520 USA.
[Cardenas, Ingrid] Tufts Univ, Dept Obstet & Gynecol, Boston, MA 02111 USA.
[Means, Robert E.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA.
[Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept HHS, Detroit, MI 48201 USA.
RP Mor, G (reprint author), Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, Reprod Immunol Unit, 333 Cedar St,LSOG 305A, New Haven, CT 06520 USA.
EM gil.mor@yale.edu
FU National Institutes of Health [NICDH P01HD054713, 3N01 HD23342]; Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Department of Health and
Human Services
FX This work was supported in part by National Institutes of Health Grants
NICDH P01HD054713 and 3N01 HD23342 and the Intramural Research Program
of the Eunice Kennedy Shriver National Institute of Child Health and
Human Development, National Institutes of Health, Department of Health
and Human Services.
NR 54
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U1 2
U2 6
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUL 15
PY 2013
VL 191
IS 2
BP 934
EP 941
DI 10.4049/jimmunol.1300661
PG 8
WC Immunology
SC Immunology
GA 175UW
UT WOS:000321260100046
PM 23752614
ER
PT J
AU Olivero, OA
Torres, LR
Gorjifard, S
Momot, D
Marrogi, E
Divi, RL
Liu, YM
Woodward, RA
Sowers, MJ
Poirier, MC
AF Olivero, Ofelia A.
Torres, Lorangelly Rivera
Gorjifard, Sayeh
Momot, Dariya
Marrogi, Eryney
Divi, Rao L.
Liu, Yongmin
Woodward, Ruth A.
Sowers, Marsha J.
Poirier, Miriam C.
TI Perinatal Exposure of Patas Monkeys to Antiretroviral Nucleoside
Reverse-Transcriptase Inhibitors Induces Genotoxicity Persistent for up
to 3 Years of Age
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE zidovudine; lamivudine; abacavir; nevirapine; Erythrocebus patas;
mesenchymal fibroblasts; micronuclei; centrosomal amplification;
aneuploidy
ID MICRONUCLEATED ERYTHROCYTES; MITOCHONDRIAL COMPROMISE; IN-UTERO; AZT;
CELLS; MICE; CARCINOGENICITY; AMPLIFICATION; TRANSMISSION; COMBINATION
AB Background. Erythrocebus patas (patas) monkeys were used to model antiretroviral (ARV) drug in human immunodeficiency virus type 1-infected pregnant women.
Methods. Pregnant patas dams were given human-equivalent doses of ARVs daily during 50% of gestation. Mesenchymal cells, cultured from bone marrow of patas offspring obtained at birth and at 1 and 3 years of age, were examined for genotoxicity, including centrosomal amplification, micronuclei, and micronuclei containing whole chromosomes.
Results. Compared with controls, statistically significant increases (P < .05) in centrosomal amplification, micronuclei, and micronuclei containing whole chromosomes were found in mesenchymal cells from most groups of offspring at the 3 time points.
Conclusions. Transplacental nucleoside reverse-transcriptase inhibitor exposures induced fetal genotoxicity that was persistent for 3 years.
C1 [Olivero, Ofelia A.; Torres, Lorangelly Rivera; Gorjifard, Sayeh; Momot, Dariya; Marrogi, Eryney; Divi, Rao L.; Liu, Yongmin; Poirier, Miriam C.] NCI, NIH, Carcinogen DNA Interact Sect, Lab Canc Biol & Genet,Ctr Canc Res, Bethesda, MD 20892 USA.
[Divi, Rao L.] NCI, NIH, Methods & Technol Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Woodward, Ruth A.; Sowers, Marsha J.] NIH, Anim Ctr, Shared Anim Facil, Dickerson, MD USA.
RP Poirier, MC (reprint author), NCI, NIH, Bldg 37,Rm 4032,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA.
EM poirierm@exchange.nih.gov
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health
FX This work was supported by the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, National Institutes of
Health.
NR 15
TC 15
Z9 15
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUL 15
PY 2013
VL 208
IS 2
BP 244
EP 248
DI 10.1093/infdis/jit146
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 170NF
UT WOS:000320858500012
PM 23559463
ER
PT J
AU Patel, M
Glass, RI
Jiang, BM
Santosham, M
Lopman, B
Parashar, U
AF Patel, Manish
Glass, Roger I.
Jiang, Baoming
Santosham, Mathuram
Lopman, Ben
Parashar, Umesh
TI A Systematic Review of Anti-Rotavirus Serum IgA Antibody Titer as a
Potential Correlate of Rotavirus Vaccine Efficacy
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Review
DE rotavirus; vaccines; diarrhea; efficacy; antibody; immunity; protection
ID 1ST 2 YEARS; PLACEBO-CONTROLLED TRIAL; ORAL POLIOVIRUS VACCINE;
DOUBLE-BLIND; AFRICAN INFANTS; RHESUS ROTAVIRUS; IMMUNOGENICITY; SAFETY;
CHILDREN; RIX4414
AB Background. Identifying an immunological correlate of protection for rotavirus vaccines (Rotarix [RV1] and RotaTeq [RV5]) would substantially facilitate testing of interventions for improving efficacy in developing countries and evaluating additional candidate rotavirus vaccines.
Methods. We accessed PubMed and ClinicalTrials.gov to identify immunogenicity and efficacy trials for RV1 and RV5 to correlate anti-rotavirus serum immunoglobulin A (IgA) antibody titers vs efficacy in regions stratified by all-cause under-5 mortality rates (u5MR). We established a cutoff point for IgA geometric mean concentration or titer (GMC) that predicted lower efficacy and calculated pooled vaccine efficacy among countries with high vs low IgA titers.
Findings. We observed an inverse correlation between u5MR and IgA titers for RV1 (r(2) = 0.72; P < .001 and RV5 (r(2) = 0.66; P < .001) and between efficacy and IgA titers for both vaccines (r(2) = 0.56; P = .005). Postimmunization anti-rotavirus IgA GMC < 90 were associated with decline in vaccine efficacy. Efficacy during first 2 years of life was significantly lower among countries with IgA GMC < 90 (44%; 95% confidence interval [CI], 30-55) compared to countries with GMC > 90 (85%; 95% CI, 82-88).
Interpretation. We observed a significant correlation between IgA titers and rotavirus vaccine efficacy and hypothesize that a critical level of IgA antibody titer is associated with a sufficient level of sustained protection after rotavirus vaccination.
C1 [Patel, Manish; Jiang, Baoming; Lopman, Ben; Parashar, Umesh] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA.
[Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Santosham, Mathuram] Johns Hopkins Univ, Bloomberg Sch Publ Hlth Baltimore, Dept Int Hlth, Ctr Amer Indian Hlth, Baltimore, MD 21218 USA.
RP Patel, M (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd,MS A-34, Atlanta, GA 30333 USA.
EM mpatel@cdc.gov
FU Merck; GSK Pharmaceuticals
FX M. S. served on scientific advisory boards and given lectures sponsored
by Merck and GSK Pharmaceuticals.
NR 50
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U2 10
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUL 15
PY 2013
VL 208
IS 2
BP 284
EP 294
DI 10.1093/infdis/jit166
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 170NF
UT WOS:000320858500017
PM 23596320
ER
PT J
AU Smith, LM
Hensley, LE
Geisbert, TW
Johnson, J
Stossel, A
Honko, A
Yen, JY
Geisbert, J
Paragas, J
Fritz, E
Olinger, G
Young, HA
Rubins, KH
Karp, CL
AF Smith, Lauren M.
Hensley, Lisa E.
Geisbert, Thomas W.
Johnson, Joshua
Stossel, Andrea
Honko, Anna
Yen, Judy Y.
Geisbert, Joan
Paragas, Jason
Fritz, Elizabeth
Olinger, Gene
Young, Howard A.
Rubins, Kathleen H.
Karp, Christopher L.
TI Interferon-beta Therapy Prolongs Survival in Rhesus Macaque Models of
Ebola and Marburg Hemorrhagic Fever
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE Filovirus; IFN-beta; Ebola virus; Marburg virus; type I interferon
ID VIRUS-INFECTED PATIENTS; NECROSIS-FACTOR-ALPHA; NONHUMAN-PRIMATES;
POSTEXPOSURE PROTECTION; IFN-ALPHA; GENE-EXPRESSION; DENDRITIC CELLS;
TNF-ALPHA; IN-VITRO; PATHOGENESIS
AB There is a clear need for novel, effective therapeutic approaches to hemorrhagic fever due to filoviruses. Ebola virus hemorrhagic fever is associated with robust interferon (IFN)-alpha production, with plasma concentrations of IFN-alpha that greatly (60- to 100-fold) exceed those seen in other viral infections, but little IFN-beta production. While all of the type I IFNs signal through the same receptor complex, both quantitative and qualitative differences in biological activity are observed after stimulation of the receptor complex with different type I IFNs. Taken together, this suggested potential for IFN-beta therapy in filovirus infection. Here we show that early postexposure treatment with IFN-beta significantly increased survival time of rhesus macaques infected with a lethal dose of Ebola virus, although it failed to alter mortality. Early treatment with IFN-beta also significantly increased survival time after Marburg virus infection. IFN-beta may have promise as an adjunctive postexposure therapy in filovirus infection.
C1 [Smith, Lauren M.; Rubins, Kathleen H.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
[Hensley, Lisa E.; Geisbert, Thomas W.; Johnson, Joshua; Stossel, Andrea; Honko, Anna; Yen, Judy Y.; Geisbert, Joan; Paragas, Jason; Fritz, Elizabeth; Olinger, Gene] US Army Med Res Inst Infect Dis, Ft Detrick, MD USA.
[Young, Howard A.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21701 USA.
[Karp, Christopher L.] Cincinnati Childrens Hosp Res Fdn, Div Mol Immunol, Cincinnati, OH USA.
[Karp, Christopher L.] Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA.
RP Karp, CL (reprint author), CCHMC, 3333 Burnet Ave, Cincinnati, OH USA.
EM chris.karp@cchmc.org
OI Karp, Christopher/0000-0002-0832-2659
FU JSTO-CBD/DTRA [19595 4.10009_06_RD_B, 19585 4.10037_07_RD_B]; National
Institute of Allergy and Infectious Diseases [AI053539, AI057159];
Cincinnati Children's Hospital Medical Center (Translational Research
Initiative Grant); US Army Medical Research and Material Command
administered by the Oak Ridge Institute for Science and Education, a
Stanford URP Major Grant; National Science Foundation Graduate Research
Fellowship [DGE-1147470]
FX This work was funded by JSTO-CBD/DTRA (Projects 19595 4.10009_06_RD_B
and 19585 4.10037_07_RD_B to L. E. H.), National Institute of Allergy
and Infectious Diseases (grants AI053539 to C. L. K. and AI057159 to L.
E. H.), and Cincinnati Children's Hospital Medical Center (Translational
Research Initiative Grant to C. L. K). L. M. S. was supported by an
appointment to the Student Research Participation Program at the US Army
Medical Research and Material Command administered by the Oak Ridge
Institute for Science and Education, a Stanford URP Major Grant, and
National Science Foundation Graduate Research Fellowship DGE-1147470.
NR 50
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U1 0
U2 23
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUL 15
PY 2013
VL 208
IS 2
BP 310
EP 318
DI 10.1093/infdis/jis921
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 170NF
UT WOS:000320858500019
PM 23255566
ER
PT J
AU Mirigian, LS
Makareeva, E
Koistinen, H
Itkonen, O
Sorsa, T
Stenman, UH
Salo, T
Leikin, S
AF Mirigian, Lynn S.
Makareeva, Elena
Koistinen, Hannu
Itkonen, Outi
Sorsa, Timo
Stenman, Ulf-Hakan
Salo, Tuula
Leikin, Sergey
TI Collagen degradation by tumor-associated trypsins
SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
LA English
DT Article
DE Collagen degradation; Collagenolysis; Trypsin; Tumor-associated trypsin;
Matrix metalloproteinases
ID I COLLAGEN; TRIPLE-HELIX; MATRIX METALLOPROTEINASES; OSTEOGENESIS
IMPERFECTA; MOLECULAR-MECHANISM; CATHEPSIN K; STABILITY; CLEAVAGE;
PROCOLLAGENASES; CONFORMATION
AB In normal soft tissues, collagen is degraded primarily by collagenases from the matrix metalloproteinase family. Yet, collagenase-like activity of tumor-associated isoforms of other enzymes might be involved in cancer invasion as well. In the present study, we systematically examined collagen degradation by non-sulfated isoforms of trypsins, which were proposed to possess such an activity. We found that non-sulfated trypsin-1, -2, and -3 were able to cleave non-helical and unfolded regions of collagen chains but not the intact triple helix, similar to sulfated trypsins produced by the pancreas. Trypsin-2 sulfation did not affect the cleavage rate either. An apparent triple helix cleavage by tumor-associated trypsin-2 reported earlier likely occurred after triple helix unfolding during sample denaturation for gel electrophoresis. Nevertheless, tumor-associated trypsins might be important for releasing collagen from fibers through telopeptide cleavage as well as for degrading unfolded collagen chains, e.g. after initial cleavage and destabilization of triple helices by collagenases. Published by Elsevier Inc.
C1 [Mirigian, Lynn S.; Makareeva, Elena; Leikin, Sergey] NICHHD, NIH, Bethesda, MD 20892 USA.
[Koistinen, Hannu; Itkonen, Outi; Stenman, Ulf-Hakan] Univ Helsinki, Dept Clin Chem, FIN-00014 Helsinki, Finland.
[Koistinen, Hannu; Itkonen, Outi; Stenman, Ulf-Hakan] Univ Helsinki, Cent Hosp, Helsinki, Finland.
[Sorsa, Timo] Univ Helsinki, HUCH, Inst Dent, Dept Oral & Maxillofacial Dis, FIN-00014 Helsinki, Finland.
[Sorsa, Timo; Salo, Tuula] Univ Helsinki, Inst Dent, Helsinki, Finland.
[Salo, Tuula] Univ Oulu, Oulu Ctr Cell Matrix Res, Inst Dent, Dept Diagnost & Oral Med, Oulu, Finland.
[Salo, Tuula] Oulu Univ Hosp, Oulu, Finland.
RP Leikin, S (reprint author), NICHHD, NIH, Bldg 9 Rm 1N111, Bethesda, MD 20892 USA.
EM leikins@mail.nih.gov
RI Makareeva, Elena/F-5183-2011; Leikin, Sergey/A-5518-2008;
OI Leikin, Sergey/0000-0001-7095-0739; Koistinen, Hannu/0000-0003-0926-3109
FU National Institute of Child Health and Human Development, National
Institutes of Health, USA; Helsinki University Central Hospital; Finnish
Cancer Foundation; Academy of Finland; Sigrid Juselius Foundation;
Finska Lakaresallskapet
FX The authors thank Ms. Maarit Leinimaa and Ms. Annikki Lofhjelm for
excellent technical assistance. This work was funded in part by the
Intramural Research Program of the National Institute of Child Health
and Human Development, National Institutes of Health, USA, Helsinki
University Central Hospital, the Finnish Cancer Foundation, the Academy
of Finland, Sigrid Juselius Foundation and Finska Lakaresallskapet.
NR 34
TC 2
Z9 2
U1 2
U2 18
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-9861
J9 ARCH BIOCHEM BIOPHYS
JI Arch. Biochem. Biophys.
PD JUL 15
PY 2013
VL 535
IS 2
BP 111
EP 114
DI 10.1016/j.abb.2013.03.008
PG 4
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 167MS
UT WOS:000320636700002
PM 23541862
ER
PT J
AU Lamart, S
Stovall, M
Simon, SL
Smith, SA
Weathers, RE
Howell, RM
Curtis, RE
Aleman, BMP
Travis, L
Kwon, D
Morton, LM
AF Lamart, Stephanie
Stovall, Marilyn
Simon, Steven L.
Smith, Susan A.
Weathers, Rita E.
Howell, Rebecca M.
Curtis, Rochelle E.
Aleman, Berthe M. P.
Travis, Lois
Kwon, Deukwoo
Morton, Lindsay M.
TI Radiation Dose to the Esophagus From Breast Cancer Radiation Therapy,
1943-1996: An International Population-Based Study of 414 Patients
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID RISK; RADIOTHERAPY; EXPOSURES
AB Purpose: To provide dosimetric data for an epidemiologic study on the risk of second primary esophageal cancer among breast cancer survivors, by reconstructing the radiation dose incidentally delivered to the esophagus of 414 women treated with radiation therapy for breast cancer during 1943-1996 in North America and Europe.
Methods and Materials: We abstracted the radiation therapy treatment parameters from each patient's radiation therapy record. Treatment fields included direct chest wall (37% of patients), medial and lateral tangentials (45%), supraclavicular (SCV, 64%), internal mammary (IM, 44%), SCV and IM together (16%), axillary (52%), and breast/chest wall boosts (7%). The beam types used were Co-60 (45% of fields), orthovoltage (33%), megavoltage photons (11%), and electrons (10%). The population median prescribed dose to the target volume ranged from 21 Gy to 40 Gy. We reconstructed the doses over the length of the esophagus using abstracted patient data, water phantom measurements, and a computational model of the human body.
Results: Fields that treated the SCV and/or IM lymph nodes were used for 85% of the patients and delivered the highest doses within 3 regions of the esophagus: cervical (population median 38 Gy), upper thoracic (32 Gy), and middle thoracic (25 Gy). Other fields (direct chest wall, tangential, and axillary) contributed substantially lower doses (approximately 2 Gy). The cervical to middle thoracic esophagus received the highest dose because of its close proximity to the SCV and IM fields and less overlying tissue in that part of the chest. The location of the SCV field border relative to the midline was one of the most important determinants of the dose to the esophagus.
Conclusions: Breast cancer patients in this study received relatively high incidental radiation therapy doses to the esophagus when the SCV and/or IM lymph nodes were treated, whereas direct chest wall, tangentials, and axillary fields contributed lower doses. (C) 2013 Elsevier Inc.
C1 [Lamart, Stephanie; Simon, Steven L.; Curtis, Rochelle E.; Morton, Lindsay M.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Stovall, Marilyn; Smith, Susan A.; Weathers, Rita E.; Howell, Rebecca M.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA.
[Aleman, Berthe M. P.] Netherlands Canc Inst, Dept Radiotherapy, Amsterdam, Netherlands.
[Travis, Lois] Univ Rochester, Med Ctr, Rubin Ctr Canc Survivorship, Rochester, NY 14642 USA.
[Travis, Lois] Univ Rochester, Med Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA.
[Kwon, Deukwoo] Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL USA.
RP Lamart, S (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS,NCI Shady Grove, 9609 Med Ctr Dr Room 7E506, Bethesda, MD 20892 USA.
EM stephanie.lamart@nih.gov
RI Morton, Lindsay/B-5234-2015
OI Morton, Lindsay/0000-0001-9767-2310
FU National Cancer Institute, National Institutes of Health, US Department
of Health and Human Services
FX This study was funded by the Intramural Research Program of the National
Cancer Institute, National Institutes of Health, US Department of Health
and Human Services.
NR 13
TC 3
Z9 3
U1 0
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JUL 15
PY 2013
VL 86
IS 4
BP 694
EP 701
DI 10.1016/j.ijrobp.2013.03.014
PG 8
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 166WL
UT WOS:000320590200024
PM 23628135
ER
PT J
AU Nemukhin, A
Topol, I
Collins, J
Khrenova, M
AF Nemukhin, Alexander
Topol, Igor
Collins, Jack
Khrenova, Maria
TI Quantum chemistry in studies of fluorescent and photosensing proteins
SO INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY
LA English
DT Article; Proceedings Paper
CT 13th V. A. Fock Meeting on Quantum and Computational Chemistry
CY APR 23-27, 2012
CL Astana, KAZAKHSTAN
DE fluorescent proteins; photoreceptor proteins; structure; optical
spectra; density functional theory; ZINDO; SOS-CIS(D)
ID PHOTORECEPTOR PROTEINS; ABSORPTION; BLUE
AB This Perspective describes some of the recent successes in modeling properties of chromophore containing domains of proteins capable to respond to visible light by using quantum chemistry methods. Applications to two distinctively different classes of such proteins are considered: those of the green fluorescent protein family with the chromophores derived from the hydroxybenzylidene-imidazolinone moiety and those containing the flavin-based chromophore. The major emphasis is on applications of economic computational strategies to estimate geometry configurations and electronic excitation energies. We show that using the molecular cluster approach and the black-box methods ZINDO and SOS-CIS(D) proves to be efficient for characterization of protein spectra. (c) 2013 Wiley Periodicals, Inc.
C1 [Nemukhin, Alexander; Khrenova, Maria] Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119991, Russia.
[Nemukhin, Alexander] Russian Acad Sci, NM Emanuel Inst Biochem Phys, Moscow 119334, Russia.
[Topol, Igor; Collins, Jack] SAIC Frederick Inc, Adv Biomed Comp Ctr, Informat Syst Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Khrenova, Maria] Russian Acad Sci, AN Bach Inst Biochem, Moscow 119071, Russia.
RP Nemukhin, A (reprint author), Moscow MV Lomonosov State Univ, Dept Chem, 1-3 Leninskie Gory, Moscow 119991, Russia.
EM anemukhin@yahoo.com
RI Khrenova, Maria/I-4829-2014; Nemukhin, Alexander/P-9662-2015;
OI Khrenova, Maria/0000-0001-7117-3089
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX Contract grant sponsor: National Cancer Institute, National Institutes
of Health; Contract grant number: HHSN261200800001E.
NR 28
TC 2
Z9 2
U1 1
U2 31
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7608
EI 1097-461X
J9 INT J QUANTUM CHEM
JI Int. J. Quantum Chem.
PD JUL 15
PY 2013
VL 113
IS 14
BP 1828
EP 1832
DI 10.1002/qua.24419
PG 5
WC Chemistry, Physical; Mathematics, Interdisciplinary Applications;
Physics, Atomic, Molecular & Chemical
SC Chemistry; Mathematics; Physics
GA 158TO
UT WOS:000319996300004
ER
PT J
AU Huen, NY
Pang, ALY
Tucker, JA
Lee, TL
Vergati, M
Jochems, C
Intrivici, C
Cereda, V
Chan, WY
Rennert, OM
Madan, RA
Gulley, JL
Schlom, J
Tsang, KY
AF Huen, Ngar-Yee
Pang, Alan Lap-Yin
Tucker, Jo A.
Lee, Tin-Lap
Vergati, Matteo
Jochems, Caroline
Intrivici, Chiara
Cereda, Vittore
Chan, Wai-Yee
Rennert, Owen M.
Madan, Ravi A.
Gulley, James L.
Schlom, Jeffrey
Tsang, Kwong Y.
TI Up-regulation of proliferative and migratory genes in regulatory T cells
from patients with metastatic castration-resistant prostate cancer
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE regulatory T cells; prostate cancer; immune suppression
ID GROWTH-FACTOR-BETA; PERIPHERAL-BLOOD; CUTTING EDGE; C-JUN; NF-AT;
EXPRESSION; CD4(+); TUMOR; CARCINOMA; APOPTOSIS
AB A higher frequency of regulatory T cells (Tregs) has been observed in peripheral blood mononuclear cells (PBMC) of patients with different types of solid tumors and hematological malignancies as compared to healthy donors. In prostate cancer patients, Tregs in PBMC have been shown to have increased suppressive function. Tumor-induced biological changes in Tregs may enable tumor cells to escape immunosurveillance. We performed genome-wide expression analyses comparing the expression levels of more than 38,500 genes in Tregs with similar suppressive activity, isolated from the peripheral blood of healthy donors and patients with metastatic castration-resistant prostate cancer (mCRPC). The differentially expressed genes in mCRPC Tregs are involved in cell cycle processes, cellular growth and proliferation, immune responses, hematological system development and function and the interleukin-2 (IL-2) and transforming growth factor- (TGF-) pathways. Studies revealed that the levels of expression of genes responsible for T-cell proliferation (C-FOS, C-JUN and DUSP1) and cellular migration (RGS1) were greater in Tregs from mCRPC patients as compared to values observed in healthy donors. Increased RGS1 expression in Tregs from mCRPC patients suggests a decrease in these Tregs' migratory ability. In addition, the higher frequency of CD4+CD25highCD127 Tregs in the peripheral blood of mCRPC patients may be the result of an increase in Treg proliferation capacity. Results also suggest that the alterations observed in gene expression profiles of Tregs in mCRPC patients may be part of the mechanism of tumor escape from host immune surveillance.
C1 [Huen, Ngar-Yee; Tucker, Jo A.; Vergati, Matteo; Jochems, Caroline; Intrivici, Chiara; Cereda, Vittore; Gulley, James L.; Schlom, Jeffrey; Tsang, Kwong Y.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Pang, Alan Lap-Yin; Lee, Tin-Lap; Chan, Wai-Yee; Rennert, Owen M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Clin & Dev Genom, NIH, Bethesda, MD USA.
[Chan, Wai-Yee] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China.
[Madan, Ravi A.; Gulley, James L.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Schlom, J (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA.
EM js141c@nih.gov
RI Lee, Tin-Lap/A-7853-2009; Gulley, James/K-4139-2016
OI Lee, Tin-Lap/0000-0002-6654-0988; Gulley, James/0000-0002-6569-2912
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health
FX Grant sponsors: Intramural Research Program of the Center for Cancer
Research, National Cancer Institute, National Institutes of Health
NR 50
TC 11
Z9 11
U1 0
U2 16
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD JUL 15
PY 2013
VL 133
IS 2
BP 373
EP 382
DI 10.1002/ijc.28026
PG 10
WC Oncology
SC Oncology
GA 144PM
UT WOS:000318951900013
PM 23319273
ER
PT J
AU Shakeri, R
Malekzadeh, R
Etemadi, A
Nasrollahzadeh, D
Aghcheli, K
Sotoudeh, M
Islami, F
Pourshams, A
Pawlita, M
Boffetta, P
Dawsey, SM
Abnet, CC
Kamangar, F
AF Shakeri, Ramin
Malekzadeh, Reza
Etemadi, Arash
Nasrollahzadeh, Dariush
Aghcheli, Karim
Sotoudeh, Masoud
Islami, Farhad
Pourshams, Akram
Pawlita, Michael
Boffetta, Paolo
Dawsey, Sanford M.
Abnet, Christian C.
Kamangar, Farin
TI Opium: An emerging risk factor for gastric adenocarcinoma
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE opium; adenocarcinoma; cardia
ID ESOPHAGEAL CANCER; HELICOBACTER-PYLORI; GOLESTAN COHORT; TOBACCO
SMOKING; IRAN; BLADDER; MUTAGENS; ALCOHOL; EPIDEMIOLOGY; METAANALYSIS
AB Opium use has been associated with higher risk of cancers of the esophagus, bladder, larynx, and lung; however, no previous study has examined its association with gastric cancer. There is also little information on the associations between hookah (water pipe) smoking or the chewing of tobacco products and the risk of gastric cancer. In a case-control study in Golestan Province of Iran, we enrolled 309 cases of gastric adenocarcinoma (118 noncardia, 161 cardia and 30 mixed-location adenocarcinomas) and 613 matched controls. Detailed information on long-term use of opium, tobacco products and other covariates were collected using structured and validated lifestyle and food frequency questionnaires. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were obtained using conditional logistic regression models. Opium use was associated with an increased risk of gastric adenocarcinoma, with an adjusted OR (95% CI) of 3.1 (1.95.1), and this increased risk was apparent for both anatomic subsites (cardia and noncardia). There was a dose-response effect, and individuals with the highest cumulative opium use had the strongest association (OR: 4.5; 95% CI: 2.38.5). We did not find a statistically significant association between the use of any of the tobacco products and risk of gastric adenocarcinoma, overall or by anatomic subsite. We showed, for the first time, an association between opium use and gastric adenocarcinoma. Given that opium use is a traditional practice in many parts of the world, these results are of public health significance.
C1 [Shakeri, Ramin; Malekzadeh, Reza; Etemadi, Arash; Nasrollahzadeh, Dariush; Aghcheli, Karim; Sotoudeh, Masoud; Islami, Farhad; Pourshams, Akram; Kamangar, Farin] Univ Tehran Med Sci, Digest Dis Res Ctr, Tehran 1411713135, Iran.
[Shakeri, Ramin; Etemadi, Arash; Dawsey, Sanford M.; Abnet, Christian C.; Kamangar, Farin] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Nasrollahzadeh, Dariush] Karolinska Inst, Stockholm, Sweden.
[Aghcheli, Karim] Gorgan Univ Med Sci, Golestan Res Ctr Gastroenterol & Hepatol, Gorgan, Iran.
[Islami, Farhad; Boffetta, Paolo] Mt Sinai Sch Med, Inst Translat Epidemiol, New York, NY USA.
[Islami, Farhad; Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
[Pawlita, Michael] German Canc Res Ctr, Genome Modificat & Carcinogenesis Div, Infect & Canc Program, Heidelberg, Germany.
[Kamangar, Farin] Morgan State Univ, Dept Publ Hlth Anal, Sch Community Hlth & Policy, Baltimore, MD 21239 USA.
RP Abnet, CC (reprint author), NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA.
EM malek@ams.ac.ir; abnetc@mail.nih.gov
RI Pawlita, Labor/C-9720-2011; Abnet, Christian/C-4111-2015; Etemadi,
Arash/C-1386-2016; Waterboer, Tim/G-1252-2010;
OI Malekzadeh, Reza/0000-0003-1043-3814; Pawlita,
Michael/0000-0002-4720-8306; Abnet, Christian/0000-0002-3008-7843;
Etemadi, Arash/0000-0002-3458-1072; , Ramin/0000-0003-0487-3629
FU Intramural NIH HHS [Z99 CA999999]
NR 45
TC 18
Z9 18
U1 0
U2 20
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD JUL 15
PY 2013
VL 133
IS 2
BP 455
EP 461
DI 10.1002/ijc.28018
PG 7
WC Oncology
SC Oncology
GA 144PM
UT WOS:000318951900021
PM 23319416
ER
PT J
AU Daugherty, SE
Lacey, JV
Pfeiffer, RM
Park, Y
Hoover, RN
Silverman, DT
AF Daugherty, Sarah E.
Lacey, James V., Jr.
Pfeiffer, Ruth M.
Park, Yikyung
Hoover, Robert N.
Silverman, Debra T.
TI Reproductive factors and menopausal hormone therapy and bladder cancer
risk in the NIH-AARP Diet and Health Study
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE reproductive factors; estrogen; progestin; parity; bladder cancer
ID ATOMIC-BOMB SURVIVORS; IOWA WOMENS HEALTH; POSTMENOPAUSAL WOMEN;
REPLACEMENT THERAPY; NATIONAL INSTITUTES; ESTROGEN; COHORT;
REPRODUCIBILITY; SMOKING; AGE
AB The incidence of bladder cancer among women is at least one-third to one-fourth that observed among men in many countries. Even after accounting for known risk factors, the reason for this gender disparity remains unexplained. We conducted a comprehensive evaluation of reproductive factors and exogenous hormone use with a primary focus on menopausal hormone therapy use and risk of bladder cancer in women in the NIH-AARP Diet and Health Study. Reproductive and hormonal factors were ascertained on the baseline questionnaire in 19951996 among 201,492 females who were followed until December 31, 2006. During follow-up, 651 cases of bladder cancer were diagnosed. A subset of women provided detailed information on use of MHT in a second questionnaire in 19961997. In this analysis, 127,361 females were followed through June 30, 2002 and 198 incident bladder cancer cases were identified. Cox proportional hazard models, adjusted for smoking status, cigarettes per day and body mass index using age as the time metric, were used to obtain hazard ratios (HRs). A reduced risk was observed among parous women (HR=0.76; 95% CI 0.620.93) and women who reported late age at menarche (15 years) (HR=0.57; 95% CI 0.390.84). Women who reported ever using estrogen and progestin therapy had a decreased risk (HR=0.53; 95% CI: 0.340.83) compared with women who did not report MHT use. No association was observed for estrogen only users (HR=0.82; 95% CI: 0.581.15). Our results suggest a putative role for sex hormones in the etiology of bladder cancer among women.
C1 [Daugherty, Sarah E.; Pfeiffer, Ruth M.; Park, Yikyung; Hoover, Robert N.; Silverman, Debra T.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Lacey, James V., Jr.] City Hope Natl Med Ctr, City Hope Comprehens Canc Ctr, Canc Control & Populat Sci Program, Duarte, CA USA.
[Lacey, James V., Jr.] City Hope Natl Med Ctr, Div Canc Etiol, Dept Populat Sci, Beckman Res Inst, Duarte, CA USA.
RP Daugherty, SE (reprint author), 6120 Execut Blvd,MSC 7240,EPS 8113, Rockville, MD 20852 USA.
EM daughers@mail.nih.gov
OI Park, Yikyung/0000-0002-6281-489X
FU Intramural Research Program of the NIH, National Cancer Institute
FX NIH-AARP Diet and Health Study research was supported [in part] by the
Intramural Research Program of the NIH, National Cancer Institute.
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.
NR 43
TC 10
Z9 10
U1 0
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD JUL 15
PY 2013
VL 133
IS 2
BP 462
EP 472
DI 10.1002/ijc.28022
PG 11
WC Oncology
SC Oncology
GA 144PM
UT WOS:000318951900022
PM 23319449
ER
PT J
AU Tsilidis, KK
Travis, RC
Appleby, PN
Allen, NE
Lindstrom, S
Albanes, D
Ziegler, RG
McCullough, ML
Siddiq, A
Barricarte, A
Berndt, SI
Bueno-de-Mesquita, HB
Chanock, SJ
Crawford, ED
Diver, WR
Gapstur, SM
Giovannucci, E
Gu, FY
Haiman, CA
Hayes, RB
Hunter, DJ
Johansson, M
Kaaks, R
Kolonel, LN
Kraft, P
Le Marchand, L
Overvad, K
Polidoro, S
Riboli, E
Schumacher, FR
Stevens, VL
Trichopoulos, D
Virtamo, J
Willett, WC
Key, TJ
AF Tsilidis, Konstantinos K.
Travis, Ruth C.
Appleby, Paul N.
Allen, Naomi E.
Lindstroem, Sara
Albanes, Demetrius
Ziegler, Regina G.
McCullough, Marjorie L.
Siddiq, Afshan
Barricarte, Aurelio
Berndt, Sonja I.
Bueno-de-Mesquita, H. Bas
Chanock, Stephen J.
Crawford, E. David
Diver, W. Ryan
Gapstur, Susan M.
Giovannucci, Edward
Gu, Fangyi
Haiman, Christopher A.
Hayes, Richard B.
Hunter, David J.
Johansson, Mattias
Kaaks, Rudolf
Kolonel, Laurence N.
Kraft, Peter
Le Marchand, Loic
Overvad, Kim
Polidoro, Silvia
Riboli, Elio
Schumacher, Fredrick R.
Stevens, Victoria L.
Trichopoulos, Dimitrios
Virtamo, Jarmo
Willett, Walter C.
Key, Timothy J.
TI Insulin-like growth factor pathway genes and blood concentrations,
dietary protein and risk of prostate cancer in the NCI Breast and
Prostate Cancer Cohort Consortium (BPC3)
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE gene*environment interaction; genetic epidemiology; insulin-like growth
factor; diet; prostate cancer
ID FACTOR BINDING-PROTEIN-3 CONCENTRATIONS; CROSS-SECTIONAL ANALYSIS;
FACTOR BINDING-PROTEINS; I IGF-I; MULTIETHNIC COHORT; FACTOR (IGF)-I;
NUTRITIONAL FACTORS; CIRCULATING LEVELS; FACTOR SYSTEM; MEN
AB It has been hypothesized that a high intake of dairy protein may increase prostate cancer risk by increasing the production of insulin-like growth factor 1 (IGF-1). Several single nucleotide polymorphisms (SNPs) have been weakly associated with circulating concentrations of IGF-1 and IGF binding protein 3 (IGFBP-3), but none of these SNPs was associated with risk of prostate cancer. We examined whether an association between 16 SNPs associated with circulating IGF-1 or IGFBP-3 concentrations and prostate cancer exists within subgroups defined by dietary protein intake in 5,253 cases and 4,963 controls of European ancestry within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). The BPC3 includes nested casecontrol studies within large North-American and European cohorts. Per-allele odds ratios for prostate cancer for the SNPs were compared across tertiles of protein intake, which was expressed as the percentage of energy derived from total, animal, dairy or plant protein sources, using conditional logistic regression models. Total, animal, dairy and plant protein intakes were significantly positively associated with blood IGF-1 (p<0.01), but not with IGFBP-3 concentrations (p>0.10) or with risk of prostate cancer (p>0.20). After adjusting for multiple testing, the SNP-prostate cancer associations did not differ by intakes of protein, although two interactions by intake of plant protein were of marginal statistical significance [SSTR5 (somatostatin receptor 5)-rs197056 (uncorrected p for interaction, 0.001); SSTR5-rs197057 (uncorrected p for interaction, 0.002)]. We found no strong evidence that the associations between 16 IGF pathway SNPs and prostate cancer differed by intakes of dietary protein.
C1 [Tsilidis, Konstantinos K.; Travis, Ruth C.; Appleby, Paul N.; Allen, Naomi E.; Key, Timothy J.] Univ Oxford, Canc Epidemiol Unit, Nuffield Dept Clin Med, Oxford OX3 7LF, England.
[Tsilidis, Konstantinos K.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece.
[Lindstroem, Sara; Giovannucci, Edward; Hunter, David J.; Kraft, Peter; Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Lindstroem, Sara; Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Albanes, Demetrius; Ziegler, Regina G.; Berndt, Sonja I.; Chanock, Stephen J.; Gu, Fangyi] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[McCullough, Marjorie L.; Diver, W. Ryan; Gapstur, Susan M.; Stevens, Victoria L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Siddiq, Afshan] Univ London Imperial Coll Sci Technol & Med, Dept Genom Common Dis, Sch Publ Hlth, London, England.
[Siddiq, Afshan; Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England.
[Barricarte, Aurelio] Publ Hlth Inst Navarra, Pamplona, Spain.
[Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Ctr Nutr & Hlth, Bilthoven, Netherlands.
[Bueno-de-Mesquita, H. Bas] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.
[Crawford, E. David] Univ Colorado, Ctr Canc, Dept Urol Oncol, Aurora, CO USA.
[Giovannucci, Edward; Hunter, David J.; Willett, Walter C.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Giovannucci, Edward; Hunter, David J.; Willett, Walter C.] Harvard Univ, Sch Med, Boston, MA USA.
[Giovannucci, Edward; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Haiman, Christopher A.; Schumacher, Fredrick R.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Hayes, Richard B.] NYU, Dept Environm Med, Div Epidemiol, Sch Med, New York, NY 10016 USA.
[Johansson, Mattias] Int Agcy Res Canc, F-69372 Lyon, France.
[Johansson, Mattias] Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.
[Kaaks, Rudolf] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Overvad, Kim] Aarhus Univ, Sch Publ Hlth, Dept Epidemiol, Aarhus, Denmark.
[Polidoro, Silvia] Human Genet Fdn, Turin, Italy.
[Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
RP Tsilidis, KK (reprint author), Univ Oxford, Canc Epidemiol Unit, Richard Doll Bldg,Roosevelt Dr, Oxford OX3 7LF, England.
EM kostas.tsilidis@ceu.ox.ac.uk
RI bagheri, firoozeh/F-1775-2013; Gu, Fangyi/I-5957-2014; Albanes,
Demetrius/B-9749-2015;
OI Hayes, Richard/0000-0002-0918-661X
FU United States National Cancer Institute (NCI) of the National Institutes
of Health (NIH) [U01-CA98233-07, U01-CA98710-06, U01-CA98216-06,
U01-CA98758-07]; NIH/NCI; Hellenic Health Foundation
FX Grant sponsor: United States National Cancer Institute (NCI) of the
National Institutes of Health (NIH); Grant numbers: U01-CA98233-07,
U01-CA98710-06, U01-CA98216-06, U01-CA98758-07; Grant sponsors: NIH/NCI
to the Division of Cancer Epidemiology and Genetics (Intramural Research
Program); Hellenic Health Foundation
NR 47
TC 11
Z9 11
U1 1
U2 30
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD JUL 15
PY 2013
VL 133
IS 2
BP 495
EP 504
DI 10.1002/ijc.28042
PG 10
WC Oncology
SC Oncology
GA 144PM
UT WOS:000318951900025
PM 23341348
ER
PT J
AU Ito, S
Satoh, J
Matsubara, T
Shah, YM
Ahn, SH
Anderson, CR
Shan, WW
Peters, JM
Gonzalez, FJ
AF Ito, Shinji
Satoh, Junko
Matsubara, Tsutomu
Shah, Yatrik M.
Ahn, Sung-hoon
Anderson, Cherie R.
Shan, Weiwei
Peters, Jeffrey M.
Gonzalez, Frank J.
TI Cholestasis induces reversible accumulation of periplakin in mouse liver
SO BMC GASTROENTEROLOGY
LA English
DT Article
DE Periplakin; Cholestasis; Bile acids; Farnesoid X receptor; Urinary
stasis
ID FARNESOID-X-RECEPTOR; PROTEIN-COUPLED RECEPTORS; INTRAHEPATIC
CHOLESTASIS; CORNIFIED ENVELOPE; PLAKIN FAMILY; BILE-ACID; BINDING;
EXPRESSION; MICE; ACTIVATION
AB Background: Periplakin (PPL) is a rod-shaped cytolinker protein thought to connect cellular adhesion junctional complexes to cytoskeletal filaments. PPL serves as a structural component of the cornified envelope in the skin and interacts with various types of proteins in cultured cells; its level decreases dramatically during tumorigenic progression in human epithelial tissues. Despite these intriguing observations, the physiological roles of PPL, especially in non-cutaneous tissues, are still largely unknown. Because we observed a marked fluctuation of PPL expression in mouse liver in association with the bile acid receptor farnesoid X receptor (FXR) and cholestasis, we sought to characterize the role of PPL in the liver and determine its contributions to the etiology and pathogenesis of cholestasis.
Methods: Time-and context-dependent expression of PPL in various mouse models of hepatic and renal disorders were examined by immunohistochemistry, western blotting, and quantitative real-time polymerase chain reactions.
Results: The hepatic expression of PPL was significantly decreased in Fxr(-/-) mice. In contrast, the expression was dramatically increased during cholestasis, with massive PPL accumulation observed at the boundaries of hepatocytes in wild-type mice. Interestingly, the hepatic accumulation of PPL resulting from cholestasis was reversible. In addition, similar accumulation of PPL at cellular boundaries was found in epithelial cells around renal tubules upon ureteral obstruction.
Conclusions: PPL may be involved in the temporal accommodation to fluid stasis in different tissues. Further examination of the roles for PPL may lead to the discovery of a novel mechanism for cellular protection by cytolinkers that is applicable to many tissues and in many contexts.
C1 [Ito, Shinji; Satoh, Junko] Kyoto Univ, Grad Sch Med, Biofrontier Platform, Sakyo Ku, Kyoto 6068501, Japan.
[Matsubara, Tsutomu] Osaka City Univ, Grad Sch Med, Dept Anat & Regenerat Biol, Abeno Ku, Osaka 5458585, Japan.
[Shah, Yatrik M.] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.
[Ahn, Sung-hoon] Korea Res Inst Chem Technol, Drug Discovery Platform Technol Team, Taejon 305343, South Korea.
[Anderson, Cherie R.; Peters, Jeffrey M.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Anderson, Cherie R.; Peters, Jeffrey M.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
[Shan, Weiwei] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Ito, S (reprint author), Kyoto Univ, Grad Sch Med, Biofrontier Platform, Sakyo Ku, Yoshida Konoe Cho, Kyoto 6068501, Japan.
EM ito.shinji.3v@kyoto-u.ac.jp
FU Japan Society for Promotion of Science; Kyoto University
FX We are grateful to John Buckley, Linda Byrd, and Tsutomu Obata for
technical assistance and to Dr. Insook Kim for useful discussions. We
also thank Drs. Jouni Uitto, John F. Klement, Akemi Ishida-Yamamoto,
Fiona M. Watt, and Paul Newman for their assistance in regeneration of
Ppl-/- mice. This work was supported in part by the Japan
Society for Promotion of Science (Grant-in-Aid for Young Scientists to
SI) and the Kyoto University Starting-Up Research Grant for Young
Scientists (to JS).
NR 42
TC 2
Z9 2
U1 2
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-230X
J9 BMC GASTROENTEROL
JI BMC Gastroenterol.
PD JUL 13
PY 2013
VL 13
AR 116
DI 10.1186/1471-230X-13-116
PG 17
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 185KH
UT WOS:000321966000001
PM 23849208
ER
PT J
AU Viboud, C
Simonsen, L
AF Viboud, Cecile
Simonsen, Lone
TI Timely estimates of influenza A H7N9 infection severity
SO LANCET
LA English
DT Editorial Material
ID H1N1 VIRUS; A/H1N1; CHINA
C1 [Viboud, Cecile; Simonsen, Lone] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Simonsen, Lone] George Washington Univ, Dept Global Hlth, Sch Publ Hlth & Hlth Serv, Washington, DC USA.
RP Viboud, C (reprint author), NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM viboudc@mail.nih.gov
OI Simonsen, Lone/0000-0003-1535-8526
NR 19
TC 2
Z9 3
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD JUL 13
PY 2013
VL 382
IS 9887
BP 106
EP 108
DI 10.1016/S0140-6736(13)61447-6
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 187JY
UT WOS:000322115300006
PM 23803486
ER
PT J
AU Saito, K
Negishi, M
Squires, EJ
AF Saito, Kosuke
Negishi, Masahiko
Squires, E. James
TI Sexual dimorphisms in zonal gene expression in mouse liver
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Hepatic zonation; Sexual dimorphism; Laser capture microdissection (LCM)
ID GROWTH-HORMONE; RAT-LIVER; GENDER DIFFERENCES; SIGNAL TRANSDUCER;
RECEPTOR-ALPHA; METABOLISM; ZONATION; HETEROGENEITY; HEPATOCYTES;
HEPATECTOMY
AB Many of the metabolic functions of the liver are localized either in the pericentral region (zone 3) or in the periportal region (zone 1). However, a systematic analysis of the heterogeneity and sexual dimorphism of gene expression in the liver is lacking. Our objective was to obtain sections of intact tissue from zone 1 and zone 3 from both male and female mouse liver, and to measure the patterns of gene expression in these sections. Zone 1 and zone 3 areas were isolated by laser capture microdissection of liver sections, total RNA was isolated and microarray analysis was conducted using Agilent Whole Mouse Genome oligo arrays. To investigate functional characteristics as well as upstream regulators of specific gene lists, we used Ingenuity Pathway Analysis. We identified more than 925 genes in zone 1 and more than 450 genes in zone 3 of both male and female mice. Sexual dimorphism in metabolic functions was present in zone 1 but not zone 3. In zone 1, canonical pathways related to gluconeogenesis were male predominant, while canonical pathways related to hepatic progenitor cells were female predominant. In addition, we also analyzed the upstream regulators of zone-specific genes. SREBF1 was male-specific in zone 1, while TRIM24 was female-specific in zone 3. These results demonstrate the heterogeneity and sexually dimorphic differences in gene expression in the liver. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Saito, Kosuke; Negishi, Masahiko; Squires, E. James] NIEHS, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA.
[Squires, E. James] Univ Guelph, Dept Anim & Poultry Sci, Guelph, ON N1G 2W1, Canada.
RP Squires, EJ (reprint author), Univ Guelph, Dept Anim & Poultry Sci, Guelph, ON N1G 2W1, Canada.
EM jsquires@uoguelph.ca
FU Intramural Research Program of National Institute of Environmental
Health Sciences [Z01ES1005-01]
FX The authors thank Rick Moore (NIEHS) for preparing liver sections; Pat
Stockton, Julie Foley and Dr. Yuichi Yamazaki (NIEHS) for technical
support of laser capture microdissections and Dr. Kevin Gerrish (NIEHS)
for performing microarray and data analysis. This research was supported
by the Intramural Research Program of National Institute of
Environmental Health Sciences, Z01ES1005-01.
NR 34
TC 9
Z9 9
U1 0
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD JUL 12
PY 2013
VL 436
IS 4
BP 730
EP 735
DI 10.1016/j.bbrc.2013.06.025
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 191LV
UT WOS:000322415400028
PM 23791742
ER
PT J
AU Grove, ML
Yu, B
Cochran, BJ
Haritunians, T
Bis, JC
Taylor, KD
Hansen, M
Borecki, IB
Cupples, LA
Fornage, M
Gudnason, V
Harris, TB
Kathiresan, S
Kraaij, R
Launer, LJ
Levy, D
Liu, YM
Mosley, T
Peloso, GM
Psaty, BM
Rich, SS
Rivadeneira, F
Siscovick, DS
Smith, AV
Uitterlinden, A
van Duijn, CM
Wilson, JG
O'Donnell, CJ
Rotter, JI
Boerwinkle, E
AF Grove, Megan L.
Yu, Bing
Cochran, Barbara J.
Haritunians, Talin
Bis, Joshua C.
Taylor, Kent D.
Hansen, Mark
Borecki, Ingrid B.
Cupples, L. Adrienne
Fornage, Myriam
Gudnason, Vilmundur
Harris, Tamara B.
Kathiresan, Sekar
Kraaij, Robert
Launer, Lenore J.
Levy, Daniel
Liu, Yongmei
Mosley, Thomas
Peloso, Gina M.
Psaty, Bruce M.
Rich, Stephen S.
Rivadeneira, Fernando
Siscovick, David S.
Smith, Albert V.
Uitterlinden, Andre
van Duijn, Cornelia M.
Wilson, James G.
O'Donnell, Christopher J.
Rotter, Jerome I.
Boerwinkle, Eric
TI Best Practices and Joint Calling of the HumanExome BeadChip: The CHARGE
Consortium
SO PLOS ONE
LA English
DT Article
ID STUDY OBJECTIVES; DESIGN; ASSOCIATION; POPULATION; MUTATION; HEART
AB Genotyping arrays are a cost effective approach when typing previously-identified genetic polymorphisms in large numbers of samples. One limitation of genotyping arrays with rare variants (e.g., minor allele frequency [MAF] < 0.01) is the difficulty that automated clustering algorithms have to accurately detect and assign genotype calls. Combining intensity data from large numbers of samples may increase the ability to accurately call the genotypes of rare variants. Approximately 62,000 ethnically diverse samples from eleven Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium cohorts were genotyped with the Illumina HumanExome BeadChip across seven genotyping centers. The raw data files for the samples were assembled into a single project for joint calling. To assess the quality of the joint calling, concordance of genotypes in a subset of individuals having both exome chip and exome sequence data was analyzed. After exclusion of low performing SNPs on the exome chip and non-overlap of SNPs derived from sequence data, genotypes of 185,119 variants (11,356 were monomorphic) were compared in 530 individuals that had whole exome sequence data. A total of 98,113,070 pairs of genotypes were tested and 99.77% were concordant, 0.14% had missing data, and 0.09% were discordant. We report that joint calling allows the ability to accurately genotype rare variation using array technology when large sample sizes are available and best practices are followed. The cluster file from this experiment is available at www.chargeconsortium.com/main/exomechip.
C1 [Grove, Megan L.; Yu, Bing; Cochran, Barbara J.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Sch Publ Hlth, Houston, TX 77030 USA.
[Haritunians, Talin; Taylor, Kent D.; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Bis, Joshua C.; Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Hansen, Mark] Illumina Inc, San Diego, CA USA.
[Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, Div Stat Gen, St Louis, MO USA.
[Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Cupples, L. Adrienne; Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Inst Mol Med, Houston, TX 77030 USA.
[Gudnason, Vilmundur; Smith, Albert V.] Iceland Heart Assoc, Res Inst, Kopavogur, Iceland.
[Gudnason, Vilmundur; Smith, Albert V.] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Populat Sci, Bethesda, MD 20892 USA.
[Peloso, Gina M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Kathiresan, Sekar] Harvard Univ, Sch Med, Boston, MA USA.
[Kathiresan, Sekar] Broad Inst Harvard, Cambridge, MA USA.
[Kathiresan, Sekar] MIT, Cambridge, MA 02139 USA.
[Kraaij, Robert; Rivadeneira, Fernando] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.
[Liu, Yongmei] Wake Forest Univ, Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA.
[Mosley, Thomas] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Res Inst, Seattle, WA USA.
[Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA USA.
[Rivadeneira, Fernando; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, ErasmusAGE, Rotterdam, Netherlands.
[Rivadeneira, Fernando; Uitterlinden, Andre; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Rivadeneira, Fernando; Uitterlinden, Andre; van Duijn, Cornelia M.] Netherlands Genom Initiat, Netherlands Consortium Hlth Aging, Leiden, Netherlands.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
RP Grove, ML (reprint author), Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Sch Publ Hlth, Houston, TX 77030 USA.
EM Megan.L.Grove@uth.tmc.edu
RI Gudnason, Vilmundur/K-6885-2015; Rivadeneira, Fernando/O-5385-2015;
Smith, Albert/K-5150-2015;
OI Gudnason, Vilmundur/0000-0001-5696-0084; Rivadeneira,
Fernando/0000-0001-9435-9441; Smith, Albert/0000-0003-1942-5845;
Cupples, L. Adrienne/0000-0003-0273-7965
FU Building on GWAS for NHLBI-diseases; U.S. CHARGE consortium through the
National Institutes of Health (NIH) American Recovery and Reinvestment
Act (ARRA) [5RC2HL102419]; NIH [N01-AG-12100]; NIA Intramural Research
Program; Icelandic Heart Association; Icelandic Parliament; National
Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN2682011000010C, HHSN2682011000011C,
HHSN2682011000012C]; National Heart, Lung, and Blood Institute [HL41993,
HL091244, N01-HC-95095, N01-HC-48047, N01-HC-48048, N01-HC-48049,
N01-HC-48050, N01-HC-45134, N01-HC-05187, N01-HC-45205, N01-HC-45204,
U01 HL56563, U01 HL56564, U01 HL56565]; University of Washington
Clinical Nutrition Research Unit [DK-35816]; Medic One Foundation,
Seattle, WA; NHLBI [N01-HC-85239, N01-HC-85079, N01-HC-85080,
N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085];
NIA [AG-023629, AG-15928, AG-20098, AG-027058, N01AG62101, N01AG62103,
N01AG62106, 1R01AG032098-01A1]; National Center of Advancing
Translational Technologies CTSI [UL1TR000124]; National Institute of
Diabetes and Digestive and Kidney Diseases [DK063491]; Cedars-Sinai
Board of Governors' Chair in Medical Genetics (JIR); Erasmus Medical
Center and Erasmus University, Rotterdam; Netherlands Organization for
the Health Research and Development (ZonMw); Research Institute for
Diseases in the Elderly (RIDE); Ministry of Education, Culture and
Science; Ministry for Health, Welfare and Sports; European Commission
(DG XII); Municipality of Rotterdam; Illumina, Inc.; Intramural Research
Program of the NIH, National Institute on Aging; National Center on
Minority Health and Health Disparities; [U01-HG-004729];
[R01-HL-084099]; [N01-HC-25195]; [N01-HC-95159]; [N01-HC-95160];
[N01-HC-95161]; [N01-HC-95162]; [N01-HC-95163]; [N01-HC-95164];
[N01-HC-95165]
FX Support for the centralized work was provided by Building on GWAS for
NHLBI-diseases: the U.S. CHARGE consortium through the National
Institutes of Health (NIH) American Recovery and Reinvestment Act of
2009 (ARRA) (5RC2HL102419) (PI: E. Boerwinkle). Funding support of the
individual cohorts is detailed below. The Age, Gene/Environment,
Susceptibility-Reykjavik (AGES) study is funded by NIH contract
N01-AG-12100, the NIA Intramural Research Program, the Icelandic Heart
Association, and the Icelandic Parliament. The Atherosclerosis Risk in
Communities (ARIC) Study is carried out as a collaborative study
supported by National Heart, Lung, and Blood Institute (NHLBI) contracts
(HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN2682011000010C,
HHSN2682011000011C, and HHSN2682011000012C). The authors thank the staff
and participants of the ARIC study for their important contributions.
The research reported in this manuscript on behalf of the Cardiac Arrest
Blood Study (CABS) was supported by grants from the National Heart,
Lung, and Blood Institute (HL41993 and HL091244); the University of
Washington Clinical Nutrition Research Unit (DK-35816); and the Medic
One Foundation, Seattle, WA. The authors gratefully acknowledge the
Coronary Artery Risk Development in Young Adults (CARDIA) study
participants and staff for their valuable contributions. The CARDIA
study is funded by contracts N01-HC-95095, N01-HC-48047, N01-HC-48048,
N01-HC-48049, N01-HC-48050, N01-HC-45134, N01-HC-05187, N01-HC-45205,
and N01-HC-45204 from the National Heart, Lung, and Blood Institute to
the CARDIA investigators. Genotyping of the CARDIA participants was
supported by grants U01-HG-004729 and R01-HL-084099. This manuscript has
been reviewed by CARDIA for scientific content and consistency of data
interpretation with previous CARDIA publications. 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, HHSN268201200036C and NHLBI grants HL080295, HL087652,
HL105756 with additional contribution from NINDS. Additional support was
provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the
NIA. See also http://www.chs-nhlbi.org/pi. DNA handling and genotyping
was supported in part by National Center of Advancing Translational
Technologies CTSI grant UL1TR000124, the National Institute of Diabetes
and Digestive and Kidney Diseases grant DK063491 to the Southern
California Diabetes Endocrinology Research Center, and Cedars-Sinai
Board of Governors' Chair in Medical Genetics (JIR). The Rotterdam Study
is supported by Erasmus Medical Center and Erasmus University,
Rotterdam, Netherlands Organization for the Health Research and
Development (ZonMw), the Research Institute for Diseases in the Elderly
(RIDE), the Ministry of Education, Culture and Science, the Ministry for
Health, Welfare and Sports, the European Commission (DG XII), and the
Municipality of Rotterdam. The authors are grateful to the study
participants, the staff from the Rotterdam Study and the participating
general practitioners and pharmacists. The NHLBI's Framingham Heart
Study is a joint project of the National Institutes of Health and Boston
University School of Medicine and was supported by contract N01-HC-25195
and its contract with Illumina, Inc. for genotyping services.; The
Family Heart Study (FamHS) was supported by grants from the National
Heart, Lung, & Blood Institute (U01 HL56563, U01 HL56564, U01 HL56565,
U01 HL56566, U01 HL56567, U01 HL56568, U01 HL56569, and K01-HL70444).
The Health, Aging, and Body Composition (HABC) Study is supported by NIA
contracts N01AG62101, N01AG62103, and N01AG62106. The genome-wide
association study was funded by NIA grant 1R01AG032098-01A1 to Wake
Forest University Health Sciences. This research was supported in part
by the Intramural Research Program of the NIH, National Institute on
Aging. The Jackson Heart Study (JHS) is supported by the National Heart,
Lung, and Blood Institute (N01 HC-95170, N01 HC-95171 and N01 HC-95172)
and the National Center on Minority Health and Health Disparities. The
authors thank the staff, interns and participants in JHS for their
long-term commitment and important contributions to the study. MESA is
supported by the National Heart, Lung, and Blood Institute (NHLBI) in
collaboration with MESA investigators. Support for MESA is provided by
contracts N01-HC-95159 through N01-HC-95169 and UL1-RR-024156. Funding
for MESA Family is provided by grants R01- HL-071051, R01-HL-071205,
R01-HL-071250, R01-HL-071251, R01-HL-071252, R01-HL-071258,
R01-HL-071259, UL1-RR-025005. The authors thank the other investigators,
the staff, and the 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. Gina Peloso was
supported by Award Number T32HL007208 from the National Heart, Lung, And
Blood Institute. The content is solely the responsibility of the authors
and does not necessarily represent the official views of the National
Heart, Lung, and Blood Institute or the National Institutes of Health.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 27
TC 74
Z9 74
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 12
PY 2013
VL 8
IS 7
AR e68095
DI 10.1371/journal.pone.0068095
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 182CS
UT WOS:000321718700009
PM 23874508
ER
PT J
AU Vaz, JD
Kac, G
Emmett, P
Davis, JM
Golding, J
Hibbeln, JR
AF Vaz, Juliana dos Santos
Kac, Gilberto
Emmett, Pauline
Davis, John M.
Golding, Jean
Hibbeln, Joseph R.
TI Dietary Patterns, n-3 Fatty Acids Intake from Seafood and High Levels of
Anxiety Symptoms during Pregnancy: Findings from the Avon Longitudinal
Study of Parents and Children
SO PLOS ONE
LA English
DT Article
ID PSYCHOSOCIAL STRESS; COGNITIVE-DEVELOPMENT; PERINATAL OUTCOMES;
LIFE-STYLE; DEPRESSION; VEGETARIAN; ASSOCIATION; HEALTH; COHORT; WOMEN
AB Background: Little is known about relationships between dietary patterns, n-3 polyunsaturated fatty acids (PUFA) intake and excessive anxiety during pregnancy.
Objective: To examine whether dietary patterns and n-3 PUFA intake from seafood are associated with high levels of anxiety during pregnancy.
Design: Pregnant women enrolled from 1991-1992 in ALSPAC (n 9,530). Dietary patterns were established from a food frequency questionnaire using principal component analysis. Total intake of n-3 PUFA (grams/week) from seafood was also examined. Symptoms of anxiety were measured at 32 weeks of gestation with the Crown-Crisp Experiential Index; scores >= 9 corresponding to the 85th percentile was defined as high anxiety symptoms. Multivariate logistic regression models were used to estimate the OR and 95% CI, adjusted by socioeconomic and lifestyle variables.
Results: Multivariate results showed that women in the highest tertile of the health-conscious (OR 0.77; 0.65-0.93) and the traditional (OR 0.84; 0.73-0.97) pattern scores were less likely to report high levels of anxiety symptoms. Women in the highest tertile of the vegetarian pattern score (OR 1.25; 1.08-1.44) were more likely to have high levels of anxiety, as well as those with no n-3 PUFA intake from seafood (OR 1.53; 1.25-1.87) when compared with those with intake of >1.5 grams/week.
Conclusions: The present study provides evidence of a relationship between dietary patterns, fish intake or n-3 PUFA intake from seafood and symptoms of anxiety in pregnancy, and suggests that dietary interventions could be used to reduce high anxiety symptoms during pregnancy.
C1 [Vaz, Juliana dos Santos] Univ Fed Pelotas, Fac Nutr, Pelotas, RS, Brazil.
[Vaz, Juliana dos Santos; Kac, Gilberto] Univ Fed Rio de Janeiro, Nutr Epidemiol Observ, Rio De Janeiro, Brazil.
[Emmett, Pauline; Golding, Jean] Univ Bristol, Sch Social & Community Med, Ctr Child & Adolescent Hlth, Bristol, Avon, England.
[Davis, John M.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA.
[Hibbeln, Joseph R.] NIAAA, NIH, Bethesda, MD 90034 USA.
RP Vaz, JD (reprint author), Univ Fed Pelotas, Fac Nutr, Pelotas, RS, Brazil.
EM juliana.vaz@gmail.com
RI Kac, Gilberto/H-6862-2012; Vaz, Juliana/A-5645-2012;
OI Kac, Gilberto/0000-0001-8603-9077; Vaz, Juliana/0000-0002-2880-767X;
Emmett, Pauline/0000-0003-1076-4779; Golding, Jean/0000-0003-2826-3307
FU Division of Intramural Basic and Clinical Research, National Institute
on Alcohol Abuse and Alcoholism, National Institutes of Health,
Bethesda, Maryland, United States of America; Coordination for the
Training and Improvement of Higher Education Personnel
FX The United Kingdom Medical Research Council, the Wellcome Trust, and the
University of Bristol currently provide core support for ALSPAC; at the
time of data collection in pregnancy support was obtained from a variety
of sources including the UK Department of the Environment and the
Ministry of Agriculture, Fisheries, and Food; and supported in part by
the Division of Intramural Basic and Clinical Research, National
Institute on Alcohol Abuse and Alcoholism, National Institutes of
Health, Bethesda, Maryland, United States of America, and by a personal
gift of John M. Davis. Vaz is a recipient of a scholarship from the
Coordination for the Training and Improvement of Higher Education
Personnel. Kac is a research fellow from the National Counsel of
Technological and Scientific Development. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 51
TC 7
Z9 7
U1 1
U2 21
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 12
PY 2013
VL 8
IS 7
AR e67671
DI 10.1371/journal.pone.0067671
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 182CS
UT WOS:000321718700003
ER
PT J
AU Rutter, L
Nadar, SR
Holroyd, T
Carver, FW
Apud, J
Weinberger, DR
Coppola, R
AF Rutter, Lindsay
Nadar, Sreenivasan R.
Holroyd, Tom
Carver, Frederick W.
Apud, Jose
Weinberger, Daniel R.
Coppola, Richard
TI Graph theoretical analysis of resting magnetoencephalographic functional
connectivity networks
SO FRONTIERS IN COMPUTATIONAL NEUROSCIENCE
LA English
DT Article
DE schizophrenia; small world; magnitude squared coherence; clustering
coefficient; path length; exponentially truncated power-law; synthetic
aperture magnetometry; default network
ID SMALL-WORLD NETWORKS; TASK-INDUCED DEACTIVATION; BRAIN NETWORKS;
CORTICAL NETWORKS; COMPLEX NETWORKS; DEFAULT NETWORK; STATE NETWORKS;
COMMUNITY STRUCTURE; CEREBRAL-CORTEX; LOW-FREQUENCY
AB Complex networks have been observed to comprise small-world properties, believed to represent an optimal organization of local specialization and global integration of information processing at reduced wiring cost. Here, we applied magnitude squared coherence to resting magnetoencephalographic time series in reconstructed source space, acquired from controls and patients with schizophrenia, and generated frequency-dependent adjacency matrices modeling functional connectivity between virtual channels. After configuring undirected binary and weighted graphs, we found that all human networks demonstrated highly localized clustering and short characteristic path lengths. The most conservatively thresholded networks showed efficient wiring, with topographical distance between connected vertices amounting to one-third as observed in surrogate randomized topologies. Nodal degrees of the human networks conformed to a heavy-tailed exponentially truncated power-law, compatible with the existence of hubs, which included theta and alpha bilateral cerebellar tonsil, beta and gamma bilateral posterior cingulate, and bilateral thalamus across all frequencies. We conclude that all networks showed small-worldness, minimal physical connection distance, and skewed degree distributions characteristic of physically-embedded networks, and that these calculations derived from graph theoretical mathematics did not quantifiably distinguish between subject populations, independent of bandwidth. However, post-hoc measurements of edge computations at the scale of the individual vertex revealed trends of reduced gamma connectivity across the posterior medial parietal cortex in patients, an observation consistent with our prior resting activation study that found significant reduction of synthetic aperture magnetometry gamma power across similar regions. The basis of these small differences remains unclear.
C1 [Rutter, Lindsay; Nadar, Sreenivasan R.; Holroyd, Tom; Carver, Frederick W.; Coppola, Richard] NIMH, MEG Core Facil, Bethesda, MD 20892 USA.
[Apud, Jose; Coppola, Richard] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA.
[Weinberger, Daniel R.] Lieber Inst Brain Dev, Baltimore, MD USA.
RP Coppola, R (reprint author), NIMH, Bldg 10 Room 3C119,10Ctr Dr, Bethesda, MD 20892 USA.
EM coppolar@mail.nih.gov
FU Intramural Research Program of the NIMH [99-M-0172]
FX This work used the super-computing capabilities of the Biowulf Linux
parallel processing cluster at the National Institutes of Health,
Bethesda, MD(http://biowulf.nih.gov). This study was supported by the
Intramural Research Program of the NIMH (protocol 99-M-0172). The
authors would like to thank participants and their families for
volunteering their time, the CBDB Sibling Study members for managing the
recruitment procedures needed for this project, Judy Mitchell-Francis
and Steven Kornweiss for assistance with data acquisition, as well as
Yong Liu from the LIAMA Center for Computational Medicine, National
Laboratory of Pattern Recognition, Institute of Automation, Chinese
Academy of Sciences for sharing best-fitting degree distribution
software.
NR 136
TC 8
Z9 8
U1 2
U2 23
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5188
J9 FRONT COMPUT NEUROSC
JI Front. Comput. Neurosci.
PD JUL 12
PY 2013
VL 7
AR UNSP 93
DI 10.3389/fncom.2013.00093
PG 21
WC Mathematical & Computational Biology; Neurosciences
SC Mathematical & Computational Biology; Neurosciences & Neurology
GA 186VJ
UT WOS:000322073800001
PM 23874288
ER
PT J
AU Murase, S
AF Murase, Sachiko
TI Signal Transducer and Activator of Transcription 3 (STAT3) Degradation
by Proteasome Controls a Developmental Switch in Neurotrophin Dependence
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID LONG-TERM DEPRESSION; ELEMENT MODULATORY FACTOR; TUMOR-SUPPRESSOR
PROTEIN; OCCURRING CELL-DEATH; PARKINSONS-DISEASE; NEURONAL SURVIVAL;
NERVOUS-SYSTEM; CALCINEURIN; UBIQUITIN; PATHWAY
AB Neonatal brains develop through a program that eliminates about half of the neurons. During this period, neurons depend on neurotrophins for their survival. Recently, we reported that, at the conclusion of the naturally occurring death period, neurons become neurotrophin-independent and, further, that this developmental switch is achieved by the emergence of a second survival pathway mediated by signal transducer and activator of transcription 3 (STAT3). Here I show that calcineurin plays a key role in controlling the developmental switch in mouse hippocampal neurons. Calcineurin promotes the degradation of STAT3 via the ubiquitin-proteasome pathway. Inhibition of calcineurin acutely increases total levels of STAT3 as well as its activated forms, resulting in decreased levels of the tumor suppressor p53 and its proapoptotic target, Bax. In vivo and in vitro, calcineurin regulates levels of STAT3 and neurotrophin dependence. TMF/ARA 160 (TATA element modulatory factor/androgen receptor co-activator 160), the key mediator of STAT3 ubiquitination, is required for calcineurin-dependent STAT3 degradation. Thus, these results show that the ubiquitin-proteasome pathway controls the critical developmental switch of neurotrophin dependence in the newborn hippocampus.
C1 NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Murase, S (reprint author), NINDS, Mol Biol Lab, NIH, 35 Lincoln Dr,Bldg 35,Rm 1C1014, Bethesda, MD 20892 USA.
EM sachikom@ninds.nih.gov
FU National Institutes of Health, NINDS, Intramural Research Program
FX This work was supported, in whole or in part, by the National Institutes
of Health, NINDS, Intramural Research Program.
NR 57
TC 9
Z9 9
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 12
PY 2013
VL 288
IS 28
BP 20151
EP 20161
DI 10.1074/jbc.M113.470583
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 182BI
UT WOS:000321715100005
PM 23733189
ER
EF