FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Koob, GF
AF Koob, George F.
TI Alcohol Use Disorders: Tracts, Twins, and Trajectories
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Editorial Material
ID SUBTHALAMIC NUCLEUS; PREFRONTAL CORTEX; DRUG-ADDICTION; INHIBITION;
ADULTHOOD; CHILDHOOD
C1 NIAAA, Rockville, MD 20852 USA.
RP Koob, GF (reprint author), NIAAA, Rockville, MD 20852 USA.
EM george.koob@nih.gov
RI koob, george/P-8791-2016
NR 23
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U1 1
U2 8
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
EI 1535-7228
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD JUN
PY 2015
VL 172
IS 6
BP 499
EP 501
DI 10.1176/appi.ajp.2015.15020240
PG 3
WC Psychiatry
SC Psychiatry
GA CJ6ZD
UT WOS:000355642800001
PM 25982661
ER
PT J
AU van Sloten, TT
Sigurdsson, S
van Buchem, MA
Phillips, CL
Jonsson, PV
Ding, J
Schram, MT
Harris, TB
Gudnason, V
Launer, LJ
AF van Sloten, Thomas T.
Sigurdsson, Sigurdur
van Buchem, Mark A.
Phillips, Caroline L.
Jonsson, Palmi V.
Ding, Jie
Schram, Miranda T.
Harris, Tamara B.
Gudnason, Vilmundur
Launer, Lenore J.
TI Cerebral Small Vessel Disease and Association With Higher Incidence of
Depressive Symptoms in a General Elderly Population: The AGES-Reykjavik
Study
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID WHITE-MATTER LESIONS; LATE-LIFE DEPRESSION; CARDIOVASCULAR-DISEASE;
VASCULAR DEPRESSION; BRAIN INFARCTS; OLDER-ADULTS; PROGRESSION; RISK;
ATROPHY; MECHANISMS
AB Objective: The vascular depression hypothesis postulates that cerebral small vessel disease (CSVD) leads to depressive symptoms by disruption of brain structures involved in mood regulation. However, longitudinal data on the association between CSVD and depressive symptoms are scarce. The authors investigated the association between CSVD and incident depressive symptoms.
Method: Longitudinal data were taken from the Age, Gene/Environment Susceptibility-Reykjavik Study of 1,949 participants free of dementia and without baseline depressive symptoms (mean age: 74.6 years [SD=4.61; women, 56.6%). MRI markers of CSVD, detected at baseline (2002-2006) and follow-up (2007-2011), included white matter hyperintensity volume, subcortical infarcts, cerebral microbleeds, Virchow-Robin spaces, and total brain parenchyma volume. Incident depressive symptoms were defined by a score >= 6 on the 15-item Geriatric Depression Scale and/or use of antidepressant medication.
Results: Depressive symptoms occurred in 10.1% of the participants. The association for a greater onset of depressive symptoms was significant for participants with 1 standard deviation increase in white matter hyperintensity volume over time, new subcortical infarcts, new Virchow-Robin spaces, 1 standard deviation lower total brain volume at baseline, and 1 standard deviation decreased total brain volume overtime, after adjustments for cognitive function and sociodemographic and cardiovascular factors. Results were qualitatively similar when change in the Geriatric Depression Scale score over time was used as the outcome instead of incident depressive symptoms.
Conclusions: Most markers of progression of CSVD overtime and some markers of baseline CSVD are associated with concurrently developing new depressive symptoms. These findings support the vascular depression hypothesis.
C1 [Launer, Lenore J.] Maastricht Univ, Med Ctr, Dept Med, Cardiovasc Res Inst, NL-6200 MD Maastricht, Netherlands.
Maastricht Univ, Med Ctr, Sch Nutr Toxicol & Metab, NL-6200 MD Maastricht, Netherlands.
Iceland Heart Assoc, Kopavogur, Iceland.
Leiden Univ, Dept Radiol, Med Ctr, Leiden, Netherlands.
NIA, Intramural Res Program, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
Landspitali Univ Hosp, Dept Geriatr, Reykjavik, Iceland.
Univ Iceland, Fac Med, Reykjavik, Iceland.
RP Launer, LJ (reprint author), Maastricht Univ, Med Ctr, Dept Med, Cardiovasc Res Inst, NL-6200 MD Maastricht, Netherlands.
EM LaunerL@nia.nih.gov
RI Gudnason, Vilmundur/K-6885-2015; Ding, Jie/K-9943-2015;
OI Gudnason, Vilmundur/0000-0001-5696-0084; Schram,
Miranda/0000-0003-0515-4124
FU AGES-Reykjavik Study - NIH [N01-AG-12100]; Intramural Research Program
of the National Institute on Aging; Icelandic Heart Association;
Icelandic Parliament
FX Supported by the AGES-Reykjavik Study, funded by NIH (contract,
N01-AG-12100); the Intramural Research Program of the National Institute
on Aging; the Icelandic Heart Association; and the Icelandic Parliament
NR 40
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U2 6
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
EI 1535-7228
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD JUN
PY 2015
VL 172
IS 6
BP 570
EP 578
DI 10.1176/appi.ajp.2014.14050578
PG 9
WC Psychiatry
SC Psychiatry
GA CJ6ZD
UT WOS:000355642800013
PM 25734354
ER
PT J
AU Sharp, D
Millum, J
AF Sharp, Daniel
Millum, Joseph
TI Perspective Piece The Post-2015 Development Agenda: Keeping Our Focus on
the Worst Off
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID HEALTH-PROGRAMS; PRIORITY; DISEASES
AB Non-communicable diseases now account for the majority of the global burden of disease and an international campaign has emerged to raise their priority on the post-2015 development agenda. We argue, to the contrary, that there remain strong reasons to prioritize maternal and child health. Policy-makers ought to assign highest priority to the health conditions that afflict the worst off. In virtue of how little healthy life they have had, children who die young are among the globally worst off. Moreover, many interventions to deal with the conditions that cause mortality in the young are low-cost and provide great benefits to their recipients. Consistent with the original Millennium Development Goals, the international community should continue to prioritize reductions in communicable diseases, neonatal conditions, and maternal health despite the shifts in the global burden of disease.
C1 [Millum, Joseph] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA.
[Millum, Joseph] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Sharp, Daniel] Vienna Univ Econ & Business, Vienna, Austria.
RP Millum, J (reprint author), NIH, Ctr Clin, Dept Bioeth, Bldg 10,Room 1C118,10 Ctr Dr, Bethesda, MD 20892 USA.
EM sharpdaniele@gmail.com; joseph.millum@nih.gov
FU National Institutes of Health Clinical Center and Fogarty International
Center
FX This work was supported, in part, by intramural funds from the National
Institutes of Health Clinical Center and Fogarty International Center.
We thank Austen Davis, Christine Grady, and David Wendler for helpful
comments on earlier drafts.
NR 19
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U1 0
U2 5
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
EI 1476-1645
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD JUN
PY 2015
VL 92
IS 6
BP 1087
EP 1089
DI 10.4269/ajtmh.15-0087
PG 3
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA CJ8WY
UT WOS:000355785400002
PM 25846294
ER
PT J
AU Huijben, S
Chan, BHK
Read, AF
AF Huijben, Silvie
Chan, Brian H. K.
Read, Andrew F.
TI Relevance of Undetectably Rare Resistant Malaria Parasites in Treatment
Failure: Experimental Evidence from Plasmodium chabaudi
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID HETERODUPLEX TRACKING ASSAY; FLUORESCENT MICROSPHERE ASSAY;
REVERSE-TRANSCRIPTION PCR; MEDIATING POLYMORPHISMS; FALCIPARUM
INFECTIONS; ANTIMALARIAL TRIALS; DRUG-RESISTANCE; VALIDATION;
CHEMOTHERAPY; DIVERSITY
AB Resistant malaria parasites are frequently found in mixed infections with drug-sensitive parasites. Particularly early in the evolutionary process, the frequency of these resistant mutants can be extremely low and below the level of molecular detection. We tested whether the rarity of resistance in infections impacted the health outcomes of treatment failure and the potential for onward transmission of resistance. Mixed infections of different ratios of resistant and susceptible Plasmodium chabaudi parasites were inoculated in laboratory mice and dynamics tracked during the course of infection using highly sensitive genotype-specific quantitative polymerase chain reaction (qPCR). Frequencies of resistant parasites ranged from 10% to 0.003% at the onset of treatment. We found that the rarer the resistant parasites were, the lower the likelihood of their onward transmission, but the worse the treatment failure was in terms of parasite numbers and disease severity. Strikingly, drug resistant parasites had the biggest impact on health outcomes when they were too rare to be detected by any molecular methods currently available for field samples. Indeed, in the field, these treatment failures would not even have been attributed to resistance.
C1 Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, University Pk, PA 16802 USA.
Penn State Univ, Ctr Infect Dis Dynam, Dept Entomol, University Pk, PA 16802 USA.
[Huijben, Silvie] Univ Barcelona, Hosp Clin, Barcelona Ctr Int Hlth Res CRESIB, ISGlobal, Barcelona, Spain.
[Chan, Brian H. K.] Univ Liverpool, Inst Integrat Biol, Liverpool L69 3BX, Merseyside, England.
NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Read, Andrew F.] Penn State Univ, Ctr Dis Dynam, University Pk, PA 16802 USA.
RP Read, AF (reprint author), Penn State Univ, Ctr Dis Dynam, University Pk, PA 16802 USA.
EM silviehuijben@gmail.com; brian.chan@liverpool.ac.uk; a.read@psu.edu
OI Chan, Brian/0000-0002-9451-4621
FU Institute of General Medical Science [R01 GM089932]; Branco Weiss
Fellowship; Marie Curie Actions IIF Project [623703]
FX This work was funded by the Institute of General Medical Science (R01
GM089932). Silvie Huijben was supported by a Branco Weiss Fellowship and
Marie Curie Actions IIF Project 623703.
NR 42
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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
EI 1476-1645
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD JUN
PY 2015
VL 92
IS 6
BP 1214
EP 1221
DI 10.4269/ajtmh.15-0036
PG 8
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA CJ8WY
UT WOS:000355785400022
PM 25940195
ER
PT J
AU Marchant, NJ
Kaganovsky, K
AF Marchant, Nathan J.
Kaganovsky, Konstantin
TI A Critical Role of Nucleus Accumbens Dopamine D1-Family Receptors in
Renewal of Alcohol Seeking After Punishment-Imposed Abstinence
SO BEHAVIORAL NEUROSCIENCE
LA English
DT Article
DE alcohol; relapse; renewal; punishment; nucleus accumbens
ID CONTEXT-INDUCED REINSTATEMENT; MEDIAL PREFRONTAL CORTEX; RAT VENTRAL
STRIATUM; INDUCED RELAPSE; HEROIN SEEKING; COCAINE-SEEKING; LATERAL
HYPOTHALAMUS; D-1-FAMILY RECEPTORS; PRIMED REINSTATEMENT; GLUTAMATE
RECEPTORS
AB In humans, places or contexts previously associated with alcohol use often provoke relapse during abstinence. This phenomenon is modeled in laboratory animals using the ABA renewal procedure, in which extinction training in context (B) suppresses alcohol seeking, and renewal of this seeking occurs when the animal returns to the original training context (A). However, extinction training does not adequately capture the motivation for abstinence in human alcoholics who typically self-initiate abstinence in response to the negative consequences of excessive use. We recently developed a procedure to study renewal in laboratory rats after abstinence imposed by negative consequences (footshock punishment). The mechanisms of renewal of punished alcohol seeking are largely unknown. Here, we used the D1-family receptor antagonist SCH 23390 to examine the role of nucleus accumbens (NAc) shell and core dopamine in renewal of alcohol seeking after punishment-imposed abstinence. We trained alcohol-preferring "P rats" to self-administer 20% alcohol in Context A and subsequently suppressed alcohol taking via response-contingent footshock punishment in Context B. We tested the effects of systemic, NAc shell, or NAc core injections of SCH 23390 on renewal of alcohol seeking after punishment-imposed abstinence. We found that both systemic and NAc shell and core injections of SCH 23390 decreased renewal of punished alcohol seeking. Our results demonstrate a critical role of NAc dopamine in renewal of alcohol seeking after punishment-imposed abstinence. We discuss these results in reference to the brain mechanisms of renewal of alcohol seeking after extinction versus punishment.
C1 [Marchant, Nathan J.; Kaganovsky, Konstantin] NIDA, Behav Neurosci Res Branch, Intramural Res Program, Baltimore, MD 21224 USA.
[Marchant, Nathan J.] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Melbourne, Vic 3010, Australia.
RP Marchant, NJ (reprint author), NIDA, Suite 200,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM nathan.marchant@nih.gov
OI Kaganovsky, Konstantin/0000-0002-1577-109X
FU National Institute on Drug Abuse, Intramural Research Program funds;
National Health and Medical Research Council [1053308]
FX Research was supported by the National Institute on Drug Abuse,
Intramural Research Program funds to the Neurobiology of Relapse Section
(PI: Yavin Shaham). Nathan J. Marchant received support from Early
Career Fellowship 1053308 by the National Health and Medical Research
Council. We thank Yavin Shaham, Antonello Bonci, and Helen Nasser for
their help in the conceptualization of the project and the write-up of
the article.
NR 52
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U1 0
U2 4
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0735-7044
EI 1939-0084
J9 BEHAV NEUROSCI
JI Behav. Neurosci.
PD JUN
PY 2015
VL 129
IS 3
BP 281
EP 291
DI 10.1037/bne0000050
PG 11
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA CJ9QV
UT WOS:000355838200005
PM 25914922
ER
PT J
AU Sayeed, SK
Zhao, J
Sathyanarayana, BK
Golla, JP
Vinson, C
AF Sayeed, Syed Khund
Zhao, Jianfei
Sathyanarayana, Bangalore K.
Golla, Jaya Prakash
Vinson, Charles
TI C/EBP beta (CEBPB) protein binding to the C/EBP vertical bar CRE DNA
8-mer TTGC vertical bar GTCA is inhibited by 5hmC and enhanced by 5mC,
5fC, and 5caC in the CG dinucleotide
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
LA English
DT Article
DE 5mC, 5hmC, 5fC, 5caC, carboxylation; C/EBP vertical bar CRE motif; CG
dinucleotide; Basic-leucine zipper; DNA binding; C/EBP beta homodimer
ID EMBRYONIC STEM-CELLS; GENE-EXPRESSION; TRANSCRIPTION FACTORS; CPG
METHYLATION; ADIPOCYTE DIFFERENTIATION; DIMERIZATION SPECIFICITY;
5-HYDROXYMETHYLCYTOSINE; GENOME; 5-FORMYLCYTOSINE; 5-METHYLCYTOSINE
AB During mammalian development, some methylated cytosines (5mC) in CG dinucleotides are iteratively oxidized by TET dioxygenases to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). The effect of these cytosine oxidative products on the sequence-specific DNA binding of transcription factors is being actively investigated. Here, we used the electrophoretic mobility shift assay (EMSA) to examine C/EBP alpha and C/EBP beta homodimers binding to all 25 chemical forms of a CG dinudeotide for two DNA sequences: the canonical C/EBP 8-mer TTGC vertical bar GCAA and the chimeric C/EBP vertical bar CRE 8-mer TTGC vertical bar GTCA. 5hmC in the CG dinucleotide in the C/EBP vertical bar CRE motif 8-mer TGAC vertical bar GCAA inhibits binding of C/EBP beta, but not C/EBP alpha. Binding was increased by 5mC, 5fC and 5caC Circular dichroism monitored thermal denaturations for C/EBP beta, bound to the C/EBP vertical bar CRE motif confirmed the EMSA. The structural differences between C/EBP alpha and C/EBP beta that may account for the difference in binding 5hmC in the 8-mer TGAC vertical bar GCAA are explored. Published by Elsevier B.V.
C1 [Sayeed, Syed Khund; Zhao, Jianfei; Golla, Jaya Prakash; Vinson, Charles] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
[Sathyanarayana, Bangalore K.] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Vinson, C (reprint author), NCI, Lab Metab, NIH, Room 3128,Bldg 37, Bethesda, MD 20892 USA.
EM vinsonc@mail.nih.gov
FU National Cancer Institute, NIH, Bethesda, USA
FX We thank our lab members for their encouragement and support. This work
is supported by the intramural research project of the National Cancer
Institute, NIH, Bethesda, USA.
NR 56
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Z9 4
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-9399
EI 0006-3002
J9 BBA-GENE REGUL MECH
JI Biochim. Biophys. Acta-Gene Regul. Mech.
PD JUN
PY 2015
VL 1849
IS 6
BP 583
EP 589
DI 10.1016/j.bbagrm.2015.03.002
PG 7
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA CK0KY
UT WOS:000355895300001
PM 25779641
ER
PT J
AU Ionescu, DF
Luckenbaugh, DA
Niciu, MJ
Richards, EM
Zarate, CA
AF Ionescu, Dawn F.
Luckenbaugh, David A.
Niciu, Mark J.
Richards, Erica M.
Zarate, Carlos A., Jr.
TI A single infusion of ketamine improves depression scores in patients
with anxious bipolar depression
SO BIPOLAR DISORDERS
LA English
DT Article
DE anxious depression; bipolar disorder; ketamine; N-methyl-d-aspartate
antagonist; predictors of response
ID D-ASPARTATE ANTAGONIST; ADD-ON TRIAL; COMORBID ANXIETY; DOUBLE-BLIND; I
DEPRESSION; DISORDER; SCALE; MONOTHERAPY; LURASIDONE; STATES
AB ObjectivePatents with anxious bipolar disorder have worse clinical outcomes and are harder to treat with traditional medication regimens compared to those with non-anxious bipolar disorder. Ketamine has been shown to rapidly and robustly decrease symptoms of depression in depressed patients with bipolar disorder. We sought to determine whether baseline anxiety status reduced ketamine's ability to decrease symptoms of depression.
MethodsThirty-six patients with anxious (n=21) and non-anxious (n=15) treatment-resistant bipolar depression (types I and II; concurrently treated with either lithium or valproate) received a single infusion of ketamine (0.5mg/kg) over 40min. Post-hoc analyses compared changes in the Montgomery-angstrom sberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HDRS) in anxious versus non-anxious depressed patients with bipolar disorder through 14days post-infusion. Anxious bipolar depression was defined as DSM-IV bipolar depression plus a HDRS Anxiety/Somatization Factor score of 7.
ResultsA linear mixed model revealed a significant effect of anxiety group on the MADRS (p=0.04) and HDRS (p=0.04). Significant drug effects (all p<0.001) suggested that both anxious and non-anxious groups had an antidepressant response to ketamine. The drug-by-anxiety interactions were not significant (all p>0.28).
ConclusionsBoth anxious and non-anxious patients with bipolar depression had significant antidepressant responses to ketamine, although the anxious depressed group did not show a clear antidepressant response disadvantage over the non-anxious group. Given that anxiety has been shown to be a predictor of poor treatment response in bipolar depression when traditional treatments are used, our findings suggest a need for further investigations into ketamine's novel role in the treatment of anxious bipolar depression.
C1 [Ionescu, Dawn F.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA.
[Ionescu, Dawn F.] Harvard Univ, Sch Med, Boston, MA USA.
[Luckenbaugh, David A.; Niciu, Mark J.; Richards, Erica M.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Ionescu, DF (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 1 Bowdoin Sq,Floor 6, Boston, MA 02114 USA.
EM dionescu@mgh.harvard.edu
RI Niciu, Mark/J-1766-2014; Ionescu, Dawn/K-5675-2015
OI Niciu, Mark/0000-0002-5612-3021;
FU Intramural Research Program at the National Institute of Mental Health,
National Institutes of Health (IRP-NIMH-NIH); NARSAD Independent
Investigator; Brain & Behavior Mood Disorders Research Award
FX Funding for this work was supported by the Intramural Research Program
at the National Institute of Mental Health, National Institutes of
Health (IRP-NIMH-NIH), by a NARSAD Independent Investigator to CAZ, and
by the Brain & Behavior Mood Disorders Research Award to CAZ.
NR 26
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Z9 5
U1 0
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2015
VL 17
IS 4
BP 438
EP 443
DI 10.1111/bdi.12277
PG 6
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA CJ9PV
UT WOS:000355835600010
PM 25400146
ER
PT J
AU Morris, CR
Kim, HY
Klings, ES
Wood, J
Porter, JB
Trachtenberg, F
Sweeters, N
Olivieri, NF
Kwiatkowski, JL
Virzi, L
Hassell, K
Taher, A
Neufeld, EJ
Thompson, AA
Larkin, S
Suh, JH
Vichinsky, EP
Kuypers, FA
AF Morris, Claudia R.
Kim, Hae-Young
Klings, Elizabeth S.
Wood, John
Porter, John B.
Trachtenberg, Felicia
Sweeters, Nancy
Olivieri, Nancy F.
Kwiatkowski, Janet L.
Virzi, Lisa
Hassell, Kathryn
Taher, Ali
Neufeld, Ellis J.
Thompson, Alexis A.
Larkin, Sandra
Suh, Jung H.
Vichinsky, Elliott P.
Kuypers, Frans A.
CA Thalassemia Clinical Res Network
TI Dysregulated arginine metabolism and cardiopulmonary dysfunction in
patients with thalassaemia
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE arginase; -thalassaemia; global arginine bioavailability ratio;
haemolysis; pulmonary hypertension
ID SICKLE-CELL-DISEASE; RIGHT HEART CATHETERIZATION; PULMONARY
ARTERIAL-HYPERTENSION; REGURGITANT JET VELOCITY; NITRIC-OXIDE;
RISK-FACTORS; BETA-THALASSEMIA; BIOAVAILABILITY RATIOS; FREE HEMOGLOBIN;
MAJOR PATIENTS
AB Pulmonary hypertension (PH) commonly develops in thalassaemia syndromes, but is poorly characterized. The goal of this study was to provide a comprehensive description of the cardiopulmonary and biological profile of patients with thalassaemia at risk for PH. A case-control study of thalassaemia patients at high versus low PH-risk was performed. A single cross-sectional measurement for variables reflecting cardiopulmonary status and biological pathophysiology were obtained, including Doppler-echocardiography, 6-min-walk-test, Borg Dyspnoea Score, New York Heart Association functional class, cardiac magnetic resonance imaging (MRI), chest-computerized tomography, pulmonary function testing and laboratory analyses targeting mechanisms of coagulation, inflammation, haemolysis, adhesion and the arginine-nitric oxide pathway. Twenty-seven thalassaemia patients were evaluated, 14 with an elevated tricuspid-regurgitant-jet-velocity (TRV)25m/s. Patients with increased TRV had a higher frequency of splenectomy, and significantly larger right atrial size, left atrial volume and left septal-wall thickness on echocardiography and/or MRI, with elevated biomarkers of abnormal coagulation, lactate dehydrogenase (LDH) levels and arginase concentration, and lower arginine-bioavailability compared to low-risk patients. Arginase concentration correlated significantly to several echocardiography/MRI parameters of cardiovascular function in addition to global-arginine-bioavailability and biomarkers of haemolytic rate, including LDH, haemoglobin and bilirubin. Thalassaemia patients with a TRV25m/s have additional echocardiography and cardiac-MRI parameters suggestive of right and left-sided cardiac dysfunction. In addition, low arginine bioavailability may contribute to cardiopulmonary dysfunction in -thalassaemia.
C1 [Morris, Claudia R.] Emory Univ, Sch Med, Emory Childrens Ctr Cyst Fibrosis & Airways Dis R, Dept Pediat,Div Emergency Med, Atlanta, GA 30329 USA.
[Kim, Hae-Young; Trachtenberg, Felicia; Virzi, Lisa] New England Res Inst Watertown, Watertown, MA USA.
[Klings, Elizabeth S.] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA.
[Wood, John] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Porter, John B.] UCL, London, England.
[Sweeters, Nancy; Vichinsky, Elliott P.] UCSF Benioff Childrens Hosp Oakland, Hematol Oncol, Oakland, CA USA.
[Olivieri, Nancy F.] Toronto Gen Hosp, Toronto, ON, Canada.
[Kwiatkowski, Janet L.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Hassell, Kathryn] NHLBI, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA.
[Taher, Ali] Amer Univ Beirut, Beirut, Lebanon.
[Neufeld, Ellis J.] Childrens Hosp Boston, Boston, MA USA.
[Thompson, Alexis A.] Childrens Mem Hosp, Haematol Oncol & Stem Cell Transplant, Chicago, IL 60614 USA.
[Larkin, Sandra; Suh, Jung H.; Kuypers, Frans A.] Childrens Hosp Oakland Res Inst, Oakland, CA USA.
RP Morris, CR (reprint author), Emory Univ, Sch Med, Emory Childrens Ctr Cyst Fibrosis & Airways Dis R, Pediat & Emergency Med, 1760 Haygood Dr,NE W458, Atlanta, GA 30329 USA.
EM claudia.r.morris@emory.edu
OI Porter, John/0000-0003-3000-9359
FU NIH-NHLBI [U01 HL065238NIH, U01-HL65232]; CTSA [UL1 RR024131]; FDA
[1R01FD003531-04]; Intramural Research Program of the NIH, NHLBI;
NIH/NCRR [UL1-RR-024134, U01-HL72291]; Harvard Catalyst CTSC
[U-01RR025758, U01-HL65233, UL1RR024131-01, U01-HL65244, CTSC
UL1-RR024996, U01-HL65238]
FX This is publication number 34 of the TCRN. A list of TCRN member
institutions and staff appears in the Appendix. The authors would like
to thank the agencies that funded this study. This study was supported
by the NIH-NHLBI cooperative agreement U01 HL065238NIH grant and CTSA
grant UL1 RR024131, FDA grant 1R01FD003531-04 (to CRM). This research
was also supported in part by the Intramural Research Program of the
NIH, NHLBI and by the following NIH-NHLBI cooperative agreements:
U01-HL65232 and NIH/NCRR UL1-RR-024134 to the Children's Hospital of
Philadelphia, U01-HL72291 and by Harvard Catalyst CTSC U-01RR025758 to
Children's Hospital, Boston, U01-HL65233 to University Health Network
Toronto General Hospital, UL1RR024131-01 to Children's Hospital &
Research Centre Oakland, U01-HL65244 and CTSC UL1-RR024996 to Weill
Medical College of Cornell University, and U01-HL65238 to New England
Research Institutes. Its contents are solely the responsibility of the
authors and do not necessarily represent the official views of the
NHLBI. The authors would also like to thank the patients with
thalassaemia and their families who participated in this study.
NR 52
TC 4
Z9 4
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
EI 1365-2141
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD JUN
PY 2015
VL 169
IS 6
BP 887
EP 898
DI 10.1111/bjh.13452
PG 12
WC Hematology
SC Hematology
GA CJ7EN
UT WOS:000355657300017
PM 25907665
ER
PT J
AU Cooper, JM
Gadian, DG
Jentschke, S
Goldman, A
Munoz, M
Pitts, G
Banks, T
Chong, WK
Hoskote, A
Deanfield, J
Baldeweg, T
de Haan, M
Mishkin, M
Vargha-Khadem, F
AF Cooper, Janine M.
Gadian, David G.
Jentschke, Sebastian
Goldman, Allan
Munoz, Monica
Pitts, Georgia
Banks, Tina
Chong, W. Kling
Hoskote, Aparna
Deanfield, John
Baldeweg, Torsten
de Haan, Michelle
Mishkin, Mortimer
Vargha-Khadem, Faraneh
TI Neonatal Hypoxia, Hippocampal Atrophy, and Memory Impairment: Evidence
of a Causal Sequence
SO CEREBRAL CORTEX
LA English
DT Article
DE developmental amnesia; hippocampal volumes; hypoxia
ID EXTRACORPOREAL MEMBRANE-OXYGENATION; COLLABORATIVE RANDOMIZED-TRIAL;
DEVELOPMENTAL AMNESIA; BRAIN-INJURY; AUTOMATIC SEGMENTATION; COGNITIVE
IMPAIRMENT; EVERYDAY MEMORY; FOLLOW-UP; MRI; TIME
AB Neonates treated for acute respiratory failure experience episodes of hypoxia. The hippocampus, a structure essential for memory, is particularly vulnerable to such insults. Hence, some neonates undergoing treatment for acute respiratory failure might sustain bilateral hippocampal pathology early in life and memory problems later in childhood. We investigated this possibility in a cohort of 40 children who had been treated neonatally for acute respiratory failure but were free of overt neurological impairment. The cohort had mean hippocampal volumes (HVs) significantly below normal control values, memory scores significantly below the standard population means, and memory quotients significantly below those predicted by their full scale IQs. Brain white matter volume also fell below the volume of the controls, but brain gray matter volumes and scores on nonmnemonic neuropsychological tests were within the normal range. Stepwise linear regression models revealed that the cohort's HVs were predictive of degree of memory impairment, and gestational age at treatment was predictive of HVs: the younger the age, the greater the atrophy. We conclude that many neonates treated for acute respiratory failure sustain significant hippocampal atrophy as a result of the associated hypoxia and, consequently, show deficient memory later in life.
C1 [Cooper, Janine M.; Jentschke, Sebastian; Munoz, Monica; Pitts, Georgia; Baldeweg, Torsten; de Haan, Michelle; Vargha-Khadem, Faraneh] UCL Inst Child Hlth, Dev Cognit Neurosci Unit, London WC1N 1EH, England.
[Gadian, David G.; Banks, Tina; Chong, W. Kling] UCL Inst Child Hlth, Imaging & Biophys Unit, London WC1N 1EH, England.
[Goldman, Allan; Hoskote, Aparna] UCL Inst Child Hlth, Cardiac Unit, London WC1N 1EH, England.
[Deanfield, John] UCL Inst Cardiovasc Sci, London WC1E 6BT, England.
[Goldman, Allan; Hoskote, Aparna] Great Ormond St Hosp Sick Children, Cardiac Intens Care, London WC1N 3JH, England.
[Banks, Tina; Chong, W. Kling] Great Ormond St Hosp Sick Children, Dept Radiol, London WC1N 3JH, England.
[Vargha-Khadem, Faraneh] Great Ormond St Hosp Sick Children, Dept Neuropsychol, London WC1N 3JH, England.
[Mishkin, Mortimer] NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA.
[Cooper, Janine M.] Murdoch Childrens Res Inst, Melbourne, Vic 3052, Australia.
[Munoz, Monica] Univ Castilla La Mancha, Albacete 02006, Spain.
[Jentschke, Sebastian] Free Univ Berlin, D-14195 Berlin, Germany.
RP Vargha-Khadem, F (reprint author), UCL Inst Child Hlth, Dev Cognit Neurosci Unit, 30 Guilford St, London WC1N 1EH, England.
EM f.vargha-khadem@ucl.ac.uk
RI Munoz-Lopez, Monica/F-3154-2016;
OI Munoz Lopez, Monica/0000-0002-5530-2394
FU Medical Research Council [G03000117/65439]; Central and East London
Research Network [5177]; National Institute of Mental Health, National
Institutes of Health, Department of Health and Human Services; Research
Councils UK
FX This work was supported by the Medical Research Council (program grant
number G03000117/65439); the Central and East London Research Network
(5177); and the Intramural Research Program of the National Institute of
Mental Health, National Institutes of Health, Department of Health and
Human Services. Funding to pay the Open Access publication charges for
this article was provided by Research Councils UK.
NR 55
TC 10
Z9 10
U1 2
U2 10
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
EI 1460-2199
J9 CEREB CORTEX
JI Cereb. Cortex
PD JUN
PY 2015
VL 25
IS 6
BP 1469
EP 1476
DI 10.1093/cercor/bht332
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA CJ7HL
UT WOS:000355665300005
PM 24343890
ER
PT J
AU Torabi-Parizi, P
Davey, RT
Suffredini, AF
Chertow, DS
AF Torabi-Parizi, Parizad
Davey, Richard T., Jr.
Suffredini, Anthony F.
Chertow, Daniel S.
TI Ethical and Practical Considerations in Providing Critical Care to
Patients With Ebola Virus Disease
SO CHEST
LA English
DT Article
ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; TO-MOUTH RESUSCITATION;
PNEUMOCYSTIS-CARINII-PNEUMONIA; INTENSIVE-CARE; IMPROVED OUTCOMES;
WEST-AFRICA; AIDS; WORKERS; RELUCTANCE; GUIDELINES
AB Infectious disease epidemics in the past have given rise to psychologic and emotional responses among health-care workers (HCWs), stemming from fear of infection during patient care. Early experiences in the AIDS epidemic provide an example where fear of contagion resulted in differential treatment of patients infected with HIV. However, with a deeper understanding of AIDS pathogenesis and treatment, fear and discrimination diminished. Parallels exist between early experiences with AIDS and the present outbreak of Ebola virus disease in West Africa, particularly regarding discussions of medical futility in seriously ill patients. We provide a historical perspective on HCWs' risk of infection during the provision of CPR, discuss physicians' duty to treat in the face of perceived or actual HCW risk, and, finally, present the protocols implemented at the National Institutes of Health to reduce HCW risk while providing lifesaving and life-sustaining care.
C1 [Torabi-Parizi, Parizad; Suffredini, Anthony F.; Chertow, Daniel S.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Davey, Richard T., Jr.] NIAID, Clin Res Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Torabi-Parizi, P (reprint author), NIH, Dept Crit Care Med, 10 Ctr Dr,2C145, Bethesda, MD 20892 USA.
EM torabiparizip@cc.nih.gov
NR 39
TC 14
Z9 14
U1 0
U2 12
PU AMER COLL CHEST PHYSICIANS
PI GLENVIEW
PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA
SN 0012-3692
J9 CHEST
JI Chest
PD JUN
PY 2015
VL 147
IS 6
BP 1460
EP 1466
DI 10.1378/chest.15-0278
PG 7
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA CJ9QS
UT WOS:000355837900025
PM 25764372
ER
PT J
AU Goh, GBB
Pagadala, MR
Dasarathy, J
Unalp-Arida, A
Pai, RK
Yerian, L
Khiyami, A
Sourianarayanane, A
Sargent, R
Hawkins, C
Dasarathy, S
McCullough, AJ
AF Goh, George Boon-Bee
Pagadala, Mangesh R.
Dasarathy, Jaividhya
Unalp-Arida, Aynur
Pai, Rish K.
Yerian, Lisa
Khiyami, Amer
Sourianarayanane, Achuthan
Sargent, Ruth
Hawkins, Carol
Dasarathy, Srinivasan
McCullough, Arthur J.
TI Age Impacts Ability of Aspartate-Alanine Aminotransferase Ratio to
Predict Advanced Fibrosis in Nonalcoholic Fatty Liver Disease
SO DIGESTIVE DISEASES AND SCIENCES
LA English
DT Article
DE NAFLD; Liver transaminases; Age-related changes; Advanced fibrosis
ID TRIGLYCERIDE SYNTHESIS; HEPATIC STEATOSIS; SCORING SYSTEM;
UNITED-STATES; PREVALENCE; POPULATION; STEATOHEPATITIS; ASSOCIATION;
VALIDATION; GLUCOSE
AB Background and Aim While histological differences have been reported between pediatric and adult nonalcoholic fatty liver disease (NAFLD), potential age-related changes in serum transaminases and liver histology remain largely unexplored. Our study sought to investigate the clinical and histological characteristics of NAFLD across age.
Methods This was a prospective cross-sectional study of 502 biopsy-proven NAFLD patients. Clinical data were evaluated and compared among different age groups; group A (ages 18-44), B (ages 45-64), and C (>= ages 65).
Results 34.9, 56.0, and 9.1 % of the cohort were distributed among group A, B, and C, respectively. While the prevalence of nonalcoholic steatohepatitis (NASH) was comparable across age groups, the prevalence of advanced fibrosis increased with age (p = 0.000). Although the mean ALT progressively decreased with age; 87, 64, 56 U/L in group A, B, and C, respectively (p = 0.000), there was no difference in mean AST (p = 0.939) across age. The AST: ALT ratio (AAR) progressively increased from 0.7, 0.9, and 1.1 in group A, B, and C, respectively (p = 0.000). In group C, an AAR >= 1 was found in 74 and 40 % of patients with and without advanced fibrosis.
Conclusion With advancing age, ALT levels progressively declined while AST levels remained stable, leading to a higher AAR. Although higher AAR is often used as a surrogate measure of advanced fibrosis, advancing age can also contribute to increased AAR. In fact, an AAR >= 1 was found in significant number of elderly patients without advanced fibrosis. Consequently, an increased AAR may be a function of decreasing ALT with age in addition to progressive fibrosis.
C1 [Goh, George Boon-Bee; Pagadala, Mangesh R.; Sourianarayanane, Achuthan; Sargent, Ruth; Dasarathy, Srinivasan; McCullough, Arthur J.] Cleveland Clin Fdn, Dept Gastroenterol, Cleveland, OH 44195 USA.
[Goh, George Boon-Bee] Singapore Gen Hosp, Dept Gastroenterol, Singapore, Singapore.
[Dasarathy, Jaividhya; Khiyami, Amer; Hawkins, Carol] Metrohlth Med Ctr, Dept Family Med, Cleveland, OH USA.
[Unalp-Arida, Aynur] NIDDK, Bethesda, MD 20817 USA.
[Pai, Rish K.; Yerian, Lisa] Cleveland Clin Fdn, Dept Pathol, Cleveland, OH 44195 USA.
[Dasarathy, Srinivasan; McCullough, Arthur J.] Cleveland Clin Fdn, Dept Pathobiol, Cleveland, OH 44195 USA.
RP McCullough, AJ (reprint author), Cleveland Clin Fdn, Dept Gastroenterol, 9500 Euclid Ave,A30, Cleveland, OH 44195 USA.
EM george.goh.b.b@sgh.com.sg; pagadam@ccf.org; j.dasarathy@metrohealth.org;
aynur.unalp-arida@nih.gov; pair@ccf.org; YERIANL@ccf.org;
akhiyami@metrohealth.org; souria.a1@uky.edu; SARGENR@ccf.org;
chawkins@metrohealth.org; DASARAS@ccf.org; mcculla@ccf.org
FU Singapore Sing Health HMDP; NIH [T32 DK061917]; NIH DK U
FX G.B.B.G. was supported by Singapore Sing Health HMDP. M.R.P. was
supported by NIH T32 DK061917. S.D., J.D., A.J.M., R.S., C.H. were
supported by NIH DK U.
NR 42
TC 2
Z9 2
U1 0
U2 5
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0163-2116
EI 1573-2568
J9 DIGEST DIS SCI
JI Dig. Dis. Sci.
PD JUN
PY 2015
VL 60
IS 6
BP 1825
EP 1831
DI 10.1007/s10620-015-3529-8
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CJ6CM
UT WOS:000355580800043
PM 25708897
ER
PT J
AU Gallardo, VE
Varshney, GK
Lee, M
Bupp, S
Xu, LS
Shinn, P
Crawford, NP
Inglese, J
Burgess, SM
AF Gallardo, Viviana E.
Varshney, Gaurav K.
Lee, Minnkyong
Bupp, Sujata
Xu, Lisha
Shinn, Paul
Crawford, Nigel P.
Inglese, James
Burgess, Shawn M.
TI Phenotype-driven chemical screening in zebrafish for compounds that
inhibit collective cell migration identifies multiple pathways
potentially involved in metastatic invasion
SO DISEASE MODELS & MECHANISMS
LA English
DT Article
DE Drug screening; Metastasis; Orthotopic implantation; Src; Tks5;
Zebrafish
ID LATERAL-LINE PRIMORDIUM; IN-VIVO; TUMOR-METASTASIS; CANCER; SRC;
MORPHOGENESIS; INFLAMMATION; EXPRESSION; KINASES; GROWTH
AB In the last decade, high-throughput chemical screening has become the dominant approach for discovering novel compounds with therapeutic properties. Automated screening using in vitro or cultured cell assays have yielded thousands of candidate drugs for a variety of biological targets, but these approaches have not resulted in an increase in drug discovery despite major increases in expenditures. In contrast, phenotype-driven screens have shown a much stronger success rate, which is why we developed an in vivo assay using transgenic zebrafish with a GFP-marked migrating posterior lateral line primordium (PLLp) to identify compounds that influence collective cell migration. We then conducted a high-throughput screen using a compound library of 2160 annotated bioactive synthetic compounds and 800 natural products to identify molecules that block normal PLLp migration. We identified 165 compounds that interfere with primordium migration without overt toxicity in vivo. Selected compounds were confirmed in their migration-blocking activity by using additional assays for cell migration. We then proved the screen to be successful in identifying anti-metastatic compounds active in vivo by performing orthotopic tumor implantation assays in mice. We demonstrated that the Src inhibitor SU6656, identified in our screen, can be used to suppress the metastatic capacity of a highly aggressive mammary tumor cell line. Finally, we used CRISPR/Cas9-targeted mutagenesis in zebrafish to genetically validate predicted targets of compounds. This approach demonstrates that the migrating PLLp in zebrafish can be used for large-scale, highthroughput screening for compounds that inhibit collective cell migration and, potentially, anti-metastatic compounds.
C1 [Gallardo, Viviana E.; Varshney, Gaurav K.; Xu, Lisha; Burgess, Shawn M.] NHGRI, Dev Genom Sect, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Lee, Minnkyong; Bupp, Sujata; Crawford, Nigel P.; Inglese, James] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Shinn, Paul; Inglese, James] NIH, Dept Preclin Innovat, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
RP Burgess, SM (reprint author), NHGRI, Dev Genom Sect, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
EM burgess@mail.nih.gov
FU Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Human Genome Research Institute, National Institutes of Health
(S.B., N.P.C.).
NR 43
TC 8
Z9 8
U1 0
U2 10
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 1754-8403
EI 1754-8411
J9 DIS MODEL MECH
JI Dis. Model. Mech.
PD JUN
PY 2015
VL 8
IS 6
BP 565
EP 576
DI 10.1242/dmm.018689
PG 12
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA CJ5VD
UT WOS:000355559100005
PM 25810455
ER
PT J
AU Spinelli, E
Barnes, AJ
Young, S
Castaneto, MS
Martin, TM
Klette, KL
Huestis, MA
AF Spinelli, Eliani
Barnes, Allan J.
Young, Sheena
Castaneto, Marisol S.
Martin, Thomas M.
Klette, Kevin L.
Huestis, Marilyn A.
TI Performance characteristics of an ELISA screening assay for urinary
synthetic cannabinoids
SO DRUG TESTING AND ANALYSIS
LA English
DT Article
DE immunoassay; synthetic cannabinoids; ELISA
ID ENDOCANNABINOID SYSTEM; HERBAL BLENDS; IMMUNOASSAY; PHARMACOLOGY;
METABOLITES; MS
AB Synthetic cannabinoids are marketed as legal alternatives to cannabis, as routine urine cannabinoid immunoassays do not detect synthetic cannabinoids. Laboratories are challenged to identify these new designer drugs that are widely available and represent a major public health and safety problem. Immunoassay testing offers rapid separation of presumptive positive and negative specimens, prior to more costly and time-consuming chromatographic confirmation. The Neogen SPICE ELISA kit targets JWH-018N-pentanoic acid as a marker for urinary synthetic cannabinoids. Assay performance was evaluated by analyzing 2469 authentic urine samples with the Neogen immunoassay and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Two immunoassay cut-off concentrations, 5 and 10 mu g/L, classified samples as presumptive positive or negative, followed by qualitative LC-MS/MS confirmation for 29 synthetic cannabinoids markers with limits of detection of 0.5-10 mu g/L to determine the assay's sensitivity, specificity and efficacy. Challenges at +/- 25% of each cut-off also were investigated to determine performance around the cut-off and intra- and inter-plate imprecision. The immunoassay was linear from 1 to 250 mu g/L (r(2)=0.992) with intra- and inter-plate imprecision of 5.3% and <9%, respectively. Sensitivity, specificity, and efficiency results with the 5 mu g/L cut-off were 79.9%, 99.7%, and 97.4% and with the 10 mu g/L cut-off 69.3%, 99.8%, and 96.3%, respectively. Cross-reactivity was shown for 18 of 73 synthetic cannabinoids markers evaluated. Good sensitivity, specificity, and efficiency, lack of sample preparation requirements, and rapid semi-automation documented that the Neogen SPICE ELISA kit is a viable method for screening synthetic cannabinoids in urine targeting JWH-018N-pentanoic acid. Copyright (c) 2014 John Wiley & Sons, Ltd.
C1 [Spinelli, Eliani; Barnes, Allan J.; Young, Sheena; Castaneto, Marisol S.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Spinelli, Eliani] Univ Fed Fluminense, CAPES Fdn BEX 1534 12 2, Sch Pharm, Rio De Janeiro, Brazil.
[Martin, Thomas M.; Klette, Kevin L.] Personel Risk Reduct, Off Secretary Def Personnel & Readiness, Drug Testing & Program Policy, Washington, DC USA.
RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab, IRP, NIH,Biomed Res Ctr, 251 Bayview Blvd,Suite 200,Room 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
OI Spinelli, Eliani/0000-0001-5488-2545
FU National Institute on Drug Abuse, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute on Drug Abuse, National Institutes of Health. We also
thank Neogen Corporation for providing the controls and assay kits for
urine analyses.
NR 16
TC 5
Z9 5
U1 4
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1942-7603
EI 1942-7611
J9 DRUG TEST ANAL
JI Drug Test. Anal.
PD JUN
PY 2015
VL 7
IS 6
BP 467
EP 474
DI 10.1002/dta.1702
PG 8
WC Biochemical Research Methods; Chemistry, Analytical; Pharmacology &
Pharmacy
SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy
GA CJ7LD
UT WOS:000355675700003
PM 25167963
ER
PT J
AU Castaneto, MS
Scheidweiler, KB
Gandhi, A
Wohlfarth, A
Klette, KL
Martin, TM
Huestis, MA
AF Castaneto, Marisol S.
Scheidweiler, Karl B.
Gandhi, Adarsh
Wohlfarth, Ariane
Klette, Kevin L.
Martin, Thomas M.
Huestis, Marilyn A.
TI Quantitative urine confirmatory testing for synthetic cannabinoids in
randomly collected urine specimens
SO DRUG TESTING AND ANALYSIS
LA English
DT Article
DE synthetic cannabinoids; immunoassay; LC-MS; MS; urine drug testing
ID TANDEM MASS-SPECTROMETRY; HUMAN HEPATOCYTES; LC-MS/MS; METABOLITES;
JWH-018; IDENTIFICATION; AM-2201; BLOOD; QUANTIFICATION; VALIDATION
AB Synthetic cannabinoid intake is an ongoing health issue worldwide, with new compounds continually emerging, making drug testing complex. Parent synthetic cannabinoids are rarely detected in urine, the most common matrix employed in workplace drug testing. Optimal identification of synthetic cannabinoid markers in authentic urine specimens and correlation of metabolite concentrations and toxicities would improve synthetic cannabinoid result interpretation. We screened 20017 randomly collected US military urine specimens between July 2011 and June 2012 with a synthetic cannabinoid immunoassay yielding 1432 presumptive positive specimens. We analyzed all presumptive positive and 1069 negative specimens with our qualitative synthetic cannabinoid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, which confirmed 290 positive specimens. All 290 positive and 487 randomly selected negative specimens were quantified with the most comprehensive urine quantitative LC-MS/MS method published to date; 290 specimens confirmed positive for 22 metabolites from 11 parent synthetic cannabinoids. The five most predominant metabolites were JWH-018 pentanoic acid (93%), JWH-N-hydroxypentyl (84%), AM2201 N-hydroxypentyl (69%), JWH-073 butanoic acid (69%), and JWH-122N-hydroxypentyl (45%) with 11.1 (0.1-2,434), 5.1 (0.1-1,239), 2.0 (0.1-321), 1.1 (0.1-48.6), and 1.1 (0.1-250) mu g/L median (range) concentrations, respectively. Alkyl hydroxy and carboxy metabolites provided suitable biomarkers for 11 parent synthetic cannabinoids; although hydroxyindoles were also observed. This is by far the largest data set of synthetic cannabinoid metabolites urine concentrations from randomly collected workplace drug testing specimens rather than acute intoxications or driving under the influence of drugs. These data improve the interpretation of synthetic cannabinoid urine test results and suggest suitable urine markers of synthetic cannabinoid intake. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Castaneto, Marisol S.; Scheidweiler, Karl B.; Gandhi, Adarsh; Wohlfarth, Ariane; Huestis, Marilyn A.] NIDA, Chem & Drug Metab, NIH, Baltimore, MD 21224 USA.
[Castaneto, Marisol S.] Univ Maryland Baltimore, Toxicol Program, Baltimore, MD USA.
[Klette, Kevin L.; Martin, Thomas M.] Personnel Risk Reduct, Drug Testing & Program Policy, Off Secretary Def Personnel & Readiness, Washington, DC USA.
RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab, NIH, 251 Bayview Blvd,BRC 05A721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU DOD Counter Narcotics Program [Y3-DA-1116-01]; National Institute on
Drug Abuse, NIH [Y3-DA-1116-01]; Forensic Toxicology Drug Testing
Laboratory, Fort Meade, MD
FX An Interagency Agreement (Y3-DA-1116-01) between DOD Counter Narcotics
Program and Intramural Research Program of the National Institute on
Drug Abuse, NIH helped fund this research. Assistance and support of the
Forensic Toxicology Drug Testing Laboratory, Fort Meade, MD and
Chemistry and Drug Metabolism staff in the conduct of this study are
greatly appreciated.
NR 57
TC 11
Z9 11
U1 6
U2 21
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1942-7603
EI 1942-7611
J9 DRUG TEST ANAL
JI Drug Test. Anal.
PD JUN
PY 2015
VL 7
IS 6
BP 483
EP 493
DI 10.1002/dta.1709
PG 11
WC Biochemical Research Methods; Chemistry, Analytical; Pharmacology &
Pharmacy
SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy
GA CJ7LD
UT WOS:000355675700005
PM 25231213
ER
PT J
AU Lee, D
Vandrey, R
Mendu, DR
Murray, JA
Barnes, AJ
Huestis, MA
AF Lee, Dayong
Vandrey, Ryan
Mendu, Damodara R.
Murray, Jeannie A.
Barnes, Allan J.
Huestis, Marilyn A.
TI Oral fluid cannabinoids in chronic frequent cannabis smokers during ad
libitum cannabis smoking
SO DRUG TESTING AND ANALYSIS
LA English
DT Article
DE cannabinoid; oral fluid; cannabis; delta-9-tetrahydrocannabinol
ID 2-DIMENSIONAL GAS-CHROMATOGRAPHY; RANDOMLY SELECTED DRIVERS;
SIMULTANEOUS QUANTIFICATION; PHARMACOKINETIC PROPERTIES;
MASS-SPECTROMETRY; DELTA(9)-TETRAHYDROCANNABINOL; MARIJUANA; PLASMA;
USERS; DRUGS
AB Oral fluid (OF) offers a simple, non-invasive, directly observable sample collection for clinical and forensic drug testing. Given that chronic cannabis smokers often engage in drug administration multiple times daily, evaluating OF cannabinoid pharmacokinetics during ad libitum smoking is important for practical development of analytical methods and informed interpretation of test results. Eleven cannabis smokers resided in a closed research unit for 51days, and underwent four, 5-day oral delta-9-tetrahydrocannabinol (THC) treatments. Each medication period was separated by 9days of ad libitum cannabis smoking from 12:00 to 23:00h daily. Ten OF samples were collected from 9:00-22:00h on each of the last ad libitum smoking days (Study Days 4, 18, 32, and 46). As the number of cannabis cigarettes smoked increased over the study days, OF THC, cannabinol (CBN), and 11-nor-9-carboxy-THC (THCCOOH) also increased with a significant effect of time since last smoking (time; range, 0.0-17.4h) and 88% detection rates; concentrations on Day 4 were significantly lower than those on Days 32 and 46 but not Day 18. Within 30min of smoking, median THC, CBN, and THCCOOH concentrations were 689 mu g/L, 116 mu g/L, and 147ng/L, respectively, decreasing to 19.4 mu g/L, 2.4 mu g/L, and 87.6ng/L after 10h. Cannabidiol and 11-hydroxy-THC showed overall lower detection rates of 29 and 8.6%, respectively. Cannabinoid disposition in OF was highly influenced by time and composition of smoked cannabis. Furthermore, cannabinoid OF concentrations increased over ad libitum smoking days, in parallel with increased cannabis self-administration, possibly reflecting development of increased cannabis tolerance. Copyright (c) 2014 John Wiley & Sons, Ltd.
C1 [Lee, Dayong; Mendu, Damodara R.; Barnes, Allan J.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Vandrey, Ryan; Murray, Jeannie A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab, IRP, NIH,Biomed Res Ctr, 251 Bayview Blvd,Suite 200,Room 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU National Institute on Drug Abuse [R01 DA025044]; National Institute on
Drug Abuse, NIH
FX This research was funded by grant R01 DA025044 from the National
Institute on Drug Abuse and by the Intramural Research Program, National
Institute on Drug Abuse, NIH. The funding sources had no role in study
design, data collection and analysis, or presentation of results. This
study was registered at clinicaltrials.gov (NCT00893074).
NR 35
TC 2
Z9 2
U1 2
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1942-7603
EI 1942-7611
J9 DRUG TEST ANAL
JI Drug Test. Anal.
PD JUN
PY 2015
VL 7
IS 6
BP 494
EP 501
DI 10.1002/dta.1718
PG 8
WC Biochemical Research Methods; Chemistry, Analytical; Pharmacology &
Pharmacy
SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy
GA CJ7LD
UT WOS:000355675700006
PM 25220020
ER
PT J
AU Walsh, NC
Waters, LR
Fowler, JA
Lin, M
Cunningham, CR
Brooks, DG
Rehg, JE
Morse, HC
Teitell, MA
AF Walsh, Nicole C.
Waters, Lynnea R.
Fowler, Jessica A.
Lin, Mark
Cunningham, Cameron R.
Brooks, David G.
Rehg, Jerold E.
Morse, Herbert C., III
Teitell, Michael A.
TI LKB1 inhibition of NF-kappa B in B cells prevents T follicular helper
cell differentiation and germinal center formation
SO EMBO REPORTS
LA English
DT Article
DE B cell; T-FH differentiation; germinal center; NF-kappa B
ID HEMATOPOIETIC STEM-CELLS; JEGHERS CANCER SYNDROME; TUMOR-SUPPRESSOR
LKB1; GENE-EXPRESSION; PROTEIN-KINASE; NUCLEAR-FACTOR; IMMUNE-SYSTEM;
ACTIVATION; BCL6; PHOSPHORYLATION
AB T-cell-dependent antigenic stimulation drives the differentiation of B cells into antibody-secreting plasma cells and memory B cells, but how B cells regulate this process is unclear. We show that LKB1 expression in B cells maintains B-cell quiescence and prevents the premature formation of germinal centers (GCs). Lkb1-deficient B cells (BKO) undergo spontaneous B-cell activation and secretion of multiple inflammatory cytokines, which leads to splenomegaly caused by an unexpected expansion of T cells. Within this cytokine response, increased IL-6 production results from heightened activation of NF-kappa B, which is suppressed by active LKB1. Secreted IL-6 drives T-cell activation and IL-21 production, promoting T follicular helper (T-FH) cell differentiation and expansion to support a similar to 100-fold increase in steady-state GC B cells. Blockade of IL-6 secretion by BKO B cells inhibits IL-21 expression, a known inducer of T-FH-cell differentiation and expansion. Together, these data reveal cell intrinsic and surprising cell extrinsic roles for LKB1 in B cells that control T-FH-cell differentiation and GC formation, and place LKB1 as a central regulator of T-cell-dependent humoral immunity.
C1 [Walsh, Nicole C.; Fowler, Jessica A.; Lin, Mark; Teitell, Michael A.] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90094 USA.
[Waters, Lynnea R.; Teitell, Michael A.] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA.
[Cunningham, Cameron R.; Brooks, David G.] Univ Calif Los Angeles, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90024 USA.
[Cunningham, Cameron R.; Brooks, David G.] Univ Calif Los Angeles, UCLA AIDS Inst, Los Angeles, CA 90024 USA.
[Rehg, Jerold E.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Morse, Herbert C., III] NIAID, Virol & Cellular Immunol Sect, Immunogenet Lab, NIH, Rockville, MD USA.
[Teitell, Michael A.] Univ Calif Los Angeles, Calif NanoSyst Inst, Dept Pediat, Broad Stem Cell Res Ctr, Los Angeles, CA USA.
[Teitell, Michael A.] Univ Calif Los Angeles, Calif NanoSyst Inst, Broad Stem Cell Res Ctr, Dept Bioengn, Los Angeles, CA USA.
[Teitell, Michael A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA USA.
RP Teitell, MA (reprint author), Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90094 USA.
EM mteitell@mednet.ucla.edu
FU NIH [T32CA009120, GM007185, CA90571, CA156674, GM073981, GM114188,
CA185189]; ACS grant [LIB-122716]; NIH Intramural Research program,
NIAID
FX We thank Tammy Phung, Steven Bensinger, and Laura Fahey (UCLA) for
assistance and feedback, and Jason Hong and Christopher Pang-Gonzalez
(UCLA) for animal colony assistance. FACS was performed at the Broad
Stem Cell Research Center FACS Facility and flow cytometry at the UCLA
IMED Flow Cytometry Core. This study was supported by NIH grants
T32CA009120 (N.C.W.), GM007185 (L.R.W.), CA90571, CA156674, GM073981,
GM114188, and CA185189 (M.A.T.), ACS grant LIB-122716 (J.A.F.), and the
NIH Intramural Research program, NIAID (H.C.M.).
NR 84
TC 4
Z9 4
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1469-221X
EI 1469-3178
J9 EMBO REP
JI EMBO Rep.
PD JUN
PY 2015
VL 16
IS 6
BP 753
EP 768
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CJ6MD
UT WOS:000355607000013
PM 25916856
ER
PT J
AU Kurbatova, EV
Dalton, T
Ershova, J
Tupasi, T
Caoili, JC
Van Der Walt, M
Kvasnovsky, C
Yagui, M
Bayona, J
Contreras, C
Leimane, V
Via, LE
Kim, H
Akksilp, S
Kazennyy, BY
Volchenkov, GV
Jou, R
Kliiman, K
Demikhova, OV
Cegielski, JP
AF Kurbatova, Ekaterina V.
Dalton, Tracy
Ershova, Julia
Tupasi, Thelma
Caoili, Janice Campos
Van Der Walt, Martie
Kvasnovsky, Charlotte
Yagui, Martin
Bayona, Jaime
Contreras, Carmen
Leimane, Vaira
Via, Laura E.
Kim, HeeJin
Akksilp, Somsak
Kazennyy, Boris Y.
Volchenkov, Grigory V.
Jou, Ruwen
Kliiman, Kai
Demikhova, Olga V.
Cegielski, J. Peter
TI Additional Drug Resistance of Multidrug-Resistant Tuberculosis in
Patients in 9 Countries
SO EMERGING INFECTIOUS DISEASES
LA English
DT Article
ID TREATMENT OUTCOMES; PNCA MUTATIONS; SURVEILLANCE; METAANALYSIS
AB Data from a large multicenter observational study of patients with multidrug-resistant tuberculosis (MDR TB) were analyzed to simulate the possible use of 2 new approaches to treatment of MDR TB: a short (9-month) regimen and a bedaquiline-containing regimen. Of 1,254 patients, 952 (75.9%) had no resistance to fluoroquinolones and second-line injectable drugs and thus would qualify as candidates for the 9-month regimen; 302 (24.1%) patients with resistance to a fluoroquinolone or second-line injectable drug would qualify as candidates for a bedaquiline-containing regimen in accordance with published guidelines. Among candidates for the 9-month regimen, standardized drug-susceptibility tests demonstrated susceptibility to a median of 5 (interquartile range 5-6) drugs. Among candidates for bedaquiline, drug-susceptibility tests demonstrated susceptibility to a median of 3 (interquartile range 2-4) drugs; 26% retained susceptibility to <= 2 drugs. These data may assist national TB programs in planning to implement new drugs and drug regimens.
C1 [Kurbatova, Ekaterina V.; Dalton, Tracy; Ershova, Julia; Caoili, Janice Campos; Kvasnovsky, Charlotte; Cegielski, J. Peter] Ctr Dis Control & Prevent, Atlanta, GA 30329 USA.
[Tupasi, Thelma; Caoili, Janice Campos] Trop Dis Fdn, Manila, Philippines.
[Van Der Walt, Martie; Kvasnovsky, Charlotte] MRC, Pretoria, South Africa.
[Yagui, Martin] Natl Inst Hlth, Lima, Peru.
[Bayona, Jaime; Contreras, Carmen] Socios Salud Sucursal Peru, Lima, Peru.
[Leimane, Vaira] Riga East Univ Hosp, Ctr TB & Lung Dis, Riga, Latvia.
[Via, Laura E.] NIAID, NIH, Bethesda, MD 20892 USA.
[Via, Laura E.] Univ Cape Town, ZA-7925 Cape Town, South Africa.
[Kim, HeeJin] Korean Inst TB, Seoul, South Korea.
[Akksilp, Somsak] Minist Publ Hlth, Bangkok, Thailand.
[Kazennyy, Boris Y.] Orel Oblast TB Dispensary, Oryol, Russia.
[Volchenkov, Grigory V.] Vladimir Oblast TB Dispensary, Vladimir, Russia.
[Jou, Ruwen] Taiwan Ctr Dis Control, Taipei, Taiwan.
[Kliiman, Kai] Tartu Univ Hosp, Tartu, Estonia.
[Demikhova, Olga V.] Russian Acad Med Sci, Moscow, Russia.
RP Kurbatova, EV (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd NE,Mailstop E10, Atlanta, GA 30329 USA.
EM ies3@cdc.gov
FU US Agency for International Development; CDC; National Institutes of
Health's National Institute of Allergy and Infectious Diseases, Division
of Intramural Research and South Korea's Center for Disease Control
FX This work was supported by the US Agency for International Development;
CDC; and, in part, by the National Institutes of Health's National
Institute of Allergy and Infectious Diseases, Division of Intramural
Research and South Korea's Center for Disease Control support of the
sites in South Korea.
NR 21
TC 6
Z9 6
U1 0
U2 6
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1080-6040
EI 1080-6059
J9 EMERG INFECT DIS
JI Emerg. Infect. Dis
PD JUN
PY 2015
VL 21
IS 6
BP 977
EP 983
DI 10.3201/eid2106.141329
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CJ3MA
UT WOS:000355386900007
PM 25988299
ER
PT J
AU Falzarano, D
Safronetz, D
Prescott, J
Marzi, A
Feldmann, F
Feldmann, H
AF Falzarano, Darryl
Safronetz, David
Prescott, Joseph
Marzi, Andrea
Feldmann, Friederike
Feldmann, Heinz
TI Lack of Protection Against Ebola Virus from Chloroquine in Mice and
Hamsters
SO EMERGING INFECTIOUS DISEASES
LA English
DT Article
ID HEMORRHAGIC-FEVER; CORONAVIRUS; INFECTION; DISEASE; MODEL
AB The antimalarial drug chloroquine has been suggested as a treatment for Ebola virus infection. Chloroquine inhibited virus replication in vitro, but only at cytotoxic concentrations. In mouse and hamster models, treatment did not improve survival. Chloroquine is not a promising treatment for Ebola. Efforts should be directed toward other drug classes.
C1 [Falzarano, Darryl; Safronetz, David; Prescott, Joseph; Marzi, Andrea; Feldmann, Friederike; Feldmann, Heinz] NIAID, Hamilton, MT USA.
RP Feldmann, H (reprint author), NIH, Virol Lab, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA.
EM feldmannh@niaid.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health.
NR 15
TC 6
Z9 6
U1 2
U2 7
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1080-6040
EI 1080-6059
J9 EMERG INFECT DIS
JI Emerg. Infect. Dis
PD JUN
PY 2015
VL 21
IS 6
BP 1065
EP 1067
DI 10.3201/eid2106.150176
PG 3
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CJ3MA
UT WOS:000355386900025
PM 25988934
ER
PT J
AU McShane, CM
Tapper, C
Murray, LJ
Landgren, O
Bradley, MC
Hughes, CM
Anderson, LA
AF McShane, Charlene M.
Tapper, Christopher
Murray, Liam J.
Landgren, Ola
Bradley, Marie C.
Hughes, Carmel M.
Anderson, Lesley A.
TI Oral statin use associated with reduced risk of monoclonal gammopathy of
undetermined significance and multiple myeloma: a population-based
nested case-control study
SO EUROPEAN JOURNAL OF CANCER CARE
LA English
DT Meeting Abstract
C1 [McShane, Charlene M.; Tapper, Christopher; Murray, Liam J.; Anderson, Lesley A.] Queens Univ Belfast, Ctr Publ Hlth, Belfast BT7 1NN, Antrim, North Ireland.
[Landgren, Ola] Mem Sloan Kettering Canc Ctr, New York, NY USA.
[Bradley, Marie C.] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA.
[Hughes, Carmel M.] Queens Univ Belfast, Sch Pharm, Belfast BT7 1NN, Antrim, North Ireland.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-5423
EI 1365-2354
J9 EUR J CANCER CARE
JI Eur. J. Cancer Care
PD JUN
PY 2015
VL 24
SU 1
SI SI
MA 0-01
BP 1
EP 1
DI 10.1111/ecc.12329
PG 1
WC Oncology; Health Care Sciences & Services; Nursing; Rehabilitation
SC Oncology; Health Care Sciences & Services; Nursing; Rehabilitation
GA CJ8FW
UT WOS:000355736600002
ER
PT J
AU Liu, Q
Li, ZZ
Gao, JL
Wan, WZ
Ganesan, S
McDermott, DH
Murphy, PM
AF Liu, Qian
Li, Zhanzhuo
Gao, Ji-Liang
Wan, Wuzhou
Ganesan, Sundar
McDermott, David H.
Murphy, Philip M.
TI CXCR4 antagonist AMD3100 redistributes leukocytes from primary immune
organs to secondary immune organs, lung, and blood in mice
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE AMD3100; CXCR4; Cell trafficking; Lymphoid organs; Leukocytes; Mouse
ID CHEMOKINE RECEPTOR CXCR4; HUMAN HEMATOPOIETIC STEM; REGULATORY T-CELLS;
BONE-MARROW; RAPID MOBILIZATION; WHIM SYNDROME; NEUTROPHIL MOBILIZATION;
STROMAL CELLS; PLERIXAFOR; EXPRESSION
AB AMD3100 (plerixafor), is a specific CXCR4 antagonist approved by the FDA for mobilizing hematopoietic stem cells from bone marrow to blood for transplantation in cancer. AMD3100 also mobilizes most mature leukocyte subsets to blood; however, their source and trafficking potential have not been fully delineated. Here, we show that a single injection of AMD3100 10 mg/kg into C57Bl/6 mice rapidly mobilizes (peak approximate to 2.5 h) the same leukocyte subsets to blood as in humans. Using this model, we found that AMD3100 mobilization of neutrophils, lymphocytes, and monocytes to blood is not reduced by splenectomy or by blockade of lymphocyte egress from lymph node with FTY720, but is coupled to (i) reduced content of each of these cell types in the bone marrow; (ii) reduced T-cell numbers in thymuses; (iii) increased lymphocytes in lymph nodes; and (iv) increased neutrophil and monocyte content in the lung. Direct intrathymic labeling showed that AMD3100 selectively mobilizes naive thymic CD4(+) and CD8(+) T cells to blood. Finally, AMD3100-induced neutrophil mobilization to blood did not reduce neutrophil trafficking to thioglycollate-inflamed peritoneum. Thus, AMD3100 redistributes lymphocytes, monocytes, and neutrophils from primary immune organs to secondary immune organs, peripheral tissues, and blood, without compromising neutrophil trafficking to inflamed sites.
C1 [Liu, Qian; Li, Zhanzhuo; Gao, Ji-Liang; Wan, Wuzhou; McDermott, David H.; Murphy, Philip M.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Ganesan, Sundar] NIAID, Res Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Murphy, PM (reprint author), NIAID, Lab Mol Immunol, NIH, Bldg 10,Room 11N113,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM pmm@nih.gov
OI McDermott, David/0000-0001-6978-0867
FU Division of Intramural Research of the National Institute of Allergy and
Infectious Diseases
FX This work was supported by the Division of Intramural Research of the
National Institute of Allergy and Infectious Diseases. We thank Dr.
Michail S. Lionakis and Dr. Estefania Claudio for providing us the lung
tissue digestion and perfusion protocol.
NR 51
TC 3
Z9 3
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
EI 1521-4141
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD JUN
PY 2015
VL 45
IS 6
BP 1855
EP 1867
DI 10.1002/eji.201445245
PG 13
WC Immunology
SC Immunology
GA CJ9QE
UT WOS:000355836500027
PM 25801950
ER
PT J
AU Hendershot, CS
Wardell, JD
Strang, NM
Markovich, MSD
Claus, ED
Ramchandani, VA
AF Hendershot, Christian S.
Wardell, Jeffrey D.
Strang, Nicole M.
Markovich, Mike S. D.
Claus, Eric D.
Ramchandani, Vijay A.
TI Application of an Alcohol Clamp Paradigm to Examine Inhibitory Control,
Subjective Responses, and Acute Tolerance in Late Adolescence
SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY
LA English
DT Article
DE adolescent; alcohol sensitivity; attention-deficit hyperactivity
disorder; impulsivity; intravenous alcohol
ID FAMILY-HISTORY; USE DISORDERS; INCREASED SENSITIVITY; HIGH-RISK;
DRINKING; IMPAIRMENT; MODEL; INTOXICATION; DEPENDENCE; DRINKERS
AB Individual differences in acute alcohol effects on cognitive control and subjective responses-and acute tolerance to these effects-are implicated in the risk for heavy drinking and alcohol-related harms. Few studies have examined these effects in drinkers under age 21. Additionally, studies of acute tolerance typically involve bolus oral alcohol administration, such that estimates of tolerance are confounded with blood alcohol concentration (BAC) limb. The current study examined cognitive control and subjective responses in young heavy drinkers (n = 88; M = 19.8 years old, SD = 0.8) during a single-session alcohol clamp protocol. Participants completed an intravenous alcohol session comprising an ascending limb (0 to 80 mg% in 20 min) and a BAC plateau (80 mg% for 80 min). Serial assessments included a cued go/no-go task and measures of stimulation, sedation, and craving. Relevant individual difference factors (attention-deficit hyperactivity disorder [ADHD] symptoms and sensation seeking) were examined as moderators. Multilevel modeling demonstrated that response inhibition worsened following initial rise in BAC and showed increasing impairment during the BAC plateau. ADHD symptoms and sensation seeking moderated this effect. Significant within-person associations between stimulation and craving were evident on the ascending limb only. Participants with higher ADHD symptoms reported steeper increases in stimulation during the ascending limb. These findings provide initial information about subjective and behavioral responses during pseudoconstant BAC, and potential moderators of these outcomes, in late adolescence. Additional studies with placebo-controlled designs are necessary to confirm these findings.
C1 [Hendershot, Christian S.; Wardell, Jeffrey D.; Strang, Nicole M.] Ctr Addict & Mental Hlth, Campbell Family Mental Hlth Res Inst, Toronto, ON M6J 1H4, Canada.
[Hendershot, Christian S.] Univ Toronto, Dept Psychiat, Toronto, ON M5S 1A1, Canada.
[Hendershot, Christian S.; Markovich, Mike S. D.] Univ Toronto, Dept Psychol, Toronto, ON M5S 1A1, Canada.
[Claus, Eric D.] Mind Res Network, Albuquerque, NM USA.
[Claus, Eric D.] Lovelace Biomed & Environm Res Inst, Albuquerque, NM USA.
[Ramchandani, Vijay A.] NIAAA, Sect Human Psychopharmacol, Lab Clin & Translat Studies, NIH, Bethesda, MD USA.
RP Hendershot, CS (reprint author), Ctr Addict & Mental Hlth, 100 Stokes St, Toronto, ON M6J 1H4, Canada.
EM christian.hendershot@utoronto.ca
RI Hendershot, Christian/C-1638-2009;
OI Hendershot, Christian/0000-0002-5328-2035
FU ABMRF/The Foundation for Alcohol Research; Canadian Institutes of Health
Research [260418, 288905/307742]; Ontario Mental Health Foundation;
Canada Foundation for Innovation; NIAAA Division of Intramural Clinical
and Biological Research; NIH [R21AA020304]; Indiana Alcohol Research
Center [NIH P60 AA007611]
FX This study was supported by a grant from ABMRF/The Foundation for
Alcohol Research (Christian S. Hendershot). The funding agency had no
role in the study other than financial support. The authors also
acknowledge support from the Canadian Institutes of Health Research
(Grants 260418, 288905/307742), the Ontario Mental Health Foundation,
and the Canada Foundation for Innovation (Christian S. Hendershot), the
NIAAA Division of Intramural Clinical and Biological Research (Vijay A.
Ramchandani), and NIH R21AA020304 (Eric D. Claus, Christian S.
Hendershot). The authors thank Sean O'Connor and Victor Vitvitskiy at
the Indiana Alcohol Research Center (NIH P60 AA007611) for software
support. The authors also express appreciation to Dr. Ariel Graff,
Vanessa Garofalo, and Matthew McPhee for their assistance with data
collection. All authors contributed significantly to the manuscript and
all authors have read and approved the final manuscript.
NR 64
TC 4
Z9 4
U1 1
U2 4
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 1064-1297
EI 1936-2293
J9 EXP CLIN PSYCHOPHARM
JI Exp. Clin. Psychopharmacol.
PD JUN
PY 2015
VL 23
IS 3
BP 147
EP 158
DI 10.1037/pha0000017
PG 12
WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy;
Psychiatry
SC Psychology; Pharmacology & Pharmacy; Psychiatry
GA CK1BK
UT WOS:000355940200002
PM 26053322
ER
PT J
AU Morgan, JT
Kwon, HS
Wood, JA
Borjesson, DL
Tomarev, SI
Murphy, CJ
Russell, P
AF Morgan, Joshua T.
Kwon, Heung Sun
Wood, Joshua A.
Borjesson, Dori L.
Tomarev, Stanislav I.
Murphy, Christopher J.
Russell, Paul
TI Thermally labile components of aqueous humor potently induce osteogenic
potential in adipose-derived mesenchymal stem cells
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE Aqueous humor; Mesenchymal stem cells; Osteogenic potential; Myocilin;
Alkaline phosphatase
ID HUMAN TRABECULAR MESHWORK; OPEN-ANGLE GLAUCOMA; TISSUE GROWTH-FACTOR;
THERAPY POSITION STATEMENT; UMBILICAL-CORD BLOOD; MATRIX GLA PROTEIN;
STROMAL CELLS; BONE-MARROW; INTERNATIONAL-SOCIETY; RAT CALVARIA
AB Adipose-derived mesenchymal stem cells (ASCs) hold promise for use in cell-based therapies. Their intrinsic anti-inflammatory properties are potentially useful for treatments of inflammatory conditions such as uveitis, while their ability to differentiate along multiple cell lineages suggests use in regenerating damaged or degenerated tissue. However, how ASCs will respond to the intraocular environment is poorly studied. We have recently reported that aqueous humor (AH), the fluid that nourishes the anterior segment of the eye, potently increases alkaline phosphatase (ALP) activity of ASCs, indicating osteogenic differentiation. Here, we expand on our previous findings to better define the nature of this response. To this end, we cultured ASCs in the presence of 0, 5, 10, and 20% AH and assayed them for ALP activity. We found ALP activity correlates with increasing AH concentrations from 5 to 20%, and that longer treatments result in increased ALP activity. By using serum free media and pretreating AH with dextran-coated charcoal, we found that serum and charcoal-adsorbable AH components augment but are not required for this response. Further, by heat-treating the AH, we established that thermally labile components are required for the osteogenic response. Finally, we showed myocilin, a protein present in AH, could induce ALP activity in ASCs. However, this was to a lesser extent than untreated 5% AH, and myocilin could only partially rescue the effect after heat treatment, documenting there were additional thermally labile constituents of AH involved in the osteogenic response. Our work adds to the understanding of the induction of ALP in ASCs following exposure to AH, providing important insight in how ASCs will be influenced by the ocular environment. In conclusion, increased osteogenic potential upon exposure to represents a potential challenge to developing ASC cell-based therapies directed at the eye. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Morgan, Joshua T.; Murphy, Christopher J.; Russell, Paul] Univ Calif Davis, Sch Vet Med, Dept Surg & Radiol Sci, Davis, CA 95616 USA.
[Kwon, Heung Sun; Tomarev, Stanislav I.] NEI, Sect Retinal Gangl Cell Biol, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Wood, Joshua A.; Borjesson, Dori L.] Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA.
[Murphy, Christopher J.] Univ Calif Davis, Sch Med, Dept Ophthalmol & Vis Sci, Davis, CA 95616 USA.
RP Russell, P (reprint author), Univ Calif Davis, Sch Vet Med, Dept Surg & Radiol Sci, 1 Shields Ave, Davis, CA 95616 USA.
EM prussell@ucdavis.edu
FU National Institutes of Health [R01EY019475, R01EY019970]; Research to
Prevent Blindness; Intramural Research Program of the National Eye
Institute, National Institutes of Health
FX This work was funded by grants from the National Institutes of Health
R01EY019475 and R01EY019970, and an unrestricted grant from Research to
Prevent Blindness, and the Intramural Research Program of the National
Eye Institute, National Institutes of Health.
NR 79
TC 1
Z9 1
U1 0
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD JUN
PY 2015
VL 135
BP 127
EP 133
DI 10.1016/j.exer.2015.02.018
PG 7
WC Ophthalmology
SC Ophthalmology
GA CJ8RC
UT WOS:000355770200014
PM 25720657
ER
PT J
AU Devine, K
Mumford, SL
Goldman, KN
Hodes-Wertz, B
Druckenmiller, S
Propst, AM
Noyes, N
AF Devine, Kate
Mumford, Sunni L.
Goldman, Kara N.
Hodes-Wertz, Brooke
Druckenmiller, Sarah
Propst, Anthony M.
Noyes, Nicole
TI Baby budgeting: oocyte cryopreservation in women delaying reproduction
can reduce cost per live birth
SO FERTILITY AND STERILITY
LA English
DT Article; Proceedings Paper
CT 68th Annual Meeting of the American-Society-for-Reproductive-Medicine
(ASRM)
CY OCT 20-24, 2012
CL San Diego, CA
SP Amer Soc Reprod Med
DE Oocyte cryopreservation; vitrification; fertility preservation; cost
analysis; ART
ID ASSISTED REPRODUCTION; DECISION-ANALYSIS; AGE; FERTILITY; VITRIFICATION;
EFFICIENCY; FRESH; SPAN
AB Objective: To determine whether oocyte cryopreservation for deferred reproduction is cost effective per live birth using a model constructed from observed clinical practice.
Design: Decision-tree mathematical model with sensitivity analyses.
Setting: Not applicable.
Patient(s): A simulated cohort of women wishing to delay childbearing until age 40 years.
Intervention(s): Not applicable.
Main Outcome Measure(s): Cost per live birth.
Result(s): Our primary model predicted that oocyte cryopreservation at age 35 years by women planning to defer pregnancy attempts until age 40 years would decrease cost per live birth from $ 55,060 to $ 39,946 (and increase the odds of live birth from 42% to 62% by the end of the model), indicating that oocyte cryopreservation is a cost-effective strategy relative to forgoing it. If fresh autologous assisted reproductive technology (ART) was added at age 40 years, before thawing oocytes, 74% obtained a live birth, and cost per live birth increased to $ 61,887. Separate sensitivity analyses demonstrated that oocyte cryopreservation remained cost effective as long as performed before age 38 years, and more than 49% of those women not obtaining a spontaneously conceived live birth returned to thaw oocytes.
Conclusion(s): In women who plan to delay childbearing until age 40 years, oocyte cryopreservation before 38 years of age reduces the cost to obtain a live birth. (C) 2015 by American Society for Reproductive Medicine.
C1 [Devine, Kate] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Mumford, Sunni L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD USA.
[Goldman, Kara N.; Hodes-Wertz, Brooke; Druckenmiller, Sarah; Noyes, Nicole] NYU, Sch Med, New York, NY USA.
[Propst, Anthony M.] Texas Fertil Ctr, Austin, TX USA.
RP Devine, K (reprint author), 10 Ctr Dr,MSC 1109,Room 1-3140, Bethesda, MD 20892 USA.
EM kate.devine@nih.gov
OI Goldman, Kara/0000-0002-5455-627X; Hodes-Wertz,
Brooke/0000-0001-8766-6216
FU Intramural NIH HHS [Z99 HD999999]
NR 30
TC 11
Z9 11
U1 2
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD JUN
PY 2015
VL 103
IS 6
BP 1446
EP U105
DI 10.1016/j.fertnstert.2015.02.029
PG 10
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA CJ5TM
UT WOS:000355552600016
PM 25813281
ER
PT J
AU Devine, K
Connell, MT
Richter, KS
Ramirez, CI
Levens, ED
DeCherney, AH
Stillman, RJ
Widra, EA
AF Devine, Kate
Connell, Matthew T.
Richter, Kevin S.
Ramirez, Christina I.
Levens, Eric D.
DeCherney, Alan H.
Stillman, Robert J.
Widra, Eric A.
TI Single vitrified blastocyst transfer maximizes liveborn children per
embryo while minimizing preterm birth
SO FERTILITY AND STERILITY
LA English
DT Article; Proceedings Paper
CT International-Federation-of-Fertility-Societies 21st World Congress on
Fertility and Sterility / 69th Annual Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 12-17, 2013
CL Boston, MA
SP Int Federat Fertil Soc, Amer Soc Reprod Med
DE Frozen embryo transfer; low birth weight; preterm birth; single embryo
transfer; vitrification
ID IN-VITRO FERTILIZATION; ASSISTED REPRODUCTIVE TECHNOLOGY; ELECTIVE
SINGLE; INFERTILITY TRIAL; UNITED-STATES; CRYOPRESERVATION; CYCLES;
WEIGHT; WOMEN; RATES
AB Objective: To compare live-birth rates, blastocyst to live-birth efficiency, gestational age, and birth weights in a large cohort of patients undergoing single versus double thawed blastocyst transfer.
Design: Retrospective cohort study.
Setting: Assisted reproduction technology (ART) practice.
Patient(s): All autologous frozen blastocyst transfers (FBT) of one or two vitrified-warmed blastocysts from January 2009 through April 2012.
Intervention(s): Single or double FBT.
Main Outcome Measure(s): Live birth, blastocyst to live-birth efficiency, preterm birth, low birth weight.
Result(s): Only supernumerary blastocysts with good morphology (grade BB or better) were vitrified, and 1,696 FBTs were analyzed. No differences were observed in patient age, rate of embryo progression, or postthaw blastomere survival. Double FBT yielded a higher live birth per transfer, but 33% of births from double FBT were twins versus only 0.6% of single FBT. Double FBT was associated with statistically significant increases in preterm birth and low birth weight, the latter of which was statistically significant even when the analysis was limited to singletons. Of the blastocysts transferred via single FBT, 38% resulted in a liveborn child versus only 34% with double FBT. This suggests that two single FBTs would result in more liveborn children with significantly fewer preterm births when compared with double FBT.
Conclusion(s): Single FBT greatly decreased multiple and preterm birth risk while providing excellent live-birth rates. Patients should be counseled that a greater overall number of live born children per couple can be expected when thawed blastocysts are transferred one at a time. (C) 2015 by American Society for Reproductive Medicine.
C1 [Devine, Kate; Connell, Matthew T.; DeCherney, Alan H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Rockville, MD USA.
[Devine, Kate; Richter, Kevin S.; Levens, Eric D.; Stillman, Robert J.; Widra, Eric A.] Shady Grove Fertil Reprod Sci Ctr, Washington, DC USA.
[Devine, Kate; Richter, Kevin S.; Levens, Eric D.; Stillman, Robert J.; Widra, Eric A.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA.
[Ramirez, Christina I.] Walter Reed Natl Mil Med Ctr, Dept Obstet & Gynecol, Bethesda, MD USA.
RP Devine, K (reprint author), Shady Grove Fertil, 2021 K St NW 701, Washington, DC 20006 USA.
EM kate.devine@nih.gov
FU Intramural NIH HHS [Z99 HD999999]
NR 40
TC 8
Z9 8
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD JUN
PY 2015
VL 103
IS 6
BP 1454
EP U113
DI 10.1016/j.fertnstert.2015.02.032
PG 8
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA CJ5TM
UT WOS:000355552600017
PM 25813283
ER
PT J
AU Louis, GMB
Druschel, C
Bell, E
Stern, JE
Luke, B
McLain, A
Sundaram, R
Yeung, E
AF Louis, Germaine M. Buck
Druschel, Charlotte
Bell, Erin
Stern, Judy E.
Luke, Barbara
McLain, Alexander
Sundaram, Rajeshwari
Yeung, Edwina
TI Use of assisted reproductive technology treatment as reported by mothers
in comparison with registry data: the Upstate KIDS Study
SO FERTILITY AND STERILITY
LA English
DT Article
DE Assisted reproductive technologies; infertility; maternal report;
sensitivity; validity
ID IN-VITRO FERTILIZATION; ASSESSMENT MONITORING-SYSTEM; BIRTH CERTIFICATE;
INFERTILITY TREATMENT; PERINATAL OUTCOMES; MASSACHUSETTS; COHORT;
METAANALYSIS; INFORMATION; CONCEPTION
AB Objective: To assess the validity of maternally reported assisted reproductive technologies (ART) use and to identify predictors of reporting errors.
Design: Linkage study.
Setting: Not applicable.
Patient(s): A total of 5,034 (27%) mothers enrolled, from whom 4,886 (97%) self-reported information about use of infertility treatment, including ART, for the index birth.
Intervention(s): None.
Main Outcome Measure(s): Four measures of validity (sensitivity, specificity, positive and negative predictive values) and use of net reclassification improvement (NRI) methods to identify predictors associated with concordant/discordant maternal reporting.
Result(s): The Upstate New York Infant Development Screening Program (Update KIDS Study) was linked with the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) using a defined algorithmfor 2008-2010. The sensitivity, specificity, positive and negative predictive values were high (0.93, 0.99, 0.80, and 1.00, respectively). The validity of maternal report was high, reflecting few differences by participant characteristics except for maternal age dichotomized at 29 years as identified with NRI methods.
Conclusion(s): Maternally reported ART is valid, with little variation across various characteristics. No strong predictors of discordant reporting were found, supporting the utility of population-based research with SART CORS linkage. (C) 2015 by American Society for Reproductive Medicine.
C1 [Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Rockville, MD 20852 USA.
[Druschel, Charlotte] SUNY Albany, New York State Dept Hlth, Albany, NY 12222 USA.
[Bell, Erin] SUNY Albany, Dept Environm Hlth Sci & Epidemiol, Albany, NY 12222 USA.
[Stern, Judy E.] Geisel Sch Med Dartmouth, Dept Obstet & Gynecol, Hanover, NH USA.
[Luke, Barbara] Michigan State Univ, Dept Obstet Gynecol & Reprod Biol, E Lansing, MI 48824 USA.
[McLain, Alexander] Univ S Carolina, Dept Epidemiol & Biostat, Columbia, SC 29208 USA.
[Sundaram, Rajeshwari] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Biostat & Bioinformat Branch, Rockville, MD 20852 USA.
[Yeung, Edwina] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Epidemiol Branch, Rockville, MD 20852 USA.
RP Louis, GMB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA.
EM louisg@mail.nih.gov
OI Yeung, Edwina/0000-0002-3851-2613; Sundaram,
Rajeshwari/0000-0002-6918-5002; Buck Louis, Germaine/0000-0002-1774-4490
FU National Institutes of Health [R01HD064595, R01HD067270, R01CA151973];
American Society for Reproductive Medicine; Society for Assisted
Reproductive Technology; Intramural Research Program, Eunice Kennedy
Shriver National Institute of Child Health and Human Development,
National Institutes of Health (NICHD) [HHSN267200700019C,
HHSN275201200005C]
FX G.M.B.L. has nothing to disclose. C.D. has nothing to disclose. E.B. has
nothing to disclose. J.E.S. has received grants from the National
Institutes of Health (R01HD064595 and R01HD067270) and the American
Society for Reproductive Medicine outside the submitted work. B.L. has
received personal fees from the Society for Assisted Reproductive
Technology and grants from the National Institutes of Health
(R01CA151973, R01HD064595, and R01HD067270) outside the submitted work.
A.M. has nothing to disclose. R.S. has nothing to disclose. E.Y. has
nothing to disclose.; Supported by the Intramural Research Program,
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health (NICHD contracts
HHSN267200700019C; HHSN275201200005C).
NR 24
TC 5
Z9 5
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD JUN
PY 2015
VL 103
IS 6
BP 1461
EP 1468
DI 10.1016/j.fertnstert.2015.02.033
PG 8
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA CJ5TM
UT WOS:000355552600018
ER
PT J
AU Hill, MJ
Royster, GD
Healy, MW
Richter, KS
Levy, G
DeCherney, AH
Levens, ED
Suthar, G
Widra, E
Levy, MJ
AF Hill, Micah J.
Royster, Greene Donald
Healy, Mae Wu
Richter, Kevin S.
Levy, Gary
DeCherney, Alan H.
Levens, Eric D.
Suthar, Geeta
Widra, Eric
Levy, Michael J.
TI Are good patient and embryo characteristics protective against the
negative effect of elevated progesterone level on the day of oocyte
maturation?
SO FERTILITY AND STERILITY
LA English
DT Article
DE Elevated progesterone; premature luteinization; implantation; IVF
ID IN-VITRO FERTILIZATION; HUMAN CHORIONIC-GONADOTROPIN; INTRACYTOPLASMIC
SPERM INJECTION; FOLLICLE-STIMULATING-HORMONE; PREMATURE LUTEINIZATION;
OVARIAN STIMULATION; SERUM PROGESTERONE; PREGNANCY RATES; ENDOMETRIAL
RECEPTIVITY; LIVE BIRTH
AB Objective: To evaluate if an elevated progesterone (P) level on the day of human chorionic gonadotropin (hCG) administration is associated with a decrease in live-birth rate in patients with a good prognosis.
Design: Retrospective cohort study.
Setting: Large, private, assisted reproductive technology (ART) practice.
Patient(s): One thousand six hundred twenty fresh autologous ART cycles.
Intervention(s): None.
Main Outcome Measure(s): Live-birth rate.
Result(s): A total of 934 blastocyst and 686 cleavage-stage embryo transfer (ET) cycles were evaluated. Serum P levels were not associated with markers of oocyte or embryo quality, including fertilization, embryo stage at transfer, and embryos available for cryopreservation. Patient age, stage of ET, embryo quality, the number of embryos transferred, and P level on the day of hCG administration were all significantly associated with live birth. Higher P levels were associated with decreased odds of live birth for cleavage- and blastocyst-stage embryos, poor-fair and good-quality embryos, and poor-and high-responder patients. The nonsignificance of interaction tests of P levels with embryo stage, embryo quality, patient age, and ovarian response indicated that the relationship between P level and live birth was similar regardless of these factors.
Conclusion(s): An elevated serum P level on the day of hCG administration was negatively associated with live birth, even in ETs with a good prognosis. (C) 2015 by American Society for Reproductive Medicine.
C1 [Hill, Micah J.; Royster, Greene Donald; Healy, Mae Wu; Richter, Kevin S.; Levy, Gary; Levens, Eric D.; Suthar, Geeta; Widra, Eric; Levy, Michael J.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA.
[Hill, Micah J.; Royster, Greene Donald; Healy, Mae Wu; Levy, Gary; DeCherney, Alan H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
RP Hill, MJ (reprint author), 10 Ctr Dr, Bethesda, MD 20876 USA.
EM hillmicah@mail.nih.gov
FU Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver
National Institute of Child Health and Human Development, National
Institutes of Health, Bethesda, Maryland
FX Supported, in part, by the Intramural Research Program of the Program in
Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, Bethesda, Maryland.
NR 32
TC 12
Z9 13
U1 1
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD JUN
PY 2015
VL 103
IS 6
BP 1477
EP U145
DI 10.1016/j.fertnstert.2015.02.038
PG 13
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA CJ5TM
UT WOS:000355552600020
PM 25881880
ER
PT J
AU Bolnick, JM
Kilburn, BA
Bolnick, AD
Diamond, MP
Singh, M
Hertz, M
Dai, J
Armant, DR
AF Bolnick, Jay M.
Kilburn, Brian A.
Bolnick, Alan D.
Diamond, Michael P.
Singh, Manvinder
Hertz, Michael
Dai, Jing
Armant, D. Randall
TI Sildenafil stimulates human trophoblast invasion through nitric oxide
and guanosine 3 ',5 '-cyclic monophosphate signaling
SO FERTILITY AND STERILITY
LA English
DT Article
DE Trophoblast invasion; phosphodiesterase-5 inhibitor; nitric oxide;
guanosine 3 ',5 '-cyclic monophosphate; integrins
ID ENDOTHELIAL PROGENITOR CELLS; IN-VITRO; PREECLAMPTIC PREGNANCIES;
PLACENTAL ISCHEMIA; TYROSINE KINASE-1; GROWTH-FACTOR; CYCLIC-GMP; HLA-G;
EXPRESSION; INHIBITOR
AB Objective: To determine the effect of sildenafil, a phosphodiesterase type 5 inhibitor, on trophoblast invasiveness.
Design: Laboratory investigation.
Setting: Academic medical center.
Patient(s): Placental tissues discarded after first-trimester terminations were obtained from patients with informed consent.
Intervention(s): A cell line, HTR-8/SVneo, established from first-trimester cytotrophoblast, and villous explants, was treated with or without sildenafil, guanosine 3',5'-cyclic monophosphate (cGMP) analog, cGMP inhibitor, or L-NAME (N-G-nitro-L-arginine methyl ester hydrochloride) and cultured on fibronectin or Matrigel. Integrins alpha 6 beta 4 and alpha 1 beta 1 were detected by immunocytochemistry.
Main Outcome Measure(s): Trophoblast outgrowth from villous tips, cytotrophoblast cell invasion, and integrin immunostaining were assessed in cytotrophoblast and explant cultures.
Result(s): Integrin expression in trophoblast cells ex vivo switched from alpha 6 to alpha 1, and invasiveness increased, when exposed to sildenafil or cGMP agonist. Either cGMP antagonist or L-NAME blocked integrin switching and invasion induced by sildenafil. Elevation of nitric oxide pharmacologically induced invasion, but not when cGMP antagonist was present.
Conclusion(s): Sildenafil altered trophoblast phenotype through a process dependent on nitric oxide availability and cGMP accumulation. In addition to its vasoactivity, sildenafil directly stimulates trophoblast extravillous differentiation, which would be favorable for implantation and reduce risk for adverse pregnancy outcomes. (C) 2015 by American Society for Reproductive Medicine.
C1 [Bolnick, Jay M.; Kilburn, Brian A.; Bolnick, Alan D.; Singh, Manvinder; Hertz, Michael; Dai, Jing; Armant, D. Randall] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Diamond, Michael P.] Georgia Regents Univ, Dept Obstet & Gynecol, Augusta, GA USA.
[Armant, D. Randall] Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48201 USA.
[Armant, D. Randall] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
RP Armant, DR (reprint author), Wayne State Univ, Mott Ctr Human Growth & Dev, 275 East Hancock St, Detroit, MI 48201 USA.
EM D.Armant@Wayne.edu
OI Diamond, Michael/0000-0001-6353-4489; Armant, D.
Randall/0000-0001-5904-9325
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institutes of Health [HD071408]; W.K. Kellogg
Foundation
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, National Institutes of Health grant HD071408, and the
W.K. Kellogg Foundation.
NR 58
TC 2
Z9 3
U1 1
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD JUN
PY 2015
VL 103
IS 6
BP 1587
EP U285
DI 10.1016/j.fertnstert.2015.02.025
PG 11
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA CJ5TM
UT WOS:000355552600034
PM 25813289
ER
PT J
AU Basudhar, D
Cheng, RC
Bharadwaj, G
Ridnour, LA
Wink, DA
Miranda, KM
AF Basudhar, Debashree
Cheng, Robert C.
Bharadwaj, Gaurav
Ridnour, Lisa A.
Wink, David A.
Miranda, Katrina M.
TI Chemotherapeutic potential of diazeniumdiolate-based aspirin prodrugs in
breast cancer
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Nitroxyl; Nitric oxide; NONOate; Diazeniumdiolate; IPA/NO; DEA/NO;
NSAID; Aspirin; Anti-inflammatory; Anticancer
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NITRIC-OXIDE SYNTHASE;
TRIOXODINITRATE ANGELIS SALT; DETERRENT AGENT CYANAMIDE; TUMOR
ANGIOGENESIS; POLY(ADP-RIBOSE) POLYMERASE; NITROXYL HNO; IN-VIVO; SODIUM
TRIOXODINITRATE; POOR SURVIVAL
AB Diazeniumdiolate-based aspirin prodrugs have previously been shown to retain the anti-inflammatory properties of aspirin while protecting against the common side effect of stomach ulceration. Initial analysis of two new prodrugs of aspirin that also release either nitroxyl (HNO) or nitric oxide (NO) demonstrated increased cytotoxicity toward human lung carcinoma cells compared to either aspirin or the parent nitrogen oxide donor. In addition, cytotoxicity was significantly lower in endothelial cells, suggesting cancer-specific sensitivity. To assess the chemotherapeutic potential of these new prodrugs in treatment of breast cancer, we studied their effect both in cultured cells and in a nude mouse model. Both prodrugs reduced growth of breast adenocarcinoma cells more effectively than the parent compounds while not being appreciably cytotoxic in a related nontumorigenic cell line (MCF-10A). The HNO donor also was more cytotoxic than the related NO donor. The basis for the observed specificity was investigated in terms of impact on metabolism, DNA damage and repair, apoptosis, angiogenesis and metastasis. The results suggest a significant pharmacological potential for treatment of breast cancer. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Basudhar, Debashree; Bharadwaj, Gaurav; Miranda, Katrina M.] Univ Arizona, Dept Chem & Biochem, Tucson, AZ 85721 USA.
[Cheng, Robert C.; Ridnour, Lisa A.; Wink, David A.] NIH, Radiat Biol Branch, Bethesda, MD 20892 USA.
RP Miranda, KM (reprint author), Univ Arizona, Dept Chem & Biochem, Tucson, AZ 85721 USA.
EM kmiranda@email.arizona.edu
FU National Institutes of Health [R01-GM076247]; Intramural Research
Program of the National Institutes of Health, National Cancer Institute;
Center for Cancer Research
FX This work is supported in part by a National Institutes of Health grant
(R01-GM076247 to K.M.M.) and the Intramural Research Program of the
National Institutes of Health, National Cancer Institute and Center for
Cancer Research (D.A.W.).
NR 148
TC 3
Z9 3
U1 2
U2 17
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 JUN
PY 2015
VL 83
BP 101
EP 114
DI 10.1016/j.freeradbiomed.2015.01.029
PG 14
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA CJ6BI
UT WOS:000355577600010
PM 25659932
ER
PT J
AU van 't Erve, TJ
Lih, FB
Kadiiska, MB
Deterding, LJ
Eling, TE
Mason, RP
AF van 't Erve, Thomas J.
Lih, Fred B.
Kadiiska, Maria B.
Deterding, Leesa J.
Eling, Thomas E.
Mason, Ronald P.
TI Reinterpreting the best biomarker of oxidative stress: The 8-iso-PGF(2
alpha)/PGF(2 alpha), ratio distinguishes chemical from enzymatic lipid
peroxidation
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE F-2-isoprostanes; Oxidative stress; Inflammation; Biomarkers; Lipid
peroxidation
ID 8-EPI-PROSTAGLANDIN F-2 ALPHA; IN-VIVO; ENDOTHELIAL EXPRESSION;
ISCHEMIA-REPERFUSION; DEPENDENT FORMATION; MASS-SPECTROMETRY;
GENERATION; INJURY; F-2-ISOPROSTANES; ISOPROSTANE
AB The biomarker 8-iso-prostaglandin F-2 alpha (8-iso-PGF(2 alpha)) is regarded as the gold standard for detection of excessive chemical lipid peroxidation in humans. However, biosynthesis of 8-iso-PGF(2 alpha) via enzymatic lipid peroxidation by prostaglandin-endoperoxide synthases (PGHSs), which are significantly induced in inflammation, could lead to incorrect biomarker interpretation. To resolve the ambiguity with this biomarker, the ratio of 8-iso-PGF(2 alpha) to prostaglandin F-2 alpha (PGF(2 alpha)) is established as a quantitative measure to distinguish enzymatic from chemical lipid peroxidation in vitro, in animal models, and in humans. Using this method, we find that chemical lipid peroxidation contributes only 3% to the total 8-iso-PGF(2 alpha) in the plasma of rats. In contrast, the 8-iso-PGF(2 alpha) levels in plasma of human males are generated > 99% by chemical lipid peroxidation. This establishes the potential for an alternate pathway of biomarker synthesis, and draws into question the source of increases in 8-iso-PGF(2 alpha) seen in many human diseases. In conclusion, increases in 8-iso-PGF(2 alpha) do not necessarily reflect increases in oxidative stress: therefore, past studies using 8-iso-PGF(2 alpha) as a marker of oxidative stress may have been misinterpreted. The 8-isoPGF(2 alpha)/PGF(2 alpha) ratio can be used to distinguish biomarker synthesis pathways and thus confirm the potential change in oxidative stress in the myriad of disease and chemical exposures known to induce 8-iso-PGFF(2 alpha). Published by Elsevier Inc.
C1 [van 't Erve, Thomas J.; Kadiiska, Maria B.; Mason, Ronald P.] NIEHS, Immun Inflammat & Dis Lab, Res Triangle Pk, NC 27709 USA.
[Lih, Fred B.; Deterding, Leesa J.] NIEHS, Epigenet & Stem Cell Biol Lab, Res Triangle Pk, NC 27709 USA.
[Eling, Thomas E.] NIEHS, Emeritus, Res Triangle Pk, NC 27709 USA.
RP van 't Erve, TJ (reprint author), NIEHS, Immun Inflammat & Dis Lab, POB 12233, Res Triangle Pk, NC 27709 USA.
EM thomas.vanterve@nih.gov
OI van 't Erve, Thomas/0000-0002-3260-6627
FU National Institutes of Health; National Institute of Environmental
Health Sciences
FX The authors gratefully acknowledge Dr. Jason Williams and Dr. Stephanie
London for their review of this manuscript and Sandra Chambers for the
literature search. We thank the staff of the NIEHS Clinical Research
Unit for their help in obtaining human plasma samples. We thank Jean
Corbett, Dr. Ann Motten, and Mary Mason for their editorial expertise.
This work was supported by the Intramural Research Program of the
National Institutes of Health and the National Institute of
Environmental Health Sciences.
NR 31
TC 10
Z9 10
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
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD JUN
PY 2015
VL 83
BP 245
EP 251
DI 10.1016/j.freeradbiomed.2015.03.004
PG 7
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA CJ6BI
UT WOS:000355577600024
PM 25772010
ER
PT J
AU Chang, CQ
Tingle, SR
Filipski, KK
Khoury, MJ
Lam, TK
Schully, SD
Ioannidis, JPA
AF Chang, Christine Q.
Tingle, Sharna R.
Filipski, Kelly K.
Khoury, Muin J.
Lam, Tram Kim
Schully, Sheri D.
Ioannidis, John P. A.
TI An overview of recommendations and translational milestones for genomic
tests in cancer
SO GENETICS IN MEDICINE
LA English
DT Review
DE cancer; genomics; genetic testing; recommendations and guidelines;
translational research
ID PERSONALIZED MEDICINE; PROGNOSTIC MARKERS
AB Purpose: To understand the translational trajectory of genomic tests in cancer screening, diagnosis, prognosis, and treatment, we reviewed tests that have been assessed by recommendation and guideline developers.
Methods: For each test, we marked translational milestones by determining when the genomic association with cancer was first discovered and studied in patients, and when a health application for a specified clinical use was successfully demonstrated and approved or cleared by the US Food and Drug Administration. To identify recommendations and guidelines, we reviewed the websites of cancer, genomic, and general guideline developers and professional organizations. We searched the in vitro diagnostics database of the US Food and Drug Administration for information, and we searched PubMed for translational milestones. Milestones were examined against type of recommendation, Food and Drug Administration approval or clearance, disease rarity, and test purpose.
Results: Of the 45 tests we identified, 9 received strong recommendations for their usage in clinical settings, 14 received positive but moderate recommendations, and 22 were not currently recommended. For 18 tests, two or more different sources had issued recommendations, with 67% concordance. Only five tests had Food and Drug Administration approval, and an additional five had clearance. The median time from discovery to recommendation statement was 14.7 years.
Conclusion: In general, there were no associations found between translational trajectory and recommendation category.
C1 [Chang, Christine Q.; Tingle, Sharna R.; Filipski, Kelly K.; Khoury, Muin J.; Lam, Tram Kim; Schully, Sheri D.; Ioannidis, John P. A.] NCI, Epidemiol & Genom Res Program, Rockville, MD 20852 USA.
[Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Gen, Atlanta, GA USA.
[Ioannidis, John P. A.] Stanford Univ, Stanford Prevent Res Ctr, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Ioannidis, John P. A.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Ioannidis, John P. A.] Stanford Univ, Sch Humanities & Sci, Dept Stat, Stanford, CA 94305 USA.
RP Chang, CQ (reprint author), NCI, Epidemiol & Genom Res Program, Rockville, MD 20852 USA.
EM christine.chang2@nih.gov
OI Chang, Christine/0000-0002-4624-898X
FU Intramural CDC HHS [CC999999]
NR 30
TC 1
Z9 1
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
EI 1530-0366
J9 GENET MED
JI Genet. Med.
PD JUN
PY 2015
VL 17
IS 6
BP 431
EP 440
DI 10.1038/gim.2014.133
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA CJ5WS
UT WOS:000355564200001
PM 25341115
ER
PT J
AU Wang, Y
Liu, G
Caggana, M
Kennedy, J
Zimmerman, R
Oyeku, SO
Werner, EM
Grant, AM
Green, NS
Grosse, SD
AF Wang, Ying
Liu, Gang
Caggana, Michele
Kennedy, Joseph
Zimmerman, Regina
Oyeku, Suzette O.
Werner, Ellen M.
Grant, Althea M.
Green, Nancy S.
Grosse, Scott D.
TI Mortality of New York children with sickle cell disease identified
through newborn screening
SO GENETICS IN MEDICINE
LA English
DT Article
DE long-term follow-up; maternal race/ethnicity; mortality; newborn
screening; sickle cell disease
ID TERM-FOLLOW-UP; UNITED-STATES; BIRTH OUTCOMES; 1ST DECADE; ANEMIA;
HYDROXYUREA; LIFE; US; ADOLESCENTS; DISORDERS
AB Purpose: Long-term follow-up of newborn screening for conditions such as sickle cell disease can be conducted using linkages to population-based data. We sought to estimate childhood sickle cell disease mortality and risk factors among a statewide birth cohort with sickle cell disease identified through newborn screening.
Methods: Children with sickle cell disease identified by newborn screening and born to New York residents in 2000-2008 were matched to birth and death certificates. Mortality rates were calculated (using numbers of deaths and observed person-years at risk) and compared with mortality rates for all New York children by maternal race/ethnicity. Stratified analyses were conducted to examine associations between selected factors and mortality.
Results: Among 1,911 infants with sickle cell disease matched to birth certificates, 21 deaths were identified. All-cause mortality following diagnosis was 3.8 per 1,000 person-years in the first 2 years of life and 1.0 per 1,000 person-years at ages 2-9 years. The mortality rate was significantly lower among children of foreign-born mothers and was significantly higher among preterm infants with low birth weight. The mortality rates were not significantly higher for infants after 28 days with sickle cell disease than for all New York births, but they were 2.7-8.4 times higher for children 1 through 9 years old with homozygous sickle cell disease than for those of all non-Hispanic black or Hispanic children born to New York residents.
Conclusion: Estimated mortality risk in children with homozygous sickle cell disease remains elevated even after adjustment for maternal race/ethnicity. These results provide evidence regarding the current burden of child mortality among children with sickle cell disease despite newborn screening.
C1 [Wang, Ying; Liu, Gang; Caggana, Michele] SUNY Albany, Sch Publ Hlth, Albany, NY 12222 USA.
[Wang, Ying] New York State Dept Hlth, Div Data Management & Res, Off Primary Care & Hlth Management Syst, Albany, NY USA.
[Caggana, Michele] New York State Dept Hlth, Wadsworth Ctr, Newborn Screening Program, Albany, NY USA.
[Zimmerman, Regina] New York City Dept Hlth & Mental Hyg, Off Vital Stat, New York, NY USA.
[Oyeku, Suzette O.] Childrens Hosp Montefiore, Albert Einstein Coll Med, Dept Pediat, New York, NY USA.
[Werner, Ellen M.] NHLBI, Div Blood Dis & Resources, Bethesda, MD 20892 USA.
[Grant, Althea M.; Grosse, Scott D.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Div Blood Disorders, Atlanta, GA USA.
[Green, Nancy S.] Columbia Univ, Med Ctr, Dept Pediat, New York, NY USA.
RP Wang, Y (reprint author), SUNY Albany, Sch Publ Hlth, Albany, NY 12222 USA.
EM wxy01@health.state.ny.us
OI Green, Nancy/0000-0002-9877-1561
FU US Centers for Disease Control and Prevention; National Heart, Lung and
Blood Institute [U50DD000722]
FX This project was supported by the US Centers for Disease Control and
Prevention and the National Heart, Lung and Blood Institute (grant
U50DD000722). The findings and conclusions in this report are those of
the authors and do not necessarily represent the official position of
the Centers for Disease Control and Prevention.
NR 40
TC 2
Z9 3
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
EI 1530-0366
J9 GENET MED
JI Genet. Med.
PD JUN
PY 2015
VL 17
IS 6
BP 452
EP 459
DI 10.1038/gim.2014.123
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA CJ5WS
UT WOS:000355564200004
PM 25255366
ER
PT J
AU Butrick, M
Kelly, S
Peshkin, BN
Luta, G
Nusbaum, R
Hooker, GW
Graves, K
Feeley, L
Isaacs, C
Valdimarsdottir, HB
Jandorf, L
DeMarco, T
Wood, M
McKinnon, W
Garber, J
McCormick, SR
Schwartz, MD
AF Butrick, Morgan
Kelly, Scott
Peshkin, Beth N.
Luta, George
Nusbaum, Rachel
Hooker, Gillian W.
Graves, Kristi
Feeley, Lisa
Isaacs, Claudine
Valdimarsdottir, Heiddis B.
Jandorf, Lina
DeMarco, Tiffani
Wood, Marie
McKinnon, Wendy
Garber, Judy
McCormick, Shelley R.
Schwartz, Marc D.
TI Disparities in uptake of BRCA1/2 genetic testing in a randomized trial
of telephone counseling
SO GENETICS IN MEDICINE
LA English
DT Article
DE cancer; genetic counseling; genetic testing; psychosocial predictors;
telephone counseling
ID BREAST-CANCER SUSCEPTIBILITY; HEREDITARY BREAST; OVARIAN-CANCER;
RACIAL-DIFFERENCES; HIGH-RISK; WOMEN; COMMUNICATION; VALIDATION;
QUALITY; PATIENT
AB Purpose: As genetic counseling and testing become more fully integrated into clinical care, alternative delivery models are increasingly prominent. This study examines predictors of genetic testing for hereditary breast/ovarian cancer among high-risk women in a randomized trial of in-person versus telephone-based genetic counseling.
Methods: Methods include multivariable logistic regression and interaction analyses.
Results: Of the 669 participants, 600 completed counseling and 523 received test results. As previously reported, participants randomized to telephone counseling were significantly less likely to be tested. In intention-to-treat analyses, completion of counseling and testing was associated with: race/ethnicity (odds ratio (OR) = 1.96, 95% confidence interval (CI): 1.20-3.20), perceived stress (OR = 0.89, 95% CI: 0.81-0.98), knowledge (OR = 1.12, 95% CI: 1.02-1.23), and randomization group (OR = 1.48, 95% CI: 1.01-2.16). Further, race/ ethnicity moderated the association between randomization group and testing; minority women receiving telephone counseling were least likely to complete testing.
Conclusion: Evidence for logistical and communication-based explanations for this interaction is presented. The overall increased access made possible with telephone genetic counseling should be considered in light of the possibility that this may also lead to lower rates of testing among high-risk minority women. Additional care should be taken to assess and address potential barriers when services are delivered by telephone.
C1 [Butrick, Morgan] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Kelly, Scott; Peshkin, Beth N.; Nusbaum, Rachel; Graves, Kristi; Feeley, Lisa; Isaacs, Claudine; DeMarco, Tiffani; Schwartz, Marc D.] Georgetown Univ, Dept Oncol, Canc Prevent & Control Program, Washington, DC 20057 USA.
[Kelly, Scott; Peshkin, Beth N.; Nusbaum, Rachel; Graves, Kristi; Feeley, Lisa; Isaacs, Claudine; DeMarco, Tiffani; Schwartz, Marc D.] Georgetown Univ, Fisher Ctr Familial Canc Res, Lombardi Comprehens Canc Ctr, Washington, DC USA.
[Luta, George] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Biostat Bioinformat & Biomath, Washington, DC USA.
[Hooker, Gillian W.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
[Valdimarsdottir, Heiddis B.; Jandorf, Lina] Icahn Sch Med Mt Sinai, Dept Oncol Sci, New York, NY 10029 USA.
[Wood, Marie; McKinnon, Wendy] Univ Vermont, Coll Med, Vermont Canc Ctr, Familial Canc Program, Burlington, VT USA.
[Garber, Judy; McCormick, Shelley R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Genet & Prevent, Boston, MA 02115 USA.
RP Schwartz, MD (reprint author), Georgetown Univ, Dept Oncol, Canc Prevent & Control Program, Washington, DC 20057 USA.
EM schwartm@georgetown.edu
RI Kelly, Scott/D-3195-2013;
OI Kelly, Scott/0000-0002-0375-1040; Luta, George/0000-0001-9013-2207;
Luta, George/0000-0002-4035-7632
FU National Cancer Institute [R01 CA108933, P30 CA051008]; Jess and Mildred
Fisher Center for Familial Cancer Research
FX Grant support was received from the National Cancer Institute (grants
R01 CA108933 and P30 CA051008) and the Jess and Mildred Fisher Center
for Familial Cancer Research. The content is solely the responsibility
of the authors and does not necessarily represent the official views of
the National Cancer Institute or the National Institutes of Health.
NR 40
TC 9
Z9 9
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
EI 1530-0366
J9 GENET MED
JI Genet. Med.
PD JUN
PY 2015
VL 17
IS 6
BP 467
EP 475
DI 10.1038/gim.2014.125
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA CJ5WS
UT WOS:000355564200006
PM 25232856
ER
PT J
AU Stavreva, DA
Coulon, A
Baek, S
Sung, MH
John, S
Stixova, L
Tesikova, M
Hakim, O
Miranda, T
Hawkins, M
Stamatoyannopoulos, JA
Chow, CC
Hager, GL
AF Stavreva, Diana A.
Coulon, Antoine
Baek, Songjoon
Sung, Myong-Hee
John, Sam
Stixova, Lenka
Tesikova, Martina
Hakim, Ofir
Miranda, Tina
Hawkins, Mary
Stamatoyannopoulos, John A.
Chow, Carson C.
Hager, Gordon L.
TI Dynamics of chromatin accessibility and long-range interactions in
response to glucocorticoid pulsing
SO GENOME RESEARCH
LA English
DT Article
ID NEUTRAL LIPID DROPLETS; DNASE-I; HYPERSENSITIVE SITES; REGULATORY
ELEMENTS; GLOBIN CHROMATIN; RECEPTOR BINDING; CHIP-SEQ; TRANSCRIPTION;
STRESS; CELLS
AB Although physiological steroid levels are often pulsatile (ultradian), the genomic effects of this pulsatility are poorly understood. By utilizing glucocorticoid receptor (GR) signaling as a model system, we uncovered striking spatiotemporal relationships between receptor loading, lifetimes of the DNase I hypersensitivity sites (DHSs), long-range interactions, and gene regulation. We found that hormone-induced DHSs were enriched within +/- 50 kb of GR-responsive genes and displayed a broad spectrum of lifetimes upon hormone withdrawal. These lifetimes dictate the strength of the DHS interactions with gene targets and contribute to gene regulation from a distance. Our results demonstrate that pulsatile and constant hormone stimulations induce unique, treatment-specific patterns of gene and regulatory element activation. These modes of activation have implications for corticosteroid function in vivo and for steroid therapies in various clinical settings.
C1 [Stavreva, Diana A.; Baek, Songjoon; Sung, Myong-Hee; Miranda, Tina; Hawkins, Mary; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
[Coulon, Antoine; Chow, Carson C.] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
[John, Sam] NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA.
[Stixova, Lenka] Acad Sci Czech Republic, Inst Biophys, Dept Mol Cytol & Cytometry, Brno 61265, Czech Republic.
[Tesikova, Martina] Univ Oslo, Dept Biosci, N-0316 Oslo, Norway.
[Hakim, Ofir] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-5290002 Ramat Gan, Israel.
[Stamatoyannopoulos, John A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
EM stavrevd@mail.nih.gov; hagerg@exchange.nih.gov
RI Coulon, Antoine/A-9006-2012
FU Center for Cancer Research; National Institute of Diabetes and Digestive
and Kidney Diseases; federal funds from the National Cancer Institute,
National Institutes of Health [HHSN261200800001E]; OPVK project
[CZ.1.07/2.3.00/30.0030]; National Institutes of Health; National Cancer
Institute
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, National Cancer Institute, Center
for Cancer Research, and National Institute of Diabetes and Digestive
and Kidney Diseases. This project was also funded in whole or in part
with federal funds from the National Cancer Institute, National
Institutes of Health, under contract no. HHSN261200800001E. The content
of this publication does not necessarily reflect the views or policies
of the Department of Health and Human Services, nor does mention of
trade names, commercial products, or organizations imply endorsement by
the U.S. Government. We acknowledge the assistance of Tatiana Karpova,
LRBGE Fluorescence Imaging Facility. The work of L.S. was supported by
OPVK project CZ.1.07/2.3.00/30.0030.
NR 55
TC 13
Z9 13
U1 1
U2 8
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1088-9051
EI 1549-5469
J9 GENOME RES
JI Genome Res.
PD JUN
PY 2015
VL 25
IS 6
BP 845
EP 857
DI 10.1101/gr.184168.114
PG 13
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA CJ5XF
UT WOS:000355565900007
PM 25677181
ER
PT J
AU Kim, J
Park, HS
Damiano, DL
AF Kim, Jonghyun
Park, Hyung-Soon
Damiano, Diane L.
TI An Interactive Treadmill Under a Novel Control Scheme for Simulating
Overground Walking by Reducing Anomalous Force
SO IEEE-ASME TRANSACTIONS ON MECHATRONICS
LA English
DT Article
DE Anomalous force (AF); locomotor training; rehabilitation; simulating
overground walking (OW); treadmill control
ID GAIT REHABILITATION; SPEED; INJURY; STROKE; SYSTEM
AB Since the purpose of treadmill-based locomotor training is to transfer lower extremity coordinative skill to overground walking (OW), it needs to simulate OW as closely as possible for optimal skill transfer. Typical treadmill walking at a preset constant speed is different from realistic overground walking because it is less engaging and more automatic. As a remedy for the limitation, this paper investigates a novel treadmill control scheme that allows users to change walking speed freely. It further simulates natural walking by reducing anomalous force (AF) due to acceleration of the treadmill belt. Adding an attenuator in the scheme effectively diminishes the AF when changing walking speed. The proposed scheme, which requires real-time measurement of pelvic and swing foot motion, was developed for a treadmill with a typical belt length (1.5 m). A clinical test was conducted with nine healthy subjects in order to quantitatively evaluate the proposed scheme by comparing it with the two existing control schemes in the literature.
C1 [Kim, Jonghyun; Park, Hyung-Soon] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA.
[Damiano, Diane L.] NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Park, HS (reprint author), Korea Adv Inst Sci & Technol, Dept Mech Engn, Taejon 305701, South Korea.
EM jhkim@dgist.ac.kr; hyungspark@kaist.ac.kr; damianod@cc.nih.gov
RI Park, Hyung-Soon/B-3334-2010; Damiano, Diane/B-3338-2010
OI Park, Hyung-Soon/0000-0003-4274-7420; Damiano, Diane/0000-0002-2770-5356
FU National Institutes of Health, Clinical Center [90-CC-0168]; DGIST R&D
Program of the Ministry of Education, Science, and Technology of Korea
[11-BD-0402]
FX This work was supported in part by the intramural research program of
the National Institutes of Health, Clinical Center (protocol number
90-CC-0168) and in part by the DGIST R&D Program of the Ministry of
Education, Science, and Technology of Korea (11-BD-0402). (Corresponding
author: Hyung-Soon Park.)
NR 21
TC 2
Z9 2
U1 0
U2 4
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 1083-4435
EI 1941-014X
J9 IEEE-ASME T MECH
JI IEEE-ASME Trans. Mechatron.
PD JUN
PY 2015
VL 20
IS 3
BP 1491
EP 1496
DI 10.1109/TMECH.2014.2341039
PG 6
WC Automation & Control Systems; Engineering, Manufacturing; Engineering,
Electrical & Electronic; Engineering, Mechanical
SC Automation & Control Systems; Engineering
GA CJ3VT
UT WOS:000355413000047
ER
PT J
AU Burke, JG
Lich, KH
Neal, JW
Meissner, HI
Yonas, M
Mabry, PL
AF Burke, Jessica G.
Lich, Kristen Hassmiller
Neal, Jennifer Watling
Meissner, Helen I.
Yonas, Michael
Mabry, Patricia L.
TI Enhancing Dissemination and Implementation Research Using Systems
Science Methods
SO INTERNATIONAL JOURNAL OF BEHAVIORAL MEDICINE
LA English
DT Article
DE Dissemination; Implementation; Systems science; System dynamics;
Agent-based modeling; Network analysis
ID NETWORK ANALYSIS; PUBLIC-HEALTH; SIMULATION; MODEL; INTERVENTIONS;
POLICY
AB Dissemination and implementation (D&I) research seeks to understand and overcome barriers to adoption of behavioral interventions that address complex problems, specifically interventions that arise from multiple interacting influences crossing socio-ecological levels. It is often difficult for research to accurately represent and address the complexities of the real world, and traditional methodological approaches are generally inadequate for this task. Systems science methods, expressly designed to study complex systems, can be effectively employed for an improved understanding about dissemination and implementation of evidence-based interventions.
The aims of this study were to understand the complex factors influencing successful D&I of programs in community settings and to identify D&I challenges imposed by system complexity.
Case examples of three systems science methods-system dynamics modeling, agent-based modeling, and network analysis-are used to illustrate how each method can be used to address D&I challenges.
The case studies feature relevant behavioral topical areas: chronic disease prevention, community violence prevention, and educational intervention. To emphasize consistency with D&I priorities, the discussion of the value of each method is framed around the elements of the established Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework.
Systems science methods can help researchers, public health decision makers, and program implementers to understand the complex factors influencing successful D&I of programs in community settings and to identify D&I challenges imposed by system complexity.
C1 [Burke, Jessica G.; Yonas, Michael] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Lich, Kristen Hassmiller] Univ N Carolina, Chapel Hill, NC 27599 USA.
[Neal, Jennifer Watling] Michigan State Univ, E Lansing, MI 48824 USA.
[Meissner, Helen I.] NIH, Off Dis Prevent, Bethesda, MD 20892 USA.
[Mabry, Patricia L.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
RP Burke, JG (reprint author), Univ Pittsburgh, Pittsburgh, PA 15260 USA.
EM jgburke@pitt.edu; klich@unc.edu; jneal@msu.edu; meissneh@mail.nih.gov;
myonas24@gmail.com; mabryp@od.nih.gov
FU National Institute Of General Medical Sciences of the National
Institutes of Health [U54 GM088491]
FX Diane R. Orenstein, we would like to recognize and sincerely thank you
for your help conceptualizing the manuscript and for the feedback on
multiple drafts. We would also like to acknowledge and thank the
following people for their contributions to the projects presented: John
Grefenstette, Richard Garland, Shawn Brown, Jeffrey Borrebach, and
Donald Burke (agent-based modeling) and Patricia Farrell, Marvin
McKinney, Giannina Fehler-Cabral, Patrick Janulis, Gabriela Saenz, and
staff at the five PAS elementary schools (network analysis). The agent
based modeling research reported in this publication was supported by
the National Institute Of General Medical Sciences of the National
Institutes of Health under Award Number U54 GM088491.
NR 39
TC 7
Z9 7
U1 6
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1070-5503
EI 1532-7558
J9 INT J BEHAV MED
JI Int. J. Behav. Med.
PD JUN
PY 2015
VL 22
IS 3
SI SI
BP 283
EP 291
DI 10.1007/s12529-014-9417-3
PG 9
WC Psychology, Clinical
SC Psychology
GA CJ2UR
UT WOS:000355340700002
PM 24852184
ER
PT J
AU Hu, YZ
Salmeron, BJ
Gu, H
Stein, EA
Yang, YH
AF Hu, Yuzheng
Salmeron, Betty Jo
Gu, Hong
Stein, Elliot A.
Yang, Yihong
TI Impaired Functional Connectivity Within and Between Frontostriatal
Circuits and Its Association With Compulsive Drug Use and Trait
Impulsivity in Cocaine Addiction
SO JAMA PSYCHIATRY
LA English
DT Article
ID ANTERIOR CINGULATE CORTEX; DORSAL STRIATUM; PREFRONTAL CORTEX;
DECISION-MAKING; BASAL GANGLIA; SEEKING; DEPENDENCE; DISORDER;
HYPOACTIVITY; PERFORMANCE
AB IMPORTANCE Converging evidence has long identified both impulsivity and compulsivity as key psychological constructs in drug addiction. Although dysregulated striatal-cortical network interactions have been identified in cocaine addiction, the association between these brain networks and addiction is poorly understood.
OBJECTIVES To test the hypothesis that cocaine addiction is associated with disturbances in striatal-cortical communication as captured by resting-state functional connectivity (rsFC), measured from coherent spontaneous fluctuations in the blood oxygenation level-dependent functional magnetic resonance imaging signal, and to explore the relationships between striatal rsFC, trait impulsivity, and uncontrolled drug use in cocaine addiction.
DESIGN, SETTING, AND PARTICIPANTS A case-control, cross-sectional study was conducted at the National Institute on Drug Abuse Intramural Research Program outpatient magnetic resonance imaging facility. Data used in the present study were collected between December 8, 2005, and September 30, 2011. Participants included 56 non-treatment-seeking cocaine users (CUs) (52 with cocaine dependence and 3 with cocaine abuse) and 56 healthy individuals serving as controls (HCs) matched on age, sex, years of education, race, estimated intelligence, and smoking status.
MAIN OUTCOMES AND MEASURES Voxelwise statistical parametric analysis testing the rsFC strength differences between CUs and HCs in brain regions functionally connected to 6 striatal subregions defined a priori. RESULTS Increased rsFC strength was observed predominantly in striatal-frontal circuits; decreased rsFC was found between the striatum and cingulate, striatal, temporal, hippocampal/amygdalar, and insular regions in the CU group compared with the HCs. Increased striatal-dorsal lateral prefrontal cortex connectivity strength was positively correlated with the amount of recent cocaine use (uncorrected P < .046) and elevated trait impulsivity in the CUs (uncorrected P < .012), and an index reflecting the balance between striatal-dorsal anterior cingulate cortex and striatal-anterior prefrontal/orbitofrontal cortex circuits was significantly associated with loss of control over cocaine use (corrected P < .012).
CONCLUSIONS AND RELEVANCE Cocaine addiction is associated with disturbed rsFC in several specific striatal-cortical circuits. Specifically, compulsive cocaine use, a defining characteristic of dependence, was associated with a balance of increased striatal-anterior prefrontal/orbitofrontal and decreased striatal-dorsal anterior cingulate connectivity; trait impulsivity, both a risk factor for and a consequence of cocaine use, was associated with increased dorsal striatal-dorsal lateral prefrontal cortex connectivity uniquely in CUs. These findings provide new insights toward the neurobiological mechanisms of addiction and suggest potential novel therapeutic targets for treatment.
C1 [Hu, Yuzheng; Salmeron, Betty Jo; Gu, Hong; Stein, Elliot A.; Yang, Yihong] NIDA, Neuroimaging Res Branch, Intramural Res Program, Baltimore, MD 21224 USA.
RP Yang, YH (reprint author), NIDA, Neuroimaging Res Branch, Intramural Res Program, 251 Bayview Blvd,Ste 200, Baltimore, MD 21224 USA.
EM yihongyang@intra.nida.nih.gov
RI Salmeron, Betty Jo/M-1793-2016
OI Salmeron, Betty Jo/0000-0003-1699-9333
FU Intramural Research Program of the National Institute on Drug Abuse
FX This work was supported by the Intramural Research Program of the
National Institute on Drug Abuse.
NR 63
TC 20
Z9 21
U1 2
U2 6
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-622X
EI 2168-6238
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD JUN
PY 2015
VL 72
IS 6
BP 584
EP 592
DI 10.1001/jamapsychiatry.2015.1
PG 9
WC Psychiatry
SC Psychiatry
GA CJ9FH
UT WOS:000355807400009
PM 25853901
ER
PT J
AU Olfson, M
King, M
Schoenbaum, M
AF Olfson, Mark
King, Marissa
Schoenbaum, Michael
TI The Popularity of Benzodiazepines, Their Advantages, and Inadequate
Pharmacological Alternatives Reply
SO JAMA PSYCHIATRY
LA English
DT Letter
ID METAANALYSIS
C1 [Olfson, Mark] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA.
[Olfson, Mark] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[King, Marissa] Yale Univ, Sch Management, New Haven, CT USA.
[Schoenbaum, Michael] NIMH, Off Director, NIH, Bethesda, MD 20892 USA.
RP Olfson, M (reprint author), Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York State Psychiat Inst, 1051 Riverside Dr, New York, NY 10027 USA.
EM mo49@columbia.edu
NR 6
TC 0
Z9 0
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-622X
EI 2168-6238
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD JUN
PY 2015
VL 72
IS 6
BP 624
EP 624
DI 10.1001/jamapsychiatry.2015.24
PG 1
WC Psychiatry
SC Psychiatry
GA CJ9FH
UT WOS:000355807400017
PM 25830609
ER
PT J
AU Strickland, M
Stephens, T
Liu, J
Tjandra, N
AF Strickland, Madeleine
Stephens, Thomas
Liu, Jian
Tjandra, Nico
TI Exploiting image registration for automated resonance assignment in NMR
SO JOURNAL OF BIOMOLECULAR NMR
LA English
DT Article
DE Automation; Backbone assignment; Fast Fourier transform;
Cross-correlation; FFT
ID NOE ASSIGNMENT; BACKBONE RESONANCES; BINDING DOMAIN; PROTEIN;
SPECTROSCOPY; SPECTRA; ALGORITHM; N-15; C-13; H-1
AB Analysis of protein NMR data involves the assignment of resonance peaks in a number of multidimensional data sets. To establish resonance assignment a three-dimensional search is used to match a pair of common variables, such as chemical shifts of the same spin system, in different NMR spectra. We show that by displaying the variables to be compared in two-dimensional plots the process can be simplified. Moreover, by utilizing a fast Fourier transform cross-correlation algorithm, more common to the field of image registration or pattern matching, we can automate this process. Here, we use sequential NMR backbone assignment as an example to show that the combination of correlation plots and segmented pattern matching establishes fast backbone assignment in fifteen proteins of varying sizes. For example, the 265-residue RalBP1 protein was 95.4 % correctly assigned in 10 s. The same concept can be applied to any multidimensional NMR data set where analysis comprises the comparison of two variables. This modular and robust approach offers high efficiency with excellent computational scalability and could be easily incorporated into existing assignment software.
C1 [Strickland, Madeleine; Stephens, Thomas; Liu, Jian; Tjandra, Nico] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
RP Tjandra, N (reprint author), NHLBI, Lab Mol Biophys, NIH, Bldg 50,Room 3503, Bethesda, MD 20892 USA.
EM tjandran@nhlbi.nih.gov
OI Strickland, Madeleine/0000-0001-8160-070X
FU NIH, National Heart, Lung, and Blood Institute
FX This work was supported by the Intramural Research Program of the NIH,
National Heart, Lung, and Blood Institute. Our software is available
free of charge by contacting Nico Tjandra (tjandran@nhlbi.nih.gov).
NR 43
TC 0
Z9 0
U1 1
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0925-2738
EI 1573-5001
J9 J BIOMOL NMR
JI J. Biomol. NMR
PD JUN
PY 2015
VL 62
IS 2
BP 143
EP 156
DI 10.1007/s10858-015-9926-7
PG 14
WC Biochemistry & Molecular Biology; Spectroscopy
SC Biochemistry & Molecular Biology; Spectroscopy
GA CJ6TM
UT WOS:000355626800003
PM 25828257
ER
PT J
AU Wu, P
Bandettini, PA
Harper, RM
Handwerker, DA
AF Wu, Paula
Bandettini, Peter A.
Harper, Ronald M.
Handwerker, Daniel A.
TI Effects of thoracic pressure changes on MRI signals in the brain
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Article
DE breath hold; cerebral blood flow; functional MRI; hypercapnia; Valsalva
ID VALSALVA MANEUVER; FUNCTIONAL MRI; BLOOD-VOLUME; BOLD FMRI; CORTEX;
TASK; NORMALIZATION; VARIABILITY; HYPERCAPNIA; METABOLISM
AB Cerebrovascular stressors, such as breath holding or CO2 inhalation, cause global magnetic resonance imaging (MRI) signal changes. In this study, we show that intrathoracic pressure changes cause rapid MRI signal alterations that have similar spatial patterns to the changes associated with breath holding or CO2 inhalation. Nine subjects performed the Valsalva maneuver during functional MRI data collection. Expiratory pressures ranged from 10 to 40 mm Hg. Breath holds ending on either inhalation or exhalation were also collected. The maximal and minimal functional MRI (fMRI) signal scaled with thoracic pressure load, and the overall amplitude of responses to the Valsalva varied, depending on brain tissue. Additionally, a Valsalva effort as short as 5 seconds yielded signal changes similar in spatial distribution and magnitude to a 20-second breath hold, suggesting potential applications of the Valsalva maneuver for calibrated fMRI experiments.
C1 [Wu, Paula; Bandettini, Peter A.; Handwerker, Daniel A.] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20814 USA.
[Bandettini, Peter A.] NIMH, Funct MRI Facil, Bethesda, MD 20814 USA.
[Harper, Ronald M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA.
[Harper, Ronald M.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA.
RP Handwerker, DA (reprint author), NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, 10 Ctr Dr,Room 1D80,MSC1148, Bethesda, MD 20814 USA.
EM handwerkerd@mail.nih.gov
FU NIMH at NIH [ZIAMH002783]
FX This research was supported by the NIMH Intramural Research Program at
NIH: ZIAMH002783. The study was approved under NIH Combined Neuroscience
Institutional Review Board protocol #93-M-0170 (ClinicalTrials.gov
identifier: NCT00001360).
NR 26
TC 3
Z9 3
U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
EI 1559-7016
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD JUN
PY 2015
VL 35
IS 6
BP 1024
EP 1032
DI 10.1038/jcbfm.2015.20
PG 9
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA CJ6AO
UT WOS:000355575600017
PM 25712496
ER
PT J
AU Wilson, RP
Ives, ML
Rao, G
Lau, A
Payne, K
Kobayashi, M
Arkwright, PD
Peake, J
Wong, M
Adelstein, S
Smart, JM
French, MA
Fulcher, DA
Picard, C
Bustamante, J
Boisson-Dupuis, S
Gray, P
Stepensky, P
Warnatz, K
Freeman, AF
Rossjohn, J
McCluskey, J
Holland, SM
Casanova, JL
Uzel, G
Ma, CS
Tangye, SG
Deenick, EK
AF Wilson, Robert P.
Ives, Megan L.
Rao, Geetha
Lau, Anthony
Payne, Kathryn
Kobayashi, Masao
Arkwright, Peter D.
Peake, Jane
Wong, Melanie
Adelstein, Stephen
Smart, Joanne M.
French, Martyn A.
Fulcher, David A.
Picard, Capucine
Bustamante, Jacinta
Boisson-Dupuis, Stephanie
Gray, Paul
Stepensky, Polina
Warnatz, Klaus
Freeman, Alexandra F.
Rossjohn, Jamie
McCluskey, James
Holland, Steven M.
Casanova, Jean-Laurent
Uzel, Gulbu
Ma, Cindy S.
Tangye, Stuart G.
Deenick, Elissa K.
TI STAT3 is a critical cell-intrinsic regulator of human unconventional T
cell numbers and function
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID HYPER-IGE SYNDROME; ROR-GAMMA-T; EFFECTOR FUNCTIONS; CLINICAL-FEATURES;
MAIT CELLS; MUTATIONS; DOMINANT; RECEPTOR; DIFFERENTIATION; DEFICIENCY
AB Unconventional T cells such as gamma delta T cells, natural killer T cells (NKT cells) and mucosal-associated invariant T cells (MAIT cells) are a major component of the immune system; however, the cytokine signaling pathways that control their development and function in humans are unknown. Primary immunodeficiencies caused by single gene mutations provide a unique opportunity to investigate the role of specific molecules in regulating human lymphocyte development and function. We found that individuals with loss-of-function mutations in STAT3 had reduced numbers of peripheral blood MAIT and NKT but not gamma delta T cells. Analysis of STAT3 mosaic individuals revealed that this effect was cell intrinsic. Surprisingly, the residual STAT3-deficient MAIT cells expressed normal levels of the transcription factor ROR gamma t. Despite this, they displayed a deficiency in secretion of IL-17A and IL-17F, but were able to secrete normal levels of cytokines such as IFN gamma and TNF The deficiency in MAIT and NKT cells in STAT3-deficient patients was mirrored by loss-of-function mutations in IL12RB1 and IL21R, respectively. Thus, these results reveal for the first time the essential role of STAT3 signaling downstream of IL-23R and IL-21R in controlling human MAIT and NKT cell numbers.
C1 [Wilson, Robert P.; Lau, Anthony] Univ Bath, Bath BA2 7AY, Avon, England.
[Wilson, Robert P.; Ives, Megan L.; Rao, Geetha; Lau, Anthony; Payne, Kathryn; Ma, Cindy S.; Tangye, Stuart G.; Deenick, Elissa K.] Garvan Inst Med Res, Immunol Div, Sydney, NSW 2010, Australia.
[Ives, Megan L.; Ma, Cindy S.; Tangye, Stuart G.; Deenick, Elissa K.] Univ New S Wales, St Vincents Clin Sch, Sydney, NSW 2052, Australia.
[Gray, Paul] Univ New S Wales, Sch Womens & Childrens Hlth, Sydney, NSW 2052, Australia.
[Kobayashi, Masao] Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Pediat, Hiroshima 7398511, Japan.
[Arkwright, Peter D.] Univ Manchester, Royal Manchester Childrens Hosp, Manchester M13 9WL, Lancs, England.
[Peake, Jane] Royal Childrens Hosp, Dept Paediat & Child Hlth, Brisbane, Qld 4006, Australia.
[Wong, Melanie] Childrens Hosp, Dept Allergy & Immunol, Westmead, NSW 2145, Australia.
[Adelstein, Stephen] Royal Prince Alfred Hosp, Dept Clin Immunol, Camperdown, NSW 2050, Australia.
[Smart, Joanne M.] Royal Childrens Hosp Melbourne, Dept Allergy & Immunol, Parkville, Vic 3052, Australia.
[French, Martyn A.] Royal Perth Hosp, Dept Clin Immunol, Perth, WA 6000, Australia.
[French, Martyn A.] Univ Western Australia, Sch Pathol & Lab Med, Crawley, WA 6009, Australia.
[Fulcher, David A.] Westmead Hosp, Inst Clin Pathol & Med Res, Dept Immunol, Westmead, NSW 2006, Australia.
[Picard, Capucine; Bustamante, Jacinta; Boisson-Dupuis, Stephanie; Casanova, Jean-Laurent] Necker Hosp Sick Children, Lab Human Genet Infect Dis, Necker Branch, French Inst Hlth & Med Res INSERM,U1163, F-75015 Paris, France.
[Casanova, Jean-Laurent] Necker Hosp Sick Children, Pediat Hematol & Immunol Unit, F-75015 Paris, France.
[Picard, Capucine; Bustamante, Jacinta] Hop Necker Enfants Malad, AP HP, Study Ctr Primary Immunodeficiencies, F-75015 Paris, France.
[Picard, Capucine; Bustamante, Jacinta; Casanova, Jean-Laurent] Paris Descartes Univ, Imagine Inst, F-75015 Paris, France.
[Boisson-Dupuis, Stephanie; Casanova, Jean-Laurent] Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, New York, NY 10065 USA.
[Stepensky, Polina] Hebrew Univ Jerusalem, Med Ctr, Hadassah Med Ctr, Dept Pediat Hematol Oncol & Bone Marrow, IL-91120 Jerusalem, Israel.
[Warnatz, Klaus] Univ Freiburg, Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, D-79106 Freiburg, Germany.
[Freeman, Alexandra F.; Holland, Steven M.; Uzel, Gulbu] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Rossjohn, Jamie] Monash Univ, Sch Biomed Sci, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia.
[Rossjohn, Jamie] Monash Univ, Ctr Excellence Adv Mol Imaging, Australian Res Council ARC, Clayton, Vic 3800, Australia.
[Rossjohn, Jamie] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF14 4XN, S Glam, Wales.
[McCluskey, James] Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Melbourne, Vic 3000, Australia.
[Casanova, Jean-Laurent] Howard Hughes Med Inst, New York, NY 10065 USA.
RP Deenick, EK (reprint author), Garvan Inst Med Res, Immunol Div, Sydney, NSW 2010, Australia.
EM s.tangye@garvan.org.au; e.deenick@garvan.org.au
RI Peake, Jane/B-4488-2011; Adelstein, Stephen/I-7936-2016; McCluskey,
James/A-1291-2007
OI Deenick, Elissa/0000-0002-9271-0004; Lau, Anthony/0000-0002-7338-7176;
Arkwright, Peter/0000-0002-7411-5375; Rossjohn,
Jamie/0000-0002-2020-7522; Adelstein, Stephen/0000-0001-7221-6298;
McCluskey, James/0000-0002-8597-815X
FU National Health and Medical Research Council (NHMRC) of Australia
[1016953, 1066694, 1027400]; Rockefeller University Center for 541
Clinical and Translational Science [5UL1RR024143]; Career Development
Fellowship [1008820]; NHMRC of Australia [1042925]
FX This work was funded by project and program grants from the National
Health and Medical Research Council (NHMRC) of Australia (1016953,
1066694, and 1027400 to E.K. Deenick and S.G. Tangye) and the
Rockefeller University Center for 541 Clinical and Translational Science
(5UL1RR024143 to J.-L. Casanova). C.S. Ma is a recipient of a Career
Development Fellowship (1008820), and S.G. Tangye is a recipient of a
Principal Research Fellowship (1042925) from the NHMRC of Australia.
NR 43
TC 13
Z9 14
U1 2
U2 10
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0022-1007
EI 1540-9538
J9 J EXP MED
JI J. Exp. Med.
PD JUN 1
PY 2015
VL 212
IS 6
BP 855
EP 864
DI 10.1084/jem.20141992
PG 10
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA CJ5YF
UT WOS:000355569300003
PM 25941256
ER
PT J
AU Kim, ML
Chae, JJ
Park, YH
De Nardo, D
Stirzaker, RA
Ko, HJ
Tye, H
Cengia, L
DiRago, L
Metcalf, D
Roberts, AW
Kastner, DL
Lew, AM
Lyras, D
Kile, BT
Croker, BA
Masters, SL
AF Kim, Man Lyang
Chae, Jae Jin
Park, Yong Hwan
De Nardo, Dominic
Stirzaker, Roslynn A.
Ko, Hyun-Ja
Tye, Hazel
Cengia, Louise
DiRago, Ladina
Metcalf, Donald
Roberts, Andrew W.
Kastner, Daniel L.
Lew, Andrew M.
Lyras, Dena
Kile, Benjamin T.
Croker, Ben A.
Masters, Seth L.
TI Aberrant actin depolymerization triggers the pyrin inflammasome and
autoinflammatory disease that is dependent on IL-18, not IL-1 beta
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID FAMILIAL MEDITERRANEAN FEVER; DISRUPT MICROFILAMENT ORGANIZATION;
GAMMA-INDUCING FACTOR; ENDOTOXIC-SHOCK; MICE DEFICIENT; PROTEIN ASC;
T-CELLS; ACTIVATION; CASPASE-1; INTERLEUKIN-1-BETA
AB Gain-of-function mutations that activate the innate immune system can cause systemic autoinflammatory diseases associated with increased IL-1 beta production. This cytokine is activated identically to IL-18 by an intracellular protein complex known as the inflammasome; however, IL-18 has not yet been specifically implicated in the pathogenesis of hereditary autoinflammatory disorders. We have now identified an autoinflammatory disease in mice driven by IL-18, but not IL-1 beta, resulting from an inactivating mutation of the actin-depolymerizing cofactor Wdr1. This perturbation of actin polymerization leads to systemic autoinflammation that is reduced when IL-18 is deleted but not when IL-1 signaling is removed. Remarkably, inflammasome activation in mature macrophages is unaltered, but IL-18 production from monocytes is greatly exaggerated, and depletion of monocytes in vivo prevents the disease. Small-molecule inhibition of actin polymerization can remove potential danger signals from the system and prevents monocyte IL-18 production. Finally, we show that the inflammasome sensor of actin dynamics in this system requires caspase-1, apoptosis-associated speck-like protein containing a caspase recruitment domain, and the innate immune receptor pyrin. Previously, perturbation of actin polymerization by pathogens was shown to activate the pyrin inflammasome, so our data now extend this guard hypothesis to host-regulated actin-dependent processes and autoinflammatory disease.
C1 [Kim, Man Lyang; De Nardo, Dominic; Tye, Hazel; Masters, Seth L.] Walter & Eliza Hall Inst Med Res, Div Inflammat, Parkville, Vic 3052, Australia.
[Stirzaker, Roslynn A.; Cengia, Louise; DiRago, Ladina; Metcalf, Donald; Roberts, Andrew W.] Walter & Eliza Hall Inst Med Res, Div Canc & Hematol, Parkville, Vic 3052, Australia.
[Ko, Hyun-Ja; Lew, Andrew M.] Walter & Eliza Hall Inst Med Res, Div Immunol, Parkville, Vic 3052, Australia.
[Kile, Benjamin T.] Walter & Eliza Hall Inst Med Res, ACRF Chem Biol Div, Parkville, Vic 3052, Australia.
[Chae, Jae Jin; Park, Yong Hwan; Kastner, Daniel L.] NHGRI, Inflammatory Dis Sect, Metab Cardiovasc & Inflammatory Dis Genom Branch, NIH, Bethesda, MD 20892 USA.
[Lyras, Dena] Monash Univ, Dept Microbiol, Clayton, Vic 3800, Australia.
[Croker, Ben A.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Kim, Man Lyang; De Nardo, Dominic; Metcalf, Donald; Roberts, Andrew W.; Lew, Andrew M.; Kile, Benjamin T.; Masters, Seth L.] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia.
RP Masters, SL (reprint author), Walter & Eliza Hall Inst Med Res, Div Inflammat, Parkville, Vic 3052, Australia.
EM masters@wehi.edu.au
RI Kile, Benjamin/F-6593-2011; Roberts, Andrew/C-6736-2012
OI Kile, Benjamin/0000-0002-8836-8947; Roberts, Andrew/0000-0002-7341-5720
FU National Institutes of Health [1008131, 1043414, 1016647, 1037321,
1R56AI103352-01A1]; National Health and Medical Research Council
[361646]; Victorian Endowment for Science Knowledge and Innovation;
Australian Research Council; Sylvia and Charles Viertel Charitable
Foundation; Cancer Council of Victoria; Australian Cancer Research
Foundation; Australian Phenomics Network
FX This work was supported by project grants (1008131 and 1043414), program
grants (1016647 and 1037321), fellowships (to B.T. Kile, B.A. Croker,
A.M. Lew, and S.L. Masters), a National Institutes of Health grant
(1R56AI103352-01A1; to B.A. Croker), and an Independent Research
Institutes Infrastructure Support Scheme grant (361646) from the
National Health and Medical Research Council; fellowships from the
Victorian Endowment for Science Knowledge and Innovation (to S.L.
Masters), the Australian Research Council (to B.A. Croker and B.T.
Kile), the Sylvia and Charles Viertel Charitable Foundation (to B.T.
Kile), and the Cancer Council of Victoria (to D. Metcalf); the
Australian Cancer Research Foundation, the Australian Phenomics Network,
and a Victorian State Government Operational Infrastructure Support
grant.
NR 54
TC 18
Z9 18
U1 3
U2 6
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0022-1007
EI 1540-9538
J9 J EXP MED
JI J. Exp. Med.
PD JUN 1
PY 2015
VL 212
IS 6
BP 927
EP 938
DI 10.1084/jem.20142384
PG 12
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA CJ5YF
UT WOS:000355569300009
PM 26008898
ER
PT J
AU Sidhu, R
Jiang, H
Farhat, NY
Carrillo-Carrasco, N
Woolery, M
Ottinger, E
Porter, FD
Schaffer, JE
Ory, DS
Jiang, XT
AF Sidhu, Rohini
Jiang, Hui
Farhat, Nicole Y.
Carrillo-Carrasco, Nuria
Woolery, Myra
Ottinger, Elizabeth
Porter, Forbes D.
Schaffer, Jean E.
Ory, Daniel S.
Jiang, Xuntian
TI A validated LC-MS/MS assay for quantification of
24(S)-hydroxycholesterol in plasma and cerebrospinal fluid
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE two-dimensional liquid chromatography-tandem mass spectrometry;
validation; Niemann-Pick C1 disease; 2-hydroxypropyl-beta-cyclodextrin
ID TANDEM MASS-SPECTROMETRY; 2-DIMENSIONAL LIQUID-CHROMATOGRAPHY; BRAIN
CHOLESTEROL-METABOLISM; ALZHEIMERS-DISEASE; MULTIPLE-SCLEROSIS;
24S-HYDROXYCHOLESTEROL REFLECT; 24S-AND 27-HYDROXYCHOLESTEROL;
QUANTITATIVE-ANALYSIS; HUNTINGTONS-DISEASE; OXIDATION-PRODUCTS
AB 24(S)-hydroxycholesterol [24(S)-HC] is a cholesterol metabolite that is formed almost exclusively in the brain. The concentrations of 24(S)-HC in cerebrospinal fluid (CSF) and/or plasma might be a sensitive marker of altered cholesterol metabolism in the CNS. A highly sensitive 2D-LC-MS/MS assay was developed for the quantification of 24(S)-HC in human plasma and CSF. In the development of an assay for 24(S)-HC in CSF, significant nonspecific binding of 24(S)-HC was observed and resolved with the addition of 2.5% 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) into CSF samples. The sample preparation consists of liquid-liquid extraction with methyl-tert-butyl ether and derivatization with nicotinic acid. Good linearity was observed in a range from 1 to 200 ng/ml and from 0.025 to 5 ng/ml, for plasma and CSF, respectively. Acceptable precision and accuracy were obtained for concentrations over the calibration curve ranges. Stability of 24(S)-HC was reported under a variety of storage conditions. This method has been successfully applied to support a National Institutes of Health-sponsored clinical trial of HP-beta-CD in Niemann-Pick type C1 patients, in which 24(S)-HC is used as a pharmacodynamic biomarker.
C1 [Sidhu, Rohini; Jiang, Hui; Schaffer, Jean E.; Ory, Daniel S.; Jiang, Xuntian] Washington Univ, Sch Med, Diabet Cardiovasc Dis Ctr, St Louis, MO 63110 USA.
[Farhat, Nicole Y.; Porter, Forbes D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Woolery, Myra] NIH, Dept Nursing, Bethesda, MD 20892 USA.
[Carrillo-Carrasco, Nuria] Natl Ctr Adv Translat Sci, Therapeut Rare & Neglected Dis, NIH, Rockville, MD 20850 USA.
[Ottinger, Elizabeth] Natl Ctr Adv Translat Sci, Div Preclin Innovat, NIH, Rockville, MD 20850 USA.
RP Jiang, XT (reprint author), Washington Univ, Sch Med, Diabet Cardiovasc Dis Ctr, St Louis, MO 63110 USA.
EM xjiang@wustl.edu
RI Carrillo-Carrasco, Nuria/B-9034-2009; Sidhu, Rohini/G-3547-2012
OI Carrillo-Carrasco, Nuria/0000-0003-0374-0808;
FU Bench-to-Bedside Program; Office of Rare Diseases Research; Therapies
for Rare and Neglected Diseases (TRND) Program in the National Center
for Advancing Translational Sciences of the National Institutes of
Health (NIH); National Institutes of Health [1ZIAHD008824-07]; Dana's
Angels Research Trust
FX This work was supported by the Bench-to-Bedside Program, the Office of
Rare Diseases Research, the Therapies for Rare and Neglected Diseases
(TRND) Program in the National Center for Advancing Translational
Sciences of the National Institutes of Health (NIH), and National
Institutes of Health Grant 1ZIAHD008824-07 (F.D.P.). Additional support
was provided by a grant from Dana's Angels Research Trust (D.S.O).
Quantification of 24(S)-HC was performed in the Metabolomics Facility at
Washington University (P30 DK020579).
NR 66
TC 5
Z9 5
U1 2
U2 12
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0022-2275
EI 1539-7262
J9 J LIPID RES
JI J. Lipid Res.
PD JUN
PY 2015
VL 56
IS 6
BP 1222
EP 1233
DI 10.1194/jlr.D058487
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CJ5MR
UT WOS:000355532400013
PM 25866316
ER
PT J
AU Wallace, GL
Eisenberg, IW
Robustelli, B
Dankner, N
Kenworthy, L
Giedd, JN
Martin, A
AF Wallace, Gregory L.
Eisenberg, Ian W.
Robustelli, Briana
Dankner, Nathan
Kenworthy, Lauren
Giedd, Jay N.
Martin, Alex
TI Longitudinal Cortical Development During Adolescence and Young Adulthood
in Autism Spectrum Disorder: Increased Cortical Thinning but Comparable
Surface Area Changes
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE autism; longitudinal; cortical thickness; surface area; executive
function
ID HUMAN CEREBRAL-CORTEX; DIAGNOSTIC INTERVIEW; EXECUTIVE FUNCTION; BRAIN;
THICKNESS; CHILDHOOD; MRI; AGE; CHILDREN; ANATOMY
AB Objective: Prior reports suggest that autism spectrum disorder (ASD) is associated with atypically excessive early brain growth. Recent cross-sectional studies suggest that later cortical development during adolescence/adulthood might also be aberrant, although longitudinal designs are required to evaluate atypical growth trajectories. The present study sought to examine longitudinal changes in cortical thickness and surface area among adolescents and young adults with ASD.
Method: Two high-resolution anatomic magnetic resonance imaging scans approximately 2 years apart were acquired from 17 adolescents with ASD and 18 typically developing (TD) adolescents, matched on age (range = 14-24 years), IQ, sex ratio, and handedness (70 scans total). The Free Surfer image analysis suite was used to quantify longitudinal changes in cortical thickness and surface area.
Results: Accelerated cortical thinning for the ASD group as compared to the TD group was found in 2 areas in the left hemisphere, the posterior portion of ventral temporal cortex and superior parietal cortex (cluster corrected p <.01). For ventral temporal cortex, cortical thinning was associated with everyday executive function impairments, and thinner cortex at time 2 was correlated with ASD social symptoms. Differences in surface area changes were not detected.
Conclusion: The present longitudinal study extends prior cross-sectional research by demonstrating increased cortical thinning (in portions of temporal and parietal cortex) but comparable surface area growth rates in participants with ASD compared to TD controls during adolescence and into young adulthood. These findings provide further evidence for atypical cortical development beyond the early years in ASD, marked by increased cortical thinning in late adolescence/young adulthood.
C1 [Wallace, Gregory L.; Eisenberg, Ian W.; Robustelli, Briana; Dankner, Nathan; Kenworthy, Lauren; Martin, Alex] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA.
[Wallace, Gregory L.] George Washington Univ, Washington, DC 20052 USA.
[Giedd, Jay N.] NIMH, Child Psychiat Branch, Rockville, MD USA.
RP Wallace, GL (reprint author), George Washington Univ, Dept Speech & Hearing Sci, 2115 G St NW,Room 201, Washington, DC 20052 USA.
EM gwallac1@gwu.edu
RI Giedd, Jay/J-9644-2015;
OI Giedd, Jay/0000-0003-2002-8978; Wallace, Gregory/0000-0003-0329-5054
FU Intramural Research Program at NIMH, National Institutes of Health (NIH)
[1-ZIA-MH002920-05]
FX This work was supported by the Intramural Research Program at NIMH,
National Institutes of Health (NIH) under grant number
1-ZIA-MH002920-05. Ethics approval for this study was granted by the NIH
Combined Neuroscience Institutional Review Board under protocol number
10-M-0027.
NR 40
TC 11
Z9 11
U1 6
U2 14
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
EI 1527-5418
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD JUN
PY 2015
VL 54
IS 6
BP 464
EP 469
DI 10.1016/j.jaac.2015.03.007
PG 6
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA CJ8VZ
UT WOS:000355782900006
PM 26004661
ER
PT J
AU Kopp, JB
Winkler, CA
Zhao, XC
Radeva, MK
Gassman, JJ
D'Agati, VD
Nast, CC
Wei, CL
Reiser, J
Guay-Woodford, LM
Pollak, MR
Hildebrandt, F
Moxey-Mims, M
Gipson, DS
Trachtman, H
Friedman, AL
Kaskel, FJ
AF Kopp, Jeffrey B.
Winkler, Cheryl A.
Zhao, Xiongce
Radeva, Milena K.
Gassman, Jennifer J.
D'Agati, Vivette D.
Nast, Cynthia C.
Wei, Changli
Reiser, Jochen
Guay-Woodford, Lisa M.
Pollak, Martin R.
Hildebrandt, Friedhelm
Moxey-Mims, Marva
Gipson, Debbie S.
Trachtman, Howard
Friedman, Aaron L.
Kaskel, Frederick J.
CA FSGS-CT Study Consortium
TI Clinical Features and Histology of Apolipoprotein L1-Associated
Nephropathy in the FSGS Clinical Trial
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; HIV-ASSOCIATED NEPHROPATHY; VARIANTS
ASSOCIATE; AFRICAN-AMERICANS; GENE VARIANTS; ADULTS
AB Genetic variants in apolipoprotein L1 (APOL1) confer risk for kidney disease. We sought to better define the phenotype of APOL1-associated nephropathy. The FSGS Clinical Trial involved 138 children and young adults who were randomized to cyclosporin or mycophenolate mofetil plus pulse oral dexamethasone with a primary outcome of proteinuria remission. DNA was available from 94 subjects who were genotyped for APOL1 renal risk variants, with two risk alleles comprising the risk genotype. Two APOL1 risk alleles were present in 27 subjects, of whom four subjects did not self-identify as African American, and 23 of 32 (72%) self-identified African Americans. Individuals with the APOL1 risk genotype tended to present at an older age and had significantly lower baseline eGFR, more segmental glomerulosclerosis and total glomerulosclerosis, and more tubular atrophy/interstitial fibrosis. There were differences in renal histology, particularly more collapsing variants in those with the risk genotype (P=0.02), although this association was confounded by age. APOL1 risk genotype did not affect response to either treatment regimen. Individuals with the risk genotype were more likely to progress to ESRD (P<0.01). In conclusion, APOL1 risk genotypes are common in African-American subjects with primary FSGS and may also be present in individuals who do not self-identify as African American. APOL1 risk status is associated with lower kidney function, more glomerulosclerosis and interstitial fibrosis, and greater propensity to progress to ESRD. The APOL1 risk genotype did not influence proteinuria responses to cyclosporin or mycophenolate mofetil/dexamethasone.
C1 [Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA.
[Zhao, Xiongce] NIDDK, Biostat Core, NIH, Bethesda, MD 20892 USA.
[Moxey-Mims, Marva] NIDDK, Div Kidney Urol & Hematol, NIH, Bethesda, MD 20892 USA.
[Winkler, Cheryl A.] Leidos Biomed Res Inc, Basic Res Lab, Ctr Canc Res, NCI,Frederick Natl Lab, Frederick, MD USA.
[Radeva, Milena K.; Gassman, Jennifer J.] Cleveland Clin, Dept Quantitat Heath Sci, Cleveland, OH 44106 USA.
[D'Agati, Vivette D.] Columbia Univ, Dept Pathol, Med Ctr, New York, NY USA.
[Nast, Cynthia C.] Cedars Sinai Med Ctr, Dept Pathol, Los Angeles, CA 90048 USA.
[Wei, Changli; Reiser, Jochen] Rush Univ, Dept Med, Med Ctr, Chicago, IL 60612 USA.
[Guay-Woodford, Lisa M.] Childrens Natl Hlth Syst, Ctr Translat Sci, Washington, DC USA.
[Pollak, Martin R.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Hildebrandt, Friedhelm] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA.
[Gipson, Debbie S.] Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA.
[Trachtman, Howard] NYU, Dept Pediat, Sch Med, New York, NY 10016 USA.
[Friedman, Aaron L.] Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA.
[Kaskel, Frederick J.] Albert Einstein Coll Med, Childrens Hosp Montefiore, Bronx, NY 10467 USA.
RP Kopp, JB (reprint author), NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM jbkopp@nih.gov
OI Trachtman, Howard/0000-0001-7447-9489
FU NIDDK; National Cancer Institute (NCI); NCI, NIH [HHSN26120080001E];
NIH, NCI, Center for Cancer Research
FX The FSGS Clinical Trial was supported by National Institute of Diabetes
and Digestive and Kidney Diseases (NIDDK), National Institutes of Health
(NIH), and this work was supported by the NIDDK and National Cancer
Institute (NCI) Intramural Research Programs. This project has been
funded in whole or part with federal funds from NCI, NIH Contract
HHSN26120080001E. This research was supported in part by the Intramural
Research Program of the NIH, NCI, Center for Cancer Research.
NR 16
TC 22
Z9 23
U1 0
U2 2
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD JUN
PY 2015
VL 26
IS 6
BP 1443
EP 1448
DI 10.1681/ASN.2013111242
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA CJ3LS
UT WOS:000355386100022
PM 25573908
ER
PT J
AU Allen, KB
Horvath, K
AF Allen, Keith B.
Horvath, Keith
TI AORTIC FILTRATION SYSTEM'S IMPACT ON PREVENTING ADVERSE CLINICAL EVENTS
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Letter
ID INTRAAORTIC FILTER; CAPTURE
C1 [Allen, Keith B.] Univ Missouri, St Lukes Mid Amer Heart Inst, Kansas City, MO 64110 USA.
[Horvath, Keith] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA.
RP Allen, KB (reprint author), Univ Missouri, St Lukes Mid Amer Heart Inst, Kansas City, MO 64110 USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
EI 1097-685X
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD JUN
PY 2015
VL 149
IS 6
BP 1674
EP 1675
DI 10.1016/j.jtcvs.2015.01.029
PG 2
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA CJ8HI
UT WOS:000355740400066
PM 26060007
ER
PT J
AU Koblin, BA
Grant, S
Frye, V
Superak, H
Sanchez, B
Lucy, D
Dunbar, D
Graham, P
Madenwald, T
Escamilia, G
Swann, E
Morgan, C
Novak, RM
Frank, I
AF Koblin, Beryl A.
Grant, Shannon
Frye, Victoria
Superak, Hillary
Sanchez, Brittany
Lucy, Debbie
Dunbar, Debora
Graham, Parrie
Madenwald, Tamra
Escamilia, Gina
Swann, Edith
Morgan, Cecilia
Novak, Richard M.
Frank, Ian
CA HVTN 906 Study Team
TI HIV Sexual Risk and Syndemics among Women in Three Urban Areas in the
United States: Analysis from HVTN 906
SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE
LA English
DT Article
DE Women; HIV; Syndemics; Sexual risk
ID INTIMATE PARTNER VIOLENCE; NEW-YORK-CITY; SUBSTANCE-ABUSE;
SOCIAL-CONTEXT; AFRICAN-AMERICANS; LOW-INCOME; DEPRESSION; INFECTION;
HIV/AIDS; INTERVENTIONS
AB Limited data are available on the longitudinal occurrence of syndemic factors among women at risk for HIV infection in the USA and how these factors relate to sexual risk over time. HVTN 906 was a longitudinal study enrolling 799 HIV-uninfected women in three cities. Assessments were done at baseline, 6, 12, and 18 months to assess syndemic factors (low education, low income, unemployment, lack of health insurance, housing instability, substance use, heavy alcohol use, partner violence, incarceration) and sexual risk outcomes. For each sexual risk outcome, a GEE model was fit with syndemic factors or syndemic score (defined as sum of binary syndemics, ranging from 0 to 9), visit, study site, age and race/ethnicity as predictors to examine the multivariable association between syndemic factors and outcomes over time. Odds of unprotected sex while drunk or high were significantly higher when women reported lack of health insurance, substance and heavy alcohol use and partner violence. Housing instability, substance and heavy alcohol use, partner violence and recent incarceration were associated with higher odds of having multiple sexual partners. Odds of sex exchange were significantly higher in the presence of unemployment, housing instability, low education, lack of health insurance, substance and heavy alcohol use, partner violence and incarceration. Housing instability, substance and heavy alcohol use, and partner violence were significantly associated with higher odds of unprotected anal sex. Odds of having a recent STI were significantly higher when women reported housing instability and partner violence. There were significantly higher odds of the reporting of any risk outcomes during follow-up with higher syndemic score. This study highlights a group of women experiencing multiple poor social and health outcomes who need to be the focus of comprehensive interventions.
C1 [Koblin, Beryl A.; Lucy, Debbie] New York Blood Ctr, Lab Infect Dis Prevent, New York, NY 10065 USA.
[Grant, Shannon; Superak, Hillary; Sanchez, Brittany; Madenwald, Tamra; Escamilia, Gina; Morgan, Cecilia] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[Frye, Victoria] New York Blood Ctr, Lab Social & Behav Sci, New York, NY 10065 USA.
[Dunbar, Debora; Frank, Ian] Univ Penn, HIV Prevent Div, Philadelphia, PA 19104 USA.
[Graham, Parrie; Novak, Richard M.] Univ Illinois, Infect Dis Sect, Chicago, IL USA.
[Swann, Edith] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
[Frank, Ian] Univ Penn, Div Infect Dis, Philadelphia, PA 19104 USA.
RP Koblin, BA (reprint author), New York Blood Ctr, Lab Infect Dis Prevent, 310 E 67th St, New York, NY 10065 USA.
EM bkoblin@nybloodcenter.org
FU Division of AIDS, National Institute of Allergy and Infectious Disease,
National Institutes of Health [1UM1AI068614, 1UM1A1069470, 1UM1A1069554,
1UM1A1069534, 1UM1AI068635, P30AI045008]
FX The HVTN 906 study team would like to thank the study participants,
community advisory board members, and the study site staff for their
commitment to this study. This research was funded by the Division of
AIDS, National Institute of Allergy and Infectious Disease, National
Institutes of Health, grants 1UM1AI068614, 1UM1A1069470, 1UM1A1069554,
1UM1A1069534, 1UM1AI068635 and P30AI045008.
NR 32
TC 5
Z9 5
U1 2
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1099-3460
EI 1468-2869
J9 J URBAN HEALTH
JI J. Urban Health
PD JUN
PY 2015
VL 92
IS 3
BP 572
EP 583
DI 10.1007/s11524-015-9944-5
PG 12
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA CJ6SR
UT WOS:000355624400013
PM 25743100
ER
PT J
AU Arock, M
Sotlar, K
Akin, C
Broesby-Olsen, S
Hoermann, G
Escribano, L
Kristensen, TK
Kluin-Nelemans, HC
Hermine, O
Dubreuil, P
Sperr, WR
Hartmann, K
Gotlib, J
Cross, NCP
Haferlach, T
Garcia-Montero, A
Orfao, A
Schwaab, J
Triggiani, M
Horny, HP
Metcalfe, DD
Reiter, A
Valent, P
AF Arock, M.
Sotlar, K.
Akin, C.
Broesby-Olsen, S.
Hoermann, G.
Escribano, L.
Kristensen, T. K.
Kluin-Nelemans, H. C.
Hermine, O.
Dubreuil, P.
Sperr, W. R.
Hartmann, K.
Gotlib, J.
Cross, N. C. P.
Haferlach, T.
Garcia-Montero, A.
Orfao, A.
Schwaab, J.
Triggiani, M.
Horny, H-P
Metcalfe, D. D.
Reiter, A.
Valent, P.
TI KIT mutation analysis in mast cell neoplasms: recommendations of the
European Competence Network on Mastocytosis
SO LEUKEMIA
LA English
DT Review
ID CHRONIC MYELOMONOCYTIC LEUKEMIA; FAMILIAL CUTANEOUS MASTOCYTOSIS;
INDOLENT SYSTEMIC MASTOCYTOSIS; POLYMERASE-CHAIN-REACTION; PROTOONCOGENE
C-KIT; OF-THE-LITERATURE; D816V MUTATION; TYROSINE KINASE; PEDIATRIC
MASTOCYTOSIS; MYELOGENOUS LEUKEMIA
AB Although acquired mutations in KIT are commonly detected in various categories of mastocytosis, the methodologies applied to detect and quantify the mutant type and allele burden in various cells and tissues are poorly defined. We here propose a consensus on methodologies used to detect KIT mutations in patients with mastocytosis at diagnosis and during follow-up with sufficient precision and sensitivity in daily practice. In addition, we provide recommendations for sampling and storage of diagnostic material as well as a robust diagnostic algorithm. Using highly sensitive assays, KIT D816V can be detected in peripheral blood leukocytes from most patients with systemic mastocytosis (SM) that is a major step forward in screening and SM diagnosis. In addition, the KIT D816V allele burden can be followed quantitatively during the natural course or during therapy. Our recommendations should greatly facilitate diagnostic and follow-up investigations in SM in daily practice as well as in clinical trials. In addition, the new tools and algorithms proposed should lead to a more effective screen, early diagnosis of SM and help to avoid unnecessary referrals.
C1 [Arock, M.] Ecole Normale Super, LBPA CNRS UMR8113, Mol Oncol & Pharmacol, Cachan, France.
[Arock, M.] Grp Hosp Pitie Salpetriere, Hematol Lab, Paris, France.
[Sotlar, K.; Horny, H-P] Univ Munich, Inst Pathol, Munich, Germany.
[Akin, C.] Harvard Univ, Sch Med, Dept Med Brigham & Womens Hosp, Div Allergy & Immunol, Boston, MA USA.
[Broesby-Olsen, S.] Odense Univ Hosp, Dept Dermatol & Allergy Ctr, DK-5000 Odense, Denmark.
[Hoermann, G.] Med Univ Vienna, Dept Lab Med, Vienna, Austria.
[Escribano, L.; Garcia-Montero, A.; Orfao, A.] Univ Salamanca, IBSAL, Serv Cent Citometria, Ctr Invest Canc,IBMCC,CSIC USAL, E-37008 Salamanca, Spain.
[Escribano, L.; Garcia-Montero, A.; Orfao, A.] Univ Salamanca, Dept Med, E-37008 Salamanca, Spain.
[Kristensen, T. K.] Odense Univ Hosp, Dept Pathol, DK-5000 Odense, Denmark.
[Kluin-Nelemans, H. C.] Univ Groningen, Univ Med Ctr Groningen, Dept Hematol, Groningen, Netherlands.
[Hermine, O.] Paris Descartes Univ, Fac Med, Dept Clin Hematol, Paris, France.
[Hermine, O.] Paris Descartes Univ, AP HP Necker Enfants Malades, Paris, France.
[Dubreuil, P.] CRCM, Inserm U1068, Signaling Hematopoiesis & Mech Oncogenesis, Marseille, France.
[Dubreuil, P.] Inst J Paoli I Calmettes, F-13009 Marseille, France.
[Dubreuil, P.] Aix Marseille Univ, UM 105, Marseille, France.
[Dubreuil, P.] CNRS, CRCM, UMR7258, Marseille, France.
[Sperr, W. R.; Valent, P.] Med Univ Vienna, Div Hematol & Hemostaseol, Dept Internal Med 1, Vienna, Austria.
[Hartmann, K.] Univ Cologne, Dept Dermatol, D-50931 Cologne, Germany.
[Gotlib, J.] Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, MD USA.
[Cross, N. C. P.] Wessex Reg Genet Lab, Salisbury, England.
[Cross, N. C. P.] Univ Southampton, Fac Med, Southampton SO9 5NH, Hants, England.
[Haferlach, T.] Munich Leukemia Lab, Munich, Germany.
[Schwaab, J.] Med Univ Mannheim, Med Clin, Hematol & Oncol, Mannheim, Germany.
[Triggiani, M.] Univ Salerno, Div Clin Immunol & Allergy, I-84100 Salerno, Italy.
[Metcalfe, D. D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Arock, M (reprint author), Ecole Normale Super, LBPA CNRS UMR8113, Mol Oncol & Pharmacol, Cachan, France.
EM arock@ens-cachan.fr
RI Cross, Nicholas/B-4817-2009; Hoermann, Gregor/B-8832-2016; Hartmann,
Karin/N-4865-2015;
OI Cross, Nicholas/0000-0001-5481-2555; Hoermann,
Gregor/0000-0002-7374-4380; Hartmann, Karin/0000-0002-4595-8226; Akin,
Cem/0000-0001-6301-4520
FU Fondation de France; La Ligue Nationale Contre le Cancer (equipe
labellisee); Ministry of Economy and Competitivity, Madrid, Spain,
(FEDER) [RD12/0036/0048, PI11/02399]; Fundacion Ramon Areces, Madrid,
Spain [CIVP16A1806]; Division of Intramural Research, NIAID; Austrian
Science Funds (FWF) [SFB F4611, SFB F4704-B20]; INCa; Instituto de Salud
Carlos III
FX We were unable to cite all the original papers because of reference
limits and apologize for not citing all relevant original papers. M
Arock is supported by Fondation de France; P Dubreuil is supported by La
Ligue Nationale Contre le Cancer (equipe labellisee) and INCa; A
Garcia-Montero and A Orfao are supported by grants from the Instituto de
Salud Carlos III, Ministry of Economy and Competitivity, Madrid, Spain
(Grant Numbers RD12/0036/0048 and PI11/02399, FEDER) and from Fundacion
Ramon Areces, Madrid, Spain (Grant Number CIVP16A1806); DD Metcalfe is
supported in part by the Division of Intramural Research, NIAID; P
Valent is supported by Austrian Science Funds (FWF) Project SFB F4611
and SFB F4704-B20.
NR 97
TC 24
Z9 24
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
EI 1476-5551
J9 LEUKEMIA
JI Leukemia
PD JUN
PY 2015
VL 29
IS 6
BP 1223
EP 1232
DI 10.1038/leu.2015.24
PG 10
WC Oncology; Hematology
SC Oncology; Hematology
GA CJ6PE
UT WOS:000355615000001
PM 25650093
ER
PT J
AU Purdue, MP
Lan, Q
Kemp, TJ
Hildesheim, A
Weinstein, SJ
Hofmann, JN
Virtamo, J
Albanes, D
Pinto, LA
Rothman, N
AF Purdue, M. P.
Lan, Q.
Kemp, T. J.
Hildesheim, A.
Weinstein, S. J.
Hofmann, J. N.
Virtamo, J.
Albanes, D.
Pinto, L. A.
Rothman, N.
TI Elevated serum sCD23 and sCD30 up to two decades prior to diagnosis
associated with increased risk of non-Hodgkin lymphoma
SO LEUKEMIA
LA English
DT Letter
ID B-CELL ACTIVATION; SOLUBLE CD30; MARKERS; IMMUNE; CD23; CYTOKINES
C1 [Purdue, M. P.; Lan, Q.; Hildesheim, A.; Weinstein, S. J.; Hofmann, J. N.; Albanes, D.; Rothman, N.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
[Purdue, M. P.] Ontario Inst Canc Res, Toronto, ON, Canada.
[Kemp, T. J.; Pinto, L. A.] Leidos Biomed Inc, HPV Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Virtamo, J.] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
RP Purdue, MP (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
EM mark.purdue@ontariohealthstudy.ca
RI Hildesheim, Allan/B-9760-2015; Purdue, Mark/C-9228-2016
OI Hildesheim, Allan/0000-0003-0257-2363; Purdue, Mark/0000-0003-1177-3108
FU Intramural NIH HHS
NR 15
TC 4
Z9 4
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
EI 1476-5551
J9 LEUKEMIA
JI Leukemia
PD JUN
PY 2015
VL 29
IS 6
BP 1429
EP 1431
DI 10.1038/leu.2015.2
PG 3
WC Oncology; Hematology
SC Oncology; Hematology
GA CJ6PE
UT WOS:000355615000022
PM 25567136
ER
PT J
AU Sun, B
Wang, Y
Kota, K
Shi, YR
Motlak, S
Makambi, K
Loffredo, CA
Shields, PG
Yang, Q
Harris, CC
Zheng, YL
AF Sun, Bing
Wang, Ying
Kota, Krishna
Shi, Yaru
Motlak, Salaam
Makambi, Kepher
Loffredo, Christopher A.
Shields, Peter G.
Yang, Qin
Harris, Curtis C.
Zheng, Yun-Ling
TI Telomere length variation: A potential new telomere biomarker for lung
cancer risk
SO LUNG CANCER
LA English
DT Article
DE Lung cancer; Telomere length variation; Telomere length; Blood-based
biomarker; Risk prediction; Telomere dysfunction
ID HEMATOPOIETIC STEM-CELLS; OXIDATIVE STRESS; DYSKERATOSIS-CONGENITA;
CHROMOSOME STABILITY; HUMAN FIBROBLASTS; DNA-DAMAGE; DYSFUNCTION;
SENESCENCE; MICE; AGE
AB Objectives: In this report the associations between telomere length variation (TLV), mean telomere length in blood lymphocytes and lung cancer risk were examined.
Materials and methods: The study design is case-control. Cases (N = 191) were patients newly diagnosed with histologically confirmed non-small cell lung cancer. Controls (N = 207) were healthy individuals recruited from the same counties as cases and matched to cases on age and gender. Telomere fluorescent in situ hybridization was used to measure telomere features using short-term cultured blood lymphocytes. Logistic regression was used to estimate the strength of association between telomere features and lung cancer risk.
Results: Telomere length variation across all chromosomal ends was significantly associated with lung cancer risk; adjusted odds ratios 4.67 [95% confidence interval (CI): 1.46-14.9] and 0.46 (95% CI: 025-0.84) for younger (age <= 60) and older (age >60) individuals, respectively. TLV and mean telomere length jointly affected lung cancer risk: when comparing individuals with short telomere length and high TLV to those with long telomere length and low TLV, adjusted odd ratios were 8.21 (95% Cl: 1.71-39.5) and 0.33 (95% CI: 0.15-0.72) for younger and older individuals, respectively.
Conclusions: TLV in blood lymphocytes is significantly associated with lung cancer risk and the associations were modulated by age. TLV in combination with mean telomere length might be useful in identifying high risk population for lung cancer computerized tomography screening. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Sun, Bing; Wang, Ying; Kota, Krishna; Shi, Yaru; Motlak, Salaam; Makambi, Kepher; Loffredo, Christopher A.; Zheng, Yun-Ling] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Canc Prevent & Control Program, Washington, DC 20057 USA.
[Makambi, Kepher; Loffredo, Christopher A.] Georgetown Univ, Med Ctr, Dept Biostat Bioinformat & Biomath, Washington, DC 20057 USA.
[Shields, Peter G.] Ohio State Univ, Wexner Med Ctr, James Canc Hosp, Columbus, OH 43220 USA.
[Yang, Qin] Washington Univ, Sch Med, Dept Radiat Oncol, Div Canc Biol, St Louis, MO USA.
[Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Zheng, YL (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Canc Prevent & Control Program, 3970 Reservoir Rd NW,Res Bldg,Room W201, Washington, DC 20057 USA.
EM yz37@georgetown.edu
FU National Cancer Institute of the National Institutes of Health
[R01CA132996]; Susan G. Komen for the Cure [KG100283]
FX We thank Donna Perlmutter, Bonnie Cooper, Terrence Clemmons, Carolynn
Harris, Laura Hall and Dawn Tucker for recruiting study subjects, and
Betty Williams for data coding and editing. We thank John Cottrell and
Zhipeng Yu for processing and handling the samples and Audrey Salabes
for examining medical records. We thank Scarlett Sun and Michael Xu for
their assistance in telomere length measurement. Research in YLZ's
laboratory is supported by grants from the National Cancer Institute of
the National Institutes of Health (R01CA132996)and Susan G. Komen for
the Cure (KG100283). The content is solely the responsibility of the
authors and does not necessarily represent the official views of the
funding agencies.
NR 50
TC 4
Z9 4
U1 1
U2 9
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0169-5002
EI 1872-8332
J9 LUNG CANCER
JI Lung Cancer
PD JUN
PY 2015
VL 88
IS 3
BP 297
EP 303
DI 10.1016/j.lungcan.2015.03.011
PG 7
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA CJ7WU
UT WOS:000355711900009
PM 25840848
ER
PT J
AU Lam, C
Golas, GA
Davids, M
Huizing, M
Kane, MS
Krasnewich, DM
Malicdan, MCV
Adams, DR
Markello, TC
Zein, WM
Gropman, AL
Lodish, MB
Stratakis, CA
Maric, I
Rosenzweig, SD
Baker, EH
Ferreira, CR
Danylchuk, NR
Kahler, S
Garnica, AD
Schaefer, GB
Boerkoel, CF
Gahl, WA
Wolfe, LA
AF Lam, Christina
Golas, Gretchen A.
Davids, Mariska
Huizing, Marjan
Kane, Megan S.
Krasnewich, Donna M.
Malicdan, May Christine V.
Adams, David R.
Markello, Thomas C.
Zein, Wadih M.
Gropman, Andrea L.
Lodish, Maya B.
Stratakis, Constantine A.
Maric, Irina
Rosenzweig, Sergio D.
Baker, Eva H.
Ferreira, Carlos R.
Danylchuk, Noelle R.
Kahler, Stephen
Garnica, Adolfo D.
Schaefer, G. Bradley
Boerkoel, Cornelius F.
Gahl, William A.
Wolfe, Lynne A.
TI Expanding the clinical and molecular characteristics of PIGT-CDG, a
disorder of glycosylphosphatidylinositol anchors
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE PIGT-CDG; Congenital disorder of glycosylation;
Glycosylphosphatidylinositol anchor; Phenotype; Flow cytometry; Exome
ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; HYPOTONIA-SEIZURES SYNDROME;
MENTAL-RETARDATION SYNDROME; INTELLECTUAL DISABILITY; UNDIAGNOSED
DISEASES; GERMLINE MUTATION; GPI; HYPERPHOSPHATASIA; PROTEINS;
DEFICIENCY
AB PIGT-CDG, an autosomal recessive syndromic intellectual disability disorder of glycosylphosphatidylinositol (GPI) anchors, was recently described in two independent kindreds [Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 3 (OMIM, #615398)]. PIGT encodes phosphatidylinositol-glycan biosynthesis class T, a subunit of the heteropentameric transamidase complex that facilitates the transfer of GPI to proteins. GPI facilitates attachment (anchoring) of proteins to cell membranes. We describe, at ages 7 and 6 years, two children of non-consanguineous parents; they had hypotonia, severe global developmental delay, and intractable seizures along with endocrine, ophthalmologic, skeletal, hearing, and cardiac anomalies. Exome sequencing revealed that both siblings had compound heterozygous variants in PIGT (NM_015937.5), i.e., c.918dupC, a novel duplication leading to a frameshift, and c.1342C > T encoding a previously described missense variant Flow cytometry studies showed decreased surface expression of GPI-anchored proteins on granulocytes, consistent with findings in previous cases. These siblings further delineate the clinical spectrum of PIGT-CDG, reemphasize the neuro-ophthalmologic presentation, clarify the endocrine features, and add hypermobility, low CSF albumin quotient, and hearing loss to the phenotypic spectrum. Our results emphasize that GPI anchor-related congenital disorders of glycosylation (CDGs) should be considered in subjects with early onset severe seizure disorders and dysmorphic facial features, even in the presence of a normal carbohydrate-deficient transferrin pattern and N-glycan profiling. Currently available screening for CDGs will not reliably detect this family of disorders, and our case reaffirms that the use of flow cytometry and genetic testing is essential for diagnosis in this group of disorders. (C) 2015 Published by Elsevier Inc.
C1 [Lam, Christina; Ferreira, Carlos R.] NHGRI, Med Genet & Genom Med Training Program, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Golas, Gretchen A.; Davids, Mariska; Kane, Megan S.; Adams, David R.; Gropman, Andrea L.; Gahl, William A.; Wolfe, Lynne A.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Golas, Gretchen A.; Davids, Mariska; Kane, Megan S.; Malicdan, May Christine V.; Adams, David R.; Markello, Thomas C.; Boerkoel, Cornelius F.; Gahl, William A.; Wolfe, Lynne A.] NIH, NIH Undiagnosed Dis Program, Common Fund, Off Director, Bethesda, MD 20892 USA.
[Huizing, Marjan; Malicdan, May Christine V.; Adams, David R.; Markello, Thomas C.; Gahl, William A.] NHGRI, Human Biochem Genet Sect, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Krasnewich, Donna M.] NHGRI, Div Genet & Dev Biol, NIH, Bethesda, MD 20892 USA.
[Zein, Wadih M.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Lodish, Maya B.] NICHD, Heritable Disorders Branch, NIH, Bethesda, MD USA.
[Stratakis, Constantine A.] NICHD, Sect Endocrinol & Genet, NIH, Bethesda, MD USA.
[Maric, Irina] NIH, Hematol Serv, Ctr Clin, Bethesda, MD 20892 USA.
[Rosenzweig, Sergio D.] NIH, Serv Immunol, Ctr Clin, Bethesda, MD 20892 USA.
[Baker, Eva H.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Danylchuk, Noelle R.; Kahler, Stephen; Garnica, Adolfo D.; Schaefer, G. Bradley] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA.
[Danylchuk, Noelle R.; Kahler, Stephen; Garnica, Adolfo D.; Schaefer, G. Bradley] Arkansas Childrens Hosp, Little Rock, AR 72202 USA.
RP Lam, C (reprint author), NHGRI, NIH, Bldg 10,Room 5D38, Bethesda, MD 20892 USA.
EM lamct@mail.nih.gov
FU Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health, Bethesda, MD, USA
FX We would like to thank the family for participating in this study. We
appreciate the expert laboratory assistance of Carla Ciccone, the
Magnetic Resonance technologists who scanned the patients (Mastaneh
Owhadi and Bonita Damaska), and Dr. F.D. Porter for the use of his
patients as a reference group. This study was supported by the by the
Common Fund, Office of the Director and the Intramural Research Program
of the National Human Genome Research Institute, National Institutes of
Health, Bethesda, MD, USA.
NR 37
TC 2
Z9 2
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD JUN-JUL
PY 2015
VL 115
IS 2-3
BP 128
EP 140
DI 10.1016/j.ymgme.2015.04.007
PG 13
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA CK0KH
UT WOS:000355893600010
PM 25943031
ER
PT J
AU Grasso, CS
Tang, YJ
Truffaux, N
Berlow, NE
Liu, LN
Debily, MA
Quist, MJ
Davis, LE
Huang, EC
Woo, PJ
Ponnuswami, A
Chen, S
Johung, TB
Sun, WC
Kogiso, M
Dui, YC
Qi, L
Huang, YL
Hutt-Cabezas, M
Warrenm, KE
Le Dret, L
Meltzerm, PS
Mao, H
Quezado, M
van Vuurden, DG
Abraham, J
Fouladi, M
Svalina, MN
Wang, N
Hawkins, C
Nazarian, J
Alonso, MM
Raabe, EH
Hulleman, E
Spellman, PT
Li, XN
Keller, C
Pal, R
Grill, J
Monje, M
AF Grasso, Catherine S.
Tang, Yujie
Truffaux, Nathalene
Berlow, Noah E.
Liu, Lining
Debily, Marie-Anne
Quist, Michael J.
Davis, Lara E.
Huang, Elaine C.
Woo, Pamelyn J.
Ponnuswami, Anitha
Chen, Spenser
Johung, Tessa B.
Sun, Wenchao
Kogiso, Mari
Dui, Yuchen
Qi, Lin
Huang, Yulun
Huett-Cabezas, Marianne
Warrenm, Katherine E.
Le Dret, Ludivine
Meltzerm, Paul S.
Mao, Hua
Quezado, Martha
van Vuurden, Dannis G.
Abraham, Jinu
Fouladi, Maryam
Svalina, Matthew N.
Wang, Nicholas
Hawkins, Cynthia
Nazarian, Javad
Alonso, Marta M.
Raabe, Eric H.
Hulleman, Esther
Spellman, Paul T.
Li, Xiao-Nan
Keller, Charles
Pal, Ranadip
Grill, Jacques
Monje, Michelle
TI Functionally defined therapeutic targets in diffuse intrinsic pontine
glioma
SO NATURE MEDICINE
LA English
DT Article
ID BRAIN-STEM; PEDIATRIC GLIOBLASTOMA; GENE-EXPRESSION; HISTONE H3.3;
MUTATIONS; INHIBITION; SUBGROUPS; PRC2; CELL
AB Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood cancer. We performed a chemical screen in patient-derived DIPG cultures along with RNA-seq analyses and integrated computational modeling to identify potentially effective therapeutic strategies. The multi histone deacetylase inhibitor panobinostat demonstrated therapeutic efficacy both in vitro and in DIPG orthotopic xenograft models. Combination testing of panobinostat and the histone demethylase inhibitor GSK-J4 revealed that the two had synergistic effects. Together, these data suggest a promising therapeutic strategy for DIPG.
C1 [Grasso, Catherine S.; Quist, Michael J.; Wang, Nicholas; Spellman, Paul T.] Oregon Hlth & Sci Univ, Ctr Spatial Syst Biomed, Dept Mol & Med Genet, Portland, OR 97201 USA.
[Grasso, Catherine S.; Tang, Yujie; Liu, Lining; Woo, Pamelyn J.; Ponnuswami, Anitha; Chen, Spenser; Johung, Tessa B.; Sun, Wenchao; Monje, Michelle] Stanford Univ, Dept Neurol, Stanford, CA 94305 USA.
[Tang, Yujie; Liu, Lining; Woo, Pamelyn J.; Ponnuswami, Anitha; Chen, Spenser; Johung, Tessa B.; Monje, Michelle] Stanford Univ, Dept Neurosurg, Stanford, CA 94305 USA.
[Tang, Yujie; Liu, Lining; Woo, Pamelyn J.; Ponnuswami, Anitha; Chen, Spenser; Johung, Tessa B.; Monje, Michelle] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA.
[Tang, Yujie; Liu, Lining; Woo, Pamelyn J.; Ponnuswami, Anitha; Chen, Spenser; Johung, Tessa B.; Monje, Michelle] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA.
[Truffaux, Nathalene; Le Dret, Ludivine; Grill, Jacques] Univ Paris Sud, CNRS, Gustave Roussy, UMR 8203, Villejuif, France.
[Berlow, Noah E.; Pal, Ranadip] Texas Tech Univ, Elect & Comp Engn, Lubbock, TX 79409 USA.
[Debily, Marie-Anne; Davis, Lara E.] Univ Evry Val dEssone, Dept Biol, Evry, France.
[Huang, Elaine C.; Abraham, Jinu; Keller, Charles] Oregon Hlth & Sci Univ, Dept Pediat, Pape Family Pediat Res Inst, Pediat Canc Biol Program, Portland, OR 97201 USA.
[Kogiso, Mari; Dui, Yuchen; Qi, Lin; Mao, Hua; Li, Xiao-Nan] Baylor Coll Med, Texas Childrens Canc Ctr, Mol Neurooncol Lab, Houston, TX 77030 USA.
[Huett-Cabezas, Marianne; Raabe, Eric H.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA.
[Huett-Cabezas, Marianne; Warrenm, Katherine E.; Quezado, Martha; Raabe, Eric H.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA.
[Meltzerm, Paul S.] NCI, Bethesda, MD 20892 USA.
[van Vuurden, Dannis G.; Hulleman, Esther] Vrije Univ Amsterdam, Med Ctr, Dept Pediat Oncol & Hematol, Amsterdam, Netherlands.
[van Vuurden, Dannis G.; Hulleman, Esther] Vrije Univ Amsterdam, Med Ctr, Neuroncol Res Grp Canc Ctr Amsterdam, Amsterdam, Netherlands.
[Fouladi, Maryam] Cincinnati Childrens Hosp Med Ctr, Canc & Blood Dis Inst, Cincinnati, OH 45229 USA.
[Svalina, Matthew N.; Keller, Charles] Childrens Canc Therapy Dev Inst, Ft Collins, CO USA.
[Hawkins, Cynthia] Univ Toronto, Dept Pediat Lab Med, Toronto, ON, Canada.
[Hawkins, Cynthia] Univ Toronto, Hosp Sick Children, Labatt Brain Tumor Res Ctr, Toronto, ON M5G 1X8, Canada.
[Nazarian, Javad] Childrens Natl Hlth Syst, Ctr Res Inst, Washington, DC USA.
[Alonso, Marta M.] Univ Hosp Navarra, Dept Oncol, Pamplona, Spain.
[Grill, Jacques] Univ Paris Sud, Inst Gustave Roussy, Dept Cancerol Enfant & Adolescent, Villejuif, France.
[Grill, Jacques] Parke Davis Res Unit, Inst Gustave Roussy, Dept Cancerol Enfant & Adolescent, Villejuif, France.
RP Monje, M (reprint author), Stanford Univ, Dept Neurol, Stanford, CA 94305 USA.
EM charles@cc-TDI.org; mmonje@stanford.edu
OI Van Vuurden, Dannis/0000-0002-1364-9007
FU Lyla Nsouli Foundation; Children's Oncology Group (COG) Central Nervous
System Committee; DIPG Collaborative (The Cure Starts Now Foundation);
DIPG Collaborative (Reflections of Grace Foundation); DIPG Collaborative
(Smiles for Sophie Foundation); DIPG Collaborative (Cancer-Free Kids
Foundation); DIPG Collaborative (Carly's Crusade Foundation); DIPG
Collaborative (Jeffrey Thomas Hayden Foundation); DIPG Collaborative
(Soar with Grace Foundation); Accelerate Brain Cancer Cures Foundation
(ABC2); CureSearch for Childhood Cancer; Team Julian Foundation; COG
Chair's Grant [5UOCA098543]; US National Institutes of Health
[K08NS070926]; Alex's Lemonade Stand Foundation; McKenna Claire
Foundation; Connor Johnson Memorial Fund; Dylan Jewett Memorial Fund;
Elizabeth Stein Memorial Fund; Dylan Frick Memorial Fund; Abigail Jensen
Memorial Fund; Zoey Ganesh Memorial Fund; Wayland Villars DIPG
Foundation; Jennifer Kranz Memorial Fund; Unravel Pediatric Cancer;
Virginia & D.K. Ludwig Fund for Cancer Research; Price Family Charitable
Fund; Matthew Larson Foundation; Godfrey Family Fund in Memory of Fiona
Penelope; Child Health Research Institute at Stanford; Anne T. and
Robert M. Bass Endowed Faculty Scholarship in Pediatric Cancer and Blood
Diseases; Etoile de Martin; Fondation Lemos; Le Defi de Fortunee; Scott
Carter Foundation; Semmy Foundation; US Department of Defense; National
Science Foundation [CCF0953366]; Marie Curie grant [IRG270459]; Spanish
Ministry of Health [PI13/0125]; St. Baldrick's Foundation; Iron Matt
Foundation
FX We thank the many children and families who selflessly contributed to
this study through tissue donations obtained from surgery or autopsy,
and A. Gajjar for his guidance and vision throughout this study. We also
thank D. Hargrave, J. Olson and S. Leary for selection of V.2 chemical
screen agents. We are grateful for the critical questions and comments
by S. Cheetham and N. Nsouli. We also acknowledge important comments by
another DIPG Preclinical Consortium member, O. Becher. We thank G. Grant
for assistance in developing rodent CED techniques. We thank R.
Hashizume and C.D. James (Northwestern University) for use of the SF7761
DIPG cell line. Short-read sequencing was performed by the OHSU
Massively Parallel Sequencing Shared Resource. This research is
supported by the Lyla Nsouli Foundation, the Children's Oncology Group
(COG) Central Nervous System Committee, the DIPG Collaborative (The Cure
Starts Now Foundation, Reflections of Grace Foundation, Smiles for
Sophie Foundation, Cancer-Free Kids Foundation, Carly's Crusade
Foundation, Jeffrey Thomas Hayden Foundation, Soar with Grace
Foundation), the Accelerate Brain Cancer Cures Foundation
(ABC2), CureSearch for Childhood Cancer, the Team Julian
Foundation and the COG Chair's Grant (5UOCA098543). Additional funding
support was provided by US National Institutes of Health grant
K08NS070926 (to M.M.), Alex's Lemonade Stand Foundation (to M.M. and
Y.T.), the McKenna Claire Foundation, the Connor Johnson Memorial Fund,
the Dylan Jewett Memorial Fund, the Elizabeth Stein Memorial Fund, the
Dylan Frick Memorial Fund, the Abigail Jensen Memorial Fund, the Zoey
Ganesh Memorial Fund, the Wayland Villars DIPG Foundation, the Jennifer
Kranz Memorial Fund, Unravel Pediatric Cancer, the Virginia & D.K.
Ludwig Fund for Cancer Research, the Price Family Charitable Fund, the
Matthew Larson Foundation, the Godfrey Family Fund in Memory of Fiona
Penelope, the Child Health Research Institute at Stanford, the Anne T.
and Robert M. Bass Endowed Faculty Scholarship in Pediatric Cancer and
Blood Diseases (all to M.M.), Etoile de Martin (to J.G. and N.T.),
Fondation Lemos and Le Defi de Fortunee (to J.G.), the Scott Carter
Foundation (to N.E.B.), the Semmy Foundation (to D.G.v.V. and E.H.), the
US Department of Defense (to X.-N.L.), National Science Foundation grant
CCF0953366 (to R.P.), Marie Curie grant IRG270459 (to M.M.A.); the
Spanish Ministry of Health grant PI13/0125 (to M.M.A.), and the St.
Baldrick's Foundation and Iron Matt Foundation (both to E.R. and
M.H.-C.).
NR 19
TC 38
Z9 39
U1 7
U2 27
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD JUN
PY 2015
VL 21
IS 6
BP 555
EP 559
DI 10.1038/nm.3855
PG 5
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA CJ8UF
UT WOS:000355778300010
PM 25939062
ER
PT J
AU Long, AH
Haso, WM
Shern, JF
Wanhainen, KM
Murgai, M
Ingaramo, M
Smith, JP
Walker, AJ
Kohler, ME
Venkateshwara, VR
Kaplan, RN
Patterson, GH
Fry, TJ
Orentas, RJ
Mackall, CL
AF Long, Adrienne H.
Haso, Waleed M.
Shern, Jack F.
Wanhainen, Kelsey M.
Murgai, Meera
Ingaramo, Maria
Smith, Jillian P.
Walker, Alec J.
Kohler, M. Eric
Venkateshwara, Vikas R.
Kaplan, Rosandra N.
Patterson, George H.
Fry, Terry J.
Orentas, Rimas J.
Mackall, Crystal L.
TI 4-1BB costimulation ameliorates T cell exhaustion induced by tonic
signaling of chimeric antigen receptors
SO NATURE MEDICINE
LA English
DT Article
ID CHRONIC VIRAL-INFECTION; ANTITUMOR-ACTIVITY; IN-VIVO; ADOPTIVE
IMMUNOTHERAPY; ENHANCED SURVIVAL; CLINICAL-TRIAL; CD28; PERSISTENCE;
CANCER; MEMORY
AB Chimeric antigen receptors (CARs) targeting CD19 have mediated dramatic antitumor responses in hematologic malignancies, but tumor regression has rarely occurred using CARs targeting other antigens. It remains unknown whether the impressive effects of CD19 CARs relate to greater susceptibility of hematologic malignancies to CAR therapies, or superior functionality of the CD19 CAR itself. We show that tonic CAR CD3-zeta, phosphorylation, triggered by antigen-independent clustering of CAR single-chain variable fragments, can induce early exhaustion of CAR T cells that limits antitumor efficacy. Such activation is present to varying degrees in all CARs studied, except the highly effective CD19 CAR. We further determine that CD28 costimulation augments, whereas 4-1BB costimulation reduces, exhaustion induced by persistent CAR signaling. Our results provide biological explanations for the antitumor effects of CD19 CARs and for the observations that CD19 CAR T cells incorporating the 4-1BB costimulatory domain are more persistent than those incorporating CD28 in clinical trials.
C1 [Long, Adrienne H.; Haso, Waleed M.; Shern, Jack F.; Wanhainen, Kelsey M.; Murgai, Meera; Smith, Jillian P.; Walker, Alec J.; Kohler, M. Eric; Venkateshwara, Vikas R.; Kaplan, Rosandra N.; Fry, Terry J.; Orentas, Rimas J.; Mackall, Crystal L.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Long, Adrienne H.] Northwestern Univ, Feinberg Sch Med, Dept Microbiol & Immunol, Chicago, IL 60611 USA.
[Wanhainen, Kelsey M.] Colgate Univ, Dept Biol, Hamilton, NY 13346 USA.
[Ingaramo, Maria; Patterson, George H.] Natl Inst Biomed Imaging & Bioengn, Sect Biophoton, NIH, Bethesda, MD USA.
[Kohler, M. Eric] Johns Hopkins Univ Hosp, Dept Pediat, Baltimore, MD 21287 USA.
RP Mackall, CL (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM mackallc@mail.nih.gov
OI Wanhainen, Kelsey/0000-0001-8666-0584
FU NIH, NCI; NIH, National Institute of Biomedical Imaging and
Bioengineering (NIBIB) [ZIA BC 011073, ZIA BC 011565, ZIA BC 011332, ZIA
EB 000071-06]; Stand Up To Cancer - St. Baldrick's - NCI Pediatric Dream
Team Translational Cancer Research Grant
FX We kindly thank S. Gottschalk (Texas Children's Hospital) for providing
sequences for the 14g2a scFv and IgG1
CH2CH3; J. Kochenderfer (National Cancer
Institute, NCI, US National Institutes of Health, NIH) for the H3
MSGV-FMC63-28z retroviral vector producer line; S. Grupp (Children's
Hospital of Philadelphia) for the NALM6-GL cell line; R. Morgan
(BlueBird Bio, previously NCI, NIH) for the MSGV-139-28z and
MSGV-4D5-28BBz vectors; and C. June (University of Pennsylvania) for
sequences to the 4-1BB CAR endodomain. We also thank L. Cooper (M.D.
Anderson) for providing the 136.20.1, FMC63 anti-idiotype antibody; the
Biological Research Branch of NCI for providing the 1A7, 14g2a
anti-idiotype antibody; the Clinical Support Laboratory of the Frederick
National Laboratory for Cancer Research (FNLCR) for assisting in
MesoScale cytokine release assays; and the Laboratory of Molecular
Technology (LMT) Microarray Group of FNLCR for assisting in microarray
assays. We thank N. Restifo and M. Roederer for careful review of this
manuscript. This work was supported by the Intramural Research Program
of the NIH, including the NCI and the National Institute of Biomedical
Imaging and Bioengineering (NIBIB): ZIA BC 011073 (A.H.L., K.M.W.,
J.P.S., A.J.W., M.E.K., V.R.V., R.J.O. and C.L.M); ZIA BC 011565 (W.M.H.
and T.J.F.); ZIA BC 011332 (M.M. and R.N.K.); and ZIA EB 000071-06 (M.I.
and G.H.P.) This research was also supported by a Stand Up To Cancer -
St. Baldrick's - NCI Pediatric Dream Team Translational Cancer Research
Grant. Stand Up To Cancer is a program of the Entertainment Industry
Foundation administered by the American Association for Cancer Research.
NR 56
TC 71
Z9 74
U1 4
U2 37
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD JUN
PY 2015
VL 21
IS 6
BP 581
EP 590
DI 10.1038/nm.3838
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA CJ8UF
UT WOS:000355778300014
PM 25939063
ER
PT J
AU Gutmanas, A
Adams, PD
Bardiaux, B
Berman, HM
Case, DA
Fogh, RH
Guntert, P
Hendrickx, PMS
Herrmann, T
Kleywegt, GJ
Kobayashi, N
Lange, OF
Markley, JL
Montelione, GT
Nilges, M
Ragan, TJ
Schwieters, CD
Tejero, R
Ulrich, EL
Velankar, S
Vranken-, WF
Wedell, JR
Westbrook, J
Wishart, DS
Vuister, GW
AF Gutmanas, Aleksandras
Adams, Paul D.
Bardiaux, Benjamin
Berman, Helen M.
Case, David A.
Fogh, Rasmus H.
Guentert, Peter
Hendrickx, Pieter M. S.
Herrmann, Torsten
Kleywegt, Gerard J.
Kobayashi, Naohiro
Lange, Oliver F.
Markley, John L.
Montelione, Gaetano T.
Nilges, Michael
Ragan, Timothy J.
Schwieters, Charles D.
Tejero, Roberto
Ulrich, Eldon L.
Velankar, Sameer
Vranken-, Wim F.
Wedell, Jonathan R.
Westbrook, John
Wishart, David S.
Vuister, Geerten W.
TI NMR Exchange Format: a unified and open standard for representation of
NMR restraint data
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Letter
ID PROTEIN DATA-BANK; WWPDB; FILE
C1 [Gutmanas, Aleksandras; Hendrickx, Pieter M. S.; Kleywegt, Gerard J.; Velankar, Sameer] European Bioinformat Inst, European Mol Biol Lab, Protein Data Bank Europe, Cambridge, England.
[Adams, Paul D.] Lawrence Berkeley Lab, Phys Biosci Div, Berkeley, CA USA.
[Bardiaux, Benjamin; Nilges, Michael] Inst Pasteur, Unite Bioinformat Struct, Dept Biol Struct & Chim, Paris, France.
[Bardiaux, Benjamin; Nilges, Michael] CNRS, Unite Mixte Rech 3528, Paris, France.
[Berman, Helen M.; Case, David A.; Westbrook, John] Rutgers State Univ, Ctr Integrat Prote Res, Dept Chem & Chem Biol, Piscataway, NJ USA.
[Fogh, Rasmus H.; Ragan, Timothy J.; Vuister, Geerten W.] Univ Leicester, Dept Biochem, Leicester LE1 7RH, Leics, England.
[Guentert, Peter] Goethe Univ Frankfurt, Frankfurt Inst Adv Studies, Inst Biophys Chem, D-60054 Frankfurt, Germany.
[Guentert, Peter] Tokyo Metropolitan Univ, Grad Sch Sci & Engn, Tokyo 158, Japan.
[Guentert, Peter] ETH, Phys Chem, Zurich, Switzerland.
[Herrmann, Torsten] Ecole Normale Super Lyon, Ctr Resonance Magnet Nucl Tres Hauts Champs, Villeurbanne, France.
[Herrmann, Torsten] CNRS, Unite Mixte Rech 5280, Inst Sci Analyt, Villeurbanne, France.
[Kobayashi, Naohiro] Osaka Univ, Inst Prot Res, Osaka, Japan.
[Lange, Oliver F.] Tech Univ Munich, Biomol NMR, Munich Ctr Integrated Prot Sci, Dept Chem, Garching, Germany.
[Markley, John L.; Ulrich, Eldon L.] Univ Wisconsin, Dept Biochem, Madison, WI 53705 USA.
[Montelione, Gaetano T.] Rutgers State Univ, Dept Mol Biol & Biochem, Ctr Adv Biotechnol & Med, Piscataway, NJ USA.
[Montelione, Gaetano T.] Rutgers State Univ, Robert Wood Johnson Med Sch, Dept Biochem & Mol Biol, Piscataway, NJ 08854 USA.
[Schwieters, Charles D.] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Tejero, Roberto] Univ Valencia, Dept Quim Fis, Valencia, Spain.
[Vranken-, Wim F.] Vlaams Inst Biotechnol, Struct Biol Res Ctr, Brussels, Belgium.
[Vranken-, Wim F.] Vrije Univ Brussel, Struct Biol Brussels, Brussels, Belgium.
[Vranken-, Wim F.] Univ Libre Bruxelles, Vrije Univ Brussel, Interuniv Inst Bioinformat Brussels, Brussels, Belgium.
[Wishart, David S.] Univ Alberta, Dept Comp Sci, Edmonton, AB, Canada.
[Wishart, David S.] Univ Alberta, Dept Biol Sci, Edmonton, AB, Canada.
RP Vuister, GW (reprint author), Univ Leicester, Dept Biochem, Leicester LE1 7RH, Leics, England.
EM gutmanas@ebi.ac.uk; gv29@le.ac.uk
RI Nilges, Michael/E-4803-2011; Herrmann, Torsten/B-9978-2008; Adams,
Paul/A-1977-2013; Tejero Toquero, Roberto/F-5104-2016; Vranken,
Wim/J-5051-2016; Guntert, Peter/L-5577-2013; Fachbereich14,
Dekanat/C-8553-2015
OI Nilges, Michael/0000-0002-1451-8092; Wishart, David
S/0000-0002-3207-2434; Herrmann, Torsten/0000-0003-2115-4781; Adams,
Paul/0000-0001-9333-8219; Tejero Toquero, Roberto/0000-0003-2504-5988;
Vranken, Wim/0000-0001-7470-4324; Guntert, Peter/0000-0002-2911-7574;
FU Biotechnology and Biological Sciences Research Council [BB/E005071/1,
BB/J007471, BB/J007897/1, BB/K021249/1]; Intramural NIH HHS; Medical
Research Council [MR/L000555/1]; NIGMS NIH HHS [P01 GM063210, R01
GM109046, R01GM109046]; NLM NIH HHS [P41 LM005799, P41LM05799]; Wellcome
Trust [088944]
NR 9
TC 2
Z9 2
U1 2
U2 14
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
EI 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD JUN
PY 2015
VL 22
IS 6
BP 433
EP 434
PG 2
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA CJ6RI
UT WOS:000355620600001
PM 26036565
ER
PT J
AU Xiao, YL
Ma, BY
McElheny, D
Parthasarathy, S
Long, F
Hoshi, M
Nussinov, R
Ishii, Y
AF Xiao, Yiling
Ma, Buyong
McElheny, Dan
Parthasarathy, Sudhakar
Long, Fei
Hoshi, Minako
Nussinov, Ruth
Ishii, Yoshitaka
TI A beta(1-42) fibril structure illuminates self-recognition and
replication of amyloid in Alzheimer's disease
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID SOLID-STATE NMR; NUCLEAR-MAGNETIC-RESONANCE; BETA-SHEET STRUCTURES;
A-BETA; EXPERIMENTAL CONSTRAINTS; PROTEIN BACKBONE; ROTATING SOLIDS;
CHEMICAL-SHIFTS; MODEL; POLYMORPHISM
AB Increasing evidence has suggested that formation and propagation of misfolded aggregates of 42-residue human amyloid beta(A beta(1-42)), rather than of the more abundant A beta(1-40), provokes the Alzheimer's disease cascade. However, structural details of misfolded A beta(1-42) have remained elusive. Here we present the atomic model of an A beta(1-42) amyloid fibril, from solid-state NMR (ssNMR) data. It displays triple parallel-beta-sheet segments that differ from reported structures of A beta(1-40) fibrils. Remarkably, A beta(1-40) is incompatible with the triple-beta-motif, because seeding with A beta(1-42) fibrils does not promote conversion of monomeric A beta(1-40) into fibrils via cross-replication. ssNMR experiments suggest that C-terminal Ala42, absent in A beta(1-40), forms a salt bridge with Lys28 to create a self-recognition molecular switch that excludes A beta(1-40). The results provide insight into the A beta(1-42)-selective self-replicating amyloid-propagation machinery in early-stage Alzheimer's disease.
C1 [Xiao, Yiling; McElheny, Dan; Parthasarathy, Sudhakar; Long, Fei; Ishii, Yoshitaka] Univ Illinois, Dept Chem, Chicago, IL 60607 USA.
[Ma, Buyong; Nussinov, Ruth] NCI, Canc & Inflammat Program, Leidos Biomed Res, Frederick, MD 21701 USA.
[Hoshi, Minako] Inst Biomed Res & Innovat, Kobe, Hyogo, Japan.
[Hoshi, Minako] Kyoto Univ, Dept Anat & Dev Biol, Grad Sch Med, Kyoto, Japan.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Inst Mol Med, Dept Human Genet & Mol Med, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
[Ishii, Yoshitaka] Univ Illinois, Struct Biol Ctr, Chicago, IL USA.
RP Ishii, Y (reprint author), Univ Illinois, Dept Chem, Chicago, IL 60607 USA.
EM yishii@uic.edu
RI Ishii, Yoshitaka/F-4558-2014; Ma, Buyong/F-9491-2011
OI Ishii, Yoshitaka/0000-0002-7724-6469; Ma, Buyong/0000-0002-7383-719X
FU US National Institutes of Health (NIH) RO1 program [GM 098033];
Alzheimer's Association Investigator-Initiated Research Grant (IIRG)
[08-91256]; federal funds from the Frederick National Laboratory for
Cancer Research, NIH [HHSN261200800001E]; Intramural Research Program of
the NIH, Frederick National Laboratory, Center for Cancer Research
FX This work was supported primarily by the US National Institutes of
Health (NIH) RO1 program (GM 098033) and by an Alzheimer's Association
Investigator-Initiated Research Grant (IIRG) (08-91256) to Y.I. This
project has been funded in part with federal funds from the Frederick
National Laboratory for Cancer Research, NIH, under contract
HHSN261200800001E, to B.M. and R.N. This research was supported in part
by the Intramural Research Program of the NIH, Frederick National
Laboratory, Center for Cancer Research, to B.M. and R.N. The content of
this publication does not necessarily reflect the views or policies of
the US Department of Health and Human Services, nor does mention of
trade names, commercial products or organizations imply endorsement by
the US Government. MD simulations to generate initial structural models
were performed at the high-performance computational facilities of the
Biowulf PC/Linux cluster at the NIH (http://biowulf.nih.gov/). Y.I. is
grateful to S. Chimon, C. Jones and N. Wickramasinghe for their initial
efforts in the preparation of A beta(1-42) fibrils at the University of
Illinois at Chicago.
NR 57
TC 82
Z9 84
U1 18
U2 118
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
EI 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD JUN
PY 2015
VL 22
IS 6
BP 499
EP U97
DI 10.1038/nsmb.2991
PG 9
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA CJ6RI
UT WOS:000355620600013
PM 25938662
ER
PT J
AU van Sloten, TT
Protogerou, AD
Henry, RMA
Schram, MT
Launer, LJ
Stehouwer, CDA
AF van Sloten, Thomas T.
Protogerou, Athanase D.
Henry, Ronald M. A.
Schram, Miranda T.
Launer, Lenore J.
Stehouwer, Coen D. A.
TI Association between arterial stiffness, cerebral small vessel disease
and cognitive impairment: A systematic review and meta-analysis
SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
LA English
DT Review
DE Arterial stiffness; Cerebral small vessel disease; White matter
hyperintensities; Cerebral microbleeds; Cerebral infarcts; Cognitive
impairment; Dementia; Meta-analysis; Systematic review
ID PULSE-WAVE VELOCITY; WHITE-MATTER HYPERINTENSITIES; COMMUNITY-DWELLING
POPULATION; HIGH BLOOD-PRESSURE; ALZHEIMERS-DISEASE; RISK-FACTORS;
CARDIOVASCULAR-DISEASE; HYPERTENSIVE PATIENTS; STROKE PATIENTS;
ROTTERDAM SCAN
AB Arterial stiffness may be a cause of cerebral small vessel disease and cognitive impairment. We therefore performed a systematic review and meta-analysis of studies on the association between stiffness, cerebral small vessel disease and cognitive impairment. For the associations between stiffness (i.e. carotid-femoral pulse wave velocity (cfPWV), brachial-ankle PVVV (baPWV), carotid stiffness and pulse pressure) on the one hand and cerebral small vessel disease and cognitive impairment on the other, we identified 23 (n = 15,666/20 cross-sectional; 1 longitudinal; 2 combined cross-sectional/longitudinal) and 41 studies (n= 57,671/26 cross-sectional; 11 longitudinal; 4 combined cross-sectional/longitudinal), respectively. Pooled analyses of cross-sectional studies showed that greater stiffness was associated with markers of cerebral small vessel disease with odds ratios, per +1 SD, of 1.29-1.32 (P<.001). Studies on cognitive impairment could not be pooled due to large heterogeneity. Some (but not all) studies showed an association between greater stiffness and cognitive impairment, and the strength of this association was relatively weak. The present study supports the hypothesis that greater arterial stiffness is a contributor to microvascular brain disease. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [van Sloten, Thomas T.; Protogerou, Athanase D.; Henry, Ronald M. A.; Schram, Miranda T.; Stehouwer, Coen D. A.] Maastricht Univ, Med Ctr, Cardiovasc Res Inst Maastricht, Dept Med, NL-6229 HX Maastricht, Netherlands.
[van Sloten, Thomas T.] Maastricht Univ, Med Ctr, Sch Nutr Toxicol & Metab, NL-6229 HX Maastricht, Netherlands.
[Launer, Lenore J.] NIA, Intramural Res Program, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
RP Stehouwer, CDA (reprint author), Maastricht Univ, Med Ctr, Dept Med, Prof Debyelaan 25, NL-6229 HX Maastricht, Netherlands.
EM cda.stehouwer@mumc.nl
OI Schram, Miranda/0000-0003-0515-4124; Protogerou,
Athanase/0000-0002-3825-532X
FU European Union [299086]
FX Dr. Protogerou has received funding from the European Union Seventh
Framework Programme ([FP7/2009-2013]) under grand agreement No. 299086.
NR 81
TC 19
Z9 19
U1 7
U2 18
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0149-7634
EI 1873-7528
J9 NEUROSCI BIOBEHAV R
JI Neurosci. Biobehav. Rev.
PD JUN
PY 2015
VL 53
BP 121
EP 130
DI 10.1016/j.neubiorev.2015.03.011
PG 10
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA CJ2ZJ
UT WOS:000355352900007
PM 25827412
ER
PT J
AU Hoffman, L
Bann, C
Higgins, R
Vohr, B
AF Hoffman, Laurie
Bann, Carla
Higgins, Rosemary
Vohr, Betty
CA Eunice Kennedy Shriver Natl Inst C
TI Developmental Outcomes of Extremely Preterm Infants Born to Adolescent
Mothers
SO PEDIATRICS
LA English
DT Article
ID BIRTH-WEIGHT INFANTS; CHILD-DEVELOPMENT; LOW-INCOME; PREDICTORS;
PSYCHOPATHOLOGY; INTERVENTION; GRANDMOTHER; TEENAGE; DELAY
AB BACKGROUND AND OBJECTIVES: Extremely preterm infants and infants born to adolescent mothers are at risk for adverse developmental. The objectives were to evaluate development and behavior outcomes of extremely low birth weight (ELBW) infants born to adolescent mothers <20 compared with adult mothers >= 20 years and to identify socioeconomic risk factors that affect outcomes.
METHODS: Retrospective cohort analysis of 211 infants >27 weeks of adolescent mothers and 1723 infants of adult mothers at Neonatal Research Network centers from 2008 to 2011. Groups were compared and regression models were run to predict 18- to 22-month adverse outcomes. Primary outcomes were Bayley-III scores, neurodevelopmental impairment, and Brief Infant Toddler Social Emotional Assessment problem scores (BITSEA/P) >= 75th percentile.
RESULTS: Adolescent mothers were more often single, Hispanic, less educated, and had public insurance. By 18 to 22 months, their children had significantly increased rates of having lived >= 3 places (21% vs 9%), state supervision (7% vs 3%), rehospitalization (56% vs 46%), and BITSEA/P >= 75th percentile (50% vs 32%) and nonsignificant Bayley-III language scores,85 (56% vs 49%, P=.07). In regression analysis, children of adolescent mothers were more likely to have BITSEA/P >= 75th percentile (relative risk 1.50, 95% confidence interval 1.08-2.07). Living >= 3 places and nonwhite race were predictors of adverse behavior. State supervision was an independent predictor of each Bayley-III composite,70 and neurodevelopmental impairment.
CONCLUSIONS: ELBW infants of adolescent mothers experience high social and environmental risks that are associated with adverse behavior outcomes. These findings inform the need for comprehensive follow-up, coordinated care services, and behavior interventions for ELBW infants of adolescent mothers.
C1 [Hoffman, Laurie; Vohr, Betty] Women & Infants Hosp Rhode Isl, Dept Pediat, Providence, RI 02908 USA.
[Bann, Carla] RTI Int, Stat & Epidemiol, Res Triangle Pk, NC USA.
[Higgins, Rosemary] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Hoffman, L (reprint author), Brown Univ, Women & Infants Hosp, Dept Pediat, 101 Dudley St, Providence, RI 02905 USA.
EM lhoffman@wihri.org
FU National Institutes of Health (NIH)
FX Eunice Kennedy Shriver National Institute of Child Health and Human
Development Research Network. Funded by the National Institutes of
Health (NIH).
NR 30
TC 1
Z9 1
U1 4
U2 9
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD JUN
PY 2015
VL 135
IS 6
BP 1082
EP 1092
DI 10.1542/peds.2014-3880
PG 11
WC Pediatrics
SC Pediatrics
GA CJ5UR
UT WOS:000355557400047
PM 25963007
ER
PT J
AU Watson, NF
Badr, MS
Belenky, G
Bliwise, DL
Buxton, OM
Buysse, D
Dinges, DF
Gangwisch, J
Grandner, MA
Kushida, C
Malhotra, RK
Martin, JL
Patel, SR
Quan, SF
Tasali, E
Twery, M
Croft, JB
Maher, E
Barrett, JA
Thomas, SM
Heald, JL
AF Watson, Nathaniel F.
Badr, M. Safwan
Belenky, Gregory
Bliwise, Donald L.
Buxton, Orfeu M.
Buysse, Daniel
Dinges, David F.
Gangwisch, James
Grandner, Michael A.
Kushida, Clete
Malhotra, Raman K.
Martin, Jennifer L.
Patel, Sanjay R.
Quan, Stuart F.
Tasali, Esra
Twery, Michael
Croft, Janet B.
Maher, Elise
Barrett, Jerome A.
Thomas, Sherene M.
Heald, Jonathan L.
TI Recommended Amount of Sleep for a Healthy Adult: A Joint Consensus
Statement of the American Academy of Sleep Medicine and Sleep Research
Society
SO SLEEP
LA English
DT Editorial Material
AB Sleep is essential for optimal health. The American Academy of Sleep Medicine (AASM) and Sleep Research Society (SRS) developed a consensus recommendation for the amount of sleep needed to promote optimal health in adults, using a modified RAND Appropriateness Method process. The recommendation is summarized here. A manuscript detailing the conference proceedings and evidence supporting the final recommendation statement will be published in SLEEP and the Journal of Clinical Sleep Medicine.
C1 Univ Washington, Seattle, WA 98195 USA.
[Badr, M. Safwan] Wayne State Univ, Detroit, MI USA.
[Belenky, Gregory] Washington State Univ, Spokane, WA USA.
[Bliwise, Donald L.] Emory Univ, Atlanta, GA 30322 USA.
[Buxton, Orfeu M.] Penn State Univ, University Pk, PA 16802 USA.
[Buysse, Daniel] Univ Pittsburgh, Pittsburgh, PA USA.
[Dinges, David F.; Grandner, Michael A.] Univ Penn, Philadelphia, PA 19104 USA.
[Gangwisch, James] Columbia Univ, New York, NY USA.
[Kushida, Clete] Stanford Univ, Stanford, CA 94305 USA.
[Malhotra, Raman K.] St Louis Univ, St Louis, MO 63103 USA.
[Martin, Jennifer L.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Patel, Sanjay R.; Quan, Stuart F.] Harvard Univ, Sch Med, Boston, MA USA.
[Tasali, Esra] Univ Chicago, Chicago, IL 60637 USA.
[Twery, Michael] NHLBI, NIH, Bethesda, MD 20892 USA.
[Croft, Janet B.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Maher, Elise] Sleep Disorders Inst, New York, NY USA.
[Barrett, Jerome A.; Thomas, Sherene M.; Heald, Jonathan L.] Amer Acad Sleep Med, Darien, IL USA.
RP Watson, NF (reprint author), 2510 Frontage Rd, Darien, IL 60561 USA.
EM research@aasmnet.org
OI Patel, Sanjay/0000-0002-9142-5172
FU NCATS NIH HHS [UL1 TR000430]; NCCDPHP CDC HHS [1U50DP004930-01]
NR 3
TC 42
Z9 43
U1 4
U2 9
PU AMER ACAD SLEEP MEDICINE
PI WESTCHESTER
PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA
SN 0161-8105
EI 1550-9109
J9 SLEEP
JI Sleep
PD JUN 1
PY 2015
VL 38
IS 6
BP 843
EP 844
AR PII sp-00231-15
DI 10.5665/sleep.4716
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CJ6PY
UT WOS:000355617000001
PM 26039963
ER
PT J
AU Williams, RM
Puetz, TW
Giza, CC
Broglio, SP
AF Williams, Richelle M.
Puetz, Tim W.
Giza, Christopher C.
Broglio, Steven P.
TI Concussion Recovery Time Among High School and Collegiate Athletes: A
Systematic Review and Meta-Analysis
SO SPORTS MEDICINE
LA English
DT Review
ID SPORT-RELATED CONCUSSION; TRAUMATIC BRAIN-INJURY; MILD HEAD-INJURY;
FOOTBALL PLAYERS; NEUROCOGNITIVE PERFORMANCE; NEUROPSYCHOLOGICAL
DEFICITS; INTERNATIONAL-CONFERENCE; CONSENSUS STATEMENT; NCAA
CONCUSSION; SOCCER PLAYERS
AB Background Concussion diagnosis and management is made through the clinical exam using assessment tools that include self-report symptomatology, postural control, and cognitive evaluations. The specific timing of concussion resolution varies between individuals. However, despite a lack of research in concussion recovery, it is widely accepted that the majority of young adults will recover in 7-10 days, with youth athletes taking longer.
Objectives The purpose of this review is to directly compare the recovery duration among high school and collegiate athletes on symptom reports and cognitive assessments following concussion.
Data Sources Data were collected from a literature search comprising high school or college athletes only. This included studies (n = 6) that reported symptom or cognitive performance recovery to the exact day.
Results High school athletes self-reported symptom recovery at 15 days compared with 6 days in collegiate athletes. Both college and high school athletes showed cognitive recovery at similar rates of 5 and 7 days.
Limitations This review only included articles that were directly related to concussed high school or college athletes. Additionally, athletes in the high school and college setting typically receive a battery of neurocognitive tests that may not be as sensitive or as comprehensive as a full neuropsychological exam.
Conclusion The review finds that neurocognitive recovery rates are similar among high school and college athletes, while symptom reporting shows longer recovery time points in high school than in college.
Implications of Key Findings An individualized and stepwise concussion management plan is important for proper concussion recovery regardless of age.
C1 [Williams, Richelle M.] Univ Michigan, Dept Kinesiol, Ann Arbor, MI 48109 USA.
[Puetz, Tim W.] NIH, Off Director, Ctr Clin, Bethesda, MD 20892 USA.
[Giza, Christopher C.] Univ Calif Los Angeles, Dept Pediat, Mattel Childrens Hosp, Los Angeles, CA 90024 USA.
[Giza, Christopher C.] Univ Calif Los Angeles, Dept Neurosurg, Mattel Childrens Hosp, Los Angeles, CA USA.
[Broglio, Steven P.] Univ Michigan, Sch Kinesiol, Univ Michigan Injury Ctr, Ann Arbor, MI 48109 USA.
RP Broglio, SP (reprint author), Univ Michigan, Dept Kinesiol, Ann Arbor, MI 48109 USA.
EM broglio@umich.edu
RI Meijer, Anna/K-5118-2016
FU Department of Defense; Joseph Drown Foundation; National Collegiate
Athletic Association (NCAA); National Institutes of Health (NIH);
Today's and Tomorrow's Children Fund; University of California, Los
Angeles (UCLA) Brain Injury Research Center (BIRC), UCLA Steve Tisch
BrainSPORT
FX Dr. Giza is supported by the Department of Defense, the Joseph Drown
Foundation, the National Collegiate Athletic Association (NCAA), the
National Institutes of Health (NIH), Today's and Tomorrow's Children
Fund, University of California, Los Angeles (UCLA) Brain Injury Research
Center (BIRC), UCLA Steve Tisch BrainSPORT.
NR 68
TC 12
Z9 12
U1 2
U2 29
PU ADIS INT LTD
PI NORTHCOTE
PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND
SN 0112-1642
EI 1179-2035
J9 SPORTS MED
JI Sports Med.
PD JUN
PY 2015
VL 45
IS 6
BP 893
EP 903
DI 10.1007/s40279-015-0325-8
PG 11
WC Sport Sciences
SC Sport Sciences
GA CJ6KP
UT WOS:000355603000009
PM 25820456
ER
PT J
AU Yin, F
Cai, JF
Zen, W
Wei, YH
Zhou, W
Yuan, F
Singh, SR
Wei, YY
AF Yin, Feng
Cai, Junfeng
Zen, Wen
Wei, Yanhui
Zhou, Wei
Yuan, Feng
Singh, Shree Ram
Wei, Yiyong
TI Cartilage Regeneration of Adipose-Derived Stem Cells in the TGF-beta
1-Immobilized PLGA-Gelatin Scaffold
SO STEM CELL REVIEWS AND REPORTS
LA English
DT Article
DE Chondrogenesis; Adipose-derived stem cells; PLGA; Gelatin microspheres;
Transforming growth factor-beta 1
ID CHONDROGENIC DIFFERENTIATION; STROMAL CELLS; HYBRID SCAFFOLD; IN-VITRO;
TISSUE; MICROSPHERES; ASSAY; VIVO
AB Articular cartilage has restricted self-regenerative capacity; therefore, treatment of cartilage lesions is a great challenge in the field of orthopedics. In the present study, we evaluate the enhancing effect of a transforming growth factor-beta 1 (TGF-beta 1)-immobilized scaffold, fabricated by incorporating TGF-beta 1-loaded gelatin microspheres into PLGA framework, on the differentiation of adipose-derived stem cells (ASCs) into chondrocytes. Significant increase in cell proliferation was observed in the TGF-beta 1-immobilized PLGA-gelatin scaffold, as compared with the ASC-seeded non-TGF-beta 1-immobilized PLGA-gelatin scaffold. When chondrogenic differentiation of ASCs was evaluated for both constructs, sulfated glycosaminoglycan (sGAG) content was significantly higher in the TGF-beta 1-immobilized scaffold. This study showed that ASCs containing the TGF-beta 1-immobilized scaffold better promoted cartilage regeneration in defective articular cartilage, which is assessed by histological observation. Based on the above results, we conclude that TGF-beta 1-immobilized PLGA-gelatin scaffold seeded with ASCs considerably enhances the quality of the tissue-engineered cartilage, therefore, advancing the field of cartilage tissue engineering.
C1 [Yin, Feng; Cai, Junfeng; Zen, Wen; Wei, Yanhui; Zhou, Wei; Yuan, Feng] Tongji Univ, Sch Med, Shanghai East Hosp, Dept Joint & Bone Dis, Shanghai 200120, Peoples R China.
[Singh, Shree Ram] NCI, Basic Res Lab, Stem Cell Regulat & Anim Aging Sect, Frederick, MD 21702 USA.
[Wei, Yiyong] Jiao Tong Univ, Sch Med, Shanghai 200025, Peoples R China.
RP Singh, SR (reprint author), NCI, Basic Res Lab, Stem Cell Regulat & Anim Aging Sect, Frederick, MD 21702 USA.
EM singhshr@mail.nih.gov; weiyiyong1232@163.com
RI Singh, Shree Ram/B-7614-2008
OI Singh, Shree Ram/0000-0001-6545-583X
FU Intramural NIH HHS [Z99 CA999999]
NR 28
TC 8
Z9 8
U1 4
U2 28
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1550-8943
EI 1558-6804
J9 STEM CELL REV REP
JI Stem Cell Rev. Rep.
PD JUN
PY 2015
VL 11
IS 3
BP 453
EP 459
DI 10.1007/s12015-014-9561-9
PG 7
WC Cell & Tissue Engineering; Cell Biology; Medicine, Research &
Experimental
SC Cell Biology; Research & Experimental Medicine
GA CJ7FZ
UT WOS:000355661300008
PM 25267436
ER
PT J
AU Kelloff, GJ
Sigman, CC
Scher, HI
AF Kelloff, Gary J.
Sigman, Caroline C.
Scher, Howard I.
TI Biomarker development in the context of urologic cancers
SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
LA English
DT Article
DE Biomarker; Analytical validation; Biomarker qualification; Prostate
cancer biomarkers; Bladder cancer biomarkers; Clinical utility;
Circulating tumor cells (CTCs)
ID SURROGATE END-POINTS; REFRACTORY PROSTATE-CANCER; CIRCULATING
TUMOR-CELLS; QUALITY-OF-LIFE; BLADDER-CANCER; DRUG DEVELOPMENT;
CLINICAL-TRIALS; CHEMOTHERAPY; SURVIVAL; MITOXANTRONE
AB Background: The Food and Drug Administration (FDA) has called for the use of analytically validated biomarkers that have strong evidence of being fit for purpose to identify patients likely to respond and to evaluate the patient response to a therapy, potential toxicity, and drug resistance. This article discusses development and application of these biomarkers in the context of urologic cancers specifically in cancers of the prostate and urinary bladder.
Methods: The FDA has defined four specific categories for contexts of biomarker use: prognostic, predictive, response-indicator, and efficacy-response (surrogate endpoints). Prognostic and predictive biomarkers include pretreatment characteristics of the patient and the tumor. Response-indicator and efficacy response biomarkers occur after treatment and show the effects of treatment on biomarkers. Efficacy response biomarkers show changes associated with clinical benefit and can be surrogates for clinical endpoints leading to drug approvals.
Results: Well-structured development plans are required to satisfy rigorous criteria that must be met to qualify biomarkers for specific contexts of use in drug development and patient management. A description of the extensive effort applied to the validation and qualification of circulating tumor cells in castration resistant prostate cancer is described as an example of the potential utility of biomarkers in urological cancers.
Conclusions: Many potential biomarkers have been identified in prostate and urinary bladder cancers, but few have sufficient demonstration of analytical and clinical validity to meet FDA standards for use in clinical settings. Circulating tumor cell (CTC) assays are particularly promising candidates for informative new biomarkers to measure disease before and after treatment. New technologies are providing opportunities for high definition, more informative analysis. Statistical and computational methodologies to describe assay results are also rapidly evolving. These advances will lead to better diagnosis, earlier indications of treatment response and failure, and better definition of patient cohorts that will respond to a specific treatment. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Kelloff, Gary J.] NCI, Div Canc Treatment & Diag, NIH, Rockville, MD USA.
[Sigman, Caroline C.] CCS Associates, Mountain View, CA 94043 USA.
[Scher, Howard I.] Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, Dept Med, New York, NY 10021 USA.
[Scher, Howard I.] Weill Cornell Med Coll, Dept Med, New York, NY USA.
RP Sigman, CC (reprint author), CCS Associates, Mountain View, CA 94043 USA.
EM csigman@ccsainc.com
RI Mendez, Pedro /J-8955-2016
OI Mendez, Pedro /0000-0001-6713-7907
FU NCI NIH HHS [P50 CA092629]
NR 50
TC 7
Z9 7
U1 1
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1078-1439
EI 1873-2496
J9 UROL ONCOL-SEMIN ORI
JI Urol. Oncol.-Semin. Orig. Investig.
PD JUN
PY 2015
VL 33
IS 6
BP 295
EP 301
DI 10.1016/j.urolonc.2015.01.007
PG 7
WC Oncology; Urology & Nephrology
SC Oncology; Urology & Nephrology
GA CJ8XF
UT WOS:000355786100007
PM 25746942
ER
PT J
AU Cai, T
Hirai, H
Xu, HY
Notkins, AL
AF Cai, Tao
Hirai, Hiroki
Xu, Huanyu
Notkins, Abner L.
TI The minimal promoter region of the dense-core vesicle protein IA-2:
transcriptional regulation by CREB
SO ACTA DIABETOLOGICA
LA English
DT Article
DE Dense-core vesicle; Insulin; IA-2; Promoter; PKA pathway; CREB-binding
site
ID DEPENDENT DIABETES-MELLITUS; INSULIN SECRETORY RESPONSES; PANCREATIC
BETA-CELLS; TYROSINE-PHOSPHATASE; TRANSMEMBRANE PROTEIN;
GENE-EXPRESSION; GLUCOSE; AUTOANTIGEN; SEQUENCE; ISLETS
AB IA-2 is a transmembrane protein found in the dense-core vesicles (DCV) of neuroendocrine cells and one of the major autoantigens in type 1 diabetes. DCV are involved in the secretion of hormones (e.g., insulin) and neurotransmitters. Stimulation of pancreatic beta cells with glucose upregulates the expression of IA-2 and an increase in IA-2 results in an increase in the number of DCV. Little is known, however, about the promoter region of IA-2 or the transcriptional factors that regulate the expression of this gene.
In the present study, we constructed eight deletion fragments from the upstream region of the IA-2 transcription start site and linked them to a luciferase reporter.
By this approach, we have identified a short bp region (-216 to +115) that has strong promoter activity. We also identified a transcription factor, cAMP responsive element-binding protein (CREB), which binds to two CREB-related binding sites located in this region. The binding of CREB to these sites enhanced IA-2 transcription by more than fivefold. We confirmed these findings by site-directed mutagenesis, chromatin immunoprecipitation assays and RNAi inhibition.
Based on these findings, we conclude that the PKA pathway is a critical, but not the exclusive signaling pathway involved in IA-2 gene expression.
C1 [Cai, Tao; Hirai, Hiroki; Xu, Huanyu; Notkins, Abner L.] NIDCR, Expt Med Sect, Lab Sensory Biol, NIH, Bethesda, MD 20892 USA.
RP Notkins, AL (reprint author), NIDCR, Expt Med Sect, Lab Sensory Biol, NIH, B30 Rm106, Bethesda, MD 20892 USA.
EM tcai@mail.nih.gov; anotkins@mail.nih.gov
FU Intramural Research Program of the NIH
FX We thank Dr. Raju Gottumukkala for his comments and Charles Wohlenberg
for technical help. This research was supported by the Intramural
Research Program of the NIH.
NR 29
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER-VERLAG ITALIA SRL
PI MILAN
PA VIA DECEMBRIO, 28, MILAN, 20137, ITALY
SN 0940-5429
EI 1432-5233
J9 ACTA DIABETOL
JI Acta Diabetol.
PD JUN
PY 2015
VL 52
IS 3
BP 573
EP 580
DI 10.1007/s00592-014-0689-5
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CJ1HB
UT WOS:000355233500017
PM 25528004
ER
PT J
AU Scadding, GW
Eifan, AO
Lao-Araya, M
Penagos, M
Poon, SY
Steveling, E
Yan, R
Switzer, A
Phippard, D
Togias, A
Shamji, MH
Durham, SR
AF Scadding, G. W.
Eifan, A. O.
Lao-Araya, M.
Penagos, M.
Poon, S. Y.
Steveling, E.
Yan, R.
Switzer, A.
Phippard, D.
Togias, A.
Shamji, M. H.
Durham, S. R.
TI Effect of grass pollen immunotherapy on clinical and local immune
response to nasal allergen challenge
SO ALLERGY
LA English
DT Article
DE allergic rhinitis; chemokine; cytokine; Th2; tryptase
ID CONTROLLED-TRIAL; LAVAGE FLUID; TIME-COURSE; RHINITIS; SECRETIONS;
MEDIATORS; CYTOKINES; CELLS; PROVOCATION; EXPOSURE
AB RationaleNasal allergen provocations may be useful in investigating the pathophysiology of allergic rhinitis and effects of treatments.
ObjectiveTo use grass pollen nasal allergen challenge (NAC) to investigate the effects of allergen immunotherapy in a cross-sectional study.
MethodsWe studied nasal and cutaneous responses in untreated subjects with seasonal grass-pollen allergic rhinitis (n=14) compared with immunotherapy-treated allergics (n=14), plus a nonatopic control group (n=14). Volunteers underwent a standardized NAC with 2000biological units of timothy grass allergen (equivalent to 1.3g major allergen, Phl p5). Nasal fluid was collected and analysed by ImmunoCAP and multiplex assays. Clinical response was assessed by symptom scores and peak nasal inspiratory flow (PNIF). Cutaneous response was measured by intradermal allergen injection. Retrospective seasonal symptom questionnaires were also completed.
ResultsImmunotherapy-treated patients had lower symptom scores (P=0.04) and higher PNIF (P=0.02) after challenge than untreated allergics. They had reduced early (P=0.0007) and late (P<0.0001) skin responses, and lower retrospective seasonal symptom scores (P<0.0001). Compared to untreated allergics, immunotherapy-treated patients had reduced nasal fluid concentrations of IL-4, IL-9 and eotaxin (all P<0.05, 8h level and/or area under the curve comparison), and trends for reduced IL-13 (P=0.07, area under the curve) and early-phase tryptase levels (P=0.06).
ConclusionsNasal allergen challenge is sensitive in the detection of clinical and biological effects of allergen immunotherapy and may be a useful surrogate marker of treatment efficacy in future studies.
C1 [Scadding, G. W.; Eifan, A. O.; Lao-Araya, M.; Penagos, M.; Poon, S. Y.; Steveling, E.; Yan, R.; Switzer, A.; Shamji, M. H.; Durham, S. R.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Allergy & Clin Immunol, London SW7 2AZ, England.
[Phippard, D.] Immune Tolerance Network, Bethesda, MD USA.
[Togias, A.] NIAID, Bethesda, MD 20892 USA.
RP Durham, SR (reprint author), Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Allergy & Clin Immunol, Sir Alexander Fleming Bldg, London SW7 2AZ, England.
EM s.durham@imperial.ac.uk
OI Eifan, Aarif/0000-0003-4098-4211
FU Imperial College Wellcome Trust Clinical PhD Fellow Programme
[097881/Z/11/Z]; ALK-Abello, Denmark; Immune Tolerance Network (NIH)
[N01 AI15416]; National Institute of Allergy and Infectious Diseases,
USA
FX This research was funded by an Imperial College Wellcome Trust Clinical
PhD Fellow Programme, awarded to Guy W. Scadding (reference:
097881/Z/11/Z), and by a research grant from ALK-Abello, Denmark.
Stephen R. Durham and Mohamed H. Shamji were part-funded by the Immune
Tolerance Network (NIH Contract # N01 AI15416), an international
clinical research consortium headquartered at the Benaroya Research
Institute, Seattle, Washington, and supported by the National Institute
of Allergy and Infectious Diseases, USA.
NR 30
TC 14
Z9 14
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-4538
EI 1398-9995
J9 ALLERGY
JI Allergy
PD JUN
PY 2015
VL 70
IS 6
BP 689
EP 696
DI 10.1111/all.12608
PG 8
WC Allergy; Immunology
SC Allergy; Immunology
GA CJ1LR
UT WOS:000355245600010
PM 25773990
ER
PT J
AU Trehan, A
Brady, JM
Maduro, V
Bone, WP
Huang, Y
Golas, GA
Kane, MS
Lee, PR
Thurm, A
Gropman, AL
Paul, SM
Vezina, G
Markello, TC
Gahl, WA
Boerkoel, CF
Tifft, CJ
AF Trehan, Aditi
Brady, Jacqueline M.
Maduro, Valerie
Bone, William P.
Huang, Yan
Golas, Gretchen A.
Kane, Megan S.
Lee, Paul R.
Thurm, Audrey
Gropman, Andrea L.
Paul, Scott M.
Vezina, Gilbert
Markello, Thomas C.
Gahl, William A.
Boerkoel, Cornelius F.
Tifft, Cynthia J.
TI MED23-associated intellectual disability in a non-consanguineous family
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE intellectual disability (ID); MED23; mediator complex; whole exome
sequencing (WES)
ID MUTATION; MED12; GENE
AB Intellectual disability (ID) is a heterogeneous condition arising from a variety of environmental and genetic factors. Among these causes are defects in transcriptional regulators. Herein, we report on two brothers in a nonconsanguineous family with novel compound heterozygous, disease-segregating mutations (NM_015979.3: [3656A>G];[4006C>T], NP_057063.2: [H1219R];[R1336X]) in MED23. This gene encodes a subunit of the Mediator complex that modulates the expression of RNA polymerase II-dependent genes. These brothers, who had profound ID, spasticity, congenital heart disease, brain abnormalities, and atypical electroencephalography, represent the first case of MED23-associated ID in a non-consanguineous family. They also expand upon the clinical features previously reported for mutations in this gene. (c) 2015 Wiley Periodicals, Inc.
C1 [Trehan, Aditi; Brady, Jacqueline M.; Maduro, Valerie; Bone, William P.; Huang, Yan; Golas, Gretchen A.; Gropman, Andrea L.; Gahl, William A.; Tifft, Cynthia J.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Trehan, Aditi; Brady, Jacqueline M.; Maduro, Valerie; Bone, William P.; Huang, Yan; Golas, Gretchen A.; Kane, Megan S.; Markello, Thomas C.; Gahl, William A.; Boerkoel, Cornelius F.; Tifft, Cynthia J.] NIH Off Rare Dis Res, NIH Undiagnosed Dis Program, Bethesda, MD USA.
[Trehan, Aditi; Brady, Jacqueline M.; Maduro, Valerie; Bone, William P.; Huang, Yan; Golas, Gretchen A.; Kane, Megan S.; Markello, Thomas C.; Gahl, William A.; Boerkoel, Cornelius F.; Tifft, Cynthia J.] NHGRI, Bethesda, MD 20892 USA.
[Lee, Paul R.] NINDS, NIH, Bethesda, MD 20892 USA.
[Thurm, Audrey] NIMH, Pediat & Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Gropman, Andrea L.; Vezina, Gilbert] George Washington Univ, Sch Med & Hlth Sci, Childrens Natl Med Ctr, Washington, DC 20052 USA.
[Paul, Scott M.] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Tifft, CJ (reprint author), NHGRI, Off Clin Director, NIH, Bldg 10 CRC3-2551 MSC 1205,10 Ctr Dr, Bethesda, MD 20892 USA.
EM cynthiat@mail.nih.gov
NR 17
TC 2
Z9 2
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4825
EI 1552-4833
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD JUN
PY 2015
VL 167
IS 6
BP 1374
EP 1380
DI 10.1002/ajmg.a.37047
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA CJ1WV
UT WOS:000355276700031
PM 25845469
ER
PT J
AU Allen-Daniels, MJ
Serrano, MG
Pflugner, LP
Fettweis, JM
Prestosa, MA
Koparde, VN
Brooks, JP
Strauss, JF
Romero, R
Chaiworapongsa, T
Eschenbach, DA
Buck, GA
Jefferson, KK
AF Allen-Daniels, Matthew Josiah
Serrano, Myrna G.
Pflugner, Lindsey P.
Fettweis, Jennifer M.
Prestosa, Melissa A.
Koparde, Vishal N.
Brooks, J. Paul
Strauss, Jerome F., III
Romero, Roberto
Chaiworapongsa, Tinnakorn
Eschenbach, David A.
Buck, Gregory A.
Jefferson, Kimberly K.
TI Identification of a gene in Mycoplasma hominis associated with preterm
birth and microbial burden in intraamniotic infection
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE chorioamnionitis; genital mycoplasmas; genome sequencing; microbial
invasion of the amniotic cavity; pathogenicity
ID AMNIOTIC-FLUID INFECTION; ABNORMAL VAGINAL FLORA; ADVERSE PREGNANCY
OUTCOMES; BACTERIAL VAGINOSIS; UREAPLASMA-UREALYTICUM; PREMATURE LABOR;
INTACT MEMBRANES; INTRAUTERINE INFECTION; PERIODONTAL-DISEASE; PRELABOR
RUPTURE
AB OBJECTIVE: Microbial invasion of the amniotic cavity is associated with spontaneous preterm labor and adverse pregnancy outcome, and Mycoplasma hominis often is present. However, the pathogenic process by which Mycoplasma hominis invades the amniotic cavity and gestational tissues, often resulting in chorioamnionitis and preterm birth, remains unknown. We hypothesized that strains of Mycoplasma hominis vary genetically with regards to their potential to invade and colonize the amniotic cavity and placenta.
STUDY DESIGN: We sequenced the entire genomes of 2 amniotic fluid isolates and a placental isolate of Mycoplasma hominis from pregnancies that resulted in preterm births and compared them with the previously sequenced genome of the type strain PG21. We identified genes that were specific to the amniotic fluid/placental isolates. We then determined the microbial burden and the presence of these genes in another set of subjects from whom samples of amniotic fluid had been collected and were positive for Mycoplasma hominis.
RESULTS: We identified 2 genes that encode surface-located membrane proteins (Lmp1 and Lmp-like) in the sequenced amniotic fluid/placental isolates that were truncated severely in PG21. We also identified, for the first time, a microbial gene of unknown function that is referred to in this study as gene of interest C that was associated significantly with bacterial burden in amniotic fluid and the risk of preterm delivery in patients with preterm labor.
CONCLUSION: A gene in Mycoplasma hominis was identified that is associated significantly with colonization and/or infection of the upper reproductive tract during pregnancy and with preterm birth.
C1 [Allen-Daniels, Matthew Josiah; Pflugner, Lindsey P.; Fettweis, Jennifer M.; Prestosa, Melissa A.; Buck, Gregory A.; Jefferson, Kimberly K.] Virginia Commonwealth Univ, Dept Microbiol & Immunol, Sch Med, Richmond, VA 23298 USA.
[Brooks, J. Paul] Virginia Commonwealth Univ, Sch Med, Dept Stat Sci & Operat Res, Richmond, VA 23298 USA.
[Strauss, Jerome F., III] Virginia Commonwealth Univ, Sch Med, Dept Obstet & Gynecol, Richmond, VA 23298 USA.
[Romero, Roberto; Chaiworapongsa, Tinnakorn] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Perinatal Res & Obstet, Perinatol Res Branch, NIH, Bethesda, MD USA.
[Romero, Roberto; Chaiworapongsa, Tinnakorn] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Eschenbach, David A.] Univ Washington, Sch Med, Dept Obstet & Gynecol, Seattle, WA 98195 USA.
RP Jefferson, KK (reprint author), Virginia Commonwealth Univ, Dept Microbiol & Immunol, Sch Med, Richmond, VA 23298 USA.
EM kkjefferson@vcu.edu
OI Koparde, Vishal/0000-0001-8978-8495
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; National Institutes of Health grant "A Multi-'omic
Analysis of the Vaginal Microbiome during Pregnancy" [4UH3AI083263, P60
MD002256, U54 DE023786, AI 31871]
FX Supported 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, and National Institutes of Health grant numbers
4UH3AI083263, P60 MD002256, U54 DE023786 "A Multi-'omic Analysis of the
Vaginal Microbiome during Pregnancy," and AI 31871.
NR 85
TC 2
Z9 2
U1 0
U2 9
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JUN
PY 2015
VL 212
IS 6
AR 779.e1
DI 10.1016/j.ajog.2015.01.032
PG 13
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA CJ1RN
UT WOS:000355262000021
PM 25637842
ER
PT J
AU Grigg, ME
Dubey, JP
Nussenblatt, RB
AF Grigg, Michael E.
Dubey, Jitender P.
Nussenblatt, Robert B.
TI Ocular Toxoplasmosis: Lessons From Brazil
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Editorial Material
ID GLOBAL REASSESSMENT; MEMORIAL-LECTURE; SOUTHERN BRAZIL; GONDII;
RETINOCHOROIDITIS; INFECTION; DISEASE; RECURRENCES; ANTIGENS; BLOOD
C1 [Grigg, Michael E.] NIAID, Parasit Dis Lab, Mol Parasitol Sect, Div Intramural Res,NIH, Bethesda, MD 20892 USA.
[Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Dubey, Jitender P.] USDA, Beltsville Agr Res Ctr, Beltsville, MD 20705 USA.
RP Grigg, ME (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr,Room B1-06, Bethesda, MD 20892 USA.
EM griggm@niaid.nih.gov
FU Intramural NIH HHS [ZIA AI001017-09]
NR 29
TC 11
Z9 11
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD JUN
PY 2015
VL 159
IS 6
BP 999
EP 1001
DI 10.1016/j.ajo.2015.04.005
PG 3
WC Ophthalmology
SC Ophthalmology
GA CI9DL
UT WOS:000355070500001
PM 25956461
ER
PT J
AU Castaneto, MS
Barnes, AJ
Concheiro, M
Klette, KL
Martin, TA
Huestis, MA
AF Castaneto, Marisol S.
Barnes, Allan J.
Concheiro, Marta
Klette, Kevin L.
Martin, Thomas A.
Huestis, Marilyn A.
TI Biochip array technology immunoassay performance and quantitative
confirmation of designer piperazines for urine workplace drug testing
SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY
LA English
DT Article
DE Piperazines; BZP; HRMS; Biochip; Novel psychoactive substances
ID N-BENZYLPIPERAZINE BZP; SYNTHETIC CANNABINOIDS; ABUSE;
1-BENZYLPIPERAZINE; METABOLISM; TRAZODONE;
1-(3-TRIFLUOROMETHYLPHENYL)-PIPERAZINE; SPECTROMETRY; TFMPP; MS
AB Designer piperazines are emerging novel psychoactive substances (NPS) with few high-throughput screening methods for their identification. We evaluated a biochip array technology (BAT) immunoassay for phenylpiperazines (PNP) and benzylpiperazines (BZP) and analyzed 20,017 randomly collected urine workplace specimens. Immunoassay performance at recommended cutoffs was evaluated for PNPI (5 mu g/L), PNPII (7.5 mu g/L), and BZP (5 mu g/L) antibodies. Eight hundred forty positive and 206 randomly selected presumptive negative specimens were confirmed by liquid chromatography high-resolution mass spectrometry (LC-HRMS). Assay limits of detection for PNPI, PNPII, and BZP were 2.9, 6.3, and 2.1 mu g/L, respectively. Calibration curves were linear (R (2) > 0.99) with upper limits of 42 mu g/L for PNPI/PNII and 100 mu g/L for BZP. Quality control samples demonstrated imprecision < 19.3 %CV and accuracies 86.0-94.5 % of target. There were no interferences from 106 non-piperazine substances. Seventy-eight of 840 presumptive positive specimens (9.3 %) were LC-HRMS positive, with 72 positive for 1-(3-chlorophenyl)piperazine (mCPP), a designer piperazine and antidepressant trazodone metabolite. Of 206 presumptive negative specimens, one confirmed positive for mCPP (3.3 mu g/L) and one for BZP (3.6 mu g/L). BAT specificity (21.1 to 91.4 %) and efficiency (27.0 to 91.6 %) increased, and sensitivity slightly decreased (97.5 to 93.8 %) with optimized cutoffs of 25 mu g/L PNPI, 42 mu g/L PNPI, and 100 mu g/L BZP. A high-throughput screening method is needed to identify piperazine NPS. We evaluated performance of the Randox BAT immunoassay to identify urinary piperazines and documented improved performance when antibody cutoffs were raised. In addition, in randomized workplace urine specimens, all but two positive specimens contained mCPP and/or trazodone, most likely from legitimate medical prescriptions.
C1 [Castaneto, Marisol S.; Barnes, Allan J.; Concheiro, Marta; Huestis, Marilyn A.] NIDA, Chem & Drug Metab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Castaneto, Marisol S.] Univ Maryland, Baltimore Sch Med, Toxicol Program, Baltimore, MD 20742 USA.
[Klette, Kevin L.; Martin, Thomas A.] Off Secretary Def Personnel & Readiness, Drug Testing & Program Policy, Personnel Risk Reduct, Washington, DC USA.
[Concheiro, Marta] CUNY John Jay Coll Criminal Justice, Dept Sci, New York, NY 10019 USA.
RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU DOD Counter Narcotics Program [Y3-DA-1116-01]; Intramural Research
Program of the National Institute on Drug Abuse, NIH; Forensic
Toxicology Drug Testing Laboratory, Fort Meade, MD; Chemistry and Drug
Metabolism
FX An Interagency Agreement (Y3-DA-1116-01) between DOD Counter Narcotics
Program and Intramural Research Program of the National Institute on
Drug Abuse, NIH helped fund this research. Assistance and support of the
Forensic Toxicology Drug Testing Laboratory, Fort Meade, MD and
Chemistry and Drug Metabolism staff in the conduct of this study are
greatly appreciated.
NR 25
TC 4
Z9 4
U1 1
U2 9
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1618-2642
EI 1618-2650
J9 ANAL BIOANAL CHEM
JI Anal. Bioanal. Chem.
PD JUN
PY 2015
VL 407
IS 16
BP 4639
EP 4648
DI 10.1007/s00216-015-8660-z
PG 10
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA CJ0FZ
UT WOS:000355152500013
PM 25903022
ER
PT J
AU Flores, KF
Robledo, CA
Hwang, BS
Leishear, K
Grantz, KL
Mendola, P
AF Flores, Katrina F.
Robledo, Candace A.
Hwang, Beom Seuk
Leishear, Kira
Grantz, Katherine Laughon
Mendola, Pauline
TI Does maternal asthma contribute to racial/ethnic disparities in
obstetrical and neonatal complications?
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
DE Asthma; Pregnancy; Infant; Ethnic groups; Health disparities
ID BLACK WOMENS HEALTH; PERINATAL OUTCOMES; PRETERM BIRTH;
RACIAL-DISCRIMINATION; DEPRESSIVE SYMPTOMS; ETHNIC DISPARITIES;
AFRICAN-AMERICAN; INFANT-MORTALITY; PREGNANT-WOMEN; UNITED-STATES
AB Purpose: To examine whether maternal asthma contributes to racial/ethnic differences in obstetrical and neonatal complications.
Methods: Data on white (n = 110,603), black (n = 50,284), and Hispanic (n = 38,831) singleton deliveries came from the Consortium on Safe Labor. Multilevel logistic regression models, with an interaction term for asthma and race/ethnicity, estimated Within-group adjusted odds ratios (aORs) for gestational diabetes, gestational hypertension, pre-eclampsia, placental abruption, premature rupture of membranes, preterm delivery, maternal hemorrhage, neonatal intensive care unit admissions, small for gestational age, apnea, respiratory distress syndrome, transient tachypnea of the newborn, anemia, and hyperbilirubinemia after adjustment for clinical and demographic confounders. Nonasthmatics of the same racial/ethnic group were the reference group.
Results: Compared with nonasthmatics, white asthmatics had increased odds of pre-eclampsia (aOR, 1.28; 95% confidence interval [CI], 1.15-1.43) and maternal hemorrhage (aOR, 1.14; 95% Cl, 1.04-1.23). White and Hispanic infants were more likely to have neonatal intensive care unit admissions (aOR, 1.19; 95% Cl, 1.11-1.28; aOR, 1.16; 95% Cl, 1.02-1.32, respectively) and be small for gestational age (aOR, 1.11; 95% Cl, 1.02-1.20; aOR, 1.26; 95% Cl, 1.10-1.44, respectively), and Hispanic infants were more likely to have apnea (aOR, 1.32; 95% Cl, 1.02-1.69).
Conclusions: Maternal asthma did not affect most obstetrical and neonatal complication risks within racial/ethnic groups. Despite their increased risk for both asthma and many complications, our findings for black women were null. Asthma did not contribute to racial/ethnic disparities in complications. Published by Elsevier Inc.
C1 [Flores, Katrina F.; Robledo, Candace A.; Grantz, Katherine Laughon; Mendola, Pauline] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA.
[Hwang, Beom Seuk] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA.
[Leishear, Kira] US FDA, Div Epidemiol, Off Surveillance & Epidemiol, Off Pharmacovigilance & Epidemiol,Ctr Drug Evalua, Silver Spring, MD USA.
RP Mendola, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd,Room 7B03F, Rockville, MD 20852 USA.
EM pauline.mendola@nih.gov
OI Mendola, Pauline/0000-0001-5330-2844; Grantz,
Katherine/0000-0003-0276-8534
FU Intramural Research Program of the National Institutes of Health (NIH);
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD); Intramural Research Program of the NIH, NICHD
[HHSN267200603425C]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH), Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD). The data
included in this article were obtained from the Consortium on Safe
Labor, supported by the Intramural Research Program of the NIH, NICHD,
through contract number HHSN267200603425C.
NR 41
TC 0
Z9 0
U1 1
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1047-2797
EI 1873-2585
J9 ANN EPIDEMIOL
JI Ann. Epidemiol.
PD JUN
PY 2015
VL 25
IS 6
BP 392
EP 397
DI 10.1016/j.annepidem.2015.01.011
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CI8KM
UT WOS:000355021200002
PM 25724829
ER
PT J
AU Hughes, JP
Haley, DF
Frew, PM
Golin, CE
Adimora, AA
Kuo, I
Justman, J
Soto-Torres, L
Wang, J
Hodder, S
AF Hughes, James P.
Haley, Danielle F.
Frew, Paula M.
Golin, Carol E.
Adimora, Adaora A.
Kuo, Irene
Justman, Jessica
Soto-Torres, Lydia
Wang, Jing
Hodder, Sally
TI Regression to the mean and changes in risk behavior following study
enrollment in a cohort of US women at risk for HIV
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
DE HIV; Risk behavior; Statistical model; Logistic regression
ID ACQUISITION; TRIAL
AB Purpose: Reductions in risk behaviors are common following enrollment in human immunodeficiency virus (HIV) prevention studies. We develop methods to quantify the proportion of change in risk behaviors that can be attributed to regression to the mean versus study participation and other factors.
Methods: A novel model that incorporates both regression to the mean and study participation effects is developed for binary measures. The model is used to estimate the proportion of change in the prevalence of "unprotected sex in the past 6 months" that can be attributed to study participation versus regression to the mean in a longitudinal cohort of women at risk for HIV infection who were recruited from ten U.S. communities with high rates of HIV and poverty. HIV risk behaviors were evaluated using audio computer-assisted self-interviews at baseline and every 6 months for up to 12 months.
Results: The prevalence of "unprotected sex in the past 6 months" declined from 96% at baseline to 77% at 12 months. However, this change could be almost completely explained by regression to the mean.
Conclusions: Analyses that examine changes over time in cohorts selected for high- or low- risk behaviors should account for regression to the mean effects. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Hughes, James P.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Hughes, James P.; Wang, Jing] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Haley, Danielle F.; Frew, Paula M.] Emory Univ, Rollins Sch Publ Hlth, Dept Behav Sci & Hlth Educ, Atlanta, GA 30322 USA.
[Haley, Danielle F.] Family Hlth Int FHI360, Durham, NC USA.
[Frew, Paula M.] Emory Univ, Sch Med, Div Infect Dis, Dept Med, Atlanta, GA 30322 USA.
[Golin, Carol E.; Adimora, Adaora A.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Golin, Carol E.; Adimora, Adaora A.] Univ N Carolina, Gillings Sch Publ Hlth, Chapel Hill, NC USA.
[Kuo, Irene] George Washington Univ, Dept Epidemiol & Biostat, Washington, DC USA.
[Justman, Jessica] Columbia Univ, ICAP Columbia, Dept Epidemiol, New York, NY USA.
[Justman, Jessica] Columbia Univ, ICAP Columbia, Dept Med, New York, NY USA.
[Soto-Torres, Lydia] NIAID, Bethesda, MD 20892 USA.
[Hodder, Sally] W Virginia Univ, Clin & Translat Sci Inst, Morgantown, WV 26506 USA.
RP Hughes, JP (reprint author), Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
EM jphughes@uw.edu
FU National Institute of Allergy and Infectious Diseases; National
Institute on Drug Abuse; National Institute of Mental Health [UM1
AI068617]
FX This study was sponsored by the National Institute of Allergy and
Infectious Diseases, National Institute on Drug Abuse and National
Institute of Mental Health under cooperative agreement UM1 AI068617.
NR 15
TC 1
Z9 1
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1047-2797
EI 1873-2585
J9 ANN EPIDEMIOL
JI Ann. Epidemiol.
PD JUN
PY 2015
VL 25
IS 6
BP 439
EP 444
DI 10.1016/j.annepidem.2015.03.013
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CI8KM
UT WOS:000355021200009
PM 25883065
ER
PT J
AU Brownson, RC
Samet, JM
Chavez, GF
Davies, MM
Galea, S
Hiatt, RA
Hornung, CA
Khoury, MJ
Koo, D
Mays, VM
Remington, P
Yarber, L
AF Brownson, Ross C.
Samet, Jonathan M.
Chavez, Gilbert F.
Davies, Megan M.
Galea, Sandro
Hiatt, Robert A.
Hornung, Carlton A.
Khoury, Muin J.
Koo, Denise
Mays, Vickie M.
Remington, Patrick
Yarber, Laura
TI Charting a future for epidemiologic training
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
DE Epidemiology; Genomics; Globalization; Medicine; Public health;
Translational research
ID PUBLIC-HEALTH; TRANSLATIONAL RESEARCH; CANCER-EPIDEMIOLOGY; POPULATION
HEALTH; BIG DATA; 21ST-CENTURY; OPPORTUNITIES; COMPETENCES; SCIENCE;
GLOBALIZATION
AB Purpose: To identify macro-level trends that are changing the needs of epidemiologic research and practice and to develop and disseminate a set of competencies and recommendations for epidemiologic training that will be responsive to these changing needs.
Methods: There were three stages to the project: (1) assembling of a working group of senior epidemiologists from multiple sectors, (2) identifying relevant literature, and (3) conducting key informant interviews with 15 experienced epidemiologists.
Results: Twelve macro trends were identified along with associated actions for the field and educational competencies. The macro trends include the following: (1) "Big Data" or informatics, (2) the changing health communication environment, (3) the Affordable Care Act or health care system reform, (4) shifting demographics, (5) globalization, (6) emerging high-throughput technologies (omics), (7) a greater focus on accountability, (8) privacy changes, (9) a greater focus on "upstream" causes of disease, (10) the emergence of translational sciences, (11) the growing centrality of team and transdisciplinary science, and (12) the evolving funding environment.
Conclusions: Addressing these issues through curricular change is needed to allow the field of epidemiology to more fully reach and sustain its full potential to benefit population health and remain a scientific discipline that makes critical contributions toward ensuring clinical, social, and population health. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Brownson, Ross C.] Washington Univ, Brown Sch, Prevent Res Ctr St Louis, St Louis, MO 63130 USA.
[Brownson, Ross C.] Washington Univ, Sch Med, Div Publ Hlth Sci, St Louis, MO 63130 USA.
[Brownson, Ross C.] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO 63130 USA.
[Samet, Jonathan M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Chavez, Gilbert F.] Calif Dept Publ Hlth, Ctr Infect Dis, Sacramento, CA USA.
[Davies, Megan M.] North Carolina Dept Hlth & Human Serv, Div Publ Hlth, Raleigh, NC USA.
[Davies, Megan M.] Council State & Terr Epidemiologists, Atlanta, GA USA.
[Galea, Sandro] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Hiatt, Robert A.] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA USA.
[Hornung, Carlton A.] Univ Louisville, Sch Med, Dept Med, Louisville, KY 40292 USA.
[Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA.
[Khoury, Muin J.] NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Koo, Denise] Ctr Dis Control & Prevent, Off Publ Hlth Sci Serv, Atlanta, GA USA.
[Mays, Vickie M.] Univ Calif Los Angeles, Dept Psychol, Fielding Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Mays, Vickie M.] Univ Calif Los Angeles, BRITE Ctr Sci Res & Policy, Los Angeles, CA USA.
[Mays, Vickie M.] Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Los Angeles, CA USA.
[Remington, Patrick] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI 53706 USA.
[Yarber, Laura] St Louis Univ, Coll Publ Hlth & Social Justice, Prevent Res Ctr St Louis, St Louis, MO 63103 USA.
RP Brownson, RC (reprint author), Washington Univ, Brown Sch, Prevent Res Ctr St Louis, 621 N Skinker Blvd, St Louis, MO 63130 USA.
EM rbrownson@wustl.edu
FU Intramural CDC HHS [CC999999]; NCCDPHP CDC HHS [U48 DP000060]; NCI NIH
HHS [P50 CA095815]; NIDDK NIH HHS [P30 DK092950]; NIMHD NIH HHS [P60
MD006923]
NR 58
TC 6
Z9 6
U1 1
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1047-2797
EI 1873-2585
J9 ANN EPIDEMIOL
JI Ann. Epidemiol.
PD JUN
PY 2015
VL 25
IS 6
BP 458
EP 465
DI 10.1016/j.annepidem.2015.03.002
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CI8KM
UT WOS:000355021200012
PM 25976024
ER
PT J
AU Ward, MM
Guthrie, LC
Alba, MI
AF Ward, Michael M.
Guthrie, Lori C.
Alba, Maria I.
TI Measures of Arthritis Activity Associated With Patient-Reported
Improvement in Rheumatoid Arthritis When Assessed Prospectively Versus
Retrospectively
SO ARTHRITIS CARE & RESEARCH
LA English
DT Article
ID PATIENTS GLOBAL ASSESSMENT; DISEASE-ACTIVITY; GENERAL HEALTH;
ASSESSMENTS; PHYSICIAN; INSTRUMENTS
AB ObjectiveThe patient global assessment (PGA) is intended to provide an integrated summary of all symptoms of arthritis, but it is not clear which disease features most impact patients' assessments of changes in their overall status. We investigated what aspects of rheumatoid arthritis (RA) activity correlated best with prospectively measured changes in the PGA and with patients' retrospective judgments of improvement.
MethodsWe studied 250 patients with active RA in a prospective longitudinal study. Disease activity measures were collected before and after treatment escalation. Prospectively measured changes in PGA and patients' judgments of improvement or worsening at the followup visit were tested for correlations with changes in patient-reported measures of symptoms and functioning, joint counts, and laboratory tests.
ResultsPatients improved during the study, with the meanSD PGA decreasing from 55.6 +/- 25.2 to 37.6 +/- 24.0. At the followup visit, 167 patients (66.8%) reported improvement in overall arthritis status. Changes in pain severity, stiffness severity, and fatigue were the only significant correlates of changes in PGA. In contrast, changes in the Health Assessment Questionnaire, tender joint count or Disease Activity Score in 28 joints (DAS28), and stiffness severity were associated with retrospective judgments of improvement.
ConclusionProspectively measured changes in PGA in RA were related solely to other patient-reported measures, but patients' retrospective judgments of improvement were related to functional limitations, tender joint count, and DAS28. Patients' subjective judgments of improvement reflect aspects of RA different from the PGA and may be a simple complementary measure of treatment efficacy.
C1 [Ward, Michael M.; Guthrie, Lori C.; Alba, Maria I.] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Ward, MM (reprint author), NIAMS, NIH, Bldg 10 CRC,Room 4-1339,10 Ctr Dr, Bethesda, MD 20892 USA.
EM wardm1@mail.nih.gov
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases,
NIH
FX Supported by the Intramural Research Program, National Institute of
Arthritis and Musculoskeletal and Skin Diseases, NIH.
NR 16
TC 2
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2151-464X
EI 2151-4658
J9 ARTHRIT CARE RES
JI Arthritis Care Res.
PD JUN
PY 2015
VL 67
IS 6
BP 776
EP 781
DI 10.1002/acr.22509
PG 6
WC Rheumatology
SC Rheumatology
GA CJ2QQ
UT WOS:000355330000005
PM 25370806
ER
PT J
AU Miloslavsky, EM
Specks, U
Merkel, PA
Seo, P
Spiera, R
Langford, CA
Hoffman, GS
Kallenberg, CGM
St Clair, EW
Tchao, NK
Ding, L
Ikle, D
Villareal, M
Lim, N
Brunetta, P
Fervenza, FC
Monach, PA
Stone, JH
AF Miloslavsky, E. M.
Specks, U.
Merkel, P. A.
Seo, P.
Spiera, R.
Langford, C. A.
Hoffman, G. S.
Kallenberg, C. G. M.
St Clair, E. W.
Tchao, N. K.
Ding, L.
Ikle, D.
Villareal, M.
Lim, N.
Brunetta, P.
Fervenza, F. C.
Monach, P. A.
Stone, J. H.
CA Rituximab Anca-Associated Vasculit
TI Outcomes of Nonsevere Relapses in Antineutrophil Cytoplasmic
Antibody-Associated Vasculitis Treated With Glucocorticoids
SO ARTHRITIS & RHEUMATOLOGY
LA English
DT Article
ID ANCA-ASSOCIATED VASCULITIS; DAILY ORAL CYCLOPHOSPHAMIDE;
WEGENERS-GRANULOMATOSIS; RANDOMIZED-TRIAL; MAINTENANCE THERAPY;
REMISSION; METHOTREXATE; INDUCTION; RITUXIMAB; AZATHIOPRINE
AB Objective. Nonsevere relapses are more common than severe relapses in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but their clinical course and treatment outcomes remain largely unexamined. We undertook this study to analyze the outcomes of patients with nonsevere relapses in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial who were treated with prednisone according to a prespecified protocol.
Methods. RAVE was a randomized, double-blind, placebo-controlled trial comparing rituximab (RTX) to cyclophosphamide (CYC) followed by azathioprine (AZA) for induction of remission. Patients who experienced nonsevere relapses between months 1 and 18 were treated with a prednisone increase without a concomitant change in their nonglucocorticoid immunosuppressants, followed by a taper.
Results. Forty-four patients with a first nonsevere relapse were analyzed. In comparison to the 71 patients who maintained relapse-free remission over 18 months, these patients were more likely to have proteinase 3-ANCAs, diagnoses of granulomatosis with polyangiitis (Wegener's), and a history of relapsing disease at baseline. A prednisone increase led to remission in 35 patients (80%). However, only 13 patients (30%) were able to maintain second remissions through the followup period (mean 12.5 months); 31 patients (70%) had a second disease relapse, 14 of them with severe disease. The mean time to second relapse was 9.4 months (4.7 months in the group treated with RTX versus 13.7 months in the group treated with CYC/AZA; P<0.01). Patients who experienced nonsevere relapses received more glucocorticoids than those who maintained remission (6.7 grams versus 3.8 grams; P<0.01).
Conclusion. Treatment of nonsevere relapses in AAV with an increase in glucocorticoids is effective in restoring temporary remission in the majority of patients, but recurrent relapses within a relatively short interval remain common. Alternative treatment approaches are needed for this important subset of patients.
C1 [Miloslavsky, E. M.; Stone, J. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Specks, U.; Fervenza, F. C.] Mayo Clin, Rochester, MN USA.
[Merkel, P. A.] Univ Penn, Philadelphia, PA 19104 USA.
[Seo, P.] Johns Hopkins Univ, Baltimore, MD USA.
[Spiera, R.] Hosp Special Surg, New York, NY 10021 USA.
[Langford, C. A.; Hoffman, G. S.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Kallenberg, C. G. M.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands.
[St Clair, E. W.] Duke Univ, Med Ctr, Durham, NC USA.
[Tchao, N. K.] Immune Tolerance Network, San Francisco, CA USA.
[Ding, L.] NIAID, NIH, Bethesda, MD 20892 USA.
[Ikle, D.; Villareal, M.] Rho, Chapel Hill, NC USA.
[Lim, N.] Immune Tolerance Network, Bethesda, MD USA.
[Brunetta, P.] Genentech Inc, San Francisco, CA 94080 USA.
[Monach, P. A.] Boston Univ, Boston, MA 02215 USA.
[Monach, P. A.] Boston Med Ctr, Boston, MA USA.
RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Yawkey 2C,55 Fruit St, Boston, MA 02114 USA.
EM jhstone@partners.org
FU Immune Tolerance Network (NIH) [N01-AI-15416, ITN021AI]; National
Institute of Allergy and Infectious Diseases, NIH; Juvenile Diabetes
Research Foundation; Genentech; Biogen Idec; NIH (Mayo Clinic: National
Center for Research Resources Clinical and Translational Science award)
[1-UL1-RR-024150-01]; NIH (Johns Hopkins University: National Center for
Research Resources Clinical and Translational Science) [UL1-RR-025005,
K23-AR-052820, K24-AR-049185]; NIH (Boston University: National Center
for Research Resources Clinical and Translational Science)
[UL1-RR-025771, M01-RR-00533, K24-AR-02224]; NIH (Cleveland Clinic:
National Center for Advancing Translational Sciences) [UL1-TR-000439];
Arthritis Foundation; ChemoCentryx; GlaxoSmithKline; Eli Lilly;
MedImmune
FX The Rituximab in ANCA-Associated Vasculitis (RAVE) trial was performed
with the support of the Immune Tolerance Network (NIH contract
N01-AI-15416, protocol number ITN021AI), an international clinical
research consortium headquartered at the University of California San
Francisco and supported by the National Institute of Allergy and
Infectious Diseases, NIH, and the Juvenile Diabetes Research Foundation.
Genentech and Biogen Idec provided the study medication and partial
funding for the RAVE trial. At the Mayo Clinic, Johns Hopkins
University, Boston University, and the Cleveland Clinic, the RAVE trial
was supported by the NIH (Mayo Clinic: National Center for Research
Resources Clinical and Translational Science award 1-UL1-RR-024150-01;
Johns Hopkins University: National Center for Research Resources
Clinical and Translational Science award UL1-RR-025005 and career
development awards K23-AR-052820 to Dr. Seo and K24-AR-049185 to Dr.
Stone; Boston University: National Center for Research Resources
Clinical and Translational Science award UL1-RR-025771, grant
M01-RR-00533, and career development award K24-AR-02224 to Dr. Merkel;
Cleveland Clinic: National Center for Advancing Translational Sciences
grant UL1-TR-000439). The RAVE trial at Boston University was also
supported by the Arthritis Foundation (Investigator Award to Dr.
Monach).; Dr. Miloslavsky has received consulting fees, speaking fees,
and/or honoraria (less than $10,000) and research funding from
Genentech. Dr. Specks has received consulting fees, speaking fees,
and/or honoraria from Genentech (less than $10,000). Dr. Kallenberg has
received consulting fees from ChemoCentryx, GlaxoSmithKline, Eli Lilly,
and MedImmune (less than $10,000 each). Dr. Brunetta owns stock or stock
options in Genentech. Dr. Monach has received consulting fees, speaking
fees, and/or honoraria (less than $10,000) from Genentech. Dr. Stone has
received consulting fees, speaking fees, and/or honoraria from Genentech
(less than $10,000).
NR 27
TC 11
Z9 11
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2326-5191
EI 2326-5205
J9 ARTHRITIS RHEUMATOL
JI Arthritis Rheumatol.
PD JUN
PY 2015
VL 67
IS 6
BP 1629
EP 1636
DI 10.1002/art.39104
PG 8
WC Rheumatology
SC Rheumatology
GA CJ2QA
UT WOS:000355328400026
PM 25776953
ER
PT J
AU Kupfer, D
Cuthbert, B
AF Kupfer, D.
Cuthbert, B.
TI The future of diagnosis in the bipolar spectrum
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
C1 [Kupfer, D.] Univ Pittsburgh, Sch Med, Psychiat, Pittsburgh, PA USA.
[Cuthbert, B.] NIMH, RDoC Unit, 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 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2015
VL 17
SU 1
SI SI
BP 8
EP 8
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA CJ2TS
UT WOS:000355338100004
ER
PT J
AU Merikangas, K
Cui, L
Lameira, D
Zipunnikov, V
Lamers, F
Swendsen, J
AF Merikangas, K.
Cui, L.
Lameira, D.
Zipunnikov, V.
Lamers, F.
Swendsen, J.
TI Targets for intervention in mood disorders: evidence from objective
measures of activity, mood, energy and sleep
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
C1 [Merikangas, K.; Cui, L.; Lameira, D.] NIMH, Bethesda, MD 20892 USA.
[Zipunnikov, V.] Johns Hopkins Univ, Sch Hlth, Baltimore, MD 21218 USA.
[Lamers, F.] Vrije Univ Amsterdam, Amsterdam, Netherlands.
[Swendsen, J.] Univ Bordeaux, Bordeaux, France.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2015
VL 17
SU 1
SI SI
BP 34
EP 34
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA CJ2TS
UT WOS:000355338100083
ER
PT J
AU Preisig, M
Vandeleur, CL
Strippoli, MPF
Castelao, E
Gholam-Rezaee, M
Merikangas, KR
Marquet, P
Aubry, JM
AF Preisig, M.
Vandeleur, C. L.
Strippoli, M. P. F.
Castelao, E.
Gholam-Rezaee, M.
Merikangas, K. R.
Marquet, P.
Aubry, J. M.
TI The specificity of mania and early age of onset in high risk youth: a 10
year prospective study
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
C1 [Preisig, M.; Vandeleur, C. L.; Strippoli, M. P. F.; Castelao, E.; Gholam-Rezaee, M.; Marquet, P.] Univ Lausanne Hosp, Dept Psychiat, Lausanne, Switzerland.
[Merikangas, K. R.] NIMH, Genet Epidemiol Res Branch, Intramural Res Program, Bethesda, MD 20892 USA.
[Aubry, J. M.] Univ Hosp Geneva, Dept Mental Hlth & Psychiat, Geneva, Switzerland.
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 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2015
VL 17
SU 1
SI SI
BP 34
EP 34
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA CJ2TS
UT WOS:000355338100084
ER
PT J
AU Miller, S
Suppes, T
Mintz, J
Hellemann, G
Frye, M
McElroy, S
Nolen, W
Kupka, R
Leverich, G
Grunze, H
Altshuler, L
Keck, P
Post, R
AF Miller, S.
Suppes, T.
Mintz, J.
Hellemann, G.
Frye, M.
McElroy, S.
Nolen, W.
Kupka, R.
Leverich, G.
Grunze, H.
Altshuler, L.
Keck, P.
Post, R.
TI Mixed depression in bipolar disorder: prevalence rate and clinical
correlates during naturalistic follow up
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
C1 [Miller, S.; Suppes, T.] VA Palo Alto Hlth Care Syst, Stanford, CA USA.
[Miller, S.; Suppes, T.] Stanford Univ, Med Ctr, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
[Mintz, J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Hellemann, G.; Altshuler, L.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA.
[Frye, M.] Mayo Clin, Dept Psychiat, Rochester, MN USA.
[McElroy, S.; Keck, P.] Lindner Ctr HOPE, Cincinnati, OH USA.
[Nolen, W.] Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands.
[Kupka, R.] Altrecht Inst Mental Hlth Care, Altrecht, Netherlands.
[Kupka, R.] Univ Med Ctr, Altrecht, Netherlands.
[Leverich, G.] NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA.
[Grunze, H.] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Post, R.] George Washington Sch Med, Washington, DC USA.
RI Mintz, Jim/N-7385-2014
OI Mintz, Jim/0000-0002-8299-5851
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUN
PY 2015
VL 17
SU 1
SI SI
BP 35
EP 35
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA CJ2TS
UT WOS:000355338100086
ER
PT J
AU Lederman, RJ
O'Neill, WW
Greenbaum, AB
AF Lederman, Robert J.
O'Neill, William W.
Greenbaum, Adam B.
TI Transcaval access for TAVR across a polyester aortic graft
SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
LA English
DT Article
DE structural heart disease; transcatheter aortic valve implantation;
caval-aortic fenestrated graft; vascular access and closure;
extra-anatomic procedures
ID IN-SITU FENESTRATION; REPLACEMENT; DURABILITY; PUNCTURE
AB Transcaval access to the aorta allows transcatheter aortic valve replacement in patients without other good access options. The resulting aorto-caval fistula is closed with a nitinol cardiac occluder device. There is no experience traversing a synthetic aortic graft to perform transcaval access and closure. We describe a patient who underwent successful traversal of a polyester aortic graft using radiofrequency energy applied from the tip of a guidewire, to allow retrograde transcatheter aortic valve replacement from a femoral vein, along with details of our technique. The patient did well and was discharged home after 3 days. There was residual aorto-caval fistulous flow immediately after implantation of a polyester-seeded nitinol muscular ventricular septal defect occluder device, but this fistula spontaneously occluded within one month. (c) 2015 Wiley Periodicals, Inc.
C1 [Lederman, Robert J.] NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[O'Neill, William W.; Greenbaum, Adam B.] Inst Struct Heart Dis, Div Cardiol, Henry Ford Hlth Syst, Detroit, MI USA.
RP Lederman, RJ (reprint author), NHLBI, NIH, Bldg 10,Room 2c713, Bethesda, MD 20892 USA.
EM lederman@nih.gov
OI lederman, robert/0000-0003-1202-6673
FU Division of Intramural Research, National Heart Lung and Blood
Institute, National Institutes of Health [Z01-HL006040]; Institute for
Structural Heart Disease, Division of Cardiology, Henry Ford Health
System
FX Supported by the Division of Intramural Research (Z01-HL006040),
National Heart Lung and Blood Institute, National Institutes of Health
(RJL), and the Institute for Structural Heart Disease, Division of
Cardiology, Henry Ford Health System (ABG, WWO). Drs. Lederman and
Greenbaum are inventors on patent applications for devices for
caval-aortic access that have been assigned to their employers, NIH and
Henry Ford Hospital, respectively.
NR 9
TC 4
Z9 4
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1522-1946
EI 1522-726X
J9 CATHETER CARDIO INTE
JI Catheter. Cardiovasc. Interv.
PD JUN
PY 2015
VL 85
IS 7
BP 1270
EP 1273
DI 10.1002/ccd.25781
PG 4
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CI8DU
UT WOS:000355000100034
PM 25510917
ER
PT J
AU Sacks, DB
Kricka, LJ
AF Sacks, David B.
Kricka, Larry J.
TI Plasmonic Chip Tackles Type 1 Diabetes Diagnosis
SO CLINICAL CHEMISTRY
LA English
DT Editorial Material
C1 [Sacks, David B.] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
[Kricka, Larry J.] Univ Penn, Dept Pathol & Lab Med, Med Ctr, Philadelphia, PA USA.
RP Kricka, LJ (reprint author), Hosp Univ Penn, Dept Pathol & Lab Med, 3400 Spruce St, Philadelphia, PA 19104 USA.
EM kricka@mail.med.upenn.edu
OI Sacks, David/0000-0003-3100-0735
FU Intramural NIH HHS
NR 5
TC 0
Z9 0
U1 0
U2 9
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
EI 1530-8561
J9 CLIN CHEM
JI Clin. Chem.
PD JUN
PY 2015
VL 61
IS 6
BP 794
EP 796
DI 10.1373/clinchem.2014.233346
PG 3
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA CJ1SW
UT WOS:000355265800003
PM 25655270
ER
PT J
AU Hartman, RL
Brown, TL
Milavetz, G
Spurgin, A
Gorelick, DA
Gaffney, G
Huestis, MA
AF Hartman, Rebecca L.
Brown, Timothy L.
Milavetz, Gary
Spurgin, Andrew
Gorelick, David A.
Gaffney, Gary
Huestis, Marilyn A.
TI Controlled Cannabis Vaporizer Administration: Blood and Plasma
Cannabinoids with and without Alcohol
SO CLINICAL CHEMISTRY
LA English
DT Article
ID CONTROLLED SMOKED CANNABIS; WHOLE-BLOOD; DELTA(9)-TETRAHYDROCANNABINOL
THC; MARIJUANA SMOKING; HUMAN VOLUNTEERS; HEAVY; USERS;
PHARMACOKINETICS; PERFORMANCE; ETHANOL
AB BACKGROUND: Increased medical and legal cannabis intake is accompanied by greater use of cannabis vaporization and more cases of driving under the influence of cannabis. Although simultaneous Delta(9)-tetrahydrocannabinol (THC) and alcohol use is frequent, potential pharmacokinetic interactions are poorly understood. Here we studied blood and plasma vaporized cannabinoid disposition, with and without simultaneous oral low-dose alcohol.
METHODS: Thirty-two adult cannabis smokers (>= 1 time/3 months, <= 3 days/week) drank placebo or lowdose alcohol (target approximately 0.065% peak breath-alcohol concentration) 10 min before inhaling 500 mg placebo, low-dose (2.9%) THC, or high-dose (6.7%) THC vaporized cannabis (6 within-individual alcoholcannabis combinations). Blood and plasma were obtained before and up to 8.3 h after ingestion.
RESULTS: Nineteen participants completed all sessions. Median (range) maximum blood concentrations (C-max) for low and high THC doses (no alcohol) were 32.7 (11.4-66.2) and 42.2 (15.2-137) mu g/L THC, respectively, and 2.8 (0-9.1) and 5.0 (0-14.2) mu g/L 11-OHTHC. With alcohol, low and high dose Cmax values were 35.3 (13.0-71.4) and 67.5 (18.1-210) mu g/L THC and 3.7 (1.4-6.0) and 6.0 (0 -23.3) mu g/L 11-OH-THC, significantly higher than without alcohol. With a THC detection cutoff of >= 1 mu g/L, >= 16.7% of participants remained positive 8.3 h postdose, whereas <= 21.1% were positive by 2.3 h with a cutoff of >= 5 mu g/L.
CONCLUSIONS: Vaporization is an effective THC delivery route. The significantly higher blood THC and 11-OHTHC Cmax values with alcohol possibly explain increased performance impairment observed from cannabisalcohol combinations. Chosen driving-related THC cutoffs should be considered carefully to best reflect performance impairment windows. Our results will help facilitate forensic interpretation and inform the debate on drugged driving legislation. (C) 2015 American Association for Clinical Chemistry
C1 [Hartman, Rebecca L.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab, Intramural Res Program, NIH, Baltimore, MD USA.
[Hartman, Rebecca L.] Univ Maryland, Toxicol Program, Baltimore, MD 21201 USA.
[Brown, Timothy L.] Univ Iowa, Natl Adv Driving Simulator, Iowa City, IA USA.
[Milavetz, Gary; Spurgin, Andrew] Univ Iowa, Coll Pharm, Iowa City, IA 52242 USA.
[Gaffney, Gary] Univ Iowa, Carver Coll Med, Iowa City, IA USA.
[Gorelick, David A.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA.
RP Huestis, MA (reprint author), Biomed Res Ctr, Suite 200,Rm 05A-721,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU NIDA; US Office of National Drug Control Policy; National Highway
Traffic Safety Administration; NIH
FX R.L. Hartman, D.A. Gorelick, and M.A. Huestis, Intramural Research
Program, NIDA, NIH and interagency agreements between NIDA and the US
Office of National Drug Control Policy and the National Highway Traffic
Safety Administration; materials transfer agreements between NIDA and
Storz & Bickel, who provided Volcano vaporizer devices/equipment for
this study. T.L. Brown, G. Milavetz, A. Spurgin, and G. Gaffney,
contract between National Highway Traffic Safety Administration and the
University of Iowa.
NR 40
TC 12
Z9 12
U1 1
U2 15
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
EI 1530-8561
J9 CLIN CHEM
JI Clin. Chem.
PD JUN
PY 2015
VL 61
IS 6
BP 850
EP 869
DI 10.1373/clinchem.2015.238287
PG 20
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA CJ1SW
UT WOS:000355265800012
PM 26019183
ER
PT J
AU Berg, AH
Powe, CE
Evans, MK
Wenger, J
Ortiz, G
Zonderman, AB
Suntharalingam, P
Lucchesi, K
Powe, NR
Karumanchi, SA
Thadhani, RI
AF Berg, Anders H.
Powe, Camille E.
Evans, Michele K.
Wenger, Julia
Ortiz, Guillermo
Zonderman, Alan B.
Suntharalingam, Pirianthini
Lucchesi, Kathryn
Powe, Neil R.
Karumanchi, S. Ananth
Thadhani, Ravi I.
TI 24,25-Dihydroxyvitamin D-3 and Vitamin D Status of Community-Dwelling
Black and White Americans
SO CLINICAL CHEMISTRY
LA English
DT Article
ID BONE-MINERAL DENSITY; D-BINDING PROTEIN; CHRONIC KIDNEY-DISEASE;
25-HYDROXYVITAMIN D; D SUPPLEMENTATION; D DEFICIENCY; SERUM
25-HYDROXYVITAMIN-D; HIP-FRACTURES; ELDERLY-WOMEN; RISK
AB BACKGROUND: 24,25-Dihydroxyvitamin D[24,25(OH)(2)D] is a metabolite of 25-hydroxyvitamin D (25D). Blacks frequently have low total 25D without manifestations of vitamin D deficiency, suggesting that total serum 25D may incorrectly reflect vitamin Dstatus in different racial groups. The ratio of serum 24,25(OH)(2)D to 25D [vitamin D metabolite ratio (VMR)] represents a new candidate biomarker for vitamin D status.
METHODS: We measured 24,25(OH)(2)D-3 and 25D(3) by mass spectrometry in a random community cohort of black (n = 212) and white (n = 164) Americans to evaluate VMR as a marker for vitamin D status. We measured parathyroid hormone concentrations by immunoassay to compare VMR and 25D(3) against a physiological indicator of vitamin D deficiency.
RESULTS: Serum 24,25(OH)(2)D-3 strongly correlated with 25D3 in both black and white study participants (r = 0.90, P < 0.001 and r = 0.86, P < 0.001 respectively). Blacks had lower mean 25D3 than whites [17.0 (7.8) vs 27.5 (11.3) ng/mL; 42.4 (19.5) vs 68.6 (28.2) nmol/L, P < 0.001] and lower mean 24,25(OH)(2)D-3 [2.1 (1.3) vs 3.6 (2.0) ng/mL; 5.1 (3.1) vs 8.7 (4.8) nmol/L, P < 0.001]. In contrast to total 25D(3) concentrations, mean VMR values were similar in blacks and whites [11.9 (4.0) vs 12.5 (3.4), P = 0.16, respectively] and were negatively correlated with parathyroid hormone concentrations in both races (r(s) = -0.26, P = 0.001, and r(s) = -0.25, P < 0.001, respectively).
CONCLUSIONS: Our results provide further evidence that measurement of total 25D for assessment of vitamin D status in patients of African descent deserves reevaluation and suggest that alternative measures such as VMR should be considered. (C) 2015 American Association for Clinical Chemistry
C1 [Berg, Anders H.; Suntharalingam, Pirianthini] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA.
[Berg, Anders H.; Suntharalingam, Pirianthini] Harvard Univ, Sch Med, Boston, MA USA.
[Powe, Camille E.] Massachusetts Gen Hosp, Div Endocrinol, Boston, MA 02215 USA.
[Evans, Michele K.; Zonderman, Alan B.] NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA.
[Wenger, Julia; Ortiz, Guillermo; Lucchesi, Kathryn; Thadhani, Ravi I.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02215 USA.
[Powe, Neil R.] San Francisco Gen Hosp, Dept Med, San Francisco, CA 94110 USA.
[Powe, Neil R.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02115 USA.
[Karumanchi, S. Ananth] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Berg, AH (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave YA309, Boston, MA 02115 USA.
EM ahberg@bidmc.harvard.edu; rthadhani@mgh.harvard.edu
FU National Institute on Aging Intramural Research Program at NIH [ZIA
AG000513]; National Institutes of Health [K08 HL121801, K24 DK094872,
R01 DK094486]; Howard Hughes Medical Institute
FX National Institute on Aging Intramural Research Program at NIH, project
#ZIA AG000513; A.H. Berg, K08 HL121801 from the National Institutes of
Health; A. Karumanchi, Howard Hughes Medical Institute; R.I. Thadhani,
K24 DK094872 and R01 DK094486 from the National Institutes of Health.
Expert Testimony: None declared.
NR 37
TC 15
Z9 16
U1 0
U2 2
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
EI 1530-8561
J9 CLIN CHEM
JI Clin. Chem.
PD JUN
PY 2015
VL 61
IS 6
BP 877
EP 884
DI 10.1373/clinchem.2015.240051
PG 8
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA CJ1SW
UT WOS:000355265800014
PM 25922442
ER
PT J
AU Panlilio, LV
Goldberg, SR
Justinova, Z
AF Panlilio, L. V.
Goldberg, S. R.
Justinova, Z.
TI Cannabinoid Abuse and Addiction: Clinical and Preclinical Findings
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Review
ID SUBSTANCE USE DISORDERS; SQUIRREL-MONKEYS; SYNTHETIC CANNABINOIDS;
DELTA(9)-TETRAHYDROCANNABINOL THC; MARIJUANA WITHDRAWAL; REINFORCING
EFFICACY; SEEKING BEHAVIOR; RECEPTOR AGONIST; CONTROLLED-TRIAL;
ADENOSINE A(2A)
AB Cannabinoid abuse disorders represent a widespread public health issue, but there are no approved medications for their treatment. This review describes efforts to understand the mechanisms of cannabinoid abuse and its adverse effects, to identify molecular targets for pharmacotherapy, and to evaluate potential treatments in human volunteers and animal models of cannabinoid reward, withdrawal, and relapse.
C1 [Panlilio, L. V.; Goldberg, S. R.; Justinova, Z.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD 21224 USA.
RP Justinova, Z (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD 21224 USA.
EM zjustino@intra.nida.nih.gov
RI Justinova, Zuzana/A-9109-2011
OI Justinova, Zuzana/0000-0001-5793-7484
FU Intramural Research Program of the National Institute on Drug Abuse,
National Institutes of Health, the Department of Health and Human
Services
FX We dedicate this article to the memory of Steven R. Goldberg
(1941-2014), whose passion for cannabinoid research was an inspiration
to us. Preparation of this manuscript was supported by the Intramural
Research Program of the National Institute on Drug Abuse, National
Institutes of Health, the Department of Health and Human Services.
NR 75
TC 9
Z9 10
U1 2
U2 25
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD JUN
PY 2015
VL 97
IS 6
BP 616
EP 627
DI 10.1002/cpt.118
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CI9ZU
UT WOS:000355131400019
PM 25788435
ER
PT J
AU Hymel, R
Jones, GC
Simone, CB
AF Hymel, Rockne
Jones, Guy C.
Simone, Charles B., II
TI Whole pelvic intensity-modulated radiotherapy for gynecological
malignancies: A review of the literature
SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
LA English
DT Review
DE IMRT; Radiation therapy; Endometrial; Cervical; Gynecologic
ID LOCALIZED PROSTATE-CANCER; RADIATION-THERAPY; CERVICAL-CANCER; UTERINE
CERVIX; ENDOMETRIAL CANCER; ADJUVANT TREATMENT; ONCOLOGY-GROUP; ORGAN
MOTION; BONE-MARROW; CARCINOMA
AB Radiation therapy has long played a major role in the treatment of gynecological malignancies. There is increasing interest in the utility of intensity-modulated radiotherapy (IMRT) and its application to treat gynecological malignancies. Herein, we review the state-of-the-art use of IMRT for gynecological malignancies and report how it is being used alone as well as in combination with chemotherapy in both the adjuvant and definitive settings. Based on dosimetric and clinical evidence, IMRT can reduce gastrointestinal, genitourinary, and hematological toxicities compared with 3D-conformal radiotherapy for gynecologic malignancies. We discuss how these attributes of IMRT may lead to improvements in disease outcomes by allowing for dose escalation of radiation therapy, intensification of chemotherapy, and limiting toxicity-related treatment breaks. Currently accruing trials investigating pelvic IMRT for cervical and endometrial cancers are discussed. Published by Elsevier Ireland Ltd.
C1 [Hymel, Rockne] Louisiana State Univ, Hlth Sci Ctr, Sch Med, New Orleans, LA 70112 USA.
[Jones, Guy C.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Simone, Charles B., II] Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA.
RP Jones, GC (reprint author), NCI, Ctr Canc Res, Radiat Oncol Branch, NIH, 10 Ctr Dr,MSC 1682,Bldg 10 CRC Room B2-3561, Bethesda, MD 20892 USA.
EM rhyme1@lsuhsc.edu; guy.jones@nih.gov; charles.simone@uphs.upenn.edu
FU Intramural NIH HHS [Z99 CA999999]
NR 34
TC 1
Z9 2
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1040-8428
EI 1879-0461
J9 CRIT REV ONCOL HEMAT
JI Crit. Rev. Oncol./Hematol.
PD JUN
PY 2015
VL 94
IS 3
BP 371
EP 379
DI 10.1016/j.critrevonc.2014.12.015
PG 9
WC Oncology; Hematology
SC Oncology; Hematology
GA CJ3FS
UT WOS:000355369400011
PM 25600840
ER
PT J
AU Fascelli, M
George, AK
Frye, T
Turkbey, B
Choyke, PL
Pinto, PA
AF Fascelli, Michele
George, Arvin K.
Frye, Thomas
Turkbey, Baris
Choyke, Peter L.
Pinto, Peter A.
TI The Role of MRI in Active Surveillance for Prostate Cancer
SO CURRENT UROLOGY REPORTS
LA English
DT Article
DE Active surveillance; Prostate cancer; Multiparametric MRI; Outcomes;
Cancer detection
ID TRANSRECTAL ULTRASOUND BIOPSY; RESONANCE-IMAGING PREDICT;
MULTIPARAMETRIC MRI; FUSION BIOPSY; FOLLOW-UP; RADICAL PROSTATECTOMY; 3
TESLA; MEN; RISK; ANTIGEN
AB Approximately one in seven American men will be diagnosed with prostate cancer during his lifetime, and at least 50 % of newly diagnosed patients will present with low-risk disease. In the last decade, the decision-making paradigm for management has shifted due to high rates of disease detection and overtreatment, attributed to prostate-specific antigen screening, with more men deferring definitive treatment for active surveillance. The advent of multiparametric magnetic resonance imaging (MP-MRI) and MRI/transrectal ultrasound-guided fusion-guided prostate biopsy has refined the process of diagnosis, identifying patients with clinically-significant cancer and larger disease burden who would most likely benefit from intervention. In parallel, the utilization of MP-MRI in the surveillance of low-grade, low-volume disease is on the rise, reflecting support in a growing body of literature. The aim of this review is to appraise and summarize the data evaluating the role of magnetic resonance imaging in active surveillance for prostate cancer.
C1 [Fascelli, Michele; George, Arvin K.; Frye, Thomas; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Turkbey, Baris; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
RP Pinto, PA (reprint author), NCI, Urol Oncol Branch, NIH, MSC 1210,10 Ctr Dr, Bethesda, MD 20892 USA.
EM pintop@mail.nih.gov
FU NIH
FX The National Institutes of Health (NIH) Medical Research Scholars
Program is a public-private partnernship supported jointly by the NIH
and generous contributions to the Foundation for the NIH from Pfizer
Inc., The Doris Duke Charitable Foundation, The Newport Foundation, The
American Association for Dental Research, The Howard Hughes Medical
Institute, and the Colgate-Palmolive Company, as well as other private
donors.
NR 56
TC 16
Z9 16
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1527-2737
J9 CURR UROL REP
JI Curr. Urol. Rep.
PD JUN
PY 2015
VL 16
IS 6
AR 42
DI 10.1007/s11934-015-0507-9
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA CJ2VW
UT WOS:000355343800009
PM 26017850
ER
PT J
AU Cunningham, TJ
Kumar, S
Yamaguchi, TP
Duester, G
AF Cunningham, Thomas J.
Kumar, Sandeep
Yamaguchi, Terry P.
Duester, Gregg
TI Wnt8a and Wnt3a cooperate in the axial stem cell niche to promote
mammalian body axis extension
SO DEVELOPMENTAL DYNAMICS
LA English
DT Article
DE Wnt8a; Wnt3a; body axis extension; somitogenesis; Fgf8; retinoic acid;
Rdh10; mouse
ID POSTERIOR NEURAL PLATE; RETINOIC ACID CONTROLS; MOUSE EMBRYO; MESODERM
FORMATION; LIMB DEVELOPMENT; GENE ACTIVATION; SEGMENTATION; FGF;
ELONGATION; GROWTH
AB Background: Vertebrate body axis extension occurs in a head-to-tail direction from a caudal progenitor zone that responds to interacting signals. Wnt/-catenin signaling is critical for generation of paraxial mesoderm, somite formation, and maintenance of the axial stem cell pool. Body axis extension requires Wnt8a in lower vertebrates, but in mammals Wnt3a is required, although the anterior trunk develops in the absence of Wnt3a. Results: We examined mouse Wnt8a(-/-) and Wnt3a(-/-) single and double mutants to explore whether mammalian Wnt8a contributes to body axis extension and to determine whether a posterior growth function for Wnt8a is conserved throughout the vertebrate lineage. We find that caudal Wnt8a is expressed only during early somite stages and is required for normal development of the anterior trunk in the absence of Wnt3a. During this time, we show that Wnt8a and Wnt3a cooperate to maintain Fgf8 expression and prevent premature Sox2 up-regulation in the axial stem cell niche, critical for posterior growth. Similar to Fgf8, Wnt8a requires retinoic acid (RA) signaling to restrict its caudal expression boundary and possesses an upstream RA response element that binds RA receptors. Conclusions: These findings provide new insight into interaction of caudal Wnt-FGF-RA signals required for body axis extension. Developmental Dynamics 244:797-807, 2015. (c) 2015 Wiley Periodicals, Inc.
C1 [Cunningham, Thomas J.; Kumar, Sandeep; Duester, Gregg] Sanford Burnham Med Res Inst, Dev Aging & Regenerat Program, La Jolla, CA 92037 USA.
[Yamaguchi, Terry P.] NCI, Canc & Dev Biol Lab, NIH, Frederick, MD 21701 USA.
RP Duester, G (reprint author), Sanford Burnham Med Res Inst, Dev & Aging Program, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM duester@sanfordburnham.org
OI Cunningham, Thomas/0000-0002-4751-3140
FU NIH [GM062848]
FX Grant sponsor: NIH; Grant number: GM062848
NR 62
TC 6
Z9 7
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1058-8388
EI 1097-0177
J9 DEV DYNAM
JI Dev. Dyn.
PD JUN
PY 2015
VL 244
IS 6
BP 797
EP 807
DI 10.1002/dvdy.24275
PG 11
WC Anatomy & Morphology; Developmental Biology
SC Anatomy & Morphology; Developmental Biology
GA CJ1DY
UT WOS:000355223500008
PM 25809880
ER
PT J
AU Willette, AA
Modanlo, N
Kapogiannis, D
AF Willette, Auriel A.
Modanlo, Nina
Kapogiannis, Dimitrios
CA Alzheimer's Dis Neuroimaging
TI Insulin Resistance Predicts Medial Temporal Hypermetabolism in Mild
Cognitive Impairment Conversion to Alzheimer Disease
SO DIABETES
LA English
DT Article
ID NEUROIMAGING INITIATIVE ADNI; GLUCOSE-METABOLISM; MEMORY IMPAIRMENT;
COMPOSITE SCORE; FDG-PET; BRAIN; DECLINE; PROGRESSION; DEMENTIA; ADULTS
AB Alzheimer disease (AD) is characterized by progressive hypometabolism on [F-18]-fluorodeoxyglucose positron emission tomography (FDG-PET) scans. Peripheral insulin resistance (IR) increases AD risk. No studies have examined associations between FDG metabolism and IR in mild cognitive impairment (MCI) and AD, as well as MCI conversion to AD. We studied 26 cognitively normal (CN), 194 MCI (39 MCI-progressors, 148 MCI-stable, 2 years after baseline), and 60 AD subjects with baseline FDG-PET from the Alzheimer's Disease Neuroimaging Initiative. Mean FDG metabolism was derived for AD-vulnerable regions of interest (ROIs), including lateral parietal and posteromedial cortices, medial temporal lobe (MTL), hippocampus, and ventral prefrontal cortices (vPFC), as well as postcentral gyrus and global cerebrum control regions. The homeostasis model assessment of IR (HOMA-IR) was used to measure IR. For AD, higher HOMA-IR predicted lower FDG in all ROIs. For MCI-progressors, higher NOMA-Ill predicted higher FDG in the MTL and hippocampus. Control regions showed no associations. Higher HOMA-IR predicted hypermetabolism in MCI-progressors and hypometabolism in AD in medial temporal regions. Future longitudinal studies should examine the pathophysiologic significance of the shift from MTL hyper- to hypometabolism associated with IR.
C1 [Willette, Auriel A.; Kapogiannis, Dimitrios] NIA, Neurosci Lab, Baltimore, MD 21224 USA.
[Modanlo, Nina] Johns Hopkins Univ, Baltimore, MD USA.
RP Kapogiannis, D (reprint author), NIA, Neurosci Lab, Baltimore, MD 21224 USA.
EM kapogiannisd@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Institute on Aging; ADNI (National Institutes of Health)
[U01-AG-024904]; Department of Defense ADNI [W81XWH-12-2-0012]; National
Institute on Aging; National Institute of Biomedical Imaging and
Bioengineering; Canadian Institutes of Health Research; Northern
California Institute for Research and Education
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, National Institute on Aging. Data
collection and sharing for this project were funded by the ADNI
(National Institutes of Health Grant U01-AG-024904) and Department of
Defense ADNI (award number W81XWH-12-2-0012). ADNI is funded by the
National Institute on Aging, the National Institute of Biomedical
Imaging and Bioengineering, and through generous contributions from the
Alzheimer's Association and the Alzheimer's Drug Discovery Foundation.
The Canadian Institutes of Health Research is providing funds to support
ADNI clinical sites in Canada. Private-sector contributions are
facilitated by the Foundation for the National Institutes of Health
(www.fnih.org). The grantee organization is the Northern California
Institute for Research and Education, and the study is coordinated by
the Alzheimer's Disease Cooperative Study at the University of
California, San Diego. ADNI data are disseminated by the Laboratory for
Neuro Imaging at the University of Southern California.
NR 47
TC 15
Z9 15
U1 0
U2 7
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
EI 1939-327X
J9 DIABETES
JI Diabetes
PD JUN
PY 2015
VL 64
IS 6
BP 1933
EP 1940
DI 10.2337/db14-1507
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CJ3GH
UT WOS:000355370900011
PM 25576061
ER
PT J
AU Gennery, AR
Holland, SM
AF Gennery, Andrew R.
Holland, Steven M.
TI Primary immunodeficiencies: not just paediatric diseases
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Editorial Material
ID CHRONIC GRANULOMATOUS-DISEASE; STEM-CELL TRANSPLANTATION; HEMATOPOIETIC
ALLOGRAFT; MULTICENTER; INFECTIONS; CHILDREN
C1 [Gennery, Andrew R.] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Gennery, AR (reprint author), Great North Childrens Hosp, Old Childrens Outpatients, Paediat Immunol Dept, Queen Victoria Rd, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
EM andrew.gennery@ncl.ac.uk
NR 17
TC 1
Z9 1
U1 0
U2 1
PU EUROPEAN RESPIRATORY SOC JOURNALS LTD
PI SHEFFIELD
PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND
SN 0903-1936
EI 1399-3003
J9 EUR RESPIR J
JI Eur. Resp. J.
PD JUN
PY 2015
VL 45
IS 6
BP 1521
EP 1523
DI 10.1183/09031936.00020215
PG 3
WC Respiratory System
SC Respiratory System
GA CJ2QN
UT WOS:000355329700002
PM 26028614
ER
PT J
AU Gonzalez, FJ
Fang, ZZ
Ma, XC
AF Gonzalez, Frank J.
Fang, Zhong-Ze
Ma, Xiaochao
TI Transgenic mice and metabolomics for study of hepatic xenobiotic
metabolism and toxicity
SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
LA English
DT Review
DE CYP; CYP3A4; genetically modified mice; metabolomics; pregnane X
receptor; UPLC-ESI-QTOFMS; xenobiotics
ID HUMAN DRUG-METABOLISM; PREGNANE-X-RECEPTOR; INHIBITOR RITONAVIR ABT-538;
HUMANIZED MOUSE MODELS; HEPATOCYTE-LIKE CELLS; MS-BASED METABOLOMICS;
INDUCED LIVER-DISEASE; PPARA-NULL MOUSE; LITHOCHOLIC ACID; IN-VITRO
AB Introduction: The study of xenobiotic metabolism and toxicity has been greatly aided by the use of genetically modified mouse models and metabolomics.
Areas covered: Gene knockout mice can be used to determine the enzymes responsible for the metabolism of xenobiotics in vivo and to examine the mechanisms of xenobiotic-induced toxicity. Humanized mouse models are especially important because there exist marked species differences in the xenobiotic-metabolizing enzymes and the nuclear receptors that regulate these enzymes. Humanized mice expressing CYPs and nuclear receptors including the pregnane X receptor, the major regulator of xenobiotic metabolism and transport were produced. With genetically modified mouse models, metabolomics can determine the metabolic map of many xenobiotics with a level of sensitivity that allows the discovery of even minor metabolites. This technology can be used for determining the mechanism of xenobiotic toxicity and to find early biomarkers for toxicity.
Expert opinion: Metabolomics and genetically modified mouse models can be used for the study of xenobiotic metabolism and toxicity by: i) comparison of the metabolomics profiles between wild-type and genetically modified mice, and searching for genotype-dependent endogenous metabolites; ii) searching for and elucidating metabolites derived from xenobiotics; and iii) discovery of specific alterations of endogenous compounds induced by xenobiotics-induced toxicity.
C1 [Gonzalez, Frank J.; Fang, Zhong-Ze] NCI, NIH, Ctr Canc Res, Lab Metab, Bethesda, MD 20892 USA.
[Fang, Zhong-Ze] Tianjin Med Univ, Sch Publ Hlth, Dept Toxicol, Tianjin 300070, Peoples R China.
[Ma, Xiaochao] Univ Pittsburgh, Sch Pharm, Ctr Pharmacogenet, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA.
RP Gonzalez, FJ (reprint author), NCI, NIH, Ctr Canc Res, Lab Metab, Bethesda, MD 20892 USA.
EM gonzalef@mail.nih.gov
FU National Cancer Institute Intramural Research Program; National
Institute of Diabetes and Digestive and Kidney Diseases [DK090305];
National Institute of Allergy and Infectious Diseases [AI095425]
FX The authors were supported in part by the National Cancer Institute
Intramural Research Program, National Institute of Diabetes and
Digestive and Kidney Diseases [DK090305] and the National Institute of
Allergy and Infectious Diseases [AI095425]. The authors have no other
relevant affiliations or financial involvement with any organization or
entity with a financial interest in or financial conflict with the
subject matter or materials discussed in the manuscript apart from those
disclosed.
NR 100
TC 5
Z9 5
U1 4
U2 16
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1742-5255
EI 1744-7607
J9 EXPERT OPIN DRUG MET
JI Expert Opin. Drug Metab. Toxicol.
PD JUN
PY 2015
VL 11
IS 6
BP 869
EP 881
DI 10.1517/17425255.2015.1032245
PG 13
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA CI7NQ
UT WOS:000354950800003
PM 25836352
ER
PT J
AU Craig, MT
McBain, CJ
AF Craig, Michael T.
McBain, Chris J.
TI Navigating the circuitry of the brain's GPS system: Future challenges
for neurophysiologists
SO HIPPOCAMPUS
LA English
DT Article
DE interneurons; hippocampus; oscillations
ID MEDIAL ENTORHINAL CORTEX; FREELY-MOVING RATS; GAMMA-FREQUENCY
OSCILLATIONS; PERSISTENT CORTICAL ACTIVITY; HIPPOCAMPAL PYRAMIDAL CELLS;
THETA-PHASE PRECESSION; GABA-B RECEPTORS; UNIT-ACTIVITY; GRID CELLS;
IN-VITRO
AB The discovery of the brain's navigation system creates a compelling challenge for neurophysiologists: how do we map the circuitry of a system that can only be definitively identified in awake, behaving animals? Do grid and border cells in the entorhinal cortex correspond to the two classes of principal cell found there, stellate and pyramidal cells? In the hippocampus, does the diversity seen in pyramidal cell subtypes have functional correlates in the place cell system? How do interneurons regulate the activity of spatially tuned principal cells in the hippocampal and entorhinal circuits? Here, we discuss recent literature relating the cellular circuitry of these circuits to in vivo studies of the brain's navigation system, and the role that interneurons have in regulating the activity of principal cells in these circuits. We propose that studying in vitro models of neuronal oscillations in the entorhinal cortex and hippocampus can provide useful insights for bridging the gap in understanding that exists in relating in vivo and behavioral studies to circuit function at the cellular level. (c) 2015 Wiley Periodicals, Inc.
C1 [Craig, Michael T.; McBain, Chris J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurobiol, NIH, Bethesda, MD USA.
RP McBain, CJ (reprint author), NICHD, Program Dev Neurobiol, NIH, Bethesda, MD 20814 USA.
EM mcbainc@mail.nih.gov
RI Craig, Michael/E-7070-2011
OI Craig, Michael/0000-0001-8481-6709
FU NICHD Intramural Award
FX Grant sponsor: NICHD Intramural Award.
NR 81
TC 1
Z9 1
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1050-9631
EI 1098-1063
J9 HIPPOCAMPUS
JI Hippocampus
PD JUN
PY 2015
VL 25
IS 6
SI SI
BP 736
EP 743
DI 10.1002/hipo.22456
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA CJ1FR
UT WOS:000355228700011
PM 25786788
ER
PT J
AU Gierach, GL
Patel, DA
Falk, RT
Pfeiffer, RM
Geller, BM
Vacek, PM
Weaver, DL
Chicoine, RE
Shepherd, JA
Mahmoudzadeh, AP
Wang, J
Fan, B
Herschorn, SD
Xu, X
Veenstra, T
Fuhrman, B
Sherman, ME
Brinton, LA
AF Gierach, Gretchen L.
Patel, Deesha A.
Falk, Roni T.
Pfeiffer, Ruth M.
Geller, Berta M.
Vacek, Pamela M.
Weaver, Donald L.
Chicoine, Rachael E.
Shepherd, John A.
Mahmoudzadeh, Amir Pasha
Wang, Jeff
Fan, Bo
Herschorn, Sally D.
Xu, Xia
Veenstra, Timothy
Fuhrman, Barbara
Sherman, Mark E.
Brinton, Louise A.
TI Relationship of Serum Estrogens and Metabolites with Area and Volume
Mammographic Densities
SO HORMONES & CANCER
LA English
DT Article
ID BREAST-CANCER RISK; TANDEM MASS-SPECTROMETRY; CIRCULATING SEX-HORMONES;
POSTMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; ASSAY REPRODUCIBILITY;
PARENCHYMAL PATTERNS; URINARY ESTROGENS; ASSOCIATION; STEROIDS
AB Elevated mammographic density is a breast cancer risk factor, which has a suggestive, but unproven, relationship with increased exposure to sex steroid hormones. We examined associations of serum estrogens and estrogen metabolites with area and novel volume mammographic density measures among 187 women, ages 40-65, undergoing diagnostic breast biopsies at an academic facility in Vermont. Serum parent estrogens, estrone and estradiol, and their 2-, 4-, and 16-hydroxylated metabolites were measured using liquid chromatography-tandem mass spectrometry. Area mammographic density was measured in the breast contralateral to the biopsy using thresholding software; volume mammographic density was quantified using a density phantom. Linear regression was used to estimate associations of estrogens with mammographic densities, adjusted for age and body mass index, and stratified by menopausal status and menstrual cycle phase. Weak, positive associations between estrogens, estrogen metabolites, and mammographic density were observed, primarily among postmenopausal women. Among premenopausal luteal phase women, the 16-pathway metabolite estriol was associated with percent area (p=0.04) and volume (p=0.05) mammographic densities and absolute area (p=0.02) and volume (p=0.05) densities. Among postmenopausal women, levels of total estrogens, the sum of parent estrogens, and 2-, 4- and 16-hydroxylation pathway metabolites were positively associated with area density measures (percent: p=0.03, p=0.04, p=0.01, p=0.02, p=0.07; absolute: p=0.02, p=0.02, p=0.01, p=0.02, p=0.03, respectively) but not volume density measures. Our data suggest that serum estrogen profiles are weak determinants of mammographic density and that analysis of different density metrics may provide complementary information about relationships of estrogen exposure to breast tissue composition.
C1 [Gierach, Gretchen L.; Patel, Deesha A.; Falk, Roni T.; Brinton, Louise A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Geller, Berta M.; Vacek, Pamela M.; Weaver, Donald L.; Chicoine, Rachael E.; Herschorn, Sally D.] Univ Vermont, Burlington, VT USA.
[Shepherd, John A.; Mahmoudzadeh, Amir Pasha; Wang, Jeff; Fan, Bo] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Xu, Xia; Veenstra, Timothy] Frederick Natl Lab Canc Res, Lab Prote & Analyt Technol, Canc Res Technol Program, Leidos Biomed Res Inc, Frederick, MD USA.
[Fuhrman, Barbara] Univ Arkansas Med Sci, Dept Epidemiol, Fay W Boozman Coll Publ Hlth, Little Rock, AR 72205 USA.
[Sherman, Mark E.] NCI, Breast & Gynecol Canc Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
RP Gierach, GL (reprint author), 9609 Med Ctr Dr,Rm 7-E108, Bethesda, MD 20892 USA.
EM gierachg@mail.nih.gov; deesha.patel@nih.gov; falkr@exchange.nih.gov;
pfeiffer@mail.nih.gov; berta.geller@uvm.edu; pvacek@uvm.edu;
Donald.Weaver@uvm.edu; rchicoin@uvm.edu; John.Shepherd@ucsf.edu;
AmirPasha.Mahmoudzadeh@ucsf.edu; jeff.wing.wang.walla.walla@gmail.com;
bo.fan@ucsf.edu; sally.herschorn@uvmhealth.org; xuxi@mail.nih.gov;
tveenstra@c2ndiagnostics.com; BJFuhrman@uams.edu;
shermanm@exchange.nih.gov; brintonl@exchange.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; Fuhrman, Barbara/0000-0002-1777-9888
FU Division of Cancer Epidemiology and Genetics of the National Cancer
Institute; National Cancer Institute [HHSN261200800001E, U01CA70013,
1R21CA157254]; Breast Cancer Research Stamp Funds from the National
Cancer Institute; National Center for Research Resources [M01 RR000109]
FX This study was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics of the National Cancer
Institute and National Cancer Institute federal funds awarded under
Contract No. HHSN261200800001E to SAIC-Frederick, Inc. Breast Cancer
Research Stamp Funds and cooperative agreement U01CA70013 (B.M. Geller,
P.M. Vacek, D.L. Weaver, R.E. Chicoine, S.D. Herschorn) and 1R21CA157254
(J.A. Shepherd, B. Fan, A.P. Mahmoudzadeh) from the National Cancer
Institute funded some of the data collection and image analysis for this
study. Grant number M01 RR000109 from the National Center for Research
Resources funded the blood processing at the University of Vermont's
General Clinical Research Center. 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 52
TC 2
Z9 2
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1868-8497
EI 1868-8500
J9 HORM CANCER-US
JI Horm. Cancer
PD JUN
PY 2015
VL 6
IS 2-3
BP 107
EP 119
DI 10.1007/s12672-015-0216-3
PG 13
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA CJ0BT
UT WOS:000355138100005
PM 25757805
ER
PT J
AU Imani, F
Zhuang, B
Tahmasebi, A
Kwak, JT
Xu, S
Agarwal, H
Bharat, S
Uniyal, N
Turkbey, IB
Choyke, P
Pinto, P
Wood, B
Moradi, M
Mousavi, P
Abolmaesumi, P
AF Imani, Farhad
Zhuang, Bo
Tahmasebi, Amir
Kwak, Jin Tae
Xu, Sheng
Agarwal, Harsh
Bharat, Shyam
Uniyal, Nishant
Turkbey, Ismail Baris
Choyke, Peter
Pinto, Peter
Wood, Bradford
Moradi, Mehdi
Mousavi, Parvin
Abolmaesumi, Purang
TI Augmenting MRI-transrectal ultrasound-guided prostate biopsy with
temporal ultrasound data: a clinical feasibility study
SO INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY
LA English
DT Article; Proceedings Paper
CT 6th International Conference on Information Processing in
Computer-Assisted Interventions (IPCAI)
CY JUN 24, 2015
CL Barcelona, SPAIN
DE Temporal ultrasound data; Cancer diagnosis; Prostate cancer
ID REAL-TIME ELASTOGRAPHY; CANCER-DETECTION; FUSION; DIAGNOSIS; GUIDANCE
AB In recent years, fusion of multi-parametric MRI (mp-MRI) with transrectal ultrasound (TRUS)-guided biopsy has enabled targeted prostate biopsy with improved cancer yield. Target identification is solely based on information from mp-MRI, which is subsequently transferred to the subject coordinates through an image registration approach. mp-MRI has shown to be highly sensitive to detect higher-grade prostate cancer, but suffers from a high rate of false positives for lower-grade cancer, leading to unnecessary biopsies. This paper utilizes a machine-learning framework to further improve the sensitivity of targeted biopsy through analyzing temporal ultrasound data backscattered from the prostate tissue.
Temporal ultrasound data were acquired during targeted fusion prostate biopsy from suspicious cancer foci identified in mp-MRI. Several spectral features, representing the signature of backscattered signal from the tissue, were extracted from the temporal ultrasound data. A supervised support vector machine classification model was trained to relate the features to the result of histopathology analysis of biopsy cores obtained from cancer foci. The model was used to predict the label of biopsy cores for mp-MRI-identified targets in an independent group of subjects.
Training of the classier was performed on data obtained from 35 biopsy cores. A fivefold cross-validation strategy was utilized to examine the consistency of the selected features from temporal ultrasound data, where we achieved the classification accuracy and area under receiver operating characteristic curve of 94 % and 0.98, respectively. Subsequently, an independent group of 25 biopsy cores was used for validation of the model, in which mp-MRI had identified suspicious cancer foci. Using the trained model, we predicted the tissue pathology using temporal ultrasound data: 16 out of 17 benign cores, as well as all three higher-grade cancer cores, were correctly identified.
The results show that temporal analysis of ultrasound data is potentially an effective approach to complement mp-MRI-TRUS-guided prostate cancer biopsy, specially to reduce the number of unnecessary biopsies and to reliably identify higher-grade cancers.
C1 [Imani, Farhad; Zhuang, Bo; Uniyal, Nishant; Moradi, Mehdi; Abolmaesumi, Purang] Univ British Columbia, Dept Elect & Comp Engn, Vancouver, BC V6T 1Z4, Canada.
[Tahmasebi, Amir; Agarwal, Harsh; Bharat, Shyam] Philips Res North Amer, Briarcliff Manor, NY USA.
[Kwak, Jin Tae; Xu, Sheng; Turkbey, Ismail Baris; Choyke, Peter; Pinto, Peter; Wood, Bradford] NIH, Bethesda, MD 20892 USA.
[Mousavi, Parvin] Queens Univ, Sch Comp, Kingston, ON, Canada.
RP Imani, F (reprint author), Univ British Columbia, Dept Elect & Comp Engn, Vancouver, BC V6T 1Z4, Canada.
EM farhadi@ece.ubc.ca
FU Natural Sciences and Engineering Research Council of Canada (NSERC);
Canadian Institutes of Health Research (CIHR)
FX The authors would like to acknowledge the help of Jochen Kruecker and
Pingkun Yan for assisting with the experiments. This work was supported
in part by the Natural Sciences and Engineering Research Council of
Canada (NSERC) and the Canadian Institutes of Health Research (CIHR).
NR 30
TC 0
Z9 0
U1 1
U2 4
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1861-6410
EI 1861-6429
J9 INT J COMPUT ASS RAD
JI Int. J. Comput. Assist. Radiol. Surg.
PD JUN
PY 2015
VL 10
IS 6
SI SI
BP 727
EP 735
DI 10.1007/s11548-015-1184-3
PG 9
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging;
Surgery
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging; Surgery
GA CJ3ZF
UT WOS:000355422800006
PM 25843948
ER
PT J
AU Bharmal, N
Kaplan, RM
Shapiro, MF
Mangione, CM
Kagawa-Singer, M
Wong, MD
McCarthy, WJ
AF Bharmal, Nazleen
Kaplan, Robert M.
Shapiro, Martin F.
Mangione, Carol M.
Kagawa-Singer, Marjorie
Wong, Mitchell D.
McCarthy, William J.
TI The Association of Duration of Residence in the United States with
Cardiovascular Disease Risk Factors Among South Asian Immigrants
SO JOURNAL OF IMMIGRANT AND MINORITY HEALTH
LA English
DT Article
DE Asian Americans; Immigrants; Acculturation; Cardiovascular disease; Risk
factors; United States
ID BODY-MASS INDEX; CORONARY-HEART-DISEASE; SELF-REPORT MEASURES; METABOLIC
SYNDROME; PHYSICAL-ACTIVITY; MYOCARDIAL-INFARCTION; DIABETES-MELLITUS;
HEALTH BEHAVIORS; ARTERY-DISEASE; ETHNIC-GROUPS
AB South Asians are disproportionately impacted by cardiovascular disease (CVD). Our objective was to examine the association between duration of residence in the US and CVD risk factors among South Asian adult immigrants. Multivariate logistic regression analyses using pooled data from the 2005, 2007, 2009 California Health Interview Surveys. Duration of residence in the US < 15 years was significantly associated with overweight/obese BMI (OR 0.59; 95 % CI 0.35, 0.98 for 5 to < 10 years), daily consumption of 5+ servings of fruits/vegetables (OR 0.37; 95 % CI 0.15, 0.94 for 10 to < 15 years), and sedentary lifestyle (OR 2.11; 95 % CI 1.17, 3.81 for 10 to < 15 years) compared with duration of residence a parts per thousand yen15 years after adjusting for illness burden, healthcare access, and socio-demographic characteristics. Duration of residence was not significantly associated with other CVD risk factors. Duration of residence is an important correlate of overweight/obesity and other risk factors among South Asian immigrants.
C1 [Bharmal, Nazleen; Shapiro, Martin F.; Mangione, Carol M.; Wong, Mitchell D.] Univ Calif Los Angeles, Dept Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA.
[Kaplan, Robert M.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
[Kagawa-Singer, Marjorie] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Community Hlth Sci, Los Angeles, CA USA.
[McCarthy, William J.] Univ Calif Los Angeles, Dept Psychol, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90024 USA.
[McCarthy, William J.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90024 USA.
RP Bharmal, N (reprint author), Univ Calif Los Angeles, Dept Med, Div Gen Internal Med & Hlth Serv Res, 911 Broxton Ave,Room 203, Los Angeles, CA 90095 USA.
EM nbharmal@mednet.ucla.edu
RI Dey, Kamalesh/E-6568-2017;
OI Wong, Mitchell/0000-0002-4800-8410
FU Division of General Internal Medicine and Health Services Research;
American Heart Association-Pharmaceutical Roundtable Spina Outcomes
Center at the University of California, Los Angeles [0875133 N]; NHLBI
[1P50HL105188-6094]
FX The authors thank Gerardo Moreno, MD, MSHS and Keith C. Norris, MD, FACP
for their review of manuscript drafts. NB was supported by the Division
of General Internal Medicine and Health Services Research and the
American Heart Association-Pharmaceutical Roundtable Spina Outcomes
Center (0875133 N) fellowship at the University of California, Los
Angeles. WJM was supported by the NHLBI - 1P50HL105188-6094. No funding
source had any role in the study design, analysis, interpretation of
data, writing of the manuscript, or decision to submit the article for
publication.
NR 77
TC 5
Z9 5
U1 0
U2 19
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1557-1912
EI 1557-1920
J9 J IMMIGR MINOR HEALT
JI J. Immigr. Minor. Health
PD JUN
PY 2015
VL 17
IS 3
BP 781
EP 790
DI 10.1007/s10903-013-9973-7
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CJ1OX
UT WOS:000355254500020
PM 24380928
ER
PT J
AU Bai, RL
Cloninger, A
Czaja, W
Sasser, PJ
AF Bai, Ruiliang
Cloninger, Alexander
Czaja, Wojciech
Sasser, Peter J.
TI Efficient 2D MRI relaxometry using compressed sensing
SO JOURNAL OF MAGNETIC RESONANCE
LA English
DT Article
DE Relaxation; 2D relaxometry; Compressed sensing; MRI; Inverse Laplace
transform; Exchange; Rician noise
ID CROSS-CORRELATION RELAXOMETRY; TIME-CORRELATION RELAXOMETRY;
MULTIDIMENSIONAL NMR; EXCHANGE SPECTROSCOPY; T-2 DISTRIBUTION; 1ST KIND;
IN-VIVO; DIFFUSION; RELAXATION; INVERSION
AB Potential applications of 2D relaxation spectrum NMR and MRI to characterize complex water dynamics (e.g., compartmental exchange) in biology and other disciplines have increased in recent years. However, the large amount of data and long MR acquisition times required for conventional 2D MR relaxometry limits its applicability for in vivo preclinical and clinical MRI. We present a new MR pipeline for 2D relaxometry that incorporates compressed sensing (CS) as a means to vastly reduce the amount of 2D relaxation data needed for material and tissue characterization without compromising data quality. Unlike the conventional CS reconstruction in the Fourier space (k-space), the proposed CS algorithm is directly applied onto the Laplace space (the joint 2D relaxation data) without compressing k-space to reduce the amount of data required for 2D relaxation spectra. This framework is validated using synthetic data, with NMR data acquired in a well-characterized urea/water phantom, and on fixed porcine spinal cord tissue. The quality of the CS-reconstructed spectra was comparable to that of the conventional 2D relaxation spectra, as assessed using global correlation, local contrast between peaks, peak amplitude and relaxation parameters, etc. This result brings this important type of contrast closer to being realized in preclinical, clinical, and other applications. (C) 2015 Published by Elsevier Inc.
C1 [Bai, Ruiliang; Sasser, Peter J.] NICHD, Sect Tissue Biophys & Biomimet, PPITS, NIH, Bethesda, MD 20892 USA.
[Bai, Ruiliang] Univ Maryland, Inst Phys Sci & Technol, Biophys Program, College Pk, MD 20740 USA.
[Cloninger, Alexander] Yale Univ, Program Appl Math, New Haven, CT 06511 USA.
[Czaja, Wojciech] Univ Maryland, Dept Math, Norbert Wiener Ctr, College Pk, MD 20742 USA.
RP Sasser, PJ (reprint author), NICHD, Sect Tissue Biophys & Biomimet, PPITS, NIH, Bethesda, MD 20892 USA.
EM pjbasser@helix.nih.gov
FU Intramural Research Program (IRP) of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH; National Science
Foundation [DMS-1402254]
FX This work was supported by the Intramural Research Program (IRP) of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH. Alexander Cloninger is supported by the National
Science Foundation under Award No. DMS-1402254. Thanks to Mrs. Joni
Taylor, Mr. T.J. Hunt, and Mr. R.R. Clevenger from the ASR Core, NHLBI,
for obtaining the spinal cord specimens and Ms. L. Salak for editing the
manuscript. We are also grateful to our colleagues Dr. Y. Gao for help
preparing the urea/water phantom and Dr. M.E. Komlosh and Dr. E.
Hutchinson for assistance with MRI experiment.
NR 49
TC 4
Z9 4
U1 4
U2 17
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1090-7807
EI 1096-0856
J9 J MAGN RESON
JI J. Magn. Reson.
PD JUN
PY 2015
VL 255
BP 88
EP 99
DI 10.1016/j.jmr.2015.04.002
PG 12
WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical;
Spectroscopy
SC Biochemistry & Molecular Biology; Physics; Spectroscopy
GA CJ3LU
UT WOS:000355386300011
PM 25917134
ER
PT J
AU Oldfield, EH
Merrill, MJ
AF Oldfield, Edward H.
Merrill, Marsha J.
TI Apoplexy of pituitary adenomas: the perfect storm
SO JOURNAL OF NEUROSURGERY
LA English
DT Article
DE pituitary adenoma; pituitary apoplexy; pituitary surgery
ID POSITRON-EMISSION-TOMOGRAPHY; PRECIPITATING FACTORS; INTRASELLAR
PRESSURE; CLINICAL-FEATURES; TISSUE PRESSURE; TUMOR APOPLEXY;
ANGIOGENESIS; PET; MANAGEMENT; HYPERPROLACTINEMIA
AB OBJECT Pituitary adenomas occasionally undergo infarction, apoplexy, which often destroys much of the tumor. It is well known that apoplexy can be precipitated by several acute factors, including cardiac surgery, other types of surgery, trauma, insulin infusion, and stimulation with administration of hypothalamic releasing factors.
METHODS The prior focus on mechanisms underlying pituitary apoplexy has been on these acute events. Less attention has been given to the endogenous features of pituitary tumors that make them susceptible to spontaneous infarction, despite that most pituitary apoplexy occurs in the absence of a recognized precipitating event. The authors examine intrinsic features of pituitary adenomas that render them vulnerable to apoplexy-features such as high metabolic demand, paucity of angiogenesis, and sparse vascularity, qualities that have previously not been linked with apoplexy-and argue that it is these features of adenomas that underlie their susceptibility to spontaneous infarction. The sensitivity of freshly cultured pituitary adenomas to hypoglycemia is assessed.
RESULTS Adenomas have high metabolic demand, limited angiogenesis, and reduced vessel density compared with the normal gland. Pituitary adenoma cells do not survive in the presence of reduced or absent concentrations of glucose.
CONCLUSIONS The authors propose that the frequent ischemic infarction of pituitary adenomas is the product of intrinsic features of these tumors. These endogenous qualities create a tenuous balance between high metabolic demand and marginal tissue perfusion. Thus, the tumor is vulnerable to spontaneous infarction or to acute ischemia by any event that acutely alters the balance between tumor perfusion and tumor metabolism, events such as acute systemic hypotension, abruptly decreased supply of nutrients, hypoglycemia with insulin administration, or increase in the tumor's metabolic demand due to administration of hypothalamic releasing factors. It may be possible to take advantage of these intrinsic features of pituitary adenomas by using aspects of this vulnerability for development of new approaches for treatment.
C1 [Oldfield, Edward H.] Univ Virginia, Dept Neurol Surg, Hlth Sci Ctr, Charlottesville, VA 22908 USA.
[Oldfield, Edward H.; Merrill, Marsha J.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Oldfield, EH (reprint author), Univ Virginia, Dept Neurol Surg, POB 800212, Charlottesville, VA 22908 USA.
EM eho4u@virginia.edu
NR 47
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Z9 5
U1 2
U2 8
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
EI 1933-0693
J9 J NEUROSURG
JI J. Neurosurg.
PD JUN
PY 2015
VL 122
IS 6
BP 1444
EP 1449
DI 10.3171/2014.10.JNS141720
PG 6
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA CI8OK
UT WOS:000355031400028
PM 25859802
ER
PT J
AU Saftlas, AF
Spracklen, CN
Ryckman, KK
Stockdale, CK
Penrose, K
Ault, K
Rubenstein, LM
Pinto, LA
AF Saftlas, Audrey F.
Spracklen, Cassandra N.
Ryckman, Kelli K.
Stockdale, Colleen K.
Penrose, Kerri
Ault, Kevin
Rubenstein, Linda M.
Pinto, Ligia A.
TI Influence of a loop electrosurgical excision procedure (LEEP) on levels
of cytokines in cervical secretions
SO JOURNAL OF REPRODUCTIVE IMMUNOLOGY
LA English
DT Article
DE Loop electrosurgical excision procedure (LEEP); Cervical intraepithelial
neoplasia (CIN); Cervical secretions; Cytokines
ID HUMAN-PAPILLOMAVIRUS INFECTION; INTRAEPITHELIAL NEOPLASIA; INFLAMMATION
MARKERS; IMMUNE-RESPONSES; IFN-GAMMA; RISK; HPV; WOMEN; CLEARANCE;
CANCER
AB Over the past decade, there has been heightened interest in determining if there is an increased risk of adverse reproductive outcomes among women who had a loop electrosurgical excision procedure (LEEP) to remove cervical intraepithelial neoplasia (CIN). The objective of this exploratory study was to determine if the treatment of CIN with a LEEP is associated with changes in cervical soluble immune markers. Cervical cytokine concentrations were measured in women treated with LEEP and a control group of women who had colposcopy only and did not undergo LEEP. Cytokines were examined in cervical secretions collected in Merocel (R) sponges at study entry and at 6-month follow-up. Cytokines were measured using a Luminex 18-plex cytokine bead assay. The mean cytokine levels were not significantly changed from baseline to follow-up in either group, with the exception of TNF-alpha, which decreased among women who underwent a LEEP. When the mean levels of cytokines of the treated and untreated groups at baseline or follow-up were compared, cytokine levels tended to be lower in the treated group (particularly IFN-gamma, IL-6, IL-8, and MCP-1). Findings from adjusted repeated measures analyses revealed no differences between the two groups with regard to changes in cytokine levels overtime. Overall, women undergoing a LEEP showed few changes in the cervical microenvironment relative to untreated women. Future studies with additional cervical environment markers and larger sample sizes are needed to determine if a LEEP is associated with dysregulation of the cervical microenvironment. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Saftlas, Audrey F.; Ryckman, Kelli K.; Rubenstein, Linda M.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA 52242 USA.
[Spracklen, Cassandra N.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Stockdale, Colleen K.] Univ Iowa, Carver Coll Med, Dept Obstet & Gynecol, Iowa City, IA 51214 USA.
[Penrose, Kerri] Univ Pittsburgh, Dept Med, Div Infect Dis, Pittsburgh, PA 15261 USA.
[Ault, Kevin] Univ Kansas, Med Ctr, Dept Obstet & Gynecol, Kansas City, KS 66160 USA.
[Pinto, Ligia A.] Leidos Biomed Res Inc, Human Papillomavirus Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Saftlas, AF (reprint author), Univ Iowa, Coll Publ Hlth, Dept Epidemiol, 145 Riverside Dr,S427 CPHB, Iowa City, IA 52242 USA.
EM audrey-saftlas@uiowa.edu; cnspracklen@unc.edu; kelli-ryckman@uiowa.edu;
colleen-stockdale@uiowa.edu; kjp43@pitt.edu; kault2@kumc.edu;
linda-rubenstein@uiowa.edu; pintol@mail.nih.gov
FU National Institute of Allergy and Infectious Diseases [R21-AI06811];
National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This work was supported by the National Institute of Allergy and
Infectious Diseases (R21-AI06811).; This project has been funded in
whole or in part by federal funds from the National Cancer Institute,
National Institutes of Health, under Contract no. HHSN261200800001E. The
content of this paper does not necessarily reflect the views or policies
of the Department of Health and Human Services, nor does the mention of
trade names, commercial products, or organizations imply endorsement by
the US Government.
NR 23
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U1 1
U2 6
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0165-0378
J9 J REPROD IMMUNOL
JI J. Reprod. Immunol.
PD JUN
PY 2015
VL 109
BP 74
EP 83
DI 10.1016/j.jri.2015.01.002
PG 10
WC Immunology; Reproductive Biology
SC Immunology; Reproductive Biology
GA CJ3DW
UT WOS:000355364600011
PM 25721621
ER
PT J
AU Collard, RM
Comijs, HC
Naarding, P
Penninx, BW
Milaneschi, Y
Ferrucci, L
Voshaar, RCO
AF Collard, Rose M.
Comijs, Hannie C.
Naarding, Paul
Penninx, Brenda W.
Milaneschi, Yuri
Ferrucci, Luigi
Voshaar, Richard C. Oude
TI Frailty as a Predictor of the Incidence and Course of Depressed Mood
SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION
LA English
DT Article
DE Depression; frailty; older persons; InCHIANTI
ID DWELLING OLDER PERSONS; LATE-LIFE DEPRESSION; COMMUNITY; ASSOCIATION;
DISABILITY; PROGNOSIS; INCHIANTI; HEALTH; ADULTS; AGE
AB Background: Late-life depression and physical frailty are supposed to be reciprocally associated, however, longitudinal studies are lacking.
Objectives: This study examines whether physical frailty predicts a higher incidence of depression, as well as a less favorable course of depression.
Methods: A population-based cohort study of 888 people aged 65 years and over with follow-up measures at 3, 6, and 9 years. Cox proportional hazards models adjusted for age, sex, education, smoking, alcohol usage, and global cognitive functioning were applied to calculate the incidence of depressed mood in those nondepressed at baseline (n = 699) and remission in those with depressed mood at baseline (n = 189). Depressed mood onset or remission was defined as crossing the cut-off score of 20 points on the Center for Epidemiological Studies-Depression Scale combined with a relevant change in this score. Physical frailty was based on the presence of >= 3 out of 5 components (ie, weight loss, weakness, slowness, exhaustion, and low physical activity level).
Results: A total of 214 out of 699 (30.6%) nondepressed persons developed depressed mood during follow-up. Physical frailty predicted the onset of depressed mood with a hazard rate of 1.26 (95% confidence interval 1.09e1.45, P = .002). Of the 189 persons with depressed mood at baseline, 96 (50.8%) experienced remission during follow-up. Remission was less likely in the presence of a higher level of physical frailty (hazard rate = 0.72, 95% confidence interval 0.58-0.91, P = .005).
Conclusions: Because physical frailty predicts both the onset and course of late-life depressed mood, physical frailty should receive more attention in mental health care planning for older persons as well as its interference with treatment. Future studies into the pathophysiological mechanisms may guide the development of new treatment opportunities for these vulnerable patients. (C) 2015 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
C1 [Collard, Rose M.; Voshaar, Richard C. Oude] Radboud Univ Nijmegen Med Ctr, Dept Psychiat, NL-6500 HB Nijmegen, Netherlands.
[Collard, Rose M.] Nijmegen Mental Hlth Ctr, Pro Persona, Nijmegen, Netherlands.
[Comijs, Hannie C.; Penninx, Brenda W.; Milaneschi, Yuri] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
[Comijs, Hannie C.; Penninx, Brenda W.; Milaneschi, Yuri] Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, GGZinGeest, Amsterdam, Netherlands.
[Naarding, Paul] GGNet, Dept Old Age Psychiat, Apeldoorn, Netherlands.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, Baltimore, MD 21224 USA.
[Voshaar, Richard C. Oude] Univ Groningen, Univ Med Ctr Groningen, Univ Ctr Psychiat, Groningen, Netherlands.
[Voshaar, Richard C. Oude] Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol Emot Regulat, Groningen, Netherlands.
RP Collard, RM (reprint author), Radboud Univ Nijmegen Med Ctr, Dept Psychiat, Hp 966,Postbus 9101, NL-6500 HB Nijmegen, Netherlands.
EM rose.collard@radboudumc.nl
FU Italian Ministry of Health [ICS110.1/RF97.71]; U.S. National Institute
on Aging, Bethesda, Maryland [236 MD 916413, 236 MD 821336]; US National
Institute on Aging [N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002]
FX The original InCHIANTI study baseline (1998-2000) was supported by the
Italian Ministry of Health (ICS110.1/RF97.71) and in part by the U.S.
National Institute on Aging, Bethesda, Maryland (contracts 236 MD 916413
and 236 MD 821336). The InCHIANTI follow-up 1 (2001-2003) was funded by
the US National Institute on Aging (Contracts: N.1-AG-1-1 and
N.1-AG-1-2111); the InCHIANTI follow-up 2 and 3 studies (2004-2010) were
financed by the US National Institute on Aging (Contract N01-AG-5-0002).
NR 46
TC 3
Z9 3
U1 3
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-8610
EI 1538-9375
J9 J AM MED DIR ASSOC
JI J. Am. Med. Dir. Assoc.
PD JUN 1
PY 2015
VL 16
IS 6
BP 509
EP 514
DI 10.1016/j.jamda.2015.01.088
PG 6
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA CJ0AQ
UT WOS:000355134100011
PM 25737263
ER
PT J
AU Polley, MYC
YLeung, SC
Gao, D
Mastropasqua, MG
Zabaglo, LA
Bartlett, JMS
McShane, LM
Enos, RA
Badve, SS
Bane, AL
Borgquist, S
Fineberg, S
Lin, MG
Gown, AM
Grabau, D
Gutierrez, C
Hugh, JC
Moriya, T
Ohi, Y
Osborne, CK
Penault-Llorca, FM
Piper, T
Porter, PL
Sakatani, T
Salgado, R
Starczynski, J
Laenkholm, AV
Viale, G
Dowsett, M
Hayes, DF
Nielsen, TO
AF Polley, Mei-Yin C.
YLeung, Samuel C.
Gao, Dongxia
Mastropasqua, Mauro G.
Zabaglo, Lila A.
Bartlett, John M. S.
McShane, Lisa M.
Enos, Rebecca A.
Badve, Sunil S.
Bane, Anita L.
Borgquist, Signe
Fineberg, Susan
Lin, Ming-Gang
Gown, Allen M.
Grabau, Dorthe
Gutierrez, Carolina
Hugh, Judith C.
Moriya, Takuya
Ohi, Yasuyo
Osborne, C. Kent
Penault-Llorca, Frederique M.
Piper, Tammy
Porter, Peggy L.
Sakatani, Takashi
Salgado, Roberto
Starczynski, Jane
Laenkholm, Anne-Vibeke
Viale, Giuseppe
Dowsett, Mitch
Hayes, Daniel F.
Nielsen, Torsten O.
CA Int Ki67 Breast Canc Working Grp
North American Breast Canc Grp BIG
TI An international study to increase concordance in Ki67 scoring
SO MODERN PATHOLOGY
LA English
DT Article
ID PRACTICE GUIDELINE UPDATE; BREAST-CANCER HIGHLIGHTS; AMERICAN SOCIETY;
CLINICAL ONCOLOGY/COLLEGE; EXPERT CONSENSUS; PRIMARY THERAPY;
RECOMMENDATIONS; INDEX; ESTROGEN; WOMEN
AB Although an important biomarker in breast cancer, Ki67 lacks scoring standardization, which has limited its clinical use. Our previous study found variability when laboratories used their own scoring methods on centrally stained tissue microarray slides. In this current study, 16 laboratories from eight countries calibrated to a specific Ki67 scoring method and then scored 50 centrally MIB-1 stained tissue microarray cases. Simple instructions prescribed scoring pattern and staining thresholds for determination of the percentage of stained tumor cells. To calibrate, laboratories scored 18 'training' and 'test' web-based images. Software tracked object selection and scoring. Success for the calibration was prespecified as Root Mean Square Error of scores compared with reference <0.6 and Maximum Absolute Deviation from reference <1.0 (log2-transformed data). Prespecified success criteria for tissue microarray scoring required intraclass correlation significantly >0.70 but aiming for observed intraclass correlation >= 0.90. Laboratory performance showed non-significant but promising trends of improvement through the calibration exercise (mean Root Mean Square Error decreased from 0.6 to 0.4, Maximum Absolute Deviation from 1.6 to 0.9; paired t-test: P=0.07 for Root Mean Square Error, 0.06 for Maximum Absolute Deviation). For tissue microarray scoring, the intraclass correlation estimate was 0.94 (95% credible interval: 0.90-0.97), markedly and significantly >0.70, the prespecified minimum target for success. Some discrepancies persisted, including around clinically relevant cutoffs. After calibrating to a common scoring method via a web-based tool, laboratories can achieve high inter-laboratory reproducibility in Ki67 scoring on centrally stained tissue microarray slides. Although these data are potentially encouraging, suggesting that it may be possible to standardize scoring of Ki67 among pathology laboratories, clinically important discrepancies persist. Before this biomarker could be recommended for clinical use, future research will need to extend this approach to biopsies and whole sections, account for staining variability, and link to outcomes.
C1 [Polley, Mei-Yin C.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[YLeung, Samuel C.; Gao, Dongxia; Nielsen, Torsten O.] Univ British Columbia, Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada.
[Mastropasqua, Mauro G.] European Inst Oncol, Div Pathol, Milan, Italy.
[Mastropasqua, Mauro G.] European Inst Oncol, Lab Med, Milan, Italy.
[Zabaglo, Lila A.; McShane, Lisa M.] Breakthrough Breast Canc Res Ctr, Inst Canc Res, London, England.
[Bartlett, John M. S.] Ontario Inst Canc Res, Transformat Pathol, Toronto, ON, Canada.
[Enos, Rebecca A.] Emmes Corp, Rockville, MD USA.
[Badve, Sunil S.] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA.
[Bane, Anita L.] McMaster Univ, Juravinski Hosp, Dept Pathol & Mol Med, Hamilton, ON, Canada.
[Bane, Anita L.] McMaster Univ, Ctr Canc, Hamilton, ON, Canada.
[Borgquist, Signe; Grabau, Dorthe] Lund Univ, Div Oncol & Pathol, Dept Clin Sci, Lund, Sweden.
[Fineberg, Susan] Montefiore Med Ctr, Bronx, NY 10467 USA.
[Fineberg, Susan] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Lin, Ming-Gang; Porter, Peggy L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Gown, Allen M.] PhenoPath Labs, Seattle, WA USA.
[Gutierrez, Carolina; Osborne, C. Kent] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA.
[Gutierrez, Carolina; Osborne, C. Kent] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
[Hugh, Judith C.] Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB T6G 2M7, Canada.
[Moriya, Takuya] Kawasaki Med Univ, Dept Pathol, Kurashiki, Okayama, Japan.
[Ohi, Yasuyo] Hakuaikai Sagara Hosp, Dept Pathol, Kagoshima, Japan.
[Penault-Llorca, Frederique M.] Ctr Jean Perrin, Dept Pathol, Clermont Ferrand, France.
[Penault-Llorca, Frederique M.] Univ Auvergne, Clermont Ferrand, France.
[Piper, Tammy] Western Gen Hosp, Edinburgh Canc Res Ctr, Edinburgh EH4 2XU, Midlothian, Scotland.
[Sakatani, Takashi] Jichi Med Univ, Dept Pathol, Shimotsuke, Tochigi, Japan.
[Salgado, Roberto] Inst Jules Bordet, B-1000 Brussels, Belgium.
[Starczynski, Jane] Natl Hlth Serv, Birmingham Heart England, Birmingham, W Midlands, England.
[Laenkholm, Anne-Vibeke] Slagelse Hosp, Slagelse, Denmark.
[Viale, Giuseppe] European Inst Oncol, Div Pathol, Milan, Italy.
[Viale, Giuseppe] European Inst Oncol, Lab Med, Milan, Italy.
[Viale, Giuseppe] Univ Milan, Milan, Italy.
[Dowsett, Mitch] Royal Marsden Hosp, Acad Dept Biochem, London SW3 6JJ, England.
[Hayes, Daniel F.] Univ Michigan, Breast Oncol Program, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
RP Nielsen, TO (reprint author), Univ British Columbia, Pathol & Lab Med, Anat Pathol, Vancouver Hosp & Hlth Sci Ctr, JP 1401,855 W 12th Ave,, Vancouver, BC V5Z 1M9, Canada.
EM torsten@mail.ubc.ca
FU Breast Cancer Research Foundation; Breakthrough Breast Cancer; National
Institute for Health Research Biomedical Research Centre at the Royal
Marsden Hospital; Government of Ontario
FX This work was supported by the Breast Cancer Research Foundation.
Additional funding for the UK laboratories was received from
Breakthrough Breast Cancer and the National Institute for Health
Research Biomedical Research Centre at the Royal Marsden Hospital.
Funding for the Ontario Institute for Cancer Research is provided by the
Government of Ontario. Judith Hugh is the Lilian McCullough Chair in
Breast Cancer Surgery Research and the CBCF Prairies/NWT Chapter. We are
grateful to the Breast International Group and North American Breast
Cancer Group (BIG-NABCG) collaboration, including the leadership of Dr
Nancy Davidson, Dr Martine Piccart, and Dr Larry Norton, and for the
support of the Breast Cancer Research Foundation.
NR 21
TC 44
Z9 46
U1 1
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD JUN
PY 2015
VL 28
IS 6
BP 778
EP 786
DI 10.1038/modpathol.2015.38
PG 9
WC Pathology
SC Pathology
GA CJ1ZW
UT WOS:000355284800004
PM 25698062
ER
PT J
AU Papathomas, TG
Oudijk, L
Persu, A
Gill, AJ
van Nederveen, F
Tischler, AS
Tissier, F
Volante, M
Matias-Guiu, X
Smid, M
Favier, J
Rapizzi, E
Libe, R
Curras-Freixes, M
Aydin, S
Huynh, T
Lichtenauer, U
van Berkel, A
Canu, L
Domingues, R
Clifton-Bligh, RJ
Bialas, M
Vikkula, M
Baretton, G
Papotti, M
Nesi, G
Badoual, C
Pacak, K
Eisenhofer, G
Timmers, HJ
Beuschlein, F
Bertherat, J
Mannelli, M
Robledo, M
Gimenez-Roqueplo, AP
Dinjens, WNM
Korpershoek, E
de Krijger, RR
AF Papathomas, Thomas G.
Oudijk, Lindsey
Persu, Alexandre
Gill, Anthony J.
van Nederveen, Francien
Tischler, Arthur S.
Tissier, Frederique
Volante, Marco
Matias-Guiu, Xavier
Smid, Marcel
Favier, Judith
Rapizzi, Elena
Libe, Rosella
Curras-Freixes, Maria
Aydin, Selda
Huynh, Thanh
Lichtenauer, Urs
van Berkel, Anouk
Canu, Letizia
Domingues, Rita
Clifton-Bligh, Roderick J.
Bialas, Magdalena
Vikkula, Miikka
Baretton, Gustavo
Papotti, Mauro
Nesi, Gabriella
Badoual, Cecile
Pacak, Karel
Eisenhofer, Graeme
Timmers, Henri J.
Beuschlein, Felix
Bertherat, Jerome
Mannelli, Massimo
Robledo, Mercedes
Gimenez-Roqueplo, Anne-Paule
Dinjens, Winand N. M.
Korpershoek, Esther
de Krijger, Ronald R.
TI SDHB/SDHA immunohistochemistry in pheochromocytomas and paragangliomas:
a multicenter interobserver variation analysis using virtual microscopy:
a Multinational Study of the European Network for the Study of Adrenal
Tumors (ENS@T)
SO MODERN PATHOLOGY
LA English
DT Article
ID GASTROINTESTINAL STROMAL TUMORS; SUCCINATE-DEHYDROGENASE DEFICIENCY;
RENAL-CARCINOMA; SDHA MUTATIONS; CARNEY TRIAD; HEREDITARY
PHEOCHROMOCYTOMA; GERMLINE MUTATIONS; GENE-MUTATIONS; IDENTIFICATION;
INACTIVATION
AB Despite the established role of SDHB/SDHA immunohistochemistry as a valuable tool to identify patients at risk for familial succinate dehydrogenase-related pheochromocytoma/paraganglioma syndromes, the reproducibility of the assessment methods has not as yet been determined. The aim of this study was to investigate interobserver variability among seven expert endocrine pathologists using a web-based virtual microscopy approach in a large multicenter pheochromocytoma/paraganglioma cohort (n=351): (1) 73 SDH mutated, (2) 105 non-SDH mutated, (3) 128 samples without identified SDH-x mutations, and (4) 45 with incomplete SDH molecular genetic analysis. Substantial agreement among all the reviewers was observed either with a two-tiered classification (SDHB kappa= 0.7338; SDHA kappa = 0.6707) or a three-tiered classification approach (SDHB kappa = 0.6543; SDHA kappa = 0.7516). Consensus was achieved in 315 cases (89.74%) for SDHB immunohistochemistry and in 348 cases (99.15%) for SDHA immunohistochemistry. Among the concordant cases, 62 of 69 (similar to 90%) SDHB-/C-/D-/AF2-mutated cases displayed SDHB immunonegativity and SDHA immunopositivity, 3 of 4 (75%) with SDHA mutations showed loss of SDHA/SDHB protein expression, whereas 98 of 105 (93%) non-SDH-x-mutated counterparts demonstrated retention of SDHA/SDHB protein expression. Two SDHD-mutated extra-adrenal paragangliomas were scored as SDHB immunopositive, whereas 9 of 128 (7%) tumors without identified SDH-x mutations, 6 of 37 (similar to 16%) VHL-mutated, as well as 1 of 21 (similar to 5%) NF1-mutated tumors were evaluated as SDHB immunonegative. Although 14 out of those 16 SDHB-immunonegative cases were nonmetastatic, an overall significant correlation between SDHB immunonegativity and malignancy was observed (P=0.00019). We conclude that SDHB/SDHA immunohistochemistry is a reliable tool to identify patients with SDH-x mutations with an additional value in the assessment of genetic variants of unknown significance. If SDH molecular genetic analysis fails to detect a mutation in SDHB-immunonegative tumor, SDHC promoter methylation and/or VHL/NF1 testing with the use of targeted next-generation sequencing is advisable.
C1 [Papathomas, Thomas G.] Kings Coll Hosp London, Dept Histopathol, London, England.
[Papathomas, Thomas G.; Oudijk, Lindsey; Dinjens, Winand N. M.; Korpershoek, Esther; de Krijger, Ronald R.] Univ Med Ctr Rotterdam, Erasmus MC Canc Inst, Dept Pathol, Rotterdam, Netherlands.
[Persu, Alexandre] Catholic Univ Louvain, Clin Univ Saint Luc, Pole Cardiovasc Res, Inst Rech Expt & Clin, B-1200 Brussels, Belgium.
[Persu, Alexandre] Catholic Univ Louvain, Clin Univ Saint Luc, Div Cardiol, B-1200 Brussels, Belgium.
[Gill, Anthony J.] Royal N Shore Hosp, Dept Anat Pathol, St Leonards, NSW 2065, Australia.
[Gill, Anthony J.] Univ Sydney, Kolling Inst Med Res, Canc Diag & Pathol Res Grp, Sydney, NSW 2006, Australia.
[van Nederveen, Francien] PAL Dordrecht, Lab Pathol, Dordrecht, Netherlands.
[Tischler, Arthur S.] Tufts Univ, Dept Pathol, Tufts Med Ctr, Sch Med, Boston, MA 02111 USA.
[Tischler, Arthur S.] Tufts Univ, Lab Med, Tufts Med Ctr, Sch Med, Boston, MA 02111 USA.
[Tissier, Frederique] Univ Paris 05, Inst Natl Sante & Rech Med U1016, Inst Cochin,Ctr Natl Rech Sci UMR8104, Sorbonne Paris Cite,Rare Adrenal Canc Network COM, Paris, France.
[Tissier, Frederique] Univ Paris 06, Hop Pitie Salpetriere, Dept Pathol, Paris, France.
[Volante, Marco; Papotti, Mauro] Univ Turin, San Luigi Hosp, Dept Oncol, Turin, Italy.
[Matias-Guiu, Xavier] Univ Lleida, IRBLLEIDA, Hosp Univ Arnau Vilanova, Dept Pathol & Mol Genet, Lleida, Spain.
[Matias-Guiu, Xavier] Univ Lleida, IRBLLEIDA, Hosp Univ Arnau Vilanova, Res Lab, Lleida, Spain.
[Smid, Marcel] Univ Med Ctr Rotterdam, Erasmus MC Canc Inst, Dept Med Oncol, Rotterdam, Netherlands.
[Favier, Judith; Badoual, Cecile; Gimenez-Roqueplo, Anne-Paule] Hop Europeen Georges Pompidou, Inserm UMR970, Paris Ctr Rech Cardiovasc PARCC, Paris, France.
[Favier, Judith; Badoual, Cecile; Gimenez-Roqueplo, Anne-Paule] Univ Paris 05, Sorbonne Paris Cite, Fac Med, Paris, France.
[Rapizzi, Elena; Canu, Letizia; Mannelli, Massimo] Univ Florence, Endocrinol Unit, Dept Expt & Clin Biomed Sci, Florence, Italy.
[Curras-Freixes, Maria; Beuschlein, Felix; Robledo, Mercedes] Spanish Natl Canc Res Ctr CNIO, Hereditary Endocrine Canc Grp, Madrid, Spain.
[Aydin, Selda] Catholic Univ Louvain, Clin Univ Saint Luc, Dept Pathol, Inst Rech Expt & Clin, B-1200 Brussels, Belgium.
[Huynh, Thanh; Pacak, Karel] NIH, Program Reprod & Adult Endocrinol, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
[Lichtenauer, Urs] Klinikum Univ Munchen, Endocrine Res Unit, Med Klin & Poliklinik 4, Munich, Germany.
[van Berkel, Anouk; Timmers, Henri J.] Radboud Univ Nijmegen Med Ctr, Endocrinol Sect, Dept Internal Med, Nijmegen, Netherlands.
[Domingues, Rita] Inst Portugues Oncol Francisco Gentil, UIPM, Lisbon, Portugal.
[Clifton-Bligh, Roderick J.] Univ Sydney, Royal N Shore Hosp, Kolling Inst Med Res, Canc Genet, Sydney, NSW 2006, Australia.
[Bialas, Magdalena] Jagiellonian Univ, Coll Med, Dept Pathomorphol, Krakow, Poland.
[Vikkula, Miikka] Catholic Univ Louvain, Duve Inst, Lab Human Mol Genet, B-1200 Brussels, Belgium.
[Baretton, Gustavo] Tech Univ Dresden, Dept Pathol, D-01062 Dresden, Germany.
[Nesi, Gabriella] Univ Florence, Div Pathol Anat, Florence, Italy.
[Badoual, Cecile] AP HP, Hop Europeen Georges Pompidou, Serv Anat Pathol, Paris, France.
[Eisenhofer, Graeme] Tech Univ Dresden, Univ Hosp, Inst Clin Chem, D-01062 Dresden, Germany.
[Eisenhofer, Graeme] Tech Univ Dresden, Univ Hosp, Lab Med, D-01062 Dresden, Germany.
[Eisenhofer, Graeme] Tech Univ Dresden, Univ Hosp, Dept Med 3, D-01062 Dresden, Germany.
[Bertherat, Jerome] Univ Paris 05, Inst Cochin, CNRS, INSERM U1016,UMR8104, Paris, France.
[Bertherat, Jerome] Hop Cochin, Assistance Publ Hop Paris, Referral Ctr Rare Adrenal Dis, Dept Endocrinol, Paris, France.
[Mannelli, Massimo] ITT, Florence, Italy.
[Robledo, Mercedes] Ctr Biomed Network Res Rare Dis CIBERER, Madrid, Spain.
[de Krijger, Ronald R.] Reinier Graaf Hosp, Dept Pathol, Delft, Netherlands.
[de Krijger, Ronald R.] Univ Med Ctr Utrecht, Princess Maxima Ctr Pediat Oncol, Dept Pathol, Utrecht, Netherlands.
RP Papathomas, TG (reprint author), Kings Coll Hosp London, Dept Histopathol, Denmark Hill, London, England.
EM t.papathomas@erasmusmc.nl
RI matias-guiu, xavier/C-3039-2009; Robledo, Mercedes/O-2230-2013; canu,
letizia/E-7718-2017;
OI matias-guiu, xavier/0000-0002-7201-6605; Robledo,
Mercedes/0000-0001-6256-5902; canu, letizia/0000-0003-4995-8108;
Vikkula, Miikka/0000-0002-6236-338X; Mannelli,
Massimo/0000-0002-8001-9857; Domingues, Rita/0000-0001-7130-3795
FU Seventh Framework Programme (FP7) (ENS@T-Cancer) [259735]; Fonds de la
Recherche Scientifique Medicale (FRSM) [3.4.587.08 F]
FX This study was supported by the Seventh Framework Programme
(FP7/2007-2013) under grant agreement no. 259735 (ENS@T-Cancer). Genetic
analysis of the Belgian subset was partly supported by the Fonds de la
Recherche Scientifique Medicale (FRSM) convention number 3.4.587.08 F
(to AP). AP, SA, and MV acknowledge the contribution of N Lannoy, A
Mendola, and L Evenepoel (Clin. Univ. St-Luc/UCL) for genetic analysis
and F Severino (Clin. Univ. St-Luc) for maintenance of the database.
Besides Professor A Mourin (Clin. Univ. St-Luc/UCL), they are also
grateful to all pathologists who contributed tumor samples: Professors M
Delos and B Weynand and Drs M-C Nollevaux and C Fervaille (Cl. Un. De
Mont-Godinne, UCL); Drs N Detrembleur, N Bletard, and I Scagnol (CHU
Sart-Tilman, Ulg); Drs E Laterre and G Beniuga (IPG Gosselies);
Professor H De Raeve and Dr W Jeuris (OLV, Aalst); Dr V Duwel
(Ziekenhuis KLINA); Drs A Janssen and S Talpe Clniques du
Sud-Luxembourg, Arlon); Drs C Robrechts and J Bekaert (Imelda
Ziekenhuis); Dr R Duttmann (CHU Brugmann); Dr N de Saint-Aubain
(Institut Bordet); and Drs R Achten and K Wouters (Jessa Ziekenhuis).
MM, ER, LC, and GN acknowledge the contribution of Dr T Ercolino for the
genetic analysis of the Italian (Florence) samples. GE and GB
acknowledge the contribution of Drs C Pamporaki, R Darr, S Richter, and
J Brutting for data collection of the German (Dresden) samples. We thank
J Shukla (Erasmus MC Cancer Institute) for her valuable technical
assistance as well as Drs M Versasky and M Gomez Morales (Hospital
Universitario San Cecilio) for providing one SDHD-mutated HNPGL sample.
NR 79
TC 14
Z9 14
U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD JUN
PY 2015
VL 28
IS 6
BP 807
EP 821
DI 10.1038/modpathol.2015.41
PG 15
WC Pathology
SC Pathology
GA CJ1ZW
UT WOS:000355284800007
PM 25720320
ER
PT J
AU Lyda, TA
Joshi, MB
Andersen, JF
Kelada, AY
Owings, JP
Bates, PA
Dwyer, DM
AF Lyda, Todd A.
Joshi, Manju B.
Andersen, John F.
Kelada, Andrew Y.
Owings, Joshua P.
Bates, Paul A.
Dwyer, Dennis M.
TI A unique, highly conserved secretory invertase is differentially
expressed by promastigote developmental forms of all species of the
human pathogen, Leishmania
SO MOLECULAR AND CELLULAR BIOCHEMISTRY
LA English
DT Article
DE Leishmania; Protozoan pathogen; Human parasite; Invertase; Secretory
enzyme
ID ACID-PHOSPHATASE; DONOVANI PROMASTIGOTES; GLUCOSE-TRANSPORTER;
BIOCHEMICAL-CHARACTERIZATION; FUNCTIONAL DOMAINS; MEMBRANE-PROTEINS;
GENE; INFECTION; NUCLEASE; SUCRASE
AB Leishmania are protozoan pathogens of humans that exist as extracellular promastigotes in the gut of their sand fly vectors and as obligate intracellular amastigotes within phagolysosomes of infected macrophages. Between infectious blood meal feeds, sand flies take plant juice meals that contain sucrose and store these sugars in their crop. Such sugars are regurgitated into the sand fly anterior midgut where they impact the developing promastigote parasite population. In this report we showed that promastigotes of all Leishmania species secreted an invertase/sucrase enzyme during their growth in vitro. In contrast, neither L. donovani nor L. mexicana amastigotes possessed any detectable invertase activity. Importantly, no released/secreted invertase activity was detected in culture supernatants from either Trypanosoma brucei or Trypanosoma cruzi. Using HPLC, the L. donovani secretory invertase was isolated and subjected to amino acid sequencing. Subsequently, we used a molecular approach to identify the LdINV and LmexINV genes encoding the similar to 72 kDa invertases produced by these organisms. Interestingly, we identified high fidelity LdINV-like homologs in the genomes of all Leishmania sp. but none were present in either T. brucei or T. cruzi. Northern blot and RT-PCR analyses showed that these genes were developmentally/differentially expressed in promastigotes but not amastigotes of these parasites. Homologous transfection studies demonstrated that these genes in fact encoded the functional secretory invertases produced by these parasites. Cumulatively, our results suggest that these secretory enzymes play critical roles in the survival/growth/development and transmission of all Leishmania parasites within their sand fly vector hosts.
C1 [Joshi, Manju B.; Kelada, Andrew Y.; Owings, Joshua P.; Dwyer, Dennis M.] NIAID, Cell Biol Sect, Parasit Dis Lab, Div Intramural Res,NIH, Bethesda, MD 20892 USA.
[Andersen, John F.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Bates, Paul A.] Univ Lancaster, Fac Hlth & Med, Div Biomed & Life Sci, Lancaster LA1 4YQ, England.
RP Lyda, TA (reprint author), 105 Collings St BRC 216, Clemson, SC 29634 USA.
EM todd.a.lyda@gmail.com
OI Bates, Paul/0000-0001-6861-5421
FU Intramural Research Program of the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases (NIAID), National
Institutes of Health (NIH); Intramural Research Training Award
Post-doctoral Fellowship from the NIAID, NIH; Oak Ridge Institute for
Science and Education (ORISE), Research Specialist Program at NIH;
Postbaccalaureate Intramural Research Training Awards from the NIAID,
NIH
FX This research was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases (NIAID), National Institutes of Health (NIH). Dr.
Todd Lyda was supported by an Intramural Research Training Award
Post-doctoral Fellowship from the NIAID, NIH. Dr. Manju Joshi was
supported by an appointment through the Oak Ridge Institute for Science
and Education (ORISE), Research Specialist Program at NIH. The program
is administered by ORISE through an inter-agency agreement between the
US Department of Energy and the NIH. Mr. Andrew Y. Kelada and Mr. Joshua
P. Owings were supported by Postbaccalaureate Intramural Research
Training Awards from the NIAID, NIH. We thank Dr. Greg Matlashewski,
Department of Microbiology and Immunology McGill University, Montreal,
CA for providing the pKSNEO leishmanial expression vector; Dr. Buddy
Ullman, Department of Biochemistry and Molecular Biology, Oregon Health
Sciences University, Portland, OR for providing the L. donovani cosmid
library used in this study.
NR 46
TC 3
Z9 3
U1 1
U2 13
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0300-8177
EI 1573-4919
J9 MOL CELL BIOCHEM
JI Mol. Cell. Biochem.
PD JUN
PY 2015
VL 404
IS 1-2
BP 53
EP 77
DI 10.1007/s11010-015-2366-6
PG 25
WC Cell Biology
SC Cell Biology
GA CJ4DE
UT WOS:000355433900008
PM 25763714
ER
PT J
AU Mishra, PK
Guo, JS
Dittman, LE
Haase, J
Yeh, E
Bloom, K
Basrai, MA
AF Mishra, Prashant K.
Guo, Jiasheng
Dittman, Lauren E.
Haase, Julian
Yeh, Elaine
Bloom, Kerry
Basrai, Munira A.
TI Pat1 protects centromere-specific histone H3 variant Cse4 from
Psh1-mediated ubiquitination
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID SACCHAROMYCES-CEREVISIAE; BUDDING YEAST; CHROMOSOME SEGREGATION; CENP-A;
ECTOPIC LOCALIZATION; N-TERMINUS; KINETOCHORE; CHROMATIN; DNA; SCM3
AB Evolutionarily conserved histone H3 variant Cse4 and its homologues are essential components of specialized centromere (CEN)-specific nucleosomes and serve as an epigenetic mark for CEN identity and propagation. Cse4 is a critical determinant for the structure and function of the kinetochore and is required to ensure faithful chromosome segregation. The kinetochore protein Pat1 regulates the levels and spatial distribution of Cse4 at centromeres. Deletion of PAT1 results in altered structure of CEN chromatin and chromosome segregation errors. In this study, we show that Pat1 protects CEN-associated Cse4 from ubiquitination in order to maintain proper structure and function of the kinetochore in budding yeast. PAT1-deletion strains exhibit increased ubiquitination of Cse4 and faster turnover of Cse4 at kinetochores. Psh1, a Cse4-specific E3-ubiquitin ligase, interacts with Pat1 in vivo and contributes to the increased ubiquitination of Cse4 in pat1 Delta strains. Consistent with a role of Psh1 in ubiquitination of Cse4, transient induction of PSH1 in a wildtype strain resulted in phenotypes similar to a pat1. strain, including a reduction in CEN-associated Cse4, increased Cse4 ubiquitination, defects in spatial distribution of Cse4 at kinetochores, and altered structure of CEN chromatin. Pat1 interacts with Scm3 and is required for its maintenance at kinetochores. In conclusion, our studies provide novel insights into mechanisms by which Pat1 affects the structure of CEN chromatin and protects Cse4 from Psh1-mediated ubiquitination for faithful chromosome segregation.
C1 [Mishra, Prashant K.; Dittman, Lauren E.; Basrai, Munira A.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
[Guo, Jiasheng; Haase, Julian; Yeh, Elaine; Bloom, Kerry] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
RP Basrai, MA (reprint author), NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
EM basraim@mail.nih.gov
OI Bloom, Kerry/0000-0002-3457-004X
FU National Cancer Institute, National Institutes of Health; National
Institute of Health [R37 GM32238]
FX We thank Jennifer Gerton, Sue Biggins, Roy Parker, Michael Lichten, and
Richard Baker for reagents, Kathy McKinnon of the National Cancer
Institute Vaccine Branch FACS Core for assistance with FACS, Wei-Chun Au
for assistance with the ubiquitin pull-down assay, and members of the
Basrai laboratory for discussions. Support for P.K.M., L.E.D., and
M.A.B. was provided by the Intramural Research Program of the National
Cancer Institute, National Institutes of Health. Support for J.G., J.H.,
E.Y., and K.B. was derived from National Institute of Health Grant R37
GM32238 to K.B.
NR 57
TC 3
Z9 3
U1 0
U2 7
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD JUN 1
PY 2015
VL 26
IS 11
BP 2067
EP 2079
DI 10.1091/mbc.E14-08-1335
PG 13
WC Cell Biology
SC Cell Biology
GA CJ1LP
UT WOS:000355245400009
PM 25833709
ER
PT J
AU Iglesias-Bartolome, R
Torres, D
Marone, R
Feng, XD
Martin, D
Simaan, M
Chen, M
Weinstein, LS
Taylor, SS
Molinolo, AA
Gutkind, JS
AF Iglesias-Bartolome, Ramiro
Torres, Daniela
Marone, Romina
Feng, Xiaodong
Martin, Daniel
Simaan, May
Chen, Min
Weinstein, Lee S.
Taylor, Susan S.
Molinolo, Alfredo A.
Gutkind, J. Silvio
TI Inactivation of a G alpha(s)-PKA tumour suppressor pathway in skin stem
cells initiates basal-cell carcinogenesis
SO NATURE CELL BIOLOGY
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; HEDGEHOG SIGNALING PATHWAY; MOUSE EPIDERMIS;
YAP PATHWAY; CANCER; DIFFERENTIATION; PROLIFERATION; KINASE; MERLIN;
ALPHA
AB Genomic alterations in GNAS, the gene coding for the G alpha(s) heterotrimeric G protein, are associated with a large number of human diseases. Here, we explored the role of G alpha(s) on stem cell fate decisions by using the mouse epidermis as a model system. Conditional epidermal deletion of Gnas or repression of PKA signalling caused a remarkable expansion of the stem cell compartment, resulting in rapid basal-cell carcinoma formation. In contrast, inducible expression of active G alpha(s) in the epidermis caused hair follicle stem cell exhaustion and hair loss. Mechanistically, we found that G alpha(s)-PKA disruption promotes the cell autonomous Sonic Hedgehog pathway stimulation and Hippo signalling inhibition, resulting in the non-canonical activation of GLI and YAP1. Our study highlights an important tumour suppressive function of G alpha(s)-PKA, limiting the proliferation of epithelial stem cells and maintaining proper hair follicle homeostasis. These findings could have broad implications in multiple pathophysiological conditions, including cancer.
C1 [Iglesias-Bartolome, Ramiro; Torres, Daniela; Marone, Romina; Feng, Xiaodong; Martin, Daniel; Simaan, May; Molinolo, Alfredo A.; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Chen, Min; Weinstein, Lee S.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Taylor, Susan S.] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA.
[Taylor, Susan S.] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
EM sg39v@nih.gov
FU Intramural Research Program at the National Institutes of Health,
National Institute of Dental and Craniofacial Research; Swiss National
Science Foundation (Advanced Postdoc Mobility fellowship, SNF);
Margarete und Walter Lichtenstein Stiftung; [DK54441]
FX This work was supported by the Intramural Research Program at the
National Institutes of Health, National Institute of Dental and
Craniofacial Research. R.M. was supported by grants from the Swiss
National Science Foundation (Advanced Postdoc Mobility fellowship, SNF)
and the Margarete und Walter Lichtenstein Stiftung. S.S.T. was supported
by grant DK54441.
NR 64
TC 18
Z9 18
U1 2
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
EI 1476-4679
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD JUN
PY 2015
VL 17
IS 6
BP 793
EP +
DI 10.1038/ncb3164
PG 24
WC Cell Biology
SC Cell Biology
GA CJ1XD
UT WOS:000355277500011
PM 25961504
ER
PT J
AU Moriarity, BS
Otto, GM
Rahrmann, EP
Rathe, SK
Wolf, NK
Weg, MT
Manlove, LA
Larue, RS
Temiz, NA
Molyneux, SD
Choi, K
Holly, KJ
Sarver, AL
Scott, MC
Forster, CL
Modiano, JF
Khanna, C
Hewitt, SM
Khokha, R
Yang, Y
Gorlick, R
Dyer, MA
Largaespada, DA
AF Moriarity, Branden S.
Otto, George M.
Rahrmann, Eric P.
Rathe, Susan K.
Wolf, Natalie K.
Weg, Madison T.
Manlove, Luke A.
LaRue, Rebecca S.
Temiz, Nuri A.
Molyneux, Sam D.
Choi, Kwangmin
Holly, Kevin J.
Sarver, Aaron L.
Scott, Milcah C.
Forster, Colleen L.
Modiano, Jaime F.
Khanna, Chand
Hewitt, Stephen M.
Khokha, Rama
Yang, Yi
Gorlick, Richard
Dyer, Michael A.
Largaespada, David A.
TI A Sleeping Beauty forward genetic screen identifies new genes and
pathways driving osteosarcoma development and metastasis
SO NATURE GENETICS
LA English
DT Article
ID NERVE SHEATH TUMOR; POOR-PROGNOSIS; HEPATOCELLULAR-CARCINOMA;
NEUROFIBROMATOSIS TYPE-1; CELL-PROLIFERATION; OSTEOGENIC-SARCOMA;
COLORECTAL-CANCER; PROSTATE-CANCER; COPY NUMBER; EXPRESSION
AB Osteosarcomas are sarcomas of the bone, derived from osteoblasts or their precursors, with a high propensity to metastasize. Osteosarcoma is associated with massive genomic instability, making it problematic to identify driver genes using human tumors or prototypical mouse models, many of which involve loss of Trp53 function. To identify the genes driving osteosarcoma development and metastasis, we performed a Sleeping Beauty (SB) transposon-based forward genetic screen in mice with and without somatic loss of Trp53. Common insertion site (CIS) analysis of 119 primary tumors and 134 metastatic nodules identified 232 sites associated with osteosarcoma development and 43 sites associated with metastasis, respectively. Analysis of CIS-associated genes identified numerous known and new osteosarcoma-associated genes enriched in the ErbB, PI3K-AKT-mTOR and MAPK signaling pathways. Lastly, we identified several oncogenes involved in axon guidance, including Sema4d and Sema6d, which we functionally validated as oncogenes in human osteosarcoma.
C1 [Moriarity, Branden S.; Otto, George M.; Rahrmann, Eric P.; Largaespada, David A.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA.
[Moriarity, Branden S.; Otto, George M.; Rahrmann, Eric P.; Largaespada, David A.] Univ Minnesota, Ctr Genome Engn, Minneapolis, MN USA.
[Moriarity, Branden S.; Otto, George M.; Rahrmann, Eric P.; Largaespada, David A.] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN USA.
[Otto, George M.; Rahrmann, Eric P.; Wolf, Natalie K.; Weg, Madison T.; Manlove, Luke A.; Holly, Kevin J.; Largaespada, David A.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA.
[LaRue, Rebecca S.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA.
[Molyneux, Sam D.; Khokha, Rama] Ontario Canc Inst, Toronto, ON M4X 1K9, Canada.
[Choi, Kwangmin] Cincinnati Childrens Hosp Med Ctr, Cincinnati Childrens Hosp Res Fdn, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA.
[Scott, Milcah C.; Modiano, Jaime F.] Univ Minnesota, Dept Vet Clin Sci, St Paul, MN 55108 USA.
[Forster, Colleen L.] Univ Minnesota, Acad Hlth Ctr, BioNet, Minneapolis, MN USA.
[Modiano, Jaime F.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
[Khanna, Chand] NCI, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Hewitt, Stephen M.] NCI, TARP, Pathol Lab, Bethesda, MD 20892 USA.
[Yang, Yi] Peking Univ, Peoples Hosp, Musculoskeletal Tumor Ctr, Dept Orthoped Surg, Beijing 100871, Peoples R China.
[Gorlick, Richard] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA.
[Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
[Gorlick, Richard] Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10467 USA.
[Dyer, Michael A.] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA.
RP Largaespada, DA (reprint author), Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA.
EM larga002@umn.edu
OI Hewitt, Stephen/0000-0001-8283-1788; Modiano, Jaime/0000-0001-6398-7648
FU US National Institutes of Health/National Institute of Arthritis and
Musculoskeletal and Skin Diseases Musculoskeletal Training Grant
[AR050938]; Sobiech Osteosarcoma Fund Award; Children's Cancer Research
Fund; American Cancer Center Research Professor Grant [123939]; National
Cancer Institute grant [R01 CA113636]; comprehensive Masonic Cancer
Center (US National Institutes of Health grant) [P30 CA077598]
FX B.S.M. was funded by US National Institutes of Health/National Institute
of Arthritis and Musculoskeletal and Skin Diseases Musculoskeletal
Training Grant AR050938. This research was funded by the Sobiech
Osteosarcoma Fund Award, the Children's Cancer Research Fund, an
American Cancer Center Research Professor Grant (123939) and National
Cancer Institute grant R01 CA113636 (to D.A.L.). We extend our thanks to
the University of Minnesota resources involved in our project. The
University of Minnesota Genomics Center provided services for RNA
sequencing, oligonudeotide preparation and Sanger sequencing. The
Minnesota Supercomputing Institute maintains the Galaxy software
platform, as well as provides data management services and training. The
cytogenetic analyses were performed in the Cytogenomics Shared Resource
at the University of Minnesota with support from the comprehensive
Masonic Cancer Center (US National Institutes of Health grant P30
CA077598).
NR 80
TC 41
Z9 41
U1 1
U2 23
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 JUN
PY 2015
VL 47
IS 6
BP 615
EP 624
DI 10.1038/ng.3293
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA CJ3LW
UT WOS:000355386500012
PM 25961939
ER
PT J
AU Li, AH
Morrison, AC
Kovar, C
Cupples, LA
Brody, JA
Polfus, LM
Yu, B
Metcalf, G
Muzny, D
Veeraraghavan, N
Liu, XM
Lumley, T
Mosley, TH
Gibbs, RA
Boerwinkle, E
AF Li, Alexander H.
Morrison, Alanna C.
Kovar, Christie
Cupples, L. Adrienne
Brody, Jennifer A.
Polfus, Linda M.
Yu, Bing
Metcalf, Ginger
Muzny, Donna
Veeraraghavan, Narayanan
Liu, Xiaoming
Lumley, Thomas
Mosley, Thomas H.
Gibbs, Richard A.
Boerwinkle, Eric
TI Analysis of loss-of-function variants and 20 risk factor phenotypes in
8,554 individuals identifies loci influencing chronic disease
SO NATURE GENETICS
LA English
DT Article
ID GENES; PREDICTIONS; MUTATIONS; DATABASE; DBNSFP
AB A typical human exome harbors dozens of loss-of-function (LOF) variants(1), which can lower disease risk factor levels and affect drug efficacy(2). We hypothesized that LOF variants are enriched in genes influencing risk factor levels and the onset of common chronic diseases, such as cardiovascular disease and diabetes. To test this hypothesis, we sequenced the exomes of 8,554 individuals and analyzed the effects of predicted LOF variants on 20 chronic disease risk factor phenotypes. Analysis of this sample as discovery and replication strata of equal size verified two relationships in well-studied genes (PCSK9 and APOC3) and identified eight new loci. Previously unknown relationships included elevated fasting glucose in carriers of heterozygous LOF variation in TXNDC5, which encodes a biomarker for type 1 diabetes progression, and apparent recessive effects of C1QTNF8 on serum magnesium levels. These data demonstrate the utility of functional-variant annotation within a large sample of deeply phenotyped individuals for gene discovery.
C1 [Li, Alexander H.; Morrison, Alanna C.; Polfus, Linda M.; Yu, Bing; Liu, Xiaoming; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA.
[Kovar, Christie; Metcalf, Ginger; Muzny, Donna; Veeraraghavan, Narayanan; Gibbs, Richard A.; Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Cupples, L. Adrienne] NHLBI Framingham Heart Study, Framingham, MA USA.
[Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Brody, Jennifer A.; Lumley, Thomas] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Lumley, Thomas] Univ Auckland, Dept Stat, Auckland 1, New Zealand.
[Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Med Geriatr, Jackson, MS 39216 USA.
RP Boerwinkle, E (reprint author), Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA.
EM eric.boerwinkle@uth.tmc.edu
FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C,
HHSN268201100012C]; National Institutes of Health through the American
Recovery and Reinvestment Act of 2009 (AREA) [5RC2HL102419]; Baylor
College of Medicine Human Genome Sequencing Center [U54 HG003273]
FX The Atherosclerosis Risk in Communities (ARIC) study is carried out as a
collaborative study supported by National Heart, Lung, and Blood
Institute (NHLBI) contracts (HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C and HHSN268201100012C). We thank
the staff and participants of the ARIC study for their important
contributions. Funding support for "Building on GWAS for NHLBI-diseases:
the U.S. CHARGE Consortium" was provided by the National Institutes of
Health through the American Recovery and Reinvestment Act of 2009 (AREA)
(5RC2HL102419). Sequencing was carried out at the Baylor College of
Medicine Human Genome Sequencing Center (U54 HG003273).
NR 16
TC 12
Z9 12
U1 1
U2 4
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 JUN
PY 2015
VL 47
IS 6
BP 640
EP 642
DI 10.1038/ng.3270
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA CJ3LW
UT WOS:000355386500015
PM 25915599
ER
PT J
AU Viswanathan, S
Williams, ME
Bloss, EB
Stasevich, TJ
Speer, CM
Nern, A
Pfeiffer, BD
Hooks, BM
Li, WP
English, BP
Tian, T
Henry, GL
Macklin, JJ
Patel, R
Gerfen, CR
Zhuang, XW
Wang, YL
Rubin, GM
Looger, LL
AF Viswanathan, Sarada
Williams, Megan E.
Bloss, Erik B.
Stasevich, Timothy J.
Speer, Colenso M.
Nern, Aljoscha
Pfeiffer, Barret D.
Hooks, Bryan M.
Li, Wei-Ping
English, Brian P.
Tian, Teresa
Henry, Gilbert L.
Macklin, John J.
Patel, Ronak
Gerfen, Charles R.
Zhuang, Xiaowei
Wang, Yalin
Rubin, Gerald M.
Looger, Loren L.
TI High-performance probes for light and electron microscopy
SO NATURE METHODS
LA English
DT Article
ID GREEN FLUORESCENT PROTEIN; LIVING CELLS; DIFFUSION-COEFFICIENTS;
MONOCLONAL-ANTIBODIES; ARRAY TOMOGRAPHY; MAMMALIAN-CELLS; NEURAL
CIRCUITS; GENE-TRANSFER; DROSOPHILA; SYSTEM
AB We describe an engineered family of highly antigenic molecules based on GFP-like fluorescent proteins. These molecules contain numerous copies of peptide epitopes and simultaneously bind IgG antibodies at each location. These 'spaghetti monster' fluorescent proteins (smFPs) distributed well in neurons, notably into small dendrites, spines and axons. smFP immunolabeling localized weakly expressed proteins not well resolved with traditional epitope tags. By varying epitope and scaffold, we generated a diverse family of mutually orthogonal antigens. In cultured neurons and mouse and fly brains, smFP probes allowed robust, orthogonal multicolor visualization of proteins, cell populations and neuropil. smFP variants complement existing tracers and greatly increase the number of simultaneous imaging channels, and they performed well in advanced preparations such as array tomography, super-resolution fluorescence imaging and electron microscopy. In living cells, the probes improved single-molecule image tracking and increased yield for RNA-seq. These probes facilitate new experiments in connectomics, transcriptomics and protein localization.
C1 [Viswanathan, Sarada; Bloss, Erik B.; Stasevich, Timothy J.; Nern, Aljoscha; Pfeiffer, Barret D.; Hooks, Bryan M.; Li, Wei-Ping; English, Brian P.; Tian, Teresa; Henry, Gilbert L.; Macklin, John J.; Patel, Ronak; Wang, Yalin; Rubin, Gerald M.; Looger, Loren L.] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
[Williams, Megan E.] Univ Utah, Dept Neurobiol & Anat, Salt Lake City, UT USA.
[Speer, Colenso M.; Zhuang, Xiaowei] Harvard Univ, Howard Hughes Med Inst, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
[Hooks, Bryan M.; Gerfen, Charles R.] NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA.
[Zhuang, Xiaowei] Harvard Univ, Howard Hughes Med Inst, Dept Phys, Cambridge, MA 02138 USA.
RP Looger, LL (reprint author), Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA 20147 USA.
EM loogerl@janelia.hhmi.org
RI English, Brian/O-8156-2016;
OI English, Brian/0000-0002-4037-6294; Williams, Megan/0000-0002-5461-4126;
Rubin, Gerald/0000-0001-8762-8703
FU Howard Hughes Medical Institute
FX We thank the Cell Culture, Vivarium, Fly Facility, Histology, Electron
Microscopy, Media and Molecular Biology Shared Resources, and the Fly
Light Project Team, at Janelia. N. Betley, A. Hantman, J. Colonell,
J.-C. Rah, S. Sengupta, M. Baird and G. Tervo provided helpful
discussions. H. Su and H. Kimura helped with reagents, B. Karsh assisted
with image alignment for immunoEM and AT, and H. Rouault helped with
statistical analysis. Members of the Looger lab and M. Jefferies
provided helpful feedback during the project. A. Hantman and K. Ritola
(Janelia) provided the mTagBFP2 virus. This work was supported by the
Howard Hughes Medical Institute.
NR 70
TC 22
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U1 13
U2 81
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1548-7091
EI 1548-7105
J9 NAT METHODS
JI Nat. Methods
PD JUN
PY 2015
VL 12
IS 6
BP 568
EP +
DI 10.1038/nmeth.3365
PG 13
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA CJ1MQ
UT WOS:000355248100028
PM 25915120
ER
PT J
AU Garfield, AS
Li, C
Madara, JC
Shah, BP
Webber, E
Steger, JS
Campbell, JN
Gavrilova, O
Lee, CE
Olson, DP
Elmquist, JK
Tannous, BA
Krashes, MJ
Lowell, BB
AF Garfield, Alastair S.
Li, Chia
Madara, Joseph C.
Shah, Bhavik P.
Webber, Emily
Steger, Jennifer S.
Campbell, John N.
Gavrilova, Oksana
Lee, Charlotte E.
Olson, David P.
Elmquist, Joel K.
Tannous, Bakhos A.
Krashes, Michael J.
Lowell, Bradford B.
TI A neural basis for melanocortin-4 receptor-regulated appetite
SO NATURE NEUROSCIENCE
LA English
DT Article
ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; MELANOCYTE-STIMULATING HORMONE;
PROTEIN-COUPLED RECEPTORS; AGOUTI-RELATED PROTEIN; PARABRACHIAL NUCLEUS;
FEEDING-BEHAVIOR; AGRP NEURONS; RNA-SEQ; LATERAL HYPOTHALAMUS;
FRAMESHIFT MUTATION
AB Pro-opiomelanocortin (POMC)- and agouti-related peptide (AgRP)-expressing neurons of the arcuate nucleus of the hypothalamus (ARC) are oppositely regulated by caloric depletion and coordinately stimulate and inhibit homeostatic satiety, respectively. This bimodality is principally underscored by the antagonistic actions of these ligands at downstream melanocortin-4 receptors (MC4R) in the paraventricular nucleus of the hypothalamus (PVH). Although this population is critical to energy balance, the underlying neural circuitry remains unknown. Using mice expressing Cre recombinase in MC4R neurons, we demonstrate bidirectional control of feeding following real-time activation and inhibition of PVHMC4R neurons and further identify these cells as a functional exponent of ARC(AgRP) neuron-driven hunger. Moreover, we reveal this function to be mediated by a PVHMC4R -> lateral parabrachial nucleus (LPBN) pathway. Activation of this circuit encodes positive valence, but only in calorically depleted mice. Thus, the satiating and appetitive nature of PVHMC4R -> LPBN neurons supports the principles of drive reduction and highlights this circuit as a promising target for antiobesity drug development.
C1 [Garfield, Alastair S.; Madara, Joseph C.; Shah, Bhavik P.; Steger, Jennifer S.; Campbell, John N.; Olson, David P.; Lowell, Bradford B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab,Dept Med, Boston, MA 02215 USA.
[Garfield, Alastair S.] Univ Edinburgh, Ctr Integrat Physiol, Edinburgh, Midlothian, Scotland.
[Li, Chia; Webber, Emily; Krashes, Michael J.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
[Li, Chia; Webber, Emily; Krashes, Michael J.] NIDA, NIH, Baltimore, MD USA.
[Gavrilova, Oksana] NIDDK, Mouse Metab Core, NIH, Bethesda, MD 20892 USA.
[Lee, Charlotte E.; Elmquist, Joel K.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Hypothalam Res, Dallas, TX 75390 USA.
[Tannous, Bakhos A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA.
[Lowell, Bradford B.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA.
RP Lowell, BB (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab,Dept Med, Boston, MA 02215 USA.
EM agarfiel@staffmail.ed.ac.uk; michael.krashes@nih.gov;
blowell@bidmc.harvard.edu
FU Boston Area Diabetes Endocrinology Research Center [BADERC P30
DK057521]; University of Edinburgh; US National Institutes of Health
[R01 DK096010, R01 DK089044, R01 DK071051, R01 DK075632, R37 DK053477,
F32 DK089710, K08 DK071561, R01 DK088423, R37 DK0053301]; US National
Institutes of Health (BNORC Transgenic Core) [P30 DK046200]; US National
Institutes of Health (BADERC Transgenic Core) [P30 DK057521]; American
Heart Association [14POST20100011]; viral vector production core [P30
NS045776]; American Diabetes Association; NIH, NIDDK [DK075087,
DK075088]
FX The authors gratefully acknowledge the National Institute of Diabetes
and Digestive and Kidney Diseases (NIDDK) Mouse Metabolism Core for
technical support, V. Petkova and the Beth Israel Deaconess Medical
Center Molecular Medicine Core Facility for assistance with quantitative
PCR and sample preparation, and D. Morse for the production of the
rabies virus. Sequencing and initial data processing were performed at
Massachusetts General Hospital's Next-Gen Sequencing Core. Sequencing
was supported in part by funding from the Boston Area Diabetes
Endocrinology Research Center (BADERC P30 DK057521). This work was
supported by the University of Edinburgh Chancellor's Fellowship
(A.S.G.); US National Institutes of Health grants to B.B.L. (R01
DK096010, R01 DK089044, R01 DK071051, R01 DK075632, R37 DK053477, BNORC
Transgenic Core P30 DK046200, BADERC Transgenic Core P30 DK057521), to
M.J.K. (F32 DK089710), to D.P.O. (K08 DK071561) and to J.K.E. (R01
DK088423 and R37 DK0053301); American Heart Association Postdoctoral
Fellowship 14POST20100011 to J.N.C.; viral vector production core P30
NS045776 to B.A.T.; and an American Diabetes Association Mentor-Based
Fellowship to B.P.S. and B.B.L. This research was supported, in part, by
the Intramural Research Program of the NIH, NIDDK (DK075087, DK075088).
NR 63
TC 50
Z9 50
U1 3
U2 26
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 JUN
PY 2015
VL 18
IS 6
BP 863
EP U299
DI 10.1038/nn.4011
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA CJ1CB
UT WOS:000355218300014
PM 25915476
ER
PT J
AU Long, MT
Pedley, A
Massaro, JM
Hoffmann, U
Esliger, DW
Vasan, RS
Fox, CS
Murabito, JM
AF Long, Michelle T.
Pedley, Alison
Massaro, Joseph M.
Hoffmann, Udo
Esliger, Dale W.
Vasan, Ramachandran S.
Fox, Caroline S.
Murabito, Joanne M.
TI Hepatic steatosis is associated with lower levels of physical activity
measured via accelerometry
SO OBESITY
LA English
DT Article
ID FATTY LIVER-DISEASE; ALL-CAUSE MORTALITY; UNITED-STATES; RISK-FACTORS;
WEIGHT-LOSS; INSULIN SENSITIVITY; EXERCISE; ADULTS; POPULATION; HEALTH
AB ObjectivePrior studies on the association of physical activity (PA) and nonalcoholic fatty liver disease are limited by reliance on subjective measures of PA. We examined the association between objectively measured PA and hepatic steatosis defined by computed tomography (CT).
MethodsWe conducted a cross-sectional study of 1,060 Framingham Heart Study participants who participated in the Multidetector CT 2 substudy and who underwent assessment of PA via accelerometry. Hepatic steatosis was estimated by liver attenuation, as measured by CT. We explored the relationship between liver attenuation and PA using multivariable regression models.
ResultsIn multivariable-adjusted models, we observed an inverse association between PA and liver attenuation. Each 30 minutes/day increase in moderate to vigorous PA (MVPA) was associated with a reduced odds of hepatic steatosis (OR = 0.62, P < 0.001). This association was attenuated and no longer statistically significant after adjustment for body mass index (BMI) (OR = 0.77, P = 0.05) or visceral adipose tissue (VAT) (OR = 0.83, P = 0.18). Participants who met the national PA recommendations of engaging in 150 minutes/week of MVPA had the lowest odds of hepatic steatosis, even after adjusting for BMI (OR = 0.63, P = 0.007) or VAT (OR = 0.67, P = 0.03).
ConclusionsThere is an inverse association between PA and hepatic steatosis. Participants who met the national PA guidelines had the lowest prevalence of hepatic steatosis.
C1 [Long, Michelle T.] Boston Univ, Sch Med, Boston Med Ctr, Div Gastroenterol, Boston, MA 02118 USA.
[Long, Michelle T.; Pedley, Alison; Massaro, Joseph M.; Vasan, Ramachandran S.; Fox, Caroline S.; Murabito, Joanne M.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Massaro, Joseph M.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA.
[Esliger, Dale W.] Univ Loughborough, Sch Sport Exercise & Hlth Sci, Loughborough, Leics, England.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA.
[Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Hypertens & Metab, Boston, MA 02115 USA.
[Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA.
RP Murabito, JM (reprint author), NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
EM murabito@bu.edu
OI Long, Michelle/0000-0001-6131-3981; Ramachandran,
Vasan/0000-0001-7357-5970
FU Boston University School of Medicine; National Heart, Lung, and Blood
Institute's Framingham Heart Study [N01-HC-25195]; Division of
Intramural Research of the National Heart, Lung, and Blood Institute;
NIH [1RO1-AG-047645]; Boston University Clinical and Translational
Science Institute [UL1-TR000157]
FX This work was supported by the Boston University School of Medicine, the
National Heart, Lung, and Blood Institute's Framingham Heart Study
(contract N01-HC-25195), and the Division of Intramural Research of the
National Heart, Lung, and Blood Institute. We received additional
support from the NIH grant 1RO1-AG-047645. Dr. Long is supported in part
by the Boston University Clinical and Translational Science Institute
(grant UL1-TR000157).
NR 39
TC 4
Z9 4
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1930-7381
EI 1930-739X
J9 OBESITY
JI Obesity
PD JUN
PY 2015
VL 23
IS 6
BP 1259
EP 1266
DI 10.1002/oby.21058
PG 8
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA CJ0FG
UT WOS:000355150300019
PM 25959049
ER
PT J
AU Kwilas, AR
Gameiro, SR
Kim, PS
Malamas, AS
Hodge, JW
AF Kwilas, Anna R.
Gameiro, Sofia R.
Kim, Peter S.
Malamas, Anthony S.
Hodge, James W.
TI Improving clinical benefit for prostate cancer patients through the
combination of androgen deprivation and immunotherapy
SO ONCOIMMUNOLOGY
LA English
DT Editorial Material
DE Androgen-deprivation therapy; cancer immunotherapy; enzalutamide;
immunogenic modulation; therapeutic cancer vaccine
ID THERAPY; SURVIVAL; VACCINE; CELLS
AB Androgen-deprivation therapy (ADT) induces prostate cancer immunogenic modulation (IM) by reducing human tumor cell expression of anti-apoptotic genes thus facilitating increased sensitivity to immune-mediated lysis. Through its stimulation of IM, ADT has been shown to synergize with active immunotherapy thereby significantly improving overall survival in a mouse model of prostate cancer.
C1 [Kwilas, Anna R.; Gameiro, Sofia R.; Kim, Peter S.; Malamas, Anthony S.; Hodge, James W.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Hodge, JW (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM jh241d@nih.gov
NR 10
TC 1
Z9 1
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 2162-402X
J9 ONCOIMMUNOLOGY
JI OncoImmunology
PD JUN
PY 2015
VL 4
IS 6
DI 10.1080/2162402X.2015.1009303
PG 3
WC Oncology; Immunology
SC Oncology; Immunology
GA CJ0XK
UT WOS:000355203300023
ER
PT J
AU Arora, NK
Hesse, BW
Clauser, SB
AF Arora, Neeraj K.
Hesse, Bradford W.
Clauser, Steven B.
TI Walking in the Shoes of Patients, Not Just in Their Genes: A
Patient-Centered Approach to Genomic Medicine
SO PATIENT-PATIENT CENTERED OUTCOMES RESEARCH
LA English
DT Article
ID BREAST-CANCER-TREATMENT; HEALTH-CARE; SYMPTOM MANAGEMENT;
COLORECTAL-CANCER; SURVEILLANCE; PREVENTION; DECISIONS; IMPACT; ASSAY;
RISK
AB Genomic technologies are increasing the precision with which clinicians can assess an individual patient's risk for developing diseases and identify which patients are likely to benefit from specific treatments. Also advocating for a shift away from a one-size-fits-all approach is the growing emphasis on "patient-centered" care. Using examples from breast cancer, we make a case for why, in order to optimize patient health outcomes, genomic medicine will need to be practiced within a patient-centered framework. We present a six-function conceptual framework for patient-centered care and discuss findings from a national survey evaluating the patient-centeredness of care delivered in the USA.
C1 [Arora, Neeraj K.; Hesse, Bradford W.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Clauser, Steven B.] Patient Ctr Outcomes Res Inst, Washington, DC USA.
RP Arora, NK (reprint author), NCI, Div Canc Control & Populat Sci, NIH, 9609 Med Ctr Dr,3E514,MSC 9762, Bethesda, MD 20892 USA.
EM aroran@mail.nih.gov
OI Hesse, Bradford/0000-0003-1142-1161
NR 46
TC 6
Z9 6
U1 4
U2 8
PU ADIS INT LTD
PI NORTHCOTE
PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND
SN 1178-1653
EI 1178-1661
J9 PATIENT
JI Patient
PD JUN
PY 2015
VL 8
IS 3
BP 239
EP 245
DI 10.1007/s40271-014-0089-5
PG 7
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA CJ0WD
UT WOS:000355199000001
PM 25300612
ER
PT J
AU Chuang, GY
Zhang, BS
Mckee, K
O'Dell, S
Do Kwon, Y
Zhou, TQ
Blinn, J
Lloyd, K
Parks, R
Von Holle, T
Ko, SY
Kong, WP
Pegu, A
Wang, KY
Baruah, K
Crispin, M
Mascola, JR
Moody, MA
Haynes, BF
Georgiev, IS
Kwong, PD
AF Chuang, Gwo-Yu
Zhang, Baoshan
McKee, Krisha
O'Dell, Sijy
Kwon, Young Do
Zhou, Tongqing
Blinn, Julie
Lloyd, Krissey
Parks, Robert
Von Holle, Tarra
Ko, Sung-Youl
Kong, Wing-Pui
Pegu, Amarendra
Wang, Keyun
Baruah, Kavitha
Crispin, Max
Mascola, John R.
Moody, M. Anthony
Haynes, Barton F.
Georgiev, Ivelin S.
Kwong, Peter D.
TI Eliminating antibody polyreactivity through addition of N-linked
glycosylation
SO PROTEIN SCIENCE
LA English
DT Article
DE polyreactivity; antibody engineering; bioinformatics; broadly
neutralizing antibody; glycan engineering
ID NEUTRALIZING HIV-1 ANTIBODY; SIDE-CHAIN CONFORMATIONS; THERAPEUTIC
ANTIBODIES; MONOCLONAL-ANTIBODY; B-CELLS; IMPROVES PROTECTION;
CD4-BINDING SITE; STRUCTURAL BASIS; VARIABLE-REGION; RATIONAL DESIGN
AB Antibody polyreactivity can be an obstacle to translating a candidate antibody into a clinical product. Standard tests such as antibody binding to cardiolipin, HEp-2 cells, or nuclear antigens provide measures of polyreactivity, but its causes and the means to resolve are often unclear. Here we present a method for eliminating antibody polyreactivity through the computational design and genetic addition of N-linked glycosylation near known sites of polyreactivity. We used the HIV-1-neutralizing antibody, VRC07, as a test case, since efforts to increase VRC07 potency at three spatially distinct sites resulted in enhanced polyreactivity. The addition of N-linked glycans proximal to the polyreactivity-enhancing mutations at each of the spatially distinct sites resulted in reduced antibody polyreactivity as measured by (i) anti-cardiolipin ELISA, (ii) Luminex AtheNA Multi-Lyte ANA binding, and (iii) HEp-2 cell staining. The reduced polyreactivity trended with increased antibody concentration over time in mice, but not with improved overall protein stability as measured by differential scanning calorimetry. Moreover, glycan proximity to the site of polyreactivity appeared to be a critical factor. The results provide evidence that antibody polyreactivity can result from local, rather than global, features of an antibody and that addition of N-linked glycosylation can be an effective approach to reducing antibody polyreactivity.
C1 [Chuang, Gwo-Yu; Zhang, Baoshan; McKee, Krisha; O'Dell, Sijy; Kwon, Young Do; Zhou, Tongqing; Ko, Sung-Youl; Kong, Wing-Pui; Pegu, Amarendra; Wang, Keyun; Mascola, John R.; Georgiev, Ivelin S.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Blinn, Julie; Lloyd, Krissey; Parks, Robert; Von Holle, Tarra; Moody, M. Anthony; Haynes, Barton F.] Duke Univ, Duke Human Vaccine Inst, Med Ctr, Durham, NC 10302 USA.
[Baruah, Kavitha; Crispin, Max] Univ Oxford, Dept Biochem, Oxford Glycobiol Inst, Oxford OX1 3QU, England.
RP Kwong, PD (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM pdkwong@nih.gov
RI Zhou, Tongqing/A-6880-2010
OI Zhou, Tongqing/0000-0002-3935-4637
FU Intramural Research Program of the Vaccine Research Center, NIAID;
Office of AIDS Research, NIH
FX Grant sponsor: Intramural Research Program of the Vaccine Research
Center, NIAID, and the Office of AIDS Research, NIH.
NR 40
TC 1
Z9 1
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-8368
EI 1469-896X
J9 PROTEIN SCI
JI Protein Sci.
PD JUN
PY 2015
VL 24
IS 6
BP 1019
EP 1030
DI 10.1002/pro.2682
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CJ0FM
UT WOS:000355151200011
PM 25800131
ER
PT J
AU Khan, I
Tang, E
Arany, P
AF Khan, Imran
Tang, Elieza
Arany, Praveen
TI Molecular pathway of near-infrared laser phototoxicity involves ATF-4
orchestrated ER stress
SO SCIENTIFIC REPORTS
LA English
DT Article
ID UNFOLDED PROTEIN RESPONSE; ACTIVATING TRANSCRIPTION FACTOR-4; BIPHASIC
DOSE-RESPONSE; LEVEL LIGHT THERAPY; ENDOPLASMIC-RETICULUM; OXIDATIVE
STRESS; IN-VITRO; CELLS; IRRADIATION; NEURONS
AB High power lasers are used extensively in medicine while lower power applications are popular for optical imaging, optogenetics, skin rejuvenation and a therapeutic modality termed photobiomodulation (PBM). This study addresses the therapeutic dose limits, biological safety and molecular pathway of near-infrared (NIR) laser phototoxicity. Increased erythema and tissue damage were noted in mice skin and cytotoxicity in cell cultures at phototoxic laser doses involving generation of reactive oxygen species (ROS) coupled with a rise in surface temperature(>45 degrees C). NIR laser phototoxicity results from Activating Transcription Factor-4 (ATF-4) mediated endoplasmic reticulum stress and autophagy. Neutralizations of heat or ROS and overexpressing ATF-4 were noted to rescue NIR laser phototoxicity. Further, NIR laser mediated phototoxicity was noted to be non-genotoxic and non-mutagenic. This study outlines the mechanism of NIR laser phototoxicity and the utility of monitoring surface temperature and ATF4 expression as potential biomarkers to develop safe and effective clinical applications.
C1 [Khan, Imran; Tang, Elieza; Arany, Praveen] Natl Inst Dent & Craniofacial Res, Cell Regulat & Control Unit, NIH, Bethesda, MD 20892 USA.
RP Arany, P (reprint author), Natl Inst Dent & Craniofacial Res, Cell Regulat & Control Unit, NIH, Bethesda, MD 20892 USA.
EM praveenarany@gmail.com
FU Intramural research program of National Institute of Dental and
Craniofacial Research, National Institutes of Health
FX We would like to thank Abhinav Seetharaman, Suneetha Gottumukkala,
Monica Ashok and Karl Engel for help with experiments. We thank Silvio
Gutkind, Kathy Carbone, Pamela Kearney, Lauren Davidson, Matthew
Starost, Murali Cherukuri, Sushil Rane and Lalage Wakefield for critical
inputs in these studies. This work was supported by the Intramural
research program of the National Institute of Dental and Craniofacial
Research, National Institutes of Health.
NR 57
TC 8
Z9 8
U1 3
U2 12
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 JUN 1
PY 2015
VL 5
AR 10581
DI 10.1038/srep10581
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CJ6JC
UT WOS:000355599100001
PM 26030745
ER
PT J
AU Feigin, VL
Krishnamurthi, R
Bhattacharjee, R
Parmar, P
Theadom, A
Hussein, T
Purohit, M
Hume, P
Abbott, M
Rush, E
Kasabov, N
Crezee, I
Frielick, S
Barker-Collo, S
Barber, PA
Arroll, B
Poulton, R
Ratnasabathy, Y
Tobias, M
Cabral, N
Martins, SCO
Furtado, LETA
Lindsay, P
Saposnik, G
Giroud, M
Bejot, Y
Hacke, W
Mehndiratta, MM
Pandian, JD
Gupta, S
Padma, V
Mandal, DK
Kokubo, Y
Ibrahim, NM
Sahathevan, R
Fu, H
Wang, WZ
Liu, L
Hou, ZG
Goncalves, AF
Correia, M
Varakin, Y
Kravchenko, M
Piradov, M
Saadah, M
Thrift, AG
Cadilhac, D
Davis, S
Donnan, G
Lopez, AD
Hankey, GJ
Maujean, A
Kendall, E
Brainin, M
Abd-Allah, F
Bornstein, NM
Caso, V
Marquez-Romero, JM
Akinyemi, RO
Bin Dhim, NF
Norrving, B
Sindi, S
Kivipelto, M
Mendis, S
Ikram, MA
Hofman, A
Mirza, SS
Rothwell, PM
Sandercock, P
Shakir, R
Sacco, RL
Culebras, A
Roth, GA
Moradi-Lakeh, M
Murray, C
Narayan, V
Mensah, GA
Wiebers, D
Moran, AE
AF Feigin, Valery L.
Krishnamurthi, Rita
Bhattacharjee, Rohit
Parmar, Priya
Theadom, Alice
Hussein, Tasleem
Purohit, Mitali
Hume, Patria
Abbott, Max
Rush, Elaine
Kasabov, Nikola
Crezee, Ineke
Frielick, Stanley
Barker-Collo, Suzanne
Barber, P. Alan
Arroll, Bruce
Poulton, Richie
Ratnasabathy, Yogini
Tobias, Martin
Cabral, Norberto
Martins, Sheila C. O.
Furtado, Luis E. T. A.
Lindsay, Patrice
Saposnik, Gustavo
Giroud, Maurice
Bejot, Yannick
Hacke, Werner
Mehndiratta, Man Mohan
Pandian, Jeyaraj Durai
Gupta, Sanjeev
Padma, Vasantha
Mandal, Dipes Kumar
Kokubo, Yoshihiro
Ibrahim, Norlinah Mohamed
Sahathevan, Ramesh
Fu, Hua
Wang, Wenzhi
Liu, Liping
Hou, Zeng-Guang
Goncalves, Antonio Freire
Correia, Manuel
Varakin, Yury
Kravchenko, Michael
Piradov, Michael
Saadah, Mohammed
Thrift, Amanda G.
Cadilhac, Dominique
Davis, Stephen
Donnan, Geoffrey
Lopez, Alan D.
Hankey, Graeme J.
Maujean, Annick
Kendall, Elizabeth
Brainin, Michael
Abd-Allah, Foad
Bornstein, Natan M.
Caso, Valeria
Manuel Marquez-Romero, Juan
Akinyemi, Rufus O.
Bin Dhim, Nasser F.
Norrving, Bo
Sindi, Shireen
Kivipelto, Miia
Mendis, Shanthi
Ikram, M. Arfan
Hofman, Albert
Mirza, Saira Saeed
Rothwell, Peter M.
Sandercock, Peter
Shakir, Raad
Sacco, Ralph L.
Culebras, Antonio
Roth, Gregory A.
Moradi-Lakeh, Maziar
Murray, Christopher
Narayan, Venkat
Mensah, George A.
Wiebers, David
Moran, Andrew E.
CA RIBURST Study Collaboration Writin
TI New Strategy to Reduce the Global Burden of Stroke
SO STROKE
LA English
DT Review
DE prevention and control; stroke
ID RANDOMIZED CONTROLLED-TRIAL; CARDIOVASCULAR-DISEASE; RISK-FACTORS;
SMARTPHONE APPLICATION; SYSTEMATIC ANALYSIS; NONCOMMUNICABLE DISEASES;
PRIMARY PREVENTION; PUBLIC AWARENESS; ISCHEMIC-STROKE; 21 REGIONS
C1 [Feigin, Valery L.; Krishnamurthi, Rita; Bhattacharjee, Rohit; Parmar, Priya; Theadom, Alice] Auckland Univ Technol, Natl Inst Stroke & Appl Neurosci, Sch Publ Hlth & Psychosocial Studies, Auckland 1142, New Zealand.
[Hume, Patria; Abbott, Max; Rush, Elaine] Auckland Univ Technol, Fac Hlth & Environm Sci, Auckland 1142, New Zealand.
[Hussein, Tasleem] Auckland Univ Technol, Informat Technol, Auckland 1142, New Zealand.
[Purohit, Mitali] Auckland Univ Technol, Res & Innovat Off, Auckland 1142, New Zealand.
[Kasabov, Nikola] Auckland Univ Technol, Knowledge Engn & Discovery Res Inst, Auckland 1142, New Zealand.
[Crezee, Ineke] Auckland Univ Technol, Translat & Interpreting Dept, Auckland 1142, New Zealand.
[Frielick, Stanley] Auckland Univ Technol, Ctr Learing & Teaching, Auckland 1142, New Zealand.
[Barker-Collo, Suzanne] Univ Auckland, Sch Psychol, Auckland 1, New Zealand.
[Barber, P. Alan] Univ Auckland, Dept Neurol, Auckland 1, New Zealand.
[Arroll, Bruce] Univ Auckland, Sch Publ Hlth, Auckland 1, New Zealand.
[Poulton, Richie] Univ Otago, Dept Prevent & Social Med, Dunedin, New Zealand.
[Ratnasabathy, Yogini] Older People Care, Waitemata DHB, Auckland, New Zealand.
[Tobias, Martin] Minist Hlth, Hlth Intelligence, Wellington, New Zealand.
[Cabral, Norberto] Univ Regiao Joinville, Joinville Stroke Register, Joinville, Brazil.
[Martins, Sheila C. O.] Hosp Clin Porto Alegre, Hosp Moinhos Vento, Minist Hlth, Porto Alegre, RS, Brazil.
[Furtado, Luis E. T. A.] Univ Fed Ceara, Dept Neurol, Sobral Ceara, Brazil.
[Lindsay, Patrice] Stroke Fdn Canada, Ottawa, ON, Canada.
[Saposnik, Gustavo] Univ Toronto, Dept Med & Hlth Policy, Management & Evaluat, Toronto, ON, Canada.
[Giroud, Maurice; Bejot, Yannick] Univ Burgundy, Univ Hosp & Med Sch Dijon, Dijon Stroke Registry, EA4184, Dijon, France.
[Hacke, Werner] Heidelberg Univ, Dept Neurol, Heidelberg, Germany.
[Mehndiratta, Man Mohan] Janakpuri Super Special Hosp, New Delhi, India.
[Pandian, Jeyaraj Durai] Christian Med Coll & Hosp, Dept Neurol, Ludhiana, Punjab, India.
[Gupta, Sanjeev] Banarsidas Chandiwala Inst Physiotherapy, New Delhi, India.
[Padma, Vasantha] All India Inst Med Sci, New Delhi, India.
[Mandal, Dipes Kumar] Stroke Fdn Bengal, Kolkata, W Bengal, India.
[Kokubo, Yoshihiro] Natl Cerebral & Cardiovasc Ctr, Dept Prevent Cardiol, Osaka, Japan.
[Ibrahim, Norlinah Mohamed; Sahathevan, Ramesh] UKM Med Ctr, Kuala Lumpur, Malaysia.
[Fu, Hua] Fudan Univ, Sch Publ Hlth, Shanghai 200433, Peoples R China.
[Wang, Wenzhi] Beijing Neurosurg Inst, Beijing, Peoples R China.
[Liu, Liping] Capital Med Univ, Beijing, Peoples R China.
[Hou, Zeng-Guang] Inst Automat, Beijing, Peoples R China.
[Goncalves, Antonio Freire] Univ Hosp Coimbra, Coimbra, Portugal.
[Correia, Manuel] Hosp Santo Antoni, Serv Neurol, Oporto, Portugal.
[Varakin, Yury; Kravchenko, Michael; Piradov, Michael] Res Ctr Neurol, Moscow, Russia.
[Saadah, Mohammed] Univ Emirates, Abu Dhabi, U Arab Emirates.
[Thrift, Amanda G.; Cadilhac, Dominique] Monash Univ, Dept Med, Clayton, Vic, Australia.
[Davis, Stephen] Univ Melbourne, Royal Melbourne Hosp, Parkville, Vic 3052, Australia.
[Donnan, Geoffrey] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3052, Australia.
[Lopez, Alan D.] Univ Melbourne, Publ Hlth, Parkville, Vic 3052, Australia.
[Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia.
[Brainin, Michael] Danube Univ, Ctr Clin Neurosci, Vienna, Austria.
[Abd-Allah, Foad] Cairo Univ, Cairo, Egypt.
[Bornstein, Natan M.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Neurol, IL-69978 Tel Aviv, Israel.
[Caso, Valeria] Stroke Unit, Perugia, Italy.
[Manuel Marquez-Romero, Juan] IMSS Aguascalientes, HGZ 2, Aguascalientes, Mexico.
[Akinyemi, Rufus O.] Fed Med Ctr Abeokuta, Abeokuta, Nigeria.
[Bin Dhim, Nasser F.] Saudi Elect Univ, Hlth Informat Dept, Riyadh, Saudi Arabia.
[Norrving, Bo] Lund Univ, Dept Neurol, Lund, Sweden.
[Sindi, Shireen] Karolinska Inst, Dept Epidemiol, Stockholm, Sweden.
[Kivipelto, Miia] Karolinska Inst, Aging Res Ctr, Ctr Alzheimer Res, Stockholm, Sweden.
[Mendis, Shanthi] WHO, Noncommun Dis, CH-1211 Geneva, Switzerland.
[Ikram, M. Arfan; Hofman, Albert; Mirza, Saira Saeed] Erasmus Univ, Med Ctr, Rotterdam, Netherlands.
[Rothwell, Peter M.] Univ Oxford, Nuffield Dept Neurosci, Oxford, England.
[Sandercock, Peter] Western Gen Hosp, Edinburgh EH4 2XU, Midlothian, Scotland.
[Shakir, Raad] Imperial Coll NHS Trust, Dept Neurol, London, England.
[Sacco, Ralph L.] Univ Miami, Miller Sch Med, Dept Neurol, Coral Gables, FL 33124 USA.
[Culebras, Antonio] SUNY Upstate Med Univ, Dept Neurol, Syracuse, NY 13210 USA.
[Roth, Gregory A.] Univ Washington, Dept Med, Div Cardiol, Seattle, WA 98195 USA.
[Roth, Gregory A.; Moradi-Lakeh, Maziar; Murray, Christopher] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
[Narayan, Venkat] Emory Univ, Atlanta, GA 30322 USA.
[Mensah, George A.] NHLBI, Ctr Translat Res & Implementat Sci, NIH, Bethesda, MD 20892 USA.
[Wiebers, David] Mayo Clin, Dept Neurol, Rochester, MN USA.
[Moran, Andrew E.] Columbia Univ, Med Ctr, Div Gen Med, New York, NY 10027 USA.
RP Feigin, VL (reprint author), Auckland Univ Technol, Fac Hlth & Environm Sci, Sch Publ Hlth & Psychosocial Studies, Natl Inst Stroke & Appl Neurosci, AUT North Shore Campus,AA254,90 Akoranga Dr, Auckland 1142, New Zealand.
EM valery.feigin@aut.ac.nz
RI Hankey, Graeme /H-4968-2014; Crezee, Ineke/B-4876-2016; Piradov,
Mikhail/B-4407-2012; Thrift, Amanda/I-6251-2012; Kravchenko,
Michael/B-2596-2012; Varakin, Yuriy/C-8634-2012;
OI Hankey, Graeme /0000-0002-6044-7328; Crezee, Ineke/0000-0001-6354-1136;
Theadom, Alice/0000-0003-0351-6216; Kendall,
Elizabeth/0000-0003-2399-1460; Piradov, Mikhail/0000-0002-6055-8335;
Thrift, Amanda/0000-0001-8533-4170; Kravchenko,
Michael/0000-0001-5187-5518; Piradov, Michael/0000-0002-6338-0392;
BinDhim, Nasser F/0000-0001-8117-1044; Donnan,
Geoffrey/0000-0001-6324-3403; Barber, P Alan/0000-0003-2469-9023; Sindi,
Shireen/0000-0002-3786-0552; Hume, Patria/0000-0003-1847-8128; Cadilhac,
Dominique/0000-0001-8162-682X; Moradi-Lakeh, Maziar/0000-0001-7381-5305
FU Auckland University of Technology, Research and Innovation Office,
Faculty of Health and Environmental Sciences, Centre for Learning and
Teaching; Kiwi Innovation Network Limited, Waikato Mail Centre,
Hamilton, New Zealand; Auckland University of Technology Enterprises Ltd
at Auckland University of Technology, Auckland, New Zealand
FX This study was supported by Auckland University of Technology, Research
and Innovation Office, Faculty of Health and Environmental Sciences,
Centre for Learning and Teaching and Auckland University of Technology
Enterprises Ltd at Auckland University of Technology, Auckland 1142, New
Zealand and Kiwi Innovation Network Limited, Waikato Mail Centre,
Hamilton, New Zealand.
NR 60
TC 14
Z9 15
U1 10
U2 25
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD JUN
PY 2015
VL 46
IS 6
BP 1740
EP +
DI 10.1161/STROKEAHA.115.008222
PG 10
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA CI7KI
UT WOS:000354941800066
PM 25882050
ER
PT J
AU Pahigiannis, K
Mott, M
Koroshetz, W
AF Pahigiannis, Katherine
Mott, Meghan
Koroshetz, Walter
TI Hypertension and Brain Health: Setting Limits National Institute of
Neurological Disorders and Stroke Organizational Update
SO STROKE
LA English
DT Editorial Material
DE cognitive impairment; dementia; hypertension; stroke
ID GUIDELINES
C1 [Pahigiannis, Katherine; Mott, Meghan; Koroshetz, Walter] NINDS, NIH, Bethesda, MD 20892 USA.
RP Koroshetz, W (reprint author), NINDS, NIH, Bldg 31,Room 8A52,31 Ctr Dr,MSC 2540, Bethesda, MD 20892 USA.
EM koroshetzw@mail.nih.gov
NR 4
TC 1
Z9 1
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD JUN
PY 2015
VL 46
IS 6
BP E147
EP E148
DI 10.1161/STROKEAHA.115.008763
PG 2
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA CI7KI
UT WOS:000354941800006
PM 25922505
ER
PT J
AU Bousquet, J
Anto, JM
Berkouk, K
Gergen, P
Antunes, JP
Auge, P
Camuzat, T
Bringer, J
Mercier, J
Best, N
Bourret, R
Akdis, M
Arshad, SH
Bedbrook, A
Berr, C
Bush, A
Cavalli, G
Charles, MA
Clavel-Chapelon, F
Gillman, M
Gold, DR
Goldberg, M
Holloway, JW
Iozzo, P
Jacquemin, S
Jeandel, C
Kauffmann, F
Keil, T
Koppelman, GH
Krauss-Etschmann, S
Kuh, D
Lehmann, S
Carlsen, KCL
Maier, D
Mechali, M
Melen, E
Moatti, JP
Momas, I
Nerin, P
Postma, DS
Ritchie, K
Robine, JM
Samolinski, B
Siroux, V
Slagboom, PE
Smit, HA
Sunyer, J
Valenta, R
Van de Perre, P
Verdier, JM
Vrijheid, M
Wickman, M
Yiallouros, P
Zins, M
AF Bousquet, J.
Anto, J. M.
Berkouk, K.
Gergen, P.
Antunes, J. Pinto
Auge, P.
Camuzat, T.
Bringer, J.
Mercier, J.
Best, N.
Bourret, R.
Akdis, M.
Arshad, S. H.
Bedbrook, A.
Berr, C.
Bush, A.
Cavalli, G.
Charles, M. A.
Clavel-Chapelon, F.
Gillman, M.
Gold, D. R.
Goldberg, M.
Holloway, J. W.
Iozzo, P.
Jacquemin, S.
Jeandel, C.
Kauffmann, F.
Keil, T.
Koppelman, G. H.
Krauss-Etschmann, S.
Kuh, D.
Lehmann, S.
Carlsen, K. C. Lodrup
Maier, D.
Mechali, M.
Melen, E.
Moatti, J. P.
Momas, I.
Nerin, P.
Postma, D. S.
Ritchie, K.
Robine, J. M.
Samolinski, B.
Siroux, V.
Slagboom, P. E.
Smit, H. A.
Sunyer, J.
Valenta, R.
Van de Perre, P.
Verdier, J. M.
Vrijheid, M.
Wickman, M.
Yiallouros, P.
Zins, M.
TI Developmental determinants in non-communicable chronic diseases and
ageing
SO THORAX
LA English
DT Article
DE Asthma; COPD u Mechanisms; Paediatric asthma
AB Prenatal and peri-natal events play a fundamental role in health, development of diseases and ageing (Developmental Origins of Health and Disease (DOHaD)). Research on the determinants of active and healthy ageing is a priority to: (i) inform strategies for reducing societal and individual costs of an ageing population and (ii) develop effective novel prevention strategies. It is important to compare the trajectories of respiratory diseases with those of other chronic diseases.
C1 [Bousquet, J.] Univ Hosp, Montpellier, France.
[Bousquet, J.] INSERM, U1168, Paris, France.
[Bousquet, J.; Auge, P.; Camuzat, T.; Bringer, J.; Mercier, J.; Best, N.; Bourret, R.; Bedbrook, A.; Berr, C.; Cavalli, G.; Jacquemin, S.; Jeandel, C.; Lehmann, S.; Nerin, P.; Ritchie, K.; Robine, J. M.; Verdier, J. M.] Contre Malad Chron Vieillissement Actif Languedoc, Site Reference EIP AHA, Montpellier, France.
[Bousquet, J.; Anto, J. M.; Akdis, M.; Kauffmann, F.; Keil, T.; Koppelman, G. H.; Carlsen, K. C. Lodrup; Maier, D.; Melen, E.; Momas, I.; Postma, D. S.; Siroux, V.; Smit, H. A.; Sunyer, J.; Valenta, R.; Wickman, M.] MeDALL, Mech Dev Allergy, Groningen, Netherlands.
[Anto, J. M.; Sunyer, J.; Vrijheid, M.] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain.
[Anto, J. M.; Sunyer, J.] IMIM Hosp Mar Med Res Inst, Barcelona, Spain.
[Anto, J. M.; Sunyer, J.; Vrijheid, M.] UPF, Barcelona, Spain.
[Anto, J. M.; Sunyer, J.; Vrijheid, M.] CIBER Epidemiol & Salud Publ CIBERESP, Barcelona, Spain.
[Berkouk, K.] Commiss European Communities, DG Res & Innovat, Unit Med Res & Challenge Ageing, Brussels, Belgium.
[Gergen, P.] NIAID, Bethesda, MD 20892 USA.
[Antunes, J. Pinto] Commiss European Communities, Directorate Gen Hlth & Consumers, B-1049 Brussels, Belgium.
[Auge, P.; Mercier, J.] Univ Montpellier I, F-34006 Montpellier, France.
[Camuzat, T.] Reg Languedoc Roussillon, Montpellier, France.
[Bringer, J.] Montpellier Med Sch, Montpellier, France.
[Mercier, J.] Montpellier Univ Hosp, Dept Physiol, Montpellier, France.
[Best, N.] Univ Nimes Hosp, Nimes, France.
[Bourret, R.] Montpellier Univ Hosp, Montpellier, France.
[Akdis, M.] Swiss Inst Allergy & Asthma Res, CH-7270 Davos, Switzerland.
[Akdis, M.] Univ Zurich, CH-8006 Zurich, Switzerland.
[Arshad, S. H.] David Hide Asthma & Allergy Res Ctr, Isle Of Wight, England.
[Berr, C.] Univ Montpellier I, INSERM, Res Unit U1061, Montpellier, France.
[Bush, A.] Royal Brompton Hosp, Dept Paediat Resp Med, London SW3 6LY, England.
[Bush, A.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England.
[Cavalli, G.; Mechali, M.] CNRS, Inst Human Genet, Montpellier, France.
[Charles, M. A.] Univ Paris 11, INSERM, Ctr Rech Epidemiol & Sante Populat, Equipe UMR 10,CESP, Villejuif, France.
[Clavel-Chapelon, F.] Paris South Univ, INSERM, UMR S 1018, Nutr Hormones & Womens Hlth Team, Villejuif, France.
[Gillman, M.] Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care Inst, Obes Prevent Program,Dept Populat Med, Boston, MA USA.
[Gillman, M.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Gold, D. R.] Harvard Univ, Brigham & Womens Hosp, Channing Div Network Med, Dept Med,Med Sch, Boston, MA USA.
[Gold, D. R.] Harvard Univ, Sch Publ Hlth, Boston, MA USA.
[Goldberg, M.] INSERM, UVSQ, UMS 011, Populat Based Epidemiol Cohorts, Villejuif, France.
[Holloway, J. W.] Univ Southampton, Fac Med, Human Dev & Hlth, Southampton SO9 5NH, Hants, England.
[Iozzo, P.] CNR, Inst Clin Physiol, I-56100 Pisa, Italy.
[Jacquemin, S.] Horiba, Montpellier, France.
[Jeandel, C.] Univ Hosp, Dept Geriatr, Montpellier, France.
[Kauffmann, F.] Univ Paris 11, CESP Team Resp & Environm Epidemiol, INSERM, UMR S1018, Villejuif, France.
[Keil, T.] Charite, Inst Social Med Epidemiol & Hlth Econ, D-13353 Berlin, Germany.
[Keil, T.] Julius Maximilian Univ Wuerzburg, Inst Clin Epidemiol & Biometry, Wurzburg, Germany.
[Koppelman, G. H.] Univ Groningen, Univ Med Ctr Groningen, Beatrix Childrens Hosp, Dept Pediat Pulmonol & Pediat Allergol,Groningen, Groningen, Netherlands.
[Krauss-Etschmann, S.] Univ Munich, Comprehens Pneumol Ctr, Grosshansdorf, Germany.
[Krauss-Etschmann, S.] Helmholtz Zentrum Muenchen, Grosshansdorf, Germany.
[Kuh, D.] UCL, MRC Unit Lifelong Hlth & Ageing, London, England.
[Lehmann, S.] Univ Hosp, INSERM, U1040, IMRB, Montpellier, France.
[Carlsen, K. C. Lodrup] Univ Oslo, Dept Paediat, Oslo, Norway.
[Carlsen, K. C. Lodrup] Oslo Univ Hosp, Oslo, Norway.
[Maier, D.] Biomax Informat AG, Planegg, Germany.
[Melen, E.; Wickman, M.] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden.
[Melen, E.; Wickman, M.] Karolinska Inst, Sachs Childrens Hosp, Stockholm, Sweden.
[Moatti, J. P.] AMU, Res Unit 912, INSERM, IRD Social & Econ Sci Appl Hlth SESSTIM, Marseille, France.
[Momas, I.] Descartes Univ, Dept Publ Hlth & Biostat, Paris, France.
[Momas, I.] Municipal Dept Social Act Childhood & Hlth, Paris, France.
[Nerin, P.] SATT AxLR, Montpellier, France.
[Postma, D. S.] Univ Groningen, Univ Med Ctr Groningen, Dept Pulmonol, GRIAC Res Inst, Groningen, Netherlands.
[Ritchie, K.] Univ London Imperial Coll Sci Technol & Med, INSERM, U1061, Neuropsychiat, London, England.
[Ritchie, K.] Univ London Imperial Coll Sci Technol & Med, Fac Med, London, England.
[Robine, J. M.] INSERM, Res Unit 988, Paris, France.
[Robine, J. M.] INSERM, Res Unit 710, Montpellier, France.
[Robine, J. M.] EPHE, F-75006 Paris, France.
[Samolinski, B.] Med Univ Warsaw, Dept Prevent Environm Hazards & Allergol, Warsaw, Poland.
[Siroux, V.] Univ Grenoble Alpes, IAB, Team Environm Epidemiol Appl Reprod & Resp Hlth, Grenoble, France.
[Siroux, V.] INSERM, IAB, Team Environm Epidemiol Appl Reprod & Resp Hlth, Grenoble, France.
[Siroux, V.] CHU Grenoble, IAB, Team Environm Epidemiol Appl Reprod & Resp Hlth, F-38043 Grenoble, France.
[Slagboom, P. E.] Leiden Univ, Med Ctr, Sect Mol Epidemiol, Leiden, Netherlands.
[Slagboom, P. E.] Leiden Univ, Med Ctr, Consortium Hlth Aging, Leiden, Netherlands.
[Smit, H. A.] Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Valenta, R.] Med Univ Vienna, Ctr Pathophysiol Infectiol & Immunol, Dept Pathophysiol & Allergy Res, Div Immunopathol, Vienna, Austria.
[Van de Perre, P.] Univ Hosp, Montpellier, France.
[Van de Perre, P.] INSERM, U1058, Montpellier, France.
[Verdier, J. M.] EPHE, Sect Sci Vie & Terre, F-75006 Paris, France.
[Verdier, J. M.] Univ Montpellier 2, UMR S 710, Paris, France.
[Verdier, J. M.] Inst Transdisciplinaire Etud Vieillissement, Montpellier, France.
[Yiallouros, P.] Cyprus Univ Technol, Harvard Sch Publ Hlth, Cyprus Int Inst Environm & Publ Hlth, Limassol, Cyprus.
[Zins, M.] UVSQ, INSERM, UMS 011, Populat Based Epidemiol Cohorts, Villejuif, France.
RP Bousquet, J (reprint author), 273 Av Occitanie, F-34090 Montpellier, France.
EM fabienne.portejoie@gmail.com
RI Holloway, John/B-5424-2009; Iozzo, Patricia/O-2893-2015; Ritchie,
Karen/G-3571-2013; Slagboom, P. Eline/R-4790-2016; Vrijheid,
M/H-2702-2014; Sunyer, J/G-6909-2014; Anto, J/H-2676-2014; Robine,
Jean-Marie/F-5439-2011;
OI Krauss-Etschmann, Susanne/0000-0001-5945-5702; Holloway,
John/0000-0001-9998-0464; Iozzo, Patricia/0000-0001-6443-7074; Slagboom,
P. Eline/0000-0002-2875-4723; Vrijheid, M/0000-0002-7090-1758; Sunyer,
J/0000-0002-2602-4110; Anto, J/0000-0002-4736-8529; Robine,
Jean-Marie/0000-0002-4111-6195; VERDIER,
Jean-Michel/0000-0002-7252-1556; Wickman, Magnus/0000-0003-2710-8620
FU Region Languedoc Roussillon
FX The meeting was supported by an unrestricted educational grant from the
Region Languedoc Roussillon awarded by Mr. C Bourquin (President).
NR 5
TC 13
Z9 13
U1 0
U2 7
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0040-6376
EI 1468-3296
J9 THORAX
JI Thorax
PD JUN
PY 2015
VL 70
IS 6
BP 595
EP 597
DI 10.1136/thoraxjnl-2014-206304
PG 3
WC Respiratory System
SC Respiratory System
GA CJ0YL
UT WOS:000355206900018
PM 25616486
ER
PT J
AU AlGhatrif, M
Choi, S
Fishbein, K
Simonsick, E
Oberdier, M
Ratchford, E
Salameh, M
Thakkar, R
Studenski, S
Spencer, R
Reiter, D
Ferrucci, L
AF AlGhatrif, Majd
Choi, Seongjin
Fishbein, Kenneth
Simonsick, Eleanor
Oberdier, Matt
Ratchford, Elizabeth
Salameh, Maya
Thakkar, Rajiv
Studenski, Stephanie
Spencer, Richard
Reiter, David
Ferrucci, Luigi
TI Lower Ankle-Brachial Index within the Normal Range is Associated with
Delayed Post-Exercise Phosphocreatine Recovery of the Thigh Muscles
SO VASCULAR MEDICINE
LA English
DT Meeting Abstract
C1 [AlGhatrif, Majd] NIA, Johns Hopkins Sch Med, Baltimore, MD 21224 USA.
[Choi, Seongjin; Fishbein, Kenneth; Simonsick, Eleanor; Oberdier, Matt; Studenski, Stephanie; Spencer, Richard; Reiter, David; Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA.
[Ratchford, Elizabeth; Salameh, Maya; Thakkar, Rajiv] Johns Hopkins Sch Med, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1358-863X
EI 1477-0377
J9 VASC MED
JI Vasc. Med.
PD JUN
PY 2015
VL 20
IS 3
MA Poster 8
BP 282
EP 282
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CJ2SE
UT WOS:000355334000027
ER
PT J
AU AlGhatrif, M
Fabbri, E
Moore, AZ
Oberdier, M
Thakkar, R
Ratchford, E
Salameh, M
Simonsick, E
Studneski, S
Ferrucci, L
AF AlGhatrif, Majd
Fabbri, Ellisa
Moore, Ann Zenobia
Oberdier, Matt
Thakkar, Rajiv
Ratchford, Elizabeth
Salameh, Maya
Simonsick, Eleanor
Studneski, Stephanie
Ferrucci, Luigi
TI Lower Ankle-Brachial Index within the Normal Range is Associated with
Accelerated Decline in Thigh Muscle Strength and Quality: Results from
the Baltimore Longitudinal Study of Aging
SO VASCULAR MEDICINE
LA English
DT Meeting Abstract
C1 [AlGhatrif, Majd] NIA, Johns Hopkins Sch Med, Baltimore, MD 21224 USA.
[Fabbri, Ellisa; Moore, Ann Zenobia; Oberdier, Matt; Simonsick, Eleanor; Studneski, Stephanie; Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA.
[Thakkar, Rajiv; Ratchford, Elizabeth; Salameh, Maya] Johns Hopkins Sch Med, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1358-863X
EI 1477-0377
J9 VASC MED
JI Vasc. Med.
PD JUN
PY 2015
VL 20
IS 3
MA Poster 11
BP 283
EP 284
PG 2
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CJ2SE
UT WOS:000355334000030
ER
PT J
AU Lange-Maia, BS
Newman, AB
Strotmeyer, ES
Harris, TB
Caserotti, P
Glynn, NW
AF Lange-Maia, Brittney S.
Newman, Anne B.
Strotmeyer, Elsa S.
Harris, Tamara B.
Caserotti, Paolo
Glynn, Nancy W.
TI Performance on fast- and usual-paced 400-m walk tests in older adults:
are they comparable?
SO AGING CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Physical function; Measurement methods; Gait speed; Physical performance
ID LOWER-EXTREMITY FUNCTION; DISTANCE CORRIDOR WALK; MOBILITY LIMITATION;
DISABILITY; ASSOCIATION; MORTALITY; FITNESS; LIFE
AB Background and aims Fast- and usual-paced 400-m walking tests are often used to assess physical fitness or function, respectively, though it is not known how performance converges on these tests. This study aims to determine whether performance on the fast- and usual-paced 400-m walks varies based upon age and physical function.
Methods Participants (26 men, 38 women aged 70-92) completed a fast- and usual-paced 400-m walk. The Short Physical Performance Battery was used to assess function (score range 0-12). Body mass index and health history were also assessed.
Results Finish times for the fast- and usual-paced 400-m walks were 333.3 and 380.3 s, respectively (P < 0.0001), and highly correlated (r = 0.88, P < 0.001). Higher functioning participants (SPPB > 10) had greater differences between tests compared to lower functioning participants (SPPB a parts per thousand currency sign 10) (52.9 vs. 26.2 s, P = 0.005), as did younger participants (age < 80) compared to those age 80 and older (56.8 vs. 32.8 s, P = 0.003).
Discussion Older and lower functioning participants had greater convergence on the fast- and usual-paced 400-m walks. Potentially some of these lower functioning and older adults may have already performed at their maximal capacity during the usual-paced walk, while the younger and higher functioning participants were able to walk substantially faster when asked.
Conclusions Choice of walking test should consider the age and functional capacity of the population as well as whether function or fitness is of interest.
C1 [Lange-Maia, Brittney S.; Newman, Anne B.; Strotmeyer, Elsa S.; Glynn, Nancy W.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Ctr Aging & Populat Hlth, Pittsburgh, PA 15261 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Glynn, Nancy W.] Univ Southern Denmark, Odense, Denmark.
RP Glynn, NW (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Ctr Aging & Populat Hlth, 130 DeSoto St,A531 Crabtree Hall, Pittsburgh, PA 15261 USA.
EM bsl14@pitt.edu; newmana@edc.pitt.edu; strotmeyere@edc.pitt.edu;
harris99@nia.nih.gov; pcaserotti@sdu.dk; epidnwg@pitt.edu
RI Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Strotmeyer, Elsa/0000-0002-4093-6036;
Glynn, Nancy/0000-0003-2265-0162
FU Pittsburgh Claude D. Pepper Older Americans Independence Center,
Research Registry and Developmental Pilot Grant [NIH P30 AG024826, NIH
P30 AG024827]; National Institute on Aging Professional Services
[HHSN271201100605P]; Intramural Research Program of the National
Institute on Aging; National Institute on Aging Training Grant
[T32-AG000181]
FX This research was supported by Pittsburgh Claude D. Pepper Older
Americans Independence Center, Research Registry and Developmental Pilot
Grant-NIH P30 AG024826 and NIH P30 AG024827 and National Institute on
Aging Professional Services Contract HHSN271201100605P. This project was
also supported, in part, by the Intramural Research Program of the
National Institute on Aging. Brittney S. Lange-Maia is funded by a
National Institute on Aging Training Grant T32-AG000181. This work was
presented as an oral presentation at the 66th Annual Meeting of the
Gerontological Society of America on November 23, 2013 in New Orleans,
Louisiana.
NR 14
TC 5
Z9 5
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1594-0667
EI 1720-8319
J9 AGING CLIN EXP RES
JI Aging Clin. Exp. Res.
PD JUN
PY 2015
VL 27
IS 3
BP 309
EP 314
DI 10.1007/s40520-014-0287-y
PG 6
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA CH9ZG
UT WOS:000354394600009
PM 25373610
ER
PT J
AU Uldrick, TS
AF Uldrick, Thomas S.
TI HAART and lungs: do HIV protease inhibitors impact cancer risk?
SO AIDS
LA English
DT Editorial Material
ID NELFINAVIR
C1 [Uldrick, Thomas S.] NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Uldrick, TS (reprint author), 10 Ctr Dr,Room 6N106,MSC 1868, Bethesda, MD 20892 USA.
EM uldrickts@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 11
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD JUN
PY 2015
VL 29
IS 9
BP 1111
EP 1112
DI 10.1097/QAD.0000000000000644
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA CI4OH
UT WOS:000354730000015
PM 26125143
ER
PT J
AU Tang, WH
Cushman, M
Green, D
Rich, SS
Lange, LA
Yang, Q
Tracy, RP
Tofler, GH
Basu, S
Wilson, JG
Keating, BJ
Weng, LC
Taylor, HA
Jacobs, DR
Delaney, JA
Palmer, CD
Young, T
Pankow, JS
O'Donnell, CJ
Smith, NL
Reiner, AP
Folsom, AR
AF Tang, Weihong
Cushman, Mary
Green, David
Rich, Stephen S.
Lange, Leslie A.
Yang, Qiong
Tracy, Russell P.
Tofler, Geoffrey H.
Basu, Saonli
Wilson, James G.
Keating, Brendan J.
Weng, Lu-Chen
Taylor, Herman A.
Jacobs, David R.
Delaney, Joseph A.
Palmer, Cameron D.
Young, Taylor
Pankow, James S.
O'Donnell, Christopher J.
Smith, Nicholas L.
Reiner, Alexander P.
Folsom, Aaron R.
TI Gene-centric approach identifies new and known loci for FVIII activity
and VWF antigen levels in European Americans and African Americans
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID VON-WILLEBRAND-FACTOR; GENOME-WIDE ASSOCIATION; PARTIAL THROMBOPLASTIN
TIME; CORONARY-HEART-DISEASE; FACTOR-VIII ACTIVITY; VENOUS
THROMBOEMBOLISM; HEMOSTATIC FACTORS; PLASMA-LEVELS;
CARDIOVASCULAR-DISEASE; ATHEROSCLEROSIS RISK
AB Coagulation factor VIII and von Willebrand factor (VWF) are key proteins in procoagulant activation. Higher FVIII coagulant activity (FVIII:C) and VWF antigen (VWF:Ag) are risk factors for cardiovascular disease and venous thromboembolism. Beyond associations with ABO blood group, genetic determinants of FVIII and VWF are not well understood, especially in non European-American populations. We performed a genetic association study of FVIII:C and VWF:Ag that assessed 50,000 gene-centric single nucleotide polymorphisms (SNPs) in 18,556 European Americans (EAs) and 5,047 African Americans (AAs) from five population-based cohorts. Previously unreported associations for FVIII:C were identified in both AAs and EAs with KNG1 (most significantly associated SNP rs710446, Ile581Thr, P=5.10 x 10(-7) in EAs and P=3.88 x 10(-3) in AAs) and VWF rs7962217 (Gly2705Arg, P=6.30 x 10(-9) in EAs and P=2.98 x 10(-2) in AAs). Significant associations for FVIII:C were also observed with F8/TMLHE region SNP rs12557310 in EAs (P=8.02 x 10(-10)), with VWF rs1800380 in AAs (P=5.62 x 10(-11)), and with MAT1A rs2236568 in AAs (P=1.69 x 10(-6)). We replicated previously reported associations of FVIII:C and VWF:Ag with the ABO blood group, VWF rs1063856 (Thr789Ala), rs216321 (Ala852Gln), and VWF rs2229446 (Arg2185Gln). Findings from this study expand our understanding of genetic influences for FVIII:C and VWF:Ag in both EAs and AAs. Am. J. Hematol. 90:534-540, 2015. (c) 2015 Wiley Periodicals, Inc.
C1 [Tang, Weihong; Weng, Lu-Chen; Jacobs, David R.; Pankow, James S.; Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA.
[Cushman, Mary] Univ Vermont, Dept Med, Burlington, VT USA.
[Cushman, Mary] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA.
[Green, David] Northwestern Univ, Dept Med, Div Hematol Oncol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Rich, Stephen S.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA.
[Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Lange, Leslie A.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Tracy, Russell P.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA.
[Tracy, Russell P.] Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA.
[Tofler, Geoffrey H.] Univ Sydney, Royal N Shore Hosp, Dept Cardiol, Sydney, NSW 2006, Australia.
[Basu, Saonli] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN USA.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[Keating, Brendan J.] Univ Penn, Dept Surg, Div Transplantat, Philadelphia, PA 19104 USA.
[Taylor, Herman A.] Univ Mississippi, Med Ctr, Dept Med, Jackson Heart Study, Jackson, MS 39216 USA.
[Delaney, Joseph A.; Reiner, Alexander P.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Palmer, Cameron D.; Young, Taylor] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA USA.
[O'Donnell, Christopher J.] NHLBI, Dept Cardiovasc Epidemiol & Human Genom, NIH, Bethesda, MD 20892 USA.
[Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Smith, Nicholas L.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Smith, Nicholas L.] VA Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA.
RP Tang, WH (reprint author), Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA.
EM tang0097@umn.edu
OI Pankow, James/0000-0001-7076-483X
FU NIH [R01-HL095603, R01-HL59367]
FX Contract grant sponsor: NIH; Contract grant number: R01-HL095603,
R01-HL59367.
NR 56
TC 3
Z9 3
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0361-8609
EI 1096-8652
J9 AM J HEMATOL
JI Am. J. Hematol.
PD JUN
PY 2015
VL 90
IS 6
BP 534
EP 540
DI 10.1002/ajh.24005
PG 7
WC Hematology
SC Hematology
GA CI5OK
UT WOS:000354806500020
PM 25779970
ER
PT J
AU Koh, DH
Locke, SJ
Chen, YC
Purdue, MP
Friesen, MC
AF Koh, Dong-Hee
Locke, Sarah J.
Chen, Yu-Cheng
Purdue, Mark P.
Friesen, Melissa C.
TI Lead exposure in US worksites: A literature review and development of an
occupational lead exposure database from the published literature
SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE
LA English
DT Article
DE lead; occupational exposure; exposure assessment; review;
population-based studies
ID BLOOD LEAD; FORMALDEHYDE EXPOSURE; UNITED-STATES; WORKERS; COHORT; SIZE;
INDUSTRIES; MORTALITY; PRESSURE; SHANGHAI
AB BackgroundRetrospective exposure assessment of occupational lead exposure in population-based studies requires historical exposure information from many occupations and industries.
MethodsWe reviewed published US exposure monitoring studies to identify lead measurement data. We developed an occupational lead exposure database from the 175 identified papers containing 1,111 sets of lead concentration summary statistics (21% area air, 47% personal air, 32% blood). We also extracted ancillary exposure-related information, including job, industry, task/location, year collected, sampling strategy, control measures in place, and sampling and analytical methods.
ResultsThe measurements were published between 1940 and 2010 and represented 27 2-digit standardized industry classification codes. The majority of the measurements were related to lead-based paint work, joining or cutting metal using heat, primary and secondary metal manufacturing, and lead acid battery manufacturing.
ConclusionsThis database can be used in future statistical analyses to characterize differences in lead exposure across time, jobs, and industries. Am. J. Ind. Med. 58:605-616, 2015. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Koh, Dong-Hee; Locke, Sarah J.; Chen, Yu-Cheng; Purdue, Mark P.; Friesen, Melissa C.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA.
[Koh, Dong-Hee; Locke, Sarah J.] Catholic Kwandong Univ, Int St Marys Hosp, Dept Occupat & Environm Med, Inchon, South Korea.
[Chen, Yu-Cheng] Natl Hlth Res Inst, Natl Environm Hlth Res Ctr, Zhunan, Taiwan.
RP Locke, SJ (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Rm 6E550, Rockville, MD 20850 USA.
EM lockesj@mail.nih.gov
RI Purdue, Mark/C-9228-2016; Friesen, Melissa/A-5362-2009
OI Purdue, Mark/0000-0003-1177-3108;
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health [Z01 CP10122]
FX This study was funded by the Intramural Research Program of the Division
of Cancer Epidemiology and Genetics, National Cancer Institute, National
Institutes of Health (Z01 CP10122).
NR 46
TC 1
Z9 1
U1 3
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0271-3586
EI 1097-0274
J9 AM J IND MED
JI Am. J. Ind. Med.
PD JUN
PY 2015
VL 58
IS 6
BP 605
EP 616
DI 10.1002/ajim.22448
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CI0TH
UT WOS:000354450400003
PM 25968240
ER
PT J
AU Margolis, L
AF Margolis, Leonid
TI Immunoactivation at the Crossroads of Human Disease
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Review
DE Inflammation; Pathogens; Pathogenesis; Viruses
ID HIV-INFECTION; RHEUMATOID-ARTHRITIS; MACULAR DEGENERATION; INFLAMMATION;
ATHEROSCLEROSIS; ACTIVATION; AGE; PATHOGENESIS; IMMUNITY; MECHANISMS
AB It is becoming increasingly clear that immunoactivation, which evolved as a system of host defense against pathogens, can become dysregulated and promote the pathogenesis of diverse diseases with both known and unknown etiologies (eg, acquired immune deficiency syndrome, age-related macular degeneration, cancer, as well as aging). Immunoactivation seems to be a "common denominator" or general mechanism of pathogenesis and may explain the association and similarities in pathology among otherwise unrelated human diseases. Identification of general mechanisms of immunoactivation may lead to the development of new therapeutic strategies applicable to many diseases even before detailed knowledge of specific etiology and pathogenesis may be available. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license
C1 [Margolis, Leonid] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Margolis, L (reprint author), NIH, 10 Ctr Dr 10-9D58, Bethesda, MD 20892 USA.
EM margolil@mail.nih.gov
FU Intramural Program, Eunice Kennedy-Shriver National Institute of Child
Health and Human Development, National Institutes of Health
FX Intramural Program, Eunice Kennedy-Shriver National Institute of Child
Health and Human Development, National Institutes of Health.
NR 35
TC 3
Z9 3
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
EI 1555-7162
J9 AM J MED
JI Am. J. Med.
PD JUN
PY 2015
VL 128
IS 6
BP 562
EP 566
DI 10.1016/j.amjmed.2014.12.026
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA CI6NR
UT WOS:000354877200012
PM 25637756
ER
PT J
AU Sipe, TA
Finnie, RKC
Knopf, JA
Qu, SL
Reynolds, JA
Thota, AB
Hahn, RA
Goetzel, RZ
Hennessy, KD
McKnight-Eily, LR
Chapman, DP
Anderson, CW
Azrin, S
Abraido-Lanza, AF
Gelenberg, AJ
Vernon-Smiley, ME
Nease, DE
AF Sipe, Theresa Ann
Finnie, Ramona K. C.
Knopf, John A.
Qu, Shuli
Reynolds, Jeffrey A.
Thota, Anilkrishna B.
Hahn, Robert A.
Goetzel, Ron Z.
Hennessy, Kevin D.
McKnight-Eily, Lela R.
Chapman, Daniel P.
Anderson, Clinton W.
Azrin, Susan
Abraido-Lanza, Ana F.
Gelenberg, Alan J.
Vernon-Smiley, Mary E.
Nease, Donald E., Jr.
CA Community Prevent Serv Task Force
TI Effects of Mental Health Benefits Legislation A Community Guide
Systematic Review
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Review
ID STATE PARITY LAWS; COMORBIDITY SURVEY REPLICATION; LARGE EMPLOYER GROUP;
DSM-IV DISORDERS; FEDERAL-EMPLOYEES; INSURANCE PARITY;
PREVENTIVE-SERVICES; MANAGED CARE; DRUG-ABUSE; COVERAGE
AB Context: Health insurance benefits for mental health services typically have paid less than benefits for physical health services, resulting in potential underutilization or financial burden for people with mental health conditions. Mental health benefits legislation was introduced to improve financial protection (i.e., decrease financial burden) and to increase access to, and use of, mental health services. This systematic review was conducted to determine the effectiveness of mental health benefits legislation, including executive orders, in improving mental health.
Evidence acquisition: Methods developed for the Guide to Community Preventive Services were used to identify, evaluate, and analyze available evidence. The evidence included studies published or reported from 1965 to March 2011 with at least one of the following outcomes: access to care, financial protection, appropriate utilization, quality of care, diagnosis of mental illness, morbidity and mortality, and quality of life. Analyses were conducted in 2012.
Evidence synthesis: Thirty eligible studies were identified in 37 papers. Implementation of mental health benefits legislation was associated with financial protection (decreased out-of-pocket costs) and appropriate utilization of services. Among studies examining the impact of legislation strength, most found larger positive effects for comprehensive parity legislation or policies than for less-comprehensive ones. Few studies assessed other mental health outcomes.
Conclusions: Evidence indicates that mental health benefits legislation, particularly comprehensive parity legislation, is effective in improving financial protection and increasing appropriate utilization of mental health services for people with mental health conditions. Evidence was limited for other mental health outcomes. Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine
C1 [Sipe, Theresa Ann; Finnie, Ramona K. C.; Knopf, John A.; Qu, Shuli; Reynolds, Jeffrey A.; Thota, Anilkrishna B.; Hahn, Robert A.] CDC, Ctr Surveillance Epidemiol & Lab Serv, Community Guide Branch, Div Epidemiol Anal & Lib Serv, Atlanta, GA 30329 USA.
[McKnight-Eily, Lela R.; Chapman, Daniel P.] CDC, Div Populat Hlth, Atlanta, GA 30329 USA.
[Vernon-Smiley, Mary E.] CDC, Div Adolescent, Atlanta, GA 30329 USA.
[Vernon-Smiley, Mary E.] CDC, Sch Hlth, Atlanta, GA 30329 USA.
[Goetzel, Ron Z.] Emory Univ, Truven Hlth Analyt & Thomson Reuters, Atlanta, GA 30322 USA.
[Anderson, Clinton W.] Amer Psychol Assoc, Washington, DC 20036 USA.
[Hennessy, Kevin D.] Subst Abuse & Mental Hlth Serv Adm, Rockville, MD USA.
[Azrin, Susan] NIMH, Bethesda, MD 20892 USA.
[Abraido-Lanza, Ana F.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
[Gelenberg, Alan J.] Penn State Hershey Med Ctr, Dept Psychiat, Hershey, PA USA.
[Nease, Donald E., Jr.] Amer Acad Family Phys, Denver, CO USA.
RP Sipe, TA (reprint author), CDC, Prevent Res Branch, Div HIV AIDS Prevent, 1600 Clifton Rd,Mailstop E 37, Atlanta, GA 30329 USA.
EM tsipe@cdc.gov
RI Nease, Donald/B-6206-2013
OI Nease, Donald/0000-0001-8323-3720
FU Oak Ridge Institute for Scientific Education (ORISE)
FX The work of Ramona K.C. Finnie, John A. Knopf, Shuli Qu, Jeffrey A.
Reynolds, Cristian Dumitru, Sierra Baker, Guthrie Byard, Su Su, and
Elena Watzke was supported with funds from the Oak Ridge Institute for
Scientific Education (ORISE).
NR 79
TC 1
Z9 1
U1 2
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
EI 1873-2607
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD JUN
PY 2015
VL 48
IS 6
BP 755
EP 766
DI 10.1016/j.amepre.2015.01.022
PG 12
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA CI5EK
UT WOS:000354776000015
PM 25998926
ER
PT J
AU Lv, QW
Zhang, W
Shi, Q
Zheng, WJ
Li, X
Chen, H
Wu, QJ
Jiang, WL
Li, HB
Gong, L
Wei, W
Liu, H
Liu, AJ
Jin, HT
Wang, JX
Liu, XM
Li, ZB
Liu, B
Shen, M
Wang, Q
Wu, XN
Liang, D
Yin, YF
Fei, YY
Su, JM
Zhao, LD
Jiang, Y
Li, J
Tang, FL
Zhang, FC
Lipsky, PE
Zhang, X
AF Lv, Qian-wen
Zhang, Wen
Shi, Qun
Zheng, Wen-jie
Li, Xin
Chen, Hua
Wu, Qing-jun
Jiang, Wan-lan
Li, Hong-bin
Gong, Lu
Wei, Wei
Liu, Hui
Liu, Ai-jing
Jin, Hong-tao
Wang, Jun-xiang
Liu, Xiu-mei
Li, Zhen-bin
Liu, Bin
Shen, Min
Wang, Qian
Wu, Xiang-ni
Liang, Di
Yin, Yu-feng
Fei, Yun-yun
Su, Jing-mei
Zhao, Li-dan
Jiang, Ying
Li, Jing
Tang, Fu-lin
Zhang, Feng-chun
Lipsky, Peter E.
Zhang, Xuan
TI Comparison of Tripterygium wilfordii Hook F with methotrexate in the
treatment of active rheumatoid arthritis (TRIFRA): a randomised,
controlled clinical trial
SO ANNALS OF THE RHEUMATIC DISEASES
LA English
DT Article
ID MALE ANTIFERTILITY COMPOUNDS; THUNDER GOD VINE; DOUBLE-BLIND;
ANTICANCER; TRIPTOLIDE; CHEMISTRY; CHANNELS; PROGRESS; EXTRACT; CELLS
AB Objectives To compare the efficacy and safety of Tripterygium wilfordii Hook F (TwHF) with methotrexate (MTX) in the treatment of active rheumatoid arthritis (RA).
Methods Design: a multicentre, open-label, randomised controlled trial. All patients were assessed by trained investigators who were unaware of the therapeutic regimen. Intervention: 207 patients with active RA were randomly allocated (1:1:1) to treatment with MTX 12.5mg once a week, or TwHF 20mg three times a day, or the two in combination. At week 12, if reduction of the 28-joint count Disease Activity Score (DAS28) was <30% in the monotherapy groups, the patient was switched to MTX+TwHF. The primary efficacy point was the proportion of patients achieving an American College of Rheumatology (ACR) 50 response at week 24.
Results 174/207 (84.1%) patients completed 24weeks of the trial. In an intention-to-treat analysis, the proportion of patients reaching the ACR50 response criteria was 46.4% (32/69), 55.1% (38/69) and 76.8% (53/69), respectively, in the MTX, TwHF and MTX+TwHF groups (TwHF vs MTX monotherapy, p=0.014; MTX+TwHF vs MTX monotherapy, p<0.001). Similar statistically significant patterns at week 24 were found for ACR20, ACR70, clinical Disease Activity Index good responses, EULAR good response, remission rate and low disease activity rate. Significant improvement in the Health Assessment Questionnaire and 36-item Short-Form Health Survey questionnaire scores from baseline to week 24 was seen in each treatment arm (p<0.05), though no significant difference was found among the treatment arms (p>0.05). The result of per-protocol analysis agreed with that seen in the intention-to-treat analysis. Seven, three and five women in the TwHF, MTX and combination groups, respectively, developed irregular menstruation (TwHF vs MTX monotherapy, p=0.216).
Conclusions TwHF monotherapy was not inferior to, and MTX+TwHF was better than, MTX monotherapy in controlling disease activity in patients with active RA.
Trial registration number NCT01613079.
C1 [Lv, Qian-wen; Zhang, Wen; Shi, Qun; Zheng, Wen-jie; Li, Xin; Chen, Hua; Wu, Qing-jun; Jiang, Wan-lan; Shen, Min; Wang, Qian; Wu, Xiang-ni; Liang, Di; Yin, Yu-feng; Fei, Yun-yun; Su, Jing-mei; Zhao, Li-dan; Jiang, Ying; Li, Jing; Tang, Fu-lin; Zhang, Feng-chun; Zhang, Xuan] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Rheumatol & Clin Immunol, Beijing 100730, Peoples R China.
[Lv, Qian-wen; Zhang, Wen; Shi, Qun; Zheng, Wen-jie; Li, Xin; Chen, Hua; Wu, Qing-jun; Jiang, Wan-lan; Shen, Min; Wang, Qian; Wu, Xiang-ni; Liang, Di; Yin, Yu-feng; Fei, Yun-yun; Su, Jing-mei; Zhao, Li-dan; Jiang, Ying; Li, Jing; Tang, Fu-lin; Zhang, Feng-chun; Zhang, Xuan] Peking Union Med Coll, Beijing 100730, Peoples R China.
[Li, Hong-bin] Inner Mongolia Med Coll, Affiliated Hosp, Dept Rheumatol, Hohhot, Peoples R China.
[Gong, Lu; Wei, Wei] Tianjin Med Univ, Gen Hosp, Dept Rheumatol, Tianjin, Peoples R China.
[Liu, Hui] Beijing Dongfang Hosp, Dept Rheumatol, Beijing, Peoples R China.
[Liu, Ai-jing; Jin, Hong-tao] Hebei Med Univ, Hosp 2, Dept Rheumatol, Shijiazhuang, Hebei, Peoples R China.
[Wang, Jun-xiang] Hebei Med Univ, Hosp 3, Dept Rheumatol, Shijiazhuang, Hebei, Peoples R China.
[Liu, Xiu-mei] Shanxi Med Univ, Hosp 1, Dept Rheumatol, Taiyuan, Shanxi, Peoples R China.
[Li, Zhen-bin] Bethune Int Heping Hosp Hebei, Dept Rheumatol, Shijiazhuang, Hebei, Peoples R China.
[Liu, Bin] Qingdao Univ, Coll Med, Affiliated Hosp, Dept Rheumatol, Qingdao, Shandong, Peoples R China.
[Lipsky, Peter E.] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Zhang, X (reprint author), Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Rheumatol & Clin Immunol, Beijing 100730, Peoples R China.
EM peterlipsky@comcast.net; zxpumch2003@sina.com
OI zhang, xuan/0000-0001-8775-1699
FU National Natural Science Foundation of China [81325019, 81172859,
81273312]; Beijing Municipal Natural Science Foundation [7141008];
Research Special Fund for Public Welfare Industry of Health [20120217];
Capital Health Research and Development of Special Fund [2011-4001-02];
National laboratory Special Fund [2060204]
FX This work was supported by the grants from the National Natural Science
Foundation of China (81325019, 81172859 and 81273312), Beijing Municipal
Natural Science Foundation (7141008), the Research Special Fund for
Public Welfare Industry of Health (20120217), the Capital Health
Research and Development of Special Fund (2011-4001-02) and the National
laboratory Special Fund (2060204).
NR 28
TC 15
Z9 17
U1 5
U2 20
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-4967
EI 1468-2060
J9 ANN RHEUM DIS
JI Ann. Rheum. Dis.
PD JUN
PY 2015
VL 74
IS 6
BP 1078
EP 1086
DI 10.1136/annrheumdis-2013-204807
PG 9
WC Rheumatology
SC Rheumatology
GA CH9QO
UT WOS:000354371200020
PM 24733191
ER
PT J
AU Hair, BY
Xu, ZL
Kirk, EL
Harlid, S
Sandhu, R
Robinson, WR
Wu, MC
Olshan, AF
Conway, K
Taylor, JA
Troester, MA
AF Hair, Brionna Y.
Xu, Zongli
Kirk, Erin L.
Harlid, Sophia
Sandhu, Rupninder
Robinson, Whitney R.
Wu, Michael C.
Olshan, Andrew F.
Conway, Kathleen
Taylor, Jack A.
Troester, Melissa A.
TI Body mass index associated with genome-wide methylation in breast tissue
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Obesity; Methylation; Breast cancer; BMI; Epigenetics
ID DEMONSTRATE FIELD CANCERIZATION; DNA METHYLATION; AROMATASE-ACTIVITY;
CANCER-RISK; OBESITY; INFLAMMATION; EXPRESSION; TUMORS; RECEPTOR;
SUBTYPES
AB Gene expression studies indicate that body mass index (BMI) is associated with molecular pathways involved in inflammation, insulin-like growth factor activation, and other carcinogenic processes in breast tissue. The goal of this study was to determine whether BMI is associated with gene methylation in breast tissue and to identify pathways that are commonly methylated in association with high BMI. Epigenome-wide methylation profiles were determined using the Illumina HumanMethylation450 BeadChip array in the non-diseased breast tissue of 81 women undergoing breast surgery between 2009 and 2013 at the University of North Carolina Hospitals. Multivariable, robust linear regression was performed to identify methylation sites associated with BMI at a false discovery rate q value < 0.05. Gene expression microarray data was used to identify which of the BMI-associated methylation sites also showed correlation with gene expression. Gene set enrichment analysis was conducted to assess which pathways were enriched among the BMI-associated methylation sites. Of the 431,568 methylation sites analyzed, 2573 were associated with BMI (q value < 0.05), 57 % of which showed an inverse correlation with BMI. Pathways enriched among the 2573 probe sites included those involved in inflammation, insulin receptor signaling, and leptin signaling. We were able to map 1251 of the BMI-associated methylation sites to gene expression data, and, of these, 226 (18 %) showed substantial correlations with gene expression. Our results suggest that BMI is associated with genome-wide methylation in non-diseased breast tissue and may influence epigenetic pathways involved in inflammatory and other carcinogenic processes.
C1 [Hair, Brionna Y.; Kirk, Erin L.; Robinson, Whitney R.; Olshan, Andrew F.; Conway, Kathleen; Troester, Melissa A.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Xu, Zongli; Harlid, Sophia; Taylor, Jack A.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Xu, Zongli; Harlid, Sophia; Taylor, Jack A.] NIEHS, Epigen & Stem Cell Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Sandhu, Rupninder; Robinson, Whitney R.; Conway, Kathleen] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Wu, Michael C.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
RP Hair, BY (reprint author), Univ N Carolina, Dept Epidemiol, CB 7435,2101 McGavran Greenberg Hall, Chapel Hill, NC 27599 USA.
EM bhair@email.unc.edu
OI Harlid, Sophia/0000-0001-8540-6891; xu, zongli/0000-0002-9034-8902;
taylor, jack/0000-0001-5303-6398; Wu, Michael C./0000-0002-3357-6570
FU National Cancer Institute Specialized Program of Research Excellence
(SPORE) in Breast Cancer [NIH/NCI P50-CA58223]; National Cancer
Institute/National Institute of Environmental Health Sciences Breast
Cancer and the Environment Research Program [U01 - ES019472]; Intramural
Research Program of the NIH, National Institute of Environmental Health
Sciences [ZIA-ES049032-18, ZIA-ES049033-18]; National Cancer Institute
[K01-CA172717-01]
FX This research was funded, in part, by the National Cancer Institute
Specialized Program of Research Excellence (SPORE) in Breast Cancer
(NIH/NCI P50-CA58223), the National Cancer Institute/National Institute
of Environmental Health Sciences Breast Cancer and the Environment
Research Program (U01 - ES019472), and the Intramural Research Program
of the NIH, National Institute of Environmental Health Sciences
(ZIA-ES049032-18, ZIA-ES049033-18). WRR was supported by the National
Cancer Institute (K01-CA172717-01).
NR 49
TC 4
Z9 4
U1 1
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD JUN
PY 2015
VL 151
IS 2
BP 453
EP 463
DI 10.1007/s10549-015-3401-8
PG 11
WC Oncology
SC Oncology
GA CI1JC
UT WOS:000354499200023
PM 25953686
ER
PT J
AU Swamydas, M
Break, TJ
Lionakis, MS
AF Swamydas, Muthulekha
Break, Timothy J.
Lionakis, Michail S.
TI Mononuclear phagocyte-mediated antifungal immunity: the role of
chemotactic receptors and ligands
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Review
DE Fungal infections; Monocytes; Macrophages; Dendritic cells; Chemotactic
factors; Candidiasis; Aspergillosis; Cryptococcosis
ID CRYPTOCOCCUS-NEOFORMANS INFECTION; TUMOR-NECROSIS-FACTOR; INVASIVE
PULMONARY ASPERGILLOSIS; RAT ALVEOLAR MACROPHAGES; SURVEILLANCE NETWORK
TRANSNET; CELL TRANSPLANT RECIPIENTS; HUMAN DENDRITIC CELLS;
FUNGAL-INFECTIONS; HISTOPLASMA-CAPSULATUM; HOST-DEFENSE
AB Over the past two decades, fungal infections have emerged as significant causes of morbidity and mortality in patients with hematological malignancies, hematopoietic stem cell or solid organ transplantation and acquired immunodeficiency syndrome. Besides neutrophils and CD4(+) T lymphocytes, which have long been known to play an indispensable role in promoting protective antifungal immunity, mononuclear phagocytes are now being increasingly recognized as critical mediators of host defense against fungi. Thus, a recent surge of research studies has focused on understanding the mechanisms by which resident and recruited monocytes, macrophages and dendritic cells accumulate and become activated at the sites of fungal infection. Herein, we critically review how a variety of G-protein coupled chemoattractant receptors and their ligands mediate mononuclear phagocyte recruitment and effector function during infection by the most common human fungal pathogens.
C1 [Swamydas, Muthulekha; Break, Timothy J.; Lionakis, Michail S.] NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Lionakis, MS (reprint author), NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, 9000 Rockville Pike,Bldg 10,Room 11C102, Bethesda, MD 20892 USA.
EM lionakism@niaid.nih.gov
FU Division of Intramural Research of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported by the Division of Intramural Research of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 134
TC 2
Z9 2
U1 0
U2 6
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
EI 1420-9071
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD JUN
PY 2015
VL 72
IS 11
BP 2157
EP 2175
DI 10.1007/s00018-015-1858-6
PG 19
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CI6PV
UT WOS:000354883800008
PM 25715741
ER
PT J
AU Grodin, EN
White, TL
AF Grodin, Erica N.
White, Tara L.
TI The neuroanatomical delineation of agentic and affiliative extraversion
SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE
LA English
DT Article
DE Positive emotion; Extraversion; Personality traits; Individual
differences; Neuroanatomical basis; Neuroanatomical differences;
Neuroanatomical dissociation; Voxel-based morphometry; VBM; MPQ; Healthy
adult volunteers; Human subjects; Discriminant validity; Personality
neuroscience
ID VOXEL-BASED MORPHOMETRY; MULTIDIMENSIONAL PERSONALITY QUESTIONNAIRE; BIG
5; PARAHIPPOCAMPAL CORTEX; INCENTIVE MOTIVATION; GENDER-DIFFERENCES;
PREFRONTAL CORTEX; CINGULATE CORTEX; BRAIN; REWARD
AB Extraversion is a fascinating personality dimension that consists of two major components, agentic extraversion and affiliative extraversion. Agentic extraversion involves incentive motivation and is expressed as a tendency toward assertiveness, persistence, and achievement. Affiliative extraversion involves the positive emotion of social warmth and is expressed as a tendency toward amicability, gregariousness, and affection. Here we investigate the neuroanatomical correlates of the personality traits of agentic and affiliative extraversion using the Multidimensional Personality Questionnaire Brief Form, structural magnetic resonance imaging, and voxel-based morphometry in a sample of 83 healthy adult volunteers. We found that trait agentic extraversion and trait affiliative extraversion were each positively associated with the volume of the medial orbitofrontal cortex bilaterally (t's a parts per thousand yen 2.03, r's a parts per thousand yen .23, p's < .05). Agentic extraversion was specifically and positively related to the volume of the left parahippocampal gyrus (t = 4.08, r = .21, p < .05), left cingulate gyrus (t = 4.75, r = .28, p < .05), left caudate (t = 4.29, r = .24, p < .05), and left precentral gyrus (t = 4.00, r = .18, p < .05) in males and females, and the volume of the right nucleus accumbens in males (t = 2.92, r = .20, p < .05). Trait affiliative extraversion was not found to be associated with additional regions beyond the medial orbitofrontal cortex. The findings provide the first evidence of a neuroanatomical dissociation between the personality traits of agentic and affiliative extraversion in healthy adults.
C1 [Grodin, Erica N.; White, Tara L.] Brown Univ, Ctr Alcohol & Addict Studies, Dept Behav & Social Sci, Providence, RI 02912 USA.
[Grodin, Erica N.] NIAAA, Brown NIH Grad Partnership Program, Bethesda, MD USA.
RP White, TL (reprint author), Brown Univ, Ctr Alcohol & Addict Studies, Dept Behav & Social Sci, Box G-S121-4,121 South Main St, Providence, RI 02912 USA.
EM Tara_White@Brown.edu
RI Grodin, Erica/G-1054-2015;
OI Grodin, Erica/0000-0001-5528-4918
FU National Institute on Drug Abuse [DA R01 020725, DA R21 029189];
Lifespan/Tufts/Brown Center for AIDS Research; Foundation for Alcohol
Research; National Institute on Alcohol Abuse and Alcoholism [AA P01
019072]
FX The authors report that they had no conflicts of interest. This research
was supported by grants from the National Institute on Drug Abuse to
T.L.W. (Grant Nos. DA R01 020725, DA R21 029189), the
Lifespan/Tufts/Brown Center for AIDS Research to T.L.W., the Foundation
for Alcohol Research to T.L.W., and the National Institute on Alcohol
Abuse and Alcoholism (Grant No. AA P01 019072). We would like to thank
Adam Nitenson for his assistance with the figures.
NR 64
TC 3
Z9 3
U1 6
U2 14
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1530-7026
EI 1531-135X
J9 COGN AFFECT BEHAV NE
JI Cogn. Affect. Behav. Neurosci.
PD JUN
PY 2015
VL 15
IS 2
BP 321
EP 334
DI 10.3758/s13415-014-0331-6
PG 14
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA CI3IQ
UT WOS:000354641800006
PM 25712871
ER
PT J
AU Decker, B
Masur, H
AF Decker, Brooke
Masur, Henry
TI Bad Bugs, No Drugs: Are We Part of the Problem, or Leaders in Developing
Solutions?
SO CRITICAL CARE MEDICINE
LA English
DT Editorial Material
ID INTENSIVE-CARE-UNIT; METALLO-BETA-LACTAMASE; ANTIMICROBIAL STEWARDSHIP;
CEFTAZIDIME-AVIBACTAM; DE-ESCALATION; HAND HYGIENE; ENTEROBACTERIACEAE;
EPIDEMIOLOGY; INFECTION
C1 [Decker, Brooke] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Masur, Henry] NIH, Ctr Clin, Bethesda, MD USA.
RP Decker, B (reprint author), Univ Pittsburgh, Pittsburgh, PA 15260 USA.
OI Decker M.D., Brooke K/0000-0002-3404-9115
NR 28
TC 0
Z9 0
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0090-3493
EI 1530-0293
J9 CRIT CARE MED
JI Crit. Care Med.
PD JUN
PY 2015
VL 43
IS 6
BP 1153
EP 1155
DI 10.1097/CCM.0000000000001039
PG 3
WC Critical Care Medicine
SC General & Internal Medicine
GA CI4LL
UT WOS:000354720300021
PM 25978153
ER
PT J
AU Torabi-Parizi, P
AF Torabi-Parizi, Parizad
TI Critical Care Management of Two Patients With Ebola: A Biocontainment
Unit Demystified
SO CRITICAL CARE MEDICINE
LA English
DT Editorial Material
C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Torabi-Parizi, P (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [Z99 CL999999]
NR 6
TC 0
Z9 0
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0090-3493
EI 1530-0293
J9 CRIT CARE MED
JI Crit. Care Med.
PD JUN
PY 2015
VL 43
IS 6
BP 1326
EP 1327
DI 10.1097/CCM.0000000000001009
PG 2
WC Critical Care Medicine
SC General & Internal Medicine
GA CI4LL
UT WOS:000354720300040
PM 25978155
ER
PT J
AU Suffredini, AF
AF Suffredini, Anthony F.
TI Targeting Sirtuin to Modulate Human Inflammation
SO CRITICAL CARE MEDICINE
LA English
DT Editorial Material
DE deacetylation; epigenetics; histones; metabolomics; sirtuin
ID IMMUNOSUPPRESSION; METABOLISM; SEPSIS; FLAME
C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Suffredini, AF (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
NR 15
TC 0
Z9 0
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0090-3493
EI 1530-0293
J9 CRIT CARE MED
JI Crit. Care Med.
PD JUN
PY 2015
VL 43
IS 6
BP 1348
EP 1349
DI 10.1097/CCM.0000000000001030
PG 2
WC Critical Care Medicine
SC General & Internal Medicine
GA CI4LL
UT WOS:000354720300053
PM 25978168
ER
PT J
AU Linetzky, M
Pergamin-Hight, L
Pine, DS
Bar-Haim, Y
AF Linetzky, Marian
Pergamin-Hight, Lee
Pine, Daniel S.
Bar-Haim, Yair
TI QUANTITATIVE EVALUATION OF THE CLINICAL EFFICACY OF ATTENTION BIAS
MODIFICATION TREATMENT FOR ANXIETY DISORDERS
SO DEPRESSION AND ANXIETY
LA English
DT Review
DE anxiety; anxiety disorders; clinical trials; treatment; cognition;
computer; Internet technology
ID RANDOMIZED CONTROLLED-TRIAL; COGNITIVE-BEHAVIORAL THERAPY; GENERALIZED
SOCIAL PHOBIA; MODIFICATION PROGRAM; INDIVIDUALS; THREAT; METAANALYSIS;
DEPRESSION; CHILDREN; STIMULI
AB BackgroundAttention bias modification treatment (ABMT) is a novel treatment for anxiety disorders. Although a number of other meta-analytic reviews exist, the purpose of the present meta-analysis is to examine issues unaddressed in prior reviews. Specifically, the review estimates the efficacy of ABMT in clinically anxious patients and examines the effect of delivery context (clinic vs. home) on symptom reduction.
MethodsA literature search using PsychInfo and Web of Science databases was performed. Only randomized controlled trials (RCTs) examining dot-probe-based ABMT in clinically diagnosed anxious patients were included. From 714 articles located through the search, 36 ABMT studies were identified and 11 studies met inclusion criteria (N = 589 patients).
ResultsABMT was associated with greater clinician-rated reductions in anxiety symptoms relative to control training: between-groups effect (d = 0.42, P = .001, confidence interval (CI) = 0.18-0.66), contrast of within-group effects (Q = 7.25, P < .01). More patients in the treatment group no longer met formal diagnostic criteria for their anxiety disorder posttreatment relative to patients in the control condition (P < .05). Analyses of patients' self-reported anxiety were nonsignificant for the between-groups contrast (P = .35), and were at a trend level of significance for the contrast between the within-group effects (P = .06). Moderation analysis of the between-groups effect revealed a significant effect for ABMT delivered in the clinic (d = 0.34, P = 0.01, CI = 0.07-0.62), and a nonsignificant effect for ABMT delivered at home (d = -0.10, P = 0.40, CI = -0.33-0.13).
ConclusionsThe current meta-analysis provides support for ABMT as a novel evidenced-based treatment for anxiety disorders. Overall, ABMT effects are mainly evident when it is delivered in the clinic and when clinical outcome is evaluated by a clinician. More RCTs of ABMT in specific anxiety disorders are warranted.
C1 [Linetzky, Marian; Pergamin-Hight, Lee; Bar-Haim, Yair] Tel Aviv Univ, Sch Psychol Sci, IL-69978 Tel Aviv, Israel.
[Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, Emot & Dev Branch, Intramural Res Program, Bethesda, MD 20892 USA.
[Bar-Haim, Yair] Tel Aviv Univ, Sagol Sch Neurosci, IL-69978 Tel Aviv, Israel.
RP Linetzky, M (reprint author), Tel Aviv Univ, Sch Psychol Sci, IL-69978 Tel Aviv, Israel.
EM marian.linetzky@post.tau.ac.il
FU United States-Israel Binational Science Foundation (BSF) [01014599]
FX This research was supported by Grant No 01014599 from the United
States-Israel Binational Science Foundation (BSF).
NR 37
TC 32
Z9 32
U1 9
U2 39
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1091-4269
EI 1520-6394
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD JUN
PY 2015
VL 32
IS 6
BP 383
EP 391
DI 10.1002/da.22344
PG 9
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA CI2IB
UT WOS:000354568500001
PM 25708991
ER
PT J
AU Maul, RW
Saribasak, H
Cao, Z
Gearhart, PJ
AF Maul, Robert W.
Saribasak, Huseyin
Cao, Zheng
Gearhart, Patricia J.
TI Topoisomerase I deficiency causes RNA polymerase II accumulation and
increases AID abundance in immunoglobulin variable genes
SO DNA REPAIR
LA English
DT Article
DE DT40; Topoisomerase I; RNA polymerase II; Activation-induced deaminase;
Somatic hypermutation; Gene conversion
ID CLASS SWITCH RECOMBINATION; ACTIVATION-INDUCED DEAMINASE; LIGHT-CHAIN
GENE; CENTER B-CELLS; SOMATIC HYPERMUTATION; SEQUENCING REVEALS; DNA;
TRANSCRIPTION; CONVERSION; REGION
AB Activation-induced deaminase (AID) is a DNA cytosine deaminase that diversifies immunoglobulin genes in B cells. Recent work has shown that RNA polymerase II (Pol II) accumulation correlates with AID recruitment. However, a direct link between Vol II and AID abundance has not been tested. We used the DT40 B-cell line to manipulate levels of Pol II by decreasing topoisomerase I (Top1), which relaxes DNA supercoiling in front of the transcription complex. Top1 was decreased by stable transfection of a short hairpin RNA against Top 1,which produced an accumulation of Pol II in transcribed genes, compared to cells transfected with sh-control RNA. The increased Pol II density enhanced AID recruitment to variable genes in the lambda light chain locus, and resulted in higher levels of somatic hypermutation and gene conversion. It has been proposed by another lab that AID itself might directly suppress Top 1 to increase somatic hypermutation. However, we found that in both AID(+/+) and AID(-/-) B cells from DT40 and mice, Top1 protein levels were identical, indicating that the presence or absence of AID did not decrease Top1 expression. Rather, our results suggest that the mechanism for increased diversity when Topl is reduced is that Pol II accumulates and recruits AID to variable genes. Published by Elsevier B.V.
C1 [Maul, Robert W.; Saribasak, Huseyin; Cao, Zheng; Gearhart, Patricia J.] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
RP Gearhart, PJ (reprint author), NIA, Lab Mol Biol & Immunol, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM gearhartp@mail.nih.gov
RI Saribasak, Huseyin/C-9331-2012
OI Saribasak, Huseyin/0000-0003-0055-062X
FU Intramural Research Program of the NIH; National Institute on Aging
FX We thank William Yang for technical assistance, Jean Marie Buerstedde
and Hiroshi Arakawa for generously providing DT40 cell lines, and Ranjan
Sen and David Wilson III for critical reading of the manuscript. This
research was supported entirely by the Intramural Research Program of
the NIH, National Institute on Aging.
NR 36
TC 2
Z9 2
U1 0
U2 2
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 JUN
PY 2015
VL 30
BP 46
EP 52
DI 10.1016/j.dnarep.2015.03.004
PG 7
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA CI8VW
UT WOS:000355050800006
PM 25869824
ER
PT J
AU London, RE
AF London, Robert E.
TI The structural basis of XRCC1-mediated DNA repair
SO DNA REPAIR
LA English
DT Review
DE XRCC1; DNA repair; DNA polymerase beta; DNA ligase 3 alpha;
Single-strand break repair
ID STRAND-BREAK REPAIR; LIGASE-III-ALPHA; N-TERMINAL DOMAIN; PROTEOME-WIDE
IDENTIFICATION; POLYMERASE-BETA INTERACTION; NUCLEOTIDE EXCISION-REPAIR;
DISULFIDE BOND FORMATION; CELL NUCLEAR ANTIGEN; ANEMIA CORE COMPLEX;
TRIPLE-A-SYNDROME
AB Scaffold proteins play a central role in DNA repair by recruiting and organizing sets of enzymes required to perform multi-step repair processes. X-ray cross complementing group 1 protein (XRCC1) forms enzyme complexes optimized for single-strand break repair, but participates in other repair pathways as well. Available structural data for XRCC1 interactions is summarized and evaluated in terms of its proposed roles in DNA repair. Mutational approaches related to the abrogation of specific XRCC1 interactions are also discussed. Although substantial progress has been made in elucidating the structural basis for XRCC1 function, the molecular mechanisms of XRCC1 recruitment related to several proposed roles of the XRCC1 DNA repair complex remain undetermined. Published by Elsevier B.V.
C1 [London, Robert E.] NIEHS, Genome Integr & Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP London, RE (reprint author), NIEHS, Genome Integr & Struct Biol Lab, MR-01,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM london@niehs.nih.gov
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences [1ZIA ES050111-26]
FX This work was supported by the Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences, project number 1ZIA
ES050111-26.
NR 166
TC 10
Z9 10
U1 8
U2 26
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 JUN
PY 2015
VL 30
BP 90
EP 103
DI 10.1016/j.dnarep.2015.02.005
PG 14
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA CI8VW
UT WOS:000355050800010
PM 25795425
ER
PT J
AU Grillon, C
Quispe-Escudero, D
Mathur, A
Ernst, M
AF Grillon, Christian
Quispe-Escudero, David
Mathur, Ambika
Ernst, Monique
TI Mental Fatigue Impairs Emotion Regulation
SO EMOTION
LA English
DT Article
DE emotion regulation; mental fatigue; ego depletion; startle
ID SELF-REGULATION; NEGATIVE AFFECT; EGO DEPLETION; COGNITIVE REAPPRAISAL;
EXECUTIVE FUNCTIONS; LIMITED RESOURCES; WORKING-MEMORY; STARTLE REFLEX;
METAANALYSIS; MODULATION
AB Because healthy physical and mental functioning depends on the ability to regulate emotions, it is important to identify moderators of such regulations. Whether mental fatigue, subsequent to the depletion of cognitive resources, impairs explicit emotion regulation to negative stimuli is currently unknown. This study explored this possibility. In a within-subject design over 2 separate sessions, healthy individuals performed easy (control session) or difficult (depletion session) cognitive tasks. Subsequently, they were presented with neutral and negative pictures, with instructions to either maintain or regulate (i.e., reduce) the emotions evoked by the pictures. Emotional reactivity was probed with the startle reflex. The negative pictures evoked a similar aversive state in the control and depletion sessions as measured by startle potentiation. However, subjects were able to down-regulate their aversive state only in the control session, not in the depletion session. These results indicate that mental fatigue following performance of cognitive tasks impairs emotion regulation without affecting emotional reactivity. These findings suggest that mental fatigue needs to be incorporated into models of emotion regulation.
C1 [Grillon, Christian; Quispe-Escudero, David; Mathur, Ambika; Ernst, Monique] NIMH, Sect Neurobiol Fear & Anxiety, Bethesda, MD 20892 USA.
RP Grillon, C (reprint author), NIMH, MAP, 15K North Dr,Bldg 15K,Room 203,MSC 2670, Bethesda, MD 20892 USA.
EM Christian.grillon@nih.gov
FU National Institute of Mental Health [MH002798, 01-M-0185]
FX Financial support for this study was provided by the Intramural Research
Program of the National Institute of Mental Health (MH002798, Protocol
01-M-0185). We declare that, except for income received from the primary
employer, no financial support or compensation has been received from
any individual or corporate entity over the past 3 years for research or
professional service and that there are no personal financial holdings
that could be perceived as constituting a potential conflict of
interest.
NR 43
TC 0
Z9 0
U1 2
U2 28
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 1528-3542
EI 1931-1516
J9 EMOTION
JI Emotion
PD JUN
PY 2015
VL 15
IS 3
BP 383
EP 389
DI 10.1037/emo0000058
PG 7
WC Psychology, Experimental
SC Psychology
GA CI1ZS
UT WOS:000354544600013
PM 25706833
ER
PT J
AU Kennedy, DA
Dukic, V
Dwyer, G
AF Kennedy, David A.
Dukic, Vanja
Dwyer, Greg
TI Combining principal component analysis with parameter line-searches to
improve the efficacy of Metropolis-Hastings MCMC
SO ENVIRONMENTAL AND ECOLOGICAL STATISTICS
LA English
DT Article
DE Birth-death model; MCMC; Parameter line-search; Survival-time data;
Within-host model
ID APPROXIMATE BAYESIAN COMPUTATION; NUCLEAR POLYHEDROSIS-VIRUS;
SURVIVAL-TIME RELATIONSHIP; MONTE-CARLO METHODS; DATA CLONING;
STOCHASTIC SIMULATION; HELIOTHIS-VIRESCENS; POPULATION-DYNAMICS;
INDEPENDENT ACTION; MODELS
AB When Markov chain Monte Carlo (MCMC) algorithms are used with complex mechanistic models, convergence times are often severely compromised by poor mixing rates and a lack of computational power. Methods such as adaptive algorithms have been developed to improve mixing, but these algorithms are typically highly sophisticated, both mathematically and computationally. Here we present a nonadaptive MCMC algorithm, which we term line-search MCMC, that can be used for efficient tuning of proposal distributions in a highly parallel computing environment, but that nevertheless requires minimal skill in parallel computing to implement. We apply this algorithm to make inferences about dynamical models of the growth of a pathogen (baculovirus) population inside a host (gypsy moth, Lymantria dispar). The line-search MCMC appeal rests on its ease of implementation, and its potential for efficiency improvements over classical MCMC in a highly parallel setting, which makes it especially useful for ecological models.
C1 [Kennedy, David A.; Dwyer, Greg] Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA.
[Kennedy, David A.] Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Kennedy, David A.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Dukic, Vanja] Univ Colorado, Dept Appl Math, Boulder, CO 80309 USA.
RP Dwyer, G (reprint author), Univ Chicago, Dept Ecol & Evolut, 940 E 57Th St, Chicago, IL 60637 USA.
EM dkenned1@gmail.com; Vanja.Dukic@colorado.edu; gdwyer@uchicago.edu
RI Dwyer, Greg/L-1134-2015
OI Dwyer, Greg/0000-0002-7387-2075
FU ARCS fellowship; GAANN training grant at the University of Chicago;
RAPIDD program of the Science and Technology Directorate, Department of
Homeland Security and Fogarty International Center, National Institutes
of Health (NIH); NIH [R01GM096655]; [NSF-DEB 1316334]; [NSF-GEO
1211668]
FX DAK was supported by an ARCS fellowship, a GAANN training grant while at
the University of Chicago, and the RAPIDD program of the Science and
Technology Directorate, Department of Homeland Security and Fogarty
International Center, National Institutes of Health (NIH). GD and VD
were supported by NIH Grant R01GM096655. VD was also supported by Grants
NSF-DEB 1316334 and NSF-GEO 1211668. We thank two anonymous reviewers
for comments that substantially improved the manuscript.
NR 78
TC 0
Z9 0
U1 2
U2 11
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1352-8505
EI 1573-3009
J9 ENVIRON ECOL STAT
JI Environ. Ecol. Stat.
PD JUN
PY 2015
VL 22
IS 2
BP 247
EP 274
DI 10.1007/s10651-014-0297-0
PG 28
WC Environmental Sciences; Mathematics, Interdisciplinary Applications;
Statistics & Probability
SC Environmental Sciences & Ecology; Mathematics
GA CI2ZW
UT WOS:000354618100003
ER
PT J
AU Tegla, CA
Cudrici, CD
Nguyen, V
Danoff, J
Kruszewski, AM
Boodhoo, D
Mekala, AP
Vlaicu, SI
Chen, C
Rus, V
Badea, TC
Rus, H
AF Tegla, Cosmin A.
Cudrici, Cornelia D.
Vinh Nguyen
Danoff, Jacob
Kruszewski, Adam M.
Boodhoo, Dallas
Mekala, Armugam P.
Vlaicu, Sonia I.
Chen, Ching
Rus, Violeta
Badea, Tudor C.
Rus, Horea
TI RGC-32 is a novel regulator of the T-lymphocyte cell cycle
SO EXPERIMENTAL AND MOLECULAR PATHOLOGY
LA English
DT Article
DE T-cells; Cell cycle; RGC-32; Knockout mouse; Akt; IL-2
ID FORKHEAD TRANSCRIPTION FACTOR; GROWTH-FACTOR-BETA; RESPONSE GENE;
COMPLEMENT 32; MULTIPLE-SCLEROSIS; ACTIVATION; AKT; P27(KIP1); SURVIVAL;
KINASE
AB We have previously shown that RGC-32 is involved in cell cycle regulation in vitro. To define the in vivo role of RGC-32, we generated RGC-32 knockout mice. These mice developed normally and did not spontaneously develop overt tumors. To assess the effect of RGC-32 deficiency on cell cycle activation in T cells, we determined the proliferative rates of CD4(+) and CD8(+) T cells from the spleens of RGC-32(-/-) mice, as compared to wild-type (WT, RGC-32(+/+)) control mice. After stimulation with anti-CD3/anti-CD28, CD4+ T cells from RGC-32(-/-) mice displayed a significant increase in [H-3]-thymidine incorporation when compared to WT mice. In addition, both CD4(+) and CD8(+) T cells from RGC-32(-/-) mice displayed a significant increase in the proportion of proliferating Ki67(+) cells, indicating that in T cells, RGC-32 has an inhibitory effect on cell cycle activation induced by T-cell receptor/CD28 engagement. Furthermore, Akt and FOXO1 phosphorylation induced in stimulated CD4(+) T-cells from RGC-32(-/-) mice were significantly higher, indicating that RGC-32 inhibits cell cycle activation by suppressing FOXO1 activation. We also found that IL-2 mRNA and protein expression were significantly increased in RGC-32(-/-) CD4(+) T cells when compared to RGC-32(+/+) CD4(+) T cells. In addition, the effect of RGC-32 on the cell cycle and IL-2 expression was inhibited by pretreatment of the samples with LY294002, indicating a role for phosphatidylinositol 3-kinase (PI3K). Thus, RGC-32 is involved in controlling the cell cycle of T cells in vivo, and this effect is mediated by IL-2 in a PI3K-dependent fashion. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Tegla, Cosmin A.; Cudrici, Cornelia D.; Danoff, Jacob; Kruszewski, Adam M.; Boodhoo, Dallas; Mekala, Armugam P.; Vlaicu, Sonia I.; Rus, Horea] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA.
[Tegla, Cosmin A.; Rus, Horea] Vet Adm Maryland Hlth Care Syst, Res Serv, Baltimore, MD USA.
[Vinh Nguyen; Rus, Violeta] Univ Maryland, Sch Med, Dept Med, Div Clin Immunol & Rheumatol, Baltimore, MD 21201 USA.
[Chen, Ching] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.
[Badea, Tudor C.] NEI, Retinal Circuit Dev & Genet Unit, N NRL, Bethesda, MD 20892 USA.
[Vlaicu, Sonia I.] Iuliu Hatieganu Univ Med & Pharm, Dept Internal Med, Cluj Napoca, Romania.
[Rus, Horea] Vet Adm Multiple Sclerosis Ctr Excellence, Baltimore, MD USA.
RP Rus, H (reprint author), Univ Maryland, Sch Med, Dept Neurol, 655 W Baltimore St,BRB 12-033, Baltimore, MD 21201 USA.
EM hrus@umaryland.edu
FU Veterans Administration [BX001458, IMMB-002-065]; POSDRU grant
[159/1.5/S/138776]
FX We thank Dr. Deborah McClellan for editing this manuscript. This work
was supported in part by Veterans Administration Merit Awards BX001458
(to H.R.) and IMMB-002-065 (to H.R.). Dr Sonia Vlaicu's work was
partially financed by POSDRU grant no. 159/1.5/S/138776 with the title:
"Model colaborativ institutional pentru translatarea cercetarii
stiintifice biomedicale in practica clinica-TRANSCENT". Cosmin A. Tegla
and Cornelia D. Cudrici have contributed equally to this manuscript.
NR 33
TC 3
Z9 3
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4800
EI 1096-0945
J9 EXP MOL PATHOL
JI Exp. Mol. Pathol.
PD JUN
PY 2015
VL 98
IS 3
BP 328
EP 337
DI 10.1016/j.yexmp.2015.03.011
PG 10
WC Pathology
SC Pathology
GA CI6YE
UT WOS:000354909300002
PM 25770350
ER
PT J
AU Hayakawa, EH
Tokumasu, F
Usukura, J
Matsuoka, H
Tsuboi, T
Wellems, TE
AF Hayakawa, Eri H.
Tokumasu, Fuyuki
Usukura, Jiro
Matsuoka, Hiroyuki
Tsuboi, Takafumi
Wellems, Thomas E.
TI Imaging of the subsurface structures of "unroofed" Plasmodium
falciparum-infected erythrocytes
SO EXPERIMENTAL PARASITOLOGY
LA English
DT Article
DE Malaria parasite; Maurer's clefts; Cytoskeleton; Electron microscopy;
Freeze etching
ID RED-BLOOD-CELLS; VESICLE-MEDIATED TRAFFICKING; PLASMA-MEMBRANE
INTERFACE; MAURERS CLEFT ORGANELLES; ETCH ELECTRON TOMOGRAPHY;
ATOMIC-FORCE MICROSCOPY; PARASITE PROTEINS; MALARIA PARASITES;
SURFACE-MEMBRANE; CYTOSKELETON
AB Intraerythrocytic stages of Plasmodium falciparum parasites modify the membranes of their host erythrocytes with numerous expressed proteins. They also install new membranous structures in the erythrocyte cytoplasm, including Maurer's clefts (MC) and a tubulovesicular network. These structures support molecular trafficking processes that are necessary for the growth and multiplication of P. falciparum intraerythrocytic stages. To study the morphology and organization of these modifications, we prepared samples of P. falciparum-infected erythrocytes by 'unroofing' techniques and examined them by transmission electron microscopy. Images of the 'unroofed' parasitized erythrocytes feature cytoskeleton alterations and the presence of new membranous structures generated by P. falciparum, including small vesicles and MC connected by extensions to the inner erythrocyte membrane. Non-parasitized erythrocytes showed no evidence of these structures or extensions. In further experiments, we observed a relative absence of MC and extensions after treatment of parasitized erythrocytes with aluminum tetrafluoride (AlF4-), an inhibitor of vesicle trafficking. The morphology and physical location of MC, extensions and small vesicles in unroofed specimens are consistent with the role of these structures in the trafficking of P. falciparum proteins to the surface of parasitized erythrocytes. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Hayakawa, Eri H.; Matsuoka, Hiroyuki] Jichi Med Univ, Dept Infect & Immun, Lab Med Zool & Parasitol, Shimotsuke, Tochigi 3290498, Japan.
[Tokumasu, Fuyuki] Univ Tokyo, Grad Sch Med, Dept Lipid, Bunkyo Ku, Tokyo 1130033, Japan.
[Usukura, Jiro] Nagoya Univ, EcoTopia Sci Inst, Div Integrated Project, Nagoya, Aichi 4648603, Japan.
[Tsuboi, Takafumi] Ehime Univ, Proteo Sci Ctr, Div Malaria Res, Matsuyama, Ehime 7908577, Japan.
[Wellems, Thomas E.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
RP Hayakawa, EH (reprint author), Jichi Med Univ, Dept Infect & Immun, Lab Med Zool & Parasitol, Shimotsuke, Tochigi 3290498, Japan.
EM erihayakawa@jichi.ac.jp; TWELLEMS@niaid.nih.gov
OI Tokumasu, Fuyuki/0000-0003-2790-1071; Hayakawa, Eri/0000-0001-5067-2161;
Matsuoka, Hiroyuki/0000-0001-8839-0012
FU NIAID, NIH; JSPS KAKENHI [24500992]; Ohyama Health Foundation Inc.
FX We thank Dr. Motomi Toni, Division of Molecular Parasitology,
Proteo-Science Center, Ehime University, for discussions and advice on
electron microscopy of the inner membrane structure of parasitized
erythrocytes. We are grateful to Japanese Red Cross Society for
supplying human erythrocytes. This research was supported in part by the
Intramural Research Program of the NIAID, NIH. E.H.H. was partially
supported by JSPS KAKENHI (Grant-in-Aid for Scientific Research (C),
grant number 24500992) and the Ohyama Health Foundation Inc..
NR 36
TC 2
Z9 2
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4894
EI 1090-2449
J9 EXP PARASITOL
JI Exp. Parasitol.
PD JUN
PY 2015
VL 153
BP 174
EP 179
DI 10.1016/j.exppara.2015.03.021
PG 6
WC Parasitology
SC Parasitology
GA CI4XA
UT WOS:000354756000024
PM 25825251
ER
PT J
AU Hsu, L
Jeon, J
Brenner, H
Gruber, SB
Schoen, RE
Berndt, SI
Chan, AT
Chang-Claude, J
Du, MM
Gong, J
Harrison, TA
Hayes, RB
Hoffmeister, M
Hutter, CM
Lin, Y
Nishihara, R
Ogino, S
Prentice, RL
Schumacher, FR
Seminara, D
Slattery, ML
Thomas, DC
Thornquist, M
Newcomb, PA
Potter, JD
Zheng, YY
White, E
Peters, U
AF Hsu, Li
Jeon, Jihyoun
Brenner, Hermann
Gruber, Stephen B.
Schoen, Robert E.
Berndt, Sonja I.
Chan, Andrew T.
Chang-Claude, Jenny
Du, Mengmeng
Gong, Jian
Harrison, Tabitha A.
Hayes, Richard B.
Hoffmeister, Michael
Hutter, Carolyn M.
Lin, Yi
Nishihara, Reiko
Ogino, Shuji
Prentice, Ross L.
Schumacher, Fredrick R.
Seminara, Daniela
Slattery, Martha L.
Thomas, Duncan C.
Thornquist, Mark
Newcomb, Polly A.
Potter, John D.
Zheng, Yingye
White, Emily
Peters, Ulrike
CA Colorectal Transdisciplinary
Genetics Epidemiology Colorectal
TI A Model to Determine Colorectal Cancer Risk Using Common Genetic
Susceptibility Loci
SO GASTROENTEROLOGY
LA English
DT Article
DE Risk Determination; Genome-Wide Association Study; Colorectal Cancer
Screening; Risk Stratification
ID GENOME-WIDE ASSOCIATION; MUTATION CARRIERS; AMERICAN-COLLEGE;
PROSTATE-CANCER; CHROMOSOME 8Q24; COLON-CANCER; TASK-FORCE; PREDICTION;
METAANALYSIS; HEALTH
AB BACKGROUND & AIMS: Risk for colorectal cancer (CRC) can be greatly reduced through screening. To aid in the development of screening strategies, we refined models designed to determine risk of CRC by incorporating information from common genetic susceptibility loci. METHODS: By using data collected from more than 12,000 participants in 6 studies performed from 1990 through 2011 in the United States and Germany, we developed risk determination models based on sex, age, family history, genetic risk score (number of risk alleles carried at 27 validated common CRC susceptibility loci), and history of endoscopic examinations. The model was validated using data collected from approximately 1800 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, conducted from 1993 through 2001 in the United States. RESULTS: We identified a CRC genetic risk score that independently predicted which patients in the training set would develop CRC. Compared with determination of risk based only on family history, adding the genetic risk score increased the discriminatory accuracy from 0.51 to 0.59 (P = .0028) for men and from 0.52 to 0.56 (P = .14) for women. We calculated age-and sex-specific 10-year CRC absolute risk estimates based on the number of risk alleles, family history, and history of endoscopic examinations. A model that included a genetic risk score better determined the recommended starting age for screening in subjects with and without family histories of CRC. The starting age for high-risk men (family history of CRC and genetic risk score, 90%) was 42 years, and for low-risk men (no family history of CRC and genetic risk score, 10%) was 52 years. For men with no family history and a high genetic risk score (90%), the starting age would be 47 years; this is an intermediate value that is 5 years earlier than it would be for men with a genetic risk score of 10%. Similar trends were observed in women. CONCLUSIONS: By incorporating information on CRC risk alleles, we created a model to determine the risk for CRC more accurately. This model might be used to develop screening and prevention strategies.
C1 [Hsu, Li; Jeon, Jihyoun; Du, Mengmeng; Gong, Jian; Harrison, Tabitha A.; Lin, Yi; Prentice, Ross L.; Thornquist, Mark; Newcomb, Polly A.; Potter, John D.; Zheng, Yingye; White, Emily; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA.
[Brenner, Hermann; Hoffmeister, Michael] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Brenner, Hermann] German Canc Consortium, Heidelberg, Germany.
[Gruber, Stephen B.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Dept Med & Epidemiol, Pittsburgh, PA USA.
[Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Hutter, Carolyn M.; Seminara, Daniela] NCI, Div Canc Control & Populat Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Chan, Andrew T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA USA.
[Chan, Andrew T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA.
[Hayes, Richard B.] NYU, Sch Med, Dept Populat Hlth, Div Epidemiol, New York, NY USA.
[Nishihara, Reiko] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Nishihara, Reiko] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Ogino, Shuji] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Schumacher, Fredrick R.; Thomas, Duncan C.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Slattery, Martha L.] Univ Utah, Dept Internal Med, Hlth Sci Ctr, Salt Lake City, UT 84112 USA.
[Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand.
RP Hsu, L (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave North,M2-B500, Seattle, WA 98109 USA.
EM lih@fhcrc.org; upeters@fhcrc.org
RI Hoffmeister, Michael/B-5745-2012; Brenner, Hermann/B-4627-2017;
OI Hoffmeister, Michael/0000-0002-8307-3197; Brenner,
Hermann/0000-0002-6129-1572; Potter, John/0000-0001-5439-1500; Hayes,
Richard/0000-0002-0918-661X
FU National Institutes of Health [P01 CA53996, R01AG14358, R25CA094880, U01
HG004446, GEI U01 HG 004438]; Genetics and Epidemiology of Colorectal
Cancer Consortium: National Cancer Institute; Genetics and Epidemiology
of Colorectal Cancer Consortium: National Institutes of Health; Genetics
and Epidemiology of Colorectal Cancer Consortium: US Department of
Health and Human Services [U01 CA137088, R01 CA059045]; Colorectal
Transdisciplinary Study: National Cancer Institute, National Institutes
of Health under Requests for Applications [CA-09-002 (U19 CA148107)];
Genes, Environment and Health Initiative [Z01 CP 010200]
FX This work was supported by the National Institutes of Health (P01
CA53996, R01AG14358, and R25CA094880). The grant support for individual
studies was as follows: Genetics and Epidemiology of Colorectal Cancer
Consortium: National Cancer Institute, National Institutes of Health,
and US Department of Health and Human Services (U01 CA137088 and R01
CA059045); Colorectal Transdisciplinary Study: National Cancer
Institute, National Institutes of Health under Requests for Applications
#CA-09-002 (U19 CA148107). The content of this manuscript does not
necessarily reflect the views or policies of the National Cancer
Institute or any of the collaborating centers in the Colorectal
Transdisciplinary Study, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government or the
Colorectal Transdisciplinary Study; Darmkrebs: Chancen der Verhutung
durch Screening: German Research Council (Deutsche
Forschungsgemeinschaft, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, and CH
117/1-1), and the German Federal Ministry of Education and Research
(01KH0404 and 01ER0814); Diet, Activity and Lifestyle Study: National
Institutes of Health (R01 CA48998 to M.L.S.); Health Professionals
Follow-up Study: National Institutes of Health (P01 CA 055075, UM1
CA167552, R01 137178, and P50 CA 127003); Nurses' Health Study: National
Institutes of Health (R01 CA137178, P01 CA 087969, and P50 CA 127003);
Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial:
Intramural Research Program of the Division of Cancer Epidemiology and
Genetics and by contracts from the Division of Cancer Prevention,
National Cancer Institute, National Institutes of Health, and the
Department of Health and Human Services. In addition, a subset of
control samples were genotyped as part of the Cancer Genetic Markers of
Susceptibility prostate cancer genome-wide association study, Colon
Cancer Genetic Markers of Susceptibility pancreatic cancer scan
(PanScan), and the Lung Cancer and Smoking study. The prostate and
PanScan study data sets were accessed with appropriate approval through
the database of Genotypes and Phenotypes online resource
(http://cgems.cancer.gov/data/) accession numbers phs000207.v1.p1 and
phs000206.v3.p2, respectively, and the lung data sets were accessed from
the dbGaP website (http://www.ncbi.nlm.nih.gov/gap) through accession
number phs000093.v2.p2. Funding for the Lung Cancer and Smoking study
was provided by the National Institutes of Health and the Genes,
Environment and Health Initiative Z01 CP 010200, National Institutes of
Health U01 HG004446 and GEI U01 HG 004438. For the lung study, the
GENEVA Coordinating Center provided assistance with genotype cleaning
and general study coordination, and the Johns Hopkins University Center
for Inherited Disease Research conducted genotyping; Vitamins And
Lifestyle Study: National Institutes of Health (K05 CA154337); Women's
Health Initiative: the National Heart, Lung, and Blood Institute,
National Institutes of Health, US Department of Health and Human
Services through contracts HHSN268201100046C, HHSN268201100001C,
HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and
HHSN271201100004C.
NR 60
TC 10
Z9 10
U1 1
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
EI 1528-0012
J9 GASTROENTEROLOGY
JI Gastroenterology
PD JUN
PY 2015
VL 148
IS 7
BP 1330
EP +
DI 10.1053/j.gastro.2015.02.010
PG 24
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CI8IC
UT WOS:000355014700025
PM 25683114
ER
PT J
AU Chalasani, N
Bonkovsky, HL
Fontana, R
Lee, W
Stolz, A
Talwalkar, J
Reddy, KR
Watkins, PB
Navarro, V
Barnhart, H
Gu, JZ
AF Chalasani, Naga
Bonkovsky, Herbert L.
Fontana, Robert
Lee, William
Stolz, Andrew
Talwalkar, Jayant
Reddy, K. Rajendar
Watkins, Paul B.
Navarro, Victor
Barnhart, Huiman
Gu, Jiezhun
CA US Drug Induced Liver Injury Netwo
TI Features and Outcomes of 899 Patients With Drug-Induced Liver Injury:
The DILIN Prospective Study
SO GASTROENTEROLOGY
LA English
DT Article
DE Idiosyncratic; DILI; DILIN; Toxicity; Medication
ID CAUSALITY ASSESSMENT; ADVERSE REACTIONS; HEPATOTOXICITY; NETWORK;
POPULATION; EXPERIENCE; HEPATITIS; CHILDREN; FAILURE; SERIES
AB BACKGROUND & AIMS: The Drug-Induced Liver Injury Network is conducting a prospective study of patients with DILI in the United States. We present characteristics and subgroup analyses from the first 1257 patients enrolled in the study. METHODS: In an observational longitudinal study, we began collecting data on eligible individuals with suspected DILI in 2004, following them for 6 months or longer. Subjects were evaluated systematically for other etiologies, causes, and severity of DILI. RESULTS: Among 1257 enrolled subjects with suspected DILI, the causality was assessed in 1091 patients, and 899 were considered to have definite, highly likely, or probable DILI. Ten percent of patients died or underwent liver transplantation, and 17% had chronic liver injury. In the 89 patients (10%) with pre-existing liver disease, DILI appeared to be more severe than in those without (difference not statistically significant; P = .09) and mortality was significantly higher (16% vs 5.2%; P < .001). Azithromycin was the implicated agent in a higher proportion of patients with pre-existing liver disease compared with those without liver disease (6.7% vs 1.5%; P = .006). Forty-one cases with latency <= 7 days were caused predominantly by antimicrobial agents (71%). Two most common causes for 60 DILI cases with latency >365 days were nitrofurantoin (25%) or minocycline (17%). There were no differences in outcomes of patients with short vs long latency of DILI. Compared with individuals younger than 65 years, individuals 65 years or older (n = 149) were more likely to have cholestatic injury, although mortality and rate of liver transplantation did not differ. Nine patients (1%) had concomitant severe skin reactions; implicated agents were lamotrigine, azithromycin, carbamazepine, moxifloxacin, cephalexin, diclofenac, and nitrofurantoin. Four of these patients died. CONCLUSIONS: Mortality from DILI is significantly higher in individuals with pre-existing liver disease or concomitant severe skin reactions compared with patients without. Additional studies are needed to confirm the association between azithromycin and increased DILI in patients with chronic liver disease. Older age and short or long latencies are not associated with DILI mortality.
C1 [Chalasani, Naga] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Bonkovsky, Herbert L.] Carolinas Hlth Care Syst, Charlotte, NC USA.
[Fontana, Robert] Univ Michigan, Ann Arbor, MI 48109 USA.
[Lee, William] Univ Texas Southwestern, Dallas, TX USA.
[Stolz, Andrew] Univ So Calif, Los Angeles, CA USA.
[Talwalkar, Jayant] Mayo Clin, Rochester, MN USA.
[Reddy, K. Rajendar] Univ Penn, Philadelphia, PA 19104 USA.
[Watkins, Paul B.] Univ N Carolina, Chapel Hill, NC USA.
[Navarro, Victor] Albert Einstein Med Ctr, Philadelphia, PA 19141 USA.
[Barnhart, Huiman; Gu, Jiezhun] Duke Clin Res Inst, Raleigh, NC USA.
[Gu, Jiezhun] NIDDK, Bethesda, MD 20892 USA.
RP Chalasani, N (reprint author), Indiana Univ Sch Med, Div Gastroenterol & Hepatol, 703 Rotary Circle,Suite 225, Indianapolis, IN 46202 USA.
RI de Boer, Ynto/D-9242-2013;
OI de Boer, Ynto/0000-0002-4066-7593; Ghabril, Marwan/0000-0002-4784-3246
FU National Institute of Diabetes and Digestive and Kidney Diseases of the
National Institutes of Health (NIH) [U01-DK065176, U01-DK065201,
U01-DK065184, U01-DK065211, U01DK065193, U01-DK065238, U01-DK083023,
U01-DK083027, U01-DK082992, U01-DK083020]; CTSA [UL1 RR025761, UL1
RR025747, UL1 RR024134, UL1 RR024986, UL1 RR024982, UL1 RR024150];
Intramural Research Program of the National Cancer Institute, National
Institutes of Health (NIH)
FX The DILIN (https://dilin.dcri.duke.edu/) is supported by the National
Institute of Diabetes and Digestive and Kidney Diseases of the National
Institutes of Health (NIH) as a Cooperative Agreement (U01s) under
grants: U01-DK065176 (Duke), U01-DK065201 (UNC), U01-DK065184
(Michigan), U01-DK065211 (Indiana), U01DK065193 (UConn), U01-DK065238
(UCSF/CPMC), U01-DK083023 (UTSW), U01-DK083027 (TJH/UPenn), U01-DK082992
(Mayo), U01-DK083020 (USC). Additional funding is provided by CTSA
Grants: UL1 RR025761 (Indiana), UL1 RR025747 (UNC), UL1 RR024134
(UPenn), UL1 RR024986 (Michigan), UL1 RR024982 (UTSW), UL1 RR024150
(Mayo) and by the Intramural Research Program of the National Cancer
Institute, National Institutes of Health (NIH). A complete list of
participants in DILIN is given in the Acknowledgments.
NR 34
TC 51
Z9 56
U1 1
U2 17
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
EI 1528-0012
J9 GASTROENTEROLOGY
JI Gastroenterology
PD JUN
PY 2015
VL 148
IS 7
BP 1340
EP +
DI 10.1053/j.gastro.2015.03.006
PG 20
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CI8IC
UT WOS:000355014700026
PM 25754159
ER
PT J
AU Palmore, TN
Barrett, K
Michelin, A
Ramsburg, A
Lee, LM
Davey, RT
Henderson, DK
AF Palmore, Tara N.
Barrett, Kevin
Michelin, Angela
Ramsburg, Amanda
Lee, Laura M.
Davey, Richard T., Jr.
Henderson, David K.
TI Challenges in Managing Patients who have Suspected or Confirmed Ebola
Virus Infection at the National Institutes of Health
SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY
LA English
DT Editorial Material
C1 [Palmore, Tara N.; Michelin, Angela; Ramsburg, Amanda] NIH, Hosp Epidemiol Serv, Ctr Clin, Bethesda, MD 20892 USA.
[Barrett, Kevin] NIAID, Intramural Clin Management & Operat Branch, NIH, Bethesda, MD 20892 USA.
[Lee, Laura M.; Henderson, David K.] NIH, Clin Care, Ctr Clin, Bethesda, MD 20892 USA.
[Davey, Richard T., Jr.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Henderson, DK (reprint author), NIH, Clin Care, Ctr Clin, Bldg 10 Room 6-1480,10 Ctr Dr, Bethesda, MD 20892 USA.
EM dkh@nih.gov
NR 0
TC 1
Z9 1
U1 2
U2 5
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0899-823X
EI 1559-6834
J9 INFECT CONT HOSP EP
JI Infect. Control Hosp. Epidemiol.
PD JUN
PY 2015
VL 36
IS 6
BP 623
EP 626
DI 10.1017/ice.2015.60
PG 4
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA CI7XZ
UT WOS:000354981400001
PM 25994322
ER
PT J
AU Lukacz, ES
Warren, LK
Richter, HE
Brubaker, L
Barber, MD
Norton, P
Weidner, AC
Nguyen, JN
Gantz, MG
Meikle, SF
AF Lukacz, E. S.
Warren, L. K.
Richter, H. E.
Brubaker, L.
Barber, M. D.
Norton, P.
Weidner, A. C.
Nguyen, J. N.
Gantz, M. G.
Meikle, S. F.
TI LONG-TERM QUALITY OF LIFE AND SEXUAL FUNCTION AFTER VAGINAL SURGERY FOR
APICAL PROLAPSE
SO INTERNATIONAL UROGYNECOLOGY JOURNAL
LA English
DT Article; Proceedings Paper
CT 40th Annual Meeting of the International-Urogynecological-Association
CY JUN 09-13, 2015
CL Nice, FRANCE
SP Int Urogynecol Assoc
C1 [Lukacz, E. S.] UC San Diego Hlth Syst, La Jolla, CA USA.
[Warren, L. K.; Gantz, M. G.] RTI Intl, Social Stat & Environm Sci, Res Triangle Pk, NC USA.
[Richter, H. E.] Univ Alabama Birmingham, Birmingham, AL USA.
[Brubaker, L.] Loyola Univ Chicago, Maywood, IL USA.
[Barber, M. D.] Cleveland Clin, Cleveland, OH 44106 USA.
[Norton, P.] Univ Utah, Salt Lake City, UT USA.
[Weidner, A. C.] Duke Univ, Durham, NC USA.
[Nguyen, J. N.] Kaiser Permanente So Calif, Obstet & Gynecol, Downey, CA USA.
[Meikle, S. F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-3462
EI 1433-3023
J9 INT UROGYNECOL J
JI Int. Urogynecol. J.
PD JUN
PY 2015
VL 26
SU 1
MA OP 089
BP S117
EP S118
PG 2
WC Obstetrics & Gynecology; Urology & Nephrology
SC Obstetrics & Gynecology; Urology & Nephrology
GA CI3AF
UT WOS:000354619100090
ER
PT J
AU Weidner, AC
Barber, MD
Markland, AD
Rahn, DD
Hsu, Y
Mueller, ER
Jakus-Waldman, S
Dyer, KY
Warren, LK
Gantz, M
Meikle, S
AF Weidner, A. C.
Barber, M. D.
Markland, A. D.
Rahn, D. D.
Hsu, Y.
Mueller, E. R.
Jakus-Waldman, S.
Dyer, K. Y.
Warren, L. K.
Gantz, M.
Meikle, S.
TI PERIOPERATIVE BEHAVIORAL THERAPY & PELVIC MUSCLE STRENGTHENING DOES NOT
IMPROVE QUALITY OF LIFE AFTER APICAL PROLAPSE SURGERY: A RANDOMIZED
CONTROLLED TRIAL
SO INTERNATIONAL UROGYNECOLOGY JOURNAL
LA English
DT Article; Proceedings Paper
CT 40th Annual Meeting of the International-Urogynecological-Association
CY JUN 09-13, 2015
CL Nice, FRANCE
SP Int Urogynecol Assoc
C1 [Weidner, A. C.] Duke Univ, Durham, NC USA.
[Barber, M. D.] Cleveland Clin, Cleveland, OH 44106 USA.
[Markland, A. D.] Univ Alabama, Birmingham, VA USA.
[Markland, A. D.] Univ Alabama Birmingham, Birmingham, AL USA.
[Rahn, D. D.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Hsu, Y.] Univ Utah, Salt Lake City, UT USA.
[Mueller, E. R.] Loyola Univ, Chicago Stritch Sch Med, Maywood, IL 60153 USA.
[Jakus-Waldman, S.] Southern Calif Kaiser Permanente, Downey, CA USA.
[Dyer, K. Y.] Kaiser Permanente, San Diego, CA USA.
[Warren, L. K.; Gantz, M.] RTI Int, Res Triangle Pk, NC USA.
[Meikle, S.] NIH, Bethesda, MD 20892 USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-3462
EI 1433-3023
J9 INT UROGYNECOL J
JI Int. Urogynecol. J.
PD JUN
PY 2015
VL 26
SU 1
MA PP 34
BP S59
EP S61
PG 3
WC Obstetrics & Gynecology; Urology & Nephrology
SC Obstetrics & Gynecology; Urology & Nephrology
GA CI3AF
UT WOS:000354619100035
ER
PT J
AU Do, K
Speranza, G
Bishop, R
Khin, S
Rubinstein, L
Kinders, RJ
Datiles, M
Eugeni, M
Lam, MH
Doyle, LA
Doroshow, JH
Kummar, S
AF Khanh Do
Speranza, Giovanna
Bishop, Rachel
Khin, Sonny
Rubinstein, Larry
Kinders, Robert J.
Datiles, Manuel
Eugeni, Michelle
Lam, Michael H.
Doyle, L. Austin
Doroshow, James H.
Kummar, Shivaani
TI Biomarker-driven phase 2 study of MK-2206 and selumetinib (AZD6244,
ARRY-142886) in patients with colorectal cancer
SO INVESTIGATIONAL NEW DRUGS
LA English
DT Article
DE MK-2206; Selumetinib; pAKT; pERK; Colorectal carcinoma
ID AKT INHIBITOR; SOLID TUMORS; IN-VIVO; KRAS; TRIALS
AB Purpose PI3K/AKT/mTOR and RAS/RAF/MEK pathways are frequently dysregulated in colorectal cancer (CRC). We conducted a biomarker-driven trial of the combination of MK-2206, an allosteric AKT 1/2/3 inhibitor, and selumetinib, a MEK 1/2 inhibitor, in patients with CRC to evaluate inhibition of phosphorylated ERK (pERK) and AKT (pAKT) in paired tumor biopsies. Patients and Methods Adult patients with advanced CRC were enrolled in successive cohorts stratified by KRAS mutation status. Initially, 12 patients received oral MK-2206 90 mg weekly with oral selumetinib 75 mg daily in 28-day cycles. Following an interim analysis, the doses of MK-2206 and selumetinib were increased to 135 mg weekly and 100 mg daily, respectively. Paired tumor biopsies were evaluated for target modulation. Results Common toxicities were gastrointestinal, hepatic, dermatologic, and hematologic. Of 21 patients enrolled, there were no objective responses. Target modulation did not achieve the pre-specified criteria of dual 70 % inhibition of pERK and pAKT levels in paired tumor biopsies. Conclusion Despite strong scientific rationale and preclinical data, clinical activity was not observed. The desired level of target inhibition was not achieved. Overlapping toxicities limited the ability to dose escalate to achieve exposures likely needed for clinical activity, highlighting the challenges in developing optimal combinations of targeted agents.
C1 [Khanh Do; Speranza, Giovanna; Rubinstein, Larry; Eugeni, Michelle; Doyle, L. Austin; Doroshow, James H.; Kummar, Shivaani] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Bishop, Rachel; Datiles, Manuel] NEI, Bethesda, MD 20892 USA.
[Khin, Sonny; Kinders, Robert J.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Lam, Michael H.] Merck Res Labs Oncol, Boston, MA USA.
RP Kummar, S (reprint author), NCI, Div Canc Treatment & Diag, 31 Ctr Dr,Bldg 31,Rm3A44, Bethesda, MD 20892 USA.
EM kummars@mail.nih.gov
OI Datiles, Manuel III B./0000-0003-4660-1664
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E, N01-CM-2011-00032]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contracts No. HHSN261200800001E and N01-CM-2011-00032. 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. MK-2206 and selumetinib were generously provided by
Merck and AstraZeneca, respectively, under a collaborative agreement
with the Division of Cancer Treatment and Diagnosis, National Cancer
Institute, NIH.
NR 17
TC 20
Z9 20
U1 1
U2 7
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-6997
EI 1573-0646
J9 INVEST NEW DRUG
JI Invest. New Drugs
PD JUN
PY 2015
VL 33
IS 3
BP 720
EP 728
DI 10.1007/s10637-015-0212-z
PG 9
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA CI3AZ
UT WOS:000354621100018
PM 25637165
ER
PT J
AU Blevins, MA
Kouznetsova, J
Krueger, AB
King, R
Griner, LM
Hu, X
Southall, N
Marugan, JJ
Zhang, QH
Ferrer, M
Zhao, R
AF Blevins, Melanie A.
Kouznetsova, Jennifer
Krueger, Aaron B.
King, Rebecca
Griner, Lesley Mathews
Hu, Xin
Southall, Noel
Marugan, Juan J.
Zhang, Qinghong
Ferrer, Marc
Zhao, Rui
TI Small Molecule, NSC95397, Inhibits the CtBP1-Protein Partner Interaction
and CtBP1-Mediated Transcriptional Repression
SO JOURNAL OF BIOMOLECULAR SCREENING
LA English
DT Article
DE CtBP1; NSC95397; E1A; AlphaScreen; protein-protein interaction
ID TERMINAL-BINDING-PROTEIN; COREPRESSOR CTBP; MITOTIC FIDELITY;
BREAST-CANCER; EXPRESSION; SITE; METABOLISM; SUBSTRATE; BRCA1; CELLS
AB Carboxyl-terminal binding protein (CtBP) is a transcriptional corepressor that suppresses multiple proapoptotic and epithelial genes. CtBP is overexpressed in many human cancers, and its overexpression increases stem cell-like features, epithelial-mesenchymal transition, and cancer cell survival. Knockdown of CtBP also increases apoptosis independent of p53 in cell culture. Therefore, targeting CtBP with small molecules that disrupt its interaction with transcription factor partners may be an effective cancer therapy. To elicit its corepressing effect, CtBP binds to a conserved peptide motif in each transcription factor partner. We developed an AlphaScreen high-throughput screening assay to monitor the interaction between CtBP and E1A (which mimics the interaction between CtBP and its transcriptional partners). We screened the LOPAC library of 1280 bioactive compounds and identified NSC95397, which inhibits the CtBP-E1A interaction (IC50 = 2.9 mu M). The inhibitory activity of NSC95397 was confirmed using two secondary assays and a counterscreen. NSC95397 also behaved as a weak substrate of CtBP dehydrogenase activity and did not inhibit another dehydrogenase, lactase dehydrogenase. Finally, NSC95397 was able to disrupt CtBP-mediated transcriptional repression of a target gene. These studies present a new possibility for the development of a therapeutic agent targeting tumors through disrupting the CtBP transcriptional complex.
C1 [Blevins, Melanie A.; Krueger, Aaron B.; Zhao, Rui] Univ Colorado, Dept Biochem & Mol Genet, Sch Med, Aurora, CO 80045 USA.
[Kouznetsova, Jennifer; King, Rebecca; Griner, Lesley Mathews; Hu, Xin; Southall, Noel; Marugan, Juan J.; Ferrer, Marc] NIH, Div Preclin Innovat, NCATS, Rockville, MD 20850 USA.
[Zhang, Qinghong] Univ Colorado, Dept Dermatol, Sch Med, Aurora, CO 80045 USA.
RP Zhang, QH (reprint author), Univ Colorado, Dept Dermatol, Sch Med, Aurora, CO 80045 USA.
EM qinghong.zhang@ucdenver.edu; marc.ferrer@nih.gov; rui.zhao@ucdenver.edu
RI Southall, Noel/H-8991-2012
OI Southall, Noel/0000-0003-4500-880X
FU NIH [R03DA033982]; NIH/NCRR Colorado CTSI [UL1 RR025780]; Golfers
Against Cancer Foundation; NIH Common Fund Molecular Libraries and
Imaging Program [U54 MH084681]
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This research
was supported by a grant NIH R03DA033982 a pilot grant from the NIH/NCRR
Colorado CTSI grant UL1 RR025780, and a pilot grant from Golfers Against
Cancer Foundation to R.Z. and Q.Z., as well as grant U54 MH084681 to the
National Center for Advancing Translational Sciences (NCATS) from the
NIH Common Fund Molecular Libraries and Imaging Program.
NR 29
TC 4
Z9 4
U1 0
U2 9
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0571
EI 1552-454X
J9 J BIOMOL SCREEN
JI J. Biomol. Screen
PD JUN
PY 2015
VL 20
IS 5
BP 663
EP 672
DI 10.1177/1087057114561400
PG 10
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Chemistry
GA CI5DV
UT WOS:000354774100011
PM 25477201
ER
PT J
AU Remoli, C
Michienzi, S
Sacchetti, B
Di Consiglio, A
Cersosimo, S
Spica, E
Robey, PG
Holmbeck, K
Cumano, A
Boyde, A
Davis, G
Saggio, I
Riminucci, M
Bianco, P
AF Remoli, Cristina
Michienzi, Stefano
Sacchetti, Benedetto
Di Consiglio, Alberto
Cersosimo, Stefania
Spica, Emanuela
Robey, Pamela G.
Holmbeck, Kenn
Cumano, Ana
Boyde, Alan
Davis, Graham
Saggio, Isabella
Riminucci, Mara
Bianco, Paolo
TI Osteoblast-specific expression of the fibrous dysplasia (FD)-causing
mutation Gs(R201C) produces a high bone mass phenotype but does not
reproduce FD in the mouse
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE FIBROUS DYSPLASIA; MOUSE MODELS; GS; GNAS; OSTEOBLASTS; BONE MARROW;
HEMATOPOIETIC NICHE
ID MCCUNE-ALBRIGHT SYNDROME; SCANNING-ELECTRON-MICROSCOPY;
SYMPATHETIC-NERVOUS-SYSTEM; STEM-CELLS; GS-ALPHA; HEMATOPOIETIC
MICROENVIRONMENT; ACTIVATING MUTATIONS; SKELETAL PROGENITORS;
PARATHYROID-HORMONE; TRABECULAR BONE
AB We recently reported the generation and initial characterization of the first direct model of human fibrous dysplasia (FD; OMIM #174800), obtained through the constitutive systemic expression of one of the disease-causing mutations, Gs(R201C), in the mouse. To define the specific pathogenetic role(s) of individual cell types within the stromal/osteogenic system in FD, we generated mice expressing Gs(R201C) selectively in mature osteoblasts using the 2.3kb Col1a1 promoter. We show here that this results in a striking high bone mass phenotype but not in a mimicry of human FD. The high bone mass phenotype involves specifically a deforming excess of cortical bone and prolonged and ectopic cortical bone remodeling. Expression of genes characteristic of late stages of bone cell differentiation/maturation is profoundly altered as a result of expression of Gs(R201C) in osteoblasts, and expression of the Wnt inhibitor Sost is reduced. Although high bone mass is, in fact, a feature of some types/stages of FD lesions in humans, it is marrow fibrosis, localized loss of adipocytes and hematopoietic tissue, osteomalacia, and osteolytic changes that together represent the characteristic pathological profile of FD, as well as the sources of specific morbidity. None of these features are reproduced in mice with osteoblast-specific expression of Gs(R201C). We further show that hematopoietic progenitor/stem cells, as well as more mature cell compartments, and adipocyte development are normal in these mice. These data demonstrate that effects of Gs mutations underpinning FD-defining tissue changes and morbidity do not reflect the effects of the mutations on osteoblasts proper. (c) 2015 American Society for Bone and Mineral Research. (c) 2014 American Society for Bone and Mineral Research
C1 [Remoli, Cristina; Michienzi, Stefano; Sacchetti, Benedetto; Di Consiglio, Alberto; Cersosimo, Stefania; Spica, Emanuela; Riminucci, Mara; Bianco, Paolo] Univ Roma La Sapienza, Dept Mol Med, I-00161 Rome, Italy.
[Robey, Pamela G.; Holmbeck, Kenn] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Cumano, Ana] Inst Pasteur, INSERM, Lymphopoiesis Unit, F-75724 Paris, France.
[Boyde, Alan; Davis, Graham] Queen Mary Univ London, Dent Phys Sci, London, England.
[Saggio, Isabella] Univ Roma La Sapienza, Dept Biol & Biotechnol C Darwin, I-00161 Rome, Italy.
[Saggio, Isabella] IBPM CNR, Rome, Italy.
RP Bianco, P (reprint author), Univ Roma La Sapienza, Dept Mol Med, Viale Regina Elena 324, I-00161 Rome, Italy.
EM paolo.bianco@uniroma1.it
RI Robey, Pamela/H-1429-2011
OI Robey, Pamela/0000-0002-5316-5576
FU Telethon [GGP09227]; Fondazione Institut Pasteur-Cenci Bolognetti; MIUR;
Ministry of Health; Sapienza University; EU (PluriMes consortium);
Fondazione Roma; DIR, NIDCR of the IRP, NIH, DHHS
FX This work was supported by grants from Telethon (grant GGP09227),
Fondazione Institut Pasteur-Cenci Bolognetti, MIUR, Ministry of Health,
Sapienza University, and EU (PluriMes consortium) to PB; by Fondazione
Roma to PB and MR; and by the DIR, NIDCR of the IRP, NIH, DHHS to PGR
and KH.
NR 71
TC 3
Z9 3
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD JUN
PY 2015
VL 30
IS 6
BP 1030
EP 1043
DI 10.1002/jbmr.2425
PG 14
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CI3CG
UT WOS:000354624500012
PM 25487351
ER
PT J
AU Leach, CR
Weaver, KE
Aziz, NM
Alfano, CM
Bellizzi, KM
Kent, EE
Forsythe, LP
Rowland, JH
AF Leach, Corinne R.
Weaver, Kathryn E.
Aziz, Noreen M.
Alfano, Catherine M.
Bellizzi, Keith M.
Kent, Erin E.
Forsythe, Laura P.
Rowland, Julia H.
TI The complex health profile of long-term cancer survivors: prevalence and
predictors of comorbid conditions
SO JOURNAL OF CANCER SURVIVORSHIP
LA English
DT Article
DE Cancer survivor; Chronic disease; Comorbidity; Multimorbidity
ID QUALITY-OF-LIFE; BREAST-CANCER; CARDIOVASCULAR COMPLICATIONS;
OLDER-ADULTS; POPULATION; THERAPY; SOCIETY; WOMEN; ASSOCIATION;
CARCINOMA
AB Adult cancer survivors have complex medical profiles that may include chronic conditions beyond cancer. Few studies have examined the prevalence of comorbidities before and after a cancer diagnosis.
Cancer cases were sampled from two California cancer registries to examine medical conditions (ever experienced and developed after cancer) among 1,527 long-term breast, prostate, colorectal, and gynecological cancer survivors by socio-demographic, cancer-related, and health behavior variables.
On average, survivors reported five medical conditions ever diagnosed (95 % CI, 4.8, 5.1) and 1.9 conditions (95 % CI, 1.8, 2.0) diagnosed after cancer. Breast cancer survivors reported the highest (5.8 ever, 2.9 post-cancer) and prostate survivors the lowest (4.0 ever, 1.0 post-cancer) comorbidity burden. Higher comorbidity burden was associated with older age, being a breast cancer survivor, divorced, widowed or separated, non-Hispanic White, overweight or obese, and not receiving chemotherapy. Breast and endometrial cancer survivors, as well as those more than 10 years post-diagnosis, obese, or physically inactive were more likely to report that these comorbidities occurred after cancer. Cancer treatment type, smoking, age, race/ethnicity, marital status, and education were not significant predictors of comorbidities acquired post-cancer.
Cancer survivors report a large number of medical conditions, many identified after a cancer diagnosis. Findings suggest that time since cancer diagnosis, body mass index, and activity level are important contextual variables when managing survivor's post-treatment follow-up care.
Survivors may benefit when health professionals recommend specific strategies to achieve a healthy weight and regular physical activity for better long-term health outcomes after cancer.
C1 [Leach, Corinne R.] Amer Canc Soc, Behav Res Ctr, Atlanta, GA 30303 USA.
[Weaver, Kathryn E.] Wake Forest Univ, Bowman Gray Sch Med, Dept Social Sci & Hlth Policy, Winston Salem, NC USA.
[Aziz, Noreen M.] NINR, NIH, Bethesda, MD 20892 USA.
[Alfano, Catherine M.; Kent, Erin E.; Rowland, Julia H.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Bellizzi, Keith M.] Univ Connecticut, Dept Human Dev & Family Studies, Storrs, CT USA.
[Forsythe, Laura P.] Patient Ctr Outcomes Res Inst, Washington, DC USA.
RP Leach, CR (reprint author), Amer Canc Soc, Behav Res Ctr, 250 Williams St, Atlanta, GA 30303 USA.
EM corinne.leach@cancer.org
FU National Cancer Institute at the National Institutes of Health
[N01-PC-35136, HHSN 261201100189P]
FX The views expressed in this paper are those of the authors and do not
necessarily reflect the views of the American Cancer Society, the
Federal Government, or the Patient-Centered Outcomes Research Institute.
This study was supported by the National Cancer Institute at the
National Institutes of Health contracts No. N01-PC-35136 and HHSN
261201100189P. The authors would like to acknowledge: Dr. Neeraj Arora
(NCI) for his survey development work and guidance, Dr. Arti Hurria
(City of Hope) for her clinical expertise and assistance in categorizing
medical conditions, and Dr. Ann Hamilton and Dr. Ingrid Oakley-Girvan
for their oversight of the FOCUS study at their respective centers. The
authors would also like to acknowledge Ms. Gretchen Keel and Mr. Todd
Gibson (Information Management Services, Inc., Rockville, MD) for their
assistance with data analysis on this project.
NR 37
TC 15
Z9 15
U1 3
U2 16
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1932-2259
EI 1932-2267
J9 J CANCER SURVIV
JI J. Cancer Surviv.-Res. Pract.
PD JUN
PY 2015
VL 9
IS 2
BP 239
EP 251
DI 10.1007/s11764-014-0403-1
PG 13
WC Oncology; Social Sciences, Biomedical
SC Oncology; Biomedical Social Sciences
GA CI8AB
UT WOS:000354988400011
PM 25319681
ER
PT J
AU Chrischilles, EA
McDowell, BD
Rubenstein, L
Charlton, M
Pendergast, J
Juarez, GY
Arora, NK
AF Chrischilles, Elizabeth A.
McDowell, Bradley D.
Rubenstein, Linda
Charlton, Mary
Pendergast, Jane
Juarez, Grelda Yazmin
Arora, Neeraj K.
TI Survivorship care planning and its influence on long-term
patient-reported outcomes among colorectal and lung cancer survivors:
the CanCORS disease-free survivor follow-up study
SO JOURNAL OF CANCER SURVIVORSHIP
LA English
DT Article
DE Cohort studies; Colorectal neoplasms; Lung neoplasms; Survivors; Quality
of life
ID BREAST-CANCER; PLANS; PHYSICIANS; PERSPECTIVES; ONCOLOGISTS; TRIAL
AB This study aims to evaluate the relationship between survivorship care planning (SCP) and survivorship care and health outcomes reported by long-term lung and colorectal cancer survivors.
Participants (n = 832) were diagnosed and enrolled during 2003-2005. In 2012, patient-reported outcomes (survivorship care and health outcomes) and two patient-reported SCP measures (receipt of written summary of cancer treatment and receipt of instructions on who to see for routine cancer follow-up) were collected. Analyses controlled for SCP predictors collected from medical records and an interview 1 year after diagnosis.
One in four survivors reported receiving both SCP elements. Those receiving both were more certain which doctor was in charge (odds ratio (OR) 7.0; 95 % confidence intervals (95 % CI) 3.9-12.5), more likely to report follow-up checkup (OR 5.1; 95 % CI 3.3-8.0), and had an MRI/PET/CT scan in the past 2 years (OR 2.8; 95 % CI 1.7-4.7) compared to those receiving neither. Physician communication experiences were significantly more positive and having physical exams (OR 2.0; 95 % CI 1.2-3.4) and meeting exercise guidelines (OR 1.6; 95 % CI 1.004-2.4) more likely. Physical health (p = 0.012) and good-to-excellent self-perceived health status (OR 2.2; 95 % CI 1.3-3.9) were better for those receiving both elements.
SCP may lead to better cancer follow-up care, long-term physical health, and physician-patient communication experiences.
The positive association between outcomes and SCP suggests that efforts to implement SCP should be fruitful.
C1 [Chrischilles, Elizabeth A.; Rubenstein, Linda; Charlton, Mary] Univ Iowa, Dept Epidemiol, Iowa City, IA 52242 USA.
[McDowell, Bradley D.] Univ Iowa, Holden Comprehens Canc Ctr, Iowa City, IA 52242 USA.
[Pendergast, Jane] Univ Iowa, Dept Biostat, Iowa City, IA 52242 USA.
[Juarez, Grelda Yazmin] Univ Iowa, Ctr Publ Hlth Stat, Iowa City, IA 52242 USA.
[Arora, Neeraj K.] NCI, Bethesda, MD 20892 USA.
RP Chrischilles, EA (reprint author), Univ Iowa, Dept Epidemiol, S424 CPHB, Iowa City, IA 52242 USA.
EM e-chrischilles@uiowa.edu
FU National Cancer Institute (NCI) [U01 CA093344]; NCI (Dana-Farber Cancer
Institute/Cancer Research Network) [U01 CA093332]; NCI (Harvard Medical
School/Northern California Cancer Center) [U01 CA093324]; NCI
(RAND/UCLA) [U01 CA093348]; NCI (University of Alabama at Birmingham)
[U01 CA093329]; NCI (University of Iowa) [U01 CA093339]; NCI (University
of North Carolina) [U01 CA093326]; Department of Veterans Affairs [CRS
02-164]; University of Iowa Holden Comprehensive Cancer Center (HCCC)
Population Research Core [P30 CA086862]; American Cancer Society
[IRG-77-004-34]
FX The work of the CanCORS Consortium was supported by grants from the
National Cancer Institute (NCI) to the Statistical Coordinating Center
(U01 CA093344) and the NCI supported Primary Data Collection and
Research Centers (Dana-Farber Cancer Institute/Cancer Research Network
U01 CA093332, Harvard Medical School/Northern California Cancer Center
U01 CA093324, RAND/UCLA U01 CA093348, University of Alabama at
Birmingham U01 CA093329, University of Iowa U01 CA093339, University of
North Carolina U01 CA093326) and by a Department of Veterans Affairs
grant to the Durham VA Medical Center CRS 02-164. This project was also
supported in part by the University of Iowa Holden Comprehensive Cancer
Center (HCCC) Population Research Core, funded in part by P30 CA086862,
as well as Institutional Research Grant IRG-77-004-34 from the American
Cancer Society to the HCCC.
NR 30
TC 2
Z9 2
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1932-2259
EI 1932-2267
J9 J CANCER SURVIV
JI J. Cancer Surviv.-Res. Pract.
PD JUN
PY 2015
VL 9
IS 2
BP 269
EP 278
DI 10.1007/s11764-014-0406-y
PG 10
WC Oncology; Social Sciences, Biomedical
SC Oncology; Biomedical Social Sciences
GA CI8AB
UT WOS:000354988400014
PM 25354481
ER
PT J
AU Ward, MM
Guthrie, LC
Alba, M
AF Ward, Michael M.
Guthrie, Lori C.
Alba, Maria
TI Domain-specific transition questions demonstrated higher validity than
global transition questions as anchors for clinically important
improvement
SO JOURNAL OF CLINICAL EPIDEMIOLOGY
LA English
DT Article
DE Clinically important difference; Outcome measures; Anchor-based methods;
Transition questions; Rheumatoid arthritis; Pain; Physical function
ID QUALITY-OF-LIFE; HEALTH-STATUS; IMPORTANT DIFFERENCE; RESPONSIVENESS;
DISABILITY; OUTCOMES; RATINGS; PAIN
AB Objectives: Estimates of minimal clinically important differences in health measures may be affected by the anchor used. We examined if domain-specific transition questions had higher construct validity than global health transition questions as anchors for measures in a given domain.
Study Design and Setting: In a prospective study of 249 patients with rheumatoid arthritis, we examined changes in pain, physical function, joint swelling, stiffness, fatigue, and depression with treatment. We related these changes to a domain-specific transition question, global arthritis transition question, and the Short Form-36 (SF-36) health transition item.
Results: Changes in all six clinical measures were more highly correlated with the domain-specific transition questions than with the global arthritis question and SF-36 transition question. Discrimination between patients who improved or not was also better using domain-specific questions. Estimates of minimal clinically important improvement (MCII) differed with the anchor when these were based on mean changes. MCII estimates from receiver operating characteristic curve analysis were not influenced by the choice of anchor when anchors had high agreement.
Conclusion: Domain-specific transition questions had higher construct validity as anchors for determining clinically important differences in health measures focused on a single domain than either global disease or general health transition questions. Published by Elsevier Inc.
C1 [Ward, Michael M.; Guthrie, Lori C.; Alba, Maria] NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20819 USA.
RP Ward, MM (reprint author), NIAMS, NIH, Bldg 10 CRC,Room 4-1339,10 Ctr Dr, Bethesda, MD 20892 USA.
EM wardm1@mail.nih.gov
FU Intramural Research Program, National Institute of Arthritis and
Musculoskeletal and Skin Diseases, National Institutes of Health [ZIA
AR041153]; U.S. Public Health Service [AR45177]
FX This study was supported by the Intramural Research Program, National
Institute of Arthritis and Musculoskeletal and Skin Diseases, National
Institutes of Health grant ZIA AR041153 and U.S. Public Health Service
grant AR45177.
NR 23
TC 3
Z9 3
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0895-4356
EI 1878-5921
J9 J CLIN EPIDEMIOL
JI J. Clin. Epidemiol.
PD JUN
PY 2015
VL 68
IS 6
BP 655
EP 661
DI 10.1016/j.jclinepi.2015.01.028
PG 7
WC Health Care Sciences & Services; Public, Environmental & Occupational
Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA CI4XE
UT WOS:000354756400008
PM 25769795
ER
PT J
AU Moutsopoulos, NM
Lionakis, MS
Hajishengallis, G
AF Moutsopoulos, N. M.
Lionakis, M. S.
Hajishengallis, G.
TI Inborn Errors in Immunity: Unique Natural Models to Dissect Oral
Immunity
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Article
DE monogenic immune defects; periodontitis susceptibility; oral candidiasis
susceptibility; human oral immunity; IL-17; Th17
ID CHRONIC MUCOCUTANEOUS CANDIDIASIS; PRIMARY IMMUNODEFICIENCY DISEASES;
SEVERE PERIODONTAL-DISEASE; PAPILLON-LEFEVRE SYNDROME; MUTATIONS;
DEFICIENCY; LESSONS; HUMANS; INFECTIONS; PHENOTYPE
AB In recent years, the study of genetic defects arising from inborn errors in immunity has resulted in the discovery of new genes involved in the function of the immune system and in the elucidation of the roles of known genes whose importance was previously unappreciated. With the recent explosion in the field of genomics and the increasing number of genetic defects identified, the study of naturally occurring mutations has become a powerful tool for gaining mechanistic insight into the functions of the human immune system. In this concise perspective, we discuss emerging evidence that inborn errors in immunity constitute real-life models that are indispensable both for the in-depth understanding of human biology and for obtaining critical insights into common diseases, such as those affecting oral health. In the field of oral mucosal immunity, through the study of patients with select gene disruptions, the interleukin-17 (IL-17) pathway has emerged as a critical element in oral immune surveillance and susceptibility to inflammatory disease, with disruptions in the IL-17 axis now strongly linked to mucosal fungal susceptibility, whereas overactivation of the same pathways is linked to inflammatory periodontitis.
C1 [Moutsopoulos, N. M.] NIDCR, Oral Immun & Inflammat Unit, NIH, Bethesda, MD 20892 USA.
[Lionakis, M. S.] NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Hajishengallis, G.] Univ Penn, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA.
RP Moutsopoulos, NM (reprint author), NIDCR, Oral Immun & Inflammat Unit, NIH, 30 Convent Dr, Bethesda, MD 20892 USA.
EM nmoutsop@mail.nih.gov
FU National Institute of Dental and Craniofacial Research (NIDCR); National
Institute of Allergy and Infectious Diseases (NIAID); NIDCR [DE024716,
DE015254]
FX The authors were funded in part by the intramural programs of the
National Institute of Dental and Craniofacial Research (NIDCR) and the
National Institute of Allergy and Infectious Diseases (NIAID) and
extramural grants from NIDCR DE024716 and DE015254. The authors declare
no potential conflicts of interest with respect to the authorship and/or
publication of this article.
NR 46
TC 4
Z9 4
U1 1
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0022-0345
EI 1544-0591
J9 J DENT RES
JI J. Dent. Res.
PD JUN
PY 2015
VL 94
IS 6
BP 753
EP 758
DI 10.1177/0022034515583533
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA CI6JX
UT WOS:000354866300001
PM 25900229
ER
PT J
AU Hatch, EE
Troisi, R
Palmer, JR
Wise, LA
Titus, L
Strohsnitter, WC
Ricker, W
Hyer, M
Hoover, RN
AF Hatch, E. E.
Troisi, R.
Palmer, J. R.
Wise, L. A.
Titus, L.
Strohsnitter, W. C.
Ricker, W.
Hyer, M.
Hoover, R. N.
TI Prenatal diethylstilbestrol exposure and risk of obesity in adult women
SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE
LA English
DT Article
DE adult; epidemiology; public health; human; pregnancy
ID ENDOCRINE DISRUPTORS; BREAST-CANCER; PERINATAL EXPOSURE; ADIPOSE-TISSUE;
WEIGHT-GAIN; IN-UTERO; PREGNANCY; OVERWEIGHT; HORMONES; METAANALYSIS
AB Diethylstilbestrol (DES) is a non-steroidal estrogen that was commonly prescribed during pregnancy from the late 1940s to 1971. A potent endocrine disruptor, prenatal DES exposure has been linked with reproductive tract malformations, adverse pregnancy outcomes, cancer, infertility and earlier menopause. DES was used for years as a growth promoter in animal production. Some animal studies suggest that prenatal DES exposure is associated with obesity and metabolic disturbances. Using data from the National Cancer Institute DES Follow-Up Study, we evaluated the association between DES and adult obesity, weight gain from age 20 to mid-life, central adiposity and height among 2871 prenatally exposed and 1352 unexposed women between 23 and 52 years of age (median 41.5) at baseline in 1994. DES exposure status was confirmed by prenatal medical record review. We used multivariable log-binomial models to calculate risk ratios (RRs) for obesity in 2006, and linear regression to calculate mean differences in body mass index, weight gain, waist circumference and height. The adjusted RR for DES and obesity was 1.09 [95% confidence interval (CI): 0.97, 1.22], and RRs were 1.23 (CI: 1.07, 1.42) and 1.05 (CI: 0.91, 1.20) for low and high estimated total DES dose, respectively, compared with no exposure. DES-exposed women gained slightly more weight than unexposed women [mean difference, 0.70 kg (CI: -0.27, 1.66)]. This study suggests that prenatal DES exposure may be associated with a small increase in adult obesity.
C1 [Hatch, E. E.; Wise, L. A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA.
[Troisi, R.; Hoover, R. N.] NCI, Div Epidemiol & Genet, Bethesda, MD 20892 USA.
[Palmer, J. R.; Wise, L. A.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA.
[Titus, L.] Hood Ctr Children & Families, Geisel Sch Med Dartmouth, Lebanon, NH USA.
[Strohsnitter, W. C.] Tufts Univ New England Med Ctr, Dept Obstet & Gynecol, Boston, MA USA.
[Ricker, W.; Hyer, M.] Informat Management Serv Inc, Rockville, MD USA.
RP Hatch, EE (reprint author), Boston Univ, Sch Publ Hlth, Dept Epidemiol, 715 Albany St Talbot 318E, Boston, MA 02118 USA.
EM eehatch@bu.edu
FU NCI [HHSN261201000 128C]
FX The study was funded by the NCI contract HHSN261201000 128C.
NR 44
TC 5
Z9 5
U1 1
U2 11
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 2040-1744
EI 2040-1752
J9 J DEV ORIG HLTH DIS
JI J. Dev. Orig. Health Dis.
PD JUN
PY 2015
VL 6
IS 3
BP 201
EP 207
DI 10.1017/S2040174415000033
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CI6OK
UT WOS:000354879500005
PM 25697972
ER
PT J
AU Wise, LA
Troisi, R
Hatch, EE
Titus, LJ
Rothman, KJ
Harlow, BL
AF Wise, L. A.
Troisi, R.
Hatch, E. E.
Titus, L. J.
Rothman, K. J.
Harlow, B. L.
TI Prenatal diethylstilbestrol exposure and reproductive hormones in
premenopausal women
SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE
LA English
DT Article
DE diethylstilbestrol; endocrine disrupting chemicals; estrogens; females;
hormones
ID FOLLICLE-STIMULATING-HORMONE; INHIBIN-B LEVELS; SERUM INHIBIN; DIMERIC
INHIBIN; MENSTRUAL-CYCLE; MENOPAUSAL AGE; FOLLOW-UP; IN-UTERO;
DEPRESSION; PATTERNS
AB Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women in the mid-1900s, is a potent endocrine disruptor. Prenatal DES exposure has been associated with reproductive disorders in women, but little is known about its effects on endogenous hormones. We assessed the association between prenatal DES exposure and reproductive hormones among participants from the Harvard Study of Moods and Cycles (HSMC), a longitudinal study of premenopausal women aged 36-45 years from Massachusetts (1995-1999). Prenatal DES exposure was reported at baseline (43 DES exposed and 782 unexposed). Early follicular-phase concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol were measured at baseline and every 6 months during 36 months of follow-up. Inhibin B concentrations were measured through 18 months. We used multivariable logistic and repeated-measures linear regression to estimate odds ratios (OR) and percent differences in mean hormone values (), respectively, comparing DES exposed with unexposed women, adjusted for potential confounders. DES-exposed women had lower mean concentrations of estradiol (pg/ml) (=-15.6%, 95% confidence interval (CI): -26.5%, -3.2%) and inhibin B (pg/ml) (=-20.3%, CI: -35.1%, -2.3%), and higher mean concentrations of FSH (IU/I) (=12.2%, CI: -1.5%, 27.9%) and LH (IU/I) (=10.4%, CI: -7.2%, 31.3%), than unexposed women. ORs for the association of DES with maximum FSH>10 IU/I and minimum inhibin B<45 pg/ml - indicators of low ovarian reserve - were 1.90 (CI: 0.86, 4.22) and 4.00 (CI: 0.88-18.1), respectively. Prenatal DES exposure was associated with variation in concentrations of FSH, estradiol and inhibin B among women of late reproductive age.
C1 [Wise, L. A.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA.
[Wise, L. A.; Hatch, E. E.; Rothman, K. J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA.
[Troisi, R.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Titus, L. J.] Geisel Sch Med Dartmouth, Hood Ctr Children & Families, Lebanon, NH USA.
[Rothman, K. J.] RTI Hlth Solut, Res Triangle Pk, NC USA.
[Harlow, B. L.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
RP Wise, LA (reprint author), Boston Univ, Slone Epidemiol Ctr, 1010 Commonwealth Ave, Boston, MA 02215 USA.
EM lwise@bu.edu
FU NIH [R01-MH50013, R01-MH69732]
FX This work was supported by NIH grants R01-MH50013 and R01-MH69732 (PI:
Harlow). The content is solely the responsibility of the authors and
does not necessarily represent the official view of the National
Institutes of Health. The authors have no competing interests to report.
NR 41
TC 5
Z9 5
U1 0
U2 9
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 2040-1744
EI 2040-1752
J9 J DEV ORIG HLTH DIS
JI J. Dev. Orig. Health Dis.
PD JUN
PY 2015
VL 6
IS 3
BP 208
EP 216
DI 10.1017/S2040174415000082
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CI6OK
UT WOS:000354879500006
PM 25698132
ER
PT J
AU Luck, ME
Muljo, SA
Collins, CB
AF Luck, Marisa E.
Muljo, Stefan A.
Collins, Colm B.
TI Prospects for Therapeutic Targeting of MicroRNAs in Human Immunological
Diseases
SO JOURNAL OF IMMUNOLOGY
LA English
DT Review
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CHIMERIC MONOCLONAL-ANTIBODY;
INFLAMMATORY-BOWEL-DISEASE; ALLERGIC AIRWAYS DISEASE;
NECROSIS-FACTOR-ALPHA; III ENZYME DICER; MESSENGER-RNA; IN-VIVO;
T-CELLS; RHEUMATOID-ARTHRITIS
AB MicroRNAs (miRNAs) are endogenous oligoribonucleotides with exciting therapeutic potential. Early studies established a clear role for miRNAs in leukocyte biology. The first miRNA-based therapy, miravirsen, is now in phase 2 clinical trials, making the reality of these therapies undeniable. The capacity for miRNAs to fine-tune inflammatory signaling make them attractive treatment targets for immunological diseases. Nonetheless, the degree of redundancy among miRNAs, coupled with the promiscuity of miRNA binding sites in the transcriptome, require consideration when designing miRNA-directed interventions. Altered miRNA expression occurs across a range of inflammatory conditions, including inflammatory bowel disease, arthritis, and diabetes. However, very few studies successfully treated murine models of immunological diseases with miRNA-based approaches. While discussing recent studies targeting miRNAs to treat immunological conditions, we also reflect on the risks of miRNA targeting and showcase some newer delivery systems that may improve the pharmacological profile of this class of therapeutics.
C1 [Luck, Marisa E.; Collins, Colm B.] Univ Colorado, Sch Med, Dept Pediat, Mucosal Inflammat Program, Aurora, CO 80045 USA.
[Muljo, Stefan A.] NIAID, Integrat Immunobiol Unit, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Muljo, SA (reprint author), NIAID, Integrat Immunobiol Unit, Immunol Lab, NIH, Bldg 10,Room 11N308,10 Ctr Dr,M51892, Bethesda, MD 20892 USA.
EM Stefan.Muljo@nih.gov; Colm.Collins@ucdenver.edu
FU National Institutes of Health Intramural Research Program of the
National Institute of Allergy and Infectious Diseases; National
Institute of Diabetes and Digestive and Kidney Diseases Grant [K01
DK099403-01]; Crohn's & Colitis Foundation of America Grant [CDA 253596]
FX This work is supported by the National Institutes of Health Intramural
Research Program of the National Institute of Allergy and Infectious
Diseases (to S.A.M.), National Institute of Diabetes and Digestive and
Kidney Diseases Grant K01 DK099403-01 (to C.B.C.), and Crohn's & Colitis
Foundation of America Grant CDA 253596 (to C.B.C.).
NR 90
TC 11
Z9 11
U1 1
U2 8
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 2015
VL 194
IS 11
BP 5047
EP 5052
DI 10.4049/jimmunol.1403146
PG 6
WC Immunology
SC Immunology
GA CI6WS
UT WOS:000354905300005
PM 25980029
ER
PT J
AU Liu, BY
Dhanda, A
Hirani, S
Williams, EL
Sen, HN
Estrada, FM
Ling, D
Thompson, I
Casady, M
Li, ZY
Si, H
Tucker, W
Wei, L
Jawad, S
Sura, A
Dailey, J
Hannes, S
Chen, P
Chien, JL
Gordon, S
Lee, RWJ
Nussenblatt, RB
AF Liu, Baoying
Dhanda, Ashwin
Hirani, Sima
Williams, Emily L.
Sen, H. Nida
Estrada, Fernando Martinez
Ling, Diamond
Thompson, Ian
Casady, Megan
Li, Zhiyu
Si, Han
Tucker, William
Wei, Lai
Jawad, Shayma
Sura, Amol
Dailey, Jennifer
Hannes, Susan
Chen, Ping
Chien, Jason L.
Gordon, Siamon
Lee, Richard W. J.
Nussenblatt, Robert B.
TI CD14(++)CD16(+) Monocytes Are Enriched by Glucocorticoid Treatment and
Are Functionally Attenuated in Driving Effector T Cell Responses
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID RHEUMATOID-ARTHRITIS; BLOOD MONOCYTES; CD16(+) MONOCYTES;
PERIPHERAL-BLOOD; ACTIVATED MONOCYTES; TISSUE MACROPHAGES;
GROWTH-FACTOR; FC-GAMMA; SUBSET; DIFFERENTIATION
AB Human peripheral monocytes have been categorized into three subsets based on differential expression levels of CD14 and CD16. However, the factors that influence the distribution of monocyte subsets and the roles that each subset plays in autoimmunity are not well studied. In this study, we show that circulating monocytes from patients with autoimmune uveitis exhibit a skewed phenotype toward intermediate CD14(++)CD16(+) cells, and that this is associated with glucocorticoid therapy. We further demonstrate that CD14(++) CD16(+) monocytes from patients and healthy control donors share a similar cell-surface marker and gene expression profile. Comparison of the effects of intermediate CD14(++)CD16(+) monocytes with classical CD14(++)CD16(-) and nonclassical CD14(+)CD16(++) monocytes revealed that the intermediate CD14(++)CD16(+) subset had an attenuated capacity to promote both naive CD4(+) T cell proliferation and polarization into a Th1 phenotype, and memory CD4(+) T cell proliferation and IL-17 expression. Furthermore, CD14(++)CD16(+) cells inhibit CD+ T cell proliferation induced by other monocyte subsets and enhance CD4(+) T regulatory cell IL-10 expression. These data demonstrate the impact of glucocorticoids on monocyte phenotype in the context of autoimmune disease and the differential effects of monocyte subsets on effector T cell responses.
C1 [Liu, Baoying; Hirani, Sima; Sen, H. Nida; Ling, Diamond; Thompson, Ian; Casady, Megan; Li, Zhiyu; Si, Han; Tucker, William; Wei, Lai; Jawad, Shayma; Sura, Amol; Dailey, Jennifer; Hannes, Susan; Chen, Ping; Chien, Jason L.; Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Dhanda, Ashwin; Williams, Emily L.; Lee, Richard W. J.] Univ Bristol, Sch Clin Sci, Bristol B58 1TD, Avon, England.
[Dhanda, Ashwin; Williams, Emily L.; Lee, Richard W. J.] Moorfields Eye Hosp, Natl Inst Hlth Res Biomed Res Ctr, London EC1V 2PD, England.
[Dhanda, Ashwin; Williams, Emily L.; Lee, Richard W. J.] UCL, Inst Ophthalmol, London EC1V 2PD, England.
[Estrada, Fernando Martinez; Gordon, Siamon] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England.
RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, 9000 Rockville Pike,Bldg 10,Room 10N109, Bethesda, MD 20892 USA.
EM drbob@nei.nih.gov
RI Lee, Richard/A-3116-2017;
OI Lee, Richard/0000-0002-9480-6843; Dhanda, Ashwin/0000-0002-0523-0193
FU Intramural Research Program of the National Eye Institute, National
Institutes of Health; National Institute for Health Research Biomedical
Research Centre based at Moorfields Eye Hospital National Health Service
Foundation Trust; University College London Institute of Ophthalmology,
United Kingdom
FX This work was supported by the Intramural Research Program of the
National Eye Institute, National Institutes of Health. A.D., E.L.W., and
R.W.J.L. also received support from the National Institute for Health
Research Biomedical Research Centre based at Moorfields Eye Hospital
National Health Service Foundation Trust and University College London
Institute of Ophthalmology, United Kingdom.
NR 46
TC 9
Z9 9
U1 2
U2 13
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 2015
VL 194
IS 11
BP 5150
EP 5160
DI 10.4049/jimmunol.1402409
PG 11
WC Immunology
SC Immunology
GA CI6WS
UT WOS:000354905300017
PM 25911752
ER
PT J
AU Sokolowska, M
Chen, LY
Liu, YQ
Martinez-Anton, A
Qi, HY
Logun, C
Alsaaty, S
Park, YH
Kastner, DL
Chae, JJ
Shelhamer, JH
AF Sokolowska, Milena
Chen, Li-Yuan
Liu, Yueqin
Martinez-Anton, Asuncion
Qi, Hai-Yan
Logun, Carolea
Alsaaty, Sara
Park, Yong Hwan
Kastner, Daniel L.
Chae, Jae Jin
Shelhamer, James H.
TI Prostaglandin E-2 Inhibits NLRP3 Inflammasome Activation through EP4
Receptor and Intracellular Cyclic AMP in Human Macrophages
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID PROTEIN-KINASE-A; INTERLEUKIN-1 PRODUCTION; NALP3 INFLAMMASOME; CUTTING
EDGE; PERITONEAL-MACROPHAGES; PROSTANOID RECEPTORS; IL-1-BETA
PRODUCTION; PHOSPHOLIPASE A(2); ADENYLYL-CYCLASE; SILICA CRYSTALS
AB PGE(2) is a potent lipid mediator involved in maintaining homeostasis but also promotion of acute inflammation or immune suppression in chronic inflammation and cancer. Nucleotide-binding domain, leucine-rich repeat-containing protein (NLR)P3 inflammasome plays an important role in host defense. Uncontrolled activation of the NLRP3 inflammasome, owing to mutations in the NLRP3 gene, causes cryopyrin-associated periodic syndromes. In this study, we showed that NLRP3 inflammasome activation is inhibited by PGE(2) in human primary monocyte-derived macrophages. This effect was mediated through PGE(2) receptor subtype 4 (EP4) and an increase in intracellular cAMP, independently of protein kinase A or exchange protein directly activated by cAMP. A specific agonist of EP4 mimicked, whereas its antagonist or EP4 knockdown reversed, PGE(2)-mediated NLRP3 inhibition. PGE(2) caused an increase in intracellular cAMP. Blockade of adenylate cyclase by its inhibitor reversed PGE(2)-mediated NLRP3 inhibition. Increase of intracellular cAMP by an activator of adenylate cyclase or an analog of cAMP, or a blockade of cAMP degradation by phosphodiesterase inhibitor decreased NLRP3 activation. Protein kinase A or exchange protein directly activated by cAMP agonists did not mimic, and their antagonists did not reverse, PGE(2)-mediated NLRP3 inhibition. Additionally, constitutive IL-1 beta secretion from LPS-primed PBMCs of cryopyrin-associated periodic fever syndromes patients was substantially reduced by high doses of PGE(2). Moreover, blocking cytosolic phospholipase A(2)alpha by its inhibitor or small interfering RNA or inhibiting cyclooxygenase 2, resulting in inhibition of endogenous PGE(2) production, caused an increase in NLRP3 inflammasome activation. Our results suggest that PGE(2) might play a role in maintaining homeostasis during the resolution phase of inflammation and might serve as an autocrine and paracrine regulator.
C1 [Sokolowska, Milena; Chen, Li-Yuan; Liu, Yueqin; Martinez-Anton, Asuncion; Qi, Hai-Yan; Logun, Carolea; Alsaaty, Sara; Shelhamer, James H.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Park, Yong Hwan; Kastner, Daniel L.; Chae, Jae Jin] NHGRI, Inflammatory Dis Sect, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Shelhamer, JH (reprint author), NIH, Dept Crit Care Med, Ctr Clin, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jshelhamer@cc.nih.gov
RI Martinez Anton, Asuncion/A-5806-2017
OI Martinez Anton, Asuncion/0000-0001-9758-5911
FU National Institutes of Health Intramural Program
FX This work was supported by the National Institutes of Health Intramural
Program.
NR 71
TC 25
Z9 25
U1 3
U2 7
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 2015
VL 194
IS 11
BP 5472
EP 5487
DI 10.4049/jimmunol.1401343
PG 16
WC Immunology
SC Immunology
GA CI6WS
UT WOS:000354905300048
PM 25917098
ER
PT J
AU Sado, DM
Maestrini, V
Piechnik, SK
Banypersad, SM
White, SK
Flett, AS
Robson, MD
Neubauer, S
Ariti, C
Arai, A
Kellman, P
Yamamura, J
Schoennagel, BP
Shah, F
Davis, B
Trompeter, S
Walker, M
Porter, J
Moon, JC
AF Sado, Daniel M.
Maestrini, Viviana
Piechnik, Stefan K.
Banypersad, Sanjay M.
White, Steven K.
Flett, Andrew S.
Robson, Matthew D.
Neubauer, Stefan
Ariti, Cono
Arai, Andrew
Kellman, Peter
Yamamura, Jin
Schoennagel, Bjoern P.
Shah, Farrukh
Davis, Bernard
Trompeter, Sara
Walker, Malcolm
Porter, John
Moon, James C.
TI Noncontrast myocardial T-1 mapping using cardiovascular magnetic
resonance for iron overload
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE MRI; iron; T-1
ID THALASSEMIA MAJOR; CARDIAC IRON; DIAGNOSTIC-ACCURACY; T1;
CARDIOMYOPATHY; QUANTIFICATION; FIBROSIS; DISEASE; REPRODUCIBILITY;
DEFEROXAMINE
AB PurposeTo explore the use and reproducibility of magnetic resonance-derived myocardial T-1 mapping in patients with iron overload.
Materials and MethodsThe research received ethics committee approval and all patients provided written informed consent. This was a prospective study of 88 patients and 67 healthy volunteers. Thirty-five patients underwent repeat scanning for reproducibility. T-1 mapping used the shortened modified Look-Locker inversion recovery sequence (ShMOLLI) with a second, confirmatory MOLLI sequence in the reproducibility group. T-2* was performed using a commercially available sequence. The analysis of the T-2* interstudy reproducibility data was performed by two different research groups using two different methods.
ResultsMyocardial T-1 was lower in patients than healthy volunteers (836138 msec vs. 968 +/- 32 msec, P<0.0001). Myocardial T-1 correlated with T-2* (R=0.79, P<0.0001). No patient with low T-2* had normal T-1, but 32% (n=28) of cases characterized by a normal T-2* had low myocardial T-1. Interstudy reproducibility of either T-1 sequence was significantly better than T-2*, with the results suggesting that the use of T-1 in clinical trials could decrease potential sample sizes by 7-fold.
ConclusionMyocardial T-1 mapping is an alternative method for cardiac iron quantification. T-1 mapping shows the potential for improved detection of mild iron loading. The superior reproducibility of T-1 has potential implications for clinical trial design and therapeutic monitoring. J. Magn. Reson. Imaging 2015;41:1505-1511. (c) 2014 Wiley Periodicals, Inc.
C1 [Sado, Daniel M.; Banypersad, Sanjay M.; White, Steven K.; Flett, Andrew S.; Walker, Malcolm; Moon, James C.] Heart Hosp, London W1G 8PH, England.
[Sado, Daniel M.; Banypersad, Sanjay M.; White, Steven K.; Walker, Malcolm; Moon, James C.] UCL, Inst Cardiovasc Sci, London, England.
[Maestrini, Viviana] Univ Roma La Sapienza, Dept Cardiovasc Resp Nephrol & Geriatr Sci, I-00185 Rome, Italy.
[Piechnik, Stefan K.; Robson, Matthew D.; Neubauer, Stefan] Univ Oxford, Dept Cardiovasc Med, Oxford Ctr Clin Magnet Resonance Res, Oxford, England.
[Ariti, Cono] London Sch Hyg & Trop Med, Dept Stat, London WC1, England.
[Arai, Andrew; Kellman, Peter] NHLBI, NIH, Bethesda, MD 20892 USA.
[Yamamura, Jin; Schoennagel, Bjoern P.] Univ Med Ctr Hamburg Eppendorf, Dept Diagnost & Intervent Radiol, Hamburg, Germany.
[Shah, Farrukh; Davis, Bernard] Whittington Hosp, London N19 5NF, England.
[Trompeter, Sara; Porter, John] Univ Coll London Hosp, London, England.
RP Moon, JC (reprint author), Heart Hosp, 16-18 Westmoreland St, London W1G 8PH, England.
EM james.moon@uclh.nhs.uk
OI moon, james/0000-0001-8071-1491
FU British Heart Foundation [FS/10/040/28260]
FX Contract grant sponsor: British Heart Foundation; Contract grant number:
FS/10/040/28260.
NR 40
TC 23
Z9 24
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-1807
EI 1522-2586
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD JUN
PY 2015
VL 41
IS 6
BP 1505
EP 1511
DI 10.1002/jmri.24727
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CI4QU
UT WOS:000354738100002
PM 25104503
ER
PT J
AU Li, NZ
Wang, WT
Pham, DL
Butman, JA
AF Li, Ningzhi
Wang, Wen-Tung
Pham, Dzung L.
Butman, John A.
TI Artifactual microhemorrhage generated by susceptibility weighted image
processing
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE susceptibility weighted imaging; homodyne filter; phase unwrapping;
microhemorrhage
ID PHASE UNWRAPPING ALGORITHM; MRI; VENOGRAPHY
AB BackgroundTo report that artifactual microhemorrhages are introduced by the two-dimensional (2D) homodyne filtering method of generating susceptibility weighted images (SWI) when open-ended fringelines (OEF) are present in phase data.
MethodsSWI data from 28 traumatic brain injury (TBI) patients was obtained on a 3 tesla clinical Siemens scanner using both the product 3D gradient echo sequence (GRE) with generalized autocalibrating partially parallel acquisition acceleration and an in-house developed segmented echo planar imaging (sEPI) sequence without GRAPPA acceleration. SWI processing included (i) 2D homodyne method implemented on the scanner console and (ii) a 3D Fourier-based phase unwrapping followed by 3D high pass filtering. Original and enhanced magnitude and phase images were carefully reviewed for sites of type III OEFs and microhemorrhages by a neuroradiologist on a PACS workstation.
ResultsNineteen of 28 (68%) phase datasets acquired using GRAPPA-accelerated GRE acquisition demonstrated type III OEFs. In SWI images, artifactual microhemorrhages were found on 17 of 19 (89%) cases generated using 2D homodyne processing. Application of a 3D Fourier-based unwrapping method prior HP filtering minimized the appearance of the phase singularities in the enhanced phase, and did not generate microhemorrhage-like artifacts in magnitude images.
ConclusionThe 2D homodyne filtering method may introduce artifacts mimicking intracranial microhemorrhages in SWI images when type III OEFs are present in phase images. Such artifacts could lead to overestimation of pathology, e.g., TBI. This work demonstrates that 3D phase unwrapping methods minimize this artifact. However, methods to properly combine phase across coils are needed to eliminate this artifact. J. Magn. Reson. Imaging 2015;41:1695-1700. (c) 2014 Wiley Periodicals, Inc.
C1 [Li, Ningzhi; Wang, Wen-Tung; Pham, Dzung L.; Butman, John A.] Ctr Neurosci & Regenerat Med, Bethesda, MD USA.
[Butman, John A.] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
RP Butman, JA (reprint author), 10 Ctr Dr,BLDG 10,RM 1C373, Bethesda, MD 21046 USA.
EM jbutman@nih.gov
RI Butman, John/J-2780-2013
OI Butman, John/0000-0002-1547-9195
FU Intramural Program in the National Institutes of Health; Department of
Defense in the Center for Neuroscience and Regenerative Medicine (CNRM)
FX Contract grant sponsor: Intramural Program in the National Institutes of
Health and the Department of Defense in the Center for Neuroscience and
Regenerative Medicine (CNRM).
NR 20
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-1807
EI 1522-2586
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD JUN
PY 2015
VL 41
IS 6
BP 1695
EP 1700
DI 10.1002/jmri.24728
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CI4QU
UT WOS:000354738100025
PM 25143262
ER
PT J
AU Pratt, D
Mehta, G
Wang, HW
Chittiboina, P
Quezado, M
AF Pratt, Drew
Mehta, Gautam
Wang, Hao-Wei
Chittiboina, Prashant
Quezado, Martha
TI Sellar atypical teratoid rhabdoid tumor (AT/RT) in an adult female
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 91st Annual Meeting of the American-Association-of-Neuropathologists-Inc
CY JUN 11-14, 2015
CL Denver, CO
SP Amer Assoc Neuropathologists Inc
C1 [Pratt, Drew; Wang, Hao-Wei] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Mehta, Gautam; Chittiboina, Prashant] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Quezado, Martha] NIH, Pathol Lab, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2015
VL 74
IS 6
MA 80
BP 609
EP 610
PG 2
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA CI5UH
UT WOS:000354824800090
ER
PT J
AU Bell, WR
Pletnikova, O
Crain, B
Rudow, G
Moghekar, A
Thambisetty, M
Rabins, P
Albert, M
Resnick, S
Troncoso, J
AF Bell, W. Robert
Pletnikova, Olga
Crain, Barbara
Rudow, Gay
Moghekar, Abhay
Thambisetty, Modhav
Rabins, Peter
Albert, Marilyn
Resnick, Susan
Troncoso, Juan
TI Primary Age-Related Tauopathy (PART) in Autopsies of the Baltimore
Longitudinal Study of Aging (BLSA)
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 91st Annual Meeting of the American-Association-of-Neuropathologists-Inc
CY JUN 11-14, 2015
CL Denver, CO
SP Amer Assoc Neuropathologists Inc
C1 [Bell, W. Robert] Johns Hopkins Sch Med, Baltimore, MD USA.
[Pletnikova, Olga; Crain, Barbara; Rudow, Gay; Troncoso, Juan] Johns Hopkins Univ, Sch Med, Neuropathol, Baltimore, MD 21218 USA.
[Moghekar, Abhay] Johns Hopkins Univ, Sch Med, Neurol, Baltimore, MD 21218 USA.
[Thambisetty, Modhav; Resnick, Susan] NIA, Behav Neurosci, NIH, Bethesda, MD 20892 USA.
[Rabins, Peter] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21218 USA.
[Albert, Marilyn] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21218 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2015
VL 74
IS 6
MA 113
BP 619
EP 619
PG 1
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA CI5UH
UT WOS:000354824800123
ER
PT J
AU Oblak, A
Epperson, F
Huey, E
Wassermann, E
Grafman, J
Ghetti, B
AF Oblak, Adrian
Epperson, Francine
Huey, Edward
Wassermann, Eric
Grafman, Jordan
Ghetti, Bernardino
TI Difficulties in Identifying Individuals with Alzheimer Disease in a
Cohort of Patients Presenting as Corticobasal Syndrome
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 91st Annual Meeting of the American-Association-of-Neuropathologists-Inc
CY JUN 11-14, 2015
CL Denver, CO
SP Amer Assoc Neuropathologists Inc
C1 [Oblak, Adrian; Epperson, Francine; Ghetti, Bernardino] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Huey, Edward] Columbia Univ, Med Ctr, New York, NY 10027 USA.
[Wassermann, Eric] NINDS, Bethesda, MD 20892 USA.
[Grafman, Jordan] Rehabil Inst Chicago, Chicago, IL USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2015
VL 74
IS 6
MA 132
BP 624
EP 625
PG 2
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA CI5UH
UT WOS:000354824800142
ER
PT J
AU Pratt, D
Edwards, N
Tinaz, S
Hallett, M
Ray-Chaudhury, A
AF Pratt, Drew
Edwards, Nancy
Tinaz, Sule
Hallett, Mark
Ray-Chaudhury, Abhik
TI Neuropathology of DYT1 dystonia: Supplementary findings
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 91st Annual Meeting of the American-Association-of-Neuropathologists-Inc
CY JUN 11-14, 2015
CL Denver, CO
SP Amer Assoc Neuropathologists Inc
C1 [Pratt, Drew] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Edwards, Nancy; Ray-Chaudhury, Abhik] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Tinaz, Sule; Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0022-3069
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2015
VL 74
IS 6
MA 142
BP 627
EP 627
PG 1
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA CI5UH
UT WOS:000354824800151
ER
PT J
AU Sloan, JL
Manoli, I
Venditti, CP
AF Sloan, Jennifer L.
Manoli, Irini
Venditti, Charles P.
TI Liver or Combined Liver-Kidney Transplantation for Patients with
Isolated Methylmalonic Acidemia: Who and When?
SO JOURNAL OF PEDIATRICS
LA English
DT Editorial Material
ID OF-THE-LITERATURE; RENAL-TRANSPLANTATION; METABOLIC-DISORDERS; ACIDURIA;
MANAGEMENT; DEFICIENCY; CHILDREN; DISEASE; MUT(0); GIRL
C1 [Sloan, Jennifer L.; Manoli, Irini; Venditti, Charles P.] NHGRI, Organ Acid Res Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
RP Venditti, CP (reprint author), NHGRI, Organ Acid Res Sect, NIH, Bldg 49,Room 4A18, Bethesda, MD 20892 USA.
EM venditti@mail.nih.gov
OI Manoli, Irini/0000-0003-1543-2941
FU Intramural NIH HHS
NR 39
TC 6
Z9 6
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
EI 1097-6833
J9 J PEDIATR-US
JI J. Pediatr.
PD JUN
PY 2015
VL 166
IS 6
BP 1346
EP 1350
DI 10.1016/j.jpeds.2015.03.026
PG 6
WC Pediatrics
SC Pediatrics
GA CI8JI
UT WOS:000355018200006
PM 25882873
ER
PT J
AU Rothman, RB
Ananthan, S
Partilla, JS
Saini, SK
Moukha-Chafiq, O
Pathak, V
Baumann, MH
AF Rothman, Richard B.
Ananthan, Subramaniam
Partilla, John S.
Saini, Surendra K.
Moukha-Chafiq, Omar
Pathak, Vibha
Baumann, Michael H.
TI Studies of the Biogenic Amine Transporters 15. Identification of Novel
Allosteric Dopamine Transporter Ligands with Nanomolar Potency
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID MONOAMINE TRANSPORTERS; SEROTONIN TRANSPORTER; AMPHETAMINE; RELEASE;
INHIBITORS; EFFLUX; DRUGS; NOREPINEPHRINE; MODULATORS; MECHANISM
AB Novel allosteric modulators of the dopamine transporter (DAT) have been identified. We have shown previously that SRI-9804 [N-(diphenylmethyl)-2-phenyl-4-quinazolinamine], SRI-20040 [N-(2,2-diphenylethyl)-2-phenyl-4-quinazolinamine], and SRI-20041 [N-(3,3-diphenylpropyl)-2-phenyl-4-quinazolinamine] partially inhibit [I-125]RTI-55 ([I-125]3 beta-(4'-iodophenyl)tropan-2 beta-carboxylic acid methyl ester) binding and [H-3] dopamine ([H-3] DA) uptake, slow the dissociation rate of [I-125] RTI-55 from the DAT, and allosterically modulate d-amphetamine-induced, DAT-mediated DA release. We synthesized and evaluated the activity of >500 analogs of these ligands and report here on 36 selected compounds. Using synaptosomes prepared from rat caudate, we conducted [3H] DA uptake inhibition assays, DAT binding assays with [H-3]WIN35428 ([H-3] 2 beta-carbomethoxy-3 beta-(4-fluorophenyl) tropane), and DAT-mediated release assays with either [H-3] MPP+ ([H-3] 1-methyl-4-phenylpyridinium) or [H-3] DA. We observed three groups of [H-3] DA uptake inhibitors: 1) full-efficacy agents with a one-site fit, 2) fullefficacy agents with a two-site fit, and 3) partial-efficacy agents with a one-site fit-the focus of further studies. These agents partially inhibited DA, serotonin, and norepinephrine uptake, yet were much less potent at inhibiting [H-3] WIN35428 binding to the DAT. For example, SRI-29574 [N-(2,2-diphenylethyl)-2-(imidazo[1,2-a] pyridin-6-yl) quinazolin-4-amine] partially inhibited DAT uptake, with an IC50 = 2.3 +/- 0.4 nM, without affecting binding to the DAT. These agents did not alter DAT-mediated release of [H-3] MPP1 in the absence or presence of 100 nM d-amphetamine. SRI-29574 had no significant effect on the d-amphetamine EC50 or E-max value for DAT-mediated release of [H-3] MPP1. These studies demonstrate the existence of potent DAT ligands that partially block [H-3] DA uptake, without affecting DAT binding or d-amphetamine-induced [H-3] MPP1 release. These compounds may prove to be useful probes of biogenic amine transporter function as well as novel therapeutics.
C1 [Rothman, Richard B.; Partilla, John S.; Baumann, Michael H.] NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Ananthan, Subramaniam; Saini, Surendra K.; Moukha-Chafiq, Omar; Pathak, Vibha] So Res Inst, Drug Discovery Div, Dept Chem, Birmingham, AL 35255 USA.
RP Rothman, RB (reprint author), NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM rrothman@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health
[National Institute on Drug Abuse]; National Institutes of Health
National Institute on Drug Abuse [R33-DA029962]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health [National Institute on Drug Abuse]; and
the National Institutes of Health National Institute on Drug Abuse
[Grant R33-DA029962 (to S.A.)].
NR 26
TC 2
Z9 2
U1 1
U2 8
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
EI 1521-0103
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD JUN
PY 2015
VL 353
IS 3
BP 529
EP 538
DI 10.1124/jpet.114.222299
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CH9YA
UT WOS:000354391400010
PM 25788711
ER
PT J
AU Jiang, B
Woodell, GA
Jobson, DJ
AF Jiang, Bo
Woodell, Glenn A.
Jobson, Daniel J.
TI Novel multi-scale retinex with color restoration on graphics processing
unit
SO JOURNAL OF REAL-TIME IMAGE PROCESSING
LA English
DT Article
DE Multi-scale Retinex; Image enhancement; Autolevels; Real time; GPU
ID IMAGE-ENHANCEMENT; VISION; GPU
AB The multi-scale retinex with color restoration (MSRCR) was developed as a general-purpose image enhancement algorithm that provides simultaneous dynamic range compression, local lightness/contrast enhancement, and good color rendition, and has been successfully used for a wide variety of imagery from diverse fields. While the MSRCR performs good enhancement in most images, the output image can sometimes be further visually optimized during our experiments. An improved MSRCR+Autolevels (AL) algorithm is presented, which can eliminate the impact of a small number of outliers in the histogram of the image and further improve the contrast of an image. New extension significantly improves the visual performance of the MSRCR algorithm. However, the MSRCR+AL containing a large number of complex calculations is computationally expensive, limiting real-time applications. In this paper, a parallel application of the MSRCR+AL algorithm on a graphics processing unit (GPU) is presented. For the various configurations in our test, the GPU-accelerated MSRCR+AL shows a scalable speedup as the resolution of an image increases. The up to 45x speedup (1,024 x 1,024) over the single-threaded CPU counterpart shows a promising direction of using the GPU-based MSRCR+AL in large-scale, time-critical applications. We also achieved 17 frames per second in video processing (1,280 x 720).
C1 [Jiang, Bo] NIA, Hampton, VA 23666 USA.
[Woodell, Glenn A.; Jobson, Daniel J.] NASA, Langley Res Ctr, Electromagnet & Sensors Branch, Hampton, VA 23665 USA.
RP Jiang, B (reprint author), NIA, 100 Explorat Way, Hampton, VA 23666 USA.
EM bjiang07@gmail.com
FU NASA [NNL09AA00A]
FX The authors wish to thank the NASA Aviation Safety Program, External
Hazards Sensing and Mitigation for the funding which made this work
possible. In particular, Dr. Jiang was funded by NASA Grant#NNL09AA00A
to the National Institute of Aerospace.
NR 37
TC 2
Z9 3
U1 2
U2 20
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1861-8200
EI 1861-8219
J9 J REAL-TIME IMAGE PR
JI J. Real-Time Image Process.
PD JUN
PY 2015
VL 10
IS 2
SI SI
BP 239
EP 253
DI 10.1007/s11554-014-0399-9
PG 15
WC Computer Science, Artificial Intelligence; Engineering, Electrical &
Electronic; Imaging Science & Photographic Technology
SC Computer Science; Engineering; Imaging Science & Photographic Technology
GA CI4JU
UT WOS:000354715300005
ER
PT J
AU Nelson, MI
Stratton, J
Killian, ML
Janas-Martindale, A
Vincent, AL
AF Nelson, Martha I.
Stratton, Jered
Killian, Mary Lea
Janas-Martindale, Alicia
Vincent, Amy L.
TI Continual Reintroduction of Human Pandemic H1N1 Influenza A Viruses into
Swine in the United States, 2009 to 2014
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID PIGS; TRANSMISSION; EVOLUTION; FARM; REASSORTMENT; MODELS
AB The diversity of influenza A viruses in swine (swIAVs) presents an important pandemic threat. Knowledge of the human-swine interface is particularly important for understanding how viruses with pandemic potential evolve in swine hosts. Through phylogenetic analysis of contemporary swIAVs in the United States, we demonstrate that human-to-swine transmission of pandemic H1N1 (pH1N1) viruses has occurred continuously in the years following the 2009 H1N1 pandemic and has been an important contributor to the genetic diversity of U.S. swIAVs. Although pandemic H1 and N1 segments had been largely removed from the U.S. swine population by 2013 via reassortment with other swIAVs, these antigens reemerged following multiple human-to-swine transmission events during the 2013-2014 seasonal epidemic. These findings indicate that the six internal gene segments from pH1N1 viruses are likely to be sustained long term in the U.S. swine population, with periodic reemergence of pandemic hemagglutinin (HA) and neuraminidase (NA) segments in association with seasonal pH1N1 epidemics in humans. Vaccinating U.S. swine workers may reduce infection of both humans and swine and in turn limit the role of humans as sources of influenza virus diversity in pigs.
IMPORTANCE
Swine are important hosts in the evolution of influenza A viruses with pandemic potential. Here, we analyze influenza virus sequence data generated by the U.S. Department of Agriculture's national surveillance system to identify the central role of humans in the reemergence of pandemic H1N1 (pH1N1) influenza viruses in U.S. swine herds in 2014. These findings emphasize the important role of humans as continuous sources of influenza virus diversity in swine and indicate that influenza viruses with pandemic HA and NA segments are likely to continue to reemerge in U.S. swine in association with seasonal pH1N1 epidemics in humans.
C1 [Nelson, Martha I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Stratton, Jered; Vincent, Amy L.] ARS, Virus & Prion Res Unit, Natl Anim Dis Ctr, USDA, Ames, IA USA.
[Killian, Mary Lea; Janas-Martindale, Alicia] APHIS, Diagnost Virol Lab, Natl Vet Serv Labs, Sci Technol & Anal Serv,Vet Serv,USDA, Ames, IA USA.
RP Nelson, MI (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM nelsonma@mail.nih.gov
FU Multinational Influenza Seasonal Mortality Study (MISMS); Office of
Global Affairs at the Department of Health and Human Services; USDA-ARS;
USDA-APHIS
FX This work was supported in part by the Multinational Influenza Seasonal
Mortality Study (MISMS), an ongoing international collaborative effort
to understand influenza epidemiology and evolution, led by the Fogarty
International Center, National Institutes of Health, with funding from
the Office of Global Affairs at the Department of Health and Human
Services (M.I.N.). Funding was provided by USDA-ARS (J.S. and A.L.V.)
and by USDA-APHIS (A.J.-M. and M.L.K.).
NR 36
TC 21
Z9 22
U1 0
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD JUN
PY 2015
VL 89
IS 12
BP 6218
EP 6226
DI 10.1128/JVI.00459-15
PG 9
WC Virology
SC Virology
GA CI3OU
UT WOS:000354657900007
PM 25833052
ER
PT J
AU Gromowski, GD
Firestone, CY
Whitehead, SS
AF Gromowski, Gregory D.
Firestone, Cai-Yen
Whitehead, Stephen S.
TI Genetic Determinants of Japanese Encephalitis Virus Vaccine Strain
SA14-14-2 That Govern Attenuation of Virulence in Mice
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID SA 14-14-2 VACCINE; NEPALESE CHILDREN; MOLECULAR-BASIS; NUCLEOTIDE;
GENOME; REGION; JE; NEUROVIRULENCE; FLAVIVIRUSES; IMMUNIZATION
AB The safety and efficacy of the live-attenuated Japanese encephalitis virus (JEV) SA14-14-2 vaccine are attributed to mutations that accumulated in the viral genome during its derivation. However, little is known about the contribution that is made by most of these mutations to virulence attenuation and vaccine immunogenicity. Here, we generated recombinant JEV (rJEV) strains containing JEV SA14-14-2 vaccine-specific mutations that are located in the untranslated regions (UTRs) and seven protein genes or are introduced from PCR-amplified regions of the JEV SA14-14-2 genome. The resulting mutant viruses were evaluated in tissue culture and in mice. The authentic JEV SA14-14-2 (E) protein, with amino acid substitutions L107F, E138K, I176V, T177A, E244G, Q264H, K279M, A315V, S366A, and K439R relative to the wild-type rJEV clone, was essential and sufficient for complete attenuation of neurovirulence. Individually, the nucleotide substitution T39A in the 5' UTR (5'-UTR-T39A), the capsid (C) protein amino acid substitution L66S (C-L66S), and the complete NS1/2A genome region containing 10 mutations each significantly reduced virus neuroinvasion but not neurovirulence. The levels of peripheral virulence attenuation imposed by the 5'-UTR-T39A and C-L66S mutations, individually, were somewhat mitigated in combination with other vaccine strain-specific mutations, which might be compensatory, and together did not affect immunogenicity. However, a marked reduction in immunogenicity was observed with the addition of the NS1/2A and NS5 vaccine virus genome regions. These results suggest that a second-generation recombinant vaccine can be rationally engineered to maximize levels of immunogenicity without compromising safety.
C1 [Gromowski, Gregory D.; Firestone, Cai-Yen; Whitehead, Stephen S.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Gromowski, GD (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
EM gregory.d.gromowski.civ@mail.mil
FU Intramural NIH HHS
NR 39
TC 3
Z9 3
U1 1
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD JUN
PY 2015
VL 89
IS 12
BP 6328
EP 6337
DI 10.1128/JVI.00219-15
PG 10
WC Virology
SC Virology
GA CI3OU
UT WOS:000354657900016
PM 25855730
ER
PT J
AU Hulot, SL
Korber, B
Giorgi, EE
Vandergrift, N
Saunders, KO
Balachandran, H
Mach, LV
Lifton, MA
Pantaleo, G
Tartaglia, J
Phogat, S
Jacobs, B
Kibler, K
Perdiguero, B
Gomez, CE
Esteban, M
Rosati, M
Felber, BK
Pavlakis, GN
Parks, R
Lloyd, K
Sutherland, L
Scearce, R
Letvin, NL
Seaman, MS
Alam, SM
Montefiori, D
Liao, HX
Haynes, BF
Santra, S
AF Hulot, Sandrine L.
Korber, Bette
Giorgi, Elena E.
Vandergrift, Nathan
Saunders, Kevin O.
Balachandran, Harikrishnan
Mach, Linh V.
Lifton, Michelle A.
Pantaleo, Giuseppe
Tartaglia, Jim
Phogat, Sanjay
Jacobs, Bertram
Kibler, Karen
Perdiguero, Beatriz
Gomez, Carmen E.
Esteban, Mariano
Rosati, Margherita
Felber, Barbara K.
Pavlakis, George N.
Parks, Robert
Lloyd, Krissey
Sutherland, Laura
Scearce, Richard
Letvin, Norman L.
Seaman, Michael S.
Alam, S. Munir
Montefiori, David
Liao, Hua-Xin
Haynes, Barton F.
Santra, Sampa
TI Comparison of Immunogenicity in Rhesus Macaques of Transmitted-Founder,
HIV-1 Group M Consensus, and Trivalent Mosaic Envelope Vaccines
Formulated as a DNA Prime, NYVAC, and Envelope Protein Boost
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; IMMUNE-RESPONSES;
LYMPHOCYTE RESPONSES; AIDS VACCINE; MONKEYS; DIVERSITY; ANTIBODIES;
INFECTION; EFFICACY
AB An effective human immunodeficiency virus type 1 (HIV-1) vaccine must induce protective antibody responses, as well as CD4(+) and CD8(+) T cell responses, that can be effective despite extraordinary diversity of HIV-1. The consensus and mosaic immunogens are complete but artificial proteins, computationally designed to elicit immune responses with improved cross-reactive breadth, to attempt to overcome the challenge of global HIV diversity. In this study, we have compared the immunogenicity of a transmitted-founder (T/F) B clade Env (B.1059), a global group M consensus Env (Con-S), and a global trivalent mosaic Env protein in rhesus macaques. These antigens were delivered using a DNA prime-recombinant NYVAC (rNYVAC) vector and Env protein boost vaccination strategy. While Con-S Env was a single sequence, mosaic immunogens were a set of three Envs optimized to include the most common forms of potential T cell epitopes. Both Con-S and mosaic sequences retained common amino acids encompassed by both antibody and T cell epitopes and were central to globally circulating strains. Mosaics and Con-S Envs expressed as full-length proteins bound well to a number of neutralizing antibodies with discontinuous epitopes. Also, both consensus and mosaic immunogens induced significantly higher gamma interferon (IFN-gamma) enzyme-linked immunosorbent spot assay (ELISpot) responses than B. 1059 immunogen. Immunization with these proteins, particularly Con-S, also induced significantly higher neutralizing antibodies to viruses than B. 1059 Env, primarily to tier 1 viruses. Both Con-S and mosaics stimulated more potent CD8-T cell responses against heterologous Envs than did B.1059. Both antibody and cellular data from this study strengthen the concept of using in silico-designed centralized immunogens for global HIV-1 vaccine development strategies.
C1 [Hulot, Sandrine L.; Balachandran, Harikrishnan; Mach, Linh V.; Lifton, Michelle A.; Letvin, Norman L.; Seaman, Michael S.; Santra, Sampa] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Korber, Bette; Giorgi, Elena E.] Los Alamos Natl Lab, Los Alamos, NM USA.
[Vandergrift, Nathan; Saunders, Kevin O.; Parks, Robert; Lloyd, Krissey; Sutherland, Laura; Scearce, Richard; Alam, S. Munir; Montefiori, David; Liao, Hua-Xin; Haynes, Barton F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA.
[Pantaleo, Giuseppe] Univ Lausanne, CHUV, Lausanne, Switzerland.
[Tartaglia, Jim; Phogat, Sanjay] Sanofi Pasteur, Toronto, ON, Canada.
[Jacobs, Bertram; Kibler, Karen] Arizona State Univ, Ctr Infect Dis & Vaccinol, Biodesign Inst, Tempe, AZ USA.
[Perdiguero, Beatriz; Gomez, Carmen E.; Esteban, Mariano] Ctr Nacl Biotecnol, Madrid, Spain.
[Rosati, Margherita; Felber, Barbara K.; Pavlakis, George N.] NCI, Frederick, MD 21701 USA.
RP Santra, S (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
EM ssantra@bidmc.harvard.edu
OI Korber, Bette/0000-0002-2026-5757
FU NIAID NIH HHS [P30-AI060354, U19 AI067854, U19-AI067854-07, UM1
AI100645, P30 AI060354, UM1-AI-100645]; NIH HHS [OD011103, P51 OD011103]
NR 50
TC 11
Z9 11
U1 2
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD JUN
PY 2015
VL 89
IS 12
BP 6462
EP 6480
DI 10.1128/JVI.00383-15
PG 19
WC Virology
SC Virology
GA CI3OU
UT WOS:000354657900028
PM 25855741
ER
PT J
AU Kuroda, M
Fujikura, D
Nanbo, A
Marzi, A
Noyori, O
Kajihara, M
Maruyama, J
Matsuno, K
Miyamoto, H
Yoshida, R
Feldmann, H
Takada, A
AF Kuroda, Makoto
Fujikura, Daisuke
Nanbo, Asuka
Marzi, Andrea
Noyori, Osamu
Kajihara, Masahiro
Maruyama, Junki
Matsuno, Keita
Miyamoto, Hiroko
Yoshida, Reiko
Feldmann, Heinz
Takada, Ayato
TI Interaction between TIM-1 and NPC1 Is Important for Cellular Entry of
Ebola Virus
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID NIEMANN-PICK C1; MARBURG VIRUS; DC-SIGN; PHOSPHATIDYLSERINE RECEPTORS;
ENVELOPE GLYCOPROTEIN; APOPTOTIC CELLS; PROTEIN; INFECTION; ANTIBODIES;
FILOVIRUS
AB Multiple host molecules are known to be involved in the cellular entry of filoviruses, including Ebola virus (EBOV); T-cell immunoglobulin and mucin domain 1 (TIM-1) and Niemann-Pick C1 (NPC1) have been identified as attachment and fusion receptors, respectively. However, the molecular mechanisms underlying the entry process have not been fully understood. We found that TIM-1 and NPC1 colocalized and interacted in the intracellular vesicles where EBOV glycoprotein (GP)-mediated membrane fusion occurred. Interestingly, a TIM-1-specific monoclonal antibody (MAb), M224/1, prevented GP-mediated membrane fusion and also interfered with the binding of TIM-1 to NPC1, suggesting that the interaction between TIM-1 and NPC1 is important for filovirus membrane fusion. Moreover, MAb M224/1 efficiently inhibited the cellular entry of viruses from all known filovirus species. These data suggest a novel mechanism underlying filovirus membrane fusion and provide a potential cellular target for antiviral compounds that can be universally used against filovirus infections.
C1 [Kuroda, Makoto; Noyori, Osamu; Kajihara, Masahiro; Maruyama, Junki; Matsuno, Keita; Miyamoto, Hiroko; Yoshida, Reiko; Takada, Ayato] Hokkaido Univ, Res Ctr Zoonosis Control, Div Global Epidemiol, Sapporo, Hokkaido, Japan.
[Fujikura, Daisuke] Hokkaido Univ, Div Infect & Immun, Res Ctr Zoonosis Control, Sapporo, Hokkaido, Japan.
[Nanbo, Asuka] Hokkaido Univ, Grad Sch Med, Dept Cell Physiol, Sapporo, Hokkaido, Japan.
[Marzi, Andrea; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
[Takada, Ayato] Hokkaido Univ, Global Inst Collaborat Res & Educ, Sapporo, Hokkaido, Japan.
RP Takada, A (reprint author), Hokkaido Univ, Res Ctr Zoonosis Control, Div Global Epidemiol, Sapporo, Hokkaido, Japan.
EM atakada@czc.hokudai.ac.jp
RI Nanbo, Asuka/C-6630-2012; YOSHIDA, Reiko/F-6883-2012; Maruyama,
Junki/H-7993-2013
OI Nanbo, Asuka/0000-0001-8764-1350;
FU Intramural NIH HHS
NR 52
TC 10
Z9 12
U1 1
U2 29
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD JUN
PY 2015
VL 89
IS 12
BP 6481
EP 6493
DI 10.1128/JVI.03156-14
PG 13
WC Virology
SC Virology
GA CI3OU
UT WOS:000354657900029
PM 25855742
ER
PT J
AU Ingale, J
Tran, K
Kong, L
Dey, B
McKee, K
Schief, W
Kwong, PD
Mascola, JR
Wyatt, RT
AF Ingale, Jidnyasa
Tran, Karen
Kong, Leopold
Dey, Barna
McKee, Krisha
Schief, William
Kwong, Peter D.
Mascola, John R.
Wyatt, Richard T.
TI Hyperglycosylated Stable Core Immunogens Designed To Present the CD4
Binding Site Are Preferentially Recognized by Broadly Neutralizing
Antibodies (vol 88, pg 14002, 2014)
SO JOURNAL OF VIROLOGY
LA English
DT Correction
C1 [Ingale, Jidnyasa; Schief, William; Wyatt, Richard T.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Tran, Karen; Schief, William; Wyatt, Richard T.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA.
[Kong, Leopold] Scripps Res Inst, Integrat Struct & Computat Biol, La Jolla, CA 92037 USA.
[Dey, Barna] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[McKee, Krisha; Kwong, Peter D.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Ingale, J (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD JUN
PY 2015
VL 89
IS 12
BP 6526
EP 6526
DI 10.1128/JVI.00596-15
PG 1
WC Virology
SC Virology
GA CI3OU
UT WOS:000354657900036
PM 25979984
ER
PT J
AU Chowell, G
Viboud, C
AF Chowell, Gerardo
Viboud, Cecile
TI Ebola vaccine trials: a race against the clock
SO LANCET INFECTIOUS DISEASES
LA English
DT Editorial Material
ID VIRUS DISEASE; TRANSMISSION; OUTBREAK
C1 [Chowell, Gerardo] Georgia State Univ, Sch Publ Hlth, Atlanta, GA 30303 USA.
[Chowell, Gerardo; Viboud, Cecile] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Chowell, G (reprint author), Georgia State Univ, Sch Publ Hlth, Atlanta, GA 30303 USA.
EM gchowell@gsu.edu
NR 12
TC 1
Z9 1
U1 1
U2 11
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 JUN
PY 2015
VL 15
IS 6
BP 624
EP 626
DI 10.1016/S1473-3099(15)70159-3
PG 4
WC Infectious Diseases
SC Infectious Diseases
GA CI3HI
UT WOS:000354638000008
PM 25886800
ER
PT J
AU Anstey, NM
Price, RN
Davis, TME
Karunajeewa, HA
Mueller, I
Karunajeewa, HA
D'Alessandro, U
Massougbodji, A
Nikiema, F
Ouedraogo, JB
Tinto, H
Zongo, I
Ouedraogo, JB
Tinto, H
Same-Ekobo, A
Kone, M
Menan, H
Toure, AO
Yavo, W
Yavo, W
Kofoed, PE
Alemayehu, BH
Jima, D
Baudin, E
Espie, E
Nabasumba, C
Pinoges, L
Schramm, B
Cot, M
Deloron, P
Faucher, JF
Cot, M
Deloron, P
Faucher, JF
Faucher, JF
Guthmann, JP
Lell, B
Borrmann, S
Lell, B
Adjei, GO
Kofoed, PE
Ursing, J
Tjitra, E
Borrmann, S
Marsh, K
Peshu, J
Juma, E
Ogutu, BR
Omar, SA
Sawa, P
Talisuna, AO
Talisuna, AO
Khanthavong, M
Mayxay, M
Newton, PN
Mayxay, M
Piola, P
Djimde, AA
Doumbo, OK
Fofana, B
Sagara, I
Bassat, Q
Gonzalez, R
Menendez, C
Smithuis, F
Smithuis, F
Bousema, T
Kager, PA
Mens, PF
Mens, PF
Schallig, HDFH
Van den Broek, I
Van Vugt, M
Ibrahim, ML
Falade, CO
Meremikwu, M
Meremikwu, M
Gil, JP
Karema, C
Ba, MS
Faye, B
Faye, O
Gaye, O
Ndiaye, JL
Pene, M
Sow, D
Sylla, K
Tine, RCK
Penali, LK
Barnes, KI
Workman, LJ
Barnes, KI
Workman, LJ
Bassat, Q
Gonzalez, R
Menendez, C
Mueller, I
Lima, A
Adam, I
Gadalla, NB
Malik, EFM
Bjorkman, A
Gil, JP
Martensson, A
Ngasala, BE
Ursing, J
Rombo, L
Rombo, L
Rombo, L
Aliu, P
Duparc, S
Filler, S
Genton, B
Genton, B
Hodel, EM
Olliaro, P
Abdulla, S
Kamugisha, E
Ngasala, BE
Premji, Z
Shekalaghe, SA
Shekalaghe, SA
Ashley, EA
Carrara, VI
McGready, R
Nosten, F
Ashley, EA
Faiz, AM
Lee, SJ
White, NJ
Carrara, VI
Dondorp, AM
Smith, JJ
D'Alessandro, U
Tarning, J
Achan, J
Bukirwa, H
Yeka, A
Arinaitwe, E
Staedke, SG
Kamya, MR
Kironde, F
Nabasumba, C
Bousema, T
Drakeley, CJ
Gadalla, NB
Oguike, M
Sutherland, CJ
Checchi, F
Dahal, P
Flegg, JA
Guerin, PJ
Moreira, C
Newton, PN
Nsanzabana, C
Price, RN
Sibley, CH
Stepniewska, K
Tarning, J
Dahal, P
Dondorp, AM
Flegg, JA
Guerin, PJ
Lee, SJ
Marsh, K
McGready, R
Moreira, C
Newton, PN
Nosten, F
Nsanzabana, C
Olliaro, P
Price, RN
Tarning, J
White, NJ
Gething, PW
Hay, SI
Greenwood, B
Hodel, EM
Ward, SA
Staedke, SG
Van den Broek, I
Winstanley, PA
Dorsey, G
Greenhouse, B
Rosenthal, PJ
Gadalla, NB
Gil, JP
Grivoyannis, A
Hamed, K
Hwang, J
Kachur, PS
Hwang, J
Sibley, CH
Nambozi, M
AF Anstey, N. M.
Price, R. N.
Davis, T. M. E.
Karunajeewa, H. A.
Mueller, I.
Karunajeewa, H. A.
D'Alessandro, U.
Massougbodji, A.
Nikiema, F.
Ouedraogo, J-B
Tinto, H.
Zongo, I.
Ouedraogo, J-B
Tinto, H.
Same-Ekobo, A.
Kone, M.
Menan, H.
Toure, A. O.
Yavo, W.
Yavo, W.
Kofoed, P-E
Alemayehu, B. H.
Jima, D.
Baudin, E.
Espie, E.
Nabasumba, C.
Pinoges, L.
Schramm, B.
Cot, M.
Deloron, P.
Faucher, J-F
Cot, M.
Deloron, P.
Faucher, J-F
Faucher, J-F
Guthmann, J-P
Lell, B.
Borrmann, S.
Lell, B.
Adjei, G. O.
Kofoed, P-E
Ursing, J.
Tjitra, E.
Borrmann, S.
Marsh, K.
Peshu, J.
Juma, E.
Ogutu, B. R.
Omar, S. A.
Sawa, P.
Talisuna, A. O.
Talisuna, A. O.
Khanthavong, M.
Mayxay, M.
Newton, P. N.
Mayxay, M.
Piola, P.
Djimde, A. A.
Doumbo, O. K.
Fofana, B.
Sagara, I.
Bassat, Q.
Gonzalez, R.
Menendez, C.
Smithuis, F.
Smithuis, F.
Bousema, T.
Kager, P. A.
Mens, P. F.
Mens, P. F.
Schallig, H. D. F. H.
Van den Broek, I.
Van Vugt, M.
Ibrahim, M. L.
Falade, C. O.
Meremikwu, M.
Meremikwu, M.
Gil, J. P.
Karema, C.
Ba, M. S.
Faye, B.
Faye, O.
Gaye, O.
Ndiaye, J-L
Pene, M.
Sow, D.
Sylla, K.
Tine, R. C. K.
Penali, L. K.
Barnes, K. I.
Workman, L. J.
Barnes, K. I.
Workman, L. J.
Bassat, Q.
Gonzalez, R.
Menendez, C.
Mueller, I.
Lima, A.
Adam, I.
Gadalla, N. B.
Malik, E. F. M.
Bjorkman, A.
Gil, J. P.
Martensson, A.
Ngasala, B. E.
Ursing, J.
Rombo, L.
Rombo, L.
Rombo, L.
Aliu, P.
Duparc, S.
Filler, S.
Genton, B.
Genton, B.
Hodel, E. M.
Olliaro, P.
Abdulla, S.
Kamugisha, E.
Ngasala, B. E.
Premji, Z.
Shekalaghe, S. A.
Shekalaghe, S. A.
Ashley, E. A.
Carrara, V. I.
McGready, R.
Nosten, F.
Ashley, E. A.
Faiz, A. M.
Lee, S. J.
White, N. J.
Carrara, V. I.
Dondorp, A. M.
Smith, J. J.
D'Alessandro, U.
Tarning, J.
Achan, J.
Bukirwa, H.
Yeka, A.
Arinaitwe, E.
Staedke, S. G.
Kamya, M. R.
Kironde, F.
Nabasumba, C.
Bousema, T.
Drakeley, C. J.
Gadalla, N. B.
Oguike, M.
Sutherland, C. J.
Checchi, F.
Dahal, P.
Flegg, J. A.
Guerin, P. J.
Moreira, C.
Newton, P. N.
Nsanzabana, C.
Price, R. N.
Sibley, C. H.
Stepniewska, K.
Tarning, J.
Dahal, P.
Dondorp, A. M.
Flegg, J. A.
Guerin, P. J.
Lee, S. J.
Marsh, K.
McGready, R.
Moreira, C.
Newton, P. N.
Nosten, F.
Nsanzabana, C.
Olliaro, P.
Price, R. N.
Tarning, J.
White, N. J.
Gething, P. W.
Hay, S. I.
Greenwood, B.
Hodel, E. M.
Ward, S. A.
Staedke, S. G.
Van den Broek, I.
Winstanley, P. A.
Dorsey, G.
Greenhouse, B.
Rosenthal, P. J.
Gadalla, N. B.
Gil, J. P.
Grivoyannis, A.
Hamed, K.
Hwang, J.
Kachur, P. S.
Hwang, J.
Sibley, C. H.
Nambozi, M.
CA Worldwide Antimalarial Resistance
TI The effect of dose on the antimalarial efficacy of
artemether-lumefantrine: a systematic review and pooled analysis of
individual patient data
SO LANCET INFECTIOUS DISEASES
LA English
DT Review
ID PLASMODIUM-FALCIPARUM MALARIA; POPULATION PHARMACOKINETICS;
UNCOMPLICATED MALARIA; AFRICAN INFANTS; CHILDREN; SAFETY;
PHARMACODYNAMICS; CHLOROQUINE; ARTESUNATE; RESISTANCE
AB Background Artemether-lumefantrine is the most widely used artemisinin-based combination therapy for malaria, although treatment failures occur in some regions. We investigated the effect of dosing strategy on efficacy in a pooled analysis from trials done in a wide range of malaria-endemic settings.
Methods We searched PubMed for clinical trials that enrolled and treated patients with artemether-lumefantrine and were published from 1960 to December, 2012. We merged individual patient data from these trials by use of standardised methods. The primary endpoint was the PCR-adjusted risk of Plasmodium falciparum recrudescence by day 28. Secondary endpoints consisted of the PCR-adjusted risk of P falciparum recurrence by day 42, PCR-unadjusted risk of P falciparum recurrence by day 42, early parasite clearance, and gametocyte carriage. Risk factors for PCR-adjusted recrudescence were identified using Cox's regression model with frailty shared across the study sites.
Findings We included 61 studies done between January, 1998, and December, 2012, and included 14 327 patients in our analyses. The PCR-adjusted therapeutic efficacy was 97.6% (95% CI 97.4-97.9) at day 28 and 96.0% (95.6-96.5) at day 42. After controlling for age and parasitaemia, patients prescribed a higher dose of artemether had a lower risk of having parasitaemia on day 1 (adjusted odds ratio [OR] 0.92, 95% CI 0.86-0.99 for every 1 mg/kg increase in daily artemether dose; p=0.024), but not on day 2 (p=0.69) or day 3 (0.087). In Asia, children weighing 10-15 kg who received a total lumefantrine dose less than 60 mg/kg had the lowest PCR-adjusted efficacy (91.7%, 95% CI 86.5-96.9). In Africa, the risk of treatment failure was greatest in malnourished children aged 1-3 years (PCR-adjusted efficacy 94.3%, 95% CI 92.3-96.3). A higher artemether dose was associated with a lower gametocyte presence within 14 days of treatment (adjusted OR 0.92, 95% CI 0.85-0.99; p=0.037 for every 1 mg/kg increase in total artemether dose).
Interpretation The recommended dose of artemether-lumefantrine provides reliable efficacy in most patients with uncomplicated malaria. However, therapeutic efficacy was lowest in young children from Asia and young underweight children from Africa; a higher dose regimen should be assessed in these groups.
C1 [Anstey, N. M.; Price, R. N.] Menzies Sch Hlth Res, Global & Trop Hlth Div, Darwin, NT, Australia.
[Anstey, N. M.] Charles Darwin Univ, Darwin, NT 0909, Australia.
[Davis, T. M. E.] Univ Western Australia, Sch Med & Pharmacol, Crawley, WA, Australia.
[Karunajeewa, H. A.; Mueller, I.] Walter & Eliza Hall Inst Med Res, Infect & Immun Div, Melbourne, Vic, Australia.
Western Hlth, Div Med, Melbourne, Vic, Australia.
[D'Alessandro, U.] Inst Trop Med, Unit Malariol, B-2000 Antwerp, Belgium.
[Massougbodji, A.] Univ dAbomey Calavi, Fac Sci Sante, Ctr Etud & Rech Paludisme Associe Grossesse & Enf, Cotonou, Benin.
[Nikiema, F.; Ouedraogo, J-B; Tinto, H.] Inst Rech Sci Sante, Direct Reg Ouest, Bobo Dioulasso, Burkina Faso.
Ctr Muraz, Bobo Dioulasso, Burkina Faso.
[Same-Ekobo, A.] Univ Yaounde, Ctr Hosp, Fac Med & Sci Biomed, Yaounde, Cameroon.
[Kone, M.; Menan, H.; Yavo, W.] Univ Cocody, Fac Pharm, Dept Parasitol & Mycol, Abidjan, Cote Ivoire.
[Toure, A. O.] Inst Pasteur Cote Ivoire, Malariol Dept, Abidjan, Cote Ivoire.
[Yavo, W.] Natl Inst Publ Hlth, Malaria Res & Control Ctr, Abidjan, Cote Ivoire.
[Kofoed, P-E] Kolding Cty Hosp, Dept Paediat, Kolding, Denmark.
[Alemayehu, B. H.] Int Ctr AIDS Care & Treatment Programs, Addis Ababa, Ethiopia.
[Jima, D.] Fed Minist Hlth, Addis Ababa, Ethiopia.
[Baudin, E.; Espie, E.; Nabasumba, C.; Pinoges, L.; Schramm, B.] Epictr, Paris, France.
[Cot, M.; Deloron, P.; Faucher, J-F] Inst Rech Dev, Mother & Child Hlth Trop Res Unit, Paris, France.
[Cot, M.; Deloron, P.; Faucher, J-F] Univ Paris 05, Sorbonne Paris Cite, PRES, Paris, France.
[Faucher, J-F] Univ Besancon, Med Ctr, Dept Infect Dis, F-25030 Besancon, France.
[Guthmann, J-P] Inst Veille Sanit, Dept Malad Infect, St Maurice, France.
[Lell, B.] Ctr Rech Med Lambarene, Lambarene, Gabon.
[Lell, B.; Borrmann, S.] Univ Tubingen, Inst Trop Med, Tubingen, Germany.
[Adjei, G. O.] Univ Ghana, Sch Med, Ctr Trop Clin Pharmacol & Therapeut, Accra, Ghana.
[Kofoed, P-E] Projecto Saude Bandim, Bissau, Guinea Bissau.
[Tjitra, E.] Minist Hlth, Natl Inst Hlth Res & Dev, Jakarta, Indonesia.
[Borrmann, S.; Marsh, K.; Peshu, J.] Kenya Govt Med Res Ctr, Kilifi, Kenya.
[Borrmann, S.; Marsh, K.; Peshu, J.] Wellcome Trust Res Programme, Kilifi, Kenya.
[Juma, E.] Kenya Govt Med Res Ctr, Nairobi, Kenya.
[Ogutu, B. R.] Kenya Govt Med Res Ctr, Kisumu, Kenya.
[Ogutu, B. R.] US Army Med Res Unit, Kisumu, Kenya.
[Omar, S. A.; Sawa, P.] Int Ctr Insect Physiol & Ecol, Human Hlth Div, Mbita Point, Kenya.
[Talisuna, A. O.] WWARN East Africa Reg Ctr, Nairobi, Kenya.
[Talisuna, A. O.] Univ Oxford, KEMRI, Oxford OX3 7LJ, England.
[Talisuna, A. O.] Wellcome Trust Res Programme, Nairobi, Kenya.
[Khanthavong, M.] Ctr Malariol Parasitol & Entomol, Viangchan, Laos.
[Mayxay, M.; Newton, P. N.] Oxford Univ Trop Med Res Collaborat, Mahosot Hosp, Wellcome Trust Mahosot Hosp, Viangchan, Laos.
[Mayxay, M.] Natl Univ Laos, Fac Med Sci, Viangchan, Laos.
[Piola, P.] Inst Pasteur Madagascar, Antananarivo, Madagascar.
[Djimde, A. A.; Doumbo, O. K.; Fofana, B.; Sagara, I.] Univ Bamako, Fac Med Pharm & Odontostomatol, Dept Epidemiol Parasit Dis, Malaria Res & Training Ctr, Bamako, Mali.
[Bassat, Q.; Gonzalez, R.; Menendez, C.] Ctr Invest Saude Manhica, Manhica, Mozambique.
[Smithuis, F.] Myanmar Oxford Clin Res Unit, Yangon, Myanmar.
[Smithuis, F.] Myanmar & Med Act Myanmar, Yangon, Myanmar.
[Bousema, T.] Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, Njimegen, Netherlands.
[Kager, P. A.; Mens, P. F.] Univ Amsterdam, Acad Med Ctr, Ctr Infect & Immun Amsterdam CINEMA, Div Infect Dis Trop Med & AIDS, NL-1105 AZ Amsterdam, Netherlands.
[Mens, P. F.; Schallig, H. D. F. H.] Royal Trop Inst, KIT Biomed Res, NL-1105 AZ Amsterdam, Netherlands.
[Van den Broek, I.] Natl Inst Publ Hlth & Environm, Ctr Infect Dis Control, NL-3720 BA Bilthoven, Netherlands.
[Van Vugt, M.] Univ Amsterdam, Acad Med Ctr, Ctr Trop Med & Travel Med, Div Infect Dis, NL-1012 WX Amsterdam, Netherlands.
[Ibrahim, M. L.] Ctr Rech Med & Sanit, Niamey, Niger.
[Falade, C. O.] Univ Ibadan, Coll Med, Ibadan, Nigeria.
[Meremikwu, M.] Univ Calabar, Dept Paediat, Calabar, Nigeria.
Inst Trop Dis Res & Prevent, Calabar, Nigeria.
[Gil, J. P.] Univ Lisbon, Fac Ciencias, Ctr Biodivers Funct & Integrat Genom, Drug Resistance & Pharmacogenet, P-1699 Lisbon, Portugal.
[Karema, C.] Minist Hlth, Malaria & Other Parasit Dis Div RBC, Kigali, Rwanda.
[Ba, M. S.; Faye, B.; Faye, O.; Gaye, O.; Ndiaye, J-L; Pene, M.; Sow, D.; Sylla, K.; Tine, R. C. K.] Univ Cheikh Anta Diop, Fac Med, Dept Parasitol & Mycol, Dakar, Senegal.
[Penali, L. K.] WWARN West Africa Reg Ctr, Dakar, Senegal.
[Barnes, K. I.; Workman, L. J.] WWARN, Pharmacol Module, Cape Town, South Africa.
[Barnes, K. I.; Workman, L. J.] Univ Cape Town, Dept Med, Div Clin Pharmacol, ZA-7925 Cape Town, South Africa.
[Bassat, Q.; Gonzalez, R.; Menendez, C.] Ctr Recerca Salut Int Barcelona, Barcelona, Spain.
[Lima, A.] Medecins Sans Frontieres Operat Ctr Barcelona Ath, Barcelona, Spain.
[Adam, I.] Univ Khartoum, Fac Med, Khartoum, Sudan.
[Gadalla, N. B.] Natl Res Ctr, Res Inst Trop Med, Dept Epidemiol, Khartoum, Sudan.
[Malik, E. F. M.] Fed Minist Hlth, Khartoum, Sudan.
[Bjorkman, A.] Karolinska Univ Hosp, Karolinska Inst, Dept Med, Infect Dis Unit, Stockholm, Sweden.
[Gil, J. P.] Karolinska Inst, Dept Physiol & Pharmacol, Drug Resistance Unit, Pharmacogenet Sect, Stockholm, Sweden.
[Ursing, J.; Martensson, A.; Ngasala, B. E.] Karolinska Inst, Dept Med Solna, Infect Dis Unit, Malaria Res, Stockholm, Sweden.
[Martensson, A.] Karolinska Inst, Dept Publ Hlth Sci, Div Global Hlth, Stockholm, Sweden.
[Rombo, L.] Karolinska Univ Hosp, Dept Med, Malaria Res Lab, Infect Dis Unit, Stockholm, Sweden.
[Rombo, L.] Dept Infect Dis, Eskilstuna, Sweden.
[Rombo, L.] Sormland Cty Council, Clin Res Ctr, Sormland, Sweden.
[Aliu, P.] Novartis Pharma AG, Basel, Switzerland.
[Duparc, S.] Med Malaria Venture, Geneva, Switzerland.
[Filler, S.] Global Fund Fight AIDS TB & Malaria, Geneva, Switzerland.
[Genton, B.] Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland.
[Genton, B.] Univ Lausanne Hosp, Div Infect Dis, Lausanne, Switzerland.
[Genton, B.] Univ Lausanne Hosp, Dept Ambulatory Care & Community Med, Lausanne, Switzerland.
[Hodel, E. M.] Swiss Trop & Publ Hlth Inst, Basel, Switzerland.
[Olliaro, P.] UNDP, UNICEF, World Bank, Geneva, Switzerland.
[Olliaro, P.] WHO, Special Programme Res & Training Trop Dis, CH-1211 Geneva, Switzerland.
[Abdulla, S.] Ifakara Hlth Inst, Dar Es Salaam, Tanzania.
[Kamugisha, E.] Catholic Univ Hlth & Allied Sci, Mwanza, Tanzania.
[Ngasala, B. E.; Premji, Z.] Muhimbili Univ Hlth & Allied Sci, Dept Parasitol, Dar Es Salaam, Tanzania.
[Shekalaghe, S. A.] Kilimanjaro Christian Med Ctr, Kilimanjaro Clin Med Res Inst, Moshi, Tanzania.
[Shekalaghe, S. A.] Ifakara Hlth Inst, Bagamoyo, Tanzania.
[Ashley, E. A.; Carrara, V. I.; McGready, R.; Nosten, F.] Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Shoklo Malaria Res Unit, Mae Sot, Thailand.
[Ashley, E. A.; Faiz, A. M.; Lee, S. J.; White, N. J.] Mahidol Univ, Fac Trop Med, Bangkok, Thailand.
[Carrara, V. I.; Dondorp, A. M.] Mahidol Univ, Mahidol Oxford Univ Res Unit, Bangkok, Thailand.
[Smith, J. J.] WWARN Asia Reg Ctr, Bangkok, Thailand.
MRC Unit, Fajara, Gambia.
[Tarning, J.] Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand.
[Achan, J.; Bukirwa, H.; Yeka, A.] Uganda Malaria Surveillance Project, Kampala, Uganda.
[Arinaitwe, E.; Staedke, S. G.] Infect Dis Res Collaborat, Kampala, Uganda.
[Kamya, M. R.] Makerere Univ, Coll Hlth Sci, Kampala, Uganda.
[Kironde, F.] Makerere Univ, Dept Biochem, Kampala, Uganda.
[Nabasumba, C.] Mbarara Univ Sci & Technol, Fac Med, Mbarara, Uganda.
[Bousema, T.; Gadalla, N. B.; Drakeley, C. J.; Oguike, M.; Sutherland, C. J.] London Sch Hyg & Trop Med, Immunol & Infect Dept, London WC1, England.
[Checchi, F.] Save Children, Humanitarian Dept, London, England.
[Newton, P. N.; Tarning, J.; Dahal, P.; Flegg, J. A.; Guerin, P. J.; Moreira, C.; Nsanzabana, C.; Sibley, C. H.; Stepniewska, K.] Worldwide Antimalarial Resistance Network, Oxford, England.
[Marsh, K.; Newton, P. N.; Olliaro, P.; McGready, R.; Nosten, F.; Lee, S. J.; White, N. J.; Dondorp, A. M.; Tarning, J.; Dahal, P.; Flegg, J. A.; Guerin, P. J.; Moreira, C.; Nsanzabana, C.] Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med & Global Hlth, Oxford, England.
[Gething, P. W.; Hay, S. I.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford, England.
[Greenwood, B.] London Sch Hyg & Trop Med, Dept Dis Control, London WC1, England.
[Hodel, E. M.; Ward, S. A.] Univ Liverpool, Liverpool Sch Trop Med, Dept Parasitol, Liverpool L3 5QA, Merseyside, England.
[Staedke, S. G.] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Clin Res, London WC1, England.
[Van den Broek, I.] Medecins Sans Frontieres, London, England.
[Winstanley, P. A.] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England.
[Dorsey, G.; Greenhouse, B.; Rosenthal, P. J.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Gadalla, N. B.] NIAID, Rockville, MD USA.
[Gil, J. P.] SUNY Binghamton, Harpur Coll Arts & Sci, Binghamton, NY USA.
[Grivoyannis, A.] Univ Washington, Div Emergency Med, Seattle, WA 98195 USA.
[Hamed, K.] Novartis, E Hanover, NJ USA.
[Hwang, J.; Kachur, P. S.] US Ctr Dis Control & Prevent, Atlanta, GA USA.
[Hwang, J.] Univ Calif San Francisco, Global Hlth Grp, San Francisco, CA 94143 USA.
[Sibley, C. H.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Nambozi, M.] Trop Dis Res Ctr, Ndola, Zambia.
RP Price, RN (reprint author), Univ Oxford, Ctr Trop Med & Global Hlth, Worldwide Antimalarial Resistance Network, S Parks Rd, Oxford OX3 7LJ, England.
EM ric.price@wwarn.org; christian.nsanzabana@wwarn.org
RI Hodel, Eva Maria/E-1258-2014; Bousema, Teun/N-3574-2014; Ward,
Steve/G-6003-2015; Hay, Simon/F-8967-2015;
OI Guerin, Philippe/0000-0002-6008-2963; Hamed, Kamal/0000-0003-1896-9736;
Price, Richard/0000-0003-2000-2874; Hodel, Eva
Maria/0000-0001-5821-1685; Ward, Steve/0000-0003-2331-3192; Hay,
Simon/0000-0002-0611-7272; Gething, Peter/0000-0001-6759-5449; GADALLA,
NAHLA/0000-0002-6177-6705; Dahal, Prabin/0000-0002-2158-846X; Flegg,
Jennifer/0000-0002-8809-726X; Nosten, Francois/0000-0002-7951-0745;
McGready, Rose/0000-0003-1621-3257
FU Bill & Melinda Gates Foundation
FX Bill & Melinda Gates Foundation.
NR 32
TC 16
Z9 16
U1 4
U2 20
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 JUN
PY 2015
VL 15
IS 6
BP 692
EP 702
DI 10.1016/S1473-3099(15)70024-1
PG 11
WC Infectious Diseases
SC Infectious Diseases
GA CI3HI
UT WOS:000354638000034
ER
PT J
AU Nachman, S
Ahmed, A
Amanullah, F
Becerra, MC
Botgros, R
Brigden, G
Browning, R
Gardiner, E
Hafner, R
Hesseling, A
How, C
Jean-Philippe, P
Lessem, E
Makhene, M
Mbelle, N
Marais, B
McIlleron, H
McNeeley, DF
Mendel, C
Murray, S
Navarro, E
Anyalechi, EG
Porcalla, AR
Powell, C
Powell, M
Rigaud, M
Rouzier, V
Samson, P
Schaaf, HS
Shah, S
Starke, J
Swaminathan, S
Wobudeya, E
Worrell, C
AF Nachman, Sharon
Ahmed, Amina
Amanullah, Farhana
Becerra, Mercedes C.
Botgros, Radu
Brigden, Grania
Browning, Renee
Gardiner, Elizabeth
Hafner, Richard
Hesseling, Anneke
How, Cleotilde
Jean-Philippe, Patrick
Lessem, Erica
Makhene, Mamodikoe
Mbelle, Nontombi
Marais, Ben
McIlleron, Helen
McNeeley, David F.
Mendel, Carl
Murray, Stephen
Navarro, Eileen
Anyalechi, E. Gloria
Porcalla, Ariel R.
Powell, Clydette
Powell, Mair
Rigaud, Mona
Rouzier, Vanessa
Samson, Pearl
Schaaf, H. Simon
Shah, Seema
Starke, Jeff
Swaminathan, Soumya
Wobudeya, Eric
Worrell, Carol
TI Towards early inclusion of children in tuberculosis drugs trials: a
consensus statement
SO LANCET INFECTIOUS DISEASES
LA English
DT Review
ID MULTIDRUG-RESISTANT TUBERCULOSIS; SOUTH-AFRICAN CHILDREN; CHILDHOOD
TUBERCULOSIS; ANTITUBERCULOSIS AGENTS; MANAGEMENT CHALLENGES; WESTERN
CAPE; RISK-FACTORS; HIV; RECOMMENDATIONS; MORTALITY
AB Children younger than 18 years account for a substantial proportion of patients with tuberculosis worldwide. Available treatments for paediatric drug-susceptible and drug-resistant tuberculosis, albeit generally effective, are hampered by high pill burden, long duration of treatment, coexistent toxic effects, and an overall scarcity of suitable child-friendly formulations. Several new drugs and regimens with promising activity against both drug-susceptible and drug-resistant strains have entered clinical development and are either in various phases of clinical investigation or have received marketing authorisation for adults; however, none have data on their use in children. This consensus statement, generated from an international panel of opinion leaders on childhood tuberculosis and incorporating reviews of published literature from January, 2004, to May, 2014, addressed four key questions: what drugs or regimens should be prioritised for clinical trials in children? Which populations of children are high priorities for study? When can phase 1 or 2 studies be initiated in children? What are the relevant elements of clinical trial design? The consensus panel found that children can be included in studies at the early phases of drug development and should be an integral part of the clinical development plan, rather than studied after regulatory approval in adults is obtained.
C1 [Nachman, Sharon] SUNY Stony Brook, Stony Brook, NY 11794 USA.
[Ahmed, Amina] Carolinas Med Ctr, Levine Childrens Hosp, Charlotte, NC 28203 USA.
[Amanullah, Farhana] Indus Hosp, Karachi, Pakistan.
[Becerra, Mercedes C.] Harvard Univ, Sch Med, Boston, MA USA.
[Botgros, Radu; Powell, Mair] European Med Agcy, London, England.
[Brigden, Grania] Access Campaign, Medecins Sans Frontieres, Geneva, Switzerland.
[Browning, Renee; Hafner, Richard; Makhene, Mamodikoe] NIAID, NIH, Div Aids, Bethesda, MD 20892 USA.
[Gardiner, Elizabeth; Mendel, Carl; Murray, Stephen] TB Alliance, New York, NY USA.
[Hesseling, Anneke; Schaaf, H. Simon] Univ Stellenbosch, Dept Paediat & Child Hlth, Desmond Tutu TB Ctr, Cape Town, South Africa.
[How, Cleotilde] Univ Philippines, Dept Pharmacol & Toxicol, Manila, Philippines.
[Jean-Philippe, Patrick] NIAID, Henry Jackson Fdn, Div Aids, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Lessem, Erica] Treatment Act Grp, New York, NY USA.
[Mbelle, Nontombi] Univ Pretoria, Dept Med Microbiol, ZA-0002 Pretoria, South Africa.
[Marais, Ben] Univ Sydney, Marie Bashir Inst Infect Dis & Biosecur, Sydney, NSW 2006, Australia.
[Marais, Ben] Univ Sydney, Sydney Emerging Infect Dis & Biosecur Inst, Sydney, NSW 2006, Australia.
[Marais, Ben] Univ Sydney, Childrens Hosp Westmead, Sydney, NSW 2006, Australia.
[McIlleron, Helen] Univ Cape Town, Dept Med, Div Clin Pharmacol, ZA-7700 Rondebosch, South Africa.
[McNeeley, David F.] Novartis Pharmaceut, E Hanover, NJ USA.
[Navarro, Eileen; Porcalla, Ariel R.] US FDA, Div Antiinfect Prod, Off Antimicrobial Prod, Off New Drugs, Silver Spring, MD USA.
[Anyalechi, E. Gloria] US Ctr Dis Control & Prevent, Div TB Eliminat, Int Res & Programs Branch, Atlanta, GA USA.
[Powell, Clydette] Agcy Int Dev, Washington, DC USA.
[Rigaud, Mona] NYU, Sch Med, New York, NY 10003 USA.
[Rouzier, Vanessa] GHESKIO, Port Au Prince, Haiti.
[Samson, Pearl] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res & Frontier Sci, Stat & Data Anal Ctr, Boston, MA 02115 USA.
[Shah, Seema] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA.
[Starke, Jeff] Baylor Coll Med, Houston, TX 77030 USA.
[Swaminathan, Soumya] Natl Inst Res TB, Madras, Tamil Nadu, India.
[Wobudeya, Eric] Makerere Univ Johns Hopkins Res Collaborat, Kampala, Uganda.
[Wobudeya, Eric] Mulago Natl Referral Hosp, Kampala, Uganda.
[Worrell, Carol] Eunice Kennedy Schriver Natl Inst Child Hlth & Hu, NIH, Rockville, MD USA.
RP Nachman, S (reprint author), Hlth Sci SUNY Stony Brook, Stony Brook Childrens Hosp, Dept Pediat, Stony Brook, NY 11794 USA.
EM sharon.nachman@stonybrook.edu
OI wobudeya, eric/0000-0001-9574-5539; McIlleron, Helen/0000-0002-0982-6226
FU National Institute of Allergy and Infectious Diseases; National
Institute of Health; Department of Health and Human Services; HHS
FX We thank the following individuals for assistance in the planning and
conduct of the workshop or drafting of the manuscript, or both: Sheryl
Zwerski, Sarah Read, Larry Fox, Devasena Gnanashanmugam, Judi Miller,
Ellen O'Gara, Paul Sato, Peter Kim, Tyseaia Squirewell McFarlane, Rahel
Abebe, and Andrea Williams. This work was funded by National Institute
of Allergy and Infectious Diseases and National Institute of Health.
This project has also been funded in part with federal funds from the
Department of Health and Human Services. The views expressed in written
conference materials or publications and by speakers and moderators at
HHS-sponsored conferences, do not necessarily show the official policies
of the Department of Health and Human Services (DHHS) or individual DHHS
or other US government agencies including the National Institute of
Health, the Center for Disease Control and Prevention, the Food and Drug
Administration or the US Agency for International Development; nor does
mention of trade names, commercial practices, or organisations imply
endorsement by the US Government. The views expressed in this consensus
statement are the personal views of the authors and cannot be understood
or quoted as made on behalf of the position of the European Medicines
Agency, or one of its committees or working parties.
NR 75
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U1 1
U2 7
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 JUN
PY 2015
VL 15
IS 6
BP 711
EP 720
DI 10.1016/S1473-3099(15)00007-9
PG 10
WC Infectious Diseases
SC Infectious Diseases
GA CI3HI
UT WOS:000354638000036
PM 25957923
ER
PT J
AU Colberg-Poley, AM
Patterson, GH
Salka, K
Bhuvanendran, S
Yang, D
Jaiswal, JK
AF Colberg-Poley, Anamaris M.
Patterson, George H.
Salka, Kyle
Bhuvanendran, Shivaprasad
Yang, David
Jaiswal, Jyoti K.
TI Superresolution imaging of viral protein trafficking
SO MEDICAL MICROBIOLOGY AND IMMUNOLOGY
LA English
DT Review
DE Cytomegalovirus; Superresolution imaging; vMIA; MAM; Mitochondria; MSIM;
PALM; STED
ID HUMAN CYTOMEGALOVIRUS-INFECTION; MITOCHONDRION-ASSOCIATED MEMBRANES;
ENDOPLASMIC-RETICULUM; RIG-I; UL37 PROTEINS; FLUORESCENCE NANOSCOPY;
LOCALIZED INHIBITOR; STRUCTURAL BASIS; INNATE IMMUNITY; INNER MEMBRANE
AB The endoplasmic reticulum (ER) membrane is closely apposed to the outer mitochondrial membrane (OMM), which facilitates communication between these organelles. These contacts, known as mitochondria-associated membranes (MAM), facilitate calcium signaling, lipid transfer, as well as antiviral and stress responses. How cellular proteins traffic to the MAM, are distributed therein, and interact with ER and mitochondrial proteins are subject of great interest. The human cytomegalovirus UL37 exon 1 protein or viral mitochondria-localized inhibitor of apoptosis (vMIA) is crucial for viral growth. Upon synthesis at the ER, vMIA traffics to the MAM and OMM, where it reprograms the organization and function of these compartments. vMIA significantly changes the abundance of cellular proteins at the MAM and OMM, including proteins that regulate calcium homeostasis and cell death. Through the use of superresolution imaging, we have shown that vMIA is distributed at the OMM in nanometer scale clusters. This is similar to the clusters reported for the mitochondrial calcium channel, VDAC, as well as electron transport chain, translocase of the OMM complex, and mitochondrial inner membrane organizing system components. Thus, aside from addressing how vMIA targets the MAM and regulates survival of infected cells, biochemical studies and superresolution imaging of vMIA offer insights into the formation, organization, and functioning of MAM. Here, we discuss these insights into trafficking, function, and organization of vMIA at the MAM and OMM and discuss how the use of superresolution imaging is contributing to the study of the formation and trafficking of viruses.
C1 [Colberg-Poley, Anamaris M.; Salka, Kyle; Bhuvanendran, Shivaprasad; Jaiswal, Jyoti K.] Childrens Natl Hlth Syst, Med Genet Res Ctr, Washington, DC 20010 USA.
[Colberg-Poley, Anamaris M.; Jaiswal, Jyoti K.] George Washington Univ, Sch Med & Hlth Sci, Dept Integrat Syst Biol, Washington, DC 20037 USA.
[Colberg-Poley, Anamaris M.; Jaiswal, Jyoti K.] George Washington Univ, Sch Med & Hlth Sci, Dept Pediat, Washington, DC 20037 USA.
[Colberg-Poley, Anamaris M.] George Washington Univ, Sch Med & Hlth Sci, Dept Biochem, Washington, DC 20037 USA.
[Colberg-Poley, Anamaris M.] George Washington Univ, Sch Med & Hlth Sci, Dept Mol Med, Washington, DC 20037 USA.
[Patterson, George H.] Natl Inst Biomed Imaging & Bioengn, Sect Biophoton, NIH, Bethesda, MD 20892 USA.
[Yang, David] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20037 USA.
RP Colberg-Poley, AM (reprint author), Childrens Natl Hlth Syst, Med Genet Res Ctr, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM acolberg-poley@childrensnational.org; pattersg@mail.nih.gov;
jkjaiswal@childrensnational.org
RI Jaiswal, Jyoti/M-5891-2013
OI Jaiswal, Jyoti/0000-0002-5992-5185
FU NSF [MCB 1244509]; National Institutes of Health; National Institute of
Biomedical Imaging and Bioengineering; [1P30HD40677]
FX This work was partially funded by the NSF Grant (MCB 1244509) to ACP and
JKJ. The confocal microscopy imaging was supported by a core Grant
(1P30HD40677) to the Children's Intellectual and Developmental
Disabilities Research Center. This work was also supported by the
Intramural Research Program of the National Institutes of Health
including the National Institute of Biomedical Imaging and
Bioengineering. We thank Kristen Rainey for assisting with imaging and
analysis. We thank Andrew York and Hari Shroff for sharing MSIM analysis
and deconvolution software. We thank Harald Hess for the use of the PALM
analysis software, PeakSelector.
NR 100
TC 3
Z9 3
U1 3
U2 11
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0300-8584
EI 1432-1831
J9 MED MICROBIOL IMMUN
JI Med. Microbiol. Immunol.
PD JUN
PY 2015
VL 204
IS 3
BP 449
EP 460
DI 10.1007/s00430-015-0395-0
PG 12
WC Immunology; Microbiology
SC Immunology; Microbiology
GA CI6UI
UT WOS:000354897600022
PM 25724304
ER
PT J
AU Boyington, J
Joseph, L
Fielding, R
Pate, R
AF Boyington, Josephine
Joseph, Lyndon
Fielding, Roger
Pate, Russell
TI Sedentary Behavior Research Priorities-NHLBI/NIA Sedentary Behavior
Workshop Summary
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
ID TYPE-2 DIABETES-MELLITUS; PHYSICAL-ACTIVITY; CARDIOVASCULAR-DISEASE;
TIME SPENT; US ADULTS; RISK; MORTALITY; MEN; OBESITY; WOMEN
C1 [Boyington, Josephine] NHLBI, NIH, Bethesda, MD 20892 USA.
[Joseph, Lyndon] NIA, NIH, Bethesda, MD 20892 USA.
[Fielding, Roger] Tufts Univ, Nutr Exercise Physiol & Sarcopenia Lab, Jean Mayer USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Pate, Russell] Univ S Carolina, Arnold Sch Publ Hlth, Columbia, SC 29208 USA.
RP Pate, R (reprint author), Univ S Carolina, Arnold Sch Publ Hlth, Suite 212,921 Assembly St, Columbia, SC 29208 USA.
EM rpate@mailbox.sc.edu
FU National Heart, Lung, and Blood Institute; National Institute on Aging;
Office of Disease Prevention of the National Institutes of Health; U.S.
Department of Agriculture [58-19500-014]; Boston Claude D. Pepper Older
Americans Independence Center [1P30AG031679]; U.S. Department of
Agriculture; National Institutes of Health; Nestec Ltd.; Regeneron
Pharmaceutical; Centers for Disease Control and Prevention; Duke
Endowment; FTZ Coca-Cola Service Company
FX The workshop was sponsored by the National Heart, Lung, and Blood
Institute, the National Institute on Aging, and the Office of Disease
Prevention of the National Institutes of Health. The views expressed in
this document reflect the collective ideas and opinions of the authors
and do not necessarily represent the official views of the National
Institutes of Health, the U.S. Department of Health and Human Services,
or the other workshop participants.; Dr. Fielding's participation in
this project was partially supported by the U.S. Department of
Agriculture, under agreement no. 58-19500-014, and the Boston Claude D.
Pepper Older Americans Independence Center (1P30AG031679). Any opinions,
findings, conclusion, or recommendations expressed in this publication
are those of the author(s) and do not necessarily reflect the views of
the U.S. Department of Agriculture.; Dr. Fielding receives grant support
from the U.S. Department of Agriculture, National Institutes of Health,
Nestec Ltd., and Regeneron Pharmaceutical; is a consultant to Regeneron
Pharmaceuticals and Nestec, Ltd; serves on the Scientific Advisory
Boards of Cytokinetics, Inc., Pronutria, Inc., Amonnett, Inc., and
Inside Tracker, Inc,; and owns stock or options in Pronutria, Amonnett,
Inc., Inside Tracker, and Myosyntax.; Dr. Pate receives grant support
from the National Institutes of Health, Centers for Disease Control and
Prevention, Duke Endowment, and FTZ Coca-Cola Service Company. He serves
on the Scientific Advisory Board of Curves, Inc.
NR 17
TC 4
Z9 4
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD JUN
PY 2015
VL 47
IS 6
BP 1291
EP 1294
DI 10.1249/MSS.0000000000000516
PG 4
WC Sport Sciences
SC Sport Sciences
GA CI4TC
UT WOS:000354745500024
PM 25222819
ER
PT J
AU Peyrot, WJ
Lee, SH
Milaneschi, Y
Abdellaoui, A
Byrne, EM
Esko, T
de Geus, EJC
Hemani, G
Hottenga, JJ
Kloiber, S
Levinson, DF
Lucae, S
Martin, NG
Medland, SE
Metspalu, A
Milani, L
Noethen, MM
Potash, JB
Rietschel, M
Rietveld, CA
Ripke, S
Shi, J
Willemsen, G
Zhu, Z
Boomsma, DI
Wray, NR
Penninx, BWJH
AF Peyrot, W. J.
Lee, S. H.
Milaneschi, Y.
Abdellaoui, A.
Byrne, E. M.
Esko, T.
de Geus, E. J. C.
Hemani, G.
Hottenga, J. J.
Kloiber, S.
Levinson, D. F.
Lucae, S.
Martin, N. G.
Medland, S. E.
Metspalu, A.
Milani, L.
Noethen, M. M.
Potash, J. B.
Rietschel, M.
Rietveld, C. A.
Ripke, S.
Shi, J.
Willemsen, G.
Zhu, Z.
Boomsma, D. I.
Wray, N. R.
Penninx, B. W. J. H.
CA Major Depressive Disorder Working
Social Sci Genetic Assoc Consortiu
TI The association between lower educational attainment and depression
owing to shared genetic effects? Results in similar to 25 000 subjects
SO MOLECULAR PSYCHIATRY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SOCIOECONOMIC DISPARITIES; DISORDER; HEALTH;
EPIDEMIOLOGY; POPULATION; STRESS; COMMON; LOCI; TWIN
AB An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14 949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15 138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884 105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on similar to 120 000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status.
C1 [Peyrot, W. J.; Milaneschi, Y.; Penninx, B. W. J. H.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
[Peyrot, W. J.; Milaneschi, Y.; Penninx, B. W. J. H.] GGZ inGeest, Amsterdam, Netherlands.
[Lee, S. H.; Byrne, E. M.; Hemani, G.; Zhu, Z.; Wray, N. R.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.
[Abdellaoui, A.; Hottenga, J. J.; Willemsen, G.; Boomsma, D. I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
[Esko, T.; Metspalu, A.; Milani, L.] Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
[Esko, T.; Metspalu, A.] Childrens Hosp Boston, Div Endocrinol, Boston, MA USA.
[Esko, T.; Metspalu, A.] Childrens Hosp Boston, Ctr Basic & Translat Obes Res, Boston, MA USA.
[Esko, T.; Metspalu, A.] Harvard Univ, Sch Med, Boston, MA USA.
[Esko, T.; Metspalu, A.] Broad Inst, Cambridge, MA USA.
[Hemani, G.] Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit IEU, Bristol, Avon, England.
[Kloiber, S.] Max Planck Inst Psychiat, D-80804 Munich, Germany.
[Levinson, D. F.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
[Martin, N. G.; Medland, S. E.] QIMR Berhgofer Inst Med Res, Genet Epidemiol Unit, Brisbane, Qld, Australia.
[Noethen, M. M.] Univ Bonn, Inst Human Genet, Bonn, Germany.
[Potash, J. B.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA.
[Rietschel, M.] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, Heidelberg, Germany.
[Rietveld, C. A.] Erasmus Univ, Erasmus Sch Econ, Rotterdam, Netherlands.
[Rietveld, C. A.] Erasmus Univ, Inst Behav & Biol, Rotterdam, Netherlands.
[Ripke, S.] MIT & Harvard, Stanley Ctr Psychiat Res, Broad Inst, Cambridge, MA USA.
[Shi, J.] Natl Canc Inst, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD USA.
RP Peyrot, WJ (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, AJ Ernststr 1187, Amsterdam, Netherlands.
EM w.peyrot@ggzingeest.nl
RI Gudnason, Vilmundur/K-6885-2015; Ripatti, Samuli/H-9446-2014; Lee, Sang
Hong/A-2569-2011; Polasek, Ozren/B-6002-2011; Mattheisen,
Manuel/B-4949-2012; Breen, Gerome/A-5540-2010; Smith,
Albert/K-5150-2015; Holle, Rolf/D-9333-2013; Lewis, Glyn/E-9944-2012;
Deloukas, Panos/B-2922-2013; Fehrmann, Rudolf/E-2551-2011; Colaus,
PsyColaus/K-6607-2013; Allik, Juri/D-5609-2009; Realo, Anu/M-9524-2016;
Lewis, Cathryn/A-5225-2010; Karjalainen, Juha/P-8624-2016; Palmer,
Lyle/K-3196-2014; Kolcic, Ivana/E-2713-2017;
OI Gudnason, Vilmundur/0000-0001-5696-0084; Ripatti,
Samuli/0000-0002-0504-1202; Lee, Sang Hong/0000-0001-9701-2718; Polasek,
Ozren/0000-0002-5765-1862; Mattheisen, Manuel/0000-0002-8442-493X;
Breen, Gerome/0000-0003-2053-1792; Smith, Albert/0000-0003-1942-5845;
Holle, Rolf/0000-0001-5395-2695; Lewis, Glyn/0000-0001-5205-8245;
Deloukas, Panos/0000-0001-9251-070X; Fehrmann,
Rudolf/0000-0002-7516-315X; Allik, Juri/0000-0002-8358-4747; Kloiber,
Stefan/0000-0002-6838-4114; Evans, David/0000-0003-0663-4621; Lawlor,
Debbie A/0000-0002-6793-2262; Middeldorp, Christel/0000-0002-6218-0428;
Thorgeirsson, Thorgeir/0000-0002-5149-7040; de Geus,
Eco/0000-0001-6022-2666; Li, Jingmei/0000-0001-8587-7511; Lewis,
Cathryn/0000-0002-8249-8476; Palmer, Lyle/0000-0002-1628-3055; Kolcic,
Ivana/0000-0001-7918-6052; Cesarini, David/0000-0002-0043-009X; Joshi,
Peter/0000-0002-6361-5059; Tozzi, Federica/0000-0002-3536-2920;
Kristiansson, Kati/0000-0003-4688-107X; Viktorin,
Alexander/0000-0003-2141-2816
FU Australian Research Council [FT0991360, DE130100614]; National Health
and Medical Research Council [613608, 1011506, 1047956]; National
Institute of Mental Health (NIMH) [U01 MH085520]; Netherlands Scientific
Organization; German Federal Ministry of Education and Research, within
the context of the National Genome Research Network 2 (NGFN2); National
Genome Research Network plus (NGFNplus); Integrated Genome Research
Network (IG) MooDS [01GS08144, 01GS08147]; European Union
[LSHM-CT-2006-037761, PIAP-GA-2008-218251, HEALTH-F2-2009-223423];
Medical Research Council (UK); Mental Health Research Network;
Innovative Medicines Initiative Joint Undertaking [115008]; NIMH
[MH061686, MH059542, MH075131, MH059552, MH059541, MH060912]; Broad
Institute Center for Genotyping and Analysis [U54 RR020278]; GenRED;
NIMH; National Alliance for Research on Schizophrenia and Depression;
Depression Genes and Networks ARRA grant [RC2MH089916]; Harvard i2b2;
i2b2 Center; NIH-funded National Center for Biomedical Computing based
at Partners HealthCare System [U54LM008748]; BMBF Program Molecular
Diagnostics: Validation of Biomarkers for Diagnosis and Outcome in Major
Depression [01ES0811]; Bavarian Ministry of Commerce; Federal Ministry
of Education and Research (BMBF) [FKZ 01GS0481, 01GS08145]; Netherlands
Organization for Scientific Research (MagW/ZonMW) [904-61-090,
985-10-002, 904-61-193, 480-04- 004, 400-05-717, 912-100-20];
Netherlands Organization for Scientific Research (Spinozapremie)
[56-464-14192]; Netherlands Organization for Scientific Research
(Geestkracht program) [10-000-1002]; Center for Medical Systems Biology
(NWO Genomics), Biobanking and Biomolecular Resources Research
Infrastructure, VU University's Institutes for Health and Care Research
and Neuroscience Campus Amsterdam, NBIC/BioAssist/RK [2008.024];
European Science Foundation [EU/QLRT-2001-01254]; European Community's
Seventh Framework Program; ENGAGE [HEALTH-F4-2007-201413]; European
Science Council (ERC) [230374]; Genetic Association Information Network
(GAIN) of the Foundation for the US National Institutes of Health; GAIN;
Swiss National Science Foundation [3200B0-105993, 3200B0-118'308,
33CSC0-122661]; GlaxoSmithKline; Australian National Health and Medical
Research Council [613608, 241944, 339462, 389927, 389875, 389891,
389892, 389938, 442915, 442981, 496675, 496739, 552485, 552498, 613602,
613674, 619667]; FP-5 GenomEUtwin Project [QLG2-CT-2002-01254]; US
National Institutes of Health [AA07535, AA10248, AA13320, AA13321,
AA13326, AA14041, MH66206, DA12854, DA019951]; Center for Inherited
Disease Research (Baltimore, MD, USA); UK Medical Research Council and
GlaxoSmithKline [G0701420]; National Institute for Health Research
(NIHR) Specialist Biomedical Research Centre for Mental Health at the
South London and Maudsley NHS Foundation Trust and the Institute of
Psychiatry, King's College London; UK Medical Research Council
[G0000647]; European Commission [LSHB-CT-2003-503428]; Federal Ministry
of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403]; Ministry of
Cultural Affairs; Social Ministry of the Federal State of
Mecklenburg-West Pomerania; Siemens Healthcare, Erlangen, Germany;
Federal State of Mecklenburg-West Pomerania; German Research Foundation
(DFG) [GR 1912/5-1]; NIMH Grant [MH072802]; National Institute of Mental
Health [N01MH90003]; Swedish Ministry for Higher Education; Swedish
Research Council [M-2005-1112]; GenomEUtwin [EU/QLRT-2001-01254,
QLG2-CT-2002-01254]; Swedish Foundation for Strategic Research; Wellcome
Trust [076113, 085475]; European Regional Development Fund
[3.2.0304.11-0312]; 'Center of Excellence in Genomics' (EXCEGEN);
Estonian Government [IUT24-6, IUT20-60]; CTG grant from Development Fund
of the University of Tartu [SP1GVAR-ENG]; National Health and Medical
Research Early Career Fellowship Scheme; [MH086026]; [MH081802];
[FT0991022]; [03ZIK012]; [U01 DK066134]; [313010]
FX NRW and SHL supported by the Australian Research Council (FT0991360 and
DE130100614) and the National Health and Medical Research Council
(613608, 1011506 and 1047956). The PGC is supported by National
Institute of Mental Health (NIMH) Grant U01 MH085520. Statistical
analyses were carried out on the Genetic Cluster Computer (see Web
Resources), which is financially supported by the Netherlands Scientific
Organization. The Bonn/Mannheim (BoMa) GWAS was supported by the German
Federal Ministry of Education and Research, within the context of the
National Genome Research Network 2 (NGFN2), the National Genome Research
Network plus (NGFNplus) and the Integrated Genome Research Network (IG)
MooDS (Grant 01GS08144 to S Cichon and MMN, and Grant 01GS08147 to MR).
The work at deCODE was funded by European Union Grants
LSHM-CT-2006-037761 (Project SGENE), PIAP-GA-2008-218251 (Project
PsychGene) and HEALTH-F2-2009-223423 (Project PsychCNVs). GenPod was
funded by the Medical Research Council (UK) and supported by the Mental
Health Research Network. Genotyping of the GenPod sample was funded by
the Innovative Medicines Initiative Joint Undertaking under Grant
Agreement number 115008 (NEWMEDS). The GenRED GWAS project was supported
by NIMH R01 Grants MH061686 (to DFL), MH059542 (to WHC), MH075131 (to
WBL), MH059552 (to JBP), MH059541 (to WAS) and MH060912 (to MMW). We
acknowledge the contributions of Dr George S Zubenko and Dr Wendy N
Zubenko, Department of Psychiatry, University of Pittsburgh School of
Medicine, to the GenRED I project. The NIMH Cell Repository at Rutgers
University and the NIMH Center for Collaborative Genetic Studies on
Mental Disorders made essential contributions to this project.
Genotyping was carried out by the Broad Institute Center for Genotyping
and Analysis with support from Grant U54 RR020278 (which partially
subsidized the genotyping of the GenRED cases). Collection and quality
control analyses of the control data set were supported by grants from
NIMH and the National Alliance for Research on Schizophrenia and
Depression. We are grateful to Knowledge Networks (Menlo Park, CA, USA)
for assistance in collecting the control data set. We express our
profound appreciation to the families who participated in this project,
and to the many clinicians who facilitated the referral of participants
to the study. The Depression Genes and Networks ARRA grant was funded by
RC2MH089916. Funding for the Harvard i2b2 sample was provided by a
subcontract to RH Perlis and JW Smoller as part of the i2b2 Center
(Informatics for Integrating Biology and the Bedside), an NIH-funded
National Center for Biomedical Computing based at Partners HealthCare
System (U54LM008748, PI: IS Kohane), and by an NIMH Grant (to RH Perlis;
MH086026). Max Planck Institute of Psychiatry MARS study was supported
by the BMBF Program Molecular Diagnostics: Validation of Biomarkers for
Diagnosis and Outcome in Major Depression (01ES0811). Genotyping was
supported by the Bavarian Ministry of Commerce, and the Federal Ministry
of Education and Research (BMBF) in the framework of the National Genome
Research Network (NGFN2 and NGFN-Plus, FKZ 01GS0481 and 01GS08145). The
Netherlands Study of Depression and Anxiety (NESDA) and the Netherlands
Twin Register (NTR) contributed to GAIN-MDD and to MDD2000.; This study
was funded by: the Netherlands Organization for Scientific Research
(MagW/ZonMW Grants 904-61-090, 985-10-002, 904-61-193, 480-04- 004,
400-05-717, 912-100-20; Spinozapremie 56-464-14192; Geestkracht program
Grant 10-000-1002); the Center for Medical Systems Biology (NWO
Genomics), Biobanking and Biomolecular Resources Research
Infrastructure, VU University's Institutes for Health and Care Research
and Neuroscience Campus Amsterdam, NBIC/BioAssist/RK (2008.024); the
European Science Foundation (EU/QLRT-2001-01254); the European
Community's Seventh Framework Program (FP7/2007-2013); ENGAGE
(HEALTH-F4-2007-201413); and the European Science Council (ERC, 230374).
Genotyping was funded, in part, 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). The PsyCoLaus study was supported by grants from the Swiss
National Science Foundation (nos. 3200B0-105993, 3200B0-118'308,
33CSC0-122661) and from GlaxoSmithKline (Psychiatry Center of Excellence
for Drug Discovery and Genetics Division, Drug Discovery-Verona, R&D).
We express our gratitude to the Lausanne inhabitants who volunteered to
participate in the PsyCoLaus study. We also thank V Mooser, G Weaber and
P Vollenweider who initiated the CoLaus project. Funding for the QIMR
samples was provided by the Australian National Health and Medical
Research Council (241944, 339462, 389927, 389875, 389891, 389892,
389938, 442915, 442981, 496675, 496739, 552485, 552498, 613602, 613608,
613674, 619667), the Australian Research Council (FT0991360, FT0991022),
the FP-5 GenomEUtwin Project (QLG2-CT-2002-01254) and the US National
Institutes of Health (AA07535, AA10248, AA13320, AA13321, AA13326,
AA14041, MH66206, DA12854, DA019951), and the Center for Inherited
Disease Research (Baltimore, MD, USA). We thank the twins and their
families registered at the Australian Twin Registry for their
participation in the many studies that have contributed to this
research. RADIANT was funded by: a joint grant from the UK Medical
Research Council and GlaxoSmithKline (G0701420); the National Institute
for Health Research (NIHR) Specialist Biomedical Research Centre for
Mental Health at the South London and Maudsley NHS Foundation Trust and
the Institute of Psychiatry, King's College London; and the UK Medical
Research Council (G0000647). The GENDEP study was funded by a European
Commission Framework 6 grant, EC Contract Ref.: LSHB-CT-2003-503428.
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 (Grant nos. 01ZZ9603, 01ZZ0103 and 01ZZ0403), the
Ministry of Cultural Affairs and 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. SHIP-LEGEND is funded by the German Research
Foundation (DFG: GR 1912/5-1). Genotyping of STAR*D was supported by an
NIMH Grant to SP Hamilton (MH072802). STAR*D was funded by the National
Institute of Mental Health (Contract No. N01MH90003) to the University
of Texas Southwestern Medical Center at Dallas (AJ Rush, principal
investigator).; The TwinGene study was supported by the Swedish Ministry
for Higher Education, the Swedish Research Council (M-2005-1112),
GenomEUtwin (EU/QLRT-2001-01254; QLG2-CT-2002-01254), the Swedish
Foundation for Strategic Research and the US National Institutes of
Health (U01 DK066134). This study makes use of data generated by the
Wellcome Trust Case-Control Consortium. A full list of the investigators
who contributed to the generation of the data is available from
http://www.wtccc.org.uk. Funding for the project was provided by the
Wellcome Trust under awards 076113 and 085475. EGCUT received financing
from FP7 Grant 313010 and from European Regional Development Fund, road
map Grant No. 3.2.0304.11-0312 and grant 'Center of Excellence in
Genomics' (EXCEGEN). EGCUT studies were covered also by targeted
financing from Estonian Government (IUT24-6, IUT20-60) and CTG grant
(SP1GVAR-ENG) from Development Fund of the University of Tartu. We
acknowledge EGCUT technical personnel, especially Mr V Soo and S Smit
and Mari-Liis Tammesoo. EMB is supported by the National Health and
Medical Research Early Career Fellowship Scheme.
NR 42
TC 6
Z9 6
U1 2
U2 29
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 JUN
PY 2015
VL 20
IS 6
BP 735
EP 743
DI 10.1038/mp.2015.50
PG 9
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA CI6SB
UT WOS:000354890200012
PM 25917368
ER
PT J
AU Cheng, Y
Rodriguiz, RM
Murthy, SRK
Senatorov, V
Thouennon, E
Cawley, NX
Aryal, DK
Ahn, S
Lecka-Czernik, B
Wetsel, WC
Loh, YP
AF Cheng, Y.
Rodriguiz, R. M.
Murthy, S. R. K.
Senatorov, V.
Thouennon, E.
Cawley, N. X.
Aryal, D. K.
Ahn, S.
Lecka-Czernik, B.
Wetsel, W. C.
Loh, Y. P.
TI Neurotrophic factor-alpha 1 prevents stress-induced depression through
enhancement of neurogenesis and is activated by rosiglitazone
SO MOLECULAR PSYCHIATRY
LA English
DT Article
ID FIBROBLAST GROWTH FACTOR-2; HIPPOCAMPAL NEUROGENESIS;
CARBOXYPEPTIDASE-E; ANTIDEPRESSANT TREATMENT; CELL-PROLIFERATION; FGF-2
ISOFORMS; MICE; BEHAVIOR; ANXIETY; EXPRESSION
AB Major depressive disorder is often linked to stress. Although short-term stress is without effect in mice, prolonged stress leads to depressive-like behavior, indicating that an allostatic mechanism exists in this difference. Here we demonstrate that mice after short-term (1 h per day for 7 days) chronic restraint stress (CRS), do not display depressive-like behavior. Analysis of the hippocampus of these mice showed increased levels of neurotrophic factor-alpha 1 (NF-alpha 1; also known as carboxypeptidase E, CPE), concomitant with enhanced fibroblast growth factor 2 (FGF2) expression, and an increase in neurogenesis in the dentate gyrus. In contrast, after prolonged (6 h per day for 21 days) CRS, mice show decreased hippocampal NF-alpha 1 and FGF2 levels and depressive-like responses. In NF-alpha 1-knockout mice, hippocampal FGF2 levels and neurogenesis are reduced. These mice exhibit depressive-like behavior that is reversed by FGF2 administration. Indeed, studies in cultured hippocampal neurons reveal that NF-alpha 1 treatment directly upregulates FGF2 expression through extracellular signal-regulated kinase-Sp1 signaling. Thus, during short-term CRS, hippocampal NF-alpha 1 expression is upregulated and has a key role in preventing the onset of depressive-like behavior through enhanced FGF2-mediated neurogenesis. To evaluate the therapeutic potential of this pathway, we examined, rosiglitazone (Rosi), a PPAR. agonist, which has been shown to have antidepressant activity in rodents and humans. Rosi upregulates FGF2 expression in a NF-alpha 1-dependent manner in hippocampal neurons. Mice fed Rosi show increased hippocampal NF-alpha 1 levels and neurogenesis compared with controls, thereby indicating the antidepressant action of this drug. Development of drugs that activate the NF-alpha 1/FGF2/neurogenesis pathway can offer a new approach to depression therapy.
C1 [Cheng, Y.; Murthy, S. R. K.; Senatorov, V.; Thouennon, E.; Cawley, N. X.; Loh, Y. P.] Program Dev Neurosci, Sect Cellular Neurobiol, Bethesda, MD 20892 USA.
[Rodriguiz, R. M.; Aryal, D. K.; Wetsel, W. C.] Dept Psychiat & Behav Sci, Durham, NC USA.
[Ahn, S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD USA.
[Lecka-Czernik, B.] Univ Toledo, Ctr Diabet & Endocrine Res, Dept Orthoped Surg, Toledo, OH 43606 USA.
[Lecka-Czernik, B.] Univ Toledo, Ctr Diabet & Endocrine Res, Dept Physiol & Pharmacol, Toledo, OH 43606 USA.
[Wetsel, W. C.] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC USA.
[Wetsel, W. C.] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC USA.
RP Loh, YP (reprint author), NICHD, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, 49 Convent Dr,Bldg 49,Room 6C80, Bethesda, MD 20892 USA.
EM lohp@mail.nih.gov
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD); National
Institutes of Health, USA; National Institutes of Health [HD36015];
American Diabetes Association Award [7-13-BS-089]
FX This research was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), National Institutes of Health, USA and in part by
National Institutes of Health grant HD36015 (WCW) and the American
Diabetes Association Award 7-13-BS-089 (BL-C). We thank Lynne Holtzclaw,
Dr Vincent Schram in the MIC at NICHD for their help in the
immunocytochemistry and confocal microscopy, Dr Cheol Lee (Program on
Genomics of Differentiation, NICHD) for his helpful discussions on
markers for detecting neurogenesis in the hippocampus, Drs Zhihong Jiang
and Lee Eiden (NIMH) for help with the sucrose preference test. We also
thank the following people from the Department of Psychiatry and
Behavioral Sciences, Duke University Medical Center: Theodore Rhodes and
Christopher Means for helping with the daily restraint and forced swim
tests. Thanks also to Dr Chris McBain (NICHD), Dr Owen Rennert (NICHD),
Dr Harold Gainer (NINDS) and Dr Hao Yang Tan (Lieber Institute for Brain
Development, Johns Hopkins University) for critical reading of the
manuscript.
NR 58
TC 10
Z9 11
U1 2
U2 7
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 JUN
PY 2015
VL 20
IS 6
BP 744
EP 754
DI 10.1038/mp.2014.136
PG 11
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA CI6SB
UT WOS:000354890200013
PM 25330741
ER
PT J
AU Tiihonen, J
Rautiainen, MR
Ollila, HM
Repo-Tiihonen, E
Virkkunen, M
Palotie, A
Pietilainen, O
Kristiansson, K
Joukamaa, M
Lauerma, H
Saarela, J
Tyni, S
Vartiainen, H
Paananen, J
Goldman, D
Paunio, T
AF Tiihonen, J.
Rautiainen, M-R
Ollila, H. M.
Repo-Tiihonen, E.
Virkkunen, M.
Palotie, A.
Pietilainen, O.
Kristiansson, K.
Joukamaa, M.
Lauerma, H.
Saarela, J.
Tyni, S.
Vartiainen, H.
Paananen, J.
Goldman, D.
Paunio, T.
TI Genetic background of extreme violent behavior
SO MOLECULAR PSYCHIATRY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER;
ANTISOCIAL PERSONALITY; CHILDHOOD MALTREATMENT; SEROTONIN REUPTAKE;
ALCOHOL DEPENDENCE; MONOAMINE-OXIDASE; AGGRESSION; CRIMINALITY; GENOTYPE
AB In developed countries, the majority of all violent crime is committed by a small group of antisocial recidivistic offenders, but no genes have been shown to contribute to recidivistic violent offending or severe violent behavior, such as homicide. Our results, from two independent cohorts of Finnish prisoners, revealed that a monoamine oxidase A (MAOA) low-activity genotype (contributing to low dopamine turnover rate) as well as the CDH13 gene (coding for neuronal membrane adhesion protein) are associated with extremely violent behavior (at least 10 committed homicides, attempted homicides or batteries). No substantial signal was observed for either MAOA or CDH13 among non-violent offenders, indicating that findings were specific for violent offending, and not largely attributable to substance abuse or antisocial personality disorder. These results indicate both low monoamine metabolism and neuronal membrane dysfunction as plausible factors in the etiology of extreme criminal violent behavior, and imply that at least about 5-10% of all severe violent crime in Finland is attributable to the aforementioned MAOA and CDH13 genotypes.
C1 [Tiihonen, J.] Karolinska Inst, Dept Clin Neurosci, S-17176 Stockholm, Sweden.
[Tiihonen, J.; Repo-Tiihonen, E.] Univ Eastern Finland, Niuvanniemi Hosp, Dept Forens Psychiat, Kuopio, Finland.
[Tiihonen, J.; Rautiainen, M-R; Ollila, H. M.; Pietilainen, O.; Kristiansson, K.; Lauerma, H.; Paunio, T.] Natl Inst Hlth & Welf, Helsinki, Finland.
[Ollila, H. M.] Stanford Univ, Ctr Sleep Sci, Palo Alto, CA 94304 USA.
[Virkkunen, M.; Paunio, T.] Univ Helsinki, Dept Psychiat, Inst Clin Med, SF-00180 Helsinki, Finland.
[Virkkunen, M.; Paunio, T.] Univ Helsinki, Cent Hosp, Dept Psychiat, Helsinki, Finland.
[Palotie, A.] Wellcome Trust Sanger Inst, Hinxton, Cambs, England.
[Palotie, A.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Palotie, A.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[Palotie, A.] Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.
[Palotie, A.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Joukamaa, M.] Univ Tampere, Sch Hlth Sci, Social Psychiat Unit, FIN-33101 Tampere, Finland.
[Lauerma, H.] Psychiat Hosp Prisoners, Turku, Finland.
[Lauerma, H.] Univ Turku, Turku, Finland.
[Saarela, J.] Finnish Genome Ctr, Helsinki, Finland.
[Tyni, S.; Vartiainen, H.] Criminal Sanct Agcy, Helsinki, Finland.
[Paananen, J.] Univ Eastern Finland, Bioinformat Ctr, Kuopio, Finland.
[Goldman, D.] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA.
RP Tiihonen, J (reprint author), Karolinska Inst, Dept Clin Neurosci, Byggnad R5, S-17176 Stockholm, Sweden.
EM jari.tiihonen@ki.se; tiina.paunio@thl.fi
RI Goldman, David/F-9772-2010
OI Paananen, Jussi/0000-0001-5100-4907; Saarela, Janna/0000-0002-0853-6219;
Kristiansson, Kati/0000-0003-4688-107X; Goldman,
David/0000-0002-1724-5405
FU Finnish Ministry of Health and Social Affairs through the development
fund for Niuvanniemi Hospital, Finland; Instrumentarium Science
Foundation; Orion-Farmos Research Foundation; Academy of Finland
[250207]
FX We thank Auli Toivola for her contribution in the Sequenom Mass Array
and MAOA VNTR genotyping and Aija Rasanen for secretarial assistance.
The study was funded by the Finnish Ministry of Health and Social
Affairs through the development fund for Niuvanniemi Hospital, Finland.
Hanna M Ollila has received funds from Instrumentarium Science
Foundation and Orion-Farmos Research Foundation. Kati Kristiansson has
received grant from Orion-Farmos Research Foundation and Academy of
Finland (grant number 250207).
NR 40
TC 17
Z9 17
U1 10
U2 61
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 JUN
PY 2015
VL 20
IS 6
BP 786
EP 792
DI 10.1038/mp.2014.130
PG 7
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA CI6SB
UT WOS:000354890200018
PM 25349169
ER
PT J
AU Migueles, SA
Connors, M
AF Migueles, Stephen A.
Connors, Mark
TI Success and failure of the cellular immune response against HIV-1
SO NATURE IMMUNOLOGY
LA English
DT Review
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD8(+) T-CELLS; LONG-TERM NONPROGRESSORS;
TYPE-1 ELITE CONTROLLERS; HIGHLY PATHOGENIC SIV; CTL ESCAPE MUTATIONS;
ANTIRETROVIRAL TREATMENT; LYMPHOCYTE RESPONSES; VIRAL REPLICATION;
INFECTED INDIVIDUALS
AB The cellular immune response to HIV-1 has now been studied in extraordinary detail. A very large body of data provides the most likely reasons that the HIV-specific cellular immune response succeeds in a small number of people but fails in most. Understanding the success and failure of the HIV-specific cellular immune response has implications that extend not only to immunotherapies and vaccines for HIV-1 but also to the cellular immune response in other disease states. This Review focuses on the mechanisms that are most likely responsible for durable and potent immunologic control of HIV-1. Although we now have a detailed picture of the cellular immune responses to HIV-1, important questions remain regarding the nature of these responses and how they arise.
C1 [Migueles, Stephen A.; Connors, Mark] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Connors, M (reprint author), NIAID, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM mconnors@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX S.A.M. and M.C. are supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 116
TC 20
Z9 20
U1 4
U2 15
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
EI 1529-2916
J9 NAT IMMUNOL
JI Nat. Immunol.
PD JUN
PY 2015
VL 16
IS 6
BP 563
EP 570
DI 10.1038/ni.3161
PG 8
WC Immunology
SC Immunology
GA CI4VM
UT WOS:000354751900004
PM 25988888
ER
PT J
AU Burton, DR
Mascola, JR
AF Burton, Dennis R.
Mascola, John R.
TI Antibody responses to envelope glycoproteins in HIV-1 infection
SO NATURE IMMUNOLOGY
LA English
DT Review
ID HUMAN-IMMUNODEFICIENCY-VIRUS; BROADLY NEUTRALIZING ANTIBODIES; DEPENDENT
CELLULAR CYTOTOXICITY; MUCOSAL SHIV CHALLENGE; NONNEUTRALIZING
ANTIBODIES; MONOCLONAL-ANTIBODIES; IN-VITRO; ENV TRIMERS; MEDIATED
CYTOTOXICITY; ANTIVIRAL ANTIBODIES
AB Antibody responses to the HIV-1 envelope glycoproteins can be classified into three groups. Binding but non-neutralizing responses are directed to epitopes that are expressed on isolated envelope glycoproteins but not on the native envelope trimer found on the surface of virions and responsible for mediating the entry of virus into target cells. Strain-specific responses and broadly neutralizing responses, in contrast, target epitopes that are expressed on the native trimer, as revealed by recently resolved structures. The past few years have seen the isolation of many broadly neutralizing antibodies of remarkable potency that have shown prophylactic and therapeutic activities in animal models. These antibodies are helping to guide rational vaccine design and therapeutic strategies for HIV-1.
C1 [Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Burton, Dennis R.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, 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.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA.
[Burton, Dennis R.] Harvard Univ, Boston, MA 02115 USA.
[Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Burton, DR (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
EM burton@scripps.edu; jmascola@nih.gov
FU National Institute of Allergy and Infectious Diseases; Center for
HIV/AIDS Vaccine Immunology and Immunogen Discovery; International AIDS
Vaccine Initiative; Bill and Melinda Gates Foundation; Ragon Institute
of MGH, MIT and Harvard; Vaccine Research Center, National Institute of
Allergy and Infectious Diseases
FX Supported by the National Institute of Allergy and Infectious Diseases
(D.R.B.), the Center for HIV/AIDS Vaccine Immunology and Immunogen
Discovery (D.R.B.), the International AIDS Vaccine Initiative (D.R.B.),
the Bill and Melinda Gates Foundation (D.R.B.), the Ragon Institute of
MGH, MIT and Harvard (D.R.B.) and the intramural research program of the
Vaccine Research Center, National Institute of Allergy and Infectious
Diseases (J.R.M.).
NR 108
TC 112
Z9 115
U1 9
U2 42
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
EI 1529-2916
J9 NAT IMMUNOL
JI Nat. Immunol.
PD JUN
PY 2015
VL 16
IS 6
BP 571
EP 576
DI 10.1038/ni.3158
PG 6
WC Immunology
SC Immunology
GA CI4VM
UT WOS:000354751900005
PM 25988889
ER
PT J
AU McLaren, PJ
Carrington, M
AF McLaren, Paul J.
Carrington, Mary
TI The impact of host genetic variation on infection with HIV-1
SO NATURE IMMUNOLOGY
LA English
DT Review
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HLA-C EXPRESSION; GENOME-WIDE
ASSOCIATION; CELL-SURFACE EXPRESSION; CLASS-I; VIRAL LOAD; UNINFECTED
INDIVIDUALS; ANTIRETROVIRAL THERAPY; RHEUMATOID-ARTHRITIS; DISEASE
PROGRESSION
AB The outcome after infection with the human immunodeficiency virus type 1 (HIV-1) is a complex phenotype determined by interactions among the pathogen, the human host and the surrounding environment. An impact of host genetic variation on HIV-1 susceptibility was identified early in the pandemic, with a major role attributed to the genes encoding class I human leukocyte antigens (HLA) and the chemokine receptor CCR5. Studies using genome-wide data sets have underscored the strength of these associations relative to variants located throughout the rest of the genome. However, the extent to which additional polymorphisms influence HIV-1 disease progression, and how much of the variability in outcome can be attributed to host genetics, remain largely unclear. Here we discuss findings concerning the functional impact of associated variants, outline methods for quantifying the host genetic component and examine how available genome-wide data sets may be leveraged to discover gene variants that affect the outcome of HIV-1 infection.
C1 [McLaren, Paul J.] Ecole Polytech Fed Lausanne, Sch Life Sci, Lausanne, Switzerland.
[Carrington, Mary] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick, MD USA.
[Carrington, Mary] Ragon Inst MGH & Harvard, Cambridge, MA USA.
RP McLaren, PJ (reprint author), Ecole Polytech Fed Lausanne, Sch Life Sci, Lausanne, Switzerland.
EM paul.mclaren@epfl.ch; carringm@mail.nih.gov
FU Frederick National Laboratory for Cancer Research [HHSN261200800001E];
National Institutes of Health, Frederick National Laboratory, Center for
Cancer Research
FX We thank A. Bashirova and I. Bartha for helpful suggestions. This
project was funded in whole or in part with federal funds from the
Frederick National Laboratory for Cancer Research, under Contract No.
HHSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products or
organizations imply endorsement by the US Government. This research was
supported in part by the Intramural Research Program of the National
Institutes of Health, Frederick National Laboratory, Center for Cancer
Research.
NR 73
TC 18
Z9 18
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
EI 1529-2916
J9 NAT IMMUNOL
JI Nat. Immunol.
PD JUN
PY 2015
VL 16
IS 6
BP 577
EP 583
DI 10.1038/ni.3147
PG 7
WC Immunology
SC Immunology
GA CI4VM
UT WOS:000354751900006
PM 25988890
ER
PT J
AU Chun, TW
Moir, S
Fauci, AS
AF Chun, Tae-Wook
Moir, Susan
Fauci, Anthony S.
TI HIV reservoirs as obstacles and opportunities for an HIV cure
SO NATURE IMMUNOLOGY
LA English
DT Article
ID ACTIVE ANTIRETROVIRAL THERAPY; CD4(+) T-CELLS; BROADLY NEUTRALIZING
ANTIBODIES; HISTONE DEACETYLASE INHIBITORS; VIRAL RESERVOIR; LATENT
RESERVOIR; HIV-1-INFECTED PATIENTS; ANTIVIRAL THERAPY; EXTENDED PERIODS;
RHESUS-MONKEYS
AB The persistence of HIV reservoirs remains a formidable obstacle to achieving sustained virologic remission in HIV-infected individuals after antiretroviral therapy (ART) is discontinued, even if plasma viremia has been successfully suppressed for prolonged periods of time. Numerous approaches aimed at eradicating the virus, as well as maintaining its prolonged suppression in the absence of ART, have had little success. A better understanding of the pathophysiologic nature of HIV reservoirs and the impact of various interventions on their persistence is essential for the development of successful therapeutic strategies against HIV or the long-term control of infection. Here, we discuss the persistent HIV reservoir as a barrier to cure as well as the current therapeutic strategies aimed at eliminating or controlling the virus in the absence of ART.
C1 [Chun, Tae-Wook; Moir, Susan; Fauci, Anthony S.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Chun, TW (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM twchun@nih.gov
FU National Institute of Allergy and Infectious Diseases, US National
Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, US National
Institutes of Health.
NR 63
TC 32
Z9 34
U1 7
U2 27
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
EI 1529-2916
J9 NAT IMMUNOL
JI Nat. Immunol.
PD JUN
PY 2015
VL 16
IS 6
BP 584
EP 589
DI 10.1038/ni.3152
PG 6
WC Immunology
SC Immunology
GA CI4VM
UT WOS:000354751900007
PM 25990814
ER
PT J
AU Holliday, GL
Bairoch, A
Bagos, PG
Chatonnet, A
Craik, DJ
Finn, RD
Henrissat, B
Landsman, D
Manning, G
Nagano, N
O'Donovan, C
Pruitt, KD
Rawlings, ND
Saier, M
Sowdhamini, R
Spedding, M
Srinivasan, N
Vriend, G
Babbitt, PC
Bateman, A
AF Holliday, Gemma L.
Bairoch, Amos
Bagos, Pantelis G.
Chatonnet, Arnaud
Craik, David J.
Finn, Robert D.
Henrissat, Bernard
Landsman, David
Manning, Gerard
Nagano, Nozomi
O'Donovan, Claire
Pruitt, Kim D.
Rawlings, Neil D.
Saier, Milton
Sowdhamini, Ramanathan
Spedding, Michael
Srinivasan, Narayanaswamy
Vriend, Gert
Babbitt, Patricia C.
Bateman, Alex
TI Key challenges for the creation and maintenance of specialist protein
resources
SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
LA English
DT Editorial Material
DE specialist protein resource; key challenges; biocuration; longevity; big
data; misannotation
ID FAMILIES DATABASE; INFORMATION; KNOWLEDGE; UPDATE; COLLECTION;
DIVERSITY; DISCOVERY; SEQUENCES; ENZYMES; BIOLOGY
AB As the volume of data relating to proteins increases, researchers rely more and more on the analysis of published data, thus increasing the importance of good access to these data that vary from the supplemental material of individual articles, all the way to major reference databases with professional staff and long-term funding. Specialist protein resources fill an important middle ground, providing interactive web interfaces to their databases for a focused topic or family of proteins, using specialized approaches that are not feasible in the major reference databases. Many are labors of love, run by a single lab with little or no dedicated funding and there are many challenges to building and maintaining them. This perspective arose from a meeting of several specialist protein resources and major reference databases held at the Wellcome Trust Genome Campus (Cambridge, UK) on August 11 and 12, 2014. During this meeting some common key challenges involved in creating and maintaining such resources were discussed, along with various approaches to address them. In laying out these challenges, we aim to inform users about how these issues impact our resources and illustrate ways in which our working together could enhance their accuracy, currency, and overall value. Proteins 2015; 83:1005-1013. (c) 2015 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.
C1 [Holliday, Gemma L.; Babbitt, Patricia C.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA.
[Bairoch, Amos] Univ Geneva, SIB, Geneva, Switzerland.
[Bagos, Pantelis G.] Univ Thessaly, Dept Comp Sci & Biomed Informat, Lamia 35100, Greece.
[Chatonnet, Arnaud] INRA, Dynam Musculaire & Metab Umr866, F-34000 Montpellier, France.
[Chatonnet, Arnaud] Univ Montpellier, F-34000 Montpellier, France.
[Craik, David J.] Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia.
[Finn, Robert D.; O'Donovan, Claire; Rawlings, Neil D.; Bateman, Alex] EBI, EMBL, Cambridge CB10 1SD, England.
[Henrissat, Bernard] Aix Marseille Univ, CNRS, Architecture & Fonct Macromol Biol, F-13288 Marseille, France.
[Henrissat, Bernard] King Abdulaziz Univ, Dept Biol Sci, Jeddah 21413, Saudi Arabia.
[Landsman, David; Pruitt, Kim D.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA.
[Manning, Gerard] Genentech Inc, Dept Bioinformat & Computat Biol, San Francisco, CA USA.
[Nagano, Nozomi] Natl Inst Adv Ind Sci & Technol, Computat Biol Res Ctr, Tokyo 1350064, Japan.
[Rawlings, Neil D.] Wellcome Trust Sanger Inst, Cambridge CB10 1SD, England.
[Saier, Milton] Univ Calif San Diego, Dept Mol Biol, La Jolla, CA 92093 USA.
[Sowdhamini, Ramanathan] TIFR, Natl Ctr Biol Sci, Bangalore 560065, Karnataka, India.
[Spedding, Michael] Spedding Res Solut SARL, Chair NC IUPHAR, F-78110 Le Vesinet, France.
[Srinivasan, Narayanaswamy] Indian Inst Sci, Mol Biophys Unit, Bangalore 560012, Karnataka, India.
[Vriend, Gert] Radboud Univ Nijmegen, Med Ctr, CMBI, NL-6525 GA Nijmegen, Netherlands.
RP Holliday, GL (reprint author), Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA.
EM gemma.holliday@ucsf.edu
RI Vriend, G./H-8112-2014; Craik, David/B-1695-2010; Nagano,
Nozomi/A-5717-2017; Chatonnet, Arnaud/E-2190-2017; Fac Sci, KAU, Biol
Sci Dept/L-4228-2013; Rawlings, Neil/M-5566-2013;
OI Holliday, Gemma/0000-0002-6731-6398; O'Donovan,
Claire/0000-0001-8051-7429; Landsman, David/0000-0002-9819-6675; Craik,
David/0000-0003-0007-6796; Nagano, Nozomi/0000-0002-2779-685X;
Chatonnet, Arnaud/0000-0002-4057-3896; Spedding,
Michael/0000-0002-1248-8221; Bateman, Alex/0000-0002-6982-4660;
Rawlings, Neil/0000-0001-5557-7665; Finn, Robert/0000-0001-8626-2148;
Bairoch, Amos/0000-0003-2826-6444; Manning, Gerard/0000-0002-5087-9151
FU British Heart Foundation [RG/13/5/30112]; Intramural NIH HHS [Z01
LM000071-13]; NHGRI NIH HHS [U41 HG002273, U41 HG007822, U41HG007822,
U41HG02273]; NIGMS NIH HHS [P20GM103446, R01 GM060595, R01 GM60595,
R01GM080646]; NLM NIH HHS [G08LM010720]; Parkinson's UK [G-1307];
Wellcome Trust [077044, 099156]
NR 50
TC 6
Z9 6
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0887-3585
EI 1097-0134
J9 PROTEINS
JI Proteins
PD JUN
PY 2015
VL 83
IS 6
BP 1005
EP 1013
DI 10.1002/prot.24803
PG 9
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA CJ0CA
UT WOS:000355138800001
PM 25820941
ER
PT J
AU Tully, LA
Grady, PA
AF Tully, Lois A.
Grady, Patricia A.
TI A Path Forward for Genomic Nursing Research
SO RESEARCH IN NURSING & HEALTH
LA English
DT Editorial Material
DE genomics; nursing research; research policy
ID SCIENCE
C1 [Tully, Lois A.; Grady, Patricia A.] NINR, NIH, Bethesda, MD 20892 USA.
RP Tully, LA (reprint author), NINR, NIH, 6701 Democracy Blvd Suite 710, Bethesda, MD 20892 USA.
EM lois.tully@nih.gov
FU NIH Office of Rare Diseases Research, National Center for Advancing
Translational Sciences
FX The National Institute of Nursing Research gratefully acknowledges the
NIH Office of Rare Diseases Research, National Center for Advancing
Translational Sciences (http://rarediseases.info.nih.gov/) as a
cosponsor of the Genomic Nursing Science Workshop.
NR 2
TC 4
Z9 4
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0160-6891
EI 1098-240X
J9 RES NURS HEALTH
JI Res. Nurs. Health
PD JUN
PY 2015
VL 38
IS 3
BP 177
EP 179
DI 10.1002/nur.21659
PG 3
WC Nursing
SC Nursing
GA CI4SN
UT WOS:000354743800001
PM 25872111
ER
PT J
AU Emoto, C
Fukuda, T
Mizuno, T
Cox, S
Schniedewind, B
Christians, U
Widemann, BC
Fisher, MJ
Weiss, B
Perentesis, J
Vinks, AA
AF Emoto, Chie
Fukuda, Tsuyoshi
Mizuno, Tomoyuki
Cox, Shareen
Schniedewind, Bjoern
Christians, Uwe
Widemann, Brigitte C.
Fisher, Michael J.
Weiss, Brian
Perentesis, John
Vinks, Alexander A.
TI Age-Dependent Changes in Sirolimus Metabolite Formation in Patients With
Neurofibromatosis Type 1
SO THERAPEUTIC DRUG MONITORING
LA English
DT Article
DE sirolimus; neurofibromatosis; pharmacokinetics; pediatric; metabolite;
body size
ID NERVE SHEATH TUMORS; PLEXIFORM NEUROFIBROMAS; LIVER VOLUME; CHILDREN;
PHARMACOKINETICS; RAPAMYCIN; RECIPIENTS
AB Background: Sirolimus is an inhibitor of mammalian target of rapamycin, which exhibits large interindividual pharmacokinetic variability. We report sirolimus pharmacokinetic data collected as part of a concentration-controlled multicenter phase II clinical trial in pediatric patients with neurofibromatosis type 1. The purpose of this study was to explore the effect of growth on age-dependent changes in sirolimus clearance with a focus on cytochrome P450 3A (CYP3A) subfamily mediated metabolism.
Methods: Predose blood samples were obtained at steady state from 18 patients with neurofibromatosis type 1. Sirolimus and its 5 CYP3A-dependent primary metabolites were quantified by HPLC-UV/MS. Concentration ratios of metabolites to sirolimus (metabolic ratio) were calculated as an index of metabolite formation.
Results: Metabolic ratios of the main metabolites, 16-O-demethylsirolimus (16-O-DM) and 24-hydroxysirolimus (24OH), were significantly correlated with sirolimus clearance, whereas this was not the case for the other 3 metabolites (25-hydroxysirolimus, 46-hydroxysirolimus, and 39-O-demethylsirolimus). The ratios for the 16-O-DM and 24OH metabolites were lower in children than adults. No significant difference in allometrically scaled metabolic ratios of 16-O-DM and 24OH was observed between children and adults.
Conclusions: This study suggests that the age-dependent changes in sirolimus clearance can be explained by size-related increases in CYP3A metabolic capacity, most likely due to liver and intestinal growth. These findings will help facilitate the development of ageappropriate dosing algorithms for sirolimus in infants and children.
C1 [Emoto, Chie; Fukuda, Tsuyoshi; Mizuno, Tomoyuki; Cox, Shareen; Vinks, Alexander A.] Cincinnati Childrens Hosp Med Ctr, Div Clin Pharmacol, Cincinnati, OH 45229 USA.
[Emoto, Chie; Fukuda, Tsuyoshi; Weiss, Brian; Perentesis, John; Vinks, Alexander A.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH 45221 USA.
[Schniedewind, Bjoern; Christians, Uwe] Univ Colorado, Integrated Solut Clin Res & Dev iC42, Aurora, CO USA.
[Widemann, Brigitte C.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Fisher, Michael J.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
[Fisher, Michael J.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Weiss, Brian; Perentesis, John] Cincinnati Childrens Hosp Med Ctr, Canc & Blood Dis Inst, Div Oncol, Cincinnati, OH 45229 USA.
[Vinks, Alexander A.] Univ Cincinnati, Coll Med, Dept Pharmacol & Cell Biophys, Cincinnati, OH 45221 USA.
RP Vinks, AA (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Clin Pharmacol, 3333 Burnet Ave,MLC 6018, Cincinnati, OH 45229 USA.
EM sander.vinks@cchmc.org
OI Mizuno, Tomoyuki/0000-0002-8471-9826
FU Department of Defense [W81XWH-05-615]; Neurofibromatosis Clinical Trials
Consortium; National Institutes of Health [5K24HD050387]; Japan Research
Foundation for Clinical Pharmacology; internship program at Otsuka
Pharmaceutical Co, Ltd, Tokushima, Japan
FX Supported in part by Department of Defense grant W81XWH-05-615,
Neurofibromatosis Clinical Trials Consortium (B.C.W., M.J.F., B.W.,
J.P., and A.A.V.), and National Institutes of Health grant 5K24HD050387
(A.A.V.). T. Mizuno is supported by the Japan Research Foundation for
Clinical Pharmacology. C. Emoto was supported by an internship program
at Otsuka Pharmaceutical Co, Ltd, Tokushima, Japan to study in
Cincinnati.
NR 20
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0163-4356
EI 1536-3694
J9 THER DRUG MONIT
JI Ther. Drug Monit.
PD JUN
PY 2015
VL 37
IS 3
BP 395
EP 399
PG 5
WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology
SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology
GA CI4NU
UT WOS:000354728400019
PM 25162215
ER
PT J
AU Dunnick, JK
Sanders, JM
Kissling, GE
Johnson, CL
Boyle, MH
Elmore, SA
AF Dunnick, J. K.
Sanders, J. M.
Kissling, G. E.
Johnson, C. L.
Boyle, M. H.
Elmore, S. A.
TI Environmental Chemical Exposure May Contribute to Uterine Cancer
Development: Studies with Tetrabromobisphenol A
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE tetrabromobisphenol A; uterine tumors; malignant mixed Mullerian tumors
(MMMT); flame retardants
ID MIXED MULLERIAN TUMORS; BROMINATED FLAME RETARDANTS; ENDOMETRIAL
HYPERPLASIA; OXIDATIVE STRESS; BISPHENOL-A; IN-VITRO; RATS; METABOLISM;
CARCINOGENICITY; UTERUS
AB Tetrabromobisphenol A (TBBPA), a widely used flame retardant, caused uterine tumors in rats. In this study, TBBPA was administered to male and female Wistar Han rats and B6C3F1/N mice by oral gavage in corn oil for 2 years at doses up to 1,000 mg/kg. TBBPA induced uterine epithelial tumors including adenomas, adenocarcinomas, and malignant mixed Mullerian tumors (MMMTs). In addition, endometrial epithelial atypical hyperplasia occurred in TBBPA-treated rats. Also found to be related to TBBPA treatment, but at lower incidence and at a lower statistical significance, were testicular tumors in rats, and hepatic tumors, hemangiosarcomas (all organs), and intestinal tumors in male mice. It is hypothesized that the TBBPA uterine tumor carcinogenic mechanisms involve altered estrogen levels and/or oxidative damage. TBBPA treatment may affect hydroxysteroid-dehydrogenase-17 (HSD17) and/or sulfotransferases, enzymes involved in estrogen homeostasis. Metabolism of TBBPA may also result in the formation of free radicals. The finding of TBBPA-mediated uterine cancer in rats is of concern because TBBPA exposure is widespread and endometrial tumors are a common malignancy in women. Further work is needed to understand TBBPA cancer mechanisms.
C1 [Dunnick, J. K.; Kissling, G. E.; Elmore, S. A.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Sanders, J. M.] NCI, NIH, Res Triangle Pk, NC USA.
[Johnson, C. L.] Pathol Associates Inc, Charles River Labs, Res Triangle Pk, NC USA.
[Boyle, M. H.] Integrated Syst Lab, Res Triangle Pk, NC USA.
RP Dunnick, JK (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM dunnickj@niehs.nih.gov
FU National Institute of Environmental Health Sciences (NIEHS), Research
Triangle Park, NC; National Cancer Institute; NIEHS [N01-ES-55541,
HHSN291200555547C]
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This work
was supported by the intramural Research Program of the National
Institute of Environmental Health Sciences (NIEHS), Research Triangle
Park, NC. Authorial contributions by J. M. Sanders were supported by the
Intramural Research Program of the National Cancer Institute. The
in-life portion of this study was conducted under the supervision of Dr.
M. Hejtmanicik, Battelle Columbus, Columbus, Ohio, under NIEHS contract
N01-ES-55541. Statistical support was provided under NIEHS contract
HHSN291200555547C.
NR 53
TC 7
Z9 7
U1 1
U2 14
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
EI 1533-1601
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD JUN
PY 2015
VL 43
IS 4
BP 464
EP 473
DI 10.1177/0192623314557335
PG 10
WC Pathology; Toxicology
SC Pathology; Toxicology
GA CI5YJ
UT WOS:000354835400002
PM 25476797
ER
PT J
AU Davis, M
Bunin, DI
Samuelsson, SJ
Altera, KP
Kinders, RJ
Lawrence, SM
Ji, JP
Ames, MM
Buhrow, SA
Walden, C
Reid, JM
Rausch, LL
Parman, T
AF Davis, Myrtle
Bunin, Deborah I.
Samuelsson, Steven J.
Altera, Kenneth P.
Kinders, Robert J.
Lawrence, Scott M.
Ji, Jiuping
Ames, Matthew M.
Buhrow, Sarah A.
Walden, Chad
Reid, Joel M.
Rausch, Linda L.
Parman, Toufan
TI Characterization of Batracylin-induced Renal and Bladder Toxicity in
Rats
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE batracylin; renal toxicity; bladder toxicity; H2AX; DNA damage
ID ANTITUMOR AGENT BATRACYLIN; SOLID TUMORS; PHASE-I; GAMMA-H2AX;
NSC-320846; APOPTOSIS; INHIBITOR; LYMPHOMAS; HISTONE; ANALOGS
AB Batracylin (NSC-320846) is a dual inhibitor of DNA topoisomerases I and II. Batracylin advanced as an anticancer agent to Phase I clinical trials where dose limiting hemorrhagic cystitis (bladder inflammation and bleeding) was observed. To further investigate batracylin's mechanism of toxicity, studies were conducted in Fischer 344 rats. Once daily oral administration of 16 or 32 mg/kg batracylin to rats for 4 days caused overt toxicity. Abnormal clinical observations and adverse effects on clinical pathology, urinalysis, and histology indicated acute renal damage and urothelial damage and bone marrow dysfunction. Scanning electron microscopy revealed sloughing of the superficial and intermediate urothelial layers. DNA damage was evident in kidney and bone marrow as indicated by histone -H2AX immunofluorescence. After a single oral administration of 16 or 32 mg/kg, the majority of batracylin was converted to N-acetylbatracylin (NAB) with a half-life of 4 hr to 11 hr. Mesna (Mesnex), a drug known to reduce the incidence of hemorrhagic cystitis induced by ifosfamide or cyclophosphamide, was administered to rats prior to batracylin, but did not alleviate batracylin-induced bladder and renal toxicity. These findings suggest that batracylin results in DNA damage-based mechanisms of toxicity and not an acrolein-based mechanism of toxicity as occurs after ifosfamide or cyclophosphamide administration.
C1 [Davis, Myrtle] NCI, Toxicol & Pharmacol Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Bunin, Deborah I.; Samuelsson, Steven J.; Altera, Kenneth P.; Rausch, Linda L.; Parman, Toufan] SRI Int, Menlo Pk, CA 94025 USA.
[Kinders, Robert J.; Lawrence, Scott M.; Ji, Jiuping] Frederick Natl Lab Canc Res, Pharmacodynam Assay Dev & Implementat Sect, Lab Human Toxicol & Pharmacol, Appl Dev Res Directorate, Frederick, MD USA.
[Ames, Matthew M.; Buhrow, Sarah A.; Walden, Chad; Reid, Joel M.] Mayo Clin, Div Oncol Res, Dept Oncol, Rochester, MN USA.
RP Davis, M (reprint author), NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM davismillinm@mail.nih.gov
FU Developmental Therapeutics Program in the Division of Cancer Treatment
and Diagnosis of the National Cancer Institute under NCI [N01-CM-42203,
N01-CM-2011-00028]
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This
research was supported (in part) by the Developmental Therapeutics
Program in the Division of Cancer Treatment and Diagnosis of the
National Cancer Institute under NCI Contracts N01-CM-42203, and
N01-CM-2011-00028.
NR 20
TC 0
Z9 0
U1 0
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
EI 1533-1601
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD JUN
PY 2015
VL 43
IS 4
BP 519
EP 529
DI 10.1177/0192623314548766
PG 11
WC Pathology; Toxicology
SC Pathology; Toxicology
GA CI5YJ
UT WOS:000354835400007
PM 25274659
ER
PT J
AU Quist, EM
Filgo, AJ
Cummings, CA
Kissling, GE
Hoenerhoff, MJ
Fenton, SE
AF Quist, Erin M.
Filgo, Adam J.
Cummings, Connie A.
Kissling, Grace E.
Hoenerhoff, Mark J.
Fenton, Suzanne E.
TI Hepatic Mitochondrial Alteration in CD-1 Mice Associated with Prenatal
Exposures to Low Doses of Perfluorooctanoic Acid (PFOA)
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE PFOA; PPAR; hepatocellular hypertrophy; mitochondrial damage; peroxisome
proliferation; mouse; liver
ID PEROXISOME PROLIFERATOR; MOUSE; LIVER; EXPRESSION; PPAR
AB Perfluorooctanoic acid (PFOA) is a perfluoroalkyl acid primarily used as an industrial surfactant. It persists in the environment and has been linked to potentially toxic and/or carcinogenic effects in animals and people. As a known activator of peroxisome proliferator-activated receptors (PPARs), PFOA exposure can induce defects in fatty acid oxidation, lipid transport, and inflammation. Here, pregnant CD-1 mice were orally gavaged with 0, 0.01, 0.1, 0.3, and 1 mg/kg of PFOA from gestation days (GD) 1 through 17. On postnatal day (PND) 21, histopathologic changes in the livers of offspring included hepatocellular hypertrophy and periportal inflammation that increased in severity by PND 91 in an apparent dose-dependent response. Transmission electron microscopy (TEM) of selected liver sections from PND 91 mice revealed PFOA-induced cellular damage and mitochondrial abnormalities with no evidence of peroxisome proliferation. Within hypertrophied hepatocytes, mitochondria were not only increased in number but also exhibited altered morphologies suggestive of increased and/or uncontrolled fission and fusion reactions. These findings suggest that peroxisome proliferation is not a component of PFOA-induced hepatic toxicity in animals that are prenatally exposed to low doses of PFOA.
C1 [Quist, Erin M.; Filgo, Adam J.; Fenton, Suzanne E.] NIEHS, NTP Lab, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Quist, Erin M.; Hoenerhoff, Mark J.] NIEHS, Cellular & Mol Pathol Branch, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Quist, Erin M.] N Carolina State Univ, Coll Vet Med, Comparat Biomed Sci, Raleigh, NC USA.
[Filgo, Adam J.] Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC USA.
[Cummings, Connie A.] UltraPath Imaging, Durham, NC USA.
[Kissling, Grace E.] NIEHS, Biostat Branch, Div Intramural Res, Res Triangle Pk, NC 27709 USA.
RP Fenton, SE (reprint author), NIEHS, NTP Lab, 111 TW Alexander Dr Bldg 101,MD E1-08, Res Triangle Pk, NC 27709 USA.
EM fentonse@niehs.nih.gov
FU National Institutes of Health (NIH); National Institute of Environmental
Health Sciences (NIEHS)
FX This research was supported (in part) by the Intramural Research Program
of the National Institutes of Health (NIH) and National Institute of
Environmental Health Sciences (NIEHS).
NR 20
TC 3
Z9 3
U1 0
U2 8
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
EI 1533-1601
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD JUN
PY 2015
VL 43
IS 4
BP 546
EP 557
DI 10.1177/0192623314551841
PG 12
WC Pathology; Toxicology
SC Pathology; Toxicology
GA CI5YJ
UT WOS:000354835400010
PM 25326589
ER
PT J
AU Filgo, AJ
Quist, EM
Hoenerhoff, MJ
Brix, AE
Kissling, GE
Fenton, SE
AF Filgo, Adam J.
Quist, Erin M.
Hoenerhoff, Mark J.
Brix, Amy E.
Kissling, Grace E.
Fenton, Suzanne E.
TI Perfluorooctanoic Acid (PFOA)-induced Liver Lesions in Two Strains of
Mice Following Developmental Exposures: PPAR Is Not Required
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE PFOA; PPAR; liver; tumor; pathology; developmental exposure
ID ACTIVATED RECEPTOR-ALPHA; MAMMARY-GLAND DEVELOPMENT; AMMONIUM
PERFLUOROOCTANOATE; POLYFLUOROALKYL COMPOUNDS; PERFLUORINATED COMPOUNDS;
MOUSE; TOXICITY; PROLIFERATION; EXPRESSION; CHEMICALS
AB Perfluorooctanoic acid (PFOA) is a ubiquitous pollutant that causes liver toxicity in rodents, a process believed to be dependent on peroxisome proliferator-activated receptor-alpha (PPAR) activation. Differences between humans and rodents have made the human relevance of some health effects caused by PFOA controversial. We analyzed liver toxicity at 18 months following gestational PFOA exposure in CD-1 and 129/Sv strains of mice and compared PFOA-induced effects between strains and in wild type (WT) and PPAR-knockout (KO) 129/Sv mice. Pregnant mice were exposed daily to doses (0.01-5 mg/kg/BW) of PFOA from gestation days 1 to 17. The female offspring were necropsied at 18 months, and liver sections underwent a full pathology review. Hepatocellular adenomas formed in PFOA-exposed PPAR-KO 129/Sv and CD-1 mice and were absent in untreated controls from those groups and WT 129/Sv. Hepatocellular hypertrophy was significantly increased by PFOA exposure in CD-1, and an increased severity was found in WT 129/Sv mice. PFOA significantly increased nonneoplastic liver lesions in PPAR-KO mice (hepatocyte hypertrophy, bile duct hyperplasia, and hematopoietic cell proliferation). Low-dose gestational exposures to PFOA induced latent PPAR-independent liver toxicity that was observed in aged mice. Evidence of liver toxicity in PPAR-KO mice warrants further investigation into PPAR-independent pathways.
C1 [Filgo, Adam J.] Univ N Carolina, Sch Med, Curriculum Toxicol, Chapel Hill, NC USA.
[Filgo, Adam J.; Quist, Erin M.; Fenton, Suzanne E.] NIEHS, NTP Lab, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Quist, Erin M.] N Carolina State Univ, Coll Vet Med, Comparat Biomed Sci, Raleigh, NC USA.
[Quist, Erin M.; Hoenerhoff, Mark J.] NIEHS, Cellular & Mol Pathol Branch, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Brix, Amy E.] Expt Pathol Labs Inc, Res Triangle Pk, NC USA.
[Kissling, Grace E.] NIEHS, Biostat Branch, Div Intramural Res, Res Triangle Pk, NC 27709 USA.
RP Fenton, SE (reprint author), NIEHS, NTP Lab, Div Natl Toxicol Program, 111 TW Alexander Dr,Bldg 101,MD E1-08, Res Triangle Pk, NC 27709 USA.
EM fentonse@niehs.nih.gov
FU Intramural NIH HHS [ZIA ES102785-05]; NIEHS NIH HHS [T32 ES007126]
NR 34
TC 1
Z9 1
U1 6
U2 10
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0192-6233
EI 1533-1601
J9 TOXICOL PATHOL
JI Toxicol. Pathol.
PD JUN
PY 2015
VL 43
IS 4
BP 558
EP 568
DI 10.1177/0192623314558463
PG 11
WC Pathology; Toxicology
SC Pathology; Toxicology
GA CI5YJ
UT WOS:000354835400011
PM 25398757
ER
PT J
AU Arama, C
Maiga, B
Dolo, A
Kouriba, B
Traore, B
Crompton, PD
Pierce, SK
Troye-Blomberg, M
Miller, LH
Doumbo, OK
AF Arama, Charles
Maiga, Bakary
Dolo, Amagana
Kouriba, Bourema
Traore, Boubacar
Crompton, Peter D.
Pierce, Susan K.
Troye-Blomberg, Marita
Miller, Louis H.
Doumbo, Ogobara K.
TI Ethnic differences in susceptibility to malaria: What have we learned
from immuno-epidemiological studies in West Africa?
SO ACTA TROPICA
LA English
DT Review
DE Malaria; Immunity; Ethnic; Fulani; Susceptibility; Sympatric
ID PLASMODIUM-FALCIPARUM INFECTION; INTERETHNIC DIFFERENCES; BURKINA-FASO;
HUMORAL RESPONSE; MALI; FULANI; POLYMORPHISM; SYMPATRY; COINFECTION;
POPULATIONS
AB There are many fundamental aspects of the immunobiology of Plasmodium falciparum infections that are not fully understood, therefore limiting our comprehension of how people become immune to malaria and why some ethnic groups living in malaria endemic areas are less susceptible than others. The complexity of parasite-host interactions and the genetic diversity of the parasites as well as the human host complicate our strategy to address this issue.
In this mini-review we discuss and summarize what we have learned about African ethnic differences in susceptibility to malaria from immuno-epidemiological studies. Additionally, we suggest research topics that might be of great value for dissecting the mechanisms of protection by providing new insights into molecular interactions between the parasite and the host. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Arama, Charles; Maiga, Bakary; Dolo, Amagana; Kouriba, Bourema; Traore, Boubacar; Doumbo, Ogobara K.] Univ Sci Tech & Technol Bamako, ICER Mali NIAID, FMOS FAPH, Malaria Res & Training Ctr,Dept Epidemiol Parasit, Bamako, Mali.
[Crompton, Peter D.; Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Troye-Blomberg, Marita] Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Stockholm, Sweden.
[Miller, Louis H.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
RP Arama, C (reprint author), Univ Sci Tech & Technol Bamako, ICER Mali NIAID, FMOS FAPH, Malaria Res & Training Ctr,Dept Epidemiol Parasit, Bamako, Mali.
EM charama@icermali.org; okd@icermali.org
RI Troye-Blomberg, Marita/B-9210-2016; Crompton, Peter/N-1130-2016
OI Troye-Blomberg, Marita/0000-0002-2804-0325;
NR 54
TC 5
Z9 5
U1 1
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0001-706X
EI 1873-6254
J9 ACTA TROP
JI Acta Trop.
PD JUN
PY 2015
VL 146
BP 152
EP 156
DI 10.1016/j.actatropica.2015.03.023
PG 5
WC Parasitology; Tropical Medicine
SC Parasitology; Tropical Medicine
GA CI3QI
UT WOS:000354662100023
PM 25820030
ER
PT J
AU Peskin, VA
Ordonez, A
Mackin, RS
Delucchi, K
Monge, S
McGough, JJ
Chavira, DA
Berrocal, M
Cheung, E
Fournier, E
Badner, JA
Herrera, LD
Mathews, CA
AF Peskin, Viviana A.
Ordonez, Anna
Mackin, R. Scott
Delucchi, Kevin
Monge, Silvia
McGough, James J.
Chavira, Denise A.
Berrocal, Monica
Cheung, Erika
Fournier, Eduardo
Badner, Judith A.
Herrera, Luis Diego
Mathews, Carol A.
TI Neuropsychological and dimensional behavioral trait profiles in Costa
Rican ADHD sib pairs: Potential intermediate phenotypes for genetic
studies
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE ADHD; heritability; pedigrees; endophenotypes; cognitive
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER;
DEFICIT-HYPERACTIVITY-DISORDER; OSTERRIETH COMPLEX FIGURE; SEVERE
BIPOLAR DISORDER; LINKAGE DISEQUILIBRIUM; EXECUTIVE FUNCTIONS;
LIFE-SPAN; POPULATION ISOLATE; WORKING-MEMORY; CHILDREN
AB Attention deficit hyperactivity disorder (ADHD) is associated with substantial functional impairment in children and in adults. Many individuals with ADHD have clear neurocognitive deficits, including problems with visual attention, processing speed, and set shifting. ADHD is etiologically complex, and although genetic factors play a role in its development, much of the genetic contribution to ADHD remains unidentified. We conducted clinical and neuropsychological assessments of 294 individuals (269 with ADHD) from 163 families (48 multigenerational families created using genealogical reconstruction, 78 affected sib pair families, and 37 trios) from the Central Valley of Costa Rica (CVCR). We used principal components analysis (PCA) to group neurocognitive and behavioral variables using the subscales of the Child Behavior Checklist (CBCL) and 15 neuropsychological measures, and created quantitative traits for heritability analyses. We identified seven cognitive and two behavioral domains. Individuals with ADHD were significantly more impaired than their unaffected siblings on most behavioral and cognitive domains. The verbal IQ domain had the highest heritability (92%), followed by auditory attention (87%), visual processing speed and problem solving (85%), and externalizing symptoms (81%). The quantitative traits identified here have high heritabilities, similar to the reported heritability of ADHD (70-90%), and may represent appropriate alternative phenotypes for genetic studies. The use of multigenerational families from a genetically isolated population may facilitate the identification of ADHD risk genes in the face of phenotypic and genetic heterogeneity. (c) 2015 Wiley Periodicals, Inc.
C1 [Peskin, Viviana A.; Mackin, R. Scott; Delucchi, Kevin; Cheung, Erika; Mathews, Carol A.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Ordonez, Anna] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
[Monge, Silvia; Berrocal, Monica; Fournier, Eduardo; Herrera, Luis Diego] Hosp CIMA, Dept Psychiat, San Jose, Costa Rica.
[McGough, James J.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA.
[Chavira, Denise A.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA.
[Badner, Judith A.] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA.
[Badner, Judith A.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
[Mathews, Carol A.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
RP Mathews, CA (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
EM cmathews@lppi.ucsf.edu
FU [R01 NS048376]; [K08 MH081065]
FX This research was supported by grant R01 NS048376 to C.A.M. and grant
K08 MH081065 to R.S.M. We would like to thank the individuals and
families who participated in this work.
NR 74
TC 1
Z9 1
U1 3
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4841
EI 1552-485X
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD JUN
PY 2015
VL 168
IS 4
BP 247
EP 257
DI 10.1002/ajmg.b.32305
PG 11
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA CI3IA
UT WOS:000354640100003
PM 25832558
ER
PT J
AU Miettinen, M
McCue, PA
Sarlomo-Rikala, M
Biernat, W
Czapiewski, P
Kopczynski, J
Thompson, LD
Lasota, J
Wang, ZF
Fetsch, JF
AF Miettinen, Markku
McCue, Peter A.
Sarlomo-Rikala, Maarit
Biernat, Wojciech
Czapiewski, Piotr
Kopczynski, Janusz
Thompson, Lester D.
Lasota, Jerzy
Wang, Zengfeng
Fetsch, John F.
TI Sox10-A Marker for Not Only Schwannian and Melanocytic Neoplasms But
Also Myoepithelial Cell Tumors of Soft Tissue A Systematic Analysis of
5134 Tumors
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE Sox10; Schwann cell; breast cancer; myoepithelioma; immunohistochemistry
ID TRANSCRIPTION FACTOR SOX10; HIRSCHSPRUNG-DISEASE; EXPRESSION;
CARCINOMAS; DIAGNOSIS; MELANOMA; GENE; MUTATIONS; LESIONS; MOUSE
AB Sox10 transcription factor is expressed in schwannian and melanocytic lineages and is important in their development and can be used as a marker for corresponding tumors. In addition, it has been reported in subsets of myoepithelial/basal cell epithelial neoplasms, but its expression remains incompletely characterized. In this study, we examined Sox10 expression in 5134 human neoplasms spanning a wide spectrum of neuroectodermal, mesenchymal, lymphoid, and epithelial tumors. A new rabbit monoclonal antibody (clone EP268) and Leica Bond Max automation were used on multitumor block libraries containing 30 to 70 cases per slide. Sox10 was consistently expressed in benign Schwann cell tumors of soft tissue and the gastrointestinal tract and in metastatic melanoma and was variably present in malignant peripheral nerve sheath tumors. In contrast, Sox10 was absent in many potential mimics of nerve sheath tumors such as cellular neurothekeoma, meningioma, gastrointestinal stromal tumors, perivascular epithelioid cell tumor and a variety of fibroblastic-myofibroblastic tumors. Sox10 was virtually absent in mesenchymal tumors but occasionally seen in alveolar rhabdomyosarcoma. In epithelial tumors of soft tissue, Sox10 was expressed only in myoepitheliomas, although often absent in malignant variants. Carcinomas, other than basal cell-type breast cancers, were only rarely positive but included 6% of squamous carcinomas of head and neck and 7% of pulmonary small cell carcinomas. Furthermore, Sox10 was often focally expressed in embryonal carcinoma reflecting a primitive Sox10-positive phenotype or neuroectodermal differentiation. Expression of Sox10 in entrapped non-neoplastic Schwann cells or melanocytes in various neoplasms has to be considered in diagnosing Sox10-positive tumors. The Sox10 antibody belongs in a modern immunohistochemical panel for the diagnosis of soft tissue and epithelial tumors.
C1 [Miettinen, Markku; Lasota, Jerzy; Wang, Zengfeng] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Fetsch, John F.] Capital Reg, Joint Pathol Ctr, Silver Spring, MD USA.
[McCue, Peter A.] Thomas Jefferson Univ, Dept Pathol, Kimmel Med Coll, Philadelphia, PA 19107 USA.
[Thompson, Lester D.] So Calif Permanente Med Grp, Woodland Hills, CA USA.
[Sarlomo-Rikala, Maarit] Univ Helsinki, Helsinki, Finland.
[Sarlomo-Rikala, Maarit] HUSLab Pathol, Helsinki, Finland.
[Biernat, Wojciech; Czapiewski, Piotr] Med Univ Gdansk, Dept Pathol, Gdansk, Poland.
[Kopczynski, Janusz] Holy Cross Canc Ctr, Kielce, Poland.
RP Miettinen, M (reprint author), NCI, Pathol Lab, Surg Pathol Sect, 9000 Rockville Pike,Bldg 10,Rm 2B50, Bethesda, MD 20892 USA.
EM miettinenmm@mail.nih.gov
FU Intramural Research Program of the NIH/NCI
FX The authors have disclosed that they have no significant relationships
with, or financial interest in, any commercial companies pertaining to
this article. This work was supported by the Intramural Research Program
of the NIH/NCI.
NR 24
TC 19
Z9 20
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0147-5185
EI 1532-0979
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD JUN
PY 2015
VL 39
IS 6
BP 826
EP 835
PG 10
WC Pathology; Surgery
SC Pathology; Surgery
GA CI1EP
UT WOS:000354485400013
PM 25724000
ER
PT J
AU Epstein, DH
Preston, KL
AF Epstein, David H.
Preston, Kenzie L.
TI No Evidence for Reduction of Opioid-Withdrawal Symptoms by Cannabis
Smoking During a Methadone Dose Taper
SO AMERICAN JOURNAL ON ADDICTIONS
LA English
DT Article
ID MAINTENANCE TREATMENT; SELF-DETOXIFICATION; OPIATE-DEPENDENCE; CONTRASTS
AB Background and ObjectivesTo support medication development with cannabinoids, smoked cannabis has been said to alleviate symptoms of opioid withdrawal. We evaluated that hypothesis.
MethodsWe analyzed data from the methadone-taper phase of a clinical trial we had conducted. Participants were 116 outpatient heroin and cocaine users (of whom 46 were also cannabis users) who stayed for the 10-week taper. Main outcome measures were weekly urine screens for cannabinoids, plus every-two-week assessments of opioid-withdrawal symptoms.
ResultsOpioid-withdrawal scores did not differ overall between users and nonusers of cannabis. In a lagged analysis in the 46 users, there was a slight (not statistically significant) indication that weeks of higher opiate-withdrawal symptoms preceded weeks of cannabis use (effect-size r=.20, 95% CI -.10 to .46, p=.52). Even if this finding is taken to suggest self-medication with cannabis, a lagged analysis in the other temporal direction showed no indication that cannabis use predicted lower opiate-withdrawal symptoms the next week (effect-size r=.01, 95% CI -.28 to .30, p=.69). These findings persisted in sensitivity analyses controlling for each of 17 potential confounds.
Discussion and ConclusionWith our findings, the clinical evidence for smoked cannabis as a reducer of opioid-withdrawal symptoms moves slightly further from inconclusive or mixed and closer to negative, at least in the context of a methadone dose taper like the one used here.
Scientific SignificanceThis finding may remove one rationale for medication development using cannabinoids to treat opioid withdrawal, but leaves other rationales intact. (Am J Addict 2015;XX: XX-XX)
C1 [Epstein, David H.; Preston, Kenzie L.] NIDA, Treatment Sect, Clin Pharmacol & Therapeut Branch, Intramural Res Branch, Baltimore, MD 21224 USA.
RP Epstein, DH (reprint author), NIDA, Treatment Sect, Clin Pharmacol & Therapeut Branch, Intramural Res Branch, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM depstein@intra.nida.nih.gov
FU NIH National Institute on Drug Abuse
FX This research was supported by the Intramural Research Program of the
NIH National Institute on Drug Abuse.
NR 22
TC 0
Z9 0
U1 2
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1055-0496
EI 1521-0391
J9 AM J ADDICTION
JI Am. J. Addict.
PD JUN
PY 2015
VL 24
IS 4
BP 323
EP 328
DI 10.1111/ajad.12183
PG 6
WC Substance Abuse
SC Substance Abuse
GA CH6YT
UT WOS:000354183200007
PM 25846329
ER
PT J
AU Enewold, L
Harlan, LC
Stevens, JL
Sharon, E
AF Enewold, Lindsey
Harlan, Linda C.
Stevens, Jennifer L.
Sharon, Elad
TI Thyroid Cancer Presentation and Treatment in the United States
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID INCREASING INCIDENCE; RADIOACTIVE IODINE; CARCINOMA; SURVIVAL; SURGERY;
EXTENT; RISK
AB Thyroid cancer incidence is rising in the United States. Although overall thyroid cancer survival is high, prognostic stratification schemes have been developed to better delineate patients with poor prognoses.
A random sample that included 1,003 adult papillary thyroid cancer patients diagnosed in 2006 and reported to the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) program had their medical records re-abstracted and additional risk factor data collected. The distribution of patient demographics, medical histories, tumor characteristics and treatment modalities were assessed. Logistic regression was used to assess factors associated with total thyroidectomy (total, subtotal or near total) and radioiodine therapy. All analyses were conducted stratified by the Age, Metastases, Extent and Size (AMES) low/high-risk classification.
Receipt of total thyroidectomy was associated with family history of thyroid disease/cancer and larger tumor size among low-risk patients and smaller tumor size among high-risk patients. Among low-risk patients, the receipt of radioiodine was associated with family history of thyroid disease/cancer, larger tumor size, total thyroidectomy, and positive lymph nodes. Among high-risk patients, the receipt of radioiodine was associated with intermediate tumor and hospital sizes.
This study provides insight into the patterns of papillary thyroid cancer care in the general population. The findings from this study indicate adherence to guideline recommendations in that family history of thyroid disease/cancer, in addition to tumor characteristics, does appear to inform treatment practices, especially among low-risk patients.
C1 [Enewold, Lindsey; Harlan, Linda C.; Sharon, Elad] NCI, Bethesda, MD 20892 USA.
[Stevens, Jennifer L.] Informat Management Serv Inc, Calverton, MD USA.
RP Harlan, LC (reprint author), NCI, Bethesda, MD 20892 USA.
EM lh50w@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 22
TC 0
Z9 0
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
EI 1534-4681
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD JUN
PY 2015
VL 22
IS 6
BP 1789
EP 1797
DI 10.1245/s10434-014-4209-1
PG 9
WC Oncology; Surgery
SC Oncology; Surgery
GA CH7ON
UT WOS:000354226600009
PM 25361888
ER
PT J
AU Enomoto, A
Saito, K
Subramanian, S
Krishna, MC
Hirata, H
Devasahayam, N
AF Enomoto, Ayano
Saito, Keita
Subramanian, Sankaran
Krishna, Murali C.
Hirata, Hiroshi
Devasahayam, Nallathamby
TI Passive Decoupling Due to Low Q-Factors of Four-Channel Coils in 300-MHz
Pulsed EPR Imaging
SO APPLIED MAGNETIC RESONANCE
LA English
DT Article
ID ELECTRON-PARAMAGNETIC-RESONANCE; TOOTH DOSIMETRY; PHASED-ARRAY;
ACQUISITION; MRI; RESONATORS; DESIGN; SYSTEM
AB This article describes a four-channel coil array for in vivo time-domain electron paramagnetic resonance (EPR) imaging applications. Decoupling of the individual element coils was achieved with the low-quality factors required in pulsed EPR at radiofrequency to accommodate the imaging bandwidth. No active decoupling method was used in the coil array. Remote control of a coaxial switch connected to the four-channel coil array was performed with voltage signals from a personal computer. To verify the operation of this four-channel coil array, a phantom tube filled with a solution of paramagnetic triarylmethyl radicals (OX063) was visualized by pulsed EPR imaging based on the single-point method involving pure phase encoding. In an in vivo experiment, OX063 in a mouse tumor-bearing right hind leg was visualized by pulsed EPR imaging. Even without active decoupling circuits, there was no shift in resonances for individual coils when those were tuned to the same frequency due to low quality factors and low coupling coefficients with neighboring coils. The coil assembly allowed us to study an object that was larger than an individual coil element, enabling the imaging of larger subjects with reduced overall specific absorption rate. Such strategies should be useful for studying larger objects by EPR imaging.
C1 [Enomoto, Ayano; Hirata, Hiroshi] Hokkaido Univ, Grad Sch Informat Sci & Technol, Div Bioengn & Bioinformat, Kita Ku, Sapporo, Hokkaido 0600814, Japan.
[Saito, Keita; Subramanian, Sankaran; Krishna, Murali C.; Devasahayam, Nallathamby] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Hirata, H (reprint author), Hokkaido Univ, Grad Sch Informat Sci & Technol, Div Bioengn & Bioinformat, Kita Ku, North 14,West 9, Sapporo, Hokkaido 0600814, Japan.
EM hhirata@ist.hokudai.ac.jp
FU JSPS KAKENHI [26249057]; JSPS [24-1486]; Center for Cancer Research,
NCI, NIH
FX This work was supported in part by JSPS KAKENHI Grant Number 26249057.
A.E. was supported by a Research Fellowship for Young Scientists
(24-1486) from JSPS. We also thank the Center for Cancer Research, NCI,
NIH for intramural research funding.
NR 21
TC 0
Z9 0
U1 2
U2 5
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0937-9347
EI 1613-7507
J9 APPL MAGN RESON
JI Appl. Magn. Reson.
PD JUN
PY 2015
VL 46
IS 6
BP 671
EP 683
DI 10.1007/s00723-015-0671-6
PG 13
WC Physics, Atomic, Molecular & Chemical; Spectroscopy
SC Physics; Spectroscopy
GA CI3AX
UT WOS:000354620900006
ER
PT J
AU Fontes, JD
Rahman, F
Lacey, S
Larson, MG
Vasan, RS
Benjamin, EJ
Harris, WS
Robins, SJ
AF Fontes, Joao D.
Rahman, Faisal
Lacey, Sean
Larson, Martin G.
Vasan, Ramachandran S.
Benjamin, Emelia J.
Harris, William S.
Robins, Sander J.
TI Red blood cell fatty acids and biomarkers of inflammation: A
cross-sectional study in a community-based cohort
SO ATHEROSCLEROSIS
LA English
DT Article
DE Omega-3 fatty acids; Biomarkers; Inflammation; Cross-sectional study
ID C-REACTIVE PROTEIN; CORONARY-ARTERY-DISEASE; PHOSPHOLIPASE A(2); FISH
CONSUMPTION; CARDIOVASCULAR-DISEASE; OXIDATIVE STRESS;
RHEUMATOID-ARTHRITIS; CIRCULATING LEVELS; HEART-DISEASE; PPAR-GAMMA
AB Introduction: Inflammation and inflammatory biomarkers have emerged as integral components and predictors of incident cardiovascular (CV) disease. Omega-3 fatty acids, particularly eicosapentaenoic and docosahexaenoic acids (EPA and DHA) have anti-inflammatory properties, and have been variably associated with lower blood pressure, favorable blood lipid changes, and reduced CV events.
Methods and results: We examined the cross-sectional association of red blood cell (RBC) fatty acids, representative of body membrane fatty acid composition, with 10 biomarkers active in multiple inflammatory pathways in 2724 participants (mean age 66 +/- 9 years, 54% women, 8% minorities) from the Framingham Offspring and minority Omni Cohorts. After multivariable adjustment, the RBC EPA and DHA content was inversely correlated (all P <= 0.001) with 8 biomarkers: urinary isoprostanes (r = -0.16); and soluble interleukin-6 (r = -0.10); C-reactive protein (r = -0.08); tumor necrosis factor receptor 2 (r = -0.08); intercellular adhesion molecule-1 (r = -0.08); P-selectin (r = -0.06); lipoprotein-associated phospholipase-A2 mass (r = -0.11) and activity (r = -0.08). The correlations for monocyte chemoattractant protein-1 was -0.05, P = 0.006 and osteoprotegerin (r = -0.06, P = 0.002) were only nominally significant.
Conclusion: In our large community-based study, we observed modest inverse associations between several types of inflammatory biomarkers with RBC omega-3 fatty acid levels. Our findings are consistent with the hypothesis that omega-3 fatty acids have anti-inflammatory properties. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Fontes, Joao D.; Lacey, Sean; Larson, Martin G.; Vasan, Ramachandran S.; Benjamin, Emelia J.; Robins, Sander J.] Natl Heart Lung & Blood Inst, Framingham, MA USA.
[Fontes, Joao D.; Lacey, Sean; Larson, Martin G.; Vasan, Ramachandran S.; Benjamin, Emelia J.; Robins, Sander J.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Fontes, Joao D.; Vasan, Ramachandran S.; Benjamin, Emelia J.; Robins, Sander J.] Boston Univ, Sch Med, Dept Cardiol & Prevent Med, Boston, MA 02118 USA.
[Fontes, Joao D.; Vasan, Ramachandran S.; Benjamin, Emelia J.; Robins, Sander J.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Rahman, Faisal] Boston Univ, Med Ctr, Boston, MA 02118 USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA.
[Harris, William S.] Univ S Dakota, Sanford Sch Med, Dept Med, Sioux Falls, SD 57106 USA.
[Harris, William S.] OmegaQuant Analyt LLC, Sioux Falls, SD 57106 USA.
RP Harris, WS (reprint author), Univ S Dakota, Sanford Sch Med, Dept Med, 5009 W 12th St,Ste 8, Sioux Falls, SD 57106 USA.
EM bill@omegaquant.com
OI Rahman, Faisal/0000-0002-7946-0311; Ramachandran,
Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336
FU [2R01HL092577]; [1RO1-HL64753]; [R01-HL076784];
[1R01-1RO1-AG0283211]; [N01-HC 25195]; [N01-HC25195]; [R01 HL089590]
FX Dr. Benjamin is supported by 2R01HL092577; 1RO1-HL64753; R01-HL076784;
1R01-1RO1-AG0283211; N01-HC 25195. Dr. Vasan is supported by
N01-HC25195, and Dr. Harris by R01 HL089590.
NR 65
TC 11
Z9 11
U1 0
U2 13
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
EI 1879-1484
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD JUN
PY 2015
VL 240
IS 2
BP 431
EP 436
DI 10.1016/j.atherosclerosis.2015.03.043
PG 6
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CI1ZQ
UT WOS:000354544300022
PM 25897795
ER
PT J
AU Lee, SJ
Wolff, D
Kitko, C
Koreth, J
Inamoto, Y
Jagasia, M
Pidala, J
Olivieri, A
Martin, PJ
Przepiorka, D
Pusic, I
Dignan, F
Mitchell, SA
Lawitschka, A
Jacobsohn, D
Hall, AM
Flowers, MED
Schultz, KR
Vogelsang, G
Pavletic, S
AF Lee, Stephanie J.
Wolff, Daniel
Kitko, Carrie
Koreth, John
Inamoto, Yoshihiro
Jagasia, Madan
Pidala, Joseph
Olivieri, Attilio
Martin, Paul J.
Przepiorka, Donna
Pusic, Iskra
Dignan, Fiona
Mitchell, Sandra A.
Lawitschka, Anita
Jacobsohn, David
Hall, Anne M.
Flowers, Mary E. D.
Schultz, Kirk R.
Vogelsang, Georgia
Pavletic, Steven
TI Measuring Therapeutic Response in Chronic Graft-versus-Host Disease.
National Institutes of Health Consensus Development Project on Criteria
for Clinical Trials in Chronic Graft-versus-Host Disease: IV. The 2014
Response Criteria Working Group Report
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Chronic graft-versus-host disease; Allogeneic hematopoietic cell
transplantation; Response criteria; Consensus; Guidelines
ID STEM-CELL TRANSPLANTATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS;
BONE-MARROW-TRANSPLANTATION; CHRONIC GVHD CONSORTIUM; 6-MINUTE WALK
TEST; OBLITERANS ORGANIZING PNEUMONIA; HUMAN ACTIVITY PROFILE;
FAILURE-FREE SURVIVAL; SLEEP QUALITY INDEX; RHEUMATOID-ARTHRITIS
AB In 2005, the National Institutes of Health (NIH) Chronic Graft-versus-Host Disease (GVHD) Consensus Response Criteria Working Group recommended several measures to document serial evaluations of chronic GVHD organ involvement. Provisional definitions of complete response, partial response, and progression were proposed for each organ and for overall outcome. Based on publications over the last 9 years, the 2014 Working Group has updated its recommendations for measures and interpretation of organ and overall responses. Major changes include elimination of several clinical parameters from the determination of response, updates to or addition of new organ scales to assess response, and the recognition that progression excludes minimal, clinically insignificant worsening that does not usually warrant a change in therapy. The response definitions have been revised to reflect these changes and are expected to enhance reliability and practical utility of these measures in clinical trials. Clarification is provided about response assessment after the addition of topical or organ-targeted treatment. Ancillary measures are strongly encouraged in clinical trials. Areas suggested for additional research include criteria to identify irreversible organ damage and validation of the modified response criteria, including in the pediatric population. Published by Elsevier Inc.
C1 [Lee, Stephanie J.; Martin, Paul J.; Hall, Anne M.; Flowers, Mary E. D.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Wolff, Daniel] Univ Regensburg, Dept Internal Med 3, D-93053 Regensburg, Germany.
[Kitko, Carrie] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA.
[Koreth, John] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA.
[Inamoto, Yoshihiro] Natl Canc Ctr, Div Hematopoiet Stem Cell Transplantat, Tokyo, Japan.
[Jagasia, Madan] Vanderbilt Univ, Div Hematol Oncol, Nashville, TN 37235 USA.
[Pidala, Joseph] Univ S Florida, H Lee Moffitt Canc Ctr, Blood & Marrow Transplantat, Tampa, FL 33682 USA.
[Olivieri, Attilio] Univ Ancona, Dept Clin & Mol Sci, Ancona, Italy.
[Przepiorka, Donna] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Pusic, Iskra] Washington Univ, Dept Med, St Louis, MO USA.
[Dignan, Fiona] Univ Manchester, Dept Clin Haematol, Manchester, Lancs, England.
[Mitchell, Sandra A.; Pavletic, Steven] NCI, Outcomes Res Branch, Bethesda, MD 20852 USA.
[Lawitschka, Anita] Med Univ Vienna, St Anna Childrens Hosp, Stem Cell Transplant Unit, Vienna, Austria.
[Jacobsohn, David] Childrens Natl Hlth Syst, Div Blood & Marrow Transplantat, Washington, DC USA.
[Schultz, Kirk R.] Univ British Columbia, BC Childrens Hosp, Vancouver, BC V5Z 1M9, Canada.
[Vogelsang, Georgia] Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA.
RP Pavletic, S (reprint author), NCI, GVHD & Autoimmun Unit, Expt Transplantat & Immunol Branch, Ctr Canc Res,NIH, 10 Ctr Dr,Bldg 10,Room CRC 4-3130, Bethesda, MD 20852 USA.
EM pavletis@mail.nih.gov
FU Millenium; Otsuka Pharmaceuticals; Prometheus Labs Inc.; Therakos;
Johnson and Johnson company
FX S.L. scientific advisory board meeting: Bristol Myers Squibb, Kadmon
Corp. J.K., research funding: Millenium, Otsuka Pharmaceuticals,
Prometheus Labs Inc.; scientific advisory board: Kadmon Corp, Amgen,
Takeda Pharmaceuticals. P.M., scientific advisory board meeting:
Pharmacyclics. F.D., received research funding, honoraria and speaker
fees: Therakos, a Johnson and Johnson company.
NR 119
TC 22
Z9 23
U1 2
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD JUN
PY 2015
VL 21
IS 6
BP 984
EP 999
DI 10.1016/j.bbmt.2015.02.025
PG 16
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CI3SO
UT WOS:000354667900004
PM 25796139
ER
PT J
AU Cuellar-Rodriguez, J
Freeman, AF
Grossman, J
Su, H
Parta, M
Murdock, H
Shah, N
Bollard, C
Kong, HH
Moutsopoulos, N
Stone, K
Gea-Banacloche, J
Holland, SM
Hickstein, DD
AF Cuellar-Rodriguez, Jennifer
Freeman, Alexandra F.
Grossman, Jennifer
Su, Helen
Parta, Mark
Murdock, Heardley
Shah, Nirali
Bollard, Catherine
Kong, Heidi H.
Moutsopoulos, Niki
Stone, Kelly
Gea-Banacloche, Juan
Holland, Steven M.
Hickstein, Dennis D.
TI Matched Related and Unrelated Donor Hematopoietic Stem Cell
Transplantation for DOCK8 Deficiency
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Allogeneic; Transplantation; DOCK8 deficiency
ID HYPER-IGE SYNDROME; TOXICITY CONDITIONING REGIMEN; DAILY INTRAVENOUS
BUSULFAN; CYTOKINESIS 8 DOCK8; DAILY IV BUSULFAN; PHARMACOKINETICS;
FLUDARABINE; DEDICATOR; MUTATIONS; RESPONSES
AB We performed allogeneic hematopoietic stem cell transplantation in 6 patients with mutations in the dedicator-of-cytokinesis-8 (DOCK8) gene using a myeloablative conditioning regimen consisting of busulfan 3.2 mg/kg/day i.v. for 4 days and fludarabine 40 mg/m(2)/day for 4 days. Three patients received allografts from matched related donors and 3 patients from matched unrelated donors Two patients received peripheral blood stem cells and 4 patients bone marrow hematopoietic stem cells. Tacrolimus and short-course methotrexate on days 1, 3, 6, and 11, were used for graft-versus-host-disease (GVHD) prophylaxis. All 6 patients are alive at a median follow-up of 22.5 months (range, 14 to 35). All patients achieved rapid and high levels of donor engraftment and complete reversal of the clinical and immunologic phenotype. Adverse events consisted of acute skin GVHD in 2 patients and post-transplant pulmonary infiltrates in a patient with extensive bronchiectasis pretransplant. Thus, a uniform myeloablative conditioning regimen followed by allogeneic hematopoietic stem cell transplantation in DOCK8 deficiency results in reconstitution of immunologic function and reversal of the clinical phenotype with a low incidence of regimen-related toxicity. Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation.
C1 [Cuellar-Rodriguez, Jennifer; Freeman, Alexandra F.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Grossman, Jennifer] Alberta Hlth Serv, Div Hematol & Hematol Malignancies, Calgary, AB, Canada.
[Su, Helen; Murdock, Heardley] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
[Parta, Mark] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Clin Res Directorate, Clin Monitoring Res Program, Frederick, MD USA.
[Shah, Nirali] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Bollard, Catherine] Childrens Natl Med Ctr, Childrens Res Inst, Ctr Canc & Immunol Res, Washington, DC 20010 USA.
[Kong, Heidi H.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
[Moutsopoulos, Niki] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
[Stone, Kelly] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Gea-Banacloche, Juan; Hickstein, Dennis D.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
RP Hickstein, DD (reprint author), 9000 Rockville Pike,Bldg 10 CRC,3-3142, Bethesda, MD 20892 USA.
EM hicksted@mail.nih.gov
RI Su, Helen/H-9541-2015;
OI Su, Helen/0000-0002-5582-9110; Kong, Heidi/0000-0003-4424-064X
FU National Cancer Institute [1ZIABCO11374]; National Institutes of Health
[HHSN261200800001E]; National Institute of Allergy and Infectious
Diseases; Division of Intramural Research, Center for Cancer Research
FX Supported in whole or in part with federal funds from the National
Cancer Institute (1ZIABCO11374), National Institutes of Health under
contract no. HHSN261200800001E, in part by the Division of Intramural
Research, Center for Cancer Research, and the National Institute of
Allergy and Infectious Diseases. The content of this publication does
not necessarily reflect the views or policies of the U.S. Department of
Health and Human Services or does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
NR 24
TC 14
Z9 14
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD JUN
PY 2015
VL 21
IS 6
BP 1037
EP 1045
DI 10.1016/j.bbmt.2015.01.022
PG 9
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CI3SO
UT WOS:000354667900009
PM 25636378
ER
PT J
AU Baird, K
Comis, LE
Joe, GO
Steinberg, SM
Hakim, FT
Rose, JJ
Mitchell, SA
Pavletic, SZ
Figg, WD
Yao, L
Flanders, KC
Takebe, N
Sarantopoulos, S
Booher, S
Cowen, EW
AF Baird, Kristin
Comis, Leora E.
Joe, Galen O.
Steinberg, Seth M.
Hakim, Fran T.
Rose, Jeremy J.
Mitchell, Sandra A.
Pavletic, Steven Z.
Figg, William D.
Yao, Lawrence
Flanders, Kathleen C.
Takebe, Naoko
Sarantopoulos, Stefanie
Booher, Susan
Cowen, Edward W.
TI Imatinib Mesylate for the Treatment of Steroid-Refractory Sclerotic-Type
Cutaneous Chronic Graft-versus-Host Disease
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Graft-versus-host disease; Imatinib mesylate; Allogeneic hematopoietic
stem cell transplantation; Sclerosis; Fasciitis
ID STEM-CELL TRANSPLANTATION; CONSENSUS DEVELOPMENT PROJECT; WORKING
GROUP-REPORT; QUALITY-OF-LIFE; SYSTEMIC-SCLEROSIS; CHRONIC GVHD;
STIMULATORY AUTOANTIBODIES; GROWTH-FACTOR; RESPONSE CRITERIA; LIMITED
EFFICACY
AB Sclerotic skin manifestations of chronic graft-versus-host disease (ScGVHD) lead to significant morbidity, including functional disability from joint range of motion (ROM) restriction. No superior second-line therapy has been established for steroid-refractory disease. Imatinib mesylate is a multikinase inhibitor of several signaling pathways implicated in skin fibrosis with in vitro antifibrotic activity. We performed an open-label pilot phase II trial of imatinib in children and adults with corticosteroid-refractory ScGVHD. Twenty patients were enrolled in a 6-month trial. Eight received a standard dose (adult, 400 mg daily; children, 260 mg/m(2) daily). Because of poor tolerability, 12 additional patients underwent a dose escalation regimen (adult, 100 mg daily initial dose up to 200 mg daily maximum; children, initial dose 65 mg/m2 daily up to 130 mg/m2 daily). Fourteen patients were assessable for primary response, improvement in joint ROM deficit, at 6 months. Primary outcome criteria for partial response was met in 5 of 14 (36%), stable disease in 7 of 14 (50%), and progressive disease in 2 of 14 (14%) patients. Eleven patients (79%). including 5 with partial response and 6 with stable disease, demonstrated a positive gain in ROM (range of 3% to 94% improvement in deficit). Of 13 patients with measurable changes at 6 months, the average improvement in ROM deficit was 24.2% (inter-quartile range, 15.5% to 30.5%; P = .011). This trial is registered at http://clinicaltrials.gov as NCT007020689. Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation.
C1 [Baird, Kristin] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Comis, Leora E.; Joe, Galen O.] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.
[Hakim, Fran T.; Rose, Jeremy J.; Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Mitchell, Sandra A.] NCI, Outcomes Res Branch, Div Canc Control & Populat Sci, Rockville, MD USA.
[Figg, William D.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Yao, Lawrence] NIH, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Flanders, Kathleen C.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
[Takebe, Naoko] NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA.
[Sarantopoulos, Stefanie] Duke Univ, Div Hematol Malignancy & Cell Therapy, Durham, NC USA.
[Sarantopoulos, Stefanie] Duke Univ, Dept Med, Duke Canc Inst, Durham, NC USA.
[Booher, Susan] NIAID, Autoimmun & Mucosal Immunol Branch, Rockville, MD USA.
[Cowen, Edward W.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
RP Cowen, EW (reprint author), 10 Ctr Dr, Bethesda, MD 20892 USA.
EM edcowen@hotmail.com
RI Figg Sr, William/M-2411-2016
FU NIH, Center for Cancer Research, National Cancer Institute; Cancer
Therapy Evaluation Program
FX This study was supported by the Intramural Research Program of the NIH,
Center for Cancer Research, National Cancer Institute, and the Cancer
Therapy Evaluation Program.
NR 45
TC 4
Z9 7
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD JUN
PY 2015
VL 21
IS 6
BP 1083
EP 1090
DI 10.1016/j.bbmt.2015.03.006
PG 8
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CI3SO
UT WOS:000354667900015
PM 25771402
ER
PT J
AU Roukos, V
Voss, TC
Misteli, T
AF Roukos, Vassilis
Voss, Ty C.
Misteli, Tom
TI Spatial dynamics of chromosome translocations in living cells
SO CHROMOSOME RESEARCH
LA English
DT Meeting Abstract
CT 20th International Chromosome Conference (ICC)
CY SEP 01-04, 2014
CL Univ Kent, Canterbury, ENGLAND
HO Univ Kent
C1 [Roukos, Vassilis; Voss, Ty C.; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 3
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0967-3849
EI 1573-6849
J9 CHROMOSOME RES
JI Chromosome Res.
PD JUN
PY 2015
VL 23
IS 2
MA S20
BP 362
EP 362
PG 1
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CI0EZ
UT WOS:000354410600036
ER
PT J
AU Chlebowski, RT
Anderson, GL
Prentice, RL
Rossouw, JE
Aragaki, AK
Manson, JE
AF Chlebowski, R. T.
Anderson, G. L.
Prentice, R. L.
Rossouw, J. E.
Aragaki, A. K.
Manson, J. E.
TI Reliable evidence from placebo-controlled, randomized, clinical trials
for menopausal hormone therapy's influence on incidence and deaths from
breast cancer
SO CLIMACTERIC
LA English
DT Editorial Material
DE PLACEBO-CONTROLS; RANDOMIZED CLINICAL TRIAL; BREAST CANCER; ESTROGEN;
ESTROGEN PLUS PROGESTIN; BREAST CANCER
ID ESTROGEN PLUS PROGESTIN; HEALTHY POSTMENOPAUSAL WOMEN; EQUINE ESTROGEN;
HYSTERECTOMY; MAMMOGRAPHY; MORTALITY
AB In an invited editorial, Dr Shapiro proposes that vaginal bleeding leading to unblinding and subsequent detection bias explains the breast cancer increase seen with estrogen plus progestin in the Women's Health Intiative (WHI) clinical trial(1). In the context of a uniform detection program of protocol-mandated annual mammography and breast examinations, such a proposal is medically implausible. Dr Shapiro suggests detection bias would identify a larger number of 'slowly growing tumors that would otherwise remain clinically silent'. The findings of more advanced cancers with increased deaths from breast cancer in the estrogen plus progestin group refute this conjecture. During early post-intervention phases of both WHI hormone therapy trials, when breast cancer detection bias is asserted by Dr Shapiro because participants had been informed of randomization assignment, breast cancer incidence rates were lower (rather than higher) than during intervention. Thus, Dr Shapiro's claims are directly refuted by findings from the WHI randomized clinical trials. Health-care providers should be aware that randomized clinical trial evidence supports estrogen plus progestin increasing breast cancer incidence and deaths from breast cancer. In contrast, among women with prior hysterectomy, randomized clinical trial evidence supports estrogen alone reducing breast cancer incidence and deaths from breast cancer.
C1 [Chlebowski, R. T.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90501 USA.
[Anderson, G. L.; Prentice, R. L.; Aragaki, A. K.] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci, Seattle, WA 98104 USA.
[Rossouw, J. E.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Manson, J. E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
RP Chlebowski, RT (reprint author), Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, 1024 W Carson St,Bldg J-3, Torrance, CA 90501 USA.
EM rowanchlebowski@gmail.com
NR 16
TC 2
Z9 2
U1 0
U2 1
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1369-7137
EI 1473-0804
J9 CLIMACTERIC
JI Climacteric
PD JUN
PY 2015
VL 18
IS 3
BP 336
EP 338
DI 10.3109/13697137.2015.1038770
PG 3
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA CI0CQ
UT WOS:000354403800003
PM 25966858
ER
PT J
AU Brady, TM
Neu, AM
Miller, ER
Appel, LJ
Siberry, GK
Solomon, BS
AF Brady, Tammy M.
Neu, Alicia M.
Miller, Edgar R.
Appel, Lawrence J.
Siberry, George K.
Solomon, Barry S.
TI Real-Time Electronic Medical Record Alerts Increase High Blood Pressure
Recognition in Children
SO CLINICAL PEDIATRICS
LA English
DT Article
DE computer alert; automated; triage; screening; hypertension;
cardiovascular health; primary care; pediatrics; quality improvement;
electronic health record
ID HEALTH RECORDS; HYPERTENSION; UNDERDIAGNOSIS
AB Objective. Pediatric hypertension remains largely unrecognized. We hypothesized that an electronic medical record (EMR) alert would increase elevated blood pressure (BP) recognition in a pediatric primary care setting. Study Design. Pre-post evaluation of a real-time EMR alert and one-time provider educational session. A total of 1305 encounters of children 3 to 21 years with elevated intake BP and no prior hypertension diagnosis were included. Elevated BP recognition and relationship of recognition with cardiovascular disease (CVD) risk factors during the intervention was compared with an historical control. Results. Recognition increased from 12.5% to 42% (P < .001). Recognition increased soon after alert implementation and was sustained without evidence of "alert fatigue." During both periods, presence of CVD risk factors was associated with recognition. However, the magnitude was lesser in the intervention period. Conclusions. Real-time EMR alerts substantially increase elevated BP recognition in children. However, underrecognition of elevated BP persisted, highlighting the need for additional strategies to improve provider recognition.
C1 [Brady, Tammy M.; Neu, Alicia M.; Miller, Edgar R.; Appel, Lawrence J.; Siberry, George K.; Solomon, Barry S.] Johns Hopkins Univ, Baltimore, MD USA.
[Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Brady, TM (reprint author), Johns Hopkins Sch Med, Div Pediat Nephrol, David M Rubenstein Child Hlth Bldg, Baltimore, MD 21287 USA.
EM tbrady8@jhmi.edu
FU American Kidney Fund Clinical Scientist in Nephrology Program; National
Institutes of Health/Johns Hopkins Institute for Clinical and
Translational Research [5KL2RR025006]
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This study
was funded in part by the American Kidney Fund Clinical Scientist in
Nephrology Program; and the National Institutes of Health/Johns Hopkins
Institute for Clinical and Translational Research KL2 Clinical Research
Scholar Award Program (5KL2RR025006; TMB).
NR 17
TC 1
Z9 1
U1 1
U2 5
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0009-9228
EI 1938-2707
J9 CLIN PEDIATR
JI Clin. Pediatr.
PD JUN
PY 2015
VL 54
IS 7
BP 667
EP 675
DI 10.1177/0009922814559379
PG 9
WC Pediatrics
SC Pediatrics
GA CI3OH
UT WOS:000354656600009
PM 25416626
ER
PT J
AU Acharya, P
Lusvarghi, S
Bewley, CA
Kwong, PD
AF Acharya, Priyamvada
Lusvarghi, Sabrina
Bewley, Carole A.
Kwong, Peter D.
TI HIV-1 gp120 as a therapeutic target: navigating a moving labyrinth
SO EXPERT OPINION ON THERAPEUTIC TARGETS
LA English
DT Review
DE HIV antibodies; miniprotein mimetics; natural products; receptor
mimetics; small molecule inhibitors; structure-based design
ID HUMAN-IMMUNODEFICIENCY-VIRUS; BROADLY NEUTRALIZING ANTIBODIES; ENVELOPE
GLYCOPROTEIN GP120; OSCILLATORIA-AGARDHII AGGLUTININ;
LECTIN-CARBOHYDRATE INTERACTIONS; SMALL-MOLECULE INHIBITORS;
CORECEPTOR-BINDING-SITES; STRUCTURE-BASED DESIGN; INFECTION IN-VIVO;
CCR5 N-TERMINUS
AB Introduction: The HIV-1 gp120 envelope (Env) glycoprotein mediates attachment of virus to human target cells that display requisite receptors, CD4 and co-receptor, generally CCR5. Despite high-affinity interactions with host receptors and proof-of-principle by the drug maraviroc that interference with CCR5 provides therapeutic benefit, no licensed drug currently targets gp120.
Areas covered: An overview of the role of gp120 in HIV-1 entry and of sites of potential gp120 vulnerability to therapeutic inhibition is presented. Viral defenses that protect these sites and turn gp120 into a moving labyrinth are discussed together with strategies for circumventing these defenses to allow therapeutic targeting of gp120 sites of vulnerability.
Expert opinion: The gp120 envelope glycoprotein interacts with host proteins through multiple interfaces and has conserved structural features at these interaction sites. In spite of this, targeting gp120 for therapeutic purposes is challenging. Env mechanisms that have evolved to evade the humoral immune response also shield it from potential therapeutics. Nevertheless, substantial progress has been made in understanding HIV-1 gp120 structure and its interactions with host receptors, and in developing therapeutic leads that potently neutralize diverse HIV-1 strains. Synergies between advances in understanding, needs for therapeutics against novel viral targets and characteristics of breadth and potency for a number of gp120-targetting lead molecules bodes well for gp120 as a HIV-1 therapeutic target.
C1 [Acharya, Priyamvada; Kwong, Peter D.] NIAID, NIH, Vaccine Res Ctr, Struct Biol Sect, Bethesda, MD 20892 USA.
[Lusvarghi, Sabrina; Bewley, Carole A.] NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA.
RP Kwong, PD (reprint author), NIAID, NIH, Vaccine Res Ctr, Struct Biol Sect, Room 4609B,40 Convent Dr, Bethesda, MD 20892 USA.
EM pdkwong@nih.gov
FU AIDS Targeted Antiviral Program, Office of the Director, NIH; Intramural
Research program, NIDDK; Intramural Research Program, Vaccine Research
Center, NIAID, NIH
FX The authors were supported by the AIDS Targeted Antiviral Program,
Office of the Director, NIH, Intramural Research program, NIDDK,
Intramural Research Program, Vaccine Research Center, NIAID, NIH. The
authors have no other relevant affiliations or financial involvement
with any organization or entity with a financial interest in or
financial conflict with the subject matter or materials discussed in the
manuscript apart from those disclosed.
NR 152
TC 6
Z9 6
U1 3
U2 22
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1472-8222
EI 1744-7631
J9 EXPERT OPIN THER TAR
JI Expert Opin. Ther. Targets
PD JUN
PY 2015
VL 19
IS 6
BP 765
EP 783
DI 10.1517/14728222.2015.1010513
PG 19
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CI1YT
UT WOS:000354541900005
PM 25724219
ER
PT J
AU Choi, CH
Chung, JY
Park, HS
Jun, M
Lee, YY
Kim, BG
Hewitt, SM
AF Choi, Chel Hun
Chung, Joan-Yang
Park, Ho-Seop
Jun, Minsik
Lee, Yoo-Young
Kim, Byung-Gie
Hewitt, Stephen M.
TI Pancreatic adenocarcinoma up-regulated factor expression is associated
with disease-specific survival in cervical cancer patients
SO HUMAN PATHOLOGY
LA English
DT Article
DE PAUF; Adenocarcinoma; Prognosis; Uterine cervical neoplasms; Survival
ID BETA-CATENIN; TUMOR PROGRESSION; CELLS; PAUF; LOCALIZATION; METASTASIS;
GALECTIN-3; NEOPLASIA; PROTEIN; PROGNOSIS
AB Pancreatic adenocarcinoma up-regulated factor (PAUF) is a novel soluble protein involved in tumor development and metastases. This study was to investigate the PAUF expression and its prognostic value in cervical cancer patients. The expression of PAUF was immunohistochemically determined in 345 formalin-fixed, paraffin-embedded cervical cancer tissues and 107 normal cervical epitheliums. Subsequently, its associations with clinicopathological characteristics and patient survival were assessed. PAUF protein was expressed both in cytoplasm and nucleus, and cytoplasmic expression was more frequent in cancers than normal tissues (32% versus 17%, P = .002), and the difference was prominent in glandular cells. Notably, the expression was more frequent in adenocarcinoma than in squamous cell carcinoma (57% versus 25%, respectively; P < .001), and the differential expression was also seen at the messenger RNA level (P = .014). Cox regression analysis showed that the cytoplasmic expression of PAUF protein was independently associated with poor disease-free (hazard ratio = 2.3; 95% confidence interval, 1.2-4.3; P = .008) and overall survival (hazard ratio = 2.9; 95% confidence interval, 1.2-7.5; P = .020). Detection of PAUF expression may aid current evaluation of prognosis in cervical adenocarcinoma. Published by Elsevier Inc.
C1 [Choi, Chel Hun; Chung, Joan-Yang; Jun, Minsik; Hewitt, Stephen M.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Lee, Yoo-Young; Kim, Byung-Gie] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Obstet & Gynecol, Seoul 135710, South Korea.
[Park, Ho-Seop] Univ Ulsan, Sch Med, Asan Med Ctr, Dept Pathol, Seoul 138736, South Korea.
RP Hewitt, SM (reprint author), NCI, Pathol Lab, NIH, MSC 1500, Bethesda, MD 20892 USA.
EM bksong.kim@samsung.com; genejock@helix.nih.gov
OI Hewitt, Stephen/0000-0001-8283-1788; Chung,
Joon-Yong/0000-0001-5041-5982
FU Basic Science Research Program through the National Research Foundation
of Korea - Ministry of Education, Republic of Korea [2013R1A1A2013629];
Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research
FX This study was supported in part by a grant from the Basic Science
Research Program through the National Research Foundation of Korea
funded by the Ministry of Education, Republic of Korea
(2013R1A1A2013629) and Intramural Research Program of the National
Institutes of Health, National Cancer Institute, Center for Cancer
Research.
NR 35
TC 4
Z9 4
U1 0
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0046-8177
EI 1532-8392
J9 HUM PATHOL
JI Hum. Pathol.
PD JUN
PY 2015
VL 46
IS 6
BP 884
EP 893
DI 10.1016/j.humpath.2015.02.016
PG 10
WC Pathology
SC Pathology
GA CI2QY
UT WOS:000354593300012
PM 25870121
ER
PT J
AU Pingili, AK
Kara, M
Khan, NS
Estes, AM
Lin, ZT
Li, W
Gonzalez, FJ
Malik, KU
AF Pingili, Ajeeth K.
Kara, Mehmet
Khan, Nayaab S.
Estes, Anne M.
Lin, Zongtao
Li, Wei
Gonzalez, Frank J.
Malik, Kafait U.
TI 6 beta-Hydroxytestosterone, a Cytochrome P450 1B1 Metabolite of
Testosterone, Contributes to Angiotensin II-Induced Hypertension and Its
Pathogenesis in Male Mice
SO HYPERTENSION
LA English
DT Article
DE castration; CYP1B1 protein; hypertension; oxidative stress
ID BLOOD-PRESSURE; RENAL DYSFUNCTION; 20-HYDROXYEICOSATETRAENOIC ACID;
SENSITIVE HYPERTENSION; CARDIAC-HYPERTROPHY; GENDER-DIFFERENCES;
ANDROGEN RECEPTOR; OXIDATIVE STRESS; FOLLOW-UP; RATS
AB Previously, we showed that Cyp1b1 gene disruption minimizes angiotensin II-induced hypertension and associated pathophysiological changes in male mice. This study was conducted to test the hypothesis that cytochrome P450 1B1-generated metabolites of testosterone, 6 beta-hydroxytestosterone and 16a-hydroxytestosterone, contribute to angiotensin II-induced hypertension and its pathogenesis. Angiotensin II infusion for 2 weeks increased cardiac cytochrome P450 1B1 activity and plasma levels of 6 beta-hydroxytestosterone, but not 16a-hydroxytestosterone, in Cyp1b1(+/+) mice without altering Cyp1b1 gene expression; these effects of angiotensin II were not observed in Cyp1b1(-/-) mice. Angiotensin II-induced increase in systolic blood pressure and associated cardiac hypertrophy, and fibrosis, measured by intracardiac accumulation of a-smooth muscle actin, collagen, and transforming growth factor-beta, and increased nicotinamide adenine dinucleotide phosphate oxidase activity and production of reactive oxygen species; these changes were minimized in Cyp1b1(-/-) or castrated Cyp1b1(+/+) mice, and restored by treatment with 6 beta-hydroxytestoterone. In Cyp1b1(+/+) mice, 6 beta-hydroxytestosterone did not alter the angiotensin II-induced increase in systolic blood pressure; the basal systolic blood pressure was also not affected by this agent in either genotype. Angiotensin II or castration did not alter cardiac, angiotensin II type 1 receptor, angiotensin-converting enzyme, Mas receptor, or androgen receptor mRNA levels in Cyp1b1(+/+) or in Cyp1b1(-/-) mice. These data suggest that the testosterone metabolite, 6 beta-hydroxytestosterone, contributes to angiotensin II-induced hypertension and associated cardiac pathogenesis in male mice, most probably by acting as a permissive factor. Moreover, cytochrome P450 1B1 could serve as a novel target for developing agents for treating renin-angiotensin and testosterone-dependent hypertension and associated pathogenesis in males.
C1 [Pingili, Ajeeth K.; Kara, Mehmet; Khan, Nayaab S.; Estes, Anne M.; Malik, Kafait U.] Univ Tennessee, Ctr Hlth Sci, Dept Pharmacol, Coll Med, Memphis, TN 38163 USA.
[Lin, Zongtao; Li, Wei] Univ Tennessee, Ctr Hlth Sci, Dept Pharmaceut Sci, Coll Pharm, Memphis, TN 38163 USA.
[Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Malik, KU (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Pharmacol, Coll Med, 874 Union Ave, Memphis, TN 38163 USA.
EM kmalik@uthsc.edu
FU National Institutes of Health National Heart, Lung, and Blood Institute
[R01-19134-39, R0-R01HL079109-08]; Department of Pharmacology, Faculty
of Medicine, Erciyes University, Kayseri, Turkey
FX This work was supported by the National Institutes of Health National
Heart, Lung, and Blood Institute grants R01-19134-39 and
R0-R01HL079109-08 (K.U. Malik). M. Kara was supported by a fellowship
from Department of Pharmacology, Faculty of Medicine, Erciyes
University, Kayseri 38039, Turkey. The contents of this article are
solely the responsibility of the authors and do not necessarily
represent the official views of the National Heart, Lung, and Blood
Institute.
NR 52
TC 8
Z9 8
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0194-911X
EI 1524-4563
J9 HYPERTENSION
JI Hypertension
PD JUN
PY 2015
VL 65
IS 6
BP 1279
EP 1287
DI 10.1161/HYPERTENSIONAHA.115.05396
PG 9
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CH9OJ
UT WOS:000354364900023
PM 25870196
ER
PT J
AU Yan, PK
Cao, YH
Yuan, Y
Turkbey, B
Choyke, PL
AF Yan, Pingkun
Cao, Yihui
Yuan, Yuan
Turkbey, Baris
Choyke, Peter L.
TI Label Image Constrained Multiatlas Selection
SO IEEE TRANSACTIONS ON CYBERNETICS
LA English
DT Article
DE Atlas-based; computer vision; image segmentation; manifold learning
ID ATLAS-BASED SEGMENTATION; NONLINEAR DIMENSIONALITY REDUCTION; BRAIN
IMAGES; MANIFOLD; STRATEGIES; VALIDATION; PROSTATE
AB Multiatlas based method is commonly used in medical image segmentation. In multiatlas based image segmentation, atlas selection and combination are considered as two key factors affecting the performance. Recently, manifold learning based atlas selection methods have emerged as very promising methods. However, due to the complexity of prostate structures in raw images, it is difficult to get accurate atlas selection results by only measuring the distance between raw images on the manifolds. Although the distance between the regions to be segmented across images can be readily obtained by the label images, it is infeasible to directly compute the distance between the test image (gray) and the label images (binary). This paper tries to address this problem by proposing a label image constrained atlas selection method, which exploits the label images to constrain the manifold projection of raw images. Analyzing the data point distribution of the selected atlases in the manifold subspace, a novel weight computation method for atlas combination is proposed. Compared with other related existing methods, the experimental results on prostate segmentation from T2w MRI showed that the selected atlases are closer to the target structure and more accurate segmentation were obtained by using our proposed method.
C1 [Yan, Pingkun; Cao, Yihui; Yuan, Yuan] Chinese Acad Sci, Xian Inst Opt & Precis Mech, State Key Lab Transient Opt & Photon, Ctr Opt Imagery Anal & Learning, Xian 710119, Peoples R China.
[Turkbey, Baris; Choyke, Peter L.] NCI, NIH, Bethesda, MD 20892 USA.
RP Yan, PK (reprint author), Chinese Acad Sci, Xian Inst Opt & Precis Mech, State Key Lab Transient Opt & Photon, Ctr Opt Imagery Anal & Learning, Xian 710119, Peoples R China.
EM pingkun.yan@opt.ac.cn; yihui.cao@opt.ac.cn; yuany@opt.ac.cn;
turkbeyi@mail.nih.gov; pchoyke@mail.nih.gov
FU National Natural Science Foundation of China [61172142, 61172143]
FX This work was supported by the National Natural Science Foundation of
China under Grant 61172142 and Grant 61172143. This paper was
recommended by Associate Editor X. You.
NR 41
TC 3
Z9 3
U1 1
U2 5
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 2168-2267
EI 2168-2275
J9 IEEE T CYBERNETICS
JI IEEE T. Cybern.
PD JUN
PY 2015
VL 45
IS 6
BP 1158
EP 1168
DI 10.1109/TCYB.2014.2346394
PG 11
WC Computer Science, Artificial Intelligence; Computer Science, Cybernetics
SC Computer Science
GA CI1VC
UT WOS:000354532000005
PM 25415994
ER
PT J
AU Philippot, E
Santosh, KC
Belaid, A
Belaid, Y
AF Philippot, Emilie
Santosh, K. C.
Belaid, Abdel
Belaid, Yolande
TI Bayesian networks for incomplete data analysis in form processing
SO INTERNATIONAL JOURNAL OF MACHINE LEARNING AND CYBERNETICS
LA English
DT Article
DE Bayesian networks; Electronic note-taking; Form processing
ID NAIVE BAYES; CLASSIFIERS; RECOGNITION; CLASSIFICATION
AB In this paper, we study Bayesian network (BN) for form identification based on partially filled fields. It uses electronic ink-tracing files without having any information about form structure. Given a form format, the ink-tracing files are used to build the BN by providing the possible relationships between corresponding fields using conditional probabilities, that goes from individual fields up to the complete model construction. To simplify the BN, we sub-divide a single form into three different areas: header, body and footer, and integrate them together, where we study three fundamental BN learning algorithms: Naive, Peter & Clark and maximum weighted spanning tree. Under this framework, we validate it with a real-world industrial problem i.e., electronic note-taking in form processing. The approach provides satisfactory results, attesting the interest of BN for exploiting the incomplete form analysis problems, in particular.
C1 [Philippot, Emilie; Santosh, K. C.; Belaid, Abdel; Belaid, Yolande] Univ Lorraine LORIA, UMR 7503, F-54506 Vandoeuvre Les Nancy, France.
[Santosh, K. C.] NIH, Commun Engn Branch, US Natl Lib Med NLM, Bethesda, MD 20894 USA.
RP Philippot, E (reprint author), Univ Lorraine LORIA, UMR 7503, Campus Sci,BP 239, F-54506 Vandoeuvre Les Nancy, France.
EM emilie.philippot@gmail.com; santosh.kc@nih.gov; abdel.belaid@loria.fr;
yolande.belaid@loria.fr
OI Santosh, K.C./0000-0003-4176-0236
NR 42
TC 0
Z9 0
U1 1
U2 13
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1868-8071
EI 1868-808X
J9 INT J MACH LEARN CYB
JI Int. J. Mach. Learn. Cybern.
PD JUN
PY 2015
VL 6
IS 3
BP 347
EP 363
DI 10.1007/s13042-014-0234-4
PG 17
WC Computer Science, Artificial Intelligence
SC Computer Science
GA CH9YB
UT WOS:000354391500001
ER
PT J
AU Zheng, G
Zhang, W
Li, QZ
Xu, JF
Yuan, A
Gastwirth, JL
AF Zheng, Gang
Zhang, Wei
Li, Qizhai
Xu, Jinfeng
Yuan, Ao
Gastwirth, Joseph L.
TI Analysis of Genetic Association Studies Incorporating Prior Information
of Genetic Models
SO JOURNAL OF AGRICULTURAL BIOLOGICAL AND ENVIRONMENTAL STATISTICS
LA English
DT Article
DE Case-control design; Estimation of genetic model; Genetic model
selection; HWE; Robustness; Replication
ID GENOME-WIDE ASSOCIATION; HARDY-WEINBERG DISEQUILIBRIUM; EFFICIENCY
ROBUST-TESTS; BAYES FACTORS; TEST STATISTICS; SAMPLE-SIZE; SURVIVAL;
POWER
AB In genetic association studies, for each underlying genetic model, there is an optimal test. Usually, the true model is unknown, but knowledge from previous genome-wide association studies for the disease under investigation is available and provides information about the underlying model. We study how to incorporate this prior information about plausible genetic models to achieve better efficiency robustness in genetic association studies. Two procedures are proposed and studied. The first one reduces the set of genetic models using the prior information. The second one derives posterior probabilities for the plausible genetic models using trend tests. Then the trend test based on the posterior mean of the genetic model or a weighted trend test over various genetic models can be employed, similar in spirit to the efficiency robustness approach. In the proposed procedures, the strong Hardy-Weinberg disequilibrium in cases is studied. Simulations are conducted to compare the proposed methods with existing ones. The usefulness of the results for the analysis of data collected in replication studies is investigated, the proposed methods are shown to have better overall performance than existing one, and the methods are applied to analyze the real data.
C1 [Zheng, Gang] NHLBI, Bethesda, MD 20892 USA.
[Zhang, Wei; Li, Qizhai] Chinese Acad Sci, Acad Math & Syst Sci, Key Lab Syst Sci, Beijing 100190, Peoples R China.
[Xu, Jinfeng] NYU, New York, NY USA.
[Yuan, Ao] Georgetown Univ, Washington, DC USA.
[Gastwirth, Joseph L.] George Washington Univ, Washington, DC USA.
RP Li, QZ (reprint author), Chinese Acad Sci, Acad Math & Syst Sci, Key Lab Syst Sci, Zhongguancun East Rd 55, Beijing 100190, Peoples R China.
EM liqz@amss.ac.cn
OI Xu, Jinfeng/0000-0002-3165-2015
FU National Science Foundation of hina [11371353, 61134013]; Breakthrough
Project of Strategic Priority Program of the Chinese Academy of Sciences
[XDB13040600]
FX Q. Li was supported in part by the National Science Foundation of hina
(Grant No. 11371353, 61134013) and the Breakthrough Project of Strategic
Priority Program of the Chinese Academy of Sciences, Grant No.
XDB13040600.
NR 25
TC 0
Z9 0
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1085-7117
EI 1537-2693
J9 J AGR BIOL ENVIR ST
JI J. Agric. Biol. Environ. Stat.
PD JUN
PY 2015
VL 20
IS 2
BP 173
EP 191
DI 10.1007/s13253-015-0200-y
PG 19
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA CI3IU
UT WOS:000354642200001
ER
PT J
AU Dolle, L
Gao, B
AF Dolle, Laurent
Gao, Bin
TI Pharmacological chaperone therapies: Can aldehyde dehydrogenase
activator make us healthier?
SO JOURNAL OF HEPATOLOGY
LA English
DT Editorial Material
DE ALDH2; Acetaldehyde; Alda-1; Pharmacological chaperone
ID ALCOHOLIC LIVER-DISEASE; HETEROZYGOTES; INJURY; GENES; CELLS
C1 [Dolle, Laurent] Free Univ Brussels VUB, Fac Med & Pharm, Dept Biomed Sci, Lab Liver Cell Biol, Brussels, Belgium.
[Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA.
RP Dolle, L (reprint author), Free Univ Brussels VUB, Fac Med & Pharm, Dept Biomed Sci, Lab Liver Cell Biol, Brussels, Belgium.
EM ldolle@vub.ac.be; bgao@mail.nih.gov
FU Intramural NIH HHS
NR 22
TC 1
Z9 2
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD JUN
PY 2015
VL 62
IS 6
BP 1228
EP 1230
DI 10.1016/j.jhep.2014.12.022
PG 3
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CI2KA
UT WOS:000354574800002
PM 25681554
ER
PT J
AU Gonzalez, FJ
Jiang, CT
Bisson, WH
Patterson, AD
AF Gonzalez, Frank J.
Jiang, Changtao
Bisson, William H.
Patterson, Andrew D.
TI Inhibition of farnesoid X receptor signaling shows beneficial effects in
human obesity
SO JOURNAL OF HEPATOLOGY
LA English
DT Editorial Material
ID URSODEOXYCHOLIC ACID; CHOLESTEROL 7-ALPHA-HYDROXYLASE;
TAUROURSODEOXYCHOLIC ACID; TRANSGENIC EXPRESSION; INSULIN SENSITIVITY;
GUT MICROBIOTA; 1 GP-BAR1; LIVER; MICE; FXR
C1 [Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20814 USA.
[Jiang, Changtao] Peking Univ, Minist Educ, Key Lab Mol Cardiovasc Sci, Dept Physiol & Pathophysiol,Sch Basic Med Sci, Beijing 100191, Peoples R China.
[Bisson, William H.] Oregon State Univ, Dept Environm & Mol Toxicol, Corvallis, OR 97331 USA.
[Patterson, Andrew D.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20814 USA.
EM gonzalef@mail.nih.gov
RI Patterson, Andrew/G-3852-2012
OI Patterson, Andrew/0000-0003-2073-0070
NR 24
TC 4
Z9 4
U1 1
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD JUN
PY 2015
VL 62
IS 6
BP 1234
EP 1236
DI 10.1016/j.jhep.2014.12.034
PG 3
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CI2KA
UT WOS:000354574800004
PM 25747705
ER
PT J
AU Gaskari, SA
Liu, HQ
D'Mello, C
Kunos, G
Lee, SS
AF Gaskari, Seyed Ali
Liu, Hongqun
D'Mello, Charlotte
Kunos, George
Lee, Samuel S.
TI Blunted cardiac response to hemorrhage in cirrhotic rats is mediated by
local macrophage-released endocannabinoids
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
DE Cirrhosis; Cardiomyopathy; Endocannabinoids; AM251; Hemorrhage; CB-1;
Monocytes; Macrophages
ID ENDOGENOUS CANNABINOIDS; LIVER-TRANSPLANTATION; PORTAL-HYPERTENSION;
RECEPTORS MEDIATE; NITRIC-OXIDE; CARDIOMYOPATHY; PRESSURE; SYSTEM;
BLOOD; CB1
AB Background & Aims: Cirrhosis is associated with blunted cardiovascular response to stimuli such as hemorrhage, but the mechanism remains unclear. We aimed to clarify the role of endocannabinoids in blunted hemorrhage response in cirrhotic rats.
Methods: Cirrhosis was induced by bile duct ligation (BDL). Hemodynamics were measured. Cannabinoid receptor-1 (CB1) antagonist, AM251, and macrophage inhibitor gadolinium chloride (GdCl3) were administered. Myocardial levels of anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) were measured and resident monocytes and macrophages quantified by immunohistochemistry. Isolated cardiomyocyte contractility was measured before and after incubation with monocytes from BDL and sham controls.
Results: Hemorrhage significantly decreased arterial pressure and left ventricular dP/dT. After hemorrhage, these changes quickly reversed in controls, but were severely prolonged in BDL rats. Chronic AM251 treatment restored this impaired response. AEA and 2-AG levels were increased in BDL hearts and further increased after hemorrhage. Sham hearts showed virtually no monocytes or macrophages before or after hemorrhage, whereas BDL hearts had significantly more white blood cells which further increased after hemorrhage. GdCl3 treatment significantly reduced cardiac endocannabinoid levels both at baseline and after hemorrhage. This treatment also restored cardiovascular response to hemorrhage in BDL rats but did not affect sham controls. Monocytes isolated from BDL rats more potently inhibited cardiomyocyte contractility than sham control monocytes.
Conclusions: The cirrhotic heart showed increased monocyte recruitment and endocannabinoid levels. CB1 blockade or GdCl3 treatment restored blunted cardiovascular response to hemorrhage. Endocannabinoids released by monocytes blunt cardiac response to hemorrhage. Preventing monocyte recruitment or blocking endocannabinoid signaling may improve cardiovascular homeostasis in cirrhosis. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
C1 [Gaskari, Seyed Ali; Liu, Hongqun; D'Mello, Charlotte; Lee, Samuel S.] Univ Calgary, Liver Unit, Calgary, AB, Canada.
[Kunos, George] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA.
RP Lee, SS (reprint author), Liver Unit, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada.
EM samlee@ucalgary.ca
FU Canadian Association for Study of Liver fellowship award; Canadian Liver
Foundation research grant
FX SAG was supported by a Canadian Association for Study of Liver
fellowship award. The study was funded by a Canadian Liver Foundation
research grant.
NR 42
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD JUN
PY 2015
VL 62
IS 6
BP 1272
EP 1277
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CI2KA
UT WOS:000354574800009
PM 25640062
ER
PT J
AU Xu, CF
Wan, XY
Xu, L
Weng, HL
Yan, M
Miao, M
Sun, Y
Xu, GY
Dooley, S
Li, YM
Yu, CH
AF Xu, Chengfu
Wan, Xingyong
Xu, Lei
Weng, Honglei
Yan, Ming
Miao, Min
Sun, Yan
Xu, Genyun
Dooley, Steven
Li, Youming
Yu, Chaohui
TI Xanthine oxidase in non-alcoholic fatty liver disease and hyperuricemia:
One stone hits two birds
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
DE Fatty liver; Hyperuricemia; Uric acid; Xanthine oxidase; NLRP3
inflammasome
ID SERUM URIC-ACID; NLRP3 INFLAMMASOME; INSULIN-RESISTANCE; METABOLIC
SYNDROME; HEPATOCELLULAR-CARCINOMA; UNITED-STATES; OXIDOREDUCTASE;
OBESITY; ACTIVATION; STEATOHEPATITIS
AB Background & Aims: Hyperuricemia is a common feature of patients with non-alcoholic fatty liver disease (NAFLD). This study aimed to explore the causal relationship and underlying mechanisms between NAFLD and hyperuricemia.
Methods: We evaluated the impact of NAFLD on the development of hyperuricemia in a cohort of 5541 baseline hyperuricemia-free individuals. We further analyzed xanthine oxidase (XO), a rate-limiting enzyme that catalyzes uric acid production, as a candidate to link NAFLD and hyperuricemia.
Results: In the first study, a 7-year prospective analysis found that NAFLD was strongly associated with subsequent development of hyperuricemia. Cox proportional hazards regression analyses showed that age, gender, and body mass index adjusted hazard ratio (95% confidence interval) for incident hyperuricemia was 1.609 (1.129-2.294) in individuals with NAFLD, as compared with those without NAFLD at baseline. In the second study, we observed that expression and activity of XO were significantly increased in cellular and mouse models of NAFLD. Knocking down XO expression or inhibiting XO activity significantly decreases uric acid production and attenuates free fatty acids-induced fat accumulation in HepG2 cells. Inhibiting XO activity also significantly prevents the development of and ameliorates established hepatic steatosis induced by a high-fat diet in mice. Further experiments indicated that XO regulates activation of the NLRP3 inflammasome, which may be essential for the regulatory effect of XO on NAFLD.
Conclusions: NAFLD significantly increases the risk of incident hyperuricemia. XO is a mediator of the relationship between NAFLD and hyperuricemia, and may serve as a novel therapeutic target for the two linked diseases. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
C1 [Xu, Chengfu; Wan, Xingyong; Xu, Lei; Li, Youming; Yu, Chaohui] Zhejiang Univ, Affiliated Hosp 1, Dept Gastroenterol, Coll Med, Hangzhou 310003, Zhejiang, Peoples R China.
[Xu, Lei] Zhejiang Univ, Dept Gastroenterol, Ningbo Hosp, Ningbo, Zhejiang, Peoples R China.
[Weng, Honglei; Dooley, Steven] Heidelberg Univ, Med Fac Mannheim, Sect Mol Hepatol, Dept Med 2, Mannheim, Germany.
[Yan, Ming; Sun, Yan] Natl Inst Minor Hlth & Hlth Dispar, Div Intramural Res, NIH, Bethesda, MD USA.
[Yan, Ming; Sun, Yan] Natl Inst Diabet & Digest & Kidney Dis, Lab Biochem & Genet, NIH, Bethesda, MD USA.
[Miao, Min] Zhenhai Lianhua Hosp, Dept Internal Med, Ningbo, Zhejiang, Peoples R China.
[Xu, Genyun] Zhejiang Univ, Affiliated Hosp 1, Dept Lab Med, Coll Med, Hangzhou 310003, Zhejiang, Peoples R China.
RP Li, YM (reprint author), Zhejiang Univ, Affiliated Hosp 1, Dept Gastroenterol, Coll Med, 79 Qingchun Rd, Hangzhou 310003, Zhejiang, Peoples R China.
EM xiaofu@zju.edu.cn; ych623@sina.com
FU National Key Basic Research Development Program [2012CB524905]; National
Science and Technology Support Plan Project [2012BAI06B04]; National
Natural Science Foundation of China [81100278, 81470838, 81300703,
81170378, 81230012, 81270487]; Zhejiang Provincial Natural Science
Foundation of China [R15H030001]; International Science and Technology
Cooperation Projects of Zhejiang Province [2013C24010]; Science
Foundation of Health Bureau of Zhejiang Province [2012RCA026]
FX This work was supported by National Key Basic Research Development
Program (No. 2012CB524905 to Y.L.), National Science and Technology
Support Plan Project (No. 2012BAI06B04 to Y.L.), National Natural
Science Foundation of China (Nos. 81100278 and 81470838 to C.X.,
81300703 to L.X., 81170378 and 81230012 to Y.L., and 81270487 to C.Y.),
Zhejiang Provincial Natural Science Foundation of China (No. R15H030001
to C.X.), International Science and Technology Cooperation Projects of
Zhejiang Province (No. 2013C24010 to C.X.), and Science Foundation of
Health Bureau of Zhejiang Province (No. 2012RCA026 to C.X.). The funders
did not play any role in the study design, data collection and analysis,
decisions regarding data release or manuscript preparation.
NR 44
TC 18
Z9 19
U1 3
U2 15
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD JUN
PY 2015
VL 62
IS 6
BP 1412
EP 1419
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CI2KA
UT WOS:000354574800026
PM 25623823
ER
PT J
AU Makarova-Rusher, OV
Medina-Echeverz, J
Duffy, AG
Greten, TF
AF Makarova-Rusher, Oxana V.
Medina-Echeverz, Jose
Duffy, Austin G.
Greten, Tim F.
TI The yin and yang of evasion and immune activation in HCC
SO JOURNAL OF HEPATOLOGY
LA English
DT Review
DE Hepatocellular carcinoma; Immunotherapy; Immune checkpoints
ID T-CELL RESPONSES; ADVANCED HEPATOCELLULAR-CARCINOMA; HEPATITIS-C VIRUS;
SINUSOIDAL ENDOTHELIAL-CELLS; PREDICTS POOR-PROGNOSIS; PULSED DENDRITIC
CELLS; GROWTH-FACTOR-BETA; PHASE-I TRIAL; ALPHA-FETOPROTEIN;
INTERFERON-ALPHA
AB Current systemic treatment options for patients with hepatocellular carcinoma (HCC) are limited to sorafenib. With the recent FDA approval of the second PD1-PD-L1 pathway inhibitor, immunotherapy has gained even more interest as a potential novel treatment option for patients with HCC. This is due not only because of the failure of other treatment approaches in the past, but also because immunological mechanisms have been shown to play an important role during tumor development, growth, and treatment. Here we present a review of immunological mechanisms in the liver relevant for tumor progression and treatment. We summarize our current knowledge on immune activating and immune suppressing mechanisms during tumor initiation, development, and treatment. We try to explain the paradox of how inflammatory responses in a setting of chronic infection promote tumor development, while the primary aim of immunotherapy is to activate immunity. Finally we summarize recent advances in addition to providing an outlook for the immunotherapy of HCC. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.
C1 [Makarova-Rusher, Oxana V.; Medina-Echeverz, Jose; Duffy, Austin G.; Greten, Tim F.] NCI, Gastrointestinal Malignancy Sect, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Greten, TF (reprint author), NCI, NIH, CCR, Bldg 10 Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM tim.greten@nih.gov
FU NCI, NIH
FX This work was supported by the Intramural Research Program of the NCI,
NIH.
NR 116
TC 20
Z9 24
U1 3
U2 13
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD JUN
PY 2015
VL 62
IS 6
BP 1420
EP 1429
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CI2KA
UT WOS:000354574800027
PM 25733155
ER
PT J
AU Crew, KD
Ho, KA
Brown, P
Greenlee, H
Bevers, TB
Arun, B
Sneige, N
Hudis, C
McArthur, HL
Chang, J
Rimawi, M
Cornelison, TL
Cardelli, J
Santella, RM
Wang, A
Lippman, SM
Hershman, DL
AF Crew, K. D.
Ho, K. A.
Brown, P.
Greenlee, H.
Bevers, T. B.
Arun, B.
Sneige, N.
Hudis, C.
McArthur, H. L.
Chang, J.
Rimawi, M.
Cornelison, T. L.
Cardelli, J.
Santella, R. M.
Wang, A.
Lippman, S. M.
Hershman, D. L.
TI Effects of a green tea extract, Polyphenon E, on systemic biomarkers of
growth factor signalling in women with hormone receptor-negative breast
cancer
SO JOURNAL OF HUMAN NUTRITION AND DIETETICS
LA English
DT Article
DE breast cancer; chemoprevention; tea polyphenols
ID (-)-EPIGALLOCATECHIN-3-GALLATE; RISK; ANGIOGENESIS; MECHANISMS; DAMAGE;
CELLS; ASSAY; EGCG
AB BackgroundObservational and experimental data support a potential breast cancer chemopreventive effect of green tea.
MethodsWe conducted an ancillary study using archived blood/urine from a phase IB randomised, placebo-controlled dose escalation trial of an oral green tea extract, Polyphenon E (Poly E), in breast cancer patients. Using an adaptive trial design, women with stage I-III breast cancer who completed adjuvant treatment were randomised to Poly E 400mg (n=16), 600mg (n=11) and 800mg (n=3) twice daily or matching placebo (n=10) for 6months. Blood and urine collection occurred at baseline, and at 2, 4 and 6months. Biological endpoints included growth factor [serum hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF)], lipid (serum cholesterol, triglycerides), oxidative damage and inflammatory biomarkers.
ResultsFrom July 2007-August 2009, 40 women were enrolled and 34 (26 Poly E, eight placebo) were evaluable for biomarker endpoints. At 2months, the Poly E group (all dose levels combined) compared to placebo had a significant decrease in mean serum HGF levels (-12.7% versus +6.3%, P=0.04). This trend persisted at 4 and 6months but was no longer statistically significant. For the Poly E group, serum VEGF decreased by 11.5% at 2months (P=0.02) and 13.9% at 4months (P=0.05) but did not differ compared to placebo. At 2months, there was a trend toward a decrease in serum cholesterol with Poly E (P=0.08). No significant differences were observed for other biomarkers.
ConclusionsOur findings suggest potential mechanistic actions of tea polyphenols in growth factor signalling, angiogenesis and lipid metabolism.
C1 [Crew, K. D.; Ho, K. A.; Greenlee, H.; Santella, R. M.; Wang, A.; Hershman, D. L.] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10107 USA.
[Brown, P.; Bevers, T. B.; Arun, B.; Sneige, N.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Hudis, C.; McArthur, H. L.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Chang, J.] Methodist Hosp Canc Ctr, Houston, TX USA.
[Rimawi, M.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
[Cornelison, T. L.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Cardelli, J.] Louisiana State Univ, Hlth Sci Ctr, Shreveport, LA 71105 USA.
[Lippman, S. M.] Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92103 USA.
RP Crew, KD (reprint author), Columbia Univ, Herbert Irving Comprehens Canc Ctr, 161 Ft Washington Ave,10-1072, New York, NY 10107 USA.
EM kd59@columbia.edu
FU National Cancer Institute [N01-CN-35159]; National Institute of
Environmental Health Sciences [ES009089]; American Cancer Society [ACS
MRSG-08-021-01-CNE]
FX The study was supported by the National Cancer Institute (grant
N01-CN-35159), the National Institute of Environmental Health Sciences
(grant ES009089) and the American Cancer Society (grant ACS
MRSG-08-021-01-CNE).
NR 31
TC 4
Z9 4
U1 3
U2 21
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0952-3871
EI 1365-277X
J9 J HUM NUTR DIET
JI J. Hum. Nutr. Diet.
PD JUN
PY 2015
VL 28
IS 3
BP 272
EP 282
DI 10.1111/jhn.12229
PG 11
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA CI1HX
UT WOS:000354495700007
PM 24646362
ER
PT J
AU Joseph, J
AF Joseph, Jeymohan
TI Eradication of HIV-1 from CNS reservoirs: current strategies and future
priorities
SO JOURNAL OF NEUROVIROLOGY
LA English
DT Editorial Material
C1 NIMH, Div AIDS Res, Bethesda, MD 20892 USA.
RP Joseph, J (reprint author), NIMH, Div AIDS Res, Room 9G20,MSC 9831 5601 Fishers Lane, Bethesda, MD 20892 USA.
EM jjeymoha@mail.nih.gov
NR 0
TC 1
Z9 1
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1355-0284
EI 1538-2443
J9 J NEUROVIROL
JI J. Neurovirol.
PD JUN
PY 2015
VL 21
IS 3
SI SI
BP 219
EP 221
DI 10.1007/s13365-015-0337-z
PG 3
WC Neurosciences; Virology
SC Neurosciences & Neurology; Virology
GA CI0SK
UT WOS:000354448000001
PM 25939608
ER
PT J
AU Nath, A
AF Nath, Avindra
TI Eradication of human immunodeficiency virus from brain reservoirs
SO JOURNAL OF NEUROVIROLOGY
LA English
DT Review
DE Compartmentalization; Astrocyte; Microglia; Macrophage; Antiretroviral;
Latency
ID CENTRAL-NERVOUS-SYSTEM; COMBINATION ANTIRETROVIRAL THERAPY; LASER
CAPTURE MICRODISSECTION; HIV-1 INFECTION; TYPE-1 INFECTION; TAT PROTEIN;
MACROPHAGE-TROPISM; NEURAL PROGENITORS; PLASMA VIREMIA; IN-VIVO
AB Isolated cases in which human immunodeficiency virus (HIV) infection was claimed to have been eradicated generated renewed interest in HIV reservoirs in the brain particularly since attempts to reproduce the findings using genetically engineered stem cells and immune- or myeloablation have failed. A clear understanding of the cell types in which the virus resides in the brain, the mechanism of viral persistence, restricted replication and latency, and the turnover rate of the infected cells is critical for us to develop ways to control or get rid of the virus in the brain. The brain has several unique features compared to other reservoirs. There are no resident T cells in the brain; the virus resides in macrophages and astrocytes where the viral infection is non-cytopathic. The virus evolves in the brain and since the turnover rate of these cells is low, the virus has the potential to reside in these cells for several decades and possibly for the life of the individual. This review discusses the HIV reservoirs in the brain, issues related to eradication of the virus from sanctuaries in the brain, and current challenges faced by neuroscientists in finding a cure.
C1 NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA.
RP Nath, A (reprint author), NINDS, Sect Infect Nervous Syst, NIH, Bldg 10-7C-103,10 Ctr Dr, Bethesda, MD 20892 USA.
EM natha@mail.nih.gov
FU NINDS, NIH
FX Dr. Dorian McGavern provided a photomicrograph of the meningeal
macrophages. This study was supported by intramural funds from NINDS,
NIH.
NR 75
TC 11
Z9 11
U1 1
U2 16
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1355-0284
EI 1538-2443
J9 J NEUROVIROL
JI J. Neurovirol.
PD JUN
PY 2015
VL 21
IS 3
SI SI
BP 227
EP 234
DI 10.1007/s13365-014-0291-1
PG 8
WC Neurosciences; Virology
SC Neurosciences & Neurology; Virology
GA CI0SK
UT WOS:000354448000003
PM 25366659
ER
PT J
AU Guendel, I
Iordanskiy, S
Sampey, GC
Van Duyne, R
Calvert, V
Petricoin, E
Saifuddin, M
Kehn-Hall, K
Kashanchi, F
AF Guendel, Irene
Iordanskiy, Sergey
Sampey, Gavin C.
Van Duyne, Rachel
Calvert, Valerie
Petricoin, Emanuel
Saifuddin, Mohammed
Kehn-Hall, Kylene
Kashanchi, Fatah
TI Role of Bruton's tyrosine kinase inhibitors in HIV-1-infected cells
SO JOURNAL OF NEUROVIROLOGY
LA English
DT Article
DE HIV-1 replication; BTK; Host cell protein; Inhibitor; Cell death
ID X-LINKED AGAMMAGLOBULINEMIA; TRANSCRIPTION FACTOR BRIGHT; PLECKSTRIN
HOMOLOGY DOMAIN; KAPPA-B ACTIVATION; LYMPHOID MALIGNANCIES; RECEPTOR
ENGAGEMENT; HIV-INFECTION; BTK FUNCTION; TEC FAMILY; T-CELLS
AB Many cellular cofactors have been documented to be critical for various stages of viral replication. Using high-throughput proteomic assays, we have previously identified Bruton's tyrosine kinase (BTK) as a host protein that was uniquely upregulated in the plasma membrane of human immunodeficiency virus (HIV-1)-infected T cells. Here, we have further characterized the BTK expression in HIV-1 infection and show that this cellular factor is specifically expressed in infected myeloid cells. Significant upregulation of the phosphorylated form of BTK was observed in infected cells. Using size exclusion chromatography, we found BTK to be virtually absent in the uninfected U937 cells; however, new BTK protein complexes were identified and distributed in both high molecular weight (similar to 600 kDa) and a small molecular weight complex (similar to 60-120 kDa) in the infected U1 cells. BTK levels were highest in cells either chronically expressing virus or induced/infected myeloid cells and that BTK translocated to the membrane following induction of the infected cells. BTK knockdown in HIV-1-infected cells using small interfering RNA (siRNA) resulted in selective death of infected, but not uninfected, cells. Using BTK-specific antibody and small-molecule inhibitors including LFM-A13 and a FDA-approved compound, ibrutinib (PCI-32765), we have found that HIV-1-infected cells are sensitive to apoptotic cell death and result in a decrease in virus production. Overall, our data suggests that HIV-1-infected cells are sensitive to treatments targeting BTK expressed in infected cells.
C1 [Guendel, Irene; Iordanskiy, Sergey; Sampey, Gavin C.; Kehn-Hall, Kylene; Kashanchi, Fatah] George Mason Univ, Natl Ctr Biodefense & Infect Dis, Dept Syst Biol, Manassas, VA 20110 USA.
[Van Duyne, Rachel] NCI, Ctr Canc Res, NIH, Ft Detrick, MD 21702 USA.
[Calvert, Valerie; Petricoin, Emanuel] George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA 20110 USA.
[Saifuddin, Mohammed] WuXi AppTec Inc, Philadelphia, PA 19112 USA.
[Kashanchi, Fatah] George Mason Univ, Mol Virol Lab, Manassas, VA 20110 USA.
RP Kashanchi, F (reprint author), George Mason Univ, Mol Virol Lab, Discovery Hall,Room 182,10900 Univ Blvd MS 1H8, Manassas, VA 20110 USA.
EM fkashanc@gmu.edu
FU National Institutes of Health [AI070740, AI043894, AI11340, AI114490];
Virginia's Commonwealth Health Research Board
FX We would like to thank the members of the Kashanchi Lab for experiments
and assistance with the manuscript, and the NIH AIDS Research and
Reference Reagent Program for the contribution of the important
reagents. This work was supported by National Institutes of Health grant
AI070740, AI043894, AI11340, and AI114490 to FK and a grant from
Virginia's Commonwealth Health Research Board to KK. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.
NR 83
TC 0
Z9 0
U1 1
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1355-0284
EI 1538-2443
J9 J NEUROVIROL
JI J. Neurovirol.
PD JUN
PY 2015
VL 21
IS 3
SI SI
BP 257
EP 275
DI 10.1007/s13365-015-0323-5
PG 19
WC Neurosciences; Virology
SC Neurosciences & Neurology; Virology
GA CI0SK
UT WOS:000354448000007
PM 25672887
ER
PT J
AU Brew, BJ
Robertson, K
Wright, EJ
Churchill, M
Crowe, SM
Cysique, LA
Deeks, S
Garcia, JV
Gelman, B
Gray, LR
Johnson, T
Joseph, J
Margolis, DM
Mankowski, JL
Spencer, B
AF Brew, B. J.
Robertson, K.
Wright, E. J.
Churchill, M.
Crowe, S. M.
Cysique, L. A.
Deeks, S.
Garcia, J. V.
Gelman, B.
Gray, L. R.
Johnson, T.
Joseph, J.
Margolis, D. M.
Mankowski, J. L.
Spencer, B.
TI HIV eradication symposium: will the brain be left behind?
SO JOURNAL OF NEUROVIROLOGY
LA English
DT Editorial Material
DE Human immunodeficiency virus type 1; Acquired immunodeficiency syndrome;
HIV-associated neurocognitive disorders; Eradication; Brain
ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY;
CEREBROSPINAL-FLUID; IN-VIVO; RALTEGRAVIR INTENSIFICATION; SUPPRESSIVE
THERAPY; LATENT HIV-1; REPLICATION-COMPETENT; REVERSE TRANSCRIPTION;
SITU HYBRIDIZATION
AB On 18 July 2014, the National Institute of Mental Health in collaboration with ViiV Health Care and Boehringer Ingelheim supported a symposium on HIV eradication and what it meant for the brain. The symposium was an affiliated event to the 20th International AIDS Conference. The meeting was held in Melbourne, Australia, and brought together investigators currently working on HIV eradication together with investigators who are working on the neurological complications of HIV. The purpose of the meeting was to bring the two fields of HIV eradication and HIV neurology together to foster dialogue and cross talk to move the eradication field forward in the context of issues relating to the brain as a potential reservoir of HIV. The outcomes of the symposium were that there was substantive but not definitive evidence for the brain as an HIV reservoir that will provide a challenge to HIV eradication. Secondly, the brain as a clinically significant reservoir for HIV is not necessarily present in all patients. Consequently, there is an urgent need for the development of biomarkers to identify and quantify the HIV reservoir in the brain. Lastly, when designing and developing eradication strategies, it is critical that approaches to target the brain reservoir be included.
C1 [Brew, B. J.; Cysique, L. A.] St Vincents Hosp, St Vincents Ctr Appl Med Res, Dept Neurol, Dept Immunol, Sydney, NSW 2010, Australia.
[Brew, B. J.; Cysique, L. A.] St Vincents Hosp, St Vincents Ctr Appl Med Res, Dept Infect Dis, Sydney, NSW 2010, Australia.
[Brew, B. J.; Cysique, L. A.] St Vincents Hosp, St Vincents Ctr Appl Med Res, Peter Duncan Neurosci Unit, Sydney, NSW 2010, Australia.
[Robertson, K.] Univ N Carolina, Dept Neurol, Chapel Hill, NC USA.
[Wright, E. J.; Crowe, S. M.] Alfred Hosp Melbourne Australia, Dept Infect Dis, Melbourne, Vic, Australia.
[Cysique, L. A.] NeuRA, Sydney, NSW, Australia.
[Churchill, M.; Gray, L. R.] Burnet Inst, Melbourne, Vic, Australia.
[Deeks, S.] Univ Calif San Francisco, Dept Infect Dis, San Francisco, CA 94143 USA.
[Garcia, J. V.] Univ N Carolina, Ctr AIDS Res, Div Infect Dis, Chapel Hill, NC USA.
[Gelman, B.] Univ Texas Austin, Austin, TX 78712 USA.
[Johnson, T.] NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA.
[Joseph, J.] NIMH, Div AIDS Res, NIH, Bethesda, MD 20892 USA.
[Margolis, D. M.] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
[Mankowski, J. L.] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD USA.
[Mankowski, J. L.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Spencer, B.] Univ Calif San Diego, San Diego, CA 92103 USA.
RP Brew, BJ (reprint author), St Vincents Hosp, St Vincents Ctr Appl Med Res, Dept Neurol, Dept Immunol, Sydney, NSW 2010, Australia.
EM B.Brew@UNSW.edu.au
OI Margolis, David/0000-0001-5714-0002
NR 73
TC 2
Z9 2
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1355-0284
EI 1538-2443
J9 J NEUROVIROL
JI J. Neurovirol.
PD JUN
PY 2015
VL 21
IS 3
SI SI
BP 322
EP 334
DI 10.1007/s13365-015-0322-6
PG 13
WC Neurosciences; Virology
SC Neurosciences & Neurology; Virology
GA CI0SK
UT WOS:000354448000012
PM 25750070
ER
PT J
AU Padgett, LS
Ferrer, RA
AF Padgett, Lynne S.
Ferrer, Rebecca A.
TI Palliative Care in Cancer: Enhancing Our View with the Science of
Emotion and Decision Making
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Letter
C1 [Padgett, Lynne S.; Ferrer, Rebecca A.] NCI, Basic Biobehav & Psychol Sci Branch, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD 20850 USA.
RP Padgett, LS (reprint author), NCI, Behav Res Program, Basic Biobehav & Psychol Sci Branch, 9609 Med Ctr Dr,Room 3E616, Rockville, MD 20850 USA.
EM lynne.padgett@nih.gov
NR 4
TC 1
Z9 1
U1 1
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1096-6218
EI 1557-7740
J9 J PALLIAT MED
JI J. Palliat. Med.
PD JUN 1
PY 2015
VL 18
IS 6
BP 479
EP 479
DI 10.1089/jpm.2015.0024
PG 1
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA CI2WJ
UT WOS:000354608100002
PM 25919185
ER
PT J
AU Elagib, KE
Xiao, M
Hussaini, IM
Delehanty, LL
Palmer, LA
Racke, FK
Birrer, MJ
Ganapathy-Kanniappan, S
McDevitt, MA
Goldfarb, AN
AF Elagib, Kamaleldin E.
Xiao, Mang
Hussaini, Isa M.
Delehanty, Lorrie L.
Palmer, Lisa A.
Racke, Frederick K.
Birrer, Michael J.
Ganapathy-Kanniappan, Shanmugasundaram
McDevitt, Michael A.
Goldfarb, Adam N.
TI Jun Blockade of Erythropoiesis: Role for Repression of GATA-1 by HERP2
(vol 24, pg 7779, 2004)
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Correction
C1 [Elagib, Kamaleldin E.; Xiao, Mang; Hussaini, Isa M.; Delehanty, Lorrie L.; Goldfarb, Adam N.] Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA.
[Palmer, Lisa A.] Univ Virginia, Sch Med, Dept Pediat, Charlottesville, VA 22908 USA.
[Racke, Frederick K.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Ganapathy-Kanniappan, Shanmugasundaram; McDevitt, Michael A.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Birrer, Michael J.] NCI, Mol Mech Sect, Rockville, MD USA.
RP Elagib, KE (reprint author), Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA.
NR 1
TC 0
Z9 0
U1 0
U2 2
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 JUN
PY 2015
VL 35
IS 12
BP 2215
EP 2215
DI 10.1128/MCB.00374-15
PG 1
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CI2ZX
UT WOS:000354618200014
PM 25987232
ER
PT J
AU Bailey, DL
Antoch, G
Bartenstein, P
Barthel, H
Beer, AJ
Bisdas, S
Bluemke, DA
Boellaard, R
Claussen, CD
Franzius, C
Hacker, M
Hricak, H
la Fougere, C
Guckel, B
Nekolla, SG
Pichler, BJ
Purz, S
Quick, HH
Sabri, O
Sattler, B
Schafer, J
Schmidt, H
van den Hoff, J
Voss, S
Weber, W
Wehrl, HF
Beyer, T
AF Bailey, D. L.
Antoch, G.
Bartenstein, P.
Barthel, H.
Beer, A. J.
Bisdas, S.
Bluemke, D. A.
Boellaard, R.
Claussen, C. D.
Franzius, C.
Hacker, M.
Hricak, H.
la Fougere, C.
Gueckel, B.
Nekolla, S. G.
Pichler, B. J.
Purz, S.
Quick, H. H.
Sabri, O.
Sattler, B.
Schaefer, J.
Schmidt, H.
van den Hoff, J.
Voss, S.
Weber, W.
Wehrl, H. F.
Beyer, T.
TI Combined PET/MR: The Real Work Has Just Started. Summary Report of the
Third International Workshop on PET/MR Imaging; February 17-21, 2014,
Tubingen, Germany
SO MOLECULAR IMAGING AND BIOLOGY
LA English
DT Review
DE Hybrid imaging; Molecular imaging; PET/CT; PET/MRI; PET; MRI;
Quantification; Attenuation correction; Oncology; Paediatric oncology;
Neurology; Cardiology
ID POSITRON-EMISSION-TOMOGRAPHY; TIME-OF-FLIGHT; PEDIATRIC DOSAGE CARD;
CONTRAST-ENHANCED MRI; WHOLE-BODY PET/MRI; ATTENUATION CORRECTION;
PROSTATE-CANCER; EXPECTED MANAGEMENT; MAGNETIC-RESONANCE;
PULMONARY-LESIONS
AB This paper summarises the proceedings and discussions at the third annual workshop held in Tubingen, Germany, dedicated to the advancement of the technical, scientific and clinical applications of combined PET/MRI systems in humans. Two days of basic scientific and technical instructions with "hands-on" tutorials were followed by 3 days of invited presentations from active researchers in this and associated fields augmented by round-table discussions and dialogue boards with specific themes. These included the use of PET/MRI in paediatric oncology and in adult neurology, oncology and cardiology, the development of multi-parametric analyses, and efforts to standardise PET/MRI examinations to allow pooling of data for evaluating the technology. A poll taken on the final day demonstrated that over 50 % of those present felt that while PET/MRI technology underwent an inevitable slump after its much-anticipated initial launch, it was now entering a period of slow, progressive development, with new key applications emerging. In particular, researchers are focusing on exploiting the complementary nature of the physiological (PET) and biochemical (MRI/MRS) data within the morphological framework (MRI) that these devices can provide. Much of the discussion was summed up on the final day when one speaker commented on the state of PET/MRI: "the real work has just started".
C1 [Bailey, D. L.] Univ Sydney, Royal N Shore Hosp, Dept Nucl Med, Sydney, NSW 2006, Australia.
[Bailey, D. L.] Univ Sydney, Fac Hlth Sci, Sydney, NSW 2006, Australia.
[Antoch, G.] Univ Clin Dusseldorf, Inst Diagnost & Intervent Radiol, Dusseldorf, Germany.
[Bartenstein, P.] Univ Munich, Dept Nucl Med, Munich, Germany.
[Barthel, H.; Purz, S.; Sabri, O.; Sattler, B.] Univ Leipzig, Dept Nucl Med, D-04109 Leipzig, Germany.
[Beer, A. J.] Univ Ulm, Dept Nucl Med, D-89069 Ulm, Germany.
[Bisdas, S.; Claussen, C. D.; Gueckel, B.; Schaefer, J.; Schmidt, H.] Univ Tubingen, Dept Intervent & Diagnost Neuroradiol, Tubingen, Germany.
[Bluemke, D. A.] NIH, Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Boellaard, R.] Vrije Univ Amsterdam, Med Ctr, Dept Radiol & Nucl Med, Amsterdam, Netherlands.
[Franzius, C.] MR & PET MRI, Ctr Morphol & Mol Diagnost ZeMoDi, Bremen, Germany.
[Franzius, C.] Ctr Nucl Med & PET CT, Bremen, Germany.
[Hacker, M.] Med Univ Vienna, Dept Biomed Imaging & Image Guided Therapy, Div Nucl Med, Vienna, Austria.
[Hricak, H.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA.
[la Fougere, C.] Univ Tubingen, Dept Nucl Med & Mol Imaging, Tubingen, Germany.
[Nekolla, S. G.] Tech Univ Munich, Clin Nucl Med, D-80290 Munich, Germany.
[Pichler, B. J.; Wehrl, H. F.] Univ Tubingen, Werner Siemens Imaging Ctr, Dept Preclin Imaging & Radiopharm, Tubingen, Germany.
[Quick, H. H.] Univ Duisburg Essen, Erwin L Hahn Inst MR Imaging, Essen, Germany.
[Quick, H. H.] Univ Hosp Essen, High Field & Hybrid MR Imaging, Essen, Germany.
[van den Hoff, J.] FZD Res Ctr Dresden, PET Ctr, Dresden, Germany.
[Voss, S.] Harvard Univ, Sch Med, Dept Radiol, Boston Childrens Hosp, Boston, MA 02115 USA.
[Weber, W.] Mem Sloan Kettering Canc Ctr, Dept Radiol Mol Imaging & Therapy Serv, New York, NY 10021 USA.
[Beyer, T.] Med Univ Vienna, Gen Hosp Vienna, Ctr Med Phys & Biomed Engn, A-1090 Vienna, Austria.
RP Beyer, T (reprint author), Med Univ Vienna, Gen Hosp Vienna, Ctr Med Phys & Biomed Engn, 4 L Waehringer Guertel 18-20, A-1090 Vienna, Austria.
EM thomas.beyer@meduniwien.ac.at
RI Bisdas, Sotirios/P-2549-2016; la Fougere, Christian/G-6514-2012;
OI Bisdas, Sotirios/0000-0001-9930-5549; Beyer, Thomas/0000-0002-8308-3918;
Boellaard, Ronald/0000-0002-0313-5686; Bluemke,
David/0000-0002-8323-8086
FU Bayer HealthCare; GE Healthcare; Hermes Medical Solutions; Mediso
Medical Imaging Systems; Mirada Medical; Pi.pmod Biomedical Image
Quantification; Siemens Healthcare; WMIS
FX We would further like to acknowledge the generous support of the
workshop sponsors: Bayer HealthCare, GE Healthcare, Hermes Medical
Solutions, Mediso Medical Imaging Systems, Mirada Medical, Pi.pmod
Biomedical Image Quantification, Siemens Healthcare and the WMIS.
NR 78
TC 21
Z9 21
U1 1
U2 20
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1536-1632
EI 1860-2002
J9 MOL IMAGING BIOL
JI Mol. Imaging. Biol.
PD JUN
PY 2015
VL 17
IS 3
BP 297
EP 312
DI 10.1007/s11307-014-0818-0
PG 16
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CH5TE
UT WOS:000354097400002
PM 25672749
ER
PT J
AU Emery, AC
Liu, XH
Xu, WQ
Eiden, MV
Eiden, LE
AF Emery, Andrew C.
Liu, Xiu-Huai
Xu, Wenqin
Eiden, Maribeth V.
Eiden, Lee E.
TI Cyclic Adenosine 3 ',5 '-Monophosphate Elevation and Biological
Signaling through a Secretin Family G(s)-Coupled G Protein-Coupled
Receptor Are Restricted to a Single Adenylate Cyclase Isoform
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID LIPID RAFTS; PC12 CELLS; CAVEOLAE; NEURITOGENESIS; COMPONENTS;
INHIBITORS; DOMAINS; PATHWAY
AB PC12 cells express five adenylate cyclase (AC) isoforms, most abundantly AC6 and AC7. These two ACs were individually silenced using lentiviral short hairpin RNAs, which lead to a decrease (>= 80%) of the protein product of each transcript. These stable PC12 sublines were then used to examine potential AC isoform preference for signaling through a family B G protein-coupled receptor (GPCR). Cells were challenged with the endogenous agonist of the pituitary adenylate cyclase-activating polypeptide type I receptor (PAC(1)), pituitary adenylate cyclase-activating polypeptide (PACAP)-38, or the diterpene forskolin as an AC-proximal control. Intracellular cAMP levels were elevated by forskolin about equally in wild-type, AC6, and AC7 knockdown cells. The ability of PACAP-38 and forskolin to activate three cAMP sensors downstream of AC [protein kinase A (PKA), exchange protein activated by cAMP (Epac) 2/Rapgef4, and neuritogenic cAMP sensor (NCS)/Rapgef2] was examined by monitoring the phosphorylation status of their respective targets, cAMP response element-binding protein, p38, and extracellular signal-regulated kinase. Forskolin stimulation of each downstream target of cAMP was unaffected by knockdown of either AC6 or AC7. PACAP-38 activation of all downstream targets of cAMP was unaffected by AC7 knockdown, but abolished following AC6 knockdown. Membrane cholesterol depletion with methyl-beta-cyclodextrin mimicked the effects of AC6 silencing on PACAP signaling, without attenuating forskolin signaling. These data suggest that vicinal constraint of the GPCR PAC(1) and AC6 determines the exclusive requirement for this AC in PACAP signaling, but that the coupling of the cAMP sensors PKA, Epac2/Rapgef4, and NCS/Rapgef2, to their respective downstream signaling targets, determines how cAMP signaling is parcellated to physiologic responses, such as neuritogenesis, upon GPCR-G(s) activation in neuroendocrine cells.
C1 [Emery, Andrew C.; Liu, Xiu-Huai; Eiden, Lee E.] Natl Inst Mental Hlth, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA.
[Xu, Wenqin; Eiden, Maribeth V.] Natl Inst Mental Hlth, Lab Cellular & Mol Regulat, Directed Gene Transfer, Bethesda, MD 20892 USA.
RP Eiden, LE (reprint author), Natl Inst Mental Hlth, 49 Convent Dr,Bldg 49,Room 5A 38, Bethesda, MD 20892 USA.
EM eidenm@mail.nih.gov; eidenl@mail.nih.gov
FU National Institutes of Health National Institute of Mental Health
Intramural Research Program [1ZIAMH002386, 1ZIAMH002592]; Brain and
Behavior Research Foundation [21356]
FX This work was supported by the National Institutes of Health National
Institute of Mental Health Intramural Research Program [Projects
1ZIAMH002386 and 1ZIAMH002592]. A.C.E.'s project is supported in part by
a 2014 NARSAD Young Investigator Grant from the Brain and Behavior
Research Foundation [Grant 21356].
NR 23
TC 1
Z9 3
U1 2
U2 4
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
EI 1521-0111
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD JUN
PY 2015
VL 87
IS 6
BP 928
EP 935
DI 10.1124/mol.115.098087
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CI2ZN
UT WOS:000354617000004
PM 25769305
ER
PT J
AU Szakadati, G
Toth, AD
Olah, I
Erdeli, LS
Balla, T
Varnai, P
Hunyady, L
Balla, A
AF Szakadati, Gyoengyi
Toth, Andras D.
Olah, Ilona
Erdeli, Laszlo Sandor
Balla, Tamas
Varnai, Peter
Hunyady, Laszlo
Balla, Andras
TI Investigation of the Fate of Type I Angiotensin Receptor after Biased
Activation
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID PROTEIN-COUPLED RECEPTOR; PHOSPHATIDYLINOSITOL 4-PHOSPHATE; SELECTIVE
REGULATION; AT(1); ENDOCYTOSIS; INTERNALIZATION; DOMAINS;
PHOSPHORYLATION; AGONIST; BINDING
AB Biased agonism on the type I angiotensin receptor (AT(1)-R) can achieve different outcomes via activation of G protein-dependent and -independent cellular responses. In this study, we investigated whether the biased activation of AT(1)-R can lead to different regulation and intracellular processing of the receptor. We analyzed beta-arrestin binding, endocytosis, and subsequent trafficking steps, such as early and late phases of recycling of AT(1)-R in human embryonic kidney 293 cells expressing wild-type or biased mutant receptors in response to different ligands. We used Renilla luciferase-tagged receptors and yellow fluorescent protein-tagged beta-arrestin2, Rab5, Rab7, and Rab11 proteins in bioluminescence resonance energy transfer measurements to follow the fate of the receptor after stimulation. We found that not only is the signaling of the receptor different upon using selective ligands, but the fate within the cells is also determined by the type of the stimulation. beta-arrestin binding and the internalization kinetics of the angiotensin II-stimulated AT(1)-R differed from those stimulated by the biased agonists. Similarly, angiotensin II-stimulated wild-type AT(1)-R showed differences compared with a biased mutant AT(1)-R (DRY/AAY AT(1)-R) with regards to beta-arrestin binding and endocytosis. We found that the differences in the internalization kinetics of the receptor in response to biased agonist stimulation are due to the differences in plasma membrane phosphatidylinositol 4,5-bisphosphate depletion. Moreover, the stability of the beta-arrestin binding is a major determinant of the later fate of the internalized AT(1)-R receptor.
C1 [Szakadati, Gyoengyi; Toth, Andras D.; Olah, Ilona; Erdeli, Laszlo Sandor; Varnai, Peter; Hunyady, Laszlo; Balla, Andras] Semmelweis Univ, Fac Med, Dept Physiol, H-1085 Budapest, Hungary.
[Erdeli, Laszlo Sandor; Varnai, Peter; Hunyady, Laszlo; Balla, Andras] Hungarian Acad Sci, Semmelweis Egyet Lab Mol Physiol, Magyar Tudomanyos Akad, Budapest, Hungary.
[Erdeli, Laszlo Sandor; Varnai, Peter; Hunyady, Laszlo; Balla, Andras] Semmelweis Univ, H-1085 Budapest, Hungary.
[Balla, Tamas] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD USA.
RP Hunyady, L (reprint author), POB 259, H-1444 Budapest, Hungary.
EM Hunyady@eok.sote.hu
OI Balla, Tamas/0000-0002-9077-3335; Balla, Andras/0000-0002-6450-2793
FU Hungarian Scientific Research Fund OTKA [NK100883, K105006]; National
Development Agency NFU TAMOP [4.2.2-08/1/KMR,
4-2.1/B-09/1/KMR-2010-0001]; Janos Bolyai Research Scholarship of the
Hungarian Academy of Sciences; Intramural Research Program of the
National Institutes of Health (Section on Molecular Signal Transduction,
Program for Developmental Neuroscience, Eunice Kennedy Shriver National
Institute of Child Health and Human Development)
FX This work was supported by the Hungarian Scientific Research Fund OTKA
[NK100883 and K105006] and National Development Agency NFU TAMOP
[4.2.2-08/1/KMR and 4-2.1/B-09/1/KMR-2010-0001]. A.B. was also supported
by the Janos Bolyai Research Scholarship of the Hungarian Academy of
Sciences. This research was supported in part by the Intramural Research
Program of the National Institutes of Health (Section on Molecular
Signal Transduction, Program for Developmental Neuroscience, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development).
NR 51
TC 4
Z9 4
U1 3
U2 7
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
EI 1521-0111
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD JUN
PY 2015
VL 87
IS 6
BP 972
EP 981
DI 10.1124/mol.114.097030
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CI2ZN
UT WOS:000354617000008
PM 25804845
ER
PT J
AU Fernandez, EV
Reece, KM
Ley, AM
Troutman, SM
Sissung, TM
Price, DK
Chau, CH
Figg, WD
AF Fernandez, Elena V.
Reece, Kelie M.
Ley, Ariel M.
Troutman, Sarah M.
Sissung, Tristan M.
Price, Douglas K.
Chau, Cindy H.
Figg, William D.
TI Dual Targeting of the Androgen Receptor and Hypoxia-Inducible Factor 1
alpha Pathways Synergistically Inhibits Castration-Resistant Prostate
Cancer Cells
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID BIOLOGY; ENZALUTAMIDE; ANTIANDROGEN; ENVIRONMENT; ACTIVATION; MECHANISMS
AB Enzalutamide is a potent second-generation androgen receptor (AR) antagonist with activity in metastatic castrate-resistant prostate cancer (CRPC). Although enzalutamide is initially effective, disease progression inevitably ensues with the emergence of resistance. Intratumoral hypoxia is also associated with CRPC progression and treatment resistance. Given that both AR and hypoxia inducible factor-1 alpha (HIF-1 alpha) are key regulators of these processes, dual targeting of both signaling axes represents an attractive therapeutic approach. Crosstalk of the AR and HIF-1a signaling pathways were examined in prostate cancer cell lines (LNCaP, 22Rv1) with assays measuring the effect of androgen and hypoxia on AR-dependent and hypoxia-inducible gene transcription, protein expression, cell proliferation, and apoptosis. HIF-1 alpha inhibition was achieved by siRNA silencing HIF-1 alpha or via chetomin, a disruptor of HIF-1 alpha-p300 interactions. In prostate cancer cells, the gene expression of AR targets (KLK3, FKBP5, TMPRSS2) was repressed by HIF-signaling; conversely, specific HIF-1 alpha target expression was induced by dihydrotestosterone-mediated AR signaling. Treatment of CRPC cells with enzalutamide or HIF-1 alpha inhibition attenuated AR-regulated and HIF-1 alpha-mediated gene transcription. The combination of enzalutamide and HIF-1 alpha inhibition was more effective than either treatment alone. Similarly, the combination also reduced vascular endothelial growth factor protein levels. HIF-1 alpha siRNA synergistically enhanced the inhibitory effect of enzalutamide on cell growth in LNCaP and enzalutamide-resistant 22Rv1 cells via increased enzalutamide-induced apoptosis. In conclusion, the combination of enzalutamide with HIF-1 alpha inhibition resulted in synergistic inhibition of AR-dependent and gene-specific HIF-dependent expression and prostate cancer cell growth.
C1 [Fernandez, Elena V.; Reece, Kelie M.; Ley, Ariel M.; Troutman, Sarah M.; Sissung, Tristan M.; Price, Douglas K.; Chau, Cindy H.; Figg, William D.] NCI, Ctr Canc Res, Genitourinary Malignancies Branch, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), Bldg 10-Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM figgw@helix.nih.gov
RI Figg Sr, William/M-2411-2016
FU Intramural Research Program of the National Institutes of Health
National Cancer Institute, Center for Cancer Research
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health National Cancer Institute, Center
for Cancer Research.
NR 26
TC 8
Z9 9
U1 5
U2 11
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
EI 1521-0111
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD JUN
PY 2015
VL 87
IS 6
BP 1006
EP 1012
DI 10.1124/mol.114.097477
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CI2ZN
UT WOS:000354617000011
PM 25829060
ER
PT J
AU Nance, JR
Mammen, AL
AF Nance, Jessica R.
Mammen, Andrew L.
TI Diagnostic evaluation of rhabdomyolysis
SO MUSCLE & NERVE
LA English
DT Review
DE etiology; inherited myopathy; metabolic myopathy; rhabdomyolysis;
symptoms
ID ACUTE-RENAL-FAILURE; PHOSPHOGLYCERATE MUTASE DEFICIENCY; B
KINASE-DEFICIENCY; MUSCLE PHOSPHOFRUCTOKINASE DEFICIENCY; DEHYDROGENASE
M-SUBUNIT; CPT-II DEFICIENCY; TRIFUNCTIONAL PROTEIN-DEFICIENCY;
SICKLE-CELL TRAIT; ACUTE EXERTIONAL RHABDOMYOLYSIS; PHOSPHOGLUCOMUTASE 1
DEFICIENCY
AB Rhabdomyolysis is characterized by severe acute muscle injury resulting in muscle pain, weakness, and/or swelling with release of myofiber contents into the bloodstream. Symptoms develop over hours to days after an inciting factor and may be associated with dark pigmentation of the urine. Serum creatine kinase and urine myoglobin levels are markedly elevated. Clinical examination, history, laboratory studies, muscle biopsy, and genetic testing are useful tools for diagnosis of rhabdomyolysis, and they can help differentiate acquired from inherited causes of rhabdomyolysis. Acquired causes include substance abuse, medication or toxic exposures, electrolyte abnormalities, endocrine disturbances, and autoimmune myopathies. Inherited predisposition to rhabdomyolysis can occur with disorders of glycogen metabolism, fatty acid -oxidation, and mitochondrial oxidative phosphorylation. Less common inherited causes of rhabdomyolysis include structural myopathies, channelopathies, and sickle-cell disease. This review focuses on the differentiation of acquired and inherited causes of rhabdomyolysis and proposes a practical diagnostic algorithm. Muscle Nerve51: 793-810, 2015
C1 [Nance, Jessica R.; Mammen, Andrew L.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Mammen, Andrew L.] NIAMSD, Muscle Dis Unit, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA.
RP Mammen, AL (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
EM andrew.mammen@nih.gov
FU Intramural Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases of the National Institutes of Health
FX This work was supported in part by the Intramural Research Program of
the National Institute of Arthritis and Musculoskeletal and Skin
Diseases of the National Institutes of Health.
NR 212
TC 9
Z9 9
U1 3
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0148-639X
EI 1097-4598
J9 MUSCLE NERVE
JI Muscle Nerve
PD JUN
PY 2015
VL 51
IS 6
BP 793
EP 810
DI 10.1002/mus.24606
PG 18
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CI1TG
UT WOS:000354526900002
PM 25678154
ER
PT J
AU Blaisdell, CJ
Weinmann, GG
AF Blaisdell, Carol J.
Weinmann, Gail G.
TI NHLBI viewpoint: Lung health and disease prevention research starting in
childhood
SO PEDIATRIC PULMONOLOGY
LA English
DT Article
DE bronchopulmonary dysplasia (BPD); asthma & early wheeze; cystic fibrosis
(CF); developmental biology; pulmonary hypertension
ID CYSTIC-FIBROSIS; PRETERM INFANTS; BRONCHOPULMONARY DYSPLASIA;
PULMONARY-FUNCTION; MATERNAL SMOKING; CONTROLLED-TRIAL; AIR-POLLUTION;
AGE; ASTHMA; SUPPLEMENTATION
AB Lung health begins in utero when the complex structure of the airway, alveolar, and vascular structures are formed. To really impact the United States and global burden of chronic lung diseases in both adults and children, we must understand normal and abnormal development, the outcomes of disrupted development, and the effects of in utero and postnatal exposures on lung health. With increasing recognition of early life origins of adult diseases,(1) it is important to know what early events and interventions can alter the trajectory of lung development, growth, and decline to help promote lung health and reduce chronic lung disease. Pediatr Pulmonol. 2015; 50:604-606. (c) 2015 Wiley Periodicals, Inc.
C1 [Blaisdell, Carol J.; Weinmann, Gail G.] NHLBI, Div Lung Dis, Bethesda, MD 20892 USA.
RP Blaisdell, CJ (reprint author), NHLBI, Div Lung Dis, 6701 Rockledge Dr 10-160, Bethesda, MD 20892 USA.
EM Blaisdellcj@nhlbi.nih.gov
NR 30
TC 1
Z9 1
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 8755-6863
EI 1099-0496
J9 PEDIATR PULM
JI Pediatr. Pulmonol.
PD JUN
PY 2015
VL 50
IS 6
BP 604
EP 606
DI 10.1002/ppul.23198
PG 3
WC Pediatrics; Respiratory System
SC Pediatrics; Respiratory System
GA CI0VZ
UT WOS:000354458600012
PM 25857257
ER
PT J
AU Lin, YJ
Ho, TJ
Lin, TH
Hsu, WY
Huang, SM
Liao, CC
Lai, CH
Liu, X
Tsang, H
Lai, CC
Tsai, FJ
AF Lin, Ying-Ju
Ho, Tsung-Jung
Lin, Ting-Hsu
Hsu, Wei-Yi
Huang, Shao-Mei
Liao, Chiu-Chu
Lai, Chih-Ho
Liu, Xiang
Tsang, Hsinyi
Lai, Chien-Chen
Tsai, Fuu-Jen
TI P-coumaric acid regulates exon 12 splicing of the ATP7B gene by
modulating hnRNP A1 protein expressions
SO BIOMEDICINE-TAIWAN
LA English
DT Article
DE Wilson's disease; Schizonepeta; p-coumaric acid; hnRNP A1; Alternative
splicing
ID SPINAL MUSCULAR-ATROPHY; WILSON DISEASE GENE; MOTOR-NEURON SMN;
POTENTIAL THERAPY; MUTATION ANALYSIS; INCLUSION; CELLS; RNA;
IDENTIFICATION; HTRA2-BETA-1
AB Background: Wilson's disease (WD) is a genetic disorder involving the metabolism of copper. WD patients exhibit a wide range of disease phenotypes, including Kayser-Fleischer rings in the cornea, predominant progressive hepatic disease, neurological diseases, and/or psychiatric illnesses, among others. Patients with exon12 mutations of the ATP7B gene have progressive hepatic disease. An ATP7B gene that lacks exon12 retains 80% of its copper transport activities, suggesting that alternative splicing of ATP7B gene may provide alternative therapeutic ways for patients with inherited sequence variants and mutations of this gene.
Purpose: We aimed to search for possible Chinese herbs and related compounds for modulating ATP7B pre-mRNA splicing.
Methods: We used an ATP7B exon11-12-13 mini-gene vector as a model and screened 18 Chinese herbal extracts and four compounds from Schizonepeta to determine their effects on ATP7B pre-mRNA splicing in vitro.
Results: We found that Schizonepeta demonstrated the greatest potential for alternative splicing activity. Specifically, we found that p-coumaric acid from this herb enhanced ATP7B exon12 exclusion through the down-regulation of heterogeneous ribonucleoprotein (hnRNP) A1 protein expressions.
Conclusion: These results suggest that there are herbs or herb-related compounds that could modify the alternative splicing of the ATP7B gene via a mechanism that regulates pre-mRNA splicing.
C1 [Lin, Ying-Ju; Lin, Ting-Hsu; Hsu, Wei-Yi; Huang, Shao-Mei; Liao, Chiu-Chu; Tsai, Fuu-Jen] China Med Univ Hosp, Dept Med Res, Genet Ctr, Taichung 404, Taiwan.
[Lin, Ying-Ju; Ho, Tsung-Jung; Tsai, Fuu-Jen] China Med Univ, Sch Chinese Med, Taichung 404, Taiwan.
[Ho, Tsung-Jung] China Med Univ, Beigang Hosp, Div Chinese Med, Peikang 651, Yunlin County, Taiwan.
[Ho, Tsung-Jung] China Med Univ, Tainan Manicipal An Nan Hosp, Div Chinese Med, Tainan 709, Taiwan.
[Lai, Chih-Ho] China Med Univ, Sch Med, Dept Microbiol, Taichung 404, Taiwan.
[Liu, Xiang; Tsang, Hsinyi] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Lai, Chien-Chen] Natl Chung Hsing Univ, Inst Mol Biol, Taichung 402, Taiwan.
[Tsai, Fuu-Jen] Asia Univ, Dept Biotechnol, Taichung 413, Taiwan.
RP Lai, CC (reprint author), China Med Univ Hosp, Dept Med Res, 2 Yuh Rd, Taichung 404, Taiwan.
EM lailai@dragon.nchu.edu.tw; d0704@mail.cmuh.org.tw
RI Liu, Xiang/F-5731-2014; Tsai, Fuu-Jen/J-4140-2015
NR 30
TC 2
Z9 2
U1 0
U2 5
PU CHINA MEDICAL UNIV-CMU
PI TAICHUNG
PA NO 91, HSUEH-SHIH RE, TAICHUNG, 40402, TAIWAN
SN 2211-8020
EI 2211-8039
J9 BIOMEDICINE-TAIWAN
JI BioMedicine-Taiwan
PD JUN
PY 2015
VL 5
IS 2
BP 22
EP 30
DI 10.7603/s40681-015-0010-0
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA DO6HL
UT WOS:000377883800004
PM 26048696
ER
PT J
AU Arai, AE
AF Arai, Andrew E.
TI New Insights from Major Prospective Cohort Studies with Cardiovascular
Magnetic Resonance (CMR)
SO CURRENT CARDIOLOGY REPORTS
LA English
DT Review
DE MRI (magnetic resonance imaging); Cardiovascular; Epidemiology;
Myocardial infarction; Cardiomyopathy; Left ventricular hypertrophy
ID LEFT-VENTRICULAR HYPERTROPHY; PROATRIAL NATRIURETIC PEPTIDE; INCIDENT
HEART-FAILURE; SERUM CYSTATIN-C; ATHEROSCLEROSIS MESA;
MYOCARDIAL-PERFUSION; ASYMPTOMATIC ADULTS; ATRIAL-FIBRILLATION;
BLOOD-PRESSURE; RISK
AB Since 1948, epidemiology studies played an important role in understanding cardiovascular disease and afforded an opportunity to learn about newer diagnostic tests. In 2000, the MESA Study incorporated several advanced cardiovascular imaging modalities including cardiac magnetic resonance imaging (MRI) and coronary artery calciumscans. The decade of follow-up enabled prognosis studies, an important step beyond association studies. In brief, left ventricular hypertrophy by cardiac MRI predicted incident heart failure and stroke. In the MESA Study, coronary artery calcium was a better predictor of coronary artery disease end points than the non-contrast-enhanced MRI scan. In the ICELAND MI substudy of the AGES-Reykjavik Study, a contrast-enhanced MRI scan detected many more unrecognized myocardial infarctions (MIs) (UMIs) than detected by electrocardiography and documented these UMI had adverse prognostic significance. Thus, cardiac MRI has been successfully incorporated into large population studies and shown added value over conventional measurements of cardiovascular disease.
C1 [Arai, Andrew E.] NHLBI, NIH, US Dept HHS, Bldg 10,Rm B1D416,MSC 1061,10 Ctr Dr, Bethesda, MD 20892 USA.
RP Arai, AE (reprint author), NHLBI, NIH, US Dept HHS, Bldg 10,Rm B1D416,MSC 1061,10 Ctr Dr, Bethesda, MD 20892 USA.
EM araia@nih.gov
FU Division of Intramural Research, National Heart, Lung and Blood
Institute, National Institutes of Health, US Department of Health and
Human Services, Bethesda, MD, USA [ZIA HL004607-16, ZIA HL004607-17]
FX This work was funded by the Division of Intramural Research, National
Heart, Lung and Blood Institute, National Institutes of Health, US
Department of Health and Human Services, Bethesda, MD, 20892-1061 USA
[ZIA HL004607-16 and ZIA HL004607-17].
NR 50
TC 0
Z9 0
U1 2
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1523-3782
EI 1534-3170
J9 CURR CARDIOL REP
JI Curr. Cardiol. Rep.
PD JUN
PY 2015
VL 17
IS 6
AR 46
DI 10.1007/s11886-015-0599-3
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DN6DY
UT WOS:000377163500002
PM 25939757
ER
PT J
AU Figg, WD
Thompson, IM
AF Figg, William D.
Thompson, Ian M.
TI Effect of 5 alpha-Reductase Inhibitor Use on Mortality From Prostate
Cancer
SO JAMA ONCOLOGY
LA English
DT Editorial Material
ID PREVENTION TRIAL; FINASTERIDE; SENSITIVITY
C1 [Figg, William D.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA.
[Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA.
RP Figg, WD (reprint author), NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA.
EM figgw@helix.nih.gov
RI Figg Sr, William/M-2411-2016
FU NCI NIH HHS [UG1 CA189974, U10 CA037429, UM1 CA182883]
NR 10
TC 2
Z9 2
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
EI 2374-2445
J9 JAMA ONCOL
JI JAMA Oncol.
PD JUN
PY 2015
VL 1
IS 3
BP 321
EP 322
DI 10.1001/jamaoncol.2015.0408
PG 2
WC Oncology
SC Oncology
GA DW5FQ
UT WOS:000383669100014
PM 26181178
ER
PT J
AU Ionescu, DF
Nugent, AC
Luckenbaugh, DA
Niciu, MJ
Richards, EM
Zarate, CA
Furey, ML
AF Ionescu, Dawn F.
Nugent, Allison C.
Luckenbaugh, David A.
Niciu, Mark J.
Richards, Erica M.
Zarate, Carlos A., Jr.
Furey, Maura L.
TI Baseline working memory activation deficits in dimensional anxious
depression as detected by magnetoencephalography
SO ACTA NEUROPSYCHIATRICA
LA English
DT Article
DE anxious depression; magnetoencephalography (MEG); major depressive
disorder; N-back task; neurobiology
ID STAR-ASTERISK-D; NONANXIOUS DEPRESSION; UNIPOLAR DEPRESSION; COGNITIVE
THERAPY; MAJOR DEPRESSION; DISORDER; BRAIN; OUTPATIENTS; TASK;
IMPROVEMENT
AB Objective Anxiety often co-occurs with major depressive disorder (MDD). This preliminary study sought to ascertain the extent to which anxious depression drives group neurobiological differences between patients with MDD and healthy volunteers (HVs).
Methods Magnetoencephalography beta-band frequency was used to compare differences in brain response during the N-back working memory task between 30 medication-free patients with treatment-resistant MDD (anxious depression=18; nonanxious depression=12) and 28 HVs.
Results Compared to HVs, patients with anxious depression had significantly reduced desynchronisation (less activation) in the left precuneus, right cuneus, and left insula extending into the inferior and middle frontal cortex during the 2-back condition compared with the 1-back condition of the N-back working memory task - indicating less activation of these neural networks in patients with anxious depression during the condition with the highest level of task demands. No other significant group differences were found during the working memory conditions.
Conclusion This preliminary study suggests that a subset of patients - those with anxious depression - may be driving observed group differences between patients with MDD and HVs. Further neurobiological studies and replication experiments are necessary to determine the extent to which this subgroup has preferentially influenced our understanding of the underlying neurobiology of depression.
C1 [Ionescu, Dawn F.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Ionescu, Dawn F.] Harvard Univ, Sch Med, Boston, MA USA.
[Nugent, Allison C.; Luckenbaugh, David A.; Niciu, Mark J.; Richards, Erica M.; Zarate, Carlos A., Jr.; Furey, Maura L.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Ionescu, DF (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 1 Bowdoin Sq,Floor 6, Boston, MA 02114 USA.
EM dionescu@mgh.harvard.edu
RI Niciu, Mark/J-1766-2014; Ionescu, Dawn/K-5675-2015;
OI Niciu, Mark/0000-0002-5612-3021; Nugent, Allison/0000-0003-2569-2480
FU Intramural Research Program at the National Institute of Mental Health,
National Institutes of Health (IRP-NIMH-NIH); NARSAD; Brain & Behavior
Mood Disorders Research Award
FX Funding for this work was supported by the Intramural Research Program
at the National Institute of Mental Health, National Institutes of
Health (IRP-NIMH-NIH), by a NARSAD Independent Investigator to C.A.Z.,
and by the Brain & Behavior Mood Disorders Research Award to C.A.Z. Dr.
Zarate is listed as a co-inventor on a patent application for the use of
ketamine and its metabolites in major depression. Dr. Zarate has
assigned his rights in the patent to the US government but will share a
percentage of any royalties that may be received by the government. Dr.
Furey is listed as a co-inventor on a patent application for the use of
scopolamine in psychiatric disorders. Dr. Furey has assigned his rights
in the patent to the US government but will share a percentage of any
royalties that may be received by the government. The remaining authors
have no conflicts of interest to disclose, financial, or otherwise.
NR 40
TC 0
Z9 0
U1 1
U2 7
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1601-5215
J9 ACTA NEUROPSYCHIATR
JI Acta Neuropsychiatr.
PD JUN
PY 2015
VL 27
IS 3
BP 143
EP 152
DI 10.1017/neu.2014.46
PG 10
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA CH9YC
UT WOS:000354391600002
PM 25600154
ER
PT J
AU Kaburu, SSK
Newton-Fisher, NE
AF Kaburu, Stefano S. K.
Newton-Fisher, Nicholas E.
TI Trading or coercion? Variation in male mating strategies between two
communities of East African chimpanzees
SO BEHAVIORAL ECOLOGY AND SOCIOBIOLOGY
LA English
DT Article
DE Pan troglodytes; Mating strategy; Social grooming; Aggression; Dominance
rank; Biological market theory
ID PAN-TROGLODYTES-SCHWEINFURTHII; KIBALE-NATIONAL-PARK; WILD MALE
CHIMPANZEES; FEMALE MATE CHOICE; CAPTIVE CHIMPANZEES; JAPANESE MACAQUES;
NUPTIAL GIFTS; REPRODUCTIVE STRATEGIES; GROOMING RECIPROCITY; MAHALE
CHIMPANZEES
AB Across taxa, males employ a variety of mating strategies, including sexual coercion and the provision, or trading, of resources. Biological market theory (BMT) predicts that trading of commodities for mating opportunities should exist only when males cannot monopolize access to females and/or obtain mating by force, in situations where power differentials between males are low; both coercion and trading have been reported for chimpanzees (Pan troglodytes). Here, we investigate whether the choice of strategy depends on the variation in male power differentials, using data from two wild communities of East African chimpanzees (Pan troglodytes schweinfurthii): the structurally despotic Sonso community (Budongo, Uganda) and the structurally egalitarian M-group (Mahale, Tanzania). We found evidence of sexual coercion by male Sonso chimpanzees, and of trading-of grooming for mating-by M-group males; females traded sex for neither meat nor protection from male aggression. Our results suggest that the despotism-egalitarian axis influences strategy choice: male chimpanzees appear to pursue sexual coercion when power differentials are large and trading when power differentials are small and coercion consequently ineffective. Our findings demonstrate that trading and coercive strategies are not restricted to particular chimpanzee subspecies; instead, their occurrence is consistent with BMT predictions. Our study raises interesting, and as yet unanswered, questions regarding female chimpanzees' willingness to trade sex for grooming, if doing so represents a compromise to their fundamentally promiscuous mating strategy. It highlights the importance of within-species cross-group comparisons and the need for further study of the relationship between mating strategy and dominance steepness.
C1 [Kaburu, Stefano S. K.] Univ Parma, Dipartimento Neurosci, I-43100 Parma, Italy.
[Kaburu, Stefano S. K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, Poolesville, MD 20842 USA.
[Newton-Fisher, Nicholas E.] Univ Kent, Sch Anthropol & Conservat, Canterbury CT2 7NR, Kent, England.
RP Kaburu, SSK (reprint author), Univ Parma, Dipartimento Neurosci, I-43100 Parma, Italy.
EM stefano.kaburu@nih.gov
OI Newton-Fisher, Nicholas/0000-0002-7657-2641
FU Wenner-Gren foundation [8216]; Leverhulme Trust [F/00236/Z]; H.F.
Guggenheim Foundation
FX This work was funded by the Wenner-Gren foundation (grant no. 8216), the
Leverhulme Trust (grant no. F/00236/Z) and the H.F. Guggenheim
Foundation. We thank the Uganda National Council for Science and
Technology, the President's Office, the Forest Department, and Vernon
Reynolds for granting permission to work in the Budongo forest and the
Tanzania Commission for Science and Technology, the Tanzania Wildlife
Research Institute and the Mahale Mountains Wildlife Research Centre for
allowing research in the Mahale Mountains National Park. We are also
very grateful to Geresomu Muhumuza and the other Ugandan and Tanzanian
field assistants for their fundamental help during data collection both
in Budongo and Mahale. Finally, we would like to thank Robin Dunbar and
two anonymous reviewers for insightful comments on a previous draft of
the article.
NR 110
TC 8
Z9 8
U1 8
U2 28
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-5443
EI 1432-0762
J9 BEHAV ECOL SOCIOBIOL
JI Behav. Ecol. Sociobiol.
PD JUN
PY 2015
VL 69
IS 6
BP 1039
EP 1052
DI 10.1007/s00265-015-1917-x
PG 14
WC Behavioral Sciences; Ecology; Zoology
SC Behavioral Sciences; Environmental Sciences & Ecology; Zoology
GA CH7OR
UT WOS:000354227000018
PM 26279605
ER
PT J
AU Wertheimer, A
AF Wertheimer, Alan
TI The Social Value Requirement Reconsidered
SO BIOETHICS
LA English
DT Article
DE social value; exploitation; research ethics
ID BENEFIT
AB It is widely assumed that it is ethical to conduct research with human subjects only if the research has social value. There are two standard arguments for this view. The allocation argument claims that public funds should not be devoted to research that lacks social value. The exploitation avoidance argument claims that subjects are exploited if research has no social value. The primary purpose of this article is to argue that these arguments do not succeed. The allocation argument has little relevance to commercial research. Social value is not necessary to avoid exploitation if subjects benefit from participation. Although the standard arguments for a social value requirement do not succeed, that view might be justified in a different way. It might be justified by appeal to the importance of social trust or the integrity of physician investigators. It is possible but doubtful that these arguments succeed.
C1 [Wertheimer, Alan] NIH, Dept Bioeth, Bethesda, MD 20892 USA.
[Wertheimer, Alan] Univ Vermont, Polit Sci, Burlington, VT 05405 USA.
RP Wertheimer, A (reprint author), NIH, Dept Bioeth, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM wertheimera@cc.nih.gov
FU NIH; Warren G. Magnuson Clinical Center
FX The Intramural Research Program of the NIH and the Warren G. Magnuson
Clinical Center supported this research. The views expressed here are
those of the author. They do not represent any position or policy of the
National Institutes of Health, the Public Health Service, or the
Department of Health and Human Services. The author also thanks several
colleagues for their comments on drafts of this article: Seema Shah,
Franklin Miller, and David Wendler.
NR 16
TC 8
Z9 8
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-9702
EI 1467-8519
J9 BIOETHICS
JI Bioethics
PD JUN
PY 2015
VL 29
IS 5
BP 301
EP 308
DI 10.1111/bioe.12128
PG 8
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA CH8JK
UT WOS:000354282400002
PM 25470450
ER
PT J
AU Dawson, L
Zwerski, S
AF Dawson, Liza
Zwerski, Sheryl
TI Clinical Trial Design for HIV Prevention Research: Determining Standards
of Prevention
SO BIOETHICS
LA English
DT Article
DE standard of care; researchers' obligations; HIV prevention; clinical
trials; biomedical research; low and middle income countries
ID CHALLENGES; INTERVENTIONS; COMMUNITY; EQUIPOISE; PREP
AB This article seeks to advance ethical dialogue on choosing standards of prevention in clinical trials testing improved biomedical prevention methods for HIV. The stakes in this area of research are high, given the continued high rates of infection in many countries and the budget limitations that have constrained efforts to expand treatment for all who are currently HIV-infected. New prevention methods are still needed; at the same time, some existing prevention and treatment interventions have been proven effective but are not yet widely available in the countries where they most urgently needed. The ethical tensions in this field of clinical research are well known and have been the subject of extensive debate. There is no single clinical trial design that can optimize all the ethically important goals and commitments involved in research. Several recent articles have described the current ethical difficulties in designing HIV prevention trials, especially in resource limited settings; however, there is no consensus on how to handle clinical trial design decisions, and existing international ethical guidelines offer conflicting advice. This article acknowledges these deep ethical dilemmas and moves beyond a simple descriptive approach to advance an organized method for considering what clinical trial designs will be ethically acceptable for HIV prevention trials, balancing the relevant criteria and providing justification for specific design decisions.
C1 [Dawson, Liza] NIAID, Res Eth, Div Aids, NIH, Bethesda, MD 20892 USA.
[Dawson, Liza] NIH, Bioeth & Human Res Protect, Bethesda, MD USA.
[Dawson, Liza] Johns Hopkins Univ, Sch Publ Hlth, Bioeth Inst, Baltimore, MD 21218 USA.
[Dawson, Liza] Natl Bioeth Advisory Commiss, Rockville, MD USA.
[Zwerski, Sheryl] NIAID, Prevent Sci Program, Div Aids, Bethesda, MD 20892 USA.
[Zwerski, Sheryl] NIAID, Bethesda, MD 20892 USA.
[Zwerski, Sheryl] NCI, Pediat Branch, Bethesda, MD 20892 USA.
[Zwerski, Sheryl] Univ Florida, Pediat Immunol Div, Gainesville, FL 32611 USA.
RP Dawson, L (reprint author), NIAID, NIH, Div Aids, 5601 Fishers Lane,Room 9G59, Bethesda, MD 20892 USA.
EM dawsonl@niaid.nih.gov
FU Intramural NIH HHS [Z99 AI999999]
NR 23
TC 1
Z9 1
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-9702
EI 1467-8519
J9 BIOETHICS
JI Bioethics
PD JUN
PY 2015
VL 29
IS 5
BP 316
EP 323
DI 10.1111/bioe.12113
PG 8
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA CH8JK
UT WOS:000354282400004
PM 25230397
ER
PT J
AU Medina, SH
Li, S
Howard, OMZ
Dunlap, M
Trivett, A
Schneider, JP
Oppenheim, JJ
AF Medina, Scott H.
Li, Sandra
Howard, O. M. Zack
Dunlap, Micah
Trivett, Anna
Schneider, Joel P.
Oppenheim, Joost J.
TI Enhanced immunostimulatory effects of DNA-encapsulated peptide hydrogels
SO BIOMATERIALS
LA English
DT Article
DE DNA; Peptide; Drug delivery; Self assembly; Gene expression
ID GENE DELIVERY; RESPONSIVE HYDROGELS; ANTIGEN PRESENTATION;
IMMUNE-RESPONSES; IN-VITRO; VACCINES; RELEASE; SYSTEMS; PROTEIN; DESIGN
AB DNA that encodes 'tumor-specific antigens represents potential immunostimulatory agents. However, rapid enzymatic degradation and fragmentation of DNA during administration can result in limited vector expression and, consequently, poor efficacy. These challenges have necessitated the use of novel strategies for DNA delivery. Herein, we study the ability of cationic self-assembling peptide hydrogels to encapsulate plasmid DNA, and enhance its immunostimulatory potential in vivo. The effect of network charge on the gel's ability to retain the DNA was assessed employing three gel-forming peptides that vary systematically in formal charge. The peptide HLT2, having a formal charge of +5 at neutral pH, was optimal in encapsulating microgram quantities of DNA with little effect on its rheological properties, allowing its effective syringe delivery in vivo. The plasmid, DNA(TA), encapsulated within these gels encodes for a melanoma-specific gp100 antigen fused to the alarmin protein adjuvant HMGN1. Implantation of DNA(TA)-loaded HLT2 gels into mice resulted in an acute inflammatory response with the presence of polymorphonuclear cells, which was followed by infiltrating macrophages. These cellular infiltrates aid in the processing of encapsulated DNA, promoting increased lymphoproliferation and producing an enhanced immune response mediated by CD4+/IFN gamma+ expressing Th1 cells, and complemented by the formation of gp100-specific antibodies. Published by Elsevier Ltd.
C1 [Medina, Scott H.; Schneider, Joel P.] NCI, Biol Chem Lab, NIH, Frederick, MD 21702 USA.
[Li, Sandra; Howard, O. M. Zack; Dunlap, Micah; Trivett, Anna; Oppenheim, Joost J.] NCI, Mol Immunoregulat Lab, NIH, Frederick, MD 21702 USA.
RP Schneider, JP (reprint author), NCI, Biol Chem Lab, NIH, Frederick, MD 21702 USA.
EM Joel.Schneider@nih.gov; oppenheJ@mail.nih.gov
RI Schneider, Joel/N-2610-2014
FU National Cancer Institute, National Institutes of Health
FX S.H.M. and S.L. contributed equally to this work. This work was
supported by the Intramural Research Program of the National Cancer
Institute, National Institutes of Health. We thank the core staff at the
Pathology/Histotechnology Laboratory (NCI) for their assistance in the
processing of histology and immunohistochemistry samples.
NR 40
TC 7
Z9 7
U1 8
U2 68
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0142-9612
EI 1878-5905
J9 BIOMATERIALS
JI Biomaterials
PD JUN
PY 2015
VL 53
BP 545
EP 553
DI 10.1016/j.biomaterials.2015.02.125
PG 9
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA CH3KO
UT WOS:000353929800050
PM 25890750
ER
PT J
AU Tran, PT
Kim, HS
Ann, J
Kim, SE
Kim, C
Hong, M
Hoang, VH
Ngo, VTH
Hong, SH
Cui, MH
Choi, S
Blumberg, PM
Frank-Foltyn, R
Bahrenberg, G
Stockhausen, H
Christoph, T
Lee, J
AF Phuong-Thao Tran
Kim, Ho Shin
Ann, Jihyae
Kim, Sung-Eun
Kim, Changhoon
Hong, Mannkyu
Hoang, Van-Hai
Ngo, Van T. H.
Hong, Sunhye
Cui, Minghua
Choi, Sun
Blumberg, Peter M.
Frank-Foltyn, Robert
Bahrenberg, Gregor
Stockhausen, Hannelore
Christoph, Thomas
Lee, Jeewoo
TI alpha-Substituted 2-(3-fluoro-4-methylsulfonamidophenyl)acetamides as
potent TRPV1 antagonists
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE TRPV1 antagonist; Analgesic; Capsaicin; Molecular modeling
ID PYRIDINE C-REGION; VANILLOID CAPSAICIN RECEPTORS; ANALGESIC AGENTS;
AGONIST ACTIVITY; ANALOGS;
2-(3-FLUORO-4-METHYLSULFONYLAMINOPHENYL)PROPANAMIDES; DERIVATIVES;
ACTIVATION
AB A series of alpha-substituted acetamide derivatives of previously reported 2-(3-fluoro-4-methylsulfonamidophenyl) propanamide leads (1, 2) were investigated for antagonism of hTRPV1 activation by capsaicin. Compound 34, which possesses an alpha-m-tolyl substituent, showed highly potent and selective antagonism of capsaicin with K-i(CAP) = 0.1 nM. It thus reflected a 3-fold improvement in potency over parent 1. Docking analysis using our homology model indicated that the high potency of 34 might be attributed to a specific hydrophobic interaction of the m-tolyl group with the receptor. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Phuong-Thao Tran; Kim, Ho Shin; Ann, Jihyae; Kim, Sung-Eun; Kim, Changhoon; Hong, Mannkyu; Hoang, Van-Hai; Ngo, Van T. H.; Lee, Jeewoo] Seoul Natl Univ, Pharmaceut Sci Res Inst, Coll Pharm, Med Chem Lab, Seoul 151742, South Korea.
[Hong, Sunhye; Cui, Minghua; Choi, Sun] Ewha Womans Univ, Grad Sch Pharmaceut Sci, Coll Pharm, Natl Leading Res Lab Mol Modeling & Drug Design, Seoul 120750, South Korea.
[Hong, Sunhye; Cui, Minghua; Choi, Sun] Ewha Womans Univ, Global Top Res Program 5, Seoul 120750, South Korea.
[Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Frank-Foltyn, Robert; Bahrenberg, Gregor; Stockhausen, Hannelore; Christoph, Thomas] Grunenthal GmbH, Grunenthal Innovat, D-52078 Aachen, Germany.
RP Lee, J (reprint author), Seoul Natl Univ, Pharmaceut Sci Res Inst, Coll Pharm, Med Chem Lab, Seoul 151742, South Korea.
EM jeewoo@snu.ac.kr
FU Grunenthal in Germany; Korea Science and Engineering Foundation (KOSEF)
[NRF-2014M3A9B5073755]; National Leading Research Lab (NLRL) program in
South Korea [2011-0028885]; Intramural Research Program of NIH, Center
for Cancer Research, NCI in USA [Z1A BC 005270]
FX This research was supported by Research Grants from Grunenthal in
Germany, Grants from the Korea Science and Engineering Foundation
(KOSEF) (NRF-2014M3A9B5073755) and National Leading Research Lab (NLRL)
program (2011-0028885) in South Korea, and in part by the Intramural
Research Program of NIH, Center for Cancer Research, NCI (Project Z1A BC
005270) in USA.
NR 29
TC 2
Z9 2
U1 0
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
EI 1464-3405
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD JUN 1
PY 2015
VL 25
IS 11
BP 2326
EP 2330
DI 10.1016/j.bmcl.2015.04.024
PG 5
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA CH5ZR
UT WOS:000354115400012
PM 25937016
ER
PT J
AU Cross, JL
Iben, J
Simpson, CL
Thurm, A
Swedo, S
Tierney, E
Bailey-Wilson, JE
Biesecker, LG
Porter, FD
Wassif, CA
AF Cross, J. L.
Iben, J.
Simpson, C. L.
Thurm, A.
Swedo, S.
Tierney, E.
Bailey-Wilson, J. E.
Biesecker, L. G.
Porter, F. D.
Wassif, C. A.
TI Determination of the allelic frequency in Smith-Lemli-Opitz syndrome by
analysis of massively parallel sequencing data sets
SO CLINICAL GENETICS
LA English
DT Article
DE allelic frequency; DHCR7; next generation sequencing; SLOS;
Smith-Lemli-Opitz
ID DHCR7; CHOLESTEROL; MUTATIONS
AB Data from massively parallel sequencing or Next Generation Sequencing' of the human exome has reached a critical mass in both public and private databases, in that these collections now allow researchers to critically evaluate population genetics in a manner that was not feasible a decade ago. The ability to determine pathogenic allele frequencies by evaluation of the full coding sequences and not merely a single nucleotide polymorphism (SNP) or series of SNPs will lead to more accurate estimations of incidence. For demonstrative purposes, we analyzed the causative gene for the disorder Smith-Lemli-Opitz Syndrome (SLOS), the 7-dehydrocholesterol reductase (DHCR7) gene and determined both the carrier frequency for DHCR7 mutations, and predicted an expected incidence of the disorder. Estimations of the incidence of SLOS have ranged widely from 1:10,000 to 1:70,000 while the carrier frequency has been reported as high as 1 in 30. Using four exome data sets with a total of 17,836 chromosomes, we ascertained a carrier frequency of pathogenic DHRC7 mutations of 1.01%, and predict a SLOS disease incidence of 1/39,215 conceptions. This approach highlights yet another valuable aspect of the exome sequencing databases, to inform clinical and health policy decisions related to genetic counseling, prenatal testing and newborn screening.
C1 [Cross, J. L.; Iben, J.; Porter, F. D.; Wassif, C. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA.
[Simpson, C. L.; Bailey-Wilson, J. E.] NHGRI, Stat Genet Sect, Computat & Stat Genom Branch, US Dept HHS,NIH, Bethesda, MD 20892 USA.
[Thurm, A.; Swedo, S.] NIMH, Pediat & Dev Neurosci Branch, US Dept HHS, NIH, Bethesda, MD 20892 USA.
[Tierney, E.] Kennedy Krieger Inst, Dept Psychiat, Baltimore, MD USA.
[Biesecker, L. G.] NHGRI, Med Genom & Metab Genet Branch, US Dept HHS, NIH, Bethesda, MD 20892 USA.
RP Wassif, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Univ Oxford Res Associate, NIH, 9000 Rockville Pike Bldg CRC Room 1E-3288, Bethesda, MD 20892 USA.
EM wassifc@mail.nih.gov
OI Simpson, Claire/0000-0003-2244-7690; Cross, Joanna/0000-0003-2323-7142;
Bailey-Wilson, Joan/0000-0002-9153-2920; Wassif,
Christopher/0000-0002-2524-1420
FU NIH intramural research program, DHHS; Wellcome Trust [BWRXEN00]; Autism
Speaks
FX J. L. C., J. I., C.L., A. T., S. S., J.E.B-W., L. G. B., F. D. P., and
C. A. W. are all funded by the NIH intramural research program, DHHS. J.
L. C. receives funding from the Wellcome Trust [BWRXEN00] E. T. is
funded by Autism Speaks.
NR 19
TC 10
Z9 10
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9163
EI 1399-0004
J9 CLIN GENET
JI Clin. Genet.
PD JUN
PY 2015
VL 87
IS 6
SI SI
BP 570
EP 575
DI 10.1111/cge.12425
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA CH7YH
UT WOS:000354252200012
PM 24813812
ER
PT J
AU Dimond, EP
St Germain, D
Nacpil, LM
Zaren, HA
Swanson, SM
Minnick, C
Carrigan, A
Denicoff, AM
Igo, KE
Acoba, JD
Gonzalez, MM
McCaskill-Stevens, W
AF Dimond, Eileen P.
St Germain, Diane
Nacpil, Lianne M.
Zaren, Howard A.
Swanson, Sandra M.
Minnick, Christopher
Carrigan, Angela
Denicoff, Andrea M.
Igo, Kathleen E.
Acoba, Jared D.
Gonzalez, Maria M.
McCaskill-Stevens, Worta
TI Creating a "culture of research'' in a community hospital: Strategies
and tools from the National Cancer Institute Community Cancer Centers
Program
SO CLINICAL TRIALS
LA English
DT Article
DE Clinical trials; community; culture of research; community hospital
research; National Cancer Institute Community Cancer Centers Program
ID CLINICAL ONCOLOGY PROGRAM; TRIALS; PARTICIPATION; SITES
AB Background The value of community-based cancer research has long been recognized. In addition to the National Cancer Institute's Community Clinical and Minority-Based Oncology Programs established in 1983, and 1991 respectively, the National Cancer Institute established the National Cancer Institute Community Cancer Centers Program in 2007 with an aim of enhancing access to high-quality cancer care and clinical research in the community setting where most cancer patients receive their treatment. This article discusses strategies utilized by the National Cancer Institute Community Cancer Centers Program to build research capacity and create a more entrenched culture of research at the community hospitals participating in the program over a 7-year period.
Methods To facilitate development of a research culture at the community hospitals, the National Cancer Institute Community Cancer Centers Program required leadership or chief executive officer engagement; utilized a collaborative learning structure where best practices, successes, and challenges could be shared; promoted site-to-site mentoring to foster faster learning within and between sites; required research program assessments that spanned clinical trial portfolio, accrual barriers, and outreach; increased identification and use of metrics; and, finally, encouraged research team engagement across hospital departments (navigation, multidisciplinary care, pathology, and disparities) to replace the traditionally siloed approach to clinical trials.
Limitations The health-care environment is rapidly changing while complexity in research increases. Successful research efforts are impacted by numerous factors (e.g. institutional review board reviews, physician interest, and trial availability). The National Cancer Institute Community Cancer Centers Program sites, as program participants, had access to the required resources and support to develop and implement the strategies described. Metrics are an important component yet often challenging to identify and collect. The model requires a strong emphasis on outreach that challenges hospitals to improve and expand their reach, particularly into underrepresented populations and catchment areas. These efforts build on trust and a referral pipeline within the community which take time and significant commitment to establish.
Conclusion The National Cancer Institute Community Cancer Centers Program experience provides a relevant model to broadly address creating a culture of research in community hospitals that are increasingly networked via systems and consortiums. The strategies used align well with the National Cancer InstituteAmerican Society of Clinical Oncology Accrual Symposium recommendations for patient-/community-, physician-/provider-, and site-/organizational-level approaches to clinical trials; they helped sites achieve organizational culture shifts that enhanced their cancer research programs. The National Cancer Institute Community Cancer Centers Program hospitals reported that the strategies were challenging to implement yet proved valuable as they provided useful metrics for programmatic assessment, planning, reporting, and growth. While focused on oncology trials, these concepts may be useful within other disease-focused research as well.
C1 [Dimond, Eileen P.; St Germain, Diane; McCaskill-Stevens, Worta] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Nacpil, Lianne M.; Gonzalez, Maria M.] St Joseph Hosp, Orange, CA USA.
[Zaren, Howard A.] St Josephs Candler, Savannah, GA USA.
[Swanson, Sandra M.] Mercy Med Ctr, Des Moines, IA USA.
[Minnick, Christopher] Albert Einstein Healthcare Network, Philadelphia, PA USA.
[Carrigan, Angela; Igo, Kathleen E.] Leidos Biomed Res Inc, Clin Res Directorate, Clin Monitoring Res Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Denicoff, Andrea M.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Acoba, Jared D.] Queens Med Ctr, Honolulu, HI USA.
[Gonzalez, Maria M.] Providence St Joseph Med Ctr, Roy & Patricia Disney Family Canc Ctr, Burbank, CA USA.
RP Dimond, EP (reprint author), NCI, Canc Prevent Div, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM dimonde@mail.nih.gov
FU Federal funds from the National Cancer Institute, National Institutes of
Health [HHSN261200800001E]
FX This project has been funded in part with Federal funds from the
National Cancer Institute, National Institutes of Health (Contract No.
HHSN261200800001E).
NR 42
TC 5
Z9 5
U1 2
U2 11
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1740-7745
EI 1740-7753
J9 CLIN TRIALS
JI Clin. Trials
PD JUN
PY 2015
VL 12
IS 3
BP 246
EP 256
DI 10.1177/1740774515571141
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CH4EC
UT WOS:000353984100009
PM 25691600
ER
PT J
AU Remy, KE
Natanson, C
Klein, HG
AF Remy, Kenneth E.
Natanson, Charles
Klein, Harvey G.
TI The influence of the storage lesion(s) on pediatric red cell transfusion
SO CURRENT OPINION IN PEDIATRICS
LA English
DT Review
DE cell-free hemoglobin; critical care; red blood cell; storage lesion;
transfusion
ID CARDIAC-SURGERY PATIENTS; CRITICALLY-ILL PATIENTS; TRANSFERRIN-BOUND
IRON; OLDER STORED-BLOOD; LUNG INJURY TRALI; OVINE MODEL; PROLONGED
STORAGE; RANDOMIZED-TRIAL; FREE HEMOGLOBIN; AFFECT OUTCOMES
AB Purpose of review
This article will analyze and evaluate the current evidence regarding the use of older, longer-stored red blood cells (RBCs) for trans fusion in pediatric patients and will examine some of the postulated mechanisms of injury related to prolonged refrigerated storage of RBCs and studies reporting clinical outcomes.
Recent findings
Three randomized controlled trials and seven observational studies have been conducted entirely in pediatric patients. The outcomes, mortality and morbidity in critically ill patients and children undergoing cardiac surgery, and necrotizing enterocolitis in premature infants, have been inconsistent. However, many of these studies have been confounded by study design, mixed patient populations, red cell preparation, and other factors.
Summary
Further exploration into the possible deleterious effects of older, longer-stored RBC transfusions on mortality and morbidity in different pediatric populations is merited. Understanding the potential mechanisms of injury should help explain the clinical findings.
C1 [Remy, Kenneth E.] Washington Univ, Sch Med, Div Pediat Crit Care Med, Dept Pediat, St Louis, MO 63110 USA.
[Remy, Kenneth E.; Natanson, Charles] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Klein, Harvey G.] NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA.
RP Remy, KE (reprint author), Washington Univ, Sch Med, Div Pediat Crit Care, Dept Pediat, 660 S Euclid Ave, St Louis, MO 63110 USA.
EM Remy_k@kids.wustl.edu
NR 72
TC 2
Z9 2
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-8703
EI 1531-698X
J9 CURR OPIN PEDIATR
JI CURR. OPIN. PEDIATR.
PD JUN
PY 2015
VL 27
IS 3
BP 277
EP 285
DI 10.1097/MOP.0000000000000224
PG 9
WC Pediatrics
SC Pediatrics
GA CH7KJ
UT WOS:000354214800002
PM 25888156
ER
PT J
AU Donahue, R
Metzger, M
Bonifacino, A
Parker, D
Leitman, S
Cullis, H
Lienesch, M
AF Donahue, R.
Metzger, M.
Bonifacino, A.
Parker, D.
Leitman, S.
Cullis, H.
Lienesch, M.
TI OPTIMIZATION OF THE SPECTRA OPTIA FOR LEUKAPHERESIS OF VERY SMALL
SUBJECTS
SO CYTOTHERAPY
LA English
DT Meeting Abstract
C1 [Donahue, R.; Metzger, M.; Bonifacino, A.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
[Parker, D.; Lienesch, M.] Terumo BCT Inc, Lakewood, CO USA.
[Leitman, S.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1465-3249
EI 1477-2566
J9 CYTOTHERAPY
JI Cytotherapy
PD JUN
PY 2015
VL 17
IS 6
SU S
MA 273
BP S79
EP S80
PG 2
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Hematology; Medicine, Research & Experimental
SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research
& Experimental Medicine
GA CH6JK
UT WOS:000354142700252
ER
PT J
AU Frank, JA
Nguyen, B
Bresler, M
Milo, B
Kim, S
Burks, S
AF Frank, J. A.
Nguyen, B.
Bresler, M.
Milo, B.
Kim, S.
Burks, S.
TI ENHANCED STEM CELL AND PROGENITOR CELL HOMING FOLLOWING IV INJECTION TO
SKELETAL MUSCLE IN A MURINE MODEL OF MUSCULAR DYSTROPHY INDUCED BY
PULSED FOCUSED ULTRASOUND (pFUS)
SO CYTOTHERAPY
LA English
DT Meeting Abstract
C1 [Frank, J. A.; Nguyen, B.; Bresler, M.; Milo, B.; Kim, S.; Burks, S.] NIH, Frank Lab, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1465-3249
EI 1477-2566
J9 CYTOTHERAPY
JI Cytotherapy
PD JUN
PY 2015
VL 17
IS 6
SU S
MA 29
BP S15
EP S15
PG 1
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Hematology; Medicine, Research & Experimental
SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research
& Experimental Medicine
GA CH6JK
UT WOS:000354142700031
ER
PT J
AU Hanley, P
Melenhorst, J
Cruz, R
Martinez, C
Heslop, H
Barrett, J
Shpall, EJ
Bollard, C
AF Hanley, P.
Melenhorst, J.
Cruz, R.
Martinez, C.
Heslop, H.
Barrett, J.
Shpall, E. J.
Bollard, C.
TI CMVpp65-SPECIFIC T CELLS GENERATED FROM NAIVE T CELL POPULATIONS
RECOGNIZE ATYPICAL BUT NOT CANONICAL EPITOPES AND MAY BE PROTECTIVE IN
VIVO
SO CYTOTHERAPY
LA English
DT Meeting Abstract
C1 [Hanley, P.; Cruz, R.; Bollard, C.] Childrens Natl Med Ctr, Program Cell Enhancement & Technol Immunotherapy, Washington, DC 20010 USA.
[Melenhorst, J.] Univ Penn, Philadelphia, PA 19104 USA.
[Martinez, C.; Heslop, H.] BCm, Houston, TX USA.
[Barrett, J.] NIH, Bethesda, MD 20892 USA.
[Shpall, E. J.] MDACC, Houston, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1465-3249
EI 1477-2566
J9 CYTOTHERAPY
JI Cytotherapy
PD JUN
PY 2015
VL 17
IS 6
SU S
MA 10
BP S9
EP S10
PG 2
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Hematology; Medicine, Research & Experimental
SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research
& Experimental Medicine
GA CH6JK
UT WOS:000354142700012
ER
PT J
AU Lin, Y
Atwell, T
Weisbrod, A
Maas, M
Armstrong, A
Deeds, M
Bulur, P
Gustafson, M
Zhang, Z
Cordes, S
Porrata, L
Markovic, S
Johnston, P
Micallef, I
Inwards, D
Colgan, J
Ansell, S
Gastineau, D
Dietz, A
Witzig, T
AF Lin, Y.
Atwell, T.
Weisbrod, A.
Maas, M.
Armstrong, A.
Deeds, M.
Bulur, P.
Gustafson, M.
Zhang, Z.
Cordes, S.
Porrata, L.
Markovic, S.
Johnston, P.
Micallef, I.
Inwards, D.
Colgan, J.
Ansell, S.
Gastineau, D.
Dietz, A.
Witzig, T.
TI DENDRITIC CELL VACCINE TREATMENT FOR INDOLENT B-CELL NON-HODGKIN
LYMPHOMA: CLINICAL TRIAL IN PROGRESS
SO CYTOTHERAPY
LA English
DT Meeting Abstract
C1 [Lin, Y.; Atwell, T.; Weisbrod, A.; Maas, M.; Armstrong, A.; Deeds, M.; Bulur, P.; Gustafson, M.; Zhang, Z.; Porrata, L.; Markovic, S.; Johnston, P.; Micallef, I.; Inwards, D.; Colgan, J.; Ansell, S.; Gastineau, D.; Dietz, A.; Witzig, T.] Mayo Clin, Rochester, MN USA.
[Cordes, S.] NIH, Bethesda, MD 20892 USA.
RI Dietz, Allan/H-7414-2015; Gustafson, Michael/H-4056-2011
OI Dietz, Allan/0000-0003-3410-9621; Gustafson, Michael/0000-0002-5514-7072
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1465-3249
EI 1477-2566
J9 CYTOTHERAPY
JI Cytotherapy
PD JUN
PY 2015
VL 17
IS 6
SU S
MA 35
BP S17
EP S17
PG 1
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Hematology; Medicine, Research & Experimental
SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research
& Experimental Medicine
GA CH6JK
UT WOS:000354142700037
ER
PT J
AU Lu, K
West, K
Buckler, A
Tian, X
Cantilena, C
Anandi, P
Dunavin, N
Jain, N
Barrett, J
Battiwalla, M
AF Lu, K.
West, K.
Buckler, A.
Tian, X.
Cantilena, C.
Anandi, P.
Dunavin, N.
Jain, N.
Barrett, J.
Battiwalla, M.
TI CLINICAL AND LABORATORY PREDICTORS IMPACTING ALLOGENEIC PERIPHERAL BLOOD
STEM CELL MOBILIZATION
SO CYTOTHERAPY
LA English
DT Meeting Abstract
C1 [Lu, K.; Anandi, P.; Dunavin, N.; Jain, N.; Barrett, J.; Battiwalla, M.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[West, K.; Buckler, A.; Cantilena, C.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
[Tian, X.] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1465-3249
EI 1477-2566
J9 CYTOTHERAPY
JI Cytotherapy
PD JUN
PY 2015
VL 17
IS 6
SU S
MA 220
BP S66
EP S66
PG 1
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Hematology; Medicine, Research & Experimental
SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research
& Experimental Medicine
GA CH6JK
UT WOS:000354142700203
ER
PT J
AU Stroncek, D
Jin, P
Reems, JA
Cancelas, J
Nayak, R
Shaw, G
O'Brien, T
McKenna, D
Armant, M
Silberstein, L
Gee, A
Hei, D
Hematti, P
Civini, S
Sabatino, M
Robey, P
AF Stroncek, D.
Jin, P.
Reems, J-A
Cancelas, J.
Nayak, R.
Shaw, G.
O'Brien, T.
McKenna, D., Jr.
Armant, M.
Silberstein, L.
Gee, A.
Hei, D.
Hematti, P.
Civini, S.
Sabatino, M.
Robey, P.
TI COMPARISON OF BONE MARROW STROMAL CELL (BMSC) PRODUCTION METHODS AND
PRODUCTS FROM MULTIPLE CENTERS
SO CYTOTHERAPY
LA English
DT Meeting Abstract
C1 [Stroncek, D.; Jin, P.; Civini, S.; Sabatino, M.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Reems, J-A] Univ Utah, Cell Therapy & Regenerat Med, Salt Lake City, UT USA.
[Cancelas, J.; Nayak, R.] Univ Cincinnati, Hoxworth Blood Ctr, Cincinnati, OH USA.
[Cancelas, J.; Nayak, R.] Univ Cincinnati, Dept Pediat, Cincinnati, OH USA.
[Shaw, G.; O'Brien, T.] Natl Univ Ireland Galway, Natl Ctr Biomed Engn & Sci, Regenerat Med Inst, Galway, Ireland.
[McKenna, D., Jr.] Univ Minnesota, Mol & Cellular Therapeut, Minneapolis, MN USA.
[Armant, M.; Silberstein, L.] Boston Childrens Hosp, Ctr Human Cell Therapy, Programs Cellular & Mol Med, Boston, MA USA.
[Gee, A.] Methodist Hosp, Texas Childrens Hosp, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
[Gee, A.] Baylor Coll Med, Houston, TX 77030 USA.
[Hei, D.] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA.
[Hematti, P.] Univ Wisconsin, Dept Internal Med, Madison, WI USA.
[Robey, P.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
RI Robey, Pamela/H-1429-2011
OI Robey, Pamela/0000-0002-5316-5576
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1465-3249
EI 1477-2566
J9 CYTOTHERAPY
JI Cytotherapy
PD JUN
PY 2015
VL 17
IS 6
SU S
MA 175
BP S51
EP S51
PG 1
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Hematology; Medicine, Research & Experimental
SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research
& Experimental Medicine
GA CH6JK
UT WOS:000354142700160
ER
PT J
AU Bao, W
Yeung, E
Tobias, DK
Hu, FB
Vaag, AA
Chavarro, JE
Mills, JL
Grunnet, LG
Bowers, K
Ley, SH
Kiely, M
Olsen, S
Zhang, CL
AF Bao, Wei
Yeung, Edwina
Tobias, Deirdre K.
Hu, Frank B.
Vaag, Allan A.
Chavarro, Jorge E.
Mills, James L.
Grunnet, Louise G.
Bowers, Katherine
Ley, Sylvia H.
Kiely, Michele
Olsen, Sjurdur F.
Zhang, Cuilin
TI Long-term risk of type 2 diabetes mellitus in relation to BMI and weight
change among women with a history of gestational diabetes mellitus: a
prospective cohort study
SO DIABETOLOGIA
LA English
DT Article
DE BMI; Gestational diabetesmellitus; Type 2 diabetes mellitus; Weight
change
ID BODY-MASS INDEX; FOOD FREQUENCY QUESTIONNAIRE; LIFE-STYLE INTERVENTION;
PHYSICAL-ACTIVITY; GLUCOSE-INTOLERANCE; WAIST CIRCUMFERENCE; FOLLOW-UP;
PREGNANCY; DETERMINANTS; METAANALYSIS
AB Aims/hypothesis Women with a history of gestational diabetes mellitus (GDM) are advised to control their weight after pregnancy. We aimed to examine how adiposity and weight change influence the long-term risk of developing type 2 diabetes after GDM.
Methods We included 1,695 women who had incident GDM between 1991 and 2001, as part of the Diabetes & Women's Health study, and followed them until the return of the 2009 questionnaire. Body weight and incident type 2 diabetic cases were reported biennially. We defined baseline as the questionnaire period when women reported an incident GDM pregnancy. We estimated HRs and 95% CIs using Cox proportional hazards models. Results We documented 259 incident cases of type 2 diabetes during up to 18 years of follow-up. The adjusted HRs of type 2 diabetes associated with each 1 kg/m(2) increase in BMI were 1.16 (95% CI 1.12, 1.19) for baseline BMI and 1.16 (95% CI 1.13, 1.20) for most recent BMI. Moreover, each 5 kg increment of weight gain after GDM development was associated with a 27% higher risk of type 2 diabetes (adjusted HR 1.27; 95% CI 1.04, 1.54). Jointly, women who had a BMI >= 30.0 kg/m(2) at baseline and gained >= 5 kg after GDM had an adjusted HR of 43.19 (95% CI 13.60, 137.11), compared with women who had a BMI <25.0 kg/m(2) at baseline and gained <5 kg after GDM.
Conclusions/interpretation Baseline BMI, most recent BMI and weight gain after GDM were significantly and positively associated with risk of progression from GDM to type 2 diabetes.
C1 [Bao, Wei; Yeung, Edwina; Mills, James L.; Kiely, Michele; Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA.
[Tobias, Deirdre K.; Hu, Frank B.; Chavarro, Jorge E.; Ley, Sylvia H.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Tobias, Deirdre K.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Tobias, Deirdre K.] Harvard Univ, Sch Med, Boston, MA USA.
[Hu, Frank B.; Chavarro, Jorge E.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Hu, Frank B.; Chavarro, Jorge E.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Hu, Frank B.; Chavarro, Jorge E.] Harvard Univ, Sch Med, Boston, MA USA.
[Vaag, Allan A.; Grunnet, Louise G.] Rigshosp, Dept Endocrinol, DK-2100 Copenhagen, Denmark.
[Bowers, Katherine] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Biostat & Epidemiol, Cincinnati, OH 45229 USA.
[Olsen, Sjurdur F.] Statens Serum Inst, Dept Epidemiol Res, Ctr Fetal Programming, DK-2300 Copenhagen, Denmark.
RP Zhang, CL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd, Rockville, MD 20852 USA.
EM zhangcu@mail.nih.gov
RI Bowers, Katherine/N-5226-2015; Yeung, Edwina/F-5992-2015;
OI Yeung, Edwina/0000-0002-3851-2613; Bao, Wei/0000-0002-7301-5786
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health [HHSN275201000020C]; National Institutes of Health [DK58845,
CA50385, P30 DK46200, UM1 CA176726]; ADA [7-12-MN-34]
FX This study was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health (contract no.
HHSN275201000020C). NHS II was funded by research grants DK58845,
CA50385, P30 DK46200 and UM1 CA176726 from the National Institutes of
Health. DKT was supported by a mentored fellowship from the ADA (no.
7-12-MN-34).
NR 44
TC 13
Z9 13
U1 1
U2 15
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
EI 1432-0428
J9 DIABETOLOGIA
JI Diabetologia
PD JUN
PY 2015
VL 58
IS 6
BP 1212
EP 1219
DI 10.1007/s00125-015-3537-4
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CH2YX
UT WOS:000353893000011
PM 25796371
ER
PT J
AU Lietman, TM
Gebre, T
Abdou, A
Alemayehu, W
Emerson, P
Blumberg, S
Keenan, JD
Porco, TC
AF Lietman, Thomas M.
Gebre, Teshome
Abdou, Amza
Alemayehu, Wondu
Emerson, Paul
Blumberg, Seth
Keenan, Jeremy D.
Porco, Travis C.
TI The distribution of the prevalence of ocular chlamydial infection in
communities where trachoma is disappearing
SO EPIDEMICS
LA English
DT Article
DE Trachoma; Eradication; Mass drug administration; Transmission model;
Geometric distribution
ID CLUSTER-RANDOMIZED TRIAL; MASS ANTIBIOTIC DISTRIBUTIONS;
QUASI-STATIONARY DISTRIBUTION; AZITHROMYCIN; ELIMINATION; REDUCTION;
ETHIOPIA; DISEASE; RETURN; NEPAL
AB Mathematical models predict that the prevalence of infection in different communities where an infectious disease is disappearing should approach a geometric distribution. Trachoma programs offer an opportunity to test this hypothesis, as the World Health Organization (WHO) has targeted trachoma to be eliminated as a public health concern by the year 2020. We assess the distribution of the community prevalence of childhood ocular chlamydia infection from periodic, cross-sectional surveys in two areas of Ethiopia. These surveys were taken in a controlled setting, where infection was documented to be disappearing over time. For both sets of surveys, the geometric distribution had the most parsimonious fit of the distributions tested, and goodness-of-fit testing was consistent with the prevalence of each community being drawn from a geometric distribution. When infection is disappearing, the single sufficient parameter describing a geometric distribution captures much of the distributional information found from examining every community. The relatively heavy tail of the geometric suggests that the presence of an occasional high-prevalence community is to be expected, and does not necessarily reflect a transmission hot spot or program failure. A single cross-sectional survey can reveal which direction a program is heading. A geometric distribution of the prevalence of infection across communities may be an encouraging sign, consistent with a disease on its way to eradication. (C) 2015 The Authors. Published by Elsevier B.V.
C1 [Lietman, Thomas M.; Alemayehu, Wondu; Blumberg, Seth; Keenan, Jeremy D.; Porco, Travis C.] FI Proctor Fdn, San Francisco, CA USA.
[Lietman, Thomas M.; Alemayehu, Wondu; Keenan, Jeremy D.; Porco, Travis C.] Dept Ophthalmol, San Francisco, CA USA.
[Lietman, Thomas M.; Alemayehu, Wondu; Porco, Travis C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Gebre, Teshome; Emerson, Paul] Ctr Canc, Atlanta, GA USA.
[Abdou, Amza; Alemayehu, Wondu] Programme Natl Lutte Contre La Cecite, Niamey, Niger.
[Alemayehu, Wondu; Blumberg, Seth] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Alemayehu, Wondu] Berhan Hlth, Addis Ababa, Ethiopia.
RP Lietman, TM (reprint author), Univ Calif San Francisco, FI Proctor Fdn, Room S309 Med Sci,513 Parnassus Ave, San Francisco, CA 94143 USA.
EM tom.lietman@ucsf.edu
FU NIH NIGMS MIDAS [GM087728]; NEI [U10 EY016214]; NIH-Fogarty
International Center RAPIDD Program of the Science and Tenchnology
Directorate
FX NIH NIGMS MIDAS GM087728, NEI U10 EY016214, NIH-Fogarty International
Center RAPIDD Program of the Science and Tenchnology Directorate.
NR 31
TC 5
Z9 5
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1755-4365
J9 EPIDEMICS-NETH
JI Epidemics
PD JUN
PY 2015
VL 11
BP 85
EP 91
DI 10.1016/j.epidem.2015.03.003
PG 7
WC Infectious Diseases
SC Infectious Diseases
GA CI0CJ
UT WOS:000354403100011
PM 25979286
ER
PT J
AU Brady, OJ
Smith, DL
Scott, TW
Hay, SI
AF Brady, Oliver J.
Smith, David L.
Scott, Thomas W.
Hay, Simon I.
TI Dengue disease outbreak definitions are implicitly variable
SO EPIDEMICS
LA English
DT Article
DE Outbreak; Response; Dengue; Decision-making; Policy
ID PLASMODIUM-FALCIPARUM MALARIA; WEATHER-BASED PREDICTION; EPIDEMIC-PRONE
REGIONS; EARLY WARNING SYSTEM; PUBLIC-HEALTH; WESTERN KENYA;
VIRUS-DISEASE; PUERTO-RICO; CLIMATE; DETERMINANTS
AB Infectious diseases rarely exhibit simple dynamics. Outbreaks (defined as excess cases beyond response capabilities) have the potential to cause a disproportionately high burden due to overwhelming health care systems. The recommendations of international policy guidelines and research agendas are based on a perceived standardised definition of an outbreak characterised by a prolonged, high-caseload, extraseasonal surge. In this analysis we apply multiple candidate outbreak definitions to reported dengue case data from Brazil to test this assumption. The methods identify highly heterogeneous outbreak characteristics in terms of frequency, duration and case burden. All definitions identify outbreaks with characteristics that vary over time and space. Further, definitions differ in their timeliness of outbreak onset, and thus may be more or less suitable for early intervention. This raises concerns about the application of current outbreak guidelines for early warning/identification systems. It is clear that quantitatively defining the characteristics of an outbreak is an essential prerequisite for effective reactive response. More work is needed so that definitions of disease outbreaks can take into account the baseline capacities of treatment, surveillance and control. This is essential if outbreak guidelines are to be effective and generalisable across a range of epidemiologically different settings. (C) 2015 The Authors. Published by Elsevier B.V.
C1 [Brady, Oliver J.; Smith, David L.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford, England.
[Smith, David L.; Scott, Thomas W.; Hay, Simon I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Smith, David L.] Sanaria Inst Global Hlth & Trop Med, Rockville, MD USA.
[Scott, Thomas W.] Univ Calif Davis, Dept Entomol & Nematol, Davis, CA 95616 USA.
[Hay, Simon I.] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
RP Brady, OJ (reprint author), Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Tinbergen Bldg,South Parks Rd, Oxford, England.
EM oliver.brady.zoo@gmail.com; smitdave@gmail.com; twscott@ucdavis.edu;
simon.i.hay@gmail.com
RI Hay, Simon/F-8967-2015;
OI Hay, Simon/0000-0002-0611-7272; Brady, Oliver/0000-0002-3235-2129
FU BBSRC studentship; Wellcome Trust [095066]; Research and Policy in
Infectious Disease Dynamics (RAPIDD) program of the Science & Technology
Directorate, Department of Homeland Security; Fogarty International
Center, National Institutes of Health; Bill and Melinda Gates Foundation
[OPP1110495]; EU [21803]
FX OJB is funded by a BBSRC studentship. SIH is funded by a Senior Research
Fellowship from the Wellcome Trust (095066). SIH, DLS and TWS
acknowledge funding support from the Research and Policy in Infectious
Disease Dynamics (RAPIDD) program of the Science & Technology
Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health. DLS acknowledges
funding from the Bill and Melinda Gates Foundation (#OPP1110495). This
study was partially funded by EU grant 21803 IDAMS (http:\\www.idams.cu)
and is designated with IDAMS publication reference number IDAMS27.
NR 59
TC 12
Z9 12
U1 1
U2 13
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1755-4365
J9 EPIDEMICS-NETH
JI Epidemics
PD JUN
PY 2015
VL 11
BP 92
EP 102
DI 10.1016/j.epidem.2015.03.002
PG 11
WC Infectious Diseases
SC Infectious Diseases
GA CI0CJ
UT WOS:000354403100012
PM 25979287
ER
PT J
AU Kramer, SC
Bansal, S
AF Kramer, S. C.
Bansal, S.
TI Assessing the use of antiviral treatment to control influenza
SO EPIDEMIOLOGY AND INFECTION
LA English
DT Article
DE Antiviral drugs; control; infectious disease epidemiology; influenza;
influenza vaccines
ID RANDOMIZED CONTROLLED-TRIAL; PANDEMIC H1N1 2009; SEASONAL INFLUENZA;
HOUSEHOLD TRANSMISSION; PROTECTIVE EFFICACY; VIRUS INFECTION;
UNITED-STATES; HONG-KONG; VACCINE; CHILDREN
AB Vaccines are the cornerstone of influenza control policy, but can suffer from several drawbacks. Seasonal influenza vaccines are prone to production problems and low efficacies, while pandemic vaccines are unlikely to be available in time to slow a rapidly spreading global outbreak. Antiviral therapy was found to be beneficial during the influenza A(H1N1)pdm09 pandemic even with limited use; however, antiviral use has decreased further since then. We sought to determine the role antiviral therapy can play in pandemic and seasonal influenza control using conservative estimates of antiviral efficacy, and to assess if conservative but targeted strategies could be employed to optimize the use of antivirals. Using an age-structured contact network model for an urban population, we compared the transmission-blocking ability of a conservative antiviral therapy strategy to the susceptibility-reducing effects of a robust influenza vaccine. Our results show that while antiviral therapy cannot replace a robust influenza vaccine, it can play a role in reducing attack rates and eliminating outbreaks, and could significantly reduce public health burden when vaccine is either unavailable or ineffective. We also found that antiviral therapy, by treating those who are infected, is naturally a highly optimized strategy, and need not be improved upon with expensive targeted campaigns.
C1 [Kramer, S. C.; Bansal, S.] Georgetown Univ, Dept Biol, Washington, DC 20057 USA.
[Bansal, S.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Bansal, S (reprint author), 406 Reiss Sci Bldg,37th & O St, Washington, DC 20057 USA.
EM sb753@georgetown.edu
OI Bansal, Shweta/0000-0002-1740-5421
FU Howard Hughes Medical Institute through the Precollege and Undergraduate
Science Education Program; RAPIDD Program of the Science & Technology
Directorate, Department of Homeland Security; Fogarty International
Center, National Institutes of Health
FX We gratefully acknowledge Lauren Ancel Meyers for use of the Vancouver
urban contact network. This work was funded by a grant to Georgetown
University from the Howard Hughes Medical Institute through the
Precollege and Undergraduate Science Education Program; and the RAPIDD
Program of the Science & Technology Directorate, Department of Homeland
Security and the Fogarty International Center, National Institutes of
Health.
NR 40
TC 2
Z9 2
U1 0
U2 4
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0950-2688
EI 1469-4409
J9 EPIDEMIOL INFECT
JI Epidemiol. Infect.
PD JUN
PY 2015
VL 143
IS 8
BP 1621
EP 1631
DI 10.1017/S0950268814002520
PG 11
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA CH5FQ
UT WOS:000354061100008
PM 25274250
ER
PT J
AU Mascalzoni, D
Dove, ES
Rubinstein, Y
Dawkins, HJS
Kole, A
McCormack, P
Woods, S
Riess, O
Schaefer, F
Lochmuller, H
Knoppers, BM
Hansson, M
AF Mascalzoni, Deborah
Dove, Edward S.
Rubinstein, Yaffa
Dawkins, Hugh J. S.
Kole, Anna
McCormack, Pauline
Woods, Simon
Riess, Olaf
Schaefer, Franz
Lochmueller, Hanns
Knoppers, Bartha M.
Hansson, Mats
TI International Charter of principles for sharing bio-specimens and data
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID BROAD CONSENT; BIOBANKS; PRIVACY; ETHICS
AB There is a growing international agreement on the need to provide greater access to research data and bio-specimen collections to optimize their long-term value and exploit their potential for health discovery and validation. This is especially evident for rare disease research. Currently, the rising value of data and bio-specimen collections does not correspond with an equal increase in data/sample-sharing and data/sample access. Contradictory legal and ethical frameworks across national borders are obstacles to effective sharing: more specifically, the absence of an integrated model proves to be a major logistical obstruction. The Charter intends to amend the obstacle by providing both the ethical foundations on which data sharing should be based, as well as a general Material and Data Transfer Agreement (MTA/DTA). This Charter is the result of a careful negotiation of different stakeholders' interest and is built on earlier consensus documents and position statements, which provided the general international legal framework. Further to this, the Charter provides tools that may help accelerate sharing. The Charter has been formulated to serve as an enabling tool for effective and transparent data and bio-specimen sharing and the general MTA/DTA constitutes a mechanism to ensure uniformity of access across projects and countries, and may be regarded as a consistent basic agreement for addressing data and material sharing globally. The Charter is forward looking in terms of emerging issues from the perspective of a multi-stakeholder group, and where possible, provides strategies that may address these issues.
C1 [Mascalzoni, Deborah; Hansson, Mats] Uppsala Univ, Ctr Res Eth & Bioeth, SE-75122 Uppsala, Sweden.
[Mascalzoni, Deborah] EURAC Res, Ctr Biomed, Bolzano, Italy.
[Dove, Edward S.; Knoppers, Bartha M.] McGill Univ, Ctr Genom & Policy, Montreal, PQ, Canada.
[Rubinstein, Yaffa] NIH, Off Rare Dis Res, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Dawkins, Hugh J. S.] Dept Hlth, Off Populat Hlth Genom, Perth, WA, Australia.
[Dawkins, Hugh J. S.] Curtin Univ Technol, Curtin Hlth Innovat Res Inst, Ctr Populat Hlth Res, Bentley, WA 6102, Australia.
[Dawkins, Hugh J. S.] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia.
[Dawkins, Hugh J. S.] Murdoch Univ, Ctr Comparat Genom, Murdoch, WA 6150, Australia.
[Kole, Anna] EURORDIS, Rare Dis Europe, Paris, France.
[McCormack, Pauline; Woods, Simon; Lochmueller, Hanns] Newcastle Univ, PEALS Policy Eth & Life Sci Res Ctr, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Riess, Olaf] Univ Tubingen, Inst Med Genet & Appl Genom, Tubingen, Germany.
[Schaefer, Franz] Univ Heidelberg Hosp, Pediat Nephrol Div, Heidelberg, Germany.
[Schaefer, Franz] Newcastle Univ, Inst Med Genet, Int Ctr Life, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
RP Mascalzoni, D (reprint author), Uppsala Univ, Ctr Res Eth & Bioeth, BMC, Husargatan 3,Entrance A11 Box 564, SE-75122 Uppsala, Sweden.
EM deborah.mascalzoni@crb.uu.se
FU European Union Seventh Framework Programme (FP7) [305444, 305121,
305608]; RD Connect from the Australian National Health and Medical
Research Council under the NHMRC-European Union Collaborative Research
Grants scheme' [APP1055319]; Innovative Medicines Initiative project
BTCure [115142-1]; BioBanking and Molecular Resource Infrastructure of
Sweden project (Swedish Research Council); Euro-TEAM; BiobankCloud;
BioSHaRE and Biobanking and Biomolecular Resources Research
Infrastructure (BBMRI)LPC [313010]
FX We thank the RD Connect Patient Ethics Council and RD Connect Patient
Advisory Council (Jean Jacques Cassiman, Tracy Dudding, Muriel Gevrey,
Emma Heslop, Joseph Irwin, Julian Isla, Sigurdur Johannesson, Lydia
Lemonnier, Chantal Loirat, Dorthe Lykke, Milan Macek, Caron Molster, Kay
Parkinson, Odile Perrousseaux, Marita Pohlschmidt, Daniel Renault, Peter
Reussner, Francoise Rouault, Balthasar Schaap, Inge Schwersenz, Chris
Sotirelis, Volker Straub, Oliver Timmis, Johannes van Delden, Marieke
van Meel, Elizabeth Vroom, Urban Wiesing) and all RD-connect partners
for their valuable inputs. This work has been supported by the European
Union Seventh Framework Programme (FP7/2007-2013) under grant agreements
no. 305444 (RD-Connect), 305121 (Neuromics), and no. 305608 (EURenOmics)
and RD Connect from the Australian National Health and Medical Research
Council APP1055319 under the NHMRC-European Union Collaborative Research
Grants scheme'. In addition, DM and MH have received funding from the
Innovative Medicines Initiative project BTCure (grant agreement no.
115142-1), the BioBanking and Molecular Resource Infrastructure of
Sweden project (financed by the Swedish Research Council), Euro-TEAM,
BiobankCloud, BioSHaRE and Biobanking and Biomolecular Resources
Research Infrastructure (BBMRI)LPC (313010). BMK and ESD wish to thank
the Government of Canada through Genome Canada and the Canadian
Institutes of Health Research, the Quebec Breast Cancer Foundation, and
the Ministere de l'enseignement superieur, de la recherche, de la
science et de la technologie du Quebec through Genome Quebec. The
funders had no influence on the design or the writing of the article.
NR 29
TC 22
Z9 23
U1 1
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
EI 1476-5438
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD JUN
PY 2015
VL 23
IS 6
BP 721
EP 728
DI 10.1038/ejhg.2014.197
PG 8
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CI1BG
UT WOS:000354474600008
PM 25248399
ER
PT J
AU Das, S
Stuart, PE
Ding, J
Tejasvi, T
Li, YM
Tsoi, LC
Chandran, V
Fischer, J
Helms, C
Duffin, KC
Voorhees, JJ
Bowcock, AM
Krueger, GG
Lathrop, GM
Nair, RP
Rahman, P
Abecasis, GR
Gladman, D
Elder, JT
AF Das, Sayantan
Stuart, Philip E.
Ding, Jun
Tejasvi, Trilokraj
Li, Yanming
Tsoi, Lam C.
Chandran, Vinod
Fischer, Judith
Helms, Cynthia
Duffin, Kristina Callis
Voorhees, John J.
Bowcock, Anne M.
Krueger, Gerald G.
Lathrop, G. Mark
Nair, Rajan P.
Rahman, Proton
Abecasis, Goncalo R.
Gladman, Dafna
Elder, James T.
TI Fine mapping of eight psoriasis susceptibility loci
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; ANALYSIS IDENTIFIES 3; RHEUMATOID-ARTHRITIS;
HLA-C; COMPLEX DISEASES; CROHN DISEASE; RESPONSES; DISEQUILIBRIUM;
HERITABILITY; DISCOVERY
AB Previous studies have identified 41 independent genome-wide significant psoriasis susceptibility loci. After our first psoriasis genome-wide association study, we designed a custom genotyping array to fine-map eight genome-wide significant susceptibility loci known at that time (IL23R, IL13, IL12B, TNIP1, MHC, TNFAIP3, IL23A and RNF114) enabling genotyping of 2269 single-nucleotide polymorphisms (SNPs) in the eight loci for 2699 psoriasis cases and 2107 unaffected controls of European ancestry. We imputed these data using the latest 1000 Genome reference haplotypes, which included both indels and SNPs, to increase the marker density of the eight loci to 49 239 genetic variants. Using stepwise conditional association analysis, we identified nine independent signals distributed across six of the eight loci. In the major histocompatibility complex (MHC) region, we detected three independent signals at rs114255771 (P = 2.94 x 10(-74)), rs6924962 (P = 3.21 x 10(-19)) and rs892666 (P = 1.11 x 10(-10)). Near IL12B we detected two independent signals at rs62377586 (P = 7.42 x 10(-16)) and rs918518 (P = 3.22 x 10(-11)). Only one signal was observed in each of the TNIP1 (rs17728338; P = 4.15 x 10(-13)), IL13 (rs1295685; P = 1.65 x 10(-7)), IL23A (rs61937678; P = 1.82 x 10(-7)) and TNFAIP3 (rs642627; P = 5.90 x 10(-7)) regions. We also imputed variants for eight HLA genes and found that SNP rs114255771 yielded a more significant association than any HLA allele or amino-acid residue. Further analysis revealed that the HLA-C*06-B*57 haplotype tagged by this SNP had a significantly higher odds ratio than other HLA-C*06-bearing haplotypes. The results demonstrate allelic heterogeneity at IL12B and identify a high-risk MHC class I haplotype, consistent with the existence of multiple psoriasis effectors in the MHC.
C1 [Das, Sayantan; Ding, Jun; Li, Yanming; Tsoi, Lam C.; Abecasis, Goncalo R.] Univ Michigan, Ctr Stat Genet, Dept Biostat, Ann Arbor, MI 48109 USA.
[Stuart, Philip E.; Tejasvi, Trilokraj; Voorhees, John J.; Nair, Rajan P.; Elder, James T.] Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA.
[Ding, Jun] NIA, Lab Genet, NIH, Baltimore, MD 21224 USA.
[Chandran, Vinod; Gladman, Dafna] Univ Toronto, Dept Med, Div Rheumatol, Toronto, ON, Canada.
[Fischer, Judith; Lathrop, G. Mark] Commissariat Energie Atom, Inst Genom, Ctr Natl Genotypage, Evry, France.
[Helms, Cynthia; Bowcock, Anne M.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England.
[Duffin, Kristina Callis; Krueger, Gerald G.] Univ Utah, Dept Dermatol, Salt Lake City, UT USA.
[Rahman, Proton] Mem Univ, Dept Med, St John, NF, Canada.
[Gladman, Dafna] Toronto Western Res Inst, Ctr Prognosis Studies Rheumat Dis, Psoriat Arthrit Program, Toronto, ON, Canada.
[Elder, James T.] Ann Arbor Veteran Affairs Hosp, Ann Arbor, MI USA.
RP Abecasis, GR (reprint author), Univ Michigan, Ctr Stat Genet, Dept Biostat, M4614 SPH I Tower,1415 Washington Hts, Ann Arbor, MI 48109 USA.
EM goncalo@umich.edu
RI Fischer, Judith/E-6327-2016;
OI Bowcock, Anne/0000-0001-8691-9090; Tsoi, Lam Cheung/0000-0003-1627-5722
FU NIH [R01AR042742, R01AR054966, R01AR050511, R01AR050266, R01AR062382];
Krembil Foundation; Ann Arbor Veterans Affairs Hospital; National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK);
National Institute of Allergy and Infectious Diseases (NIAID); National
Human Genome Research Institute (NHGRI); National Institute of Child
Health and Human Development; Juvenile Diabetes Research Foundation
International (JDRF) [U01 DK062418]; CIHR
FX We thank all the psoriasis patients and normal controls who contributed
samples to this study. This work was supported by NIH Grants
R01AR042742, R01AR054966, R01AR050511, R01AR050266 and R01AR062382. The
University of Toronto Psoriatic Arthritis Program is supported by the
Krembil Foundation and the CIHR. JTE is supported by the Ann Arbor
Veterans Affairs Hospital. This research uses resources provided by the
Type 1 Diabetes Genetics Consortium (T1DGC); a collaborative clinical
study sponsored by the National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK); National Institute of Allergy and Infectious
Diseases (NIAID); National Human Genome Research Institute (NHGRI);
National Institute of Child Health and Human Development; Juvenile
Diabetes Research Foundation International (JDRF), supported by U01
DK062418.
NR 51
TC 4
Z9 4
U1 2
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
EI 1476-5438
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD JUN
PY 2015
VL 23
IS 6
BP 844
EP 853
DI 10.1038/ejhg.2014.172
PG 10
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CI1BG
UT WOS:000354474600026
PM 25182136
ER
PT J
AU Li, FY
Chaigne-Delalande, B
Rao, VK
Zhang, Y
Matthews, H
Kuijpers, T
Su, H
Uzel, G
Lenardo, MJ
AF Li, Feng-Yen
Chaigne-Delalande, Benjamin
Rao, V. Koneti
Zhang, Yu
Matthews, Helen
Kuijpers, Taco (TW)
Su, Helen
Uzel, Gulbu
Lenardo, Michael J.
TI Clinical utility gene card for: X-linked immunodeficiency with magnesium
defect, Epstein-Barr virus infection, and neoplasia (XMEN)
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Editorial Material
ID NKG2D
C1 [Li, Feng-Yen; Chaigne-Delalande, Benjamin; Rao, V. Koneti; Matthews, Helen; Lenardo, Michael J.] NIAID, Mol Dev Immune Syst Sect, Clin Genom Unit, Immunol Lab,NIH, Bethesda, MD 20892 USA.
[Zhang, Yu; Su, Helen] NIAID, Human Immunol Dis Unit, Lab Host Def, NIH, Bethesda, MD 20892 USA.
[Kuijpers, Taco (TW)] Univ Amsterdam, Acad Med Ctr, Pediat Immunol & Infect Dis, NL-1105 AZ Amsterdam, Netherlands.
[Uzel, Gulbu] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Rao, VK (reprint author), NIAID, Mol Dev Immune Syst Sect, Clin Genom Unit, Immunol Lab,NIH, Bldg 10,Room 11N311,10 Ctr Dr MSC 1892, Bethesda, MD 20892 USA.
EM koneti@nih.gov; lenardo@nih.gov
RI Su, Helen/H-9541-2015
OI Su, Helen/0000-0002-5582-9110
NR 5
TC 0
Z9 0
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
EI 1476-5438
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD JUN
PY 2015
VL 23
IS 6
DI 10.1038/ejhg.2014.179
PG 4
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CI1BG
UT WOS:000354474600004
ER
PT J
AU Pretegiani, E
Rosini, F
Federighi, P
Cerase, A
Dotti, MT
Rufa, A
AF Pretegiani, E.
Rosini, F.
Federighi, P.
Cerase, A.
Dotti, M. T.
Rufa, A.
TI Pendular nystagmus, palatal tremor and progressive ataxia in
GM2-gangliosidosis
SO EUROPEAN JOURNAL OF NEUROLOGY
LA English
DT Letter
DE ataxia; GM2-gangliosidosis; palatal tremor; pendular nystagmus; Sandhoff
disease
ID OCULOPALATAL TREMOR; DISEASE
C1 [Pretegiani, E.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
[Pretegiani, E.; Rosini, F.; Federighi, P.; Dotti, M. T.; Rufa, A.] Univ Siena, Dept Med Surg & Neurol Sci, I-53100 Siena, Italy.
[Cerase, A.] Azienda Osped Univ Senese, Neuroimaging & Neurointervent Unit, Siena, Italy.
RP Pretegiani, E (reprint author), NEI, NIH, 49 Convent Dr,Room 2A50, Bethesda, MD 20892 USA.
EM elena.pretegiani@nih.gov
NR 7
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1351-5101
EI 1468-1331
J9 EUR J NEUROL
JI Eur. J. Neurol.
PD JUN
PY 2015
VL 22
IS 6
BP E67
EP E69
DI 10.1111/ene.12661
PG 3
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CH4HP
UT WOS:000353994900001
PM 25916337
ER
PT J
AU Stevens, WD
Tessler, MH
Peng, CS
Martin, A
AF Stevens, W. Dale
Tessler, Michael Henry
Peng, Cynthia S.
Martin, Alex
TI Functional Connectivity Constrains the Category-Related Organization of
Human Ventral Occipitotemporal Cortex
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE functional MRI; resting-state; tools; objects; scenes; parahippocampal
place area; hemispheric asymmetry; lateralization; concepts;
localization
ID FUSIFORM FACE AREA; SELECTIVE CORTICAL REGIONS; AUTISM SPECTRUM
DISORDERS; GLOBAL SIGNAL REGRESSION; RESTING HUMAN BRAIN; HUMAN OBJECT
AREAS; WORD FORM AREA; MANIPULATABLE OBJECTS; TEMPORAL CORTEX;
INDIVIDUAL VARIABILITY
AB One of the most robust and oft-replicated findings in cognitive neuroscience is that several spatially distinct, functionally dissociable ventral occipitotemporal cortex (VOTC) regions respond preferentially to different categories of concrete entities. However, the determinants of this category-related organization remain to be fully determined. One recent proposal is that privileged connectivity of these VOTC regions with other regions that store and/or process category-relevant properties may be a major contributing factor. To test this hypothesis, we used a multicategory functional magnetic resonance imaging (MRI) localizer to individually define category-related brain regions of interest (ROIs) in a large group of subjects (n=33). We then used these ROIs in resting-state functional connectivity MRI analyses to explore spontaneous functional connectivity among these regions. We demonstrate that during rest, distinct category-preferential VOTC regions show differentially stronger functional connectivity with other regions that have congruent category-preference, as defined by the functional localizer. Importantly, a tool-preferential region in the left medial fusiform gyrus showed differentially stronger functional connectivity with other left lateralized cortical regions associated with perceiving and knowing about common toolsposterior middle temporal gyrus (involved in perception of nonbiological motion), lateral parietal cortex (critical for reaching, grasping, manipulating), and ventral premotor cortex (involved in storing/executing motor programs)relative to other category-related regions in VOTC of both the right and left hemisphere. Our findings support the claim that privileged connectivity with other cortical regions that store and/or process category-relevant properties constrains the category-related organization of VOTC. Hum Brain Mapp 36:2187-2206, 2015. (c) Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Stevens, W. Dale; Tessler, Michael Henry; Peng, Cynthia S.; Martin, Alex] NIMH, Sect Cognit Neuropsychol, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
RP Stevens, WD (reprint author), York Univ, Dept Psychol, Sherman Hlth Sci Res Ctr, 281 Ian Macdonald Blvd, Toronto, ON M3J 1P3, Canada.
EM stevensd@yorku.ca
FU National Institute of Mental Health, National Institutes of Health,
Division of Intramural Research
FX Contract grant sponsor: The National Institute of Mental Health,
National Institutes of Health, Division of Intramural Research.
NR 83
TC 11
Z9 11
U1 4
U2 16
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1065-9471
EI 1097-0193
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD JUN
PY 2015
VL 36
IS 6
BP 2187
EP 2206
DI 10.1002/hbm.22764
PG 20
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA CH4AF
UT WOS:000353972000013
PM 25704493
ER
PT J
AU Weise, CM
Thiyyagura, P
Reiman, EM
Chen, KW
Krakoff, J
AF Weise, Christopher M.
Thiyyagura, Pradeep
Reiman, Eric M.
Chen, Kewei
Krakoff, Jonathan
TI A Potential Role for the Midbrain in Integrating Fat-Free Mass
Determined Energy Needs: An (H2O)-O-15 PET Study
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE energy homeostasis; hunger; brain; body composition; regional cerebral
blood flow
ID MEDIAL PREFRONTAL CORTEX; VISUAL FOOD CUES; PERIAQUEDUCTAL GRAY;
NEURONAL RESPONSE; FEEDING-BEHAVIOR; CINGULATE CORTEX; BODY-COMPOSITION;
MACAQUE MONKEYS; BRAIN; NETWORKS
AB Little is known on how sensing of energy needs is centrally represented, integrated, and translated into the behavioral aspects of energy homeostasis. Fat free mass (FFM) is the major determinant of energy expenditure. We investigated how interindividual variances in FFM relate to neuronal activity in humans. Healthy adults (n=64, 21F/43M; age 31.3 +/- 9.1y; percentage of body fat [PFAT] 25.6 +/- 10.7%; BMI 30.4 +/- 9) underwent a 36h fast and subsequent (H2O)-O-15 positron emission tomographic (PET) measurement of regional cerebral blood flow (rCBF). Multiple variable regression analysis revealed significant associations of FFM with rCBF within the midbrain [including parts of the periaqueductal gray (PAG), ventral tegmental area (VTA), thalamic and hypothalamic regions], the bilateral parahippocampal region, left anterior cingulate, left insular cortex, right cerebellum, and distinct regions within the temporal and occipital cortex. In contrast, no significant associations were found for fat mass (FM). We investigated the potential functional-anatomical link between FFM and central regulation of food intake by performing a conjunction analysis of FFM and the perceived hunger feelings. This showed a significant overlap within the midbrain PAG. Mediation analysis demonstrated a significant indirect effect of FFM on hunger with PAG rCBF as mediator. Most regions we found to be associated with FFM form part in ascending homeostatic pathways and cortical circuitries implicated in the regulation of basic bodily functions indicating a potential role of these central networks in the integration of FFM determined energy needs. Hum Brain Mapp 36:2406-2415, 2015. (c) 2015 Wiley Periodicals, Inc.
C1 [Weise, Christopher M.; Krakoff, Jonathan] NIDDK, Obes & Diabet Clin Res Sect, NIH, DHHS, Phoenix, AZ USA.
[Weise, Christopher M.] Univ Leipzig, Dept Neurol, Liebigstr 20, D-04103 Leipzig, Germany.
[Thiyyagura, Pradeep; Reiman, Eric M.; Chen, Kewei] Banner Alzheimers Inst, Dept Psychiat, Phoenix, AZ USA.
[Reiman, Eric M.] Translat Genom Res Inst, Neurogen Div, Phoenix, AZ USA.
RP Weise, CM (reprint author), Univ Leipzig, Dept Neurol, Liebigstr 20, D-04103 Leipzig, Germany.
EM christopher.weise@medizin.uni-leipzig.de
FU NIH; National Institute of Diabetes, Digestive and Kidney Diseases
(NIDDK)
FX Contract grant sponsors: Intramural Research Program of the NIH, The
National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK)
NR 64
TC 6
Z9 6
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1065-9471
EI 1097-0193
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD JUN
PY 2015
VL 36
IS 6
BP 2406
EP 2415
DI 10.1002/hbm.22780
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA CH4AF
UT WOS:000353972000029
PM 25766283
ER
PT J
AU Vargas-Inchaustegui, DA
Xiao, P
Demberg, T
Pal, R
Robert-Guroff, M
AF Vargas-Inchaustegui, Diego A.
Xiao, Peng
Demberg, Thorsten
Pal, Ranajit
Robert-Guroff, Marjorie
TI Therapeutic envelope vaccination in combination with antiretroviral
therapy temporarily rescues SIV-specific CD4(+) T-cell-dependent natural
killer cell effector responses in chronically infected rhesus macaques
SO IMMUNOLOGY
LA English
DT Article
DE antiretroviral therapy; envelope immunization; natural killer cells; T
cells
ID SIMIAN IMMUNODEFICIENCY VIRUS; NK CELLS; HIV-INFECTION; INNATE IMMUNITY;
LYMPH-NODES; IFN-GAMMA; IN-VIVO; ANTIBODIES; MEMORY; ACTIVATION
AB Natural killer (NK) cells are essential components of the immune system, and due to their rapid response potential, can have a great impact during early anti-viral immune responses. We have previously shown that interleukin-2-dependent NK and CD4(+) T-cell co-operative immune responses exist in long-term simian immunodeficiency virus (SIV) -infected controlling macaques and can be rescued in SIV-infected non-controlling macaques by a short course of antiretroviral therapy (ART). Given that co-operative responses may play an important role in disease prevention and therapeutic treatment, in the present study we sought to determine if these responses can be enhanced in chronically SIV-infected macaques by vaccination with a single-dose of envelope protein given during ART. To this end, we treated 14 chronically SIV-infected macaques with ART for 11weeks and gave 10 of these macaques a single intramuscular dose of SIV gp120 at week 9 of treatment. ART significantly decreased plasma and mucosal viral loads, increased the numbers of circulating CD4(+) T cells in all macaques, and increased T-cell-dependent envelope- and gag-specific interferon- and tumour necrosis factor- production by circulatory CD56(+) NK cells. The therapeutic envelope immunization resulted in higher envelope-specific responses compared with those in macaques that received ART only. Functional T-cell responses restored by ART and therapeutic Env immunization were correlated with transiently reduced plasma viraemia levels following ART release. Collectively our results indicate that SIV-specific T-cell-dependent NK cell responses can be efficiently rescued by ART in chronically SIV-infected macaques and that therapeutic immunization may be beneficial in previously vaccinated individuals.
C1 [Vargas-Inchaustegui, Diego A.; Xiao, Peng; Demberg, Thorsten; Robert-Guroff, Marjorie] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA.
[Pal, Ranajit] Adv Biosci Labs Inc, Rockville, MD USA.
RP Robert-Guroff, M (reprint author), NCI, NIH, 41 Medlars Dr,Bldg 41,Room D804, Bethesda, MD 20892 USA.
EM guroffm@mail.nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute
FX We gratefully acknowledge the animal caretakers at Advanced BioScience
Laboratories and Katherine McKinnon (Vaccine Branch Flow Core, NCI/NIH)
for expert advice. The following reagents were obtained through the NIH
Nonhuman Primate Reagent Resource: QDot655 anti-CD4. The following
reagents were obtained through the AIDS Research and Reference Reagent
Program, Division of AIDS, NIAID, NIH: SIVmac239 Gag and Env peptides
(complete sets). This study was supported by the Intramural Research
Program of the NIH, National Cancer Institute.
NR 43
TC 1
Z9 1
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0019-2805
EI 1365-2567
J9 IMMUNOLOGY
JI Immunology
PD JUN
PY 2015
VL 145
IS 2
BP 288
EP 299
DI 10.1111/imm.12447
PG 12
WC Immunology
SC Immunology
GA CH6ZN
UT WOS:000354185400011
PM 25626488
ER
PT J
AU Kirkland, RS
Nanda, RH
Alazraki, A
Esiashvili, N
AF Kirkland, Robert S.
Nanda, Ronica H.
Alazraki, Adina
Esiashvili, Natia
TI Influence of Pulmonary Nodules on Chest Computed Tomography and Risk of
Recurrence in Stage IV Wilms Tumor
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID CT; METASTASES
AB Purpose: Chest computed tomography (CT) is currently accepted as the main modality for initial disease staging and response assessment in Wilms tumor (WT). However, there is great variability in the number and size of lung metastases at the time of diagnosis and after induction chemotherapy. There is a lack of clinical evidence as to how this variability in tumor burden affects choice of therapy and disease outcome. This study sought to evaluate a previously proposed lung metastases risk stratification system based on CT findings and clinical outcomes in stage IV WT patients.
Methods and Materials: Thirty-five pediatric patients with a diagnosis of stage IV WT with evaluable pre- and postdiagnosis CT scans between 1997 and 2012 were included in the analysis. Patients were divided into low-, intermediate-, and high-risk categories based on the size and number of pulmonary metastases before and after 6 weeks of chemotherapy. Association of the lung risk groups with lung recurrence-free survival and overall survival at each time point was analyzed with relevant covariates.
Results: Risk group distribution both at diagnosis and after induction chemotherapy was not influenced by tumor histology. Initial risk grouping suggested an association with disease-free survival at 5 years (P=. 074); however, the most significant correlation was with postinduction chemotherapy disease status (PZ. 027). In patients with an intermediate or high burden of disease after 6 weeks of chemotherapy, despite receiving whole-lung and boost irradiation, survival outcomes were poorer.
Conclusions: Pulmonary tumor burden in stage IV WTon chest CT can predict disease outcome. Patients with intermediate-or low-risk disease, especially after induction therapy, have a higher risk for recurrence. After prospective validation, this method may become a valuable tool in adaptation of therapy to improve outcome. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Kirkland, Robert S.] NIH, Bethesda, MD 20892 USA.
[Nanda, Ronica H.; Esiashvili, Natia] Emory Univ, Winship Canc Inst, Dept Radiat Oncol, Atlanta, GA 30322 USA.
[Alazraki, Adina] Childrens Healthcare Atlanta, Aflac Canc Ctr, Dept Radiol, Atlanta, GA USA.
RP Nanda, RH (reprint author), 1365 Clifton Rd NE,Ste A1301, Atlanta, GA 30322 USA.
EM rhazari@emory.edu
NR 12
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JUN 1
PY 2015
VL 92
IS 2
BP 332
EP 338
DI 10.1016/j.ijrobp.2015.01.012
PG 7
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA CH4FO
UT WOS:000353989000023
PM 25754630
ER
PT J
AU Muller, N
Michen, S
Tietze, S
Topfer, K
Schulte, A
Lamszus, K
Schmitz, M
Schackert, G
Pastan, I
Temme, A
AF Mueller, Nadja
Michen, Susanne
Tietze, Stefanie
Toepfer, Katrin
Schulte, Alexander
Lamszus, Katrin
Schmitz, Marc
Schackert, Gabriele
Pastan, Ira
Temme, Achim
TI Engineering NK Cells Modified With an EGFRvIII-specific Chimeric Antigen
Receptor to Overexpress CXCR4 Improves Immunotherapy of CXCL12/SDF-1
alpha-secreting Glioblastoma
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE adoptive immunotherapy; engineered NK cell chemotaxis; chimeric antigen
receptor; EGFRvIII; CXCR4; CXCL12/SDF-1 alpha
ID NATURAL-KILLER-CELLS; GROWTH-FACTOR; T-CELLS; CHEMOKINE RECEPTORS;
TUMOR-CELLS; IN-VIVO; RETROVIRAL VECTORS; GLIOMA XENOGRAFTS;
ENDOTHELIAL-CELLS; EXPRESSION
AB Natural killer (NK) cells are promising effector cells for adjuvant immunotherapy of cancer. So far, several preclinical studies have shown the feasibility of gene-engineered NK cells, which upon expression of chimeric antigen receptors (CARs) are redirected to otherwise NK cell-resistant tumors. Yet, we reasoned that the efficiency of an immunotherapy using CAR-modified NK cells critically relies on efficient migration to the tumor site and might be improved by the engraftment of a receptor specific for a chemokine released by the tumor. On the basis of the DNAX-activation protein 12 (DAP12), a signaling adapter molecule involved in signal transduction of activating NK cell receptors, we constructed an epidermal growth factor variant III (EGFRvIII)-CAR, designated MR1.1-DAP12 which confers specific cytotoxicity of NK cell towards EGFRvIII(+) glioblastoma cells in vitro and to established subcutaneous U87-MG(EGFRvIII) tumor xenografts. So far, infusion of NK cells with expression of MR1.1DAP12 caused a moderate but significantly delayed tumor growth and increased median survival time when compared with NK cells transduced with an ITAM-defective CAR. Notably, the further genetic engineering of these EGFRvIII-specific NK cells with the chemokine receptor CXCR4 conferred a specific chemotaxis to CXCL12/SDF-1 alpha secreting U87-MG glioblastoma cells. Moreover, the administration of such NK cells resulted in complete tumor remission in a number of mice and a significantly increased survival when compared with the treatment of xenografts with NK cells expressing only the EGFRvIII-specific CAR or mock control. We conclude that chemokine receptor-engineered NK cells with concomitant expression of a tumor-specific CAR are a promising tool to improve adoptive tumor immunotherapy.
C1 [Mueller, Nadja; Michen, Susanne; Tietze, Stefanie; Toepfer, Katrin; Schackert, Gabriele; Temme, Achim] Tech Univ Dresden, Dept Neurosurg, Sect Expt Neurosurg Tumor Immunol, Univ Hosp Carl Gustav Carus, D-01307 Dresden, Germany.
[Schmitz, Marc] Tech Univ Dresden, Inst Immunol, Med Fac Carl Gustav Carus, D-01307 Dresden, Germany.
[Schackert, Gabriele; Temme, Achim] German Canc Consortium DKTK, Dresden, Germany.
[Schulte, Alexander; Lamszus, Katrin] Univ Med Ctr Hamburg Eppendorf, Dept Neurosurg, Lab Brain Tumor Biol, Hamburg, Germany.
[Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Temme, A (reprint author), Tech Univ Dresden, Dept Neurosurg, Sect Expt Neurosurg Tumor Immunol, Univ Hosp Carl Gustav Carus, Fetscherstasse 74, D-01307 Dresden, Germany.
EM Achim.Temme@uniklinikum-dresden.de
FU Deutsche Krebshilfe e.V. [Az.: 109377]; Doktor Robert Pfleger-Stiftung;
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; Forschungs und Wissenschaftsstiftung Hamburg
FX Supported by the Deutsche Krebshilfe e.V. (Az.: 109377) (A.T.) and
Doktor Robert Pfleger-Stiftung (A.T.). This research was also supported
in part by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research (I.P.), and in part by a grant
from the Forschungs und Wissenschaftsstiftung Hamburg (K.L.).
NR 66
TC 7
Z9 8
U1 1
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1524-9557
EI 1537-4513
J9 J IMMUNOTHER
JI J. Immunother.
PD JUN
PY 2015
VL 38
IS 5
BP 197
EP 210
PG 14
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA CI1EH
UT WOS:000354484300003
PM 25962108
ER
PT J
AU Screen, HRC
Berk, DE
Kadler, KE
Ramirez, F
Young, MF
AF Screen, Hazel R. C.
Berk, David E.
Kadler, Karl E.
Ramirez, Francesco
Young, Marian F.
TI Tendon Functional Extracellular Matrix
SO JOURNAL OF ORTHOPAEDIC RESEARCH
LA English
DT Article
DE tenocyte; cell; tendinopathy; collagen; proteoglycans; hierarchy;
structure; mechanics
ID LEUCINE-RICH PROTEOGLYCANS; FIBRILLOGENESIS IN-SITU; ENERGY-STORING
TENDONS; HUMAN ROTATOR CUFF; RAT-TAIL-TENDON; MECHANICAL-PROPERTIES;
COLLAGEN FIBRILLOGENESIS; PLASMA-MEMBRANE; ACHILLES-TENDON;
SKELETAL-MUSCLE
AB This article is one of a series, summarizing views expressed at the Orthopaedic Research Society New Frontiers in Tendon Research Conference. This particular article reviews the three workshops held under the Functional Extracellular Matrix stream. The workshops focused on the roles of the tendon extracellular matrix, such as performing the mechanical functions of tendon, creating the local cell environment, and providing cellular cues. Tendon is a complex network of matrix and cells, and its biological functions are influenced by widely varying extrinsic and intrinsic factors such as age, nutrition, exercise levels, and biomechanics. Consequently, tendon adapts dynamically during development, aging, and injury. The workshop discussions identified research directions associated with understanding cell-matrix interactions to be of prime importance for developing novel strategies to target tendon healing or repair. (c) 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:793-799, 2015.
C1 [Screen, Hazel R. C.] Queen Mary Univ London, Sch Engn & Mat Sci, Inst Bioengn, London E1 4NS, England.
[Berk, David E.] Univ S Florida, Morsani Coll Med, Dept Mol Pharmacol & Physiol, Tampa, FL USA.
[Kadler, Karl E.] Univ Manchester, Fac Life Sci, Wellcome Trust Ctr Cell Matrix Res, Manchester M13 9PT, Lancs, England.
[Ramirez, Francesco] Thomas Jefferson Univ, Jefferson Med Coll, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA.
[Young, Marian F.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Screen, HRC (reprint author), Queen Mary Univ London, Sch Engn & Mat Sci, Inst Bioengn, Mile End Rd, London E1 4NS, England.
EM h.r.c.screen@qmul.ac.uk
RI Birk, David/I-4072-2012
OI Birk, David/0000-0002-4865-9088
FU BBSRC; Arthritis Research UK; Orthopaedic Research UK; Wellcome Trust;
DIR; NIDCR part of the IRP; NIH; DHHS; National Institutes of Health,
NIAMS [AR044745, AR065995]
FX Grant sponsor: BBSRC, Arthritis Research UK; Grant sponsor: Orthopaedic
Research UK; Grant sponsor: The Wellcome Trust; Grant sponsor: DIR,
NIDCR, part of the IRP, NIH, and DHHS; Grant sponsor: National
Institutes of Health, NIAMS; Grant numbers: AR044745, AR065995.
NR 80
TC 8
Z9 8
U1 6
U2 29
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0736-0266
EI 1554-527X
J9 J ORTHOP RES
JI J. Orthop. Res.
PD JUN
PY 2015
VL 33
IS 6
BP 793
EP 799
DI 10.1002/jor.22818
PG 7
WC Orthopedics
SC Orthopedics
GA CH4SX
UT WOS:000354024300005
PM 25640030
ER
PT J
AU Leyva, B
Nguyen, AB
Allen, JD
Taplin, SH
Moser, RP
AF Leyva, Bryan
Nguyen, Anh B.
Allen, Jennifer D.
Taplin, Stephen H.
Moser, Richard P.
TI Is Religiosity Associated with Cancer Screening? Results from a National
Survey
SO JOURNAL OF RELIGION & HEALTH
LA English
DT Article
DE Religiosity; Health care use; Cancer screening; Social support;
Ethnicity
ID AFRICAN-AMERICAN WOMEN; SOCIAL SUPPORT; MENTAL-HEALTH; PARTICIPATORY
APPROACH; CHURCH ATTENDANCE; MODERATING ROLE; BLACK CHURCHES;
UNITED-STATES; OLDER-ADULTS; BREAST
AB This study examined the following: (1) relationships between religiosity-as measured by religious service attendance-and screening for breast, cervical, and colorectal cancers; (2) the potential mediating role of social support; and (3) the potential moderating effect of race/ethnicity. Statistical analyses showed that religiosity was associated with greater utilization of breast, cervical, and colorectal cancer screening. Social support fully mediated the relationship between religiosity and Pap screening, and partially mediated the relationship between religiosity and colorectal screening, but had no effect on the relationship between religiosity and mammography screening. Race/ethnicity moderated the relationship between religiosity and social support in the cervical cancer screening model, such that the positive association between religiosity and social support was stronger for non-Hispanic Blacks than it was for non-Hispanic Whites. These findings have implications for the role of social networks in health promotion and can inform cancer screening interventions in faith-based settings.
C1 [Leyva, Bryan; Taplin, Stephen H.] NCI, Div Canc Control & Populat Sci, Behav Res Program, Proc Care Res Branch, Rockville, MD 20850 USA.
[Nguyen, Anh B.; Moser, Richard P.] NCI, Div Canc Control & Populat Sci, Behav Res Program, Sci Res & Technol Branch, Rockville, MD 20850 USA.
[Allen, Jennifer D.] Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, Boston, MA 02115 USA.
[Allen, Jennifer D.] Harvard Univ, Sch Med, Boston, MA USA.
RP Leyva, B (reprint author), NCI, Div Canc Control & Populat Sci, Behav Res Program, Proc Care Res Branch, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM leyvavengoechb@mail.nih.gov; Anh.nguyen3@nih.gov;
jennifer_allen@dfci.harvard.edu; taplins@mail.nih.gov;
moserr@mail.nih.gov
RI Allen, Jennifer/M-2113-2015
FU Centers for Disease Control and Prevention [U48DP001946]
FX This study was supported in part by Cooperative Agreement Number
U48DP001946 from the Centers for Disease Control and Prevention. The
findings and conclusions in this journal article are those of the
author(s) and do not necessarily represent the official position of the
Centers for Disease Control and Prevention.
NR 72
TC 3
Z9 3
U1 1
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0022-4197
EI 1573-6571
J9 J RELIG HEALTH
JI J. Relig. Health
PD JUN
PY 2015
VL 54
IS 3
BP 998
EP 1013
DI 10.1007/s10943-014-9843-1
PG 16
WC Public, Environmental & Occupational Health; Religion
SC Public, Environmental & Occupational Health; Religion
GA CH2UA
UT WOS:000353879000015
PM 24833158
ER
PT J
AU Siddiqui, MM
Truong, H
Rais-Bahrami, S
Stamatakis, L
Logan, J
Walton-Diaz, A
Turkbey, B
Choyke, PL
Wood, BJ
Simon, RM
Pinto, PA
AF Siddiqui, M. Minhaj
Hong Truong
Rais-Bahrami, Soroush
Stamatakis, Lambros
Logan, Jennifer
Walton-Diaz, Annerleim
Turkbey, Baris
Choyke, Peter L.
Wood, Bradford J.
Simon, Richard M.
Pinto, Peter A.
TI Clinical Implications of a Multiparametric Magnetic Resonance Imaging
Based Nomogram Applied to Prostate Cancer Active Surveillance
SO JOURNAL OF UROLOGY
LA English
DT Article
DE prostatic neoplasms; magnetic resonance imaging; biopsy; nomograms; risk
ID TRANSRECTAL ULTRASOUND BIOPSY; RADICAL PROSTATECTOMY; FUSION BIOPSY;
GLEASON SCORE; PREDICTION; UPDATE; RISK; MEN; CANDIDATES; MANAGEMENT
AB Purpose: Multiparametric magnetic resonance imaging may be beneficial in the search for rational ways to decrease prostate cancer intervention in patients on active surveillance. We applied a previously generated nomogram based on multiparametric magnetic resonance imaging to predict active surveillance eligibility based on repeat biopsy outcomes.
Materials and Methods: We reviewed the records of 85 patients who met active surveillance criteria at study entry based on initial biopsy and who then underwent 3.0 Tesla multiparametric magnetic resonance imaging with subsequent magnetic resonance imaging/ultrasound fusion guided prostate biopsy between 2007 and 2012. We assessed the accuracy of a previously published nomogram in patients on active surveillance before confirmatory biopsy. For each cutoff we determined the number of biopsies avoided (ie reliance on magnetic resonance imaging alone without rebiopsy) over the full range of nomogram cutoffs.
Results: We assessed the performance of the multiparametric magnetic resonance imaging active surveillance nomogram based on a decision to perform biopsy at various nomogram generated probabilities. Based on cutoff probabilities of 19% to 32% on the nomogram the number of patients who could be spared repeat biopsy was 27% to 68% of the active surveillance cohort. The sensitivity of the test in this interval was 97% to 71% and negative predictive value was 91% to 81%.
Conclusions: Multiparametric magnetic resonance imaging based nomograms may reasonably decrease the number of repeat biopsies in patients on active surveillance by as much as 68%. Analysis over the full range of nomogram generated probabilities allows patient and caregiver preference based decision making on the risk assumed for the benefit of fewer repeat biopsies.
C1 NCI, Urol Oncol Branch, Canc Prevent Div, Mol Imaging Program,NIH, Bethesda, MD 20892 USA.
NCI, Ctr Intervent Oncol, Dept Radiol & Imaging Sci, NIH, Bethesda, MD 20892 USA.
NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Rockville, MD USA.
RP Pinto, PA (reprint author), NCI, Urol Oncol Branch, NIH, 10 Ctr Dr,MSC 1210,Bldg 10 CRC Room 2W-5940, Bethesda, MD 20892 USA.
EM pintop@mail.nih.gov
OI Rais-Bahrami, Soroush/0000-0001-9466-9925
FU NIH NCI Center for Cancer Research Intramural Research Program; Philips
Healthcare; NIH Health Medical Research Scholars Program; Pfizer; Leona
M. and Harry B. Helmsley Charitable Trust; Howard Hughes Medical
Institute
FX Supported by the NIH NCI Center for Cancer Research Intramural Research
Program, Philips Healthcare, NIH Health Medical Research Scholars
Program, Pfizer, The Leona M. and Harry B. Helmsley Charitable Trust,
Howard Hughes Medical Institute and others
(http://www.fnih.org/work/programs-development/medical-research-scholars
-program).
NR 26
TC 16
Z9 16
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
EI 1527-3792
J9 J UROLOGY
JI J. Urol.
PD JUN
PY 2015
VL 193
IS 6
BP 1943
EP 1949
DI 10.1016/j.juro.2015.01.088
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA CH7DV
UT WOS:000354196700022
PM 25633923
ER
PT J
AU Richter, HE
Whitehead, N
Arya, L
Ridgeway, B
Allen-Brady, K
Norton, P
Sung, V
Shepherd, JP
Komesu, Y
Gaddis, N
Fraser, MO
Tan-Kim, J
Meikle, S
Page, GP
AF Richter, Holly E.
Whitehead, Nedra
Arya, Lily
Ridgeway, Beri
Allen-Brady, Kristina
Norton, Peggy
Sung, Vivian
Shepherd, Jonathan P.
Komesu, Yuko
Gaddis, Nathan
Fraser, Matthew O.
Tan-Kim, Jasmine
Meikle, Susan
Page, Grier P.
CA Pelvic Floor Disorders Network
TI Genetic Contributions to Urgency Urinary Incontinence in Women
SO JOURNAL OF UROLOGY
LA English
DT Article
DE genome-wide association study; urinary incontinence, urge; urinary
bladder, overactive
ID GENOME-WIDE ASSOCIATION; EFFICIENT; DISEASE
AB Purpose: We identify genetic variants associated with urgency urinary incontinence in postmenopausal women.
Materials and Methods: A 2-stage genome-wide association analysis was conducted to identify variants associated with urgency urinary incontinence. The WHI GARNET substudy with 4,894 genotyped post-reproductive white women was randomly split into independent discovery and replication cohorts. Genome-wide imputation was performed using IMPUTE2 with the 1000 Genomes ALL Phase I integrated variant set as a reference. Controls reported no urgency urinary incontinence at enrollment or followup. Cases reported monthly or greater urgency urinary incontinence and leaked sufficiently to wet/soak underpants/clothes. Logistic regression models were used to predict urgency urinary incontinence case vs control status based on genotype, assuming additive inheritance. Age, obesity, diabetes and depression were included in the models as covariates.
Results: Following quality control, 975,508 single nucleotide polymorphisms in 2,241 cases (discovery 1,102; replication 1,133) and 776 controls (discovery 405, replication 371) remained. Genotype imputation resulted in 9,077,347 single nucleotide polymorphisms and insertions/deletions with minor allele frequency greater than 0.01 available for analysis. Meta-analysis of the discovery and replication samples identified 6 loci on chromosomes 5, 10, 11, 12 and 18 associated with urgency urinary incontinence at p < 10(-6). Of the loci 3 were within genes, the zinc finger protein 521 (ZFP521) gene on chromosome 18q11, the ADAMTS16 gene on chromosome 5p15 and the CIT gene on chromosome 12q24. The other 3 loci were intergenic.
Conclusions: Although environmental factors also likely contribute, this first exploratory genome-wide association study for urgency urinary incontinence suggests that genetic variants in the ZFP521, CIT and ADAMTS16 genes might account for some of the observed heritability of the condition.
C1 [Richter, Holly E.] Univ Alabama Birmingham, Birmingham, AL 35249 USA.
[Whitehead, Nedra; Gaddis, Nathan; Page, Grier P.] Res Triangle Int, Res Triangle Pk, NC USA.
[Fraser, Matthew O.] Duke Univ, Durham, NC USA.
[Arya, Lily] Univ Penn, Philadelphia, PA 19104 USA.
[Shepherd, Jonathan P.] Univ Pittsburgh, Pittsburgh, PA USA.
[Ridgeway, Beri] Cleveland Clin, Cleveland, OH 44106 USA.
[Allen-Brady, Kristina; Norton, Peggy] Univ Utah, Salt Lake City, UT USA.
[Sung, Vivian] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Komesu, Yuko] Univ New Mexico, Albuquerque, NM 87131 USA.
[Tan-Kim, Jasmine] Kaiser Permanente, San Diego, CA USA.
[Meikle, Susan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Richter, HE (reprint author), Univ Alabama Birmingham, Div Urogynecol & Pelv Reconstruct Surg, 619 19th St South,176F,Suite 10382, Birmingham, AL 35249 USA.
EM hrichter@uabmc.edu
OI Gaddis, Nathan/0000-0001-5205-7138
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [2-U10-HD04267, 2-U10-HD041261, 2-U10-HD054215,
2-U10-HD054214, 1-U10-HD069006, 1-U10-HD069025, RO1 HD061821,
1-U10-HD069013, 1-U10-HD069010, 1-U01-HD069010-01]; NIH Office of
Research on Women's Health; Pfizer Inc.
FX Supported by grants from The Eunice Kennedy Shriver National Institute
of Child Health and Human Development (Duke University: 2-U10-HD04267,
University of Alabama at Birmingham: 2-U10-HD041261, Cleveland Clinic:
2-U10-HD054215, UCSD: 2-U10-HD054214, University of Pittsburgh:
1-U10-HD069006, University of New Mexico: 1-U10-HD069025, University of
Utah: RO1 HD061821, Brown University: 1-U10-HD069013, University of
Pennsylvania: 1-U10-HD069010, RTI: 1-U01-HD069010-01), the NIH Office of
Research on Women's Health and investigator initiated research support
from Pfizer Inc.
NR 27
TC 2
Z9 2
U1 2
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
EI 1527-3792
J9 J UROLOGY
JI J. Urol.
PD JUN
PY 2015
VL 193
IS 6
BP 2020
EP 2027
DI 10.1016/j.juro.2014.12.023
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA CH7DV
UT WOS:000354196700054
PM 25524241
ER
PT J
AU Blasi, G
Selvaggi, P
Fazio, L
Antonucci, LA
Taurisano, P
Masellis, R
Romano, R
Mancini, M
Zhang, FY
Caforio, G
Popolizio, T
Apud, J
Weinberger, DR
Bertolino, A
AF Blasi, Giuseppe
Selvaggi, Pierluigi
Fazio, Leonardo
Antonucci, Linda Antonella
Taurisano, Paolo
Masellis, Rita
Romano, Raffaella
Mancini, Marina
Zhang, Fengyu
Caforio, Grazia
Popolizio, Teresa
Apud, Jose
Weinberger, Daniel R.
Bertolino, Alessandro
TI Variation in Dopamine D2 and Serotonin 5-HT2A Receptor Genes is
Associated with Working Memory Processing and Response to Treatment with
Antipsychotics
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
ID DORSOLATERAL PREFRONTAL CORTEX; PRIMATE CEREBRAL-CORTEX; ATTENTIONAL
CONTROL; CLINICAL-RESPONSE; HIS452TYR POLYMORPHISM; COGNITIVE
IMPAIRMENTS; OLANZAPINE TREATMENT; CANDIDATE GENES; SCHIZOPHRENIA; RISK
AB Dopamine D2 and serotonin 5-HT2A receptors contribute to modulate prefrontal cortical physiology and response to treatment with antipsychotics in schizophrenia. Similarly, functional variation in the genes encoding these receptors is also associated with these phenotypes. In particular, the DRD2 rs1076560 T allele predicts a lower ratio of expression of D2 short/long isoforms, suboptimal working memory processing, and better response to antipsychotic treatment compared with the G allele. Furthermore, the HTR2A T allele is associated with lower 5-HT2A expression, impaired working memory processing, and poorer response to antipsychotics compared with the C allele. Here, we investigated in healthy subjects whether these functional polymorphisms have a combined effect on prefrontal cortical physiology and related cognitive behavior linked to schizophrenia as well as on response to treatment with second-generation antipsychotics in patients with schizophrenia. In a total sample of 620 healthy subjects, we found that subjects with the rs1076560 T and rs6314 T alleles have greater fMRI prefrontal activity during working memory. Similar results were obtained within the attentional domain. Also, the concomitant presence of the rs1076560 T/rs6314 T alleles also predicted lower behavioral accuracy during working memory. Moreover, we found that rs1076560 T carrier/rs6314 CC individuals had better responses to antipsychotic treatment in two independent samples of patients with schizophrenia (n = 63 and n = 54, respectively), consistent with the previously reported separate effects of these genotypes. These results indicate that DRD2 and HTR2A genetic variants together modulate physiological prefrontal efficiency during working memory and also modulate the response to antipsychotics. Therefore, these results suggest that further exploration is needed to better understand the clinical consequences of these genotype-phenotype relationships.
C1 [Blasi, Giuseppe; Selvaggi, Pierluigi; Antonucci, Linda Antonella; Taurisano, Paolo; Masellis, Rita; Romano, Raffaella; Mancini, Marina; Caforio, Grazia; Bertolino, Alessandro] Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, Grp Psychiat Neurosci, I-70124 Bari, Italy.
[Blasi, Giuseppe; Fazio, Leonardo; Taurisano, Paolo; Popolizio, Teresa] IRCCS Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy.
[Antonucci, Linda Antonella] Aldo Moro Univ, Commun Sci, Dept Educ Sci, Psychol, Bari, Italy.
[Zhang, Fengyu; Weinberger, Daniel R.] Johns Hopkins Med Campus, Lieber Inst Brain Dev, Baltimore, MD USA.
[Apud, Jose] NIMH, NIH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA.
[Bertolino, Alessandro] F Hoffman La Roche Ltd, pRED, NORD DTA, Basel, Switzerland.
RP Bertolino, A (reprint author), Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, Piazza Giulio Cesare 11, I-70124 Bari, Italy.
EM alessandro.bertolino@uniba.it
OI Selvaggi, Pierluigi/0000-0001-9069-0700
NR 59
TC 8
Z9 8
U1 1
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD JUN
PY 2015
VL 40
IS 7
BP 1600
EP 1608
DI 10.1038/npp.2015.5
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CH8YC
UT WOS:000354321600005
PM 25563748
ER
PT J
AU Barlow, RL
Alsio, J
Jupp, B
Rabinovich, R
Shrestha, S
Roberts, AC
Robbins, TW
Dalley, JW
AF Barlow, Rebecca L.
Alsio, Johan
Jupp, Bianca
Rabinovich, Rebecca
Shrestha, Saurav
Roberts, Angela C.
Robbins, Trevor W.
Dalley, Jeffrey W.
TI Markers of Serotonergic Function in the Orbitofrontal Cortex and Dorsal
Raphe Nucleus Predict Individual Variation in Spatial-Discrimination
Serial Reversal Learning
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
ID OBSESSIVE-COMPULSIVE DISORDER; PREFRONTAL CORTEX; TRYPTOPHAN DEPLETION;
COGNITIVE INFLEXIBILITY; ATTENTIONAL CONTROL; DOPAMINE DEPLETION;
IMPULSIVE BEHAVIOR; SELECTIVE LESIONS; CORTICAL-LESIONS; CAUDATE-NUCLEUS
AB Dysfunction of the orbitofrontal cortex (OFC) impairs the ability of individuals to flexibly adapt behavior to changing stimulus-reward (S-R) contingencies. Impaired flexibility also results from interventions that alter serotonin (5-HT) and dopamine (DA) transmission in the OFC and dorsomedial striatum (DMS). However, it is unclear whether similar mechanisms underpin naturally occurring variations in behavioral flexibility. In the present study, we used a spatial-discrimination serial reversal procedure to investigate interindividual variability in behavioral flexibility in rats. We show that flexibility on this task is improved following systemic administration of the 5-HT reuptake inhibitor citalopram and by low doses of the DA reuptake inhibitor GBR12909. Rats in the upper quintile of the distribution of perseverative responses during repeated S-R reversals showed significantly reduced levels of the 5-HT metabolite, 5-hydroxy-indoleacetic acid, in the OFC. Additionally, 5-HT2A receptor binding in the OFC of mid-and high-quintile rats was significantly reduced compared with rats in the low-quintile group. These perturbations were accompanied by an increase in the expression of monoamine oxidase-A (MAO-A) and MAO-B in the lateral OFC and by a decrease in the expression of MAO-A, MAO-B, and tryptophan hydroxylase in the dorsal raphe nucleus of highly perseverative rats. We found no evidence of significant differences in markers of DA and 5-HT function in the DMS or MAO expression in the ventral tegmental area of low-vs high-perseverative rats. These findings indicate that diminished serotonergic tone in the OFC may be an endophenotype that predisposes to behavioral inflexibility and other forms of compulsive behavior.
C1 [Barlow, Rebecca L.; Alsio, Johan; Jupp, Bianca; Rabinovich, Rebecca; Roberts, Angela C.; Robbins, Trevor W.; Dalley, Jeffrey W.] Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge CB2 3EB, England.
[Barlow, Rebecca L.; Alsio, Johan; Jupp, Bianca; Rabinovich, Rebecca; Roberts, Angela C.; Robbins, Trevor W.; Dalley, Jeffrey W.] Univ Cambridge, Dept Psychol, Cambridge CB2 3EB, England.
[Alsio, Johan] Uppsala Univ, Dept Neurosci, Uppsala, Sweden.
[Jupp, Bianca] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Parkville, Vic 3052, Australia.
[Shrestha, Saurav] NIMH, IRP, Bethesda, MD 20892 USA.
[Roberts, Angela C.] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3EB, England.
[Dalley, Jeffrey W.] Univ Cambridge, Dept Psychiat, Cambridge CB2 3EB, England.
RP Dalley, JW (reprint author), Univ Cambridge, Dept Psychol, Downing St, Cambridge CB2 3EB, England.
EM jwd20@cam.ac.uk
FU Lilly; Lundbeck
FX TWR consults for Cambridge Cognition, Lilly, Merck Sharpe and Dohme,
Lundbeck, Teva, Shire Pharmaceuticals, Otsuka, and Chempartners, and has
held recent research grants with Lilly and Lundbeck. TWR has also
received royalties from Cambridge Cognition (CANTAB), Springer, and
Elsevier. All the other authors declare no conflict of interest.
NR 63
TC 8
Z9 8
U1 6
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD JUN
PY 2015
VL 40
IS 7
BP 1619
EP 1630
DI 10.1038/npp.2014.335
PG 12
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CH8YC
UT WOS:000354321600007
PM 25567428
ER
PT J
AU John, CS
Sypek, EI
Carlezon, WA
Cohen, BM
Ongur, D
Bechtholt, AJ
AF John, Catherine S.
Sypek, Elizabeth I.
Carlezon, William A.
Cohen, Bruce M.
Oenguer, Dost
Bechtholt, Anita J.
TI Blockade of the GLT-1 Transporter in the Central Nucleus of the Amygdala
Induces both Anxiety and Depressive-Like Symptoms
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
ID FEAR-POTENTIATED STARTLE; ASTROCYTIC GLUTAMATE UPTAKE; BRAIN-STIMULATION
REWARD; MEDIAL PREFRONTAL CORTEX; MAJOR DEPRESSION; BIPOLAR DISORDER;
RAT-BRAIN; MOOD DISORDERS; PERIAQUEDUCTAL GRAY; SELF-STIMULATION
AB Depression has been associated with abnormalities in glutamatergic neurotransmission and decreased astrocyte number in limbic areas. We previously demonstrated that global and prefrontal cortical blockade of the astrocytic glutamate transporter (GLT-1) induces anhedonia and c-Fos expression in areas that regulate anxiety, including the central amygdala (CEA). Given the role of the amygdala in anxiety and the high degree of comorbidity between anxiety and depression, we hypothesized that GLT-1 blockade in the CEA would induce symptoms of anhedonia and anxiety in rats. We microinjected the GLT-1 inhibitor, dihydrokainic acid (DHK), into the CEA and examined effects on intracranial self-stimulation (ICSS) as an index of hedonic state, and on behavior in two anxiety paradigms, elevated plus maze (EPM) and fear conditioning. At lower doses, intra-CEA DHK produced modest increases in ICSS responding (T0). Higher doses resulted in complete cessation of responding for 15 min, suggesting an anhedonic or depressive-like effect. Intra-CEA DHK also increased anxiety-like behavior such that percent time in the open arms and total entries were decreased in the EPM and acquisition of freezing behavior to the tone was increased in a fear-conditioning paradigm. These effects did not appear to be explained by non-specific changes in activity, because effects on fear conditioning were assessed in a drug-free state, and a separate activity test showed no significant effects of intra-CEA DHK on locomotion. Taken together, these studies suggest that blockade of GLT-1 in the CEA is sufficient to induce both anhedonia and anxiety and therefore that a lack of glutamate uptake resulting from glial deficits may contribute to the comorbidity of depression and anxiety.
C1 [John, Catherine S.; Sypek, Elizabeth I.; Carlezon, William A.; Cohen, Bruce M.; Oenguer, Dost] Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA USA.
[Bechtholt, Anita J.] NIAAA, NIH, Bethesda, MD 20892 USA.
RP Bechtholt, AJ (reprint author), NIAAA, Div Treatment & Recovery Res, NIH, 5635 Fishers Lane,Room 2046, Bethesda, MD 20892 USA.
EM Anita.bechtholt@gmail.com
OI sypek, elizabeth/0000-0001-6904-2426
FU American College of Neuropsychopharmacology; Myneurolab.com
FX The authors have no conflicts of interest relating to this report and Dr
Bechtholt, Catherine John, and Elizabeth Sypek have no other potential
conflicts to report. Dr Carlezon has a US patent covering the use of
kappa antagonists in the treatment of depression (Assignee: McLean
Hospital) and is a member of a collaborative group, including Dr Cohen,
that has submitted a patent application covering the synthesis and use
of salvinorin derivatives (Assignees: McLean Hospital and Temple
University). In the last three years, Dr Carlezon has received
compensation for professional services from The American College of
Neuropsychopharmacology and Myneurolab.com. Dr Ongur is a Principal
Investigator on a research contract with Rules Based Medicine Inc., has
served on an advisory board for Lilly, and has received income from
Archives of General Psychiatry for services in 2012. Dr Cohen has three
additional pending patents on Pyrimidines to treat bipolar disorders,
Kappa agonists in bipolar mania, and Mitochondrial replacement therapy
and a book on bipolar disorder that has been published by
Jossey-Bass/Wiley.
NR 60
TC 6
Z9 7
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD JUN
PY 2015
VL 40
IS 7
BP 1700
EP 1708
DI 10.1038/npp.2015.16
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CH8YC
UT WOS:000354321600015
PM 25586634
ER
PT J
AU Cha, J
Fekete, T
Siciliano, F
Biezonski, D
Greenhill, L
Pliszka, SR
Blader, JC
Roy, AK
Leibenluft, E
Posner, J
AF Cha, Jiook
Fekete, Tomer
Siciliano, Francesco
Biezonski, Dominik
Greenhill, Laurence
Pliszka, Steven R.
Blader, Joseph C.
Roy, Amy Krain
Leibenluft, Ellen
Posner, Jonathan
TI Neural Correlates of Aggression in Medication-Naive Children with ADHD:
Multivariate Analysis of Morphometry and Tractography
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; HUMAN CEREBRAL-CORTEX; DEFICIT
HYPERACTIVITY DISORDER; SUPPORT VECTOR MACHINES; SURFACE-BASED ANALYSIS;
PREFRONTAL CORTEX; WHITE-MATTER; HUMAN BRAIN; CONNECTIVITY; PERFORMANCE
AB Aggression is widely observed in children with attention deficit/hyperactivity disorder (ADHD) and has been frequently linked to frustration or the unsatisfied anticipation of reward. Although animal studies and human functional neuroimaging implicate altered reward processing in aggressive behaviors, no previous studies have documented the relationship between fronto-accumbal circuitry-a critical cortical pathway to subcortical limbic regions-and aggression in medication-naive children with ADHD. To address this, we collected behavioral measures and parental reports of aggression and impulsivity, as well as structural and diffusion MRI, from 30 children with ADHD and 31 healthy controls (HC) (mean age, 10 +/- 2.1 SD). Using grey matter morphometry and probabilistic tractography combined with multivariate statistical modeling (partial least squares regression and support vector regression), we identified anomalies within the fronto-accumbal circuit in childhood ADHD, which were associated with increased aggression. More specifically, children with ADHD showed reduced right accumbal volumes and frontal-accumbal white matter connectivity compared with HC. The magnitude of the accumbal volume reductions within the ADHD group was significantly correlated with increased aggression, an effect mediated by the relationship between the accumbal volume and impulsivity. Furthermore, aggression, but not impulsivity, was significantly explained by multivariate measures of fronto-accumbal white matter connectivity and cortical thickness within the orbitofrontal cortex. Our multi-modal imaging, combined with multivariate statistical modeling, indicates that the fronto-accumbal circuit is an important substrate of aggression in children with ADHD. These findings suggest that strategies aimed at probing the fronto-accumbal circuit may be beneficial for the treatment of aggressive behaviors in childhood ADHD.
C1 [Cha, Jiook; Siciliano, Francesco; Biezonski, Dominik; Greenhill, Laurence; Posner, Jonathan] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
[Cha, Jiook; Siciliano, Francesco; Biezonski, Dominik; Greenhill, Laurence; Posner, Jonathan] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Fekete, Tomer] Katholieke Univ Leuven, Fac Psychol & Educ Sci, Lab Perceptual Dynam, Leuven, Belgium.
[Pliszka, Steven R.; Blader, Joseph C.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, Sch Med, San Antonio, TX 78229 USA.
[Roy, Amy Krain] Fordham Univ, Dept Psychol, New York, NY 10023 USA.
[Leibenluft, Ellen] NIMH, Bethesda, MD 20892 USA.
RP Cha, J (reprint author), Columbia Univ Coll Phys & Surg, Dept Psychiat, 1051 Riverside Dr Unit 74,Room 2420, New York, NY 10032 USA.
EM chajioo@nyspi.columbia.edu
OI Cha, Jiook/0000-0002-5314-7992
FU NIMH [R01-MH101172, K23-MH091249]; Edwin S. Webster Foundation; Shire
Pharmaceuticals; Shire US, Inc.; Purdue Pharma
FX This study was supported in part by NIMH Grants R01-MH101172 (JP) and
K23-MH091249 (JP), and by funding from the Edwin S. Webster Foundation.
Dr Posner is a principal investigator on an investigator-initiated grant
from Shire Pharmaceuticals. The authors declare that over the last three
years, Steven R. Pliszka MD has had research support from Shire US, Inc.
and Purdue Pharma. He has received Honoria for participation in advisory
boards for Shire and Ironside Pharmaceutical.
NR 59
TC 12
Z9 12
U1 2
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD JUN
PY 2015
VL 40
IS 7
BP 1717
EP 1725
DI 10.1038/npp.2015.18
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CH8YC
UT WOS:000354321600017
PM 25645374
ER
PT J
AU Wang, XF
Bi, GH
He, Y
Yang, HJ
Gao, JT
Okunola-Bakare, OM
Slack, RD
Gardner, EL
Xi, ZX
Newman, AH
AF Wang, Xiao-Fei
Bi, Guo-Hua
He, Yi
Yang, Hong-Ju
Gao, Jun-Tao
Okunola-Bakare, Oluyomi M.
Slack, Rachel D.
Gardner, Eliot L.
Xi, Zheng-Xiong
Newman, Amy Hauck
TI R-Modafinil Attenuates Nicotine-Taking and Nicotine-Seeking Behavior in
Alcohol-Preferring Rats
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; COCAINE DEPENDENCE;
METHAMPHETAMINE DEPENDENCE; DISCRIMINATIVE STIMULUS; LOCOMOTOR
SENSITIZATION; REINSTATEMENT; ARMODAFINIL; DOPAMINE; ABUSE
AB (+/-)-Modafinil (MOD) is used clinically for the treatment of sleep disorders and has been investigated as a potential medication for the treatment of psychostimulant addiction. However, the therapeutic efficacy of (+/-)-MOD for addiction is inconclusive. Herein we used animal models of self-administration and in vivo microdialysis to study the pharmacological actions of R-modafinil (R-MOD) and S-modafinil (S-MOD) on nicotine-taking and nicotine-seeking behavior, and mechanisms underlying such actions. We found that R-MOD is more potent and effective than S-MOD in attenuating nicotine self-administration in Long-Evans rats. As Long-Evans rats did not show a robust reinstatement response to nicotine, we used alcohol-preferring rats (P-rats) that display much higher reinstatement responses to nicotine than Long-Evans rats. We found that R-MOD significantly inhibited intravenous nicotine self-administration, nicotine-induced reinstatement, and nicotine-associated cue-induced drug-seeking behavior in P-rats. R-MOD alone neither sustained self-administration in P-rats previously self-administering nicotine nor reinstated extinguished nicotine-seeking behavior. The in vivo brain microdialysis assays demonstrated that R-MOD alone produced a slow-onset moderate increase in extracellular DA. Pretreatment with R-MOD dose-dependently blocked nicotine-induced dopamine (DA) release in the nucleus accumbens (NAc) in both naive and nicotine self-administrating rats, suggesting a DA-dependent mechanism underlying mitigation of nicotine's effects. In conclusion, the present findings support further investigation of R-MOD for treatment of nicotine dependence in humans.
C1 [Wang, Xiao-Fei; Bi, Guo-Hua; He, Yi; Yang, Hong-Ju; Gao, Jun-Tao; Gardner, Eliot L.; Xi, Zheng-Xiong] NIDA, Neuropsychopharmacol Sect, Mol Target & Medicat Discovery Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Okunola-Bakare, Oluyomi M.; Slack, Rachel D.; Newman, Amy Hauck] NIDA, Med Chem Sect, Mol Target & Medicat Discovery Branch, NIH,Intramural Res Program, Baltimore, MD 21224 USA.
RP Xi, ZX (reprint author), NIDA, Neuropsychopharmacol Sect, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM zxi@mail.nih.gov; anewman@mail.nih.gov
FU Intramural Research Program (IRP) of the National Institute on Drug
Abuse (NIDA), National Institutes of Health (NIH)
FX This research was supported by the Intramural Research Program (IRP) of
the National Institute on Drug Abuse (NIDA), National Institutes of
Health (NIH). We acknowledge Ms J Cao for synthesizing S-MOD, Dr Tom
Prisinzano for supplying intermediates and methods for the syntheses of
R- and S-modafinil, and Drs Yavin Shaham and Gianluigi Tanda for their
helpful suggestions on experimental design and comments on an earlier
draft of this manuscript.
NR 45
TC 1
Z9 1
U1 1
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD JUN
PY 2015
VL 40
IS 7
BP 1762
EP 1771
DI 10.1038/npp.2015.24
PG 10
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CH8YC
UT WOS:000354321600022
PM 25613829
ER
PT J
AU Nutman, TB
AF Nutman, T. B.
TI Looking beyond the induction of Th2 responses to explain
immunomodulation by helminths
SO PARASITE IMMUNOLOGY
LA English
DT Review
DE alternatively activated macrophages; dendritic cells; helminths; IgE;
IgG4; IL-10; immune modulation; innate lymphoid cells; regulatory B
cells; regulatory T cells; Th2 responses
ID HUMAN LYMPHATIC FILARIASIS; REGULATORY T-CELLS; MIGRATION INHIBITORY
FACTOR; HOST IMMUNE-RESPONSES; HUMAN DENDRITIC CELLS;
GROWTH-FACTOR-BETA; NEMATODE ONCHOCERCA-VOLVULUS; MALAYI MICROFILARIAE
INDUCE; HOOKWORM NECATOR-AMERICANUS; SCHISTOSOMA-MANSONI EGGS
AB Although helminth infections are characteristically associated with Th2-mediated responses that include the production of the prototypical cytokines IL-4, IL-5 and IL-13 by CD4(+) cells, the production of IgE, peripheral blood eosinophilia and mucus production in localized sites, these responses are largely attenuated when helminth infections become less acute. This modulation of the immune response that occurs with chronic helminth infection is often induced by molecules secreted by helminth parasites, by non-Th2 regulatory CD4(+) cells, and by nonclassical B cells, macrophages and dendritic cells. This review will focus on those parasite- and host-mediated mechanisms underlying the modulated T-cell response that occurs as the default in chronic helminth infections.
C1 NIH, Helminth Immunol Sect, Parasit Dis Lab, Bethesda, MD 20892 USA.
RP Nutman, TB (reprint author), NIH, Helminth Immunol Sect, Parasit Dis Lab, 4 Ctr Dr Bldg 4 Rm B1-03, Bethesda, MD 20892 USA.
EM tnutman@niaid.nih.gov
FU Division of Intramural Research (DIR), National Institute of Allergy and
Infectious Diseases, NIH
FX This work was funded in part by the Division of Intramural Research
(DIR), National Institute of Allergy and Infectious Diseases, NIH.
NR 131
TC 5
Z9 5
U1 4
U2 28
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0141-9838
EI 1365-3024
J9 PARASITE IMMUNOL
JI Parasite Immunol.
PD JUN
PY 2015
VL 37
IS 6
SI SI
BP 304
EP 313
DI 10.1111/pim.12194
PG 10
WC Immunology; Parasitology
SC Immunology; Parasitology
GA CH6DX
UT WOS:000354127600004
PM 25869527
ER
PT J
AU Massilamany, C
Gangaplara, A
Reddy, J
AF Massilamany, C.
Gangaplara, A.
Reddy, J.
TI Environmental Microbes and Uveitis: Is Microbial Exposure Always Bad?
SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY
LA English
DT Review
ID EXPERIMENTAL AUTOIMMUNE UVEITIS; ACUTE ANTERIOR UVEITIS; CANINE
MONOCYTIC EHRLICHIOSIS; MYELIN BASIC-PROTEIN; T-REGULATORY CELLS;
RETINAL S-ANTIGEN; MOLECULAR MIMICRY; CROSS-REACTIVITY; UVEITOPATHOGENIC
SITE; THYMIC EXPRESSION
AB The eye generally is considered to be an immune-privileged organ, but this notion is being increasingly challenged as ocular antigens can be expressed in the generative lymphoid organs, resulting in attainment of self-tolerance. What triggers a break in this tolerant state is a fundamental question in autoimmunity research. The general belief is that exposure to environmental microbes can break self-tolerance in genetically susceptible individuals, leading to the induction of autoimmune responses. The molecular mimicry hypothesis has been proposed as one major mechanistic, pathway through which microbes, by generating cross-reactive immune responses, can induce ocular damage of the kind that might occur in uveitis. However, our recent data suggest that exposure to microbial products containing mimicry epitopes for retinal antigens can potentially be beneficial to the host. In this review, we discuss the immune mechanisms with particular reference to the molecular mimicry hypothesis as it relates to immune-mediated uveitis.
C1 [Massilamany, C.; Gangaplara, A.; Reddy, J.] Univ Nebraska, Sch Vet Med & Biomed Sci, Lincoln, NE 68583 USA.
[Gangaplara, A.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Reddy, J (reprint author), Univ Nebraska, Sch Vet Med & Biomed Sci, Room 202,Bldg VBS, Lincoln, NE 68583 USA.
EM nreddy2@unl.edu
RI Massilamany, Chandirasegaran/D-9305-2016;
OI Massilamany, Chandirasegaran/0000-0002-0205-282X; Gangaplara,
Arunakumar/0000-0001-6307-9391
NR 76
TC 2
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0300-9475
EI 1365-3083
J9 SCAND J IMMUNOL
JI Scand. J. Immunol.
PD JUN
PY 2015
VL 81
IS 6
BP 469
EP 475
DI 10.1111/sji.12297
PG 7
WC Immunology
SC Immunology
GA CI0TU
UT WOS:000354451900002
PM 25833717
ER
PT J
AU Massey, PR
Okman, JS
Wilkerson, J
Cowen, EW
AF Massey, Paul R.
Okman, Jonathan S.
Wilkerson, Julia
Cowen, Edward W.
TI Tyrosine kinase inhibitors directed against the vascular endothelial
growth factor receptor (VEGFR) have distinct cutaneous toxicity
profiles: a meta-analysis and review of the literature
SO SUPPORTIVE CARE IN CANCER
LA English
DT Article
DE Palmoplantar erythrodysesthesia; Hand-foot syndrome; Hand-foot skin
reaction; Toxic erythema of chemotherapy; Tyrosine kinase inhibitor;
Vascular endothelial growth factor
ID FOOT SKIN REACTION; RENAL-CELL CARCINOMA; HEPATOCELLULAR-CARCINOMA;
CONTROLLED-TRIALS; CLINICAL-TRIALS; ADVERSE EVENTS; SORAFENIB;
SUNITINIB; CANCER; THERAPY
AB Inhibition of the vascular endothelial growth factor receptor (VEGFR) with tyrosine kinase inhibitors (TKIs) is associated with cutaneous adverse effects that increase patient morbidity. Our objective was to examine the skin toxicity profile of anti-VEGFR TKIs and determine the changing incidence in clinical trials.
PubMed was queried for phase II or III trials of anti-VEGFR TKIs between 2000 and 2013 involving a parts per thousand yen50 patients. Adverse events were abstracted, with results presented in both fixed and random effects models. Odds ratios (OR) and 95 % confidence intervals (CIs) were estimated for studies with at least two arms.
Across 82 included studies, all grades rash (OR, 2.68; 95 % CI, 2.45-2.94), hand-foot skin reaction (HFSR) (OR, 2.70; 95 % CI, 2.43-3.00), and pruritus (OR, 1.25; 95 % CI, 1.12-1.39) were associated with anti-VEGFR TKIs. Vandetanib had the highest incidence of rash (41 %), while sorafenib was most commonly associated with HFSR (37 %) and pruritus (14 %). The incidence of HFSR from 2000 to 2013 showed an upward trend (r (2) = 0.042, p = 0.10) and in sunitinib therapy increased significantly (r (2) = 0.237, p = 0.04).
The incidence of HFSR, rash, and pruritus varies considerably by drug. Our data suggest a continued need to address skin toxicities and improve reporting strategies.
C1 [Massey, Paul R.] Univ Texas Austin, Dell Med Sch, Austin, TX 78701 USA.
[Okman, Jonathan S.] Lankenau Med Ctr, Dept Internal Med, Philadelphia, PA USA.
[Wilkerson, Julia] NCI, Med Oncol, NIH, Bethesda, MD 20892 USA.
[Cowen, Edward W.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
RP Massey, PR (reprint author), Univ Texas Austin, Dell Med Sch, 601 E 15th St,CEC 2-470, Austin, TX 78701 USA.
EM Prmassey@seton.org
OI Wilkerson, Julia/0000-0002-6965-0867
FU Intramural Research Program of the NIH, National Cancer Institute
FX This research was made possible in part by the Intramural Research
Program of the NIH, National Cancer Institute.
NR 40
TC 3
Z9 3
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0941-4355
EI 1433-7339
J9 SUPPORT CARE CANCER
JI Support. Care Cancer
PD JUN
PY 2015
VL 23
IS 6
BP 1827
EP 1835
DI 10.1007/s00520-014-2520-9
PG 9
WC Oncology; Health Care Sciences & Services; Rehabilitation
SC Oncology; Health Care Sciences & Services; Rehabilitation
GA CH1ON
UT WOS:000353791200041
PM 25471178
ER
PT J
AU Rice, OV
Schonhar, CA
Gaal, J
Gardner, EL
Ashby, CR
AF Rice, Onarae V.
Schonhar, Charles A.
Gaal, J.
Gardner, Eliot L.
Ashby, Charles R., Jr.
TI The Selective Dopamine D-3 Receptor Antagonist SB-277011-A Significantly
Decreases Binge-Like Consumption of Ethanol in C57BL/J6 Mice
SO SYNAPSE
LA English
DT Article
DE dopamine; D3 receptor; binge drinking; ethanol
ID ALCOHOL-SEEKING; HIGH-AFFINITY; BRAIN REWARD; ADDICTION; RATS
AB The authors show that the dopamine D3 antagonist SB-277011-A consistently and persistently decrease binge-like EtOH consumption at 30 mg/kg and it decreases binge-like consumption on days 3, 7, 9, and 11-13 at 15 mg/kg. These findings suggest that the brain's D3 receptor may also be involved in not only ethanol reward but binge drinking as well. Synapse 69:295-298, 2015. (c) 2015 Wiley Periodicals, Inc.
C1 [Rice, Onarae V.; Schonhar, Charles A.] Furman Univ, Dept Psychol, Greenville, SC 29613 USA.
[Gaal, J.] MegaPharma Pharmaceut Kft, Budapest, Hungary.
[Gardner, Eliot L.] NIDA, Neuropsychopharmacol Sect, Intramural Res Program, Baltimore, MD 21224 USA.
[Ashby, Charles R., Jr.] St Johns Univ, Dept Pharmaceut Sci, Coll Pharm & Allied Hlth Profess, Jamaica, NY 11439 USA.
RP Rice, OV (reprint author), Furman Univ, Dept Psychol, 3300 Poinsett Highway, Greenville, SC 29613 USA.
EM onarae.rice@furman.edu
FU National Institute of General Medical Sciences [P20-GM103499]; U.S.
National Institutes of Health
FX Contract grant sponsor: National Institute of General Medical Sciences;
Contract grant number: P20-GM103499; Contract grant sponsor: U.S.
National Institutes of Health.
NR 17
TC 2
Z9 2
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0887-4476
EI 1098-2396
J9 SYNAPSE
JI Synapse
PD JUN
PY 2015
VL 69
IS 6
BP 295
EP 298
DI 10.1002/syn.21816
PG 4
WC Neurosciences
SC Neurosciences & Neurology
GA CH4WM
UT WOS:000354034000001
PM 25764479
ER
PT J
AU Ashby, CR
Rice, OV
Heidbreder, CA
Gardner, EL
AF Ashby, Charles R., Jr.
Rice, Onarae V.
Heidbreder, Christian A.
Gardner, Eliot L.
TI The Selective Dopamine D-3 Receptor Antagonist SB-277011A Attenuates
Drug-or Food-Deprivation Reactivation of Expression of Conditioned Place
Preference for Cocaine in Male Sprague-Dawley Rats
SO SYNAPSE
LA English
DT Article
DE conditioned place preference; dopamine D-3 receptors; SB-277011A
ID SEEKING BEHAVIOR; INDUCED REINSTATEMENT; MESSENGER-RNA; HUMAN BRAIN;
MEASURING REWARD; INDUCED RELAPSE; STRESS; ADDICTION; NEUROBIOLOGY;
CORTICOSTERONE
AB We determined the effect of the selective dopamine D-3 receptor antagonist SB-277011A on reactivation of conditioned place preference (CPP) to cocaine elicited by priming injections of cocaine or exposure to food deprivation stress (21 h) in male Sprague-Dawley rats. Animals paired with the cocaine-associated chamber displayed a robust and consistent CPP response. This CPP was extinguished after repeated pairings of the conditioned stimuli (cocaine-paired chamber contextual cues) in the absence of the unconditioned stimulus (cocaine). Twenty-four hours later, the administration of 5 mgkg(-1) i.p. of cocaine (immediately before the test) or exposure to 21 h of food deprivation reactivated the expression of the cocaine-induced CPP. In contrast, administration of 1 mlkg(-1) i.p. of vehicle did not reactivate the CPP response. Administration of the selective dopamine D-3 receptor antagonist SB-277011A (3-24 mgkg(-1) i.p.) 30 min before cocaine administration on the test day produced a significant attenuation of CPP reactivation. Reactivation of the CPP response produced by food deprivation was also significantly attenuated by SB-277011A (6 or 12 mgkg(-1) i.p.) given 30 min before the test session. SB-277011A (12 or 24 mgkg(-1) i.p.) did not itself produce reactivation of the CPP response. Overall, these results suggest that the reactivation of the incentive value of drug-associated cues by cocaine or food deprivation is attenuated by selective antagonism of D-3 receptors. Synapse 69:336-344, 2015. (c) 2015 Wiley Periodicals, Inc.
C1 [Ashby, Charles R., Jr.] St Johns Univ, Coll Pharm & Allied Hlth Profess, Dept Pharmaceut Sci, Jamaica, NY 11439 USA.
[Rice, Onarae V.] Furman Univ, Dept Psychol, Greenville, SC 29613 USA.
[Heidbreder, Christian A.] Indivior PLC, Richmond, VA USA.
[Gardner, Eliot L.] NIDA, Neuropsychopharmacol Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH, Baltimore, MD 21224 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; U.S. National Institutes
of Health [P20-GM103499]
FX Contract grant sponsor: National Institute of General Medical Sciences;
Contract grant sponsor: U.S. National Institutes of Health; Contract
grant number: P20-GM103499.
NR 71
TC 3
Z9 3
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0887-4476
EI 1098-2396
J9 SYNAPSE
JI Synapse
PD JUN
PY 2015
VL 69
IS 6
BP 336
EP 344
DI 10.1002/syn.21820
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA CH4WM
UT WOS:000354034000005
PM 25851636
ER
PT J
AU Shive, HR
West, RR
Embree, LJ
Sexton, JM
Hickstein, DD
AF Shive, Heather R.
West, Robert R.
Embree, Lisa J.
Sexton, Jamie M.
Hickstein, Dennis D.
TI Expression of KRAS(G12V) in Zebrafish Gills Induces Hyperplasia and
CXCL8-Associated Inflammation
SO ZEBRAFISH
LA English
DT Article
ID INCREASING COMPLEXITY; RAS; SOX9; INTERLEUKIN-8; GROWTH; GONAD; CELLS
AB The zebrafish (Danio rerio) represents an important animal model for analyzing genetic contributors to carcinogenesis. To assess the role for mutationally activated Ras in ovarian cancer, we developed a transgenic zebrafish model using the putative promoter for zebrafish insulin-like growth factor 3 (igf3) to drive expression of the human oncogene KRAS(G12V) fused to EGFP. A member of the IGF family, igf3 is unique to teleosts and reportedly exhibits gonad-specific expression in fish species. In contrast to previous studies, we observed igf3 expression in wild-type zebrafish gills in addition to gonads, indicating that igf3 expression is not necessarily gonad specific. In transgenic zebrafish, expression of EGFP-KRAS(G12V) driven by the igf3 promoter occurred only in the gills and resulted in proliferation of a putative progenitor cell population, chondroid hyperplasia, and localized inflammation. KRAS(G12V)-transformed cells in transgenic zebrafish showed activation of the ERK-MAP kinase pathway and expressed the zebrafish homologue for human CXCL8, a cytokine produced by mammalian Ras-transformed cells in tumor-associated inflammatory lesions. These findings indicate that KRAS(G12V)-transformed cells in zebrafish recruit inflammatory cells, but may require additional mutational events for neoplastic transformation. The conserved role for mutationally activated KRAS in leukocyte recruitment indicates that zebrafish can provide a valuable comparative model for Ras-associated inflammation.
C1 [Shive, Heather R.; West, Robert R.; Embree, Lisa J.; Sexton, Jamie M.; Hickstein, Dennis D.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Shive, HR (reprint author), N Carolina State Univ, Dept Populat Hlth & Pathobiol, Coll Vet Med, CVM Res Bldg,Room 248 1060 William Moore Dr, Raleigh, NC 27607 USA.
EM hrshive@ncsu.edu
FU U.S. National Institutes of Health, National Cancer Institute, Center
for Cancer Research
FX The authors thank Ms. Veena Kapoor for isolation and collection of
zebrafish cells by FACS. This work was supported by the Intramural
Research Program of the U.S. National Institutes of Health, National
Cancer Institute, Center for Cancer Research.
NR 24
TC 0
Z9 0
U1 1
U2 9
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1545-8547
EI 1557-8542
J9 ZEBRAFISH
JI Zebrafish
PD JUN 1
PY 2015
VL 12
IS 3
BP 221
EP 229
DI 10.1089/zeb.2014.1038
PG 9
WC Developmental Biology; Zoology
SC Developmental Biology; Zoology
GA CI1SU
UT WOS:000354525600003
PM 25798815
ER
PT J
AU Garcia-Matas, S
Paul, RK
Molina-Martinez, P
Palacios, H
Gutierrez, VM
Corpas, R
Pallas, M
Cristofol, R
de Cabo, R
Sanfeliu, C
AF Garcia-Matas, Silvia
Paul, Rajib K.
Molina-Martinez, Patricia
Palacios, Hector
Gutierrez, Vincent M.
Corpas, Ruben
Pallas, Merce
Cristofol, Rosa
de Cabo, Rafael
Sanfeliu, Coral
TI In vitro caloric restriction induces protective genes and functional
rejuvenation in senescent SAMP8 astrocytes
SO AGING CELL
LA English
DT Article
DE astrocytes; caloric restriction; mitochondria; oxidative stress; RNA
microarrays; SAMP8
ID ALZHEIMERS-DISEASE; OXIDATIVE STRESS; MOUSE MODEL; NEUROPROTECTIVE
CAPACITY; ACCELERATED MICE; RHESUS-MONKEYS; WISTAR RATS; HUMANS;
HEALTHSPAN; LONGEVITY
AB Astrocytes are key cells in brain aging, helping neurons to undertake healthy aging or otherwise letting them enter into a spiral of neurodegeneration. We aimed to characterize astrocytes cultured from senescence-accelerated prone 8 (SAMP8) mice, a mouse model of brain pathological aging, along with the effects of caloric restriction, the most effective rejuvenating treatment known so far. Analysis of the transcriptomic profiles of SAMP8 astrocytes cultured in control conditions and treated with caloric restriction serum was performed using mRNA microarrays. A decrease in mitochondrial and ribosome mRNA, which was restored by caloric restriction, confirmed the age-related profile of SAMP8 astrocytes and the benefits of caloric restriction. An amelioration of antioxidant and neurodegeneration-related pathways confirmed the brain benefits of caloric restriction. Studies of oxidative stress and mitochondrial function demonstrated a reduction of oxidative damage and partial improvement of mitochondria after caloric restriction. In summary, caloric restriction showed a significant tendency to normalize pathologically aged astrocytes through the activation of pathways that are protective against the age-related deterioration of brain physiology.
C1 [Garcia-Matas, Silvia; Molina-Martinez, Patricia; Corpas, Ruben; Cristofol, Rosa; Sanfeliu, Coral] CSIC, Biomed Res Inst Barcelona IIBB, Aging & Neurodegenerat Unit, Barcelona 08036, Spain.
[Garcia-Matas, Silvia; Molina-Martinez, Patricia; Corpas, Ruben; Cristofol, Rosa; Sanfeliu, Coral] IDIBAPS, Barcelona 08036, Spain.
[Paul, Rajib K.; Palacios, Hector; Gutierrez, Vincent M.; de Cabo, Rafael] NIA, Expt Gerontol Sect, TGB, NIH, Baltimore, MD 21224 USA.
[Pallas, Merce] Univ Barcelona, Fac Pharm, Dept Pharmacol & Therapeut Chem, IBUB, E-08028 Barcelona, Spain.
[Pallas, Merce] CIBERNED, Barcelona 08028, Spain.
RP de Cabo, R (reprint author), NIA, Expt Gerontol Sect, TGB, NIH, Suite 100 Room 9C218,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM decabora@grc.nia.nih.gov
RI de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693;
Pallas, Merce/0000-0003-3095-4254
FU Spanish MINECO [SAF2009-13093, SAF2012-39852, CSD2010-00045];
Generalitat of Catalonia [2009/SGR/214]; European Regional evelopment
Fund (ERDF)
FX This study was supported by grants SAF2009-13093, SAF2012-39852, and
CSD2010-00045 from the Spanish MINECO, 2009/SGR/214 from the Generalitat
of Catalonia, and the European Regional evelopment Fund (ERDF).
NR 45
TC 2
Z9 2
U1 1
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9718
EI 1474-9726
J9 AGING CELL
JI Aging Cell
PD JUN
PY 2015
VL 14
IS 3
BP 334
EP 344
DI 10.1111/acel.12259
PG 11
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA CH0DN
UT WOS:000353689400004
PM 25711920
ER
PT J
AU Brockie, TN
Dana-Sacco, G
Wallen, GR
Wilcox, HC
Campbell, JC
AF Brockie, Teresa N.
Dana-Sacco, Gail
Wallen, Gwenyth R.
Wilcox, Holly C.
Campbell, Jacquelyn C.
TI The Relationship of Adverse Childhood Experiences to PTSD, Depression,
Poly-Drug Use and Suicide Attempt in Reservation-Based Native American
Adolescents and Young Adults
SO AMERICAN JOURNAL OF COMMUNITY PSYCHOLOGY
LA English
DT Article
DE Native American; Youth; Adverse childhood experiences; Risk behavior;
Mental health; Reservation-based; Perceived discrimination; Historical
loss associated symptoms
ID SHORT SCREENING SCALE; POSTTRAUMATIC-STRESS-DISORDER; PERCEIVED
DISCRIMINATION; HOUSEHOLD DYSFUNCTION; INDIGENOUS ADOLESCENTS; PARTNER
VIOLENCE; HISTORICAL LOSS; ALCOHOL-ABUSE; SUBSTANCE USE; RISK
AB Adverse childhood experiences (ACEs) are associated with numerous risk behaviors and mental health outcomes among youth. This study examines the relationship between the number of types of exposures to ACEs and risk behaviors and mental health outcomes among reservation-based Native Americans. In 2011, data were collected from Native American (N = 288; 15-24 years of age) tribal members from a remote plains reservation using an anonymous web-based questionnaire. We analyzed the relationship between six ACEs, emotional, physical, and sexual abuse, physical and emotional neglect, witness to intimate partner violence, for those < 18 years, and included historical loss associated symptoms, and perceived discrimination for those < 19 years; and four risk behavior/mental health outcomes: post-traumatic stress disorder (PTSD) symptoms, depression symptoms, poly-drug use, and suicide attempt. Seventy-eight percent of the sample reported at least one ACE and 40 % reported at least two. The cumulative impact of the ACEs were significant (p < .001) for the four outcomes with each additional ACE increasing the odds of suicide attempt (37 %), poly-drug use (51 %), PTSD symptoms (55 %), and depression symptoms (57 %). To address these findings culturally appropriate childhood and adolescent interventions for reservation-based populations must be developed, tested and evaluated longitudinally.
C1 [Brockie, Teresa N.; Wallen, Gwenyth R.] NIH, Nursing Res & Translat Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Dana-Sacco, Gail] Univ Maine, Orono, ME USA.
[Wilcox, Holly C.] Johns Hopkins Sch Med, Baltimore, MD USA.
[Campbell, Jacquelyn C.] Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA.
RP Brockie, TN (reprint author), NIH, Nursing Res & Translat Sci, Ctr Clin, 10 Ctr Dr,Room 3C440, Bethesda, MD 20892 USA.
EM brockiet@cc.nih.gov; gail.danasacco@gmail.com; GWallen@cc.nih.gov;
hwilcox1@jhmi.edu
FU National Institutes of Health Clinical Center; Johns Hopkins Bloomberg
School of Public Health Center for American Indian Health
FX We gratefully acknowledge Dr. John Umhau, Indian Health Service, for his
expertise. This work was supported in part by the intramural research
program at the National Institutes of Health Clinical Center and the
Johns Hopkins Bloomberg School of Public Health Center for American
Indian Health.
NR 57
TC 9
Z9 9
U1 2
U2 36
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0091-0562
EI 1573-2770
J9 AM J COMMUN PSYCHOL
JI Am. J. Community Psychol.
PD JUN
PY 2015
VL 55
IS 3-4
BP 411
EP 421
DI 10.1007/s10464-015-9721-3
PG 11
WC Public, Environmental & Occupational Health; Psychology,
Multidisciplinary; Social Work
SC Public, Environmental & Occupational Health; Psychology; Social Work
GA CH1JT
UT WOS:000353778300015
PM 25893815
ER
PT J
AU Piao, YS
Hall, FS
Moriya, Y
Ito, M
Ohara, A
Kikura-Hanajiri, R
Goda, Y
Lesch, KP
Murphy, DL
Uhl, GR
Sora, I
AF Piao, Ying-Shan
Hall, Frank Scott
Moriya, Yuki
Ito, Miki
Ohara, Arihisa
Kikura-Hanajiri, Ruri
Goda, Yukihiro
Lesch, Klaus-Peter
Murphy, Dennis L.
Uhl, George R.
Sora, Ichiro
TI Methylone-induced hyperthermia and lethal toxicity: role of the dopamine
and serotonin transporters
SO BEHAVIOURAL PHARMACOLOGY
LA English
DT Article
DE dopamine; hyperthermia; knockout mice; lethality; methylone; serotonin;
toxicity; transporter
ID CONDITIONED PLACE PREFERENCE; BODY-TEMPERATURE;
3,4-METHYLENEDIOXYMETHAMPHETAMINE ECSTASY; MONOAMINE TRANSPORTERS;
AMBIENT-TEMPERATURE; PHARMACOLOGICAL CHARACTERIZATION; METHAMPHETAMINE
NEUROTOXICITY; BRAIN HYPERTHERMIA; COCAINE REWARD; MICE LACKING
AB Methylone (2-methylamino-1-[3,4-methylenedioxy-phenyl] propan-1-one), an amphetamine analog, has emerged as a popular drug of abuse worldwide. Methylone induces hyperthermia, which is thought to contribute toward the lethal consequences of methylone overdose. Methylone has been assumed to induce hyperthermic effects through inhibition of serotonin and/or dopamine transporters (SERT and DAT, respectively). To examine the roles of each of these proteins in methylone-induced toxic effects, we used SERT and DAT knockout (KO) mice and assessed the hyperthermic and lethal effects caused by a single administration of methylone. Methylone produced higher rates of lethal toxicity compared with other amphetamine analogs in wild-type mice. Compared with wild-type mice, lethality was significantly lower in DAT KO mice, but not in SERT KO mice. By contrast, only a slight diminution in the hyperthermic effects of methylone was observed in DAT KO mice, whereas a slight enhancement of these effects was observed in SERT KO mice. Administration of the selective D1 receptor antagonist SCH 23390 and the D2 receptor antagonist raclopride reduced methylone-induced hyperthermia, but these drugs also had hypothermic effects in saline-treated mice, albeit to a smaller extent than the effects observed in methylone-treated mice. In contradistinction to 3,4-methylenedioxymethamphetamine, which induces its toxicity through SERT and DAT, these data indicate that DAT, but not SERT, is strongly associated with the lethal toxicity produced by methylone, which did not seem to be dependent on the hyperthermic effects of methylone. DAT is therefore a strong candidate molecule for interventions aimed at preventing acute neurotoxic and lethal effects of methylone. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.
C1 [Piao, Ying-Shan; Moriya, Yuki; Ito, Miki; Ohara, Arihisa; Sora, Ichiro] Tohoku Univ, Grad Sch Med, Dept Biol Psychiat, Sendai, Miyagi 980, Japan.
[Kikura-Hanajiri, Ruri; Goda, Yukihiro] Natl Inst Hlth Sci, Div Pharmacognosy Phytochem & Narcot, Tokyo, Japan.
[Sora, Ichiro] Kobe Univ, Dept Psychiat, Grad Sch Med, Kobe, Hyogo 6500017, Japan.
[Hall, Frank Scott] Univ Toledo, Coll Pharm & Pharmaceut Sci, Dept Pharmacol, Toledo, OH 43606 USA.
[Murphy, Dennis L.] NIMH, Clin Sci Lab, Bethesda, MD 20892 USA.
[Uhl, George R.] NIA, Mol Neurobiol Branch, Intramural Res Program, Baltimore, MD 21224 USA.
[Lesch, Klaus-Peter] Univ Wurzburg, Dept Psychiat, Wurzburg, Germany.
[Piao, Ying-Shan] Capital Med Univ, Dept Geriatr, Beijing Tiantan, Beijing, Peoples R China.
RP Sora, I (reprint author), Kobe Univ, Dept Psychiat, Grad Sch Med, Chuo Ku, 7-5-1 Kusunoki Cho, Kobe, Hyogo 6500017, Japan.
EM sora@med.kobe-u.ac.jp
RI Hall, Frank/C-3036-2013; Lesch, Klaus-Peter/J-4906-2013
OI Hall, Frank/0000-0002-0822-4063; Lesch, Klaus-Peter/0000-0001-8348-153X
FU Ministry of Health, Labor, and Welfare of Japan; Ministry of Education,
Culture, Sports, Science, and Technology of Japan; National Institute on
Drug abuse, Intramural Research Program, NIH (USA)
FX This study was supported in part by a Grant-in-Aid for Health and Labor
Science Research (Research on Pharmaceutical and Medical Safety) from
the Ministry of Health, Labor, and Welfare of Japan (I.S.), by
Grants-in-Aid for Scientific Research (B), Scientific Research on
Priority Areas-System study on higher-order brain functions and Research
on Pathomechanisms of Brain Disorders, Core Research for Evolutional
Science and Technology (CREST), from the Ministry of Education, Culture,
Sports, Science, and Technology of Japan (I.S.), and by the National
Institute on Drug abuse, Intramural Research Program, NIH (USA)
(G.R.U.).
NR 52
TC 2
Z9 2
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0955-8810
EI 1473-5849
J9 BEHAV PHARMACOL
JI Behav. Pharmacol.
PD JUN
PY 2015
VL 26
IS 4
BP 345
EP 352
DI 10.1097/FBP.0000000000000135
PG 8
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA CH2GT
UT WOS:000353844400003
PM 25794333
ER
PT J
AU Maio, N
Rouault, TA
AF Maio, Nunziata
Rouault, Tracey A.
TI Iron-sulfur cluster biogenesis in mammalian cells: New insights into the
molecular mechanisms of cluster delivery
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
LA English
DT Review
DE LYR motif protein; HSC20; HSPA9; ISCU; SDHB; Mammalian Fe-S cluster
assembly
ID COMPLEX I DEFICIENCY; LINKED SIDEROBLASTIC ANEMIA; SCAFFOLD PROTEIN
ISCU; MITOCHONDRIAL CYSTEINE DESULFURASE; MOLYBDENUM COFACTOR
BIOSYNTHESIS; MONOTHIOL GLUTAREDOXINS FUNCTION; RESPIRATORY-CHAIN
COMPLEXES; FRIEDREICH ATAXIA PATIENTS; TRIPLET-REPEAT EXPANSION; ABC
TRANSPORTER ATM1P
AB Iron-sulfur (Fe-S) clusters are ancient, ubiquitous cofactors composed of iron and inorganic sulfur. The combination of the chemical reactivity of iron and sulfur, together with many variations of cluster composition, oxidation states and protein environments, enables Fe-S clusters to participate in numerous biological processes. Fe-S clusters are essential to redox catalysis in nitrogen fixation, mitochondrial respiration and photosynthesis, to regulatory sensing in key metabolic pathways (i.e. cellular iron homeostasis and oxidative stress response), and to the replication and maintenance of the nuclear genome.
Fe-S cluster biogenesis is a multistep process that involves a complex sequence of catalyzed protein-protein interactions and coupled conformational changes between the components of several dedicated multimeric complexes. Intensive studies of the assembly process have clarified key points in the biogenesis of Fe-S proteins. However several critical questions still remain, such as: what is the role of frataxin? Why do some defects of Fe-S cluster biogenesis cause mitochondrial iron overload? How are specific Fe-S recipient proteins recognized in the process of Fe-S transfer?
This review focuses on the basic steps of Fe-S cluster biogenesis, drawing attention to recent advances achieved on the identification of molecular features that guide selection of specific subsets of nascent Fe-S recipients by the cochaperone HSC20. Additionally, it outlines the distinctive phenotypes of human diseases due to mutations in the components of the basic pathway. This article is part of a Special Issue entitled: Fe/S proteins: Analysis, structure, function, biogenesis and diseases. Published by Elsevier B.V.
C1 [Maio, Nunziata; Rouault, Tracey A.] 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, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rouault@mail.nih.gov
FU Intramural program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development
FX The authors are grateful to Dr. Wing-Hang Tong for critical reading of
the manuscript and for insightful discussion. This work was supported by
the Intramural program of the Eunice Kennedy Shriver National Institute
of Child Health and Human Development.
NR 330
TC 33
Z9 34
U1 6
U2 29
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-4889
EI 0006-3002
J9 BBA-MOL CELL RES
JI Biochim. Biophys. Acta-Mol. Cell Res.
PD JUN
PY 2015
VL 1853
IS 6
SI SI
BP 1493
EP 1512
DI 10.1016/j.bbamcr.2014.09.009
PG 20
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CH0RG
UT WOS:000353729500020
PM 25245479
ER
PT J
AU Rossini, PM
Burke, D
Chen, R
Cohen, LG
Daskalakis, Z
Di Iorio, R
Di Lazzaro, V
Ferreri, F
Fitzgerald, PB
George, MS
Hallett, M
Lefaucheur, JP
Langguth, B
Matsumoto, H
Miniussi, C
Nitsche, MA
Pascual-Leone, A
Paulus, W
Rossi, S
Rothwell, JC
Siebner, HR
Ugawa, Y
Walsh, V
Ziemann, U
AF Rossini, P. M.
Burke, D.
Chen, R.
Cohen, L. G.
Daskalakis, Z.
Di Iorio, R.
Di Lazzaro, V.
Ferreri, F.
Fitzgerald, P. B.
George, M. S.
Hallett, M.
Lefaucheur, J. P.
Langguth, B.
Matsumoto, H.
Miniussi, C.
Nitsche, M. A.
Pascual-Leone, A.
Paulus, W.
Rossi, S.
Rothwell, J. C.
Siebner, H. R.
Ugawa, Y.
Walsh, V.
Ziemann, U.
TI Non-invasive electrical and magnetic stimulation of the brain, spinal
cord, roots and peripheral nerves: Basic principles and procedures for
routine clinical and research application. An updated report from an
IFCN Committee
SO CLINICAL NEUROPHYSIOLOGY
LA English
DT Review
DE Non-invasive stimulation; Transcranial magnetic stimulation; Human
cortex; Clinical neurophysiology; TMS measures; Excitability threshold
ID HUMAN MOTOR CORTEX; THETA-BURST-STIMULATION; PAIRED ASSOCIATIVE
STIMULATION; INTRACTABLE DEAFFERENTATION PAIN; DORSOLATERAL PREFRONTAL
CORTEX; AMYOTROPHIC-LATERAL-SCLEROSIS; LATENCY AFFERENT INHIBITION;
FORAMEN MAGNUM LEVEL; INTERVAL INTRACORTICAL INHIBITION; PROGRESSIVE
MYOCLONUS EPILEPSY
AB These guidelines provide an up-date of previous IFCN report on ``Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application'' (Rossini et al., 1994). A new Committee, composed of international experts, some of whom were in the panel of the 1994 ''Report'', was selected to produce a current state-of-the-art review of non-invasive stimulation both for clinical application and research in neuroscience.
Since 1994, the international scientific community has seen a rapid increase in non-invasive brain stimulation in studying cognition, brain-behavior relationship and pathophysiology of various neurologic and psychiatric disorders. New paradigms of stimulation and new techniques have been developed. Furthermore, a large number of studies and clinical trials have demonstrated potential therapeutic applications of non-invasive brain stimulation, especially for TMS. Recent guidelines can be found in the literature covering specific aspects of non-invasive brain stimulation, such as safety (Rossi et al., 2009), methodology (Groppa et al., 2012) and therapeutic applications (Lefaucheur et al., 2014).
This up-dated review covers theoretical, physiological and practical aspects of non-invasive stimulation of brain, spinal cord, nerve roots and peripheral nerves in the light of more updated knowledge, and include some recent extensions and developments. (C) 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd.
C1 [Rossini, P. M.; Di Iorio, R.] Univ Cattolica Sacro Cuore, Dept Geriatr Neurosci & Orthoped, Policlin A Gemelli, Inst Neurol, I-00168 Rome, Italy.
[Burke, D.] Univ Sydney, Royal Prince Alfred Hosp, Dept Neurol, Sydney, NSW 2006, Australia.
[Chen, R.] Univ Toronto, Toronto Western Res Inst, Div Neurol, Toronto, ON, Canada.
[Cohen, L. G.] NINDS, Human Cort Physiol & Neurorehabil Sect, NIH, Bethesda, MD 20892 USA.
[Daskalakis, Z.] Univ Toronto, Temerty Ctr Therapeut Brain Intervent, Ctr Addict & Mental Hlth, Toronto, ON, Canada.
[Di Lazzaro, V.; Ferreri, F.] Univ Campus Biomed, Dept Neurol, Rome, Italy.
[Ferreri, F.] Univ Eastern Finland, Dept Clin Neurophysiol, Kuopio, Finland.
[Fitzgerald, P. B.] Monash Univ, Cent Clin Sch, Monash Alfred Psychiat Res Ctr, Melbourne, Vic 3004, Australia.
[Fitzgerald, P. B.] The Alfred, Melbourne, Vic, Australia.
[George, M. S.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA.
[Hallett, M.] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Lefaucheur, J. P.] Henri Mondor Hosp, AP HP, Dept Physiol, F-94010 Creteil, France.
[Lefaucheur, J. P.] Paris Est Creteil Univ, Fac Med, Nerve Excitabil & Therapeut Team, EA 4391, F-94010 Creteil, France.
[Langguth, B.] Univ Regensburg, Dept Psychiat & Psychotherapy, D-93053 Regensburg, Germany.
[Matsumoto, H.] Japanese Red Cross Med Ctr, Dept Neurol, Tokyo, Japan.
[Miniussi, C.] Univ Brescia, Dept Clin & Expt Sci, Brescia, Italy.
[Miniussi, C.] IRCCS, Ctr San Giovanni Dio Fatebenefratelli, Brescia, Italy.
[Nitsche, M. A.] Univ Gottingen, Univ Med Ctr Groningen, Dept Clin Neurophysiol, D-37073 Gottingen, Germany.
[Pascual-Leone, A.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA USA.
[Paulus, W.] Univ Gottingen, Dept Clin Neurophysiol, D-37073 Gottingen, Germany.
[Rossi, S.] Univ Siena, Brain Invest & Neuromodulat Lab, Unit Neurol & Clin Neurophysiol, Dept Neurosci, I-53100 Siena, Italy.
[Rothwell, J. C.] UCL, Inst Neurol, London, England.
[Siebner, H. R.] Univ Copenhagen, Bispebjerg Hosp, Dept Neurol, Copenhagen, Denmark.
[Siebner, H. R.] Univ Copenhagen, Hvidovre Hosp, Danish Res Ctr Magnet Resonance, Ctr Funct & Diagnost Imaging & Res, DK-2650 Hvidovre, Denmark.
[Ugawa, Y.] Fukushima Med Univ, Dept Neurol, Sch Med, Fukushima, Japan.
[Walsh, V.] UCL, Inst Cognit Neurosci, London, England.
[Ziemann, U.] Univ Tubingen, Dept Neurol & Stroke, Tubingen, Germany.
[Ziemann, U.] Univ Tubingen, Hertie Inst Clin Brain Res, Tubingen, Germany.
RP Di Iorio, R (reprint author), Univ Cattolica Sacro Cuore, Dept Geriatr Neurosci & Orthoped, Policlin A Gemelli, Inst Neurol, Lgo A Gemelli 8, I-00168 Rome, Italy.
EM r.diiorio@live.it
RI Siebner, Hartwig/G-4052-2016; Miniussi, Carlo/E-7602-2010; Chen,
Robert/B-3899-2009; Paulus, Walter/A-3544-2009;
OI Miniussi, Carlo/0000-0002-5436-4745; Chen, Robert/0000-0002-8371-8629;
Paulus, Walter/0000-0001-5549-8377; Ferreri,
Florinda/0000-0002-7938-905X; Rothwell, John/0000-0003-1367-6467; Di
Lazzaro, Vincenzo/0000-0002-9113-5925; rossi, simone/0000-0001-6697-9459
NR 493
TC 140
Z9 141
U1 25
U2 101
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1388-2457
EI 1872-8952
J9 CLIN NEUROPHYSIOL
JI Clin. Neurophysiol.
PD JUN
PY 2015
VL 126
IS 6
BP 1071
EP 1107
DI 10.1016/j.clinph.2015.02.001
PG 37
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CH1ME
UT WOS:000353785000006
PM 25797650
ER
PT J
AU Penesova, A
Koska, J
Ortega, E
Bunt, JC
Bogardus, C
de Courten, B
AF Penesova, A.
Koska, J.
Ortega, E.
Bunt, J. C.
Bogardus, C.
de Courten, B.
TI Salsalate has no effect on insulin secretion but decreases insulin
clearance: a randomized, placebo-controlled trial in subjects without
diabetes
SO DIABETES OBESITY & METABOLISM
LA English
DT Article
DE C-peptide; insulin secretion; salicylates; salsalate; stepped
hyperglycaemia
ID GLUCOSE-TOLERANCE; HEALTHY
AB To elucidate whether increased insulin concentration after salsalate treatment (3 g/day for 7 days) is attributable to an increased insulin secretion rate (ISR) or to reduced metabolic clearance of endogenous insulin (MCI) during stepped glucose infusion (SGI). The analysis was performed in obese subjects who participated in a randomized double-blind, parallel, placebo-controlled clinical trial. A total of 27 participants (16 on salsalate, 11 on placebo) completed baseline and follow-up SGI. During SGI in the salsalate group, C-peptide concentrations were reduced by 11%, while plasma insulin concentrations were increased by 30%, corresponding to a 30% reduction in MCI (p< 0.0001). At molar increments of glucose, insulin concentrations were increased by 27% (p= 0.02), but ISR was unchanged. Salsalate did not alter insulin secretion, but lowered MCI, indicating that a reduction in insulin clearance is the principal mechanism for increased insulin levels after salsalate administration.
C1 [Penesova, A.; Koska, J.; Ortega, E.; Bunt, J. C.; Bogardus, C.; de Courten, B.] NIDDK, Obes & Diabet Clin Res Sect, Phoenix Epidemiol & Clin Res Branch, NIH,DHHS, Phoenix, AZ USA.
[Penesova, A.] Slovak Acad Sci, Inst Expt Endocrinol, Ctr Mol Med, Bratislava, Slovakia.
[Koska, J.] Phoenix VA Hlth Care Syst, Phoenix, AZ USA.
[Ortega, E.] CIBEROBN, IDIBAPS, Hosp Clin, Dept Endocrinol & Nutr,ICMDM, Barcelona, Spain.
[de Courten, B.] Monash Univ, Sch Publ Hlth & Prevent Med, MCHRI, Melbourne, Vic 3004, Australia.
RP de Courten, B (reprint author), Monash Univ, Sch Publ Hlth & Prevent Med, Monash Ctr Hlth Res & Implementat, 43-51 Kanooka Grove, Clayton, Vic 3186, Australia.
EM barbora.decourten@monash.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX We would like to thank John Graves, Carol Massengill, Jeanette Impson,
metabolic kitchen, nursing and technical staff, and the individuals who
volunteered for this study. The contents of this article do not
represent the views of the Department of Health and Human Services,
Department of Veterans Affairs or the US Government. All the research
was supported by the National Institute of Diabetes and Digestive and
Kidney Diseases intramural programme.
NR 12
TC 2
Z9 2
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1462-8902
EI 1463-1326
J9 DIABETES OBES METAB
JI Diabetes Obes. Metab.
PD JUN
PY 2015
VL 17
IS 6
BP 608
EP 612
DI 10.1111/dom.12450
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CH1EX
UT WOS:000353765000013
PM 25683256
ER
PT J
AU Bornstein, MH
Putnick, DL
Lansford, JE
Pastorelli, C
Skinner, AT
Sorbring, E
Tapanya, S
Tirado, LMU
Zelli, A
Alampay, LP
Al-Hassan, SM
Bacchini, D
Bombi, AS
Chang, L
Deater-Deckard, K
Di Giunta, L
Dodge, KA
Malone, PS
Oburu, P
AF Bornstein, Marc H.
Putnick, Diane L.
Lansford, Jennifer E.
Pastorelli, Concetta
Skinner, Ann T.
Sorbring, Emma
Tapanya, Sombat
Uribe Tirado, Liliana Maria
Zelli, Arnaldo
Pena Alampay, Liane
Al-Hassan, Suha M.
Bacchini, Dario
Bombi, Anna Silvia
Chang, Lei
Deater-Deckard, Kirby
Di Giunta, Laura
Dodge, Kenneth A.
Malone, Patrick S.
Oburu, Paul
TI Mother and father socially desirable responding in nine countries: Two
kinds of agreement and relations to parenting self-reports
SO INTERNATIONAL JOURNAL OF PSYCHOLOGY
LA English
DT Article
DE Mothers; Socially desirable responding; Fathers; Culture
ID CROSS-NATIONAL SAMPLES; SHORT FORMS; MULTIATTRIBUTIONAL CAUSALITY;
ORGANIZATIONAL-BEHAVIOR; MARLOWE; BIAS; SCALE; CULTURE; GENDER; STYLES
AB We assessed 2 forms of agreement between mothers' and fathers' socially desirable responding in China, Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand and the United States (N = 1110 families). Mothers and fathers in all 9 countries reported socially desirable responding in the upper half of the distribution, and countries varied minimally (but China was higher than the cross-country grand mean and Sweden lower). Mothers and fathers did not differ in reported levels of socially desirable responding, and mothers' and fathers' socially desirable responding were largely uncorrelated. With one exception, mothers' and fathers' socially desirable responding were similarly correlated with self-perceptions of parenting, and correlations varied somewhat across countries. These findings are set in a discussion of socially desirable responding, cultural psychology and family systems.
C1 [Bornstein, Marc H.; Putnick, Diane L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Child & Family Res, Bethesda, MD 20892 USA.
[Lansford, Jennifer E.; Skinner, Ann T.; Dodge, Kenneth A.] Duke Univ, Ctr Child & Family Policy, Durham, NC USA.
[Pastorelli, Concetta; Uribe Tirado, Liliana Maria; Bombi, Anna Silvia; Di Giunta, Laura] Univ Roma La Sapienza, Fac Psychol, I-00185 Rome, Italy.
[Sorbring, Emma] Univ West, Dept Psychol, Trollhottan, Sweden.
[Tapanya, Sombat] Chiang Mai Univ, Dept Psychiat, Chiang Mai, Thailand.
[Uribe Tirado, Liliana Maria] Univ San Buenaventura, Consultorio Psicol Popular, Bolivar, Colombia.
[Zelli, Arnaldo] Univ Rome Foro Italico, Dept Educ Sci, Rome, Italy.
[Pena Alampay, Liane] Ateneo Manila Univ, Dept Psychol, Quezon City, Philippines.
[Al-Hassan, Suha M.] Hashemite Univ, Queen Rania Fac Childhood, Az Zarqa, Jordan.
[Bacchini, Dario] Univ Naples 2, Dept Psychol, Naples, Italy.
[Chang, Lei] Chinese Univ Hong Kong, Dept Educ Psychol, Hong Kong, Hong Kong, Peoples R China.
[Deater-Deckard, Kirby] Virginia Polytech Inst & State Univ, Dept Psychol, Blacksburg, VA 24061 USA.
[Malone, Patrick S.] Univ S Carolina, Dept Psychol, Columbia, SC 29208 USA.
[Oburu, Paul] Maseno Univ, Dept Psychol, Maseno, Kenya.
RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Child & Family Res, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA.
EM Marc_H_Bornstein@nih.gov
RI ZELLI, ARNALDO/N-2333-2015;
OI ZELLI, ARNALDO/0000-0003-4020-8159; Bacchini, Dario/0000-0001-6140-9377;
Putnick, Diane/0000-0002-6323-749X
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [RO1-HD054805]; Fogarty International Center [RO3-TW008141];
NIH, NICHD
FX MHB, DLP and JEL designed the study. MHB and DLP drafted the initial
manuscript. DLP conducted the analyses. All other authors collected and
coded the data and contributed to revising the manuscript. We thank A.
Dovidio and the families who participated in this research. This
research was funded by the Eunice Kennedy Shriver National Institute of
Child Health and Human Development (grant RO1-HD054805) and the Fogarty
International Center (grant RO3-TW008141) and was supported by the
Intramural Research Program of the NIH, NICHD. This article has been
contributed to by US Government employees and their work is in the
public domain in the USA.
NR 87
TC 11
Z9 11
U1 5
U2 19
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 0020-7594
EI 1464-066X
J9 INT J PSYCHOL
JI Int. J. Psychol.
PD JUN
PY 2015
VL 50
IS 3
BP 174
EP 185
DI 10.1002/ijop.12084
PG 12
WC Psychology, Multidisciplinary
SC Psychology
GA CH4AB
UT WOS:000353971500002
PM 25043708
ER
PT J
AU Gonzalez, CE
Pacheco, J
Beason-Held, LL
Resnick, SM
AF Gonzalez, Christopher E.
Pacheco, Jennifer
Beason-Held, Lori L.
Resnick, Susan M.
TI Longitudinal changes in cortical thinning associated with hypertension
SO JOURNAL OF HYPERTENSION
LA English
DT Article
DE blood pressure variability; brain aging; cortical thickness;
longitudinal change; midlife blood pressure
ID MIDLIFE BLOOD-PRESSURE; MAGNETIC-RESONANCE IMAGES; HUMAN
CEREBRAL-CORTEX; WHITE-MATTER LESIONS; ALZHEIMERS-DISEASE; OLDER-ADULTS;
GEOMETRICALLY ACCURATE; COGNITIVE FUNCTION; BRAIN MORPHOLOGY;
SEGMENTATION
AB Background: Cross-sectional studies of the association between hypertension (HTN) and brain atrophy have shown reductions in prefrontal, temporal, and hippocampal volumes, and have identified thinner cortices across the cortical mantle.
Method: In the current study, we followed 96 participants enrolled in the Baltimore Longitudinal Study of Aging over a mean interval of 8 years (mean age at baseline = 68.7) and compared those who are hypertensive (n = 49) throughout the study with those who are normotensive (n = 47).
Results: Hypertensive individuals show an increased rate of thinning compared with normotensive individuals in several regions, including the frontomarginal gyrus in the left hemisphere, and the superior temporal, fusiform, and lateral orbitofrontal cortex in the right hemisphere. We also investigated the effects of midlife blood pressure (BP), intervisit variability in BP prior to imaging, and duration of HTN on areas that show subsequent differences in the rates of cortical thinning between groups. We found that higher midlife BP and longer durations of HTN predicted a higher rate of thinning in the right superior temporal gyrus. We also found that greater variability in SBP but not DBP predicted a higher rate of thinning in the right superior temporal gyrus, frontomarginal gyrus, and occipital pole.
Conclusion: These findings demonstrate that hypertensive individuals show increased rates of thinning compared with normotensive individuals and suggest intervisit BP variability and midlife BP contribute to these longitudinal differences.
C1 [Gonzalez, Christopher E.; Pacheco, Jennifer; Beason-Held, Lori L.; Resnick, Susan M.] NIA, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA.
[Pacheco, Jennifer] Walter Reed Natl Mil Med Ctr, Natl Intrepid Ctr Excellence, Bethesda, MD USA.
RP Beason-Held, LL (reprint author), NIA, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM heldlo@mail.nih.gov
FU NIH, National Institute on Aging; [N01-AG-3-2124]
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute on Aging and by Research and Development
Contract N01-AG-3-2124.
NR 44
TC 4
Z9 4
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0263-6352
EI 1473-5598
J9 J HYPERTENS
JI J. Hypertens.
PD JUN
PY 2015
VL 33
IS 6
BP 1242
EP 1248
DI 10.1097/HJH.0000000000000531
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CH1YN
UT WOS:000353819700019
PM 25693060
ER
PT J
AU Ortiz, AM
DiNapoli, SR
Brenchley, JM
AF Ortiz, Alexandra M.
DiNapoli, Sarah R.
Brenchley, Jason M.
TI Macrophages Are Phenotypically and Functionally Diverse across Tissues
in Simian Immunodeficiency Virus-Infected and Uninfected Asian Macaques
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID DENDRITIC CELLS; MICROBIAL TRANSLOCATION; IMMUNE ACTIVATION; ALVEOLAR
MACROPHAGES; EXPERIMENTAL COLITIS; LY6C(HI) MONOCYTES; INNATE IMMUNITY;
SIV INFECTION; HIV-INFECTION; PHAGOCYTOSIS
AB Macrophages regulate tissue immunity, orchestrating the initiation and resolution of antimicrobial immune responses and repair of damaged tissue architecture. Their dysfunction can, thus, manifest in either pro-and anti-inflammatory responses. Indeed, despite the importance of macrophage function in health and disease, the role of tissue-resident macrophages in human immunodeficiency virus (HIV) disease progression remains incompletely defined. Here, we use flow cytometry to assess the phenotypes and functions of macrophages isolated from the spleens, axillary lymph nodes, colons, jejuna, and livers of healthy and chronically simian immunodeficiency virus (SIV)-infected Asian macaques, the prominent nonhuman primate model for HIV infection. Our data demonstrate that macrophages from healthy animals exhibit considerable phenotypic and functional heterogeneity across tissues and across a variety of stimuli. Further, our analysis reveals changes in the lipopolysaccharide (LPS) responsiveness of macrophages isolated from SIV-infected animals. We anticipate that our findings will inform future research into macrophage-directed immunity across a variety of primate diseases.
IMPORTANCE
These findings highlight the functional and phenotypic heterogeneity of tissue macrophages in different anatomic sites and as a result of SIV infection. We believe that our data will lead to novel therapeutic interventions aimed at altering the proinflammatory capacity of tissue macrophages in progressively HIV-infected individuals.
C1 [Brenchley, Jason M.] NIAID, Program Tissue Immun & Repair, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
NIAID, Immunopathogenesis Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
RP Brenchley, JM (reprint author), NIAID, Program Tissue Immun & Repair, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jbrenchl@niaid.nih.gov
OI DiNapoli, Sarah/0000-0002-3675-9030
FU Division of Intramural Research/NIAID/NIH
FX Funding for this study was provided by the Division of Intramural
Research/NIAID/NIH.
NR 48
TC 6
Z9 6
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD JUN
PY 2015
VL 89
IS 11
BP 5883
EP 5894
DI 10.1128/JVI.00005-15
PG 12
WC Virology
SC Virology
GA CH3DU
UT WOS:000353907900013
PM 25787286
ER
PT J
AU Saunders, KO
Pegu, A
Georgiev, IS
Zeng, M
Joyce, MG
Yang, ZY
Ko, SY
Chen, XJ
Schmidt, SD
Haase, AT
Todd, JP
Bao, S
Kwong, PD
Rao, SS
Mascola, JR
Nabel, GJ
AF Saunders, Kevin O.
Pegu, Amarendra
Georgiev, Ivelin S.
Zeng, Ming
Joyce, M. Gordon
Yang, Zhi-Yong
Ko, Sung-Youl
Chen, Xuejun
Schmidt, Stephen D.
Haase, Ashley T.
Todd, John-Paul
Bao, Saran
Kwong, Peter D.
Rao, Srinivas S.
Mascola, John R.
Nabel, Gary J.
TI Sustained Delivery of a Broadly Neutralizing Antibody in Nonhuman
Primates Confers Long-Term Protection against Simian/Human
Immunodeficiency Virus Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN MONOCLONAL-ANTIBODIES; HIV-1/SIV CHIMERIC VIRUS; MUCOSAL SHIV
CHALLENGE; NEONATAL FC-RECEPTOR; IN-VITRO; IMPROVES PROTECTION; RATIONAL
DESIGN; MACAQUES; HIV; ENVELOPE
AB Pathogen-specific neutralizing antibodies protect against many viral infections and can potentially prevent human immunodeficiency virus (HIV) transmission in humans. However, neutralizing antibodies have so far only been shown to protect nonhuman primates (NHP) against lentiviral infection when given shortly before challenge. Thus, the clinical utility and feasibility of passive antibody transfer to confer long-term protection against HIV-1 are still debated. Here, we investigate the potential of a broadly neutralizing HIV-1 antibody to provide long-term protection in a NHP model of HIV-1 infection. A human antibody was simianized to avoid immune rejection and used to sustain therapeutic levels for similar to 5 months. Two months after the final antibody administration, animals were completely protected against viral challenge. These findings demonstrate the feasibility and potential of long-term passive antibody for protection against HIV-1 in humans and provide a model to test antibody therapies for other diseases in NHP.
IMPORTANCE
Antibodies against HIV are potential drugs that may be able to prevent HIV infection in humans. However, the long-term protective capacity of antibodies against HIV has not been assessed. Here, we repetitively administered a macaque version of a human anti-HIV antibody to monkeys, after which the antibody persisted in the blood for >5 months. Moreover, the antibody could be sustained at protective levels for 108 days, conferring protection 52 days after the last dose in a monkey model of HIV infection. Thus, passive antibody transfer can provide durable protection against infection by viruses that cause AIDS in primates.
C1 [Saunders, Kevin O.; Pegu, Amarendra; Georgiev, Ivelin S.; Joyce, M. Gordon; Yang, Zhi-Yong; Ko, Sung-Youl; Chen, Xuejun; Schmidt, Stephen D.; Todd, John-Paul; Bao, Saran; Kwong, Peter D.; Rao, Srinivas S.; Mascola, John R.; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Zeng, Ming; Haase, Ashley T.] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA.
RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM John.Mascola@nih.gov; Gary.Nabel@sanofi.com
RI Schmidt, Stephen/B-5398-2012;
OI Pegu, Amarendra/0000-0003-3564-6453
FU Intramural Research Program of the Vaccine Research Center, NIAID,
National Institutes of Health; NIH Nonhuman Primate Reagent Resource
(NIAID) [HHSN 2722000900037C]
FX We are thankful for veterinary assistance from the members of the
Vaccine Research Center Laboratory of Animal Medicine. We thank Tatsiana
Kirys for her help with sequence alignments and VRC01 images. We express
our gratitude to the Duke Human Vaccine Institute IVQAC for performing
the viral load analyses. We also thank Brenda Hartman for manuscript
preparation. The macaque IgG used in these studies was provided by the
NIH Nonhuman Primate Reagent Resource (R24 RR016001 and NIAID contract
HHSN 2722000900037C).; This work was supported by the Intramural
Research Program of the Vaccine Research Center, NIAID, National
Institutes of Health.
NR 42
TC 20
Z9 21
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD JUN
PY 2015
VL 89
IS 11
BP 5895
EP 5903
DI 10.1128/JVI.00210-15
PG 9
WC Virology
SC Virology
GA CH3DU
UT WOS:000353907900014
PM 25787288
ER
PT J
AU Race, B
Phillips, K
Meade-White, K
Striebel, J
Chesebro, B
AF Race, Brent
Phillips, Katie
Meade-White, Kimberly
Striebel, James
Chesebro, Bruce
TI Increased Infectivity of Anchorless Mouse Scrapie Prions in Transgenic
Mice Overexpressing Human Prion Protein
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CREUTZFELDT-JAKOB-DISEASE; BOVINE SPONGIFORM ENCEPHALOPATHY; CELL-FREE
FORMATION; AMINO-ACID; MOLECULAR-CLONING; SPECIES BARRIERS;
GENE-EXPRESSION; CULTURED-CELLS; HAMSTER PRP; WILD-TYPE
AB Prion protein (PrP) is found in all mammals, mostly as a glycoprotein anchored to the plasma membrane by a C-terminal glycosylphosphatidylinositol (GPI) linkage. Following prion infection, host protease-sensitive prion protein (PrPsen or PrPC) is converted into an abnormal, disease-associated, protease-resistant form (PrPres). Biochemical characteristics, such as the PrP amino acid sequence, and posttranslational modifications, such as glycosylation and GPI anchoring, can affect the transmissibility of prions as well as the biochemical properties of the PrPres generated. Previous in vivo studies on the effects of GPI anchoring on prion infectivity have not examined cross-species transmission. In this study, we tested the effect of lack of GPI anchoring on a species barrier model using mice expressing human PrP. In this model, anchorless 22L prions derived from tg44 mice were more infectious than 22L prions derived from C57BL/10 mice when tested in tg66 transgenic mice, which expressed wild-type anchored human PrP at 8- to 16-fold above normal. Thus, the lack of the GPI anchor on the PrPres from tg44 mice appeared to reduce the effect of the mouse-human PrP species barrier. In contrast, neither source of prions induced disease in tgRM transgenic mice, which expressed human PrP at 2- to 4-fold above normal.
IMPORTANCE
Prion protein (PrP) is found in all mammals, usually attached to cells by an anchor molecule called GPI. Following prion infection, PrP is converted into a disease-associated form (PrPres). While most prion diseases are species specific, this finding is not consistent, and species barriers differ in strength. The amino acid sequence of PrP varies among species, and this variability affects prion species barriers. However, other PrP modifications, including glycosylation and GPI anchoring, may also influence cross-species infectivity. We studied the effect of PrP GPI anchoring using a mouse-to-human species barrier model. Experiments showed that prions produced by mice expressing only anchorless PrP were more infectious than prions produced in mice expressing anchored PrP. Thus, the lack of the GPI anchor on prions reduced the effect of the mouse-human species barrier. Our results suggest that prion diseases that produce higher levels of anchorless PrP may pose an increased risk for cross-species infection.
C1 [Race, Brent; Phillips, Katie; Striebel, James; Chesebro, Bruce] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA.
[Meade-White, Kimberly] NIAID, Rocky Mt Labs, Rocky Mt Vet Branch, NIH, Hamilton, MT 59840 USA.
RP Race, B (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA.
EM raceb@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 75
TC 5
Z9 5
U1 0
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD JUN
PY 2015
VL 89
IS 11
BP 6022
EP 6032
DI 10.1128/JVI.00362-15
PG 11
WC Virology
SC Virology
GA CH3DU
UT WOS:000353907900024
PM 25810548
ER
PT J
AU Liu, YN
Yin, JJ
Barrett, B
Sheppard-Tillman, H
Li, DM
Casey, OM
Fang, L
Hynes, PG
Ameri, AH
Kelly, K
AF Liu, Yen-Nien
Yin, JuanJuan
Barrett, Ben
Sheppard-Tillman, Heather
Li, Dongmei
Casey, Orla M.
Fang, Lei
Hynes, Paul G.
Ameri, Amir H.
Kelly, Kathleen
TI Loss of Androgen-Regulated MicroRNA 1 Activates SRC and Promotes
Prostate Cancer Bone Metastasis
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID RECEPTOR TYROSINE KINASES; TUMOR-SUPPRESSOR; FAMILY KINASES; MOUSE
MODEL; DASATINIB; THERAPIES; SELECTION; PROGRAM; PTEN; PHOSPHORYLATION
AB Bone metastasis is the hallmark of progressive and castration-resistant prostate cancers. MicroRNA 1 (miR-1) levels are decreased in clinical samples of primary prostate cancer and further reduced in metastases. SRC has been implicated as a critical factor in bone metastasis, and here we show that SRC is a direct target of miR-1. In prostate cancer patient samples, miR-1 levels are inversely correlated with SRC expression and a SRC-dependent gene signature. Ectopic miR-1 expression inhibited extracellular signal-regulated kinase (ERK) signaling and bone metastasis in a xenograft model. In contrast, SRC overexpression was sufficient to reconstitute bone metastasis and ERK signaling in cells expressing high levels of miR-1. Androgen receptor (AR) activity, defined by an AR output signature, is low in a portion of castration-resistant prostate cancer. We show that AR binds to the miR-1-2 regulatory region and regulates miR-1 transcription. Patients with low miR-1 levels displayed correlated low canonical AR gene signatures. Our data support the existence of an AR-miR-1-SRC regulatory network. We propose that loss of miR-1 is one mechanistic link between low canonical AR output and SRC-promoted metastatic phenotypes.
C1 [Liu, Yen-Nien] Taipei Med Univ, Grad Inst Canc Biol & Drug Discovery, Taipei, Taiwan.
[Yin, JuanJuan; Barrett, Ben; Sheppard-Tillman, Heather; Casey, Orla M.; Fang, Lei; Hynes, Paul G.; Ameri, Amir H.; Kelly, Kathleen] NCI, Lab Genitourinary Canc Pathogenesis, NIH, Bethesda, MD 20892 USA.
[Li, Dongmei] Nanjing Univ, Sch Med, Immunol & Reprod Biol Lab, Nanjing 210008, Jiangsu, Peoples R China.
RP Liu, YN (reprint author), Taipei Med Univ, Grad Inst Canc Biol & Drug Discovery, Taipei, Taiwan.
EM liuy@tmu.edu; kellyka@mail.nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; National Health Research Institutes
[NHRI-EX103-10308BC]; Ministry of Science and Technology of Taiwan [MOST
103-2314-B-038-051]
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research, by the
National Health Research Institutes (NHRI-EX103-10308BC), and by the
Ministry of Science and Technology (MOST 103-2314-B-038-051) of Taiwan.
NR 45
TC 9
Z9 10
U1 0
U2 8
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 JUN
PY 2015
VL 35
IS 11
BP 1940
EP 1951
DI 10.1128/MCB.00008-15
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CH3FI
UT WOS:000353913000005
PM 25802280
ER
PT J
AU Tsukiyama, T
Fukui, A
Terai, S
Fujioka, Y
Shinada, K
Takahashi, H
Yamaguchi, TP
Ohba, Y
Hatakeyama, S
AF Tsukiyama, Tadasuke
Fukui, Akimasa
Terai, Sayuri
Fujioka, Yoichiro
Shinada, Keisuke
Takahashi, Hidehisa
Yamaguchi, Terry P.
Ohba, Yusuke
Hatakeyama, Shigetsugu
TI Molecular Role of RNF43 in Canonical and Noncanonical Wnt Signaling
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID BETA-CATENIN DEGRADATION; ADENOMATOUS POLYPOSIS-COLI; WNT/BETA-CATENIN;
STEM-CELLS; E3 LIGASE; PATHWAY; PROTEIN; UBIQUITIN; SPECIFICITY;
COMPONENTS
AB Wnt signaling pathways are tightly regulated by ubiquitination, and dysregulation of these pathways promotes tumorigenesis. It has been reported that the ubiquitin ligase RNF43 plays an important role in frizzled-dependent regulation of the Wnt/beta-catenin pathway. Here, we show that RNF43 suppresses both Wnt/beta-catenin signaling and noncanonical Wnt signaling by distinct mechanisms. The suppression of Wnt/beta-catenin signaling requires interaction between the extracellular protease-associated (PA) domain and the cysteine-rich domain (CRD) of frizzled and the intracellular RING finger domain of RNF43. In contrast, these N-terminal domains of RNF43 are not required for inhibition of noncanonical Wnt signaling, but interaction between the C-terminal cytoplasmic region of RNF43 and the PDZ domain of dishevelled is essential for this suppression. We further show the mechanism by which missense mutations in the extracellular portion of RNF43 identified in patients with tumors activate Wnt/beta-catenin signaling. Missense mutations of RNF43 change their localization from the endosome to the endoplasmic reticulum (ER), resulting in the failure of frizzled-dependent suppression of Wnt/beta-catenin signaling. However, these mutants retain the ability to suppress noncanonical Wnt signaling, probably due to interaction with dishevelled. RNF43 is also one of the potential target genes of Wnt/beta-catenin signaling. Our results reveal the molecular role of RNF43 and provide an insight into tumorigenesis.
C1 [Tsukiyama, Tadasuke; Terai, Sayuri; Shinada, Keisuke; Takahashi, Hidehisa; Hatakeyama, Shigetsugu] Hokkaido Univ, Grad Sch Med, Dept Biochem, Sapporo, Hokkaido, Japan.
[Fukui, Akimasa] Hokkaido Univ, Fac Adv Life Sci, Lab Tissue & Polymer Sci, Div Adv Interdisciplinary Sci, Sapporo, Hokkaido, Japan.
[Fujioka, Yoichiro; Ohba, Yusuke] Hokkaido Univ, Grad Sch Med, Dept Cell Physiol, Sapporo, Hokkaido, Japan.
[Yamaguchi, Terry P.] NCI, Canc & Dev Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21701 USA.
RP Hatakeyama, S (reprint author), Hokkaido Univ, Grad Sch Med, Dept Biochem, Sapporo, Hokkaido, Japan.
EM hatas@med.hokudai.ac.jp
RI Tsukiyama, Tadasuke/D-7589-2012; Hatakeyama, Shigetsugu/C-8333-2012
OI Hatakeyama, Shigetsugu/0000-0002-2150-9979
FU KAKENHI from the Ministry of Education, Culture, Sports, Science and
Technology in Japan [24112006, 24390065, 25430102]
FX This work was supported by KAKENHI (funds to S.H. [grants 24112006 and
24390065] and to T.T. [grant 25430102]) from the Ministry of Education,
Culture, Sports, Science and Technology in Japan.
NR 47
TC 3
Z9 4
U1 1
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
EI 1098-5549
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD JUN
PY 2015
VL 35
IS 11
BP 2007
EP 2023
DI 10.1128/MCB.00159-15
PG 17
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CH3FI
UT WOS:000353913000010
PM 25825523
ER
PT J
AU Moretti, F
Rolando, C
Winker, M
Ivanek, R
Rodriguez, J
Von Kriegsheim, A
Taylor, V
Bustin, M
Pertz, O
AF Moretti, Francesca
Rolando, Chiara
Winker, Moritz
Ivanek, Robert
Rodriguez, Javier
Von Kriegsheim, Alex
Taylor, Verdon
Bustin, Michael
Pertz, Olivier
TI Growth Cone Localization of the mRNA Encoding the Chromatin Regulator
HMGN5 Modulates Neurite Outgrowth
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID NUCLEOSOMAL BINDING-PROTEIN; NEUROBLASTOMA-CELLS; TRANSLATIONAL
REGULATION; INTRAAXONAL TRANSLATION; ACTIN CYTOSKELETON; HIGH-MOBILITY;
TRANSCRIPTION; EXPRESSION; FAMILY; SIGNAL
AB Neurons exploit local mRN Atranslation and retrograde transport of transcription factors to regulate gene expression in response to signaling events at distal neuronal ends. Whether epigenetic factors could also be involved in such regulation is not known. We report that them RNA encoding the high-mobility group N5 (HMGN5) chromatin binding protein localizes to growth cones of both neuronlike cells and of hippocampal neurons, where it has the potential to be translated, and that HMGN5 can be retrogradely transported into the nucleus along neurites. Loss of HMGN5 function induces transcriptional changes and impairs neurite outgrowth, while HMGN5 overexpression induces neurite outgrowth and chromatin decompaction; these effects are dependent on growth cone localization of Hmgn5 mRNA. We suggest that the localization and local translation of transcripts coding for epigenetic factors couple the dynamic neuronal outgrowth process with chromatin regulation in the nucleus.
C1 [Moretti, Francesca; Winker, Moritz; Pertz, Olivier] Univ Basel, Dept Biomed, Cell Migrat & Neuritogenesis, Basel, Switzerland.
[Rolando, Chiara; Taylor, Verdon] Univ Basel, Embryol & Stem Cell Biol, Dept Biomed, Basel, Switzerland.
[Ivanek, Robert] Univ Basel, Bioinformat, Dept Biomed, Basel, Switzerland.
[Ivanek, Robert] Swiss Inst Bioinformat, Basel, Switzerland.
[Rodriguez, Javier; Von Kriegsheim, Alex] Univ Dublin Trinity Coll, Syst Biol Ireland Conway Inst, Dublin 2, Ireland.
[Bustin, Michael] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
RP Pertz, O (reprint author), Univ Basel, Dept Biomed, Cell Migrat & Neuritogenesis, Basel, Switzerland.
EM olivier.pertz@unibas.ch
RI von Kriegsheim, Alex/C-2371-2016; Bustin, Michael/G-6155-2015;
OI von Kriegsheim, Alex/0000-0002-4952-8573; Rolando,
Chiara/0000-0003-2418-8346
FU EMBO Long-Term Postdoctoral Fellowship; Swiss National Science
Foundation
FX This work was supported by an EMBO Long-Term Postdoctoral Fellowship to
F.M. and by a grant of the Swiss National Science Foundation to O.P.
NR 53
TC 2
Z9 2
U1 1
U2 3
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 JUN
PY 2015
VL 35
IS 11
BP 2035
EP 2050
DI 10.1128/MCB.00133-15
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CH3FI
UT WOS:000353913000012
PM 25825524
ER
PT J
AU Hathaway, HA
Pshenichkin, S
Grajkowska, E
Gelb, T
Emery, AC
Wolfe, BB
Wroblewski, JT
AF Hathaway, Hannah A.
Pshenichkin, Sergey
Grajkowska, Ewa
Gelb, Tara
Emery, Andrew C.
Wolfe, Barry B.
Wroblewski, Jarda T.
TI Pharmacological characterization of mGlu1 receptors in cerebellar
granule cells reveals biased agonism
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Metabotropic glutamate receptor 1; Biased agonism; Glutamate;
Quisqualate; DHPG; Cerebellar granule cells
ID METABOTROPIC GLUTAMATE-RECEPTOR; 7-TRANSMEMBRANE RECEPTORS;
HUMAN-MELANOMA; LIGAND BIAS; RAT-BRAIN; SURVIVAL; ACTIVATION; CULTURE;
GLUTAMATE-RECEPTOR-1; DEPOLARIZATION
AB The majority of existing research on the function of metabotropic glutamate (mGlu) receptor 1 focuses on G protein-mediated outcomes. However, similar to other G protein-coupled receptors (GPCR), it is becoming apparent that mGlu(1) receptor signaling is multi-dimensional and does not always involve G protein activation. Previously, in transfected CHO cells, we showed that mGlu(1) receptors activate a G protein-independent, beta-arrestin-dependent signal transduction mechanism and that some mGlu(1) receptor ligands were incapable of stimulating this response. Here we set out to investigate the physiological relevance of these findings in a native system using primary cultures of cerebellar granule cells. We tested the ability of a panel of compounds to stimulate two mGlu(1) receptor-mediated outcomes: (1) protection from decreased cell viability after withdrawal of trophic support and (2) G protein-mediated phosphoinositide (PI) hydrolysis. We report that the commonly used mGlu(1) receptor ligands quisqualate, DHPG, and ACPD are completely biased towards PI hydrolysis and do not induce mGlu(1) receptor-stimulated neuroprotection. On the other hand, endogenous compounds including glutamate, aspartate, cysteic acid, cysteine sulfinic acid, and homocysteic acid stimulate both responses. These results show that some commonly used mGlu(1) receptor ligands are biased agonists, stimulating only a fraction of mGlu(1) receptor-mediated responses in neurons. This emphasizes the importance of utilizing multiple agonists and assays when studying GPCR function. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Hathaway, Hannah A.; Pshenichkin, Sergey; Grajkowska, Ewa; Gelb, Tara; Wolfe, Barry B.; Wroblewski, Jarda T.] Georgetown Univ, Dept Physiol & Pharmacol, Washington, DC 20057 USA.
[Emery, Andrew C.] NIMH, Sect Mol Neuroscience, IRP, Bethesda, MD 20892 USA.
RP Hathaway, HA (reprint author), Georgetown Univ, Dept Pharmacol, 3900 Reservoir Rd,NW,Med Dent Bldg SW406, Washington, DC 20057 USA.
EM hah32@georgetown.edu
OI Emery, Andrew/0000-0002-6760-2570; Hathaway, Hannah/0000-0003-0906-1726
FU National Institutes of Health [NS37436]
FX This work was supported by The National Institutes of Health Grant
NS37436 to JTW.
NR 44
TC 5
Z9 5
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
EI 1873-7064
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD JUN
PY 2015
VL 93
BP 199
EP 208
DI 10.1016/j.neuropharm.2015.02.007
PG 10
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA CH0RK
UT WOS:000353729900020
PM 25700650
ER
PT J
AU Hammond, GRV
Balla, T
AF Hammond, Gerald R. V.
Balla, Tamas
TI Polyphosphoinositide binding domains: Key to inositol lipid biology
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
LA English
DT Review
DE Phosphoinositide; PH-domain; PX-domain; Phospholipase C; Fluorescence
imaging; Membrane
ID PLECKSTRIN-HOMOLOGY-DOMAIN; HIGH-AFFINITY BINDING; BRUTONS TYROSINE
KINASE; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE LEVELS; BABY
HAMSTER-KIDNEY; PLASMA-MEMBRANE; IN-VIVO; LIVING CELLS; PROTEIN-KINASE;
PH-DOMAIN
AB Polyphosphoinositides (PPIn) are an important family of phospholipids located on the cytoplasmic leaflet of eukaryotic cell membranes. Collectively, they are critical for the regulation of many aspects of membrane homeostasis and signaling, with notable relevance to human physiology and disease. This regulation is achieved through the selective interaction of these lipids with hundreds of cellular proteins, and thus the capability to study these localized interactions is crucial to understanding their functions. In this review, we discuss current knowledge of the principle types of PPIn-protein interactions, focusing on specific lipid-binding domains. We then discuss how these domains have been re-tasked by biologists as molecular probes for these lipids in living cells. Finally, we describe how the knowledge gained with these probes, when combined with other techniques, has led to the current view of the lipids' localization and function in eulcaryotes, focusing mainly on animal cells. This article is part of a Special Issue entitled Phosphoinositides. Published by Elsevier B.V.
C1 [Hammond, Gerald R. V.] Univ Pittsburgh, Sch Med, Dept Cell Biol, Pittsburgh, PA 15260 USA.
[Balla, Tamas] Eunice Shriver Kennedy Natl Inst Child Hlth & Hum, Sect Mol Signal Transduct, NIH, Bethesda, MD USA.
RP Hammond, GRV (reprint author), Univ Pittsburgh, Sch Med, Dept Cell Biol, Pittsburgh, PA 15260 USA.
EM ghammond@pitt.edu2; ballat@mail.nih.gov
RI Hammond, Gerald/A-5759-2016;
OI Hammond, Gerald/0000-0002-6660-3272; Balla, Tamas/0000-0002-9077-3335
FU Intramural NIH HHS [ZIA HD000196-14]
NR 169
TC 31
Z9 33
U1 2
U2 27
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1388-1981
EI 0006-3002
J9 BBA-MOL CELL BIOL L
JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids
PD JUN
PY 2015
VL 1851
IS 6
SI SI
BP 746
EP 758
DI 10.1016/j.bbalip.2015.02.013
PG 13
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA CG2HP
UT WOS:000353095800006
PM 25732852
ER
PT J
AU Rauner, M
Thiele, S
Fert, I
Araujo, LM
Layh-Schmitt, G
Colbert, RA
Hofbauer, C
Bernhardt, R
Burki, A
Schwiedrzik, J
Zysset, PK
Pietschmann, P
Taurog, JD
Breban, M
Hofbauer, LC
AF Rauner, Martina
Thiele, Sylvia
Fert, Ingrid
Araujo, Luiza M.
Layh-Schmitt, Gerlinde
Colbert, Robert A.
Hofbauer, Christine
Bernhardt, Ricardo
Buerki, Alexander
Schwiedrzik, Jakob
Zysset, Philippe K.
Pietschmann, Peter
Taurog, Joel D.
Breban, Maxime
Hofbauer, Lorenz C.
TI Loss of bone strength in HLA-B27 transgenic rats is characterized by a
high bone turnover and is mainly osteoclast-driven
SO BONE
LA English
DT Article
DE Spondyloarthritis; HLA-B27 transgenic rat; Bone loss; Bone remodeling;
Inflammatory bowel disease
ID TUMOR-NECROSIS-FACTOR; UNFOLDED PROTEIN RESPONSE;
ANKYLOSING-SPONDYLITIS; MINERAL DENSITY; HLA-B27-TRANSGENIC RATS;
INFLAMMATORY DISEASE; COMPUTED-TOMOGRAPHY; DENDRITIC CELLS;
FACTOR-ALPHA; MARKERS
AB Objective: Although osteopenia is frequent in spondyloarthritis (SpA), the underlying cellular mechanisms and association with other symptoms are poorly understood. This study aimed to characterize bone loss during disease progression, determine cellular alterations, and assess the contribution of inflammatory bowel disease (IBD) to bone loss in HLA-B27 transgenic rats.
Methods: Bones of 2-, 6-, and 12-month-old non-transgenic, disease-free HLA-B7 and disease-associated HLA-B27 transgenic rats were examined using peripheral quantitative computed tomography, mu CT, and nanoindentation. Cellular characteristics were determined by histomorphometry and ex vivo cultures. The impact of IBD was determined using [21-3 x 283-2]F-1 rats, which develop arthritis and spondylitis, but not IBD.
Results: HLA-B27 transgenic rats continuously lost bone mass with increasing age and had impaired bone material properties, leading to a 3-fold decrease in bone strength at 12 months of age. Bone turnover was increased in HLA-B27 transgenic rats, as evidenced by a 3-fold increase in bone formation and a 6-fold increase in bone resorption parameters. Enhanced osteoclastic markers were associated with a larger number of precursors in the bone marrow and a stronger osteoclastogenic response to RANKL or TNF alpha. Further, IBD-free [21-3 x 283-2]F-1 rats also displayed decreased total and trabecular bone density.
Conclusions: HLA-B27 transgenic rats lose an increasing amount of bone density and strength with progressing age, which is primarily mediated via increased bone remodeling in favor of bone resorption. Moreover, IBD and bone loss seem to be independent features of SpA in HLA-B27 transgenic rats. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Rauner, Martina; Thiele, Sylvia; Hofbauer, Lorenz C.] Tech Univ Dresden, Med Ctr, Dept Med 3, D-01307 Dresden, Germany.
[Fert, Ingrid; Araujo, Luiza M.; Breban, Maxime] Hop Cochin, Inst Cochin, F-75674 Paris, France.
[Layh-Schmitt, Gerlinde; Colbert, Robert A.] Natl Inst Arthrit Musculoskeletal & Skin Dis NIAM, Pediat Translat Res Branch, Bethesda, MD USA.
[Hofbauer, Christine] Tech Univ Dresden, Med Ctr, Dept Orthoped, D-01307 Dresden, Germany.
[Bernhardt, Ricardo] Tech Univ Dresden, Max Bergmann Ctr Biomat, D-01307 Dresden, Germany.
[Buerki, Alexander; Schwiedrzik, Jakob; Zysset, Philippe K.] Univ Bern, Inst Surg Technol & Biomech, CH-3012 Bern, Switzerland.
[Pietschmann, Peter] Med Univ Vienna, Dept Pathophysiol & Allergy Res, Vienna, Austria.
[Taurog, Joel D.] Univ TX SW Med Ctr, Dallas, TX USA.
[Hofbauer, Lorenz C.] Ctr Regenerat Therapies, Dresden, Germany.
RP Rauner, M (reprint author), Tech Univ Dresden, Med Ctr, Div Endocrinol Diabet & Metab Bone Dis, Dept Med 3, Fetscherstr 74, D-01307 Dresden, Germany.
EM martina.rauner@uniklinikum-dresden.de
RI Schwiedrzik, Johann Jakob/I-3346-2016; Hofbauer, Lorenz/G-2490-2010
OI Schwiedrzik, Johann Jakob/0000-0002-6689-2828; Hofbauer,
Lorenz/0000-0002-8691-8423
FU Deutsche Forschungsgemeinschaft [RA1923/1-1]; Deutsche
Forschungsgemeinschaft ("IMMUNOBONE" priority program 1468) [HO1875/8-2,
RA1923/4-2]; Habilitationsforderung fur Frauen der TU Dresden; NIAMS
[Z01-AR-041184]
FX This work was supported by grants from Deutsche Forschungsgemeinschaft
(RA1923/1-1 and the "IMMUNOBONE" priority program 1468 (HO1875/8-2 and
RA1923/4-2)) to MR and LCH, the Habilitationsforderung fur Frauen der TU
Dresden to MR, and the NIAMS Intramural Research Program, Z01-AR-041184,
to RAC. We would like to thank Patrick Bohme, Ina Gloe, and Tina Listner
for excellent technical assistance and Riku Kiviranta for stimulating
discussions.
NR 50
TC 2
Z9 3
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
EI 1873-2763
J9 BONE
JI Bone
PD JUN
PY 2015
VL 75
BP 183
EP 191
DI 10.1016/j.bone.2015.02.024
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CG1ZQ
UT WOS:000353075100024
PM 25746795
ER
PT J
AU Zilbermint, M
Stratakis, CA
AF Zilbermint, Mihail
Stratakis, Constantine A.
TI Protein kinase A defects and cortisol-producing adrenal tumors
SO Current Opinion in Endocrinology Diabetes and Obesity
LA English
DT Review
DE adrenal tumor; cortisol-producing adrenal adenoma; Cushing syndrome;
protein kinase A; protein kinase catalytic subunit alpha; protein kinase
catalytic subunit beta; protein kinase type 1 alpha regulatory subunit
ID NODULAR ADRENOCORTICAL DISEASE; PKA CATALYTIC SUBUNIT; CARNEY COMPLEX;
CUSHINGS-SYNDROME; SOMATIC MUTATIONS; ARMC5 MUTATIONS;
HEPATOCELLULAR-CARCINOMA; REGULATORY SUBUNIT; PRKAR1A GENE; HYPERPLASIA
AB Purpose of reviewCushing syndrome caused by cortisol-producing adrenal adenomas is a rare condition, associated with high morbidity due to weight gain, diabetes mellitus, osteoporosis, hypertension, muscle weakness, mood disturbance and others. The first gene to be identified as causative of Cushing syndrome was PRKAR1A. We present an update on protein kinase A (PKA) defects and Cushing syndrome.Recent findingsThe cyclic AMP-dependent PKA catalytic subunit alpha (PRKACA) hotspot point mutation (c.617A>C [p.Leu206Arg]), leading to an increase of basal PKA activity, and formation of cortisol-producing adenoma has been frequently shown to cause the most common form of adrenocorticotropic hormone-independent Cushing syndrome.SummarySomatic PRKACA mutations have been found in up to 50% of patients with adrenal adenomas. Germline PRKACA amplification was also seen in bilateral adrenal hyperplasias. PRKACA activation was associated with higher cortisol levels, smaller tumor size and overt Cushing syndrome. This breakthrough is expected to improve our understanding of how PKA defects lead to Cushing syndrome and may spearhead the development of new, molecularly designed therapies.
C1 [Zilbermint, Mihail; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & 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,NIH Clin Res Ctr, 10 Ctr Dr,Bldg 10,Room 1-3330,MSC 1103, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
FU Intramural Research Program of Eunice Kennedy Shriver National Institute
of Child Health and Human Development, National Institutes of Health
(NIH)
FX This research was supported by the Intramural Research Program of Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health (NIH).
NR 48
TC 4
Z9 4
U1 1
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1752-296X
EI 1752-2978
J9 CURR OPIN ENDOCRINOL
JI Curr. Opin. Endocrinol. Diabetes Obes.
PD JUN
PY 2015
VL 22
IS 3
BP 157
EP 162
DI 10.1097/MED.0000000000000149
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CG7CB
UT WOS:000353458700003
PM 25871963
ER
PT J
AU Nieman, LK
AF Nieman, Lynnette K.
TI Update on subclinical Cushing's syndrome
SO Current Opinion in Endocrinology Diabetes and Obesity
LA English
DT Review
DE adrenalectomy; hypercortisolism; subclinical Cushing's syndrome
ID ADRENAL INCIDENTALOMAS; CORTISOL HYPERSECRETION; HYPERCORTISOLISM;
DIAGNOSIS; MORTALITY; PATTERNS
AB Purpose of reviewThe present review summarizes recent findings in the diagnosis and treatment of subclinical Cushing's syndrome, a condition of subtle cortisol dysregulation with a spectrum of clinical and biochemical abnormalities.Recent findingsThe diagnosis of subclinical Cushing's syndrome is suggested by abnormal suppression to dexamethasone in a patient with an adrenal mass. The natural history of this disorder includes progression in a minority of cases, and increased cardiovascular disease in patients with more severe and progressive disease, much as is found in overt Cushing's syndrome. In patients with an abnormal response to dexamethasone, additional biochemical and metabolic features increase confidence in the ability of adrenalectomy to reverse clinical abnormalities. In addition, bilateral masses and larger masses are more likely to be associated with hypercortisolism.SummaryWe review the recent literature on subclinical cortisol secretion and suggest that additional studies are needed to define optimal diagnostic and therapeutic approaches.
C1 [Nieman, Lynnette K.] Eunice Kennedy Shriver Inst Child Hlth & Human De, Bethesda, MD 20892 USA.
RP Nieman, LK (reprint author), Eunice Kennedy Shriver Inst Child Hlth & Human De, CRC, Bldg 10,1 East,Room 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA.
EM NiemanL@nih.gov
FU intramural division of the National Institutes of Health
FX This work was funded by the intramural division of the National
Institutes of Health.
NR 22
TC 5
Z9 5
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1752-296X
EI 1752-2978
J9 CURR OPIN ENDOCRINOL
JI Curr. Opin. Endocrinol. Diabetes Obes.
PD JUN
PY 2015
VL 22
IS 3
BP 180
EP 184
DI 10.1097/MED.0000000000000159
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CG7CB
UT WOS:000353458700006
PM 25887388
ER
PT J
AU Jiang, LL
Chen, SH
Chu, CH
Wang, SJ
Oyarzabal, E
Wilson, B
Sanders, V
Xie, KQ
Wang, QS
Hong, JS
AF Jiang, Lulu
Chen, Shih-Heng
Chu, Chun-Hsien
Wang, Shi-Jun
Oyarzabal, Esteban
Wilson, Belinda
Sanders, Virginia
Xie, Keqin
Wang, Qingshan
Hong, Jau-Shyong
TI A Novel Role of Microglial NADPH Oxidase in Mediating Extra-Synaptic
Function of Norepinephrine in Regulating Brain Immune Homeostasis
SO GLIA
LA English
DT Article
DE extra-synaptic; neurotransmitter; volume transmission; DSP-4;
neurodegeneration
ID BETA-ADRENERGIC-RECEPTOR; LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY;
B-LYMPHOCYTE FUNCTION; TUMOR-NECROSIS-FACTOR; DOPAMINERGIC-NEURONS;
NORADRENERGIC NEURONS; LOCUS-COERULEUS; IN-VIVO; SUPEROXIDE-PRODUCTION;
PARKINSONS-DISEASE
AB Although the peripheral anti-inflammatory effect of norepinephrine (NE) is well documented, the mechanism by which this neurotransmitter functions as an anti-inflammatory/neuroprotective agent in the central nervous system (CNS) is unclear. This article aimed to determine the anti-inflammatory/neuroprotective effects and underlying mechanisms of NE in inflammation-based dopaminergic neurotoxicity models. In mice, NE-depleting toxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) was injected at 6 months of lipopolysaccharide (LPS)-induced neuroinflammation. It was found that NE depletion enhanced LPS-induced dopaminergic neuron loss in the substantia nigra. This piece of in vivo data prompted us to conduct a series of studies in an effort to elucidate the mechanism as to how NE affects dopamine neuron survival by using primary midbrain neuron/glia cultures. Results showed that submicromolar concentrations of NE dose-dependently protected dopaminergic neurons from LPS-induced neurotoxicity by inhibiting microglia activation and subsequent release of pro-inflammatory factors. However, NE-elicited neuroprotection was not totally abolished in cultures from 2-adrenergic receptor (2-AR)-deficient mice, suggesting that novel pathways other than 2-AR are involved. To this end, It was found that submicromolar NE dose-dependently inhibited NADPH oxidase (NOX2)-generated superoxide, which contributes to the anti-inflammatory and neuroprotective effects of NE. This novel mechanism was indeed adrenergic receptors independent since both (+) and (-) optic isomers of NE displayed the same potency. We further demonstrated that NE inhibited LPS-induced NOX2 activation by blocking the translocation of its cytosolic subunit to plasma membranes. In summary, we revealed a potential physiological role of NE in maintaining brain immune homeostasis and protecting neurons via a novel mechanism. GLIA 2015;63:1057-1072
C1 [Jiang, Lulu; Xie, Keqin] Shandong Univ, Inst Toxicol, Sch Publ Hlth, Jinan 250012, Shandong, Peoples R China.
[Jiang, Lulu; Chen, Shih-Heng; Chu, Chun-Hsien; Wang, Shi-Jun; Oyarzabal, Esteban; Wilson, Belinda; Wang, Qingshan; Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, Neurobiol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Sanders, Virginia] Ohio State Univ, Inst Behav Med Res, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
RP Hong, JS (reprint author), NIEHS, F1-01,POB 12233, Res Triangle Pk, NC 27709 USA.
EM keqinx@sdu.edu.cn; wangq4@niehs.nih.gov; hong3@niehs.nih.gov
FU National Institute of Environmental Health Sciences, National Institutes
of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Environmental Health Sciences, National Institutes
of Health. We thank Anthony Lockhart for assistance with animal colony
management and maintenance. We also thank Dr. Honglei Chen (Epidemiology
Branch, NIEHS/NIH), Dr. Ronald E. Cannon (Laboratory of Toxicology and
Pharmacology, NIEHS/NIH), and Dr. Sabrina D Robertson (Laboratory of
Neurobiology, NIEHS/NIH) for reviewing this manuscript, and Dr.
Kissling, Grace (Biostatistics Branch) for the assistance of statistical
analysis.
NR 76
TC 5
Z9 5
U1 0
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0894-1491
EI 1098-1136
J9 GLIA
JI Glia
PD JUN
PY 2015
VL 63
IS 6
BP 1057
EP 1072
DI 10.1002/glia.22801
PG 16
WC Neurosciences
SC Neurosciences & Neurology
GA CG4GU
UT WOS:000353244400009
PM 25740080
ER
PT J
AU Resnik, DB
AF Resnik, David B.
TI Food and Beverage Policies and Public Health Ethics
SO HEALTH CARE ANALYSIS
LA English
DT Article
DE Food; Ethics; Policy; Public health; Paternalism; Justice
ID OBESITY; FRAMEWORK; INTERVENTIONS
AB Government food and beverage policies can play an important role in promoting public health. Few people would question this assumption. Difficult questions can arise, however, when policymakers, public health officials, citizens, and businesses deliberate about food and beverage policies, because competing values may be at stake, such as public health, individual autonomy, personal responsibility, economic prosperity, and fairness. An ethically justified policy strikes a reasonable among competing values by meeting the following criteria: (1) the policy serves important social goal(s); (2) the policy is likely to be effective at achieving those goal(s); (3) less burdensome options are not likely to be effective at achieving the goals; (4) the policy is fair.
C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
RP Resnik, DB (reprint author), NIEHS, NIH, 111 Alexander Dr,Mail Drop CU 03,Box 12233, Res Triangle Pk, NC 27709 USA.
EM resnikd@niehs.nih.gov
NR 41
TC 2
Z9 2
U1 2
U2 6
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1065-3058
EI 1573-3394
J9 HEALTH CARE ANAL
JI Health Care Anal.
PD JUN
PY 2015
VL 23
IS 2
BP 122
EP 133
DI 10.1007/s10728-013-0266-z
PG 12
WC Ethics; Health Policy & Services; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Health Care Sciences & Services;
Biomedical Social Sciences
GA CG4WI
UT WOS:000353287800002
PM 24132618
ER
PT J
AU Bao, W
Baecker, A
Song, YQ
Kiely, M
Liu, SM
Zhang, CL
AF Bao, Wei
Baecker, Aileen
Song, Yiqing
Kiely, Michele
Liu, Simin
Zhang, Cuilin
TI Adipokine levels during the first or early second trimester of pregnancy
and subsequent risk of gestational diabetes mellitus: A systematic
review
SO METABOLISM-CLINICAL AND EXPERIMENTAL
LA English
DT Article
DE Gestational diabetes mellitus; Adipokines; Adiponectin; Leptin
ID SOLUBLE LEPTIN RECEPTOR; BINDING-PROTEIN 4; BODY-MASS INDEX;
INSULIN-RESISTANCE; PATHOLOGICAL PREGNANCIES; ADIPONECTIN LEVELS;
LIPID-METABOLISM; PLASMA LEPTIN; TNF-ALPHA; WOMEN
AB Objective. We aimed to systematically review available literature linking adipokines to gestational diabetes mellitus (GDM) for a comprehensive understanding of the roles of adipokines in the development of GDM.
Methods. We searched PubMed/MEDLINE and EMBASE databases for published studies on adipokines and GDM through October 21, 2014. We included articles if they had a prospective study design (i.e., blood samples for adipokines measurement were collected before GDM diagnosis). Random-effects models were used to pool the weighted mean differences comparing levels of adipokines between GDM cases and non-GDM controls.
Results. Of 1523 potentially relevant articles, we included 25 prospective studies relating adipokines to incident GDM. Our meta-analysis of nine prospective studies on adiponectin and eight prospective studies on leptin indicated that adiponectin levels in the first or early second trimester of pregnancy were 2.25 mu g/ml lower (95% CI: 1.75-2.75), whereas leptin levels were 7.25 ng/ml higher (95% CI 3.27-11.22), among women who later developed GDM than women who did not. Prospective data were sparse and findings were inconsistent for visfatin, retinol binding protein (RBP-4), resistin, tumor necrosis factor-alpha (TNF-alpha), interleuldn-6 (IL-6), and vaspin. We did not identify prospective studies for several novel adipokines, including chemerin, apelin, omentin, or adipocyte fatty acid-binding protein. Moreover, no published prospective studies with longitudinal assessment of adipokines and incident GDM were identified.
Conclusion. Adiponectin levels in the first or second trimester of pregnancy are lower among pregnant women who later develop GDM than non-GDM women, whereas leptin levels are higher. Well-designed prospective studies with longitudinal assessment of adipokines during pregnancy are needed to understand the trajectories and dynamic associations of adipoldnes with GDM risk. Published by Elsevier Inc.
C1 [Bao, Wei; Kiely, Michele; Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA.
[Baecker, Aileen] Univ Calif Los Angeles, Dept Epidemiol, Los Angeles, CA USA.
[Song, Yiqing] Indiana Univ, Richard M Fairbanks Sch Publ Hlth, Dept Epidemiol, Indianapolis, IN 46204 USA.
[Liu, Simin] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA.
[Liu, Simin] Brown Univ, Dept Med, Providence, RI 02912 USA.
RP Zhang, CL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd, Rockville, MD 20852 USA.
EM zhangcu@mail.nih.gov
OI Bao, Wei/0000-0002-7301-5786
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; National Institute of
Diabetes and Digestive and Kidney Diseases, National Institutes of
Health [R01-DK-062290, R01-DK-58845, R01-DK-088078]
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(to C.Z., W.B., and M.K.) and research grants R01-DK-062290 (to S. L.),
R01-DK-58845 and R01-DK-088078 (to Y.S.) from the National Institute of
Diabetes and Digestive and Kidney Diseases, National Institutes of
Health.
NR 60
TC 18
Z9 19
U1 3
U2 12
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0026-0495
EI 1532-8600
J9 METABOLISM
JI Metab.-Clin. Exp.
PD JUN
PY 2015
VL 64
IS 6
BP 756
EP 764
DI 10.1016/j.metabol.2015.01.013
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CG7ZW
UT WOS:000353527400013
PM 25749468
ER
PT J
AU Vajda, S
Rangoni, Y
Cecotti, H
AF Vajda, Szilard
Rangoni, Yves
Cecotti, Hubert
TI Semi-automatic ground truth generation using unsupervised clustering and
limited manual labeling: Application to handwritten character
recognition
SO PATTERN RECOGNITION LETTERS
LA English
DT Article
DE Character recognition; Classifier combination; Clustering; Feature
selection
AB For training supervised classifiers to recognize different patterns, large data collections with accurate labels are necessary. In this paper, we propose a generic, semi-automatic labeling technique for large handwritten character collections. In order to speed up the creation of a large scale ground truth, the method combines unsupervised clustering and minimal expert knowledge. To exploit the potential discriminant complementarities across features, each character is projected into five different feature spaces. After clustering the images in each feature space, the human expert labels the cluster centers. Each data point inherits the label of its cluster's center. A majority (or unanimity) vote decides the label of each character image. The amount of human involvement (labeling) is strictly controlled by the number of clusters - produced by the chosen clustering approach. To test the efficiency of the proposed approach, we have compared, and evaluated three state-of-the art clustering methods (k-means, self-organizing maps, and growing neural gas) on the MNIST digit data set, and a Lampung Indonesian character data set, respectively. Considering a k-nn classifier, we show that labeling manually only 1.3% (MNIST), and 3.2% (Lampung) of the training data, provides the same range of performance than a completely labeled data set would. Published by Elsevier B.V.
C1 [Vajda, Szilard] NIH, Natl Lib Med, Bethesda, MD 20894 USA.
[Rangoni, Yves] Henri Tudor Publ Res Ctr, L-1855 Kirchberg, Luxembourg.
[Cecotti, Hubert] Univ Ulster, Fac Comp & Engn, Londonderry BT48 7JL, North Ireland.
RP Vajda, S (reprint author), NIH, Natl Lib Med, Bethesda, MD 20894 USA.
EM szilard.vajda@nih.gov
FU Intramural NIH HHS [Z99 LM999999]
NR 33
TC 4
Z9 4
U1 0
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-8655
EI 1872-7344
J9 PATTERN RECOGN LETT
JI Pattern Recognit. Lett.
PD JUN 1
PY 2015
VL 58
BP 23
EP 28
DI 10.1016/j.patrec.2015.02.001
PG 6
WC Computer Science, Artificial Intelligence
SC Computer Science
GA CG5RA
UT WOS:000353350300004
PM 25870463
ER
PT J
AU Shah, NN
Stevenson, MS
Yuan, CM
Richards, K
Delbrook, C
Kreitman, RJ
Pastan, I
Wayne, AS
AF Shah, Nirali N.
Stevenson, Maryalice Stetler
Yuan, Constance M.
Richards, Kelly
Delbrook, Cindy
Kreitman, Robert J.
Pastan, Ira
Wayne, Alan S.
TI Characterization of CD22 Expression in Acute Lymphoblastic Leukemia
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE CD22; monoclonal antibody; acute lymphoblastic leukemia; relapse
ID HAIRY-CELL LEUKEMIA; RECOMBINANT IMMUNOTOXIN; FLOW-CYTOMETRY;
SIGNAL-TRANSDUCTION; T-CELLS; B-CELLS; RECEPTOR; CHEMOIMMUNOTHERAPY;
ADHESION; ANTIBODY
AB BackgroundCD22 is a B-lineage differentiation antigen that has emerged as a leading therapeutic target in acute lymphoblastic leukemia (ALL).
ProcedureProperties of CD22 expression relevant to therapeutic targeting were characterized in primary samples obtained from children and young adults with relapsed and chemotherapy refractory B-precursor (pre-B) ALL.
ResultsCD22 expression was demonstrated in all subjects (n=163) with detection on at least 90% of blasts in 155 cases. Median antigen site density of surface CD22 was 3,470 sites/cell (range 349-19,653, n=160). Blasts from patients with known 11q23 (MLL) rearrangement had lower site density (median 1,590 sites/cell, range 349-3,624, n=20 versus 3,853 sites/cell, range 451-19,653, n=140; P=<0.0001) and 6 of 21 cases had sub-populations of blasts lacking CD22 expression (22%-82% CD22+). CD22 expression was maintained in serial studies of 73 subjects, including those treated with anti-CD22 targeted therapy. The levels of soluble CD22 in blood and marrow by ELISA were low and not expected to influence the pharmacokinetics of anti-CD22 directed agents.
ConclusionsThese characteristics make CD22 an excellent potential therapeutic target in patients with relapsed and chemotherapy-refractory ALL, although cases with MLL rearrangement require close study to exclude the presence of a CD22-negative blast population. Pediatr Blood Cancer Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Shah, Nirali N.; Richards, Kelly; Delbrook, Cindy; Wayne, Alan S.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Stevenson, Maryalice Stetler; Yuan, Constance M.] NCI, Pathol Lab, CCR, NIH, Bethesda, MD 20892 USA.
[Kreitman, Robert J.; Pastan, Ira; Wayne, Alan S.] NCI, Mol Biol Lab, CCR, NIH, Bethesda, MD 20892 USA.
[Wayne, Alan S.] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Childrens Ctr Canc & Blood Dis,Div Hematol Oncol, Los Angeles, CA 90033 USA.
RP Shah, NN (reprint author), NCI, Pediat Oncol Branch, NIH, Bldg 10,Room 1W-3750,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM Nirali.Shah@nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research; Warren Grant
Magnuson Clinical Center
FX Grant sponsor: Intramural Research Program of the National Institutes of
Health, National Cancer Institute, Center for Cancer Research; Grant
sponsor: Warren Grant Magnuson Clinical Center
NR 30
TC 14
Z9 14
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUN
PY 2015
VL 62
IS 6
BP 964
EP 969
DI 10.1002/pbc.25410
PG 6
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA CG4DC
UT WOS:000353231500008
PM 25728039
ER
PT J
AU Kolb, EA
Gorlick, R
Keir, ST
Maris, JM
Kang, MH
Reynolds, CP
Lock, RB
Carol, H
Wu, JR
Kurmasheva, RT
Houghton, PJ
Smith, MA
AF Kolb, E. Anders
Gorlick, Richard
Keir, Stephen T.
Maris, John M.
Kang, Min H.
Reynolds, C. Patrick
Lock, Richard B.
Carol, Hernan
Wu, Jianrong
Kurmasheva, Raushan T.
Houghton, Peter J.
Smith, Malcolm A.
TI Initial Testing (Stage 1) of BAL101553, a Novel Tubulin Binding Agent,
by the Pediatric Preclinical Testing Program
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE developmental therapeutics; microtubule-binding agents; preclinical
testing; vascular-disrupting agents
ID ONCOLOGY-GROUP; PHASE-II; PACLITAXEL; CHILDREN; MODELS; ABT-751; TUMORS
AB BAL101553 is a highly water soluble prodrug of BAL27862 that arrests tumor cell proliferation and induces cell death in cancer cells through disruption of the microtubule network. In vitro BAL27862 demonstrated potent activity, with the median relative IC50 (rIC(50)) of 13.8nM (range 5.4-25.2nM). The in vitro activity of BAL27862 against the PPTP cell lines is distinctive from that previously described for vincristine. BAL101553 induced significant differences in EFS distribution compared to control in 16 of 30 (53%) solid tumor xenografts and in two of four (67%) of the evaluable ALL xenografts. No objective responses were observed. Pediatr Blood Cancer 2015;62:1106-1109. (c) 2014 Wiley Periodicals, Inc.
C1 [Kolb, E. Anders] Nemours AI duPont Hosp Children, Wilmington, DE 19803 USA.
[Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
[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 19104 USA.
[Kang, Min H.; Reynolds, C. Patrick] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA.
[Lock, Richard B.; Carol, Hernan] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia.
[Wu, Jianrong] St Jude Childrens Res Hosp, Memphis, TN 38105 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), Nemours AI duPont Hosp Children, Dept Oncol, 1600 Rockland Rd, Wilmington, DE 19803 USA.
EM eakolb@nemours.org
RI Lock, Richard/G-4253-2013;
OI Reynolds, C. Patrick/0000-0002-2827-8536
FU National Cancer Institute [NO1-CM-42216, CA21765, CA108786]; Basilea
Pharmaceutica International Ltd [BAl101553, BAL27862]
FX Grant sponsor: National Cancer Institute; Grant number: NO1-CM-42216,
CA21765, CA108786; Grant sponsor: Basilea Pharmaceutica International
Ltd,; Grant number: BAl101553, BAL27862
NR 15
TC 2
Z9 2
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUN
PY 2015
VL 62
IS 6
BP 1106
EP 1109
DI 10.1002/pbc.25329
PG 4
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA CG4DC
UT WOS:000353231500039
PM 25407467
ER
PT J
AU Nesterova, G
Williams, C
Bernardini, I
Gahl, WA
AF Nesterova, Galina
Williams, Caitlyn
Bernardini, Isa
Gahl, William A.
TI Cystinosis: renal glomerular and renal tubular function in relation to
compliance with cystine-depleting therapy
SO PEDIATRIC NEPHROLOGY
LA English
DT Article
DE Nephropathic cystinosis; Cystine; Fanconi syndrome; Cysteamine;
End-stage renal disease
ID NEPHROPATHIC CYSTINOSIS; CYSTEAMINE THERAPY; HUMAN-FIBROBLASTS;
EPITHELIAL-CELLS; FANCONI-SYNDROME; ORAL CYSTEAMINE; CHILDREN; FAILURE;
PROTEIN; LYSOSOMES
AB Nephropathic cystinosis is a lysosomal storage disorder characterized by renal tubular Fanconi syndrome in infancy and glomerular damage leading to renal failure at similar to 10 years of age. Therapy with the cystine-depleting agent cysteamine postpones renal failure, but the degree of compliance with this treatment has not been correlated with preservation of kidney function.
We assessed leucocyte cystine depletion by cysteamine and created the composite compliance score that incorporates the extent of leucocyte cystine depletion, as well as duration of cysteamine treatment, into a single integer. Age at renal failure was used to gauge preservation of renal function, and the Fanconi syndrome index (FSI), a measure of aminoaciduria, was used to assess renal tubular Fanconi syndrome.
Age at renal failure varied directly and linearly with the composite compliance score (y = 0.3x +8.8; R-2 = 0.61). The slope indicated that for every year of excellent cystine depletion, nearly 1 year of renal function was preserved. Age at renal failure correlated roughly with mean leucocyte cystine level, but not with mean cysteamine dosage. There was no correlation between the FSI and the composite compliance score.
Greater compliance with oral cysteamine therapy yields greater preservation of renal glomerular, but not tubular, function. Oral cysteamine therapy should be given at the maximum tolerated dose, within the recommended limits.
C1 [Nesterova, Galina; Williams, Caitlyn; Bernardini, Isa; Gahl, William A.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Nesterova, G (reprint author), NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
EM nesterovag@mail.nih.gov
NR 32
TC 4
Z9 4
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0931-041X
EI 1432-198X
J9 PEDIATR NEPHROL
JI Pediatr. Nephrol.
PD JUN
PY 2015
VL 30
IS 6
BP 945
EP 951
DI 10.1007/s00467-014-3018-x
PG 7
WC Pediatrics; Urology & Nephrology
SC Pediatrics; Urology & Nephrology
GA CG4YY
UT WOS:000353296700010
PM 25526929
ER
PT J
AU Raran-Kurussi, S
Keefe, K
Waugh, DS
AF Raran-Kurussi, Sreejith
Keefe, Karina
Waugh, David S.
TI Positional effects of fusion partners on the yield and solubility of MBP
fusion proteins
SO PROTEIN EXPRESSION AND PURIFICATION
LA English
DT Article
DE Gateway cloning; Fusion protein; Inclusion bodies; MBP; Solubility
enhancer
ID MALTOSE-BINDING PROTEIN; ETCH VIRUS PROTEASE; ESCHERICHIA-COLI;
TYROSINE-PHOSPHATASE; MAMMALIAN PROTEINS; EXPRESSION; PURIFICATION;
SPECIFICITY
AB Escherichia coli maltose-binding protein (MBP) is exceptionally effective at promoting the solubility of its fusion partners. However, there are conflicting reports in the literature claiming that (1) MBP is an effective solubility enhancer only when it is joined to the N-terminus of an aggregation-prone passenger protein, and (2) MBP is equally effective when fused to either end of the passenger. Here, we endeavor to resolve this controversy by comparing the solubility of a diverse set of MBP fusion proteins that, unlike those analyzed in previous studies, are identical in every way except for the order of the two domains. The results indicate that fusion proteins with an N-terminal MBP provide an excellent solubility advantage along with more robust expression when compared to analogous fusions in which MBP is the C-terminal fusion partner. We find that only intrinsically soluble passenger proteins (i.e., those not requiring a solubility enhancer) are produced as soluble fusions when they precede MBP. We also report that even subtle differences in inter-domain linker sequences can influence the solubility of fusion proteins. Published by Elsevier Inc.
C1 [Raran-Kurussi, Sreejith; Keefe, Karina; Waugh, David S.] NCI, Prot Engn Sect, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Waugh, DS (reprint author), NCI, Prot Engn Sect, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21702 USA.
EM waughd@mail.nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; Werner H. Kirsten Student Intern Program
(W.H.K. SIP), Office of the Director, NCI-Frederick
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. Karina Keefe
was supported in part by the Werner H. Kirsten Student Intern Program
(W.H.K. SIP), Office of the Director, NCI-Frederick. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does the mention of trade
names, commercial products or organizations imply endorsement by the US
Government.
NR 20
TC 5
Z9 7
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 1046-5928
EI 1096-0279
J9 PROTEIN EXPRES PURIF
JI Protein Expr. Purif.
PD JUN
PY 2015
VL 110
BP 159
EP 164
DI 10.1016/j.pep.2015.03.004
PG 6
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA CG5EI
UT WOS:000353313500023
PM 25782741
ER
PT J
AU Wang, AT
Chandra, K
Xu, RH
Sun, JF
AF Wang, Antai
Chandra, Krishnendu
Xu, Ruihua
Sun, Junfeng
TI The Identifiability of Dependent Competing Risks Models Induced by
Bivariate Frailty Models
SO SCANDINAVIAN JOURNAL OF STATISTICS
LA English
DT Article
DE Archimedean copula models; bivariate frailty models; competing risks
models; discrete covariates; identifiability
ID ARCHIMEDEAN COPULA; MARGINAL SURVIVAL; DISTRIBUTIONS
AB In this paper, we propose to use a special class of bivariate frailty models to study dependent censored data. The proposed models are closely linked to Archimedean copula models. We give sufficient conditions for the identifiability of this type of competing risks models. The proposed conditions are derived based on a property shared by Archimedean copula models and satisfied by several well-known bivariate frailty models. Compared with the models studied by Heckman and Honore and Abbring and van den Berg, our models are more restrictive but can be identified with a discrete (even finite) covariate. Under our identifiability conditions, expectation-maximization (EM) algorithm provides us with consistent estimates of the unknown parameters. Simulation studies have shown that our estimation procedure works quite well. We fit a dependent censored leukaemia data set using the Clayton copula model and end our paper with some discussions.
C1 [Wang, Antai] New Jersey Inst Technol, Dept Math Sci, Newark, NJ 07102 USA.
[Chandra, Krishnendu] Columbia Univ, Dept Biostat, New York, NY 10027 USA.
[Xu, Ruihua] NHGRI, NIH, Bethesda, MD USA.
[Sun, Junfeng] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Wang, AT (reprint author), New Jersey Inst Technol, Dept Math Sci, Newark, NJ 07102 USA.
EM aw224@njit.edu
FU National Science Foundation [DMS1106608, DMS1343889]
FX The authors would like to thank the Editor, an Associate Editor and two
anonymous reviewers of this paper for a thorough review and for their
valuable comments that led to great improvement of this paper. The
research was supported by grant nos. DMS1106608 and DMS1343889 from the
National Science Foundation.
NR 15
TC 0
Z9 0
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0303-6898
EI 1467-9469
J9 SCAND J STAT
JI Scand. J. Stat.
PD JUN
PY 2015
VL 42
IS 2
BP 427
EP 437
DI 10.1111/sjos.12114
PG 11
WC Statistics & Probability
SC Mathematics
GA CG8FS
UT WOS:000353543300007
ER
PT J
AU Yeung, M
Hurren, R
Nemr, C
Wang, XM
Hershenfeld, S
Gronda, M
Liyanage, S
Wu, Y
Augustine, J
Lee, EA
Spagnuolo, PA
Southall, N
Chen, C
Zheng, W
Jeyaraju, DV
Minden, MD
Laposa, R
Schimmer, AD
AF Yeung, ManTek
Hurren, Rose
Nemr, Carine
Wang, Xiaoming
Hershenfeld, Samantha
Gronda, Marcela
Liyanage, Sanduni
Wu, Yan
Augustine, Jeevan
Lee, Eric A.
Spagnuolo, Paul A.
Southall, Noel
Chen, Catherine
Zheng, Wei
Jeyaraju, Danny V.
Minden, Mark D.
Laposa, Rebecca
Schimmer, Aaron D.
TI Mitochondrial DNA damage by bleomycin induces AML cell death
SO APOPTOSIS
LA English
DT Article
DE AML; Mitochondria; Mitochondrial DNA; Mitochondrial DNA damage;
Bleomycin
ID RADICAL SURGERY; REPAIR; CANCER; INHIBITION; CARCINOMA; LEUKEMIA
AB Mitochondria contain multiple copies of their own 16.6 kb circular genome. To explore the impact of mitochondrial DNA (mtDNA) damage on mitochondrial (mt) function and viability of AML cells, we screened a panel of DNA damaging chemotherapeutic agents to identify drugs that could damage mtDNA. We identified bleomycin as an agent that damaged mtDNA in AML cells at concentrations that induced cell death. Bleomycin also induced mtDNA damage in primary AML samples. Consistent with the observed mtDNA damage, bleomycin reduced mt mass and basal oxygen consumption in AML cells. We also demonstrated that the observed mtDNA damage was functionally important for bleomycin-induced cell death. Finally, bleomycin delayed tumor growth in xenograft mouse models of AML and anti-leukemic concentrations of the drug induced mtDNA damage in AML cells preferentially over normal lung tissue. Taken together, mtDNA-targeted therapy may be an effective strategy to target AML cells and bleomycin could be useful in the treatment of this disease.
C1 [Yeung, ManTek; Hurren, Rose; Nemr, Carine; Wang, Xiaoming; Hershenfeld, Samantha; Gronda, Marcela; Liyanage, Sanduni; Wu, Yan; Augustine, Jeevan; Jeyaraju, Danny V.; Minden, Mark D.; Schimmer, Aaron D.] Univ Hlth Network, Ontario Canc Inst, Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, Canada.
[Lee, Eric A.; Spagnuolo, Paul A.] Univ Waterloo, Sch Pharm, Kitchener, ON, Canada.
[Southall, Noel; Chen, Catherine; Zheng, Wei] NIH, Natl Ctr Advancing Translat Sci, Bethesda, MD 20892 USA.
[Laposa, Rebecca] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON, Canada.
RP Schimmer, AD (reprint author), Univ Hlth Network, Ontario Canc Inst, Princess Margaret Canc Ctr, Room 7-116,610 Univ Ave, Toronto, ON M5G 2M9, Canada.
EM aaron.schimmer@utoronto.ca
RI Southall, Noel/H-8991-2012
OI Southall, Noel/0000-0003-4500-880X
FU Canadian Stem Cell Network; LLSC
FX This work was supported by the Canadian Stem Cell Network and a Grant
from the LLSC to PAS. We thank Jill Flewelling for administrative
assistance and Bhozena Jhas for help in preparing the manuscript.
NR 26
TC 2
Z9 2
U1 1
U2 20
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1360-8185
EI 1573-675X
J9 APOPTOSIS
JI Apoptosis
PD JUN
PY 2015
VL 20
IS 6
BP 811
EP 820
DI 10.1007/s10495-015-1119-z
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CF8EW
UT WOS:000352789700005
PM 25820141
ER
PT J
AU Kwak, JT
Xu, S
Wood, BJ
AF Kwak, Jin Tae
Xu, Sheng
Wood, Bradford J.
TI Efficient data mining for local binary pattern in texture image analysis
SO EXPERT SYSTEMS WITH APPLICATIONS
LA English
DT Article
DE Local binary pattern; Frequent pattern mining; Texture image; Feature
selection; Classification
ID MULTIRESOLUTION GRAY-SCALE; FACE RECOGNITION; FACIAL EXPRESSION;
CLASSIFICATION; FEATURES; IDENTIFICATION; DESCRIPTORS; RETRIEVAL;
WAVELET
AB Local binary pattern (LBP) is a simple gray scale descriptor to characterize the local distribution of the gray levels in an image. Multi-resolution LBP and/or combinations of the LBPs have shown to be effective in texture image analysis. However, it is unclear what resolutions or combinations to choose for texture analysis. Examining all the possible cases is impractical and intractable due to the exponential growth in a feature space. This limits the accuracy and time- and space-efficiency of LBP. Here, we propose a data mining approach for LBP, which efficiently explores a high-dimensional feature space and finds a relatively smaller number of discriminative features. The features can be any combinations of LBPs. These may not be achievable with conventional approaches. Hence, our approach not only fully utilizes the capability of LBP but also maintains the low computational complexity. We incorporated three different descriptors (LBP, local contrast measure, and local directional derivative measure) with three spatial resolutions and evaluated our approach using two comprehensive texture databases. The results demonstrated the effectiveness and robustness of our approach to different experimental designs and texture images. Published by Elsevier Ltd.
C1 [Kwak, Jin Tae; Xu, Sheng; Wood, Bradford J.] NIH, Hlth Clin Ctr, Ctr Intervent Oncol, Bethesda, MD 20892 USA.
RP Kwak, JT (reprint author), 10 Ctr Dr, Bethesda, MD 20892 USA.
EM jintae.kwak@nih.gov; xus2@cc.nih.gov; bwood@cc.nih.gov
FU National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institutes of Health. 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 74
TC 2
Z9 2
U1 3
U2 41
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0957-4174
EI 1873-6793
J9 EXPERT SYST APPL
JI Expert Syst. Appl.
PD JUN 1
PY 2015
VL 42
IS 9
BP 4529
EP 4539
DI 10.1016/j.eswa.2015.01.055
PG 11
WC Computer Science, Artificial Intelligence; Engineering, Electrical &
Electronic; Operations Research & Management Science
SC Computer Science; Engineering; Operations Research & Management Science
GA CF7PN
UT WOS:000352748900031
PM 25767332
ER
PT J
AU Rodgers, MM
Pai, VM
Conroy, RS
AF Rodgers, Mary M.
Pai, Vinay M.
Conroy, Richard S.
TI Recent Advances in Wearable Sensors for Health Monitoring
SO IEEE SENSORS JOURNAL
LA English
DT Article
DE Wearable sensors; biomedical and environmental monitoring; sensor
systems; accelerometers; patient monitoring
ID PARKINSONS-DISEASE; FLEXIBLE ELECTRONICS; STRETCHABLE ELECTRONICS;
EPIDERMAL ELECTRONICS; PHYSICAL-ACTIVITY; SUBACUTE STROKE; MOTOR
FUNCTION; SYSTEM; DEVICES; SKIN
AB Wearable sensor technology continues to advance and provide significant opportunities for improving personalized healthcare. In recent years, advances in flexible electronics, smart materials, and low-power computing and networking have reduced barriers to technology accessibility, integration, and cost, unleashing the potential for ubiquitous monitoring. This paper discusses recent advances in wearable sensors and systems that monitor movement, physiology, and environment, with a focus on applications for Parkinson's disease, stroke, and head and neck injuries.
C1 [Rodgers, Mary M.; Pai, Vinay M.; Conroy, Richard S.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
[Rodgers, Mary M.] Univ Maryland, Sch Med, Dept Phys Therapy & Rehabil Sci, Baltimore, MD 21201 USA.
RP Rodgers, MM (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
EM mary.rodgers@nih.gov; vinay.pai@nih.gov; richard.conroy@nih.gov
RI Conroy, Richard/D-1979-2009
OI Conroy, Richard/0000-0002-8896-6090
NR 76
TC 12
Z9 14
U1 13
U2 132
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 1530-437X
EI 1558-1748
J9 IEEE SENS J
JI IEEE Sens. J.
PD JUN
PY 2015
VL 15
IS 6
BP 3119
EP 3126
DI 10.1109/JSEN.2014.2357257
PG 8
WC Engineering, Electrical & Electronic; Instruments & Instrumentation;
Physics, Applied
SC Engineering; Instruments & Instrumentation; Physics
GA CG3AS
UT WOS:000353149400004
ER
PT J
AU Sandoval-Jaime, C
Green, KY
Sosnovtsev, SV
AF Sandoval-Jaime, Carlos
Green, Kim Y.
Sosnovtsev, Stanislav V.
TI Recovery of murine norovirus and feline calicivirus from plasmids
encoding EMCV IRES in stable cell lines expressing T7 polymerase
SO JOURNAL OF VIROLOGICAL METHODS
LA English
DT Article
DE Murine norovirus; Feline calicivirus; Reverse genetics system; T7 RNA
polymerase; EMCV IRES
ID REVERSE GENETICS SYSTEM; HEMORRHAGIC-DISEASE VIRUS; MAMMALIAN-CELLS;
TISSUE-CULTURE; LINKED PROTEIN; RNA-POLYMERASE; VPG; CDNA; REPLICATION;
TRANSLATION
AB Reverse genetics systems constitute one of the most important and powerful tools to study the molecular biology of viruses. We developed a new strategy for the recovery of murine norovirus from a single plasmid in which a bacteriophage T7 RNA polymerase (T7pol) promoter for transcription and an EMCV IRES for efficient translation were engineered immediately upstream of the viral genome. Infectious noroviruses were recovered following transfection of the newly designed plasmid into nonpermissive BHK-21 and HEK293T cell lines that were engineered to express T7pol constitutively. Recovery of the virus did not require the presence of a ribozyme at the 3 '-end of the virus genome. The strategy worked also for the efficient recovery of feline calicivirus in these normally nonpermissive cell types. This simplified reverse genetics approach may be broadly applicable to other caliciviruses. Published by Elsevier B.V.
C1 [Sandoval-Jaime, Carlos; Green, Kim Y.; Sosnovtsev, Stanislav V.] NIAID, Caliciviruses Sect, Infect Dis Lab, NIH,DHHS, Bethesda, MD 20892 USA.
RP Sosnovtsev, SV (reprint author), South Dr MSC8007,Bldg 50,Room 6314, Bethesda, MD 20892 USA.
EM ss216m@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 32
TC 0
Z9 0
U1 0
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-0934
EI 1879-0984
J9 J VIROL METHODS
JI J. Virol. Methods
PD JUN 1
PY 2015
VL 217
BP 1
EP 7
DI 10.1016/j.jviromet.2015.02.003
PG 7
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Virology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Virology
GA CG2FV
UT WOS:000353091200001
PM 25698463
ER
PT J
AU Sakkhachornphop, S
Kijak, GH
Beyrer, C
Razak, MH
Sanders-Buell, E
Jittiwutikarn, J
Suriyanon, V
Robb, ML
Kim, JH
Celentano, DD
McCutchan, FE
Tovanabutra, S
AF Sakkhachornphop, Supachai
Kijak, Gustavo H.
Beyrer, Chris
Razak, Myat Htoo
Sanders-Buell, Eric
Jittiwutikarn, Jaroon
Suriyanon, Vinai
Robb, Merlin L.
Kim, Jerome H.
Celentano, David D.
McCutchan, Francine E.
Tovanabutra, Sodsai
TI An effective tool for identifying HIV-1 subtypes B, C, CRF01_AE, their
recombinant forms, and dual infections in Southeast Asia by the
multi-region subtype specific PCR (MSSP) assay
SO JOURNAL OF VIROLOGICAL METHODS
LA English
DT Article
DE HIV-1; Subtyping; MSSP assay; Subtype specific PCR; Southeast Asia
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HETERODUPLEX MOBILITY ASSAY;
POLYMERASE-CHAIN-REACTION; THAI DRUG-USERS; MOLECULAR EPIDEMIOLOGY;
DISEASE PROGRESSION; NORTHERN THAILAND; GENOTYPING ASSAY; VACCINE
EFFICACY; HIGH-THROUGHPUT
AB The RV144 Thai vaccine trial has been the only vaccine study to show efficacy in preventing HIV infection. Ongoing molecular surveillance of HIV-1 in Southeast Asia is vital for vaccine development and evaluation. In this study a novel tool, the multi-region subtype specific PCR (MSSP) assay, that was able to identify subtypes B, C, CRF01_AE for Thailand, other Southeast Asian countries, India and China is described. The MSSP assay is based on a nested PCR strategy and amplifies eight short regions distributed along the HIV-1 genome using subtype-specific primers. A panel of 41 clinical DNA samples obtained primarily from opiate users in northern Thailand was used to test the assay performance. The MSSP assay provided 73-100% sensitivity and 100% specificity for the three subtypes in each genome region. The assay was then field-tested on 337 sera from HIV infected northern Thai drug users collected between 1999 and 2002. Subtype distribution was CRF01_AE 77.4% (n=261), subtype B 33% (n =11), CRFOLAE/B recombinant 12.2% (n= 41), CRF01_AE/C recombinant 0.6% (n = 2), and non-typeable 6.5% (n =22). The MSSP assay is a simple, cost-effective, and accurate genotyping tool for laboratory settings with limited resources and is sensitive enough to capture the recombinant genomes and dual infections. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Sakkhachornphop, Supachai; Suriyanon, Vinai] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50200, Thailand.
[Kijak, Gustavo H.; Sanders-Buell, Eric; Robb, Merlin L.; McCutchan, Francine E.; Tovanabutra, Sodsai] US Mil HIV Res Program MHRP, Henry M Jackson Fdn Adv Mil Med, Silver Spring, MD 20910 USA.
[Beyrer, Chris; Celentano, David D.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Razak, Myat Htoo] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Jittiwutikarn, Jaroon] Northern Drug Treatment Ctr, Chiang Mai 50200, Thailand.
[Kim, Jerome H.] US Mil HIV Res Program MHRP, Walter Reed Army Inst Res, Silver Spring, MD 20910 USA.
RP Tovanabutra, S (reprint author), Walter Reed Army Inst Res, MHRP & Henry M Jackson Fdn Adv Mil Med HJF, 503 Robert Grant Ave,Room 2N25, Silver Spring, MD 20910 USA.
EM stovanabutra@hivresearch.org
FU Fogarty AIDS International for Research and Training Program; Johns
Hopkins Bloomberg School of Public Health [D43TW000010-25]; Henry M.
Jackson Foundation for the Advancement of Military Medicine, Inc.
[W81XWH-11-2-0174]; U.S. Department of Defense (DOD); National Research
University Project under Thailand's Office of the Higher Education
Commission
FX We are very grateful to the subjects for their participation in this
study. The authors thank staff members at the Henry M. Jackson
Foundation for technical advice, the research staffs at Northern Drug
Treatment Center and RIHES for Cohort building and specimen collections.
We extend our gratitude to Dr. Thira Sirisanthana, Dr. Namtip Srirak,
Mr. Kittipong Rungruengthanakit, Mr. Rassamee Keawvichit, Mrs. Kanlaya
Wongworapat and Mr. Peter Lange for their advice and supports on
conducting the study. We are indebted to Ms. Meera Bose and Mr. Peter
Phuc Pham for HIV-1 sequence analysis. This study was supported by the
Fogarty AIDS International for Research and Training Program, Johns
Hopkins Bloomberg School of Public Health, grants number D43TW000010-25
and 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 (DOD). We wish to thank the National
Research University Project under Thailand's Office of the Higher
Education Commission for partial financial support.
NR 49
TC 0
Z9 0
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-0934
EI 1879-0984
J9 J VIROL METHODS
JI J. Virol. Methods
PD JUN 1
PY 2015
VL 217
BP 70
EP 78
DI 10.1016/j.jviromet.2015.02.015
PG 9
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Virology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Virology
GA CG2FV
UT WOS:000353091200012
PM 25725414
ER
PT J
AU Rao, VK
Price, S
Similuk, M
Niemela, J
McElwee, J
Rosenzweig, S
Su, H
Milner, J
Uzel, G
Lenardo, M
AF Rao, V. Koneti
Price, Susan
Similuk, Morgan
Niemela, Julie
McElwee, Joshua
Rosenzweig, Sergio
Su, Helen
Milner, Joshua
Uzel, Gulbu
Lenardo, Michael
TI EXTENDED GENETIC TESTING OF ALPS AND ALPS LIKE DISORDERS REVEALS NOVEL
DISORDERS OF IMMUNE DYSFUNCTION, INCLUDING DEFECTS IN CTLA4, PI3KCD, AND
STAT3 GENES
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Rao, V. Koneti; Price, Susan; Similuk, Morgan; Niemela, Julie; McElwee, Joshua; Rosenzweig, Sergio; Su, Helen; Milner, Joshua; Uzel, Gulbu; Lenardo, Michael] NIH, Bethesda, MD 20892 USA.
RI Su, Helen/H-9541-2015
OI Su, Helen/0000-0002-5582-9110
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUN
PY 2015
VL 62
SU 2
BP 23
EP 23
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA CF9BD
UT WOS:000352855600012
ER
PT J
AU Farrar, J
O'Brien, K
Anderson, S
Atsidaftos, E
Lipton, J
Ellis, S
Bodine, D
Vlachos, A
AF Farrar, Jason
O'Brien, Kelly
Anderson, Stacie
Atsidaftos, Eva
Lipton, Jeffrey
Ellis, Steven
Bodine, David
Vlachos, Adrianna
TI ERYTHROID CELLS FROM DIAMOND BLACKFAN ANEMIA (DBA) PATIENTS WITH GATA1
AND RIBOSOMAL PROTEIN (RP) MUTATIONS SHOW MARKED DIFFERENCES IN RNA
EXPRESSION
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Farrar, Jason; O'Brien, Kelly; Anderson, Stacie; Atsidaftos, Eva; Lipton, Jeffrey; Ellis, Steven; Bodine, David; Vlachos, Adrianna] NHGRI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUN
PY 2015
VL 62
SU 2
BP 28
EP 28
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA CF9BD
UT WOS:000352855600029
ER
PT J
AU Akshintala, S
Dombi, E
Glod, J
Fox, E
Lodish, M
Whitcomb, P
Balis, F
Widemann, B
AF Akshintala, Srivandana
Dombi, Eva
Glod, John
Fox, Elizabeth
Lodish, Maya
Whitcomb, Patricia
Balis, Frank
Widemann, Brigitte
TI RESPONSE AND RESISTANCE TO THE RECEPTOR TYROSINE KINASE INHIBITOR (TKI)
VANDETANIB IN PEDIATRIC PATIENTS WITH MEDULLARY THYROID CARCINOMA (MTC)
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Akshintala, Srivandana; Dombi, Eva; Glod, John; Fox, Elizabeth; Lodish, Maya; Whitcomb, Patricia; Balis, Frank; Widemann, Brigitte] Natl Canc Inst, Pediat Oncol Branch, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUN
PY 2015
VL 62
SU 2
MA 750
BP 102
EP 102
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA CF9BD
UT WOS:000352855600281
ER
PT J
AU Bradford, D
Akshintala, S
Chen, C
Jung, S
Jones, E
Dombi, E
Whatley, M
Glod, J
Whitcomb, T
Widemann, B
AF Bradford, Diana
Akshintala, Srivandana
Chen, Clara
Jung, Seungyeon
Jones, Elizabeth
Dombi, Eva
Whatley, Millie
Glod, John
Whitcomb, Trish
Widemann, Brigitte
TI THE ROLE OF 18F-FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY (18F-FDG
PET) IN PEDIATRIC MEDULLARY THYROID CARCINOMA (MTC)
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Bradford, Diana; Akshintala, Srivandana; Chen, Clara; Jung, Seungyeon; Jones, Elizabeth; Dombi, Eva; Whatley, Millie; Glod, John; Whitcomb, Trish; Widemann, Brigitte] Natl Canc Inst, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUN
PY 2015
VL 62
SU 2
MA 752
BP 103
EP 103
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA CF9BD
UT WOS:000352855600283
ER
PT J
AU Damiano, DL
Leonard, R
AF Damiano, Diane L.
Leonard, Rebecca
TI 5 2014 Section on Pediatrics Knowledge Translation Lecture: Clinicians
and Researchers on the Same Path Toward Facilitating Family Goals for
Mobility and Participation
SO PEDIATRIC PHYSICAL THERAPY
LA English
DT Article
DE cerebral palsy; knowledge translation; lecture; physical therapy;
research design
ID CEREBRAL-PALSY; CHILDREN
AB Background: The knowledge translation (KT) lecture at the Combined Sections Meeting 2014 was a personal perspective from a researcher who had been a therapist and a longtime clinician, now a PhD candidate. Objective: To better integrate research and clinical care, KT is a seamless rather than separate process. Key Points: Knowledge translation can be enhanced by improved receptivity to evidence, and increasing use of research designs that encourage and even require clinician involvement, from single-subject designs to large-scale pragmatic trials. Clinical practice databases and hiring therapists to provide intervention in research efforts also serve to integrate research and clinical care. Limitations of applying mean group research results to an individual patient were also discussed and suggest an important unanswered topic for future research. Conclusion: We all need to assume responsibility for the researcher-clinician partnership, making our jobs more joyful and fulfilling, and hopefully the biggest beneficiaries will be our current and future patients.
C1 [Damiano, Diane L.] NIH, Funct & Appl Biomech Sect, Bethesda, MD 20892 USA.
[Leonard, Rebecca] Early Intervent Associates, Rockville, MD USA.
RP Damiano, DL (reprint author), NIH, Funct & Appl Biomech Sect, 10 Ctr Dr,Room 1-1469, Bethesda, MD 20892 USA.
EM damianod@cc.nih.gov
RI Damiano, Diane/B-3338-2010
OI Damiano, Diane/0000-0002-2770-5356
FU Intramural Research Program at the NIH Clinical Center
FX Grant Funding: The Intramural Research Program at the NIH Clinical
Center funded this work.
NR 17
TC 1
Z9 1
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0898-5669
EI 1538-005X
J9 PEDIATR PHYS THER
JI Pediatr. Phys. Ther.
PD SUM
PY 2015
VL 27
IS 2
BP 105
EP 112
DI 10.1097/PEP.0000000000000147
PG 8
WC Pediatrics; Rehabilitation
SC Pediatrics; Rehabilitation
GA CE8EW
UT WOS:000352075400002
PM 25822350
ER
PT J
AU Roy, K
Wu, YZ
Meitzler, JL
Juhasz, A
Liu, H
Jiang, GJ
Lu, JM
Antony, S
Doroshow, JH
AF Roy, Krishnendu
Wu, Yongzhong
Meitzler, Jennifer L.
Juhasz, Agnes
Liu, Han
Jiang, Guojian
Lu, Jiamo
Antony, Smitha
Doroshow, James H.
TI NADPH oxidases and cancer
SO CLINICAL SCIENCE
LA English
DT Review
DE cancer; cytokine; NADPH oxidase; oxidative stress; reactive oxygen
species.
ID NF-KAPPA-B; EPITHELIAL-MESENCHYMAL TRANSITION; ESOPHAGEAL ADENOCARCINOMA
CELLS; SUPEROXIDE-PRODUCING ENZYME; NITRIC-OXIDE SYNTHASE;
NECROSIS-FACTOR-ALPHA; HUMAN COLON CANCERS; PANCREATIC-CANCER;
GROWTH-FACTOR; CHRONIC INFLAMMATION
AB The mechanism by which reactive oxygen species (ROS) are produced by tumour cells remained incompletely understood until the discovery over the last 15 years of the family of NADPH oxidases (NOXs 1-5 and dual oxidases DUOX1/2) which are structural homologues of gp91(phox), the major membrane-bound component of the respiratory burst oxidase of leucocytes. Knowledge of the roles of the NOX isoforms in cancer is rapidly expanding. Recent evidence suggests that both NOX1 and DUOX2 species produce ROS in the gastrointestinal tract as a result of chronic inflammatory stress; cytokine induction (by interferon-gamma, tumour necrosis factor a, and interleukins IL-4 and IL-13) of NOX1 and DUOX2 may contribute to the development of colorectal and pancreatic carcinomas in patients with inflammatory bowel disease and chronic pancreatitis, respectively. NOX4 expression is increased in pre-malignant fibrotic states which may lead to carcinomas of the lung and liver. NOX5 is highly expressed in malignant melanomas, prostate cancer and Barrett's oesophagus-associated adenocarcinomas, and in the last it is related to chronic gastro-oesophageal reflux and inflammation. Over-expression of functional NOX proteins in many tissues helps to explain tissue injury and DNA damage from ROS that accompany pre-malignant conditions, as well as elucidating the potential mechanisms of NOX-related damage that contribute to both the initiation and the progression of a wide range of solid and haematopoietic malignancies.
C1 [Roy, Krishnendu; Liu, Han; Doroshow, James H.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Wu, Yongzhong; Meitzler, Jennifer L.; Juhasz, Agnes; Jiang, Guojian; Lu, Jiamo; Antony, Smitha; Doroshow, James H.] NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Doroshow, JH (reprint author), NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
EM doroshoj@mail.nih.gov
FU federal funds from the Center for Cancer Research; Division of Cancer
Treatment and Diagnosis, National Cancer Institute, National Institutes
of Health
FX d This work was supported by federal funds from the Center for Cancer
Research and the Division of Cancer Treatment and Diagnosis, 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.
NR 136
TC 19
Z9 22
U1 3
U2 37
PU PORTLAND PRESS LTD
PI LONDON
PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND
SN 0143-5221
EI 1470-8736
J9 CLIN SCI
JI Clin. Sci.
PD JUN
PY 2015
VL 128
IS 12
BP 863
EP 875
DI 10.1042/CS20140542
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CE6CP
UT WOS:000351924000002
PM 25818486
ER
PT J
AU Wargon, V
Riggio, M
Giulianelli, S
Sequeira, GR
Rojas, P
May, M
Polo, ML
Gorostiaga, MA
Jacobsen, B
Molinolo, A
Novaro, V
Lanari, C
AF Wargon, Victoria
Riggio, Marina
Giulianelli, Sebastian
Sequeira, Gonzalo R.
Rojas, Paola
May, Maria
Polo, Maria L.
Gorostiaga, Maria A.
Jacobsen, Britta
Molinolo, Alfredo
Novaro, Virginia
Lanari, Claudia
TI Progestin and antiprogestin responsiveness in breast cancer is driven by
the PRA/PRB ratio via AIB1 or SMRT recruitment to the CCND1 and MYC
promoters
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE breast cancer; progesterone receptor isoforms; antiprogestins;
mifepristone; AIB1; SMRT; cyclin D1; MYC; antiprogestin therapy; hormone
responsiveness
ID MAMMARY-GLAND DEVELOPMENT; RECEPTOR ISOFORM RATIO; CELL-CYCLE
PROGRESSION; B-ISOFORM; PROXIMITY LIGATION; TUMOR XENOGRAFTS;
GENE-REGULATION; IN-SITU; PR-A; EXPRESSION
AB There is emerging interest in understanding the role of progesterone receptors (PRs) in breast cancer. The aim of this study was to investigate the proliferative effect of progestins and antiprogestins depending on the relative expression of the A (PRA) and B (PRB) isoforms of PR. In mifepristone (MFP)-resistant murine carcinomas antiprogestin responsiveness was restored by re-expressing PRA using demethylating agents and histone deacetylase inhibitors. Consistently, in two human breast cancer xenograft models, one manipulated to overexpress PRA or PRB (IBH-6 cells), and the other expressing only PRA (T47D-YA) or PRB (T47D-YB), MFP selectively inhibited the growth of PRA-overexpressing tumors and stimulated IBH-6-PRB xenograft growth. Furthermore, in cells with high or equimolar PRA/PRB ratios, which are stimulated to proliferate in vitro by progestins, and are inhibited by MFP, MPA increased the interaction between PR and the coactivator AIB1, and MFP favored the interaction between PR and the corepressor SMRT. In a PRB-dominant context in which MFP stimulates and MPA inhibits cell proliferation, the opposite interactions were observed. Chromatin immunoprecipitation assays in T47D cells in the presence of MPA or MFP confirmed the interactions between PR and the coregulators at the CCND1 and MYC promoters. SMRT downregulation by siRNA abolished the inhibitory effect of MFP on MYC expression and cell proliferation. Our results indicate that antiprogestins are therapeutic tools that selectively inhibit PRA-overexpressing tumors by increasing the SMRT/AIB1 balance at the CCND1 and MYC promoters.
What's new? There is emerging interest in understanding the role of progesterone receptors (PRs)of which two isoforms have been described, PRA and PRBin breast cancer. This study investigates the proliferative effect of antiprogestins depending on the relative expression of PRA and PRB. The results provide mechanistic evidence that the responsiveness of breast cancer to antiprogestin treatment is determined by the ratio of expression of PRA and PRB isoforms. Antiprogestins selectively inhibit PRA-overexpressing tumors by increasing the SMRT/AIB1 balance at the CCND1 and MYC promoters. The results may pave the way for a personalized use of antiprogestins in breast cancer treatment.
C1 [Wargon, Victoria; Riggio, Marina; Giulianelli, Sebastian; Sequeira, Gonzalo R.; Rojas, Paola; May, Maria; Polo, Maria L.; Gorostiaga, Maria A.; Novaro, Virginia; Lanari, Claudia] Consejo Nacl Invest Cient & Tecn, Inst Expt Biol & Med IBYME, Lab Hormonal Carcinogenesis, RA-1033 Buenos Aires, DF, Argentina.
[Jacobsen, Britta] Univ Colorado, Aurora, CO USA.
[Molinolo, Alfredo] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
RP Lanari, C (reprint author), IBYME CONICET, Vuelta Obligado 2490,C1428ADN, Buenos Aires, DF, Argentina.
EM lanari.claudia@gmail.com
FU ANAPCYT [PICT2007/932, PICT2007/939, PICT2012/1091, PICT2012/1244];
CONICET [PIP2010/692]; Fundacion Sales, Intramural Research Program,
NIDCR, NIH; CONICET
FX Grant sponsor: ANAPCYT; Grant numbers: PICT2007/932 and 939 and
PICT2012/1091 and 1244; Grant sponsor: CONICET; Grant number:
PIP2010/692; Grant sponsor: Fundacion Sales, Intramural Research
Program, NIDCR, NIH and CONICET
NR 55
TC 8
Z9 9
U1 0
U2 6
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 JUN 1
PY 2015
VL 136
IS 11
BP 2680
EP 2692
DI 10.1002/ijc.29304
PG 13
WC Oncology
SC Oncology
GA CD8PL
UT WOS:000351357700019
PM 25363551
ER
PT J
AU Bang, J
Huh, JH
Na, JW
Lu, Q
Carlson, BA
Tobe, R
Tsuji, PA
Gladyshev, VN
Hatfield, DL
Lee, BJ
AF Bang, Jeyoung
Huh, Jang Hoe
Na, Ji-Woon
Lu, Qiao
Carlson, Bradley A.
Tobe, Ryuta
Tsuji, Petra A.
Gladyshev, Vadim N.
Hatfield, Dolph L.
Lee, Byeong Jae
TI Cell Proliferation and Motility Are Inhibited by G1 Phase Arrest in
15-kDa Selenoprotein-Deficient Chang Liver Cells
SO MOLECULES AND CELLS
LA English
DT Article
DE 15-kDa selenoprotein; cell cycle arrest; cell proliferation; cyclin E;
selenium
ID HUMAN HEALTH; SELENIUM; SEP15; PROTEIN; SEQUENCE; BINDING; FAMILY;
GROWTH; ROLES
AB The 15-kDa selenoprotein (Sep15) is a selenoprotein residing in the lumen of the endoplasmic reticulum (ER) and implicated in quality control of protein folding. Herein, we established an inducible RNAi cell line that targets Sep15 mRNA in Chang liver cells. RNAi-induced Sep15 deficiency led to inhibition of cell proliferation, whereas cell growth was resumed after removal of the knockdown inducer. Sep15-deficient cells were arrested at the G1 phase by upregulating p21 and p27, and these cells were also characterized by ER stress. In addition, Sep15 deficiency led to the relocation of focal adhesions to the periphery of the cell basement and to the decrease of the migratory and invasive ability. All these changes were reversible depending on Sep15 status. Rescuing the knockdown state by expressing a silent mutant Sep15 mRNA that is resistant to siRNA also reversed the phenotypic changes. Our results suggest that SEP15 plays important roles in the regulation of the G1 phase during the cell cycle as well as in cell motility in Chang liver cells, and that this selenoprotein offers a novel functional link between the cell cycle and cell motility.
C1 [Bang, Jeyoung; Huh, Jang Hoe; Na, Ji-Woon; Lu, Qiao; Lee, Byeong Jae] Seoul Natl Univ, Sch Biol Sci, Seoul 151742, South Korea.
[Bang, Jeyoung; Lee, Byeong Jae] Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul 151742, South Korea.
[Lee, Byeong Jae] Seoul Natl Univ, Inst Mol Biol & Genet, Seoul 151742, South Korea.
[Carlson, Bradley A.; Tobe, Ryuta; Hatfield, Dolph L.] NCI, Mouse Canc Genet Program, NIH, Bethesda, MD 20892 USA.
[Tsuji, Petra A.] Towson Univ, Dept Biol Sci, Towson, MD 21252 USA.
[Gladyshev, Vadim N.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Lee, BJ (reprint author), Seoul Natl Univ, Sch Biol Sci, Seoul 151742, South Korea.
EM imbglmg@snu.ac.kr
FU Priority Research Centers Program through the National Research
Foundation of Korea (NRF) - Ministry of Education, Science and
Technology [2010-0029694]; Basic Science Research Program through the
National Research Foundation of Korea (NRF) - Ministry of Education,
Science and Technology [2011-0012947]; Bio & Medical Technology
Development Program of the National Research Foundation (NRF) - Ministry
of Science, ICT & Future Planning [2012M3A9D1054622]; Intramural
Research Program of the National Institutes of Health, National Cancer
Institute, Center for Cancer Research; NIH [CA080946]
FX This work was supported by the Priority Research Centers Program (Grant
No. 2010-0029694) and Basic Science Research Program through the
National Research Foundation of Korea (NRF) funded by the Ministry of
Education, Science and Technology (Grant No. 2011-0012947), the Bio &
Medical Technology Development Program of the National Research
Foundation (NRF) funded by the Ministry of Science, ICT & Future
Planning (2012M3A9D1054622) to BJL, and in part by the Intramural
Research Program of the National Institutes of Health, National Cancer
Institute, Center for Cancer Research to DLH and NIH CA080946 to VNG.
NR 31
TC 2
Z9 2
U1 0
U2 1
PU KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
PI SEOUL
PA 635-4, YUCKSAM-DONG, GANGNAM-GU, SEOUL 135-703, SOUTH KOREA
SN 1016-8478
EI 0219-1032
J9 MOL CELLS
JI Mol. Cells
PD MAY 31
PY 2015
VL 38
IS 5
BP 457
EP 465
DI 10.14348/molcells.2015.0007
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CJ5VB
UT WOS:000355558800011
PM 25728752
ER
PT J
AU Park, O
Ki, SH
Xu, MJ
Wang, H
Feng, DC
Tam, J
Osei-Hyiaman, D
Kunos, G
Gao, B
AF Park, Ogyi
Ki, Sung Hwan
Xu, Mingjiang
Wang, Hua
Feng, Dechun
Tam, Joseph
Osei-Hyiaman, Douglas
Kunos, George
Gao, Bin
TI Biologically active, high levels of interleukin-22 inhibit hepatic
gluconeogenesis but do not affect obesity and its metabolic consequences
SO CELL AND BIOSCIENCE
LA English
DT Article
DE Obesity; Insulin resistance; Hyperglycemia; Cytokine; Liver
ID HEPATOCELLULAR-CARCINOMA; LIVER INFLAMMATION; IL-22; MICE; CYTOKINES;
PANCREATITIS; HEPATOCYTES; ACTIVATION; FIBROSIS; IMMUNITY
AB Background: Interleukin-22 (IL-22), a cytokine with important functions in anti-microbial defense and tissue repair, has been recently suggested to have beneficial effects in obesity and metabolic syndrome in some but not in other studies. Here, we re-examined the effects of IL-22 on obesity, insulin resistance, and hepatic glucose metabolism.
Results: Genetic deletion of IL-22 did not affect high-fat-diet (HFD)-induced obesity and insulin resistance. IL-22 transgenic mice with relatively high levels of circulating IL-22 (similar to 600 pg/ml) were completely resistant to Concanavalin A-induced liver injury but developed the same degree of high fat diet (HFD)-induced obesity, insulin resistance, and fatty liver as the wild-type littermate controls. Similarly, chronic treatment with recombinant mouse IL-22 (rmIL-22) protein did not affect HFD-induced obesity and the associated metabolic syndrome. In vivo treatment with a single dose of rmIL-22 downregulated the hepatic expression of gluconeogenic genes and subsequently inhibited hepatic gluconeogenesis and reduced blood glucose levels both in HFD-fed and streptozotocin (STZ)-treated mice without affecting insulin production. In vitro exposure of mouse primary hepatocytes to IL-22 suppressed glucose production and the expression of gluconeogenic genes. These inhibitory effects were partially reversed by blocking STAT3 or the AMPK signaling pathway.
Conclusion: Biologically active, high levels of IL-22 do not affect obesity and the associated metabolic syndrome. Acute treatment with IL-22 inhibits hepatic gluconeogenesis, which is mediated via the activation of STAT3 and AMPK in hepatocytes.
C1 [Park, Ogyi; Ki, Sung Hwan; Xu, Mingjiang; Wang, Hua; Feng, Dechun; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA.
[Tam, Joseph; Osei-Hyiaman, Douglas; Kunos, George] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
[Ki, Sung Hwan] Chosun Univ, Coll Pharm, Lab Toxicol, Gwangju, South Korea.
[Tam, Joseph] Hebrew Univ Jerusalem, Fac Med, Sch Pharm, Obes & Metab Lab,Inst Drug Res, IL-91120 Jerusalem, Israel.
RP Gao, B (reprint author), NIAAA, Lab Liver Dis, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA.
EM bgao@mail.nih.gov
RI Feng, Dechun/Q-5962-2016
NR 39
TC 6
Z9 6
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2045-3701
J9 CELL BIOSCI
JI Cell Biosci.
PD MAY 30
PY 2015
VL 5
AR 25
DI 10.1186/s13578-015-0015-0
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CK0OE
UT WOS:000355903700001
PM 26064446
ER
PT J
AU Bentley, AR
Divers, J
Shriner, D
Doumatey, AP
Gutierrez, OM
Adeyemo, AA
Freedman, BI
Rotimi, CN
AF Bentley, Amy R.
Divers, Jasmin
Shriner, Daniel
Doumatey, Ayo P.
Gutierrez, Orlando M.
Adeyemo, Adebowale A.
Freedman, Barry I.
Rotimi, Charles N.
TI APOL1 G1 genotype modifies the association between HDLC and kidney
function in African Americans
SO BMC GENOMICS
LA English
DT Article
DE Apolipoprotein L1; High-density lipoprotein cholesterol; African
ancestry; Glomerular filtration rate
ID GLOMERULAR-FILTRATION-RATE; STAGE RENAL-DISEASE; FOCAL SEGMENTAL
GLOMERULOSCLEROSIS; HIGH-DENSITY-LIPOPROTEINS; CARDIOVASCULAR-DISEASE;
GENETIC-VARIANTS; SERUM CREATININE; RISK; ATHEROSCLEROSIS; CHOLESTEROL
AB Background: Despite evidence of an association between variants at the apolipoprotein L1 gene (APOL1) locus and a spectrum of related kidney diseases, underlying biological mechanisms remain unknown. An earlier preliminary study published by our group showed that an APOL1 variant (rs73885319) modified the association between high-density lipoprotein cholesterol (HDLC) and estimated glomerular filtration rate (eGFR) in African Americans. To further understand this relationship, we evaluated the interaction in two additional large cohorts of African Americans for a total of 3,592 unrelated individuals from the Howard University Family Study (HUFS), the Natural History of APOL1-Associated Nephropathy Study (NHAAN), and the Atherosclerosis Risk in Communities Study (ARIC). The association between HDLC and eGFR was determined using linear mixed models, and the interaction between rs73885319 genotype and HDLC was evaluated using a multiplicative term.
Results: Among individuals homozygous for the risk genotype, a strong inverse HDLC-eGFR association was observed, with a positive association in others (p for the interaction of the rs73885319 x HDLC =0.0001). The interaction was similar in HUFS and NHAAN, and attenuated in ARIC. Given that ARIC participants were older, we investigated an age effect; age was a significant modifier of the observed interaction. When older individuals were excluded, the interaction in ARIC was similar to that in the other studies.
Conclusions: Based on these findings, it is clear that the relationship between HDLC and eGFR is strongly influenced by the APOL1 rs73885319 kidney risk genotype. Moreover, the degree to which this variant modifies the association may depend on the age of the individual. More detailed physiological studies are warranted to understand how rs73885319 may affect the relationship between HDLC and eGFR in individuals with and without disease and across the lifespan.
C1 [Bentley, Amy R.; Shriner, Daniel; Doumatey, Ayo P.; Adeyemo, Adebowale A.; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
[Divers, Jasmin] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
[Gutierrez, Orlando M.] Univ Alabama Birmingham, Div Nephrol, Birmingham, AL USA.
[Freedman, Barry I.] Wake Forest Sch Med, Dept Internal Med Nephrol, Winston Salem, NC USA.
RP Rotimi, CN (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 National Institutes of Health [S06GM008016-320107, S06GM008016-380111];
NIGMS/MBRS/SCORE Program; National Center for Research Resources, a
component of the National Institutes of Health [2M01RR010284];
Intramural Research Program of the National Human Genome Research
Institute in the Center for Research in Genomics and Global Health
[CRGGH-Z01HG200362]; National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK), Center for Information Technology; Office of
the Director at the National Institutes of Health; National Heart, Lung,
and Blood Institute [HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; National Human
Genome Research Institute [U01HG004402]; [DK084149]; [DK070941]
FX The contents of this paper are solely the responsibility of the authors
and do not necessarily represent the official view of the National
Institutes of Health. The study was supported by National Institutes of
Health grants S06GM008016-320107 to C. Rotimi and S06GM008016-380111 to
A. Adeyemo, both from the NIGMS/MBRS/SCORE Program. Participant
enrollment was carried out at the Howard University General Clinical
Research Center, which is supported by grant 2M01RR010284 from the
National Center for Research Resources, a component of the National
Institutes of Health. This research was supported in part by the
Intramural Research Program of the National Human Genome Research
Institute in the Center for Research in Genomics and Global Health
(CRGGH-Z01HG200362). CRGGH is also supported by National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK), Center for
Information Technology, and the Office of the Director at the National
Institutes of Health. The Atherosclerosis Risk in Communities Study is
carried out as a collaborative study supported by National Heart, Lung,
and Blood Institute 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. Funding for GENEVA was provided by National
Human Genome Research Institute grant U01HG004402 (Eric Boerwinkle). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript. The NHAAN study
is supported by RO1 grants DK084149 and DK070941 to B.I. Freedman.
NR 40
TC 3
Z9 4
U1 0
U2 0
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 MAY 30
PY 2015
VL 16
AR 421
DI 10.1186/s12864-015-1645-7
PG 8
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA CJ2GU
UT WOS:000355303000001
PM 26025194
ER
PT J
AU Ramalho-Ortigao, M
Coutinho-Abreu, IV
Balbino, VQ
Figueiredo, CAS
Mukbel, R
Dayem, H
Hanafi, HA
El-Hossary, SS
Fawaz, EEDY
Abo-Shehada, M
Hoel, DF
Stayback, G
Wadsworth, M
Shoue, DA
Abrudan, J
Lobo, NF
Mahon, AR
Emrich, SJ
Kamhawi, S
Collins, FH
McDowell, MA
AF Ramalho-Ortigao, Marcelo
Coutinho-Abreu, Iliano V.
Balbino, Valdir Q.
Figueiredo, Carlos Alberto S., Jr.
Mukbel, Rami
Dayem, Hussan
Hanafi, Hanafi A.
El-Hossary, Shabaan S.
Fawaz, Emad El-Din Y.
Abo-Shehada, Mahmoud
Hoel, David F.
Stayback, Gwen
Wadsworth, Mariha
Shoue, Douglas A.
Abrudan, Jenica
Lobo, Neil F.
Mahon, Andrew R.
Emrich, Scott J.
Kamhawi, Shaden
Collins, Frank H.
McDowell, Mary Ann
TI Phlebotomus papatasi SP15: mRNA expression variability and amino acid
sequence polymorphisms of field populations
SO PARASITES & VECTORS
LA English
DT Article
DE Sand fly; Saliva; PpSP15; Leishmaniasis; Vaccine; Expression
variability; MHC class II epitopes
ID SAND FLY VECTOR; LEISHMANIA AMAZONENSIS INFECTION; LUTZOMYIA-LONGIPALPIS
COMPLEX; ANTI-MOSQUITO ANTIBODIES; SALIVARY-GLAND PROTEINS; SOUTHERN
JORDAN-VALLEY; T-CELL RECOGNITION; CUTANEOUS LEISHMANIASIS; WILD-CAUGHT;
VISCERAL LEISHMANIASIS
AB Background: The Phlebotomus papatasi salivary protein PpSP15 was shown to protect mice against Leishmania major, suggesting that incorporation of salivary molecules in multi-component vaccines may be a viable strategy for anti-Leishmania vaccines.
Methods: Here, we investigated PpSP15 predicted amino acid sequence variability and mRNA profile of P. papatasi field populations from the Middle East. In addition, predicted MHC class II T-cell epitopes were obtained and compared to areas of amino acid sequence variability within the secreted protein.
Results: The analysis of PpSP15 expression from field populations revealed significant intra-and interpopulation variation.. In spite of the variability detected for P. papatasi populations, common epitopes for MHC class II binding are still present and may potentially be used to boost the response against Le. major infections.
Conclusions: Conserved epitopes of PpSP15 could potentially be used in the development of a salivary gland antigen-based vaccine.
C1 [Ramalho-Ortigao, Marcelo] Kansas State Univ, Dept Entomol, Manhattan, KS 66506 USA.
[Coutinho-Abreu, Iliano V.; Kamhawi, Shaden] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Balbino, Valdir Q.; Figueiredo, Carlos Alberto S., Jr.] Univ Fed Pernambuco, Dept Genet, Recife, PE, Brazil.
[Mukbel, Rami; Dayem, Hussan; Hanafi, Hanafi A.; Abo-Shehada, Mahmoud] Jordan Univ Sci & Technol, Fac Vet Med, Irbid 22110, Jordan.
[Fawaz, Emad El-Din Y.] NAMRU 3, US Naval Med Res Unit 3, Vector Biol Res Program, Cairo, Egypt.
[Hoel, David F.] Uniformed Serv Univ Hlth Sci, Dept Biostat, Bethesda, MD 20814 USA.
[Stayback, Gwen; Wadsworth, Mariha; Shoue, Douglas A.; Lobo, Neil F.; Emrich, Scott J.; Collins, Frank H.; McDowell, Mary Ann] Univ Notre Dame, Dept Biol Sci, Eck Inst Global Hlth, Notre Dame, IN 46556 USA.
[Abrudan, Jenica] Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Mahon, Andrew R.] Cent Michigan Univ, Dept Biol, Detroit, MI 48859 USA.
[Emrich, Scott J.; Collins, Frank H.] Univ Notre Dame, Dept Comp Sci & Engn, Notre Dame, IN 46556 USA.
RP McDowell, MA (reprint author), Univ Notre Dame, Dept Biol Sci, Eck Inst Global Hlth, Notre Dame, IN 46556 USA.
EM mcdowell.11@nd.edu
FU Department of Defense (DoD) Defense Advanced Research Projects Agency
(DARPA) [W911NF0410380]; National Institute of Allergy and Infectious
Diseases [R01AI074691]
FX We are grateful to the Egyptian Ministry of Health for their aid and in
sand fly collections and the Multi National Force and Observers (MFO)
military units for transportation in the Sinai Peninsula. Special
gratitude goes to Ms. Maria Badra for her organizational skills and
support of the work in Eygpt. We are also indebted to the Sand Fly
Genome Consortium and allowed us to submit our mapping results prior to
the completion and publication of the sand fly genome analysis. This
project was supported by contract # W911NF0410380 from the Department of
Defense (DoD) Defense Advanced Research Projects Agency (DARPA) awarded
to MAM. MR-O was supported by a grant from the National Institute of
Allergy and Infectious Diseases (R01AI074691).
NR 74
TC 2
Z9 2
U1 0
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-3305
J9 PARASITE VECTOR
JI Parasites Vectors
PD MAY 29
PY 2015
VL 8
AR 298
DI 10.1186/s13071-015-0914-2
PG 14
WC Parasitology
SC Parasitology
GA CL0XL
UT WOS:000356666300001
PM 26022221
ER
PT J
AU Tin, A
Kottgen, A
Folsom, AR
Maruthur, NM
Tajuddin, SM
Nalls, MA
Evans, MK
Zonderman, AB
Friedrich, CA
Boerwinkle, E
Coresh, J
Kao, WHL
AF Tin, Adrienne
Koettgen, Anna
Folsom, Aaron R.
Maruthur, Nisa M.
Tajuddin, Salman M.
Nalls, Mike A.
Evans, Michele K.
Zonderman, Alan B.
Friedrich, Christopher A.
Boerwinkle, Eric
Coresh, Josef
Kao, Wen Hong Linda
TI Genetic loci for serum magnesium among African-Americans and
gene-environment interaction at MUC1 and TRPM6 in European-Americans:
the Atherosclerosis Risk in Communities (ARIC) study
SO BMC GENETICS
LA English
DT Article
DE Gene-environment interaction; Serum magnesium; MUC1; TRPM6
ID DIAGNOSING INSULIN-RESISTANCE; GENOME-WIDE ASSOCIATION; DIETARY
MAGNESIUM; EXPRESSION; METAANALYSIS; POPULATION; DISEASE
AB Background: Low serum magnesium levels have been associated with multiple chronic diseases. The regulation of serum magnesium homeostasis is not well understood. A previous genome-wide association study (GWAS) of European ancestry (EA) populations identified nine loci for serum magnesium. No such study has been conducted in African-Americans, nor has there been an evaluation of the interaction of magnesium-associated SNPs with environmental factors. The goals of this study were to identify genetic loci associated with serum magnesium in an African-American (AA) population using both genome-wide and candidate region interrogation approaches and to evaluate gene-environment interaction for the magnesium-associated variants in both EA and AA populations. We conducted a GWAS of serum magnesium in 2737 AA participants of the Atherosclerosis Risk in Communities (ARIC) Study and interrogated the regions of the nine published candidate loci in these results. Literature search identified the influence of progesterone on MUC1 expression and insulin on TRPM6 expression.
Results: The GWAS approach in African-American participants identified a locus near MUC1 as genome-wide significant (rs2974937, beta = -0.013, p = 6.1x10(-9)). The candidate region interrogation approach identified two of the nine loci previously discovered in EA populations as containing SNPs that were significantly associated in African-American participants (SHROOM3 and TRPM6). The index variants at these three loci together explained 2.8 % of the variance in serum magnesium concentration in ARIC African-American participants. On the test of gene-environment interaction in ARIC EA participants, the index variant at MUC1 had 2.5 times stronger association in postmenopausal women with progestin use (beta = -0.028, p = 7.3x10(-5)) than in those without any hormone use (beta = -0.011, p = 7.0x10(-8), p for interaction 0.03). At TRPM6, the index variant had 1.6 times stronger association in those with lower fasting insulin levels (<80pmol/L: beta = -0.013, p = 1.6x10(-7); >= 80pmol/L: beta = -0.008, p = 1.8x10(-2), p for interaction 0.03).
Conclusions: We identified three loci that explained 2.8 % of the variance in serum magnesium concentration in ARIC African-American participants. Following-up on functional studies of gene expression identified gene-environment interactions between progestin use and MUC1 and between insulin and TRPM6 on serum magnesium concentration in ARIC European-American participants. These results extend our understanding of the metabolism of serum magnesium.
C1 [Tin, Adrienne; Koettgen, Anna; Coresh, Josef] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Koettgen, Anna] Univ Med Ctr Freiburg, Freiburg, Germany.
[Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA.
[Maruthur, Nisa M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Tajuddin, Salman M.; Nalls, Mike A.; Evans, Michele K.; Zonderman, Alan B.] NIA, NIH, Bethesda, MD 20892 USA.
[Friedrich, Christopher A.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[Boerwinkle, Eric; Kao, Wen Hong Linda] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA.
RP Tin, A (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
EM atin1@jhu.edu
OI Zonderman, Alan B/0000-0002-6523-4778; Tajuddin, Salman
M./0000-0002-7919-8528
FU NIH/NIDDK Renal Disease Epidemiology Training Program [T32 DK007732];
National Heart, Lung, and Blood Institute [HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C,
HHSN268201100012C]; Emmy Noether Programme of the German Research
Foundation [KO 3598/2-1]
FX Dr. Tin is supported by the NIH/NIDDK T32 DK007732 Renal Disease
Epidemiology Training Program.; The Atherosclerosis Risk in Communities
Study is carried out as a collaborative study supported by National
Heart, Lung, and Blood Institute contracts (HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and
HHSN268201100012C). AK was supported by the Emmy Noether Programme of
the German Research Foundation (KO 3598/2-1).
NR 32
TC 2
Z9 2
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2156
J9 BMC GENET
JI BMC Genet.
PD MAY 29
PY 2015
VL 16
AR 56
DI 10.1186/s12863-015-0219-7
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA CJ8ZD
UT WOS:000355791100001
PM 26058915
ER
PT J
AU Eichelberger, L
Murphy, G
Etemadi, A
Abnet, CC
Islami, F
Shakeri, R
Malekzadeh, R
Dawsey, SM
AF Eichelberger, Laura
Murphy, Gwen
Etemadi, Arash
Abnet, Christian C.
Islami, Farhad
Shakeri, Ramin
Malekzadeh, Reza
Dawsey, Sanford M.
TI Risk of Gastric Cancer by Water Source: Evidence from the Golestan
Case-Control Study
SO PLOS ONE
LA English
DT Article
ID HELICOBACTER-PYLORI INFECTION; STOMACH-CANCER; MULTIPLEX SEROLOGY;
ESOPHAGEAL CANCER; DRINKING-WATER; TRANSMISSION; IRAN; EPIDEMIOLOGY;
SEROPREVALENCE; ADENOCARCINOMA
AB Background
Gastric cancer (GC) is the world's fifth most common cancer, and the third leading cause of cancer-related death. Over 70% of incident cases and deaths occur in developing countries. We explored whether disparities in access to improved drinking water sources were associated with GC risk in the Golestan Gastric Cancer Case Control Study.
Methods and Findings
306 cases and 605 controls were matched on age, gender, and place of residence. We conducted unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CI), adjusted for age, gender, ethnicity, marital status, education, head of household education, place of birth and residence, homeownership, home size, wealth score, vegetable consumption, and H. pylori seropositivity. Fully-adjusted ORs were 0.23 (95% CI: 0.05-1.04) for chlorinated well water, 4.58 (95% CI: 2.07-10.16) for unchlorinated well water, 4.26 (95% CI: 1.81-10.04) for surface water, 1.11 (95% CI: 0.61-2.03) for water from cisterns, and 1.79 (95% CI: 1.20-2.69) for all unpiped sources, compared to in-home piped water. Comparing unchlorinated water to chlorinated water, we found over a two-fold increased GC risk (OR 2.37, 95% CI: 1.56-3.61).
Conclusions
Unpiped and unchlorinated drinking water sources, particularly wells and surface water, were significantly associated with the risk of GC.
C1 [Eichelberger, Laura] Univ Texas San Antonio, Dept Anthropol, San Antonio, TX 78249 USA.
[Eichelberger, Laura; Murphy, Gwen; Etemadi, Arash; Abnet, Christian C.; Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Etemadi, Arash; Islami, Farhad; Shakeri, Ramin; Malekzadeh, Reza] Univ Tehran Med Sci, Digest Oncol Res Ctr, Digest Dis Res Inst, Tehran, Iran.
[Islami, Farhad] Amer Canc Soc, Surveillance & Hlth Serv Res, Atlanta, GA 30303 USA.
RP Eichelberger, L (reprint author), Univ Texas San Antonio, Dept Anthropol, One UTSA Circle, San Antonio, TX 78249 USA.
EM laura.eichelberger@utsa.edu
RI Murphy, Gwen/G-7443-2015; Abnet, Christian/C-4111-2015; Etemadi,
Arash/C-1386-2016
OI , Ramin/0000-0003-0487-3629; Abnet, Christian/0000-0002-3008-7843;
Etemadi, Arash/0000-0002-3458-1072
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute, National Institutes of Health;
Digestive Disease Research Institute of Tehran University of Medical
Sciences [82-603]; Cancer Research UK [C20/A5860]; International Agency
for Research on Cancer
FX This work was supported in part by the Intramural Research Program of
the Division of Cancer Epidemiology and Genetics, National Cancer
Institute, National Institutes of Health; the Digestive Disease Research
Institute of Tehran University of Medical Sciences (grant No 82-603);
Cancer Research UK (C20/A5860); and by the International Agency for
Research on Cancer. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 49
TC 3
Z9 3
U1 1
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 MAY 29
PY 2015
VL 10
IS 5
AR e0128491
DI 10.1371/journal.pone.0128491
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CJ2MQ
UT WOS:000355319400094
PM 26023788
ER
PT J
AU Hinnebusch, AG
AF Hinnebusch, Alan G.
TI Blocking stress response for better memory?
SO SCIENCE
LA English
DT Editorial Material
ID NUCLEOTIDE EXCHANGE FACTOR; EIF2B COMPLEX; EIF2-ALPHA; INITIATION;
SUBUNIT; PROTEIN; TERM
C1 NIH, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA.
RP Hinnebusch, AG (reprint author), NIH, Lab Gene Regulat & Dev, Bldg 10, Bethesda, MD 20892 USA.
EM ahinnebusch@nih.gov
NR 13
TC 0
Z9 0
U1 1
U2 18
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD MAY 29
PY 2015
VL 348
IS 6238
BP 967
EP 968
DI 10.1126/science.aac4832
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CJ1WU
UT WOS:000355276600021
PM 26023119
ER
PT J
AU Mahanty, S
Prigent, A
Garraud, O
AF Mahanty, Siddhartha
Prigent, Antoine
Garraud, Olivier
TI Immunogenicity of infectious pathogens and vaccine antigens
SO BMC IMMUNOLOGY
LA English
DT Review
DE Immunogenicity; Infection; Pathogen; Antigen presentation; Vaccine;
Antibody isotype
ID ANTIBODY-RESPONSES; IMMUNE-RESPONSE; MALARIA; PLASMODIUM; SELECTION;
MOLECULES; FUTURE
AB The concept of the immunogenicity of an antigen is frequently encountered in the context of vaccine development, an area of intense interest currently due to the emergence or re-emergence of infectious pathogens with the potential for worldwide spread. However, the theoretical notion of immunogenicity as discussed in older textbooks of immunology needs reconsideration due to advances in our understanding of immunologic responses. Immunogenicity is a property that can either be a desirable attribute, for example in the generation of an effective protective immunity against infectious pathogens or an undesirable trait, for example when it relates to novel therapeutic compounds and drugs, where an immune response needs to be prevented or inhibited. In this Forum Article, we aimed to revisit the issue of immunogenicity to discuss a series of simple questions relevant to the concept that are frequently rephrased but incompletely resolved in the immunologic literature.
C1 [Mahanty, Siddhartha] NIAID, Lab Parasit Dis, NIH, Bethesda, MD 20892 USA.
[Prigent, Antoine] EFS, F-42023 St Etienne, France.
[Prigent, Antoine; Garraud, Olivier] Univ Lyon, EA3064, F-42023 St Etienne, France.
[Garraud, Olivier] Inst Natl Transfus Sanguine, F-75015 Paris, France.
RP Garraud, O (reprint author), Univ Lyon, EA3064, F-42023 St Etienne, France.
EM ogarraud@ints.fr
OI Mahanty, Siddhartha/0000-0003-1068-0524
FU National Institute of Allergy and Infectious Diseases, NIH
FX This research was supported in part by the Intramural Research Program
of the National Institute of Allergy and Infectious Diseases, NIH.
NR 36
TC 5
Z9 5
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2172
J9 BMC IMMUNOL
JI BMC Immunol.
PD MAY 29
PY 2015
VL 16
AR 31
DI 10.1186/s12865-015-0095-y
PG 6
WC Immunology
SC Immunology
GA CJ0EJ
UT WOS:000355146900001
PM 26021448
ER
PT J
AU Braunschweig, T
Chung, JY
Choi, CH
Cho, H
Chen, QR
Xie, R
Perry, C
Khan, J
Hewitt, SM
AF Braunschweig, Till
Chung, Joon-Yong
Choi, Chel Hun
Cho, Hanbyoul
Chen, Qing-Rong
Xie, Ran
Perry, Candice
Khan, Javed
Hewitt, Stephen M.
TI Assessment of a panel of tumor markers for the differential diagnosis of
benign and malignant effusions by well-based reverse phase protein array
SO DIAGNOSTIC PATHOLOGY
LA English
DT Article
DE Cytodiagnosis; Tumor biomarkers; Neoplasms; Mucin 1; Epithelial membrane
antigen; Pleural effusion
ID EPITHELIAL MEMBRANE ANTIGEN; ASCITES ALBUMIN GRADIENT; PLEURAL FLUID;
CARCINOEMBRYONIC ANTIGEN; MONOCLONAL-ANTIBODIES; CELL CARCINOMA;
CLINICAL-VALUE; LUNG-CANCER; E-CADHERIN; SERUM
AB Background: The differential diagnosis of benign and malignant effusion is often hampered by low cell content or insufficiently preserved tumor cells. In this study, we evaluated the combined diagnostic value of six tumor markers measured by well-based reverse-phase protein array (RPPA) for diagnosis of malignant effusion.
Methods: A total of 114 patients (46 with malignant effusions, 32 with probable malignant effusions, and 36 with benign effusions) were enrolled. Expressional levels of MUC1, EMA, Pan-CK, HSP90, TGF-beta and CA125 were determined by well-based RPPA.
Results: Median relative expression of MUC1, Pan-CK and EMA were significantly higher in malignant effusion than those in probable malignant or benign (p < 0.001, p = 0.003, p < 0.001, respectively), whereas the level of TGF-beta in malignant effusions were significantly lower than that in the other groups (p = 0.005). For predicting malignancy, EMA presented the best areas under the curve of 0.728 followed by MUC1 of 0.701. The sensitivity of 52.0% for MUC1 and 48.0% for EMA were not better than cytology. However, sensitivity, negative predictive value, and accuracy of the tumor marker panel were better than cytology by 14.7%, 7.5%, and 6.1%, respectively.
Conclusions: Tumor marker panel measured by well-based RPPA showed values in the differential diagnosis between benign and malignant effusions. Further large scale studies need to be performed to evaluate the utility of this panel of markers.
C1 [Braunschweig, Till; Chung, Joon-Yong; Choi, Chel Hun; Cho, Hanbyoul; Xie, Ran; Perry, Candice; Hewitt, Stephen M.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Braunschweig, Till] Rhein Westfal TH Aachen, Inst Pathol, D-52074 Aachen, Germany.
[Choi, Chel Hun] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Obstet & Gynecol, Seoul 135710, South Korea.
[Cho, Hanbyoul] Yonsei Univ, Gangnam Severance Hosp, Coll Med, Dept Obstet & Gynecol, Seoul 135720, South Korea.
[Chen, Qing-Rong; Khan, Javed] NCI, Oncogen Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Perry, Candice] Leidos Biomed Res Inc, Adv Technol Program, Antibody Characterizat Lab, Frederick, MD USA.
RP Hewitt, SM (reprint author), NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
EM genejock@helix.nih.gov
OI Hewitt, Stephen/0000-0001-8283-1788; Chung,
Joon-Yong/0000-0001-5041-5982
FU National Institutes of Health National Cancer Institute, Center for
Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health National Cancer Institute, Center for
Cancer Research.
NR 46
TC 1
Z9 1
U1 1
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1746-1596
J9 DIAGN PATHOL
JI Diagn. Pathol.
PD MAY 29
PY 2015
VL 10
AR 53
DI 10.1186/s13000-015-0290-4
PG 10
WC Pathology
SC Pathology
GA CJ0OQ
UT WOS:000355176500002
PM 26022333
ER
PT J
AU Wright, FA
Lu, JP
Sliter, DA
Dupre, N
Rouleau, GA
Wojcikiewicz, RJH
AF Wright, Forrest A.
Lu, Justine P.
Sliter, Danielle A.
Dupre, Nicolas
Rouleau, Guy A.
Wojcikiewicz, Richard J. H.
TI A Point Mutation in the Ubiquitin Ligase RNF170 That Causes Autosomal
Dominant Sensory Ataxia Destabilizes the Protein and Impairs Inositol
1,4,5-Trisphosphate Receptor-mediated Ca2+ Signaling
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID RETICULUM-ASSOCIATED DEGRADATION; ER-ASSOCIATED DEGRADATION;
SPINOCEREBELLAR ATAXIAS; RELEASE CHANNELS; SYSTEM; ERLIN2; PROTEASOME;
TOPOLOGY; RESIDUES; DOMAINS
AB RNF170 is an endoplasmic reticulum membrane ubiquitin ligase that contributes to the ubiquitination of activated inositol 1,4,5-trisphosphate (IP3) receptors, and also, when point mutated (arginine to cysteine at position 199), causes autosomal dominant sensory ataxia (ADSA), a disease characterized by neurodegeneration in the posterior columns of the spinal cord. Here we demonstrate that this point mutation inhibits RNF170 expression and signaling via IP3 receptors. Inhibited expression of mutant RNF170 was seen in cells expressing exogenous RNF170 constructs and in ADSA lymphoblasts, and appears to result from enhanced RNF170 autoubiquitination and proteasomal degradation. The basis for these effects was probed via additional point mutations, revealing that ionic interactions between charged residues in the transmembrane domains of RNF170 are required for protein stability. In ADSA lymphoblasts, platelet-activating factor-induced Ca2+ mobilization was significantly impaired, whereas neither Ca2+ store content, IP3 receptor levels, nor IP3 production were altered, indicative of a functional defect at the IP3 receptor locus, which may be the cause of neurodegeneration. CRISPR/Cas9-mediated genetic deletion of RNF170 showed that RNF170 mediates the addition of all of the ubiquitin conjugates known to become attached to activated IP3 receptors (monoubiquitin and Lys(48)-and Lys(63)-linked ubiquitin chains), and that wild-type and mutant RNF170 have apparently identical ubiquitin ligase activities toward IP3 receptors. Thus, the Ca2+ mobilization defect seen in ADSA lymphoblasts is apparently not due to aberrant IP3 receptor ubiquitination. Rather, the defect likely reflects abnormal ubiquitination of other substrates, or adaptation to the chronic reduction in RNF170 levels.
C1 [Wright, Forrest A.; Lu, Justine P.; Wojcikiewicz, Richard J. H.] SUNY Upstate Med Univ, Dept Pharmacol, Syracuse, NY 13210 USA.
[Sliter, Danielle A.] NINDS, NIH, Bethesda, MD 20892 USA.
[Dupre, Nicolas] Univ Laval, CHU Quebec, Neuromuscular & Neurogenet Dis Clin, Quebec City, PQ G1J 1Z4, Canada.
[Rouleau, Guy A.] McGill Univ, Montreal Neurol Inst & Hosp, Montreal, PQ H3A 2B4, Canada.
[Rouleau, Guy A.] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada.
RP Wojcikiewicz, RJH (reprint author), 750 E Adams St, Syracuse, NY 13210 USA.
EM wojcikir@upstate.edu
RI Regan, Clinton/E-6250-2012
FU National Institutes of Health [DK049194]; National Ataxia Foundation
FX This work was supported, in whole or in part, by National Institutes of
Health Grant DK049194 and the National Ataxia Foundation.
NR 47
TC 4
Z9 4
U1 0
U2 1
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 MAY 29
PY 2015
VL 290
IS 22
BP 13948
EP 13957
DI 10.1074/jbc.M115.655043
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CJ2KK
UT WOS:000355313000026
PM 25882839
ER
PT J
AU Stolzenberg, S
Quick, M
Zhao, CF
Gotfryd, K
Khelashvili, G
Gether, U
Loland, CJ
Javitch, JA
Noskov, S
Weinstein, H
Shi, L
AF Stolzenberg, Sebastian
Quick, Matthias
Zhao, Chunfeng
Gotfryd, Kamil
Khelashvili, George
Gether, Ulrik
Loland, Claus J.
Javitch, Jonathan A.
Noskov, Sergei
Weinstein, Harel
Shi, Lei
TI Mechanism of the Association between Na+ Binding and Conformations at
the Intracellular Gate in Neurotransmitter: Sodium Symporters
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DOPAMINE TRANSPORTER; MOLECULAR-DYNAMICS; BACTERIAL HOMOLOG; ION
SELECTIVITY; OCCLUDED STATE; OUTWARD-OPEN; LEUT; SUBSTRATE; PROTEIN;
SITE
AB Neurotransmitter: sodium symporters (NSSs) terminate neurotransmission by Na+-dependent reuptake of released neurotransmitters. Previous studies suggested that Na+-binding reconfigures dynamically coupled structural elements in an allosteric interaction network (AIN) responsible for function-related conformational changes, but the intramolecular pathway of this mechanism has remained uncharted. We describe a new approach for the modeling and analysis of intramolecular dynamics in the bacterial NSS homolog LeuT. From microsecond-scale molecular dynamics simulations and cognate experimental verifications in both LeuT and human dopamine transporter (hDAT), we apply the novel method to identify the composition and the dynamic properties of their conserved AIN. In LeuT, two different perturbations disrupting Na+ binding and transport (i.e. replacing Na+ with Li+ or the Y268A mutation at the intracellular gate) affect the AIN in strikingly similar ways. In contrast, other mutations that affect the intracellular gate (i.e. R5A and D369A) do not significantly impair Na+ cooperativity and transport. Our analysis shows these perturbations to have much lesser effects on the AIN, underscoring the sensitivity of this novel method to the mechanistic nature of the perturbation. Notably, this set of observations holds as well for hDAT, where the aligned Y335A, R60A, and D436A mutations also produce different impacts on Na+ dependence. Thus, the detailed AIN generated from our method is shown to connect Na+ binding with global conformational changes that are critical for the transport mechanism. That the AIN between the Na+ binding sites and the intracellular gate in bacterial LeuT resembles that in eukaryotic hDAT highlights the conservation of allosteric pathways underlying NSS function.
C1 [Stolzenberg, Sebastian; Khelashvili, George; Weinstein, Harel; Shi, Lei] Cornell Univ, Dept Physiol & Biophys, New York, NY 10065 USA.
[Weinstein, Harel; Shi, Lei] Cornell Univ, Weill Med Coll, Inst Computat Biomed, New York, NY 10065 USA.
[Stolzenberg, Sebastian] Cornell Univ, Dept Phys, Ithaca, NY 14850 USA.
[Quick, Matthias; Javitch, Jonathan A.] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
[Javitch, Jonathan A.] Columbia Univ Coll Phys & Surg, Dept Pharmacol, New York, NY 10032 USA.
[Quick, Matthias; Javitch, Jonathan A.] New York State Psychiat Inst & Hosp, Div Mol Therapeut, New York, NY 10032 USA.
[Zhao, Chunfeng; Noskov, Sergei] Univ Calgary, Ctr Mol Simulat, Calgary, AB T2N 1N4, Canada.
[Zhao, Chunfeng; Noskov, Sergei] Univ Calgary, Dept Biol Sci, Calgary, AB T2N 1N4, Canada.
[Gotfryd, Kamil; Gether, Ulrik; Loland, Claus J.] Univ Copenhagen, Dept Neurosci & Pharmacol, Copenhagen, Denmark.
[Shi, Lei] NIDA, Computat Chem & Mol Biophys Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Weinstein, H (reprint author), Weill Cornell Med Coll, 1300 York Ave,Box 75, New York, NY 10065 USA.
EM haw2002@med.cornell.edu; les2007@med.cornell.edu
OI Gether, Ulrik/0000-0002-0020-3807; Loland, Claus/0000-0002-1773-1446
FU United States Department of Energy Office of Science User Facility
[DE-AC05-00OR22725]
FX We thank MiEstrella Miller-Cruz and Trang Nguyen for the preparation of
bacterial membrane vesicles and the purification of LeuT variants and
Lone Rosenquist for technical assistance in the hDAT experiments.
Computations were performed on Ranger at the Texas Advanced Computing
Center (TG-MCB090022); the resources of the Oak Ridge Leadership
Computing Facility, which is a United States Department of Energy Office
of Science User Facility supported under Contract DE-AC05-00OR22725; the
West-Grid/Compute Canada facilities; and the local Tielemann, Noskov,
and Kusalik cluster supported by the Canadian Foundation for Innovation.
NR 42
TC 16
Z9 16
U1 0
U2 10
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 MAY 29
PY 2015
VL 290
IS 22
BP 13992
EP 14003
DI 10.1074/jbc.M114.625343
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CJ2KK
UT WOS:000355313000030
PM 25869126
ER
PT J
AU Maeda, A
Ono, M
Holmbeck, K
Li, L
Kilts, TM
Kram, V
Noonan, ML
Yoshioka, Y
McNerny, EMB
Tantillo, MA
Kohn, DH
Lyons, KM
Robey, PG
Young, MF
AF Maeda, Azusa
Ono, Mitsuaki
Holmbeck, Kenn
Li, Li
Kilts, Tina M.
Kram, Vardit
Noonan, Megan L.
Yoshioka, Yuya
McNerny, Erin M. B.
Tantillo, Margaret A.
Kohn, David H.
Lyons, Karen M.
Robey, Pamela G.
Young, Marian F.
TI WNT1-induced Secreted Protein-1 (WISP1), a Novel Regulator of Bone
Turnover and Wnt Signaling
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TISSUE GROWTH-FACTOR; CCN FAMILY PROTEINS; OSTEOBLAST DIFFERENTIATION;
SKELETAL DEVELOPMENT; CAUSES OSTEOPENIA; MICE; OSTEOGENESIS; EXPRESSION;
PATHWAYS; GENES
AB WISP1/CCN4 (hereafter referred to as WISP1), a member of the CCN family, is found in mineralized tissues and is produced by osteoblasts and their precursors. In this study, Wisp1-deficient (Wisp1(-/-)) mice were generated. Using dual-energy x-ray absorptiometry, we showed that by 3 months, the total bone mineral density of Wisp1(-/-) mice was significantly lower than that of WT mice. Further investigation by micro-computed tomography showed that female Wisp1(-/-) mice had decreased trabecular bone volume/total volume and that both male and female Wisp1(-/-) mice had decreased cortical bone thickness accompanied by diminished biomechanical strength. The molecular basis for decreased bone mass in Wisp1(-/-) mice arises from reduced bone formation likely caused by osteogenic progenitors that differentiate poorly compared with WT cells. Osteoclast precursors from Wisp1(-/-) mice developed more tartrate-resistant acid phosphatase-positive cells in vitro and in transplants, suggesting that WISP1 is also a negative regulator of osteoclast differentiation. When bone turnover (formation and resorption) was induced by ovariectomy, Wisp1(-/-) mice had lower bone mineral density compared WT mice, confirming the potential for multiple roles for WISP1 in controlling bone homeostasis. Wisp1(-/-) bone marrow stromal cells had reduced expression of beta-catenin and its target genes, potentially caused by WISP1 inhibition of SOST binding to LRP6. Taken together, our data suggest that the decreased bone mass found in Wisp1(-/-) mice could potentially be caused by an insufficiency in the osteodifferentiation capacity of bone marrow stromal cells arising from diminished Wnt signaling, ultimately leading to altered bone turnover and weaker biomechanically compromised bones.
C1 [Maeda, Azusa; Ono, Mitsuaki; Holmbeck, Kenn; Li, Li; Kilts, Tina M.; Kram, Vardit; Noonan, Megan L.; Yoshioka, Yuya; Robey, Pamela G.; Young, Marian F.] NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
[McNerny, Erin M. B.; Tantillo, Margaret A.; Kohn, David H.] Univ Michigan, Biol & Mat Sci, Ann Arbor, MI 48109 USA.
[McNerny, Erin M. B.; Tantillo, Margaret A.; Kohn, David H.] Univ Michigan, Div Prosthodont, Ann Arbor, MI 48109 USA.
[Lyons, Karen M.] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Orthoped Hosp, Los Angeles, CA 90095 USA.
[Lyons, Karen M.] Univ Calif Los Angeles, Orthoped Hosp, Dept Orthoped Surg, Los Angeles, CA 90095 USA.
[Maeda, Azusa; Ono, Mitsuaki; Yoshioka, Yuya] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Oral Rehabil & Regenerat Med, Okayama, Okayama 7008558, Japan.
RP Young, MF (reprint author), NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bldg 30,Rm 225, Bethesda, MD 20892 USA.
EM myoung@dir.nidcr.nih.gov
RI Robey, Pamela/H-1429-2011
OI Robey, Pamela/0000-0002-5316-5576
FU National Institutes of Health from NIDCR [1 Z01 DE000379-21]; NIAMS [R01
AR056657, AR052686]; NIDCR [T32 DE007057]; Japan Society for the
Promotion of Science
FX This work was supported, in whole or in part, by National Institutes of
Health Intramural Research Program Grant 1 Z01 DE000379-21 from NIDCR
(to M. O., K. H., L. L., T. M. K., V. K., M. L. N., P. G. R., and M. F.
Y.), Award R01 AR056657 from NIAMS and Award T32 DE007057 from NIDCR (to
E. M., B. M., M. A. T., and D. H. K.), and Award AR052686 from NIAMS (to
K. M. L.). This work was also supported by a fellowship from the Japan
Society for the Promotion of Science (to A. M.).
NR 27
TC 8
Z9 8
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 MAY 29
PY 2015
VL 290
IS 22
BP 14004
EP 14018
DI 10.1074/jbc.M114.628818
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CJ2KK
UT WOS:000355313000031
PM 25864198
ER
PT J
AU Huang, SYN
Ghosh, S
Pommier, Y
AF Huang, Shar-yin Naomi
Ghosh, Sanchari
Pommier, Yves
TI Topoisomerase I Alone Is Sufficient to Produce Short DNA Deletions and
Can Also Reverse Nicks at Ribonucleotide Sites
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID VACCINIA TOPOISOMERASE; GENOME INTEGRITY; EXCISION-REPAIR;
LEADING-STRAND; DUPLEX DNA; COMPLEXES; CLEAVAGE; MECHANISMS; COVALENT;
YEAST
AB Ribonucleotide monophosphates (rNMPs) are among the most frequent form of DNA aberration, as high ratios of ribonucleotide triphosphate: deoxyribonucleotide triphosphate pools result in approximately two misincorporated rNMPs/kb of DNA. The main pathway for the removal of rNMPs is by RNase H2. However, in a RNase H2 knock-out yeast strain, a topoisomerase I (Top1)-dependent mutator effect develops with accumulation of short deletions within tandem repeats. Proposed models for these deletions implicated processing of Top1-generated nicks at rNMP sites and/or sequential Top1 binding, but experimental support has been lacking thus far. Here, we investigated the biochemical mechanism of the Top1-induced short deletions at the rNMP sites by generating nicked DNA substrates bearing 2',3'-cyclic phosphates at the nick sites, mimicking the Top1-induced nicks. We demonstrate that a second Top1 cleavage complex adjacent to the nick and subsequent faulty Top1 religation led to the short deletions. Moreover, when acting on the nicked DNA substrates containing 2',3'-cyclic phosphates, Top1 generated not only the short deletion, but also a full-length religated DNA product. Acatalytically inactive Top1 mutant (Top1-Y723F) also induced the full-length products, indicating that Top1 binding independent of its enzymatic activity promotes the sealing of DNA backbones via nucleophilic attacks by the 5'-hydroxyl on the 2',3'-cyclic phosphate. The resealed DNA would allow renewed attempt for repair by the error-free RNase H2-dependent pathway in vivo. Our results provide direct evidence for the generation of short deletions by sequential Top1 cleavage events and for the promotion of nick religation at rNMP sites by Top1.
C1 [Pommier, Yves] NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Pommier, Y (reprint author), NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
EM pommier@nih.gov
FU National Institutes of Health from the Center for Cancer Research, NCI
[Z01 BC006161]
FX This work was supported, in whole or in part, by National Institutes of
Health Intramural Program Grant Z01 BC006161 from the Center for Cancer
Research, NCI.
NR 50
TC 11
Z9 11
U1 0
U2 1
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 MAY 29
PY 2015
VL 290
IS 22
BP 14068
EP 14076
DI 10.1074/jbc.M115.653345
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CJ2KK
UT WOS:000355313000036
PM 25887397
ER
PT J
AU Ueda, T
Nagamachi, A
Takubo, K
Yamasaki, N
Matsui, H
Kanai, A
Nakata, Y
Ikeda, K
Konuma, T
Oda, H
Wolff, L
Honda, Z
Wu, XD
Helin, K
Iwama, A
Suda, T
Inaba, T
Honda, H
AF Ueda, Takeshi
Nagamachi, Akiko
Takubo, Keiyo
Yamasaki, Norimasa
Matsui, Hirotaka
Kanai, Akinori
Nakata, Yuichiro
Ikeda, Kenichiro
Konuma, Takaaki
Oda, Hideaki
Wolff, Linda
Honda, Zen-ichiro
Wu, Xudong
Helin, Kristian
Iwama, Atsushi
Suda, Toshio
Inaba, Toshiya
Honda, Hiroaki
TI Fbxl10 overexpression in murine hematopoietic stem cells induces
leukemia involving metabolic activation and upregulation of Nsg2
SO BLOOD
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; OXIDATIVE-PHOSPHORYLATION; EMBRYONIC
FIBROBLASTS; CANCER METABOLISM; EXPRESSION; STRESS; FAMILY;
PROLIFERATION; MALIGNANCIES; MUTATIONS
AB We previously reported that deficiency for Samd9L, which was cloned as a candidate gene for -7/7q- syndrome, accelerated leukemia cooperatively with enhanced expression of a histone demethylase: F-box and leucine-rich repeat protein 10 (Fbxl10, also known as Jhdm1b, Kdm2b, and Ndy1). To further investigate the role of Fbxl10 in leukemogenesis, we generated transgenic (Tg) mice that overexpress Fbxl10 in hematopoietic stem cells (HSCs). Interestingly, Fbxl10 Tg mice developed myeloid or B-lymphoid leukemia with complete penetrance. HSCs from the Tg mice exhibited an accelerated G0/G1-to-S transition with a normal G0 to G1 entry, resulting in pleiotropic progenitor cell expansion. Fbxl10Tg HSCs displayed enhanced expression of neuron-specific gene family member 2 (Nsg2), and forced expression of Nsg2 in primary bone marrow cells resulted in expansion of immature cells. In addition, the genes involved in mitochondrial oxidative phosphorylation were markedly enriched in Fbxl10 Tg HSCs, coupled with increased cellular adenosine 59-triphosphate levels. Moreover, chromatin immunoprecipitation followed by sequencing analysis demonstrated that Fbxl10 directly binds to the regulatory regions of Nsg2 and oxidative phosphorylation genes. These findings define Fbxl10 as a bona fide oncogene, whose deregulated expression contributes to the development of leukemia involving metabolic proliferative advantage and Nsg2-mediated impaired differentiation.
C1 [Ueda, Takeshi; Yamasaki, Norimasa; Nakata, Yuichiro; Ikeda, Kenichiro; Honda, Hiroaki] Hiroshima Univ, Dept Dis Model, Res Inst Radiat Biol & Med, Hiroshima 7348553, Japan.
[Nagamachi, Akiko; Matsui, Hirotaka; Kanai, Akinori; Inaba, Toshiya] Hiroshima Univ, Dept Mol Oncol, Res Inst Radiat Biol & Med, Hiroshima 7348553, Japan.
[Takubo, Keiyo; Suda, Toshio] Keio Univ, Sch Med, Dept Cell Differentiat, Sakaguchi Lab Dev Biol, Tokyo, Japan.
[Konuma, Takaaki; Iwama, Atsushi] Chiba Univ, Dept Cellular & Mol Med, Grad Sch Med, Chiba, Japan.
[Oda, Hideaki] Tokyo Womens Med Univ, Dept Pathol, Tokyo, Japan.
[Wolff, Linda] NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Honda, Zen-ichiro] Ochanomizu Univ, Hlth Care Ctr, Tokyo 112, Japan.
[Honda, Zen-ichiro] Ochanomizu Univ, Grad Sch Humanities & Sci, Inst Environm Sci Human Life, Tokyo 112, Japan.
[Wu, Xudong; Helin, Kristian] Univ Copenhagen, BRIC, Copenhagen, Denmark.
[Wu, Xudong; Helin, Kristian] Univ Copenhagen, Ctr Epigenet, Copenhagen, Denmark.
RP Ueda, T (reprint author), Hiroshima Univ, Dept Dis Model, Res Inst Radiat Biol & Med, Minami Ku, 1-2-3 Kasumi, Hiroshima 7348553, Japan.
EM takeshiueda@hiroshima-u.ac.jp; hhonda@hiroshima-u.ac.jp
RI Suda, Toshio/H-6761-2013;
OI Suda, Toshio/0000-0001-7540-1771; Helin, Kristian/0000-0003-1975-6097
FU Ministry of Education, Science and Culture of Japan
FX This work was in part supported by a Grant in-Aid for Scientific
Research from the Ministry of Education, Science and Culture of Japan.
NR 44
TC 7
Z9 7
U1 2
U2 5
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAY 28
PY 2015
VL 125
IS 22
BP 3437
EP 3446
DI 10.1182/blood-2014-03-562694
PG 10
WC Hematology
SC Hematology
GA CK1PR
UT WOS:000355979800015
PM 25872778
ER
PT J
AU Lynn, RC
Poussin, M
Kalota, A
Feng, Y
Low, PS
Dimitrov, DS
Powell, DJ
AF Lynn, Rachel C.
Poussin, Mathilde
Kalota, Anna
Feng, Yang
Low, Philip S.
Dimitrov, Dimiter S.
Powell, Daniel J., Jr.
TI Targeting of folate receptor beta on acute myeloid leukemia blasts with
chimeric antigen receptor-expressing T cells
SO BLOOD
LA English
DT Article
ID TRANS-RETINOIC ACID; IN-VIVO PERSISTENCE; OVARIAN-CANCER;
ANTITUMOR-ACTIVITY; VITAMIN-A; RHEUMATOID-ARTHRITIS; CLINICAL-TRIAL;
PHASE-I; INDUCTION; TUMOR
AB T cells expressing a chimeric antigen receptor (CAR) can produce dramatic results in lymphocytic leukemia patients; however, therapeutic strategies for myeloid leukemia remain limited. Folate receptor beta (FR beta) is a myeloid-lineage antigen expressed on 70% of acute myeloid leukemia (AML) patient samples. Here, we describe the development and evaluation of the first CARs specific for human FR beta (m909) in vitro and in vivo. m909 CAR T cells exhibited selective activation and lytic function against engineered C30-FR beta as well as endogenous FR beta(+) AML cell lines in vitro. In mouse models of human AML, m909 CAR T cells mediated the regression of engrafted FR beta(+) THP1 AML in vivo. In addition, we demonstrated that treatment of AML with all-trans retinoic acid (ATRA) enhanced FR beta expression, resulting in improved immune recognition by m909 CAR T cells. Because many cell surface markers are shared between AML blasts and healthy hematopoietic stem and progenitor cells (HSCs), we evaluated FR beta expression and recognition of HSCs by CAR T cells. m909 CAR T cells were not toxic against healthy human CD34(+) HSCs in vitro. Our results indicate that FR beta is a promising target for CAR T-cell therapy of AML, which may be augmented by combination with ATRA.
C1 [Lynn, Rachel C.; Poussin, Mathilde; Powell, Daniel J., Jr.] Univ Penn, Perelman Sch Med, Ovarian Canc Res Ctr, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA.
[Kalota, Anna] Univ Penn, Div Hematol Oncol, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Feng, Yang; Dimitrov, Dimiter S.] NCI, Prot Interact Sect, Expt Immunol Lab, Canc & Inflammat Program,Ctr Canc Res, Frederick, MD 21701 USA.
[Low, Philip S.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
[Powell, Daniel J., Jr.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
RP Powell, DJ (reprint author), Univ Penn, Perelman Sch Med, Smilow Ctr, 3400 Civ Ctr Blvd,Bldg 421,Room 08-103, Philadelphia, PA 19104 USA.
EM poda@mail.med.upenn.edu
FU National Institutes of Health National Cancer Institute (NCI)
[RO1-CA168900]; National Institute of Allergy and Infectious Diseases
[T32-AI070099]; Joint Fox Chase Cancer Center and University of
Pennsylvania Ovarian Cancer Specialized Program of Research Excellence
NCI [P50 CA083638]; Intramural Research Program at the NCI Center for
Cancer Research; NCI [CA016520]
FX This work was supported by the National Institutes of Health National
Cancer Institute (NCI) grant RO1-CA168900 (D.J.P.), National Institute
of Allergy and Infectious Diseases grant T32-AI070099 (R.C.L.), Joint
Fox Chase Cancer Center and University of Pennsylvania Ovarian Cancer
Specialized Program of Research Excellence NCI grant P50 CA083638
(D.J.P.), the Intramural Research Program at the NCI Center for Cancer
Research (D.S.D.), and NCI grant CA016520, which supported imaging at
the University of Pennsylvania Small Animal Imaging Facility
Optical/Bioluminescence Core.
NR 59
TC 18
Z9 19
U1 1
U2 11
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAY 28
PY 2015
VL 125
IS 22
BP 3466
EP 3476
DI 10.1182/blood-2014-11-612721
PG 11
WC Hematology
SC Hematology
GA CK1PR
UT WOS:000355979800018
PM 25887778
ER
PT J
AU Palardy, G
Chitnis, AB
AF Palardy, Gregory
Chitnis, Ajay B.
TI Identification of the Mind Bomb1 Interaction Domain in Zebrafish DeltaD
SO PLOS ONE
LA English
DT Article
ID RECEPTOR INTERNALIZATION; JUXTAMEMBRANE DOMAIN; PRIMARY NEUROGENESIS;
UBIQUITIN LIGASE; NOTCH; ENDOCYTOSIS; ACTIVATION; DROSOPHILA;
INHIBITION; HOMOLOG
AB Ubiquitylation promotes endocytosis of the Notch ligands like Delta and Serrate and is essential for them to effectively activate Notch in a neighboring cell. The RING E3 ligase Mind bomb1 (Mib1) ubiquitylates DeltaD to facilitate Notch signaling in zebrafish. We have identified a domain in the intracellular part of the zebrafish Notch ligand DeltaD that is essential for effective interactions with Mib1. We show that elimination of the Mind bomb1 Interaction Domain (MID) or mutation of specific conserved motifs in this domain prevents effective Mib1-mediated ubiquitylation and internalization of DeltaD. Lateral inhibition mediated by Notch signaling regulates early neurogenesis in zebrafish. In this context, Notch activation suppresses neurogenesis, while loss of Notch-mediated lateral inhibition results in a neurogenic phenotype, where too many cells are allowed to become neurons. While Mib1-mediated endocytosis of DeltaD is essential for effective activation of Notch in a neighboring cell (in trans) it is not required for DeltaD to inhibit function of Notch receptors in the same cell (in cis). As a result, forms of DeltaD that have the MID can activate Notch in trans and suppress early neurogenesis when mRNA encoding it is ectopically expressed in zebrafish embryos. On the other hand, when the MID is eliminated/mutated in DeltaD, its ability to activate Notch in trans fails but ability to inhibit in cis is retained. As a result, ectopic expression of DeltaD lacking an effective MID results in a failure of Notch-mediated lateral inhibition and a neurogenic phenotype.
C1 [Palardy, Gregory; Chitnis, Ajay B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
RP Chitnis, AB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
EM chitnisa@mail.nih.gov
FU Eunice Kennedy Shriver National Insitute of Child Health and Human
Development [1ZIAHD001012]
FX This research was funded by the intramural program of the Eunice Kennedy
Shriver National Insitute of Child Health and Human Development
1ZIAHD001012.
NR 25
TC 1
Z9 1
U1 0
U2 1
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 MAY 28
PY 2015
VL 10
IS 5
AR e0127864
DI 10.1371/journal.pone.0127864
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CJ0SC
UT WOS:000355187300060
PM 26020642
ER
PT J
AU Prasad, R
Dyrkheeva, N
Williams, J
Wilson, SH
AF Prasad, Rajendra
Dyrkheeva, Nadezhda
Williams, Jason
Wilson, Samuel H.
TI Mammalian Base Excision Repair: Functional Partnership between PARP-1
and APE1 in AP-Site Repair
SO PLOS ONE
LA English
DT Article
ID DNA-POLYMERASE-BETA; STRAND BREAK REPAIR; APURINIC APYRIMIDINIC SITES;
CELL NUCLEAR ANTIGEN; POLY(ADP-RIBOSE) POLYMERASE-1;
APURINIC/APYRIMIDINIC ENDONUCLEASE-1; MOUSE FIBROBLASTS; PROTEIN XRCC1;
LIGASE-III; IN-VITRO
AB The apurinic/apyrimidinic-(AP-) site in genomic DNA arises through spontaneous base loss and base removal by DNA glycosylases and is considered an abundant DNA lesion in mammalian cells. The base excision repair (BER) pathway repairs the AP-site lesion by excising and replacing the site with a normal nucleotide via template directed gap-filling DNA synthesis. The BER pathway is mediated by a specialized group of proteins, some of which can be found in multiprotein complexes in cultured mouse fibroblasts. Using a DNA polymerase (pol) beta immunoaffinity-capture technique to isolate such a complex, we identified five tightly associated and abundant BER factors in the complex: PARP-1, XRCC1, DNA ligase III, PNKP, and Tdp1. AP endonuclease 1 (APE1), however, was not present. Nevertheless, the complex was capable of BER activity, since repair was initiated by PARP-1's AP lyase strand incision activity. Addition of purified APE1 increased the BER activity of the pol beta complex. Surprisingly, the pol beta complex stimulated the strand incision activity of APE1. Our results suggested that PARP-1 was responsible for this effect, whereas other proteins in the complex had no effect on APE1 strand incision activity. Studies of purified PARP-1 and APE1 revealed that PARP-1 was able to stimulate APE1 strand incision activity. These results illustrate roles of PARP-1 in BER including a functional partnership with APE1.
C1 [Prasad, Rajendra; Dyrkheeva, Nadezhda; Wilson, Samuel H.] NIEHS, Genome Integr & Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Williams, Jason] NIEHS, Epigenet & Stem Cell Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Wilson, SH (reprint author), NIEHS, Genome Integr & Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM wilson5@niehs.nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH),
National Institute of Environmental Health Sciences [Z01ES050158,
Z01ES050159]; Eli Lilly and Co.; United States Department of State,
United States-Russia
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health (NIH), National Institute of
Environmental Health Sciences, project numbers Z01ES050158 and
Z01ES050159. ND is supported in part by Eli Lilly and Co. and the United
States Department of State, as part of the United States-Russia
Collaboration in the Biomedical Sciences NIH Visiting Fellows Program.
NR 79
TC 4
Z9 4
U1 0
U2 13
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 MAY 28
PY 2015
VL 10
IS 5
AR e0124269
DI 10.1371/journal.pone.0124269
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CJ0SC
UT WOS:000355187300007
PM 26020771
ER
PT J
AU Puetz, TW
Youngstedt, SD
Herring, MP
AF Puetz, Timothy W.
Youngstedt, Shawn D.
Herring, Matthew P.
TI Effects of Pharmacotherapy on Combat-Related PTSD, Anxiety, and
Depression: A Systematic Review and Meta-Regression Analysis
SO PLOS ONE
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; OF-VETERANS-AFFAIRS; SYMPTOMS;
METAANALYSIS; EXERCISE; QUALITY; TRIALS; COMORBIDITY; PREVALENCE;
GUIDELINES
AB The efficacy of pharmacotherapy for PTSD, anxiety, and depression among combat veterans is not well-established.
Objectives
To estimate the effect of pharmacotherapy on PTSD, anxiety, and depression among combat veterans; to determine whether the effects varied according to patient and intervention characteristics; and to examine differential effects of pharmacotherapy on outcomes.
Materials and Methods
Google Scholar, PILOTS, PsycINFO, PubMed, and Web of Science databases were searched through November 2014. Searches resulted in eighteen double-blind, placebo controlled trials of 773 combat veterans diagnosed with PTSD and included only validated pre- and post-intervention PTSD and anxiety or depression measures. Authors extracted data on effect sizes, moderators, and study quality. Hedges' d effect sizes were computed and random effects models estimated sampling error and population variance. The Johnson-Neyman procedure identified the critical points in significant interactions to define regions of significance.
Results
Pharmacotherapy significantly reduced (Delta, 95% CI) PTSD (0.38, 0.23-0.52), anxiety (0.42, 0.30-0.54), and depressive symptoms (0.52, 0.35-0.70). The effects of SSRIs and tricyclic antidepressants on PTSD were greater than other medications independent of treatment duration. The effect of SSRIs and tricyclic antidepressants were greater than other medications up to 5.2 and 13.6 weeks for anxiety and depression, respectively. The magnitude of the effect of pharmacotherapy on concurrently-measured PTSD, anxiety, and depression did not significantly differ.
Conclusions
Pharmacotherapy reduced PTSD, anxiety, and depressive symptoms in combat veterans. The effects of SSRIs and tricyclic antidepressants were greater for PTSD and occurred quicker for anxiety and depression than other medications.
C1 [Puetz, Timothy W.] NIH, Ctr Clin, Off Director, Bethesda, MD 20892 USA.
[Youngstedt, Shawn D.] Arizona State Univ, Coll Nursing & Hlth Innovat, Phoenix, AZ USA.
[Youngstedt, Shawn D.] Arizona State Univ, Sch Nutr & Hlth Promot, Phoenix, AZ USA.
[Youngstedt, Shawn D.] Phoenix VA Hlth Care Syst, Phoenix, AZ USA.
[Herring, Matthew P.] Univ Limerick, Dept Phys Educ & Sport Sci, Limerick, Ireland.
RP Herring, MP (reprint author), Univ Limerick, Dept Phys Educ & Sport Sci, Limerick, Ireland.
EM matthew.herring@ul.ie
RI Herring, Matthew/O-2265-2014
OI Herring, Matthew/0000-0002-6835-5321
FU National Institutes of Health [R01 HL095799]
FX Funding for this work was provided by the National Institutes of Health
under grant R01 HL095799. The funders had no role in the study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 45
TC 1
Z9 2
U1 3
U2 12
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 MAY 28
PY 2015
VL 10
IS 5
AR e0126529
DI 10.1371/journal.pone.0126529
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CJ0SC
UT WOS:000355187300025
PM 26020791
ER
PT J
AU Cohen, JI
AF Cohen, Jeffrey I.
TI A New Vaccine to Prevent Herpes Zoster
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID VARICELLA; RECIPIENTS; EFFICACY
C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Cohen, JI (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
NR 10
TC 6
Z9 6
U1 1
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 MAY 28
PY 2015
VL 372
IS 22
BP 2149
EP 2150
DI 10.1056/NEJMe1505050
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA CJ0EI
UT WOS:000355146800013
PM 25916342
ER
PT J
AU Lack, G
Plaut, M
Sayre, PH
AF Lack, Gideon
Plaut, Marshall
Sayre, Peter H.
TI Peanut Consumption in Infants at Risk for Peanut Allergy REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Lack, Gideon] Kings Coll London, London WC2R 2LS, England.
[Plaut, Marshall] NIAID, Bethesda, MD 20892 USA.
[Sayre, Peter H.] Immune Tolerance Network, San Francisco, CA USA.
RP Lack, G (reprint author), Kings Coll London, London WC2R 2LS, England.
EM gideon.lack@kcl.ac.uk
NR 5
TC 1
Z9 1
U1 0
U2 1
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 MAY 28
PY 2015
VL 372
IS 22
BP 2165
EP 2166
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA CJ0EI
UT WOS:000355146800021
PM 26017828
ER
PT J
AU Carter, BD
Freedman, ND
Jacobs, EJ
AF Carter, Brian D.
Freedman, Neal D.
Jacobs, Eric J.
TI Smoking and Mortality - Beyond Established Causes REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Carter, Brian D.; Jacobs, Eric J.] Amer Canc Soc, Atlanta, GA 30329 USA.
[Freedman, Neal D.] NCI, Bethesda, MD 20892 USA.
RP Carter, BD (reprint author), Amer Canc Soc, Atlanta, GA 30329 USA.
EM brian.carter@cancer.org
RI Freedman, Neal/B-9741-2015
OI Freedman, Neal/0000-0003-0074-1098
NR 2
TC 5
Z9 5
U1 0
U2 2
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 MAY 28
PY 2015
VL 372
IS 22
BP 2170
EP 2170
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA CJ0EI
UT WOS:000355146800029
PM 26017836
ER
PT J
AU Grady, C
AF Grady, Christine
TI Enduring and Emerging Challenges of Informed Consent REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Grady, C (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA.
EM cgrady@nih.gov
NR 5
TC 4
Z9 4
U1 0
U2 1
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 MAY 28
PY 2015
VL 372
IS 22
BP 2172
EP 2172
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA CJ0EI
UT WOS:000355146800032
PM 26017840
ER
PT J
AU Liang, X
He, Y
Salmeron, BJ
Gu, H
Stein, EA
Yang, YH
AF Liang, Xia
He, Yong
Salmeron, Betty Jo
Gu, Hong
Stein, Elliot A.
Yang, Yihong
TI Interactions between the Salience and Default-Mode Networks Are
Disrupted in Cocaine Addiction
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE brain circuits; cocaine addiction; modularity analysis; network
interactions; resting fMRI
ID STATE FUNCTIONAL CONNECTIVITY; TORONTO-ALEXITHYMIA-SCALE; ANTERIOR
CINGULATE CORTEX; SUBSTANCE USE DISORDERS; BRAIN NETWORKS;
DRUG-ADDICTION; GLOBAL SIGNAL; HEAD MOTION; INSULA; USERS
AB Cocaine dependence is a complex neuropsychiatric disorder manifested as dysregulation of multiple behavioral, emotional, and cognitive constructs. Neuroimaging studies have begun to identify specific neurobiological circuit impairments in cocaine-dependent (CD) individuals that may underlie these symptoms. However, whether, where, and how the interactions within and between these circuits are disrupted remain largely unknown. We used resting-state fMRI and modularity network analysis to identify brain modules of a priori interest (default-mode network [DMN], salience network [SN], executive control network [ECN], medial temporal lobe [MTL], and striatum) in 47 CD and 47 matched healthy control (HC) participants and explored alterations within and between these brain modules as a function of addiction. At the module level, intermodule connectivity decreased between DMN and SN in CD. At the nodal level, several regions showed decreased connections with multiple modules in CD: the rostral anterior cingulate connection strength was reduced with SN and MTL; the posterior cingulate had reduced connections with ECN; and the bilateral insula demonstrated decreased connections with DMN. Furthermore, alexithymia, a personality trait previously associated with addiction, correlated negatively with intramodule connectivity within SN only in cocaine users. Our results indicate that cocaine addiction is associated with disrupted interactions among DMN, MTL, and SN, which have been implicated, respectively, in self-referential functions, emotion and memory, and coordinating between internal and external stimuli, providing novel and important insights into the neurobiological mechanisms of cocaine addiction.
C1 [Liang, Xia; Salmeron, Betty Jo; Gu, Hong; Stein, Elliot A.; Yang, Yihong] NIDA, Neuroimaging Res Branch, NIH, Baltimore, MD 21224 USA.
[Liang, Xia; He, Yong] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China.
[Liang, Xia; He, Yong] Beijing Normal Univ, IDG McGovern Inst Brain Res, Beijing 100875, Peoples R China.
RP Yang, YH (reprint author), NIDA, Neuroimaging Res Branch, NIH, Baltimore, MD 21224 USA.
EM yihongyang@intra.nida.nih.gov
RI Salmeron, Betty Jo/M-1793-2016
OI Salmeron, Betty Jo/0000-0003-1699-9333
FU National Institute on Drug Abuse, National Institutes of Health; Natural
Science Foundation of China [81030028, 31221003]; National Science Fund
for Distinguished Young Scholars [81225012]
FX This work was supported by the Intramural Research Program of the
National Institute on Drug Abuse, National Institutes of Health. Y.H.
was supported by Natural Science Foundation of China Grants 81030028 and
31221003 and National Science Fund for Distinguished Young Scholars
Grant 81225012.
NR 73
TC 7
Z9 7
U1 3
U2 21
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 MAY 27
PY 2015
VL 35
IS 21
BP 8081
EP 8090
DI 10.1523/JNEUROSCI.3188-14.2015
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA CL1AB
UT WOS:000356673100005
PM 26019326
ER
PT J
AU Li, X
Rubio, FJ
Zeric, T
Bossert, JM
Kambhampati, S
Cates, HM
Kennedy, PJ
Liu, QR
Cimbro, R
Hope, BT
Nestler, EJ
Shaham, Y
AF Li, Xuan
Rubio, F. Javier
Zeric, Tamara
Bossert, Jennifer M.
Kambhampati, Sarita
Cates, Hannah M.
Kennedy, Pamela J.
Liu, Qing-Rong
Cimbro, Raffaello
Hope, Bruce T.
Nestler, Eric J.
Shaham, Yavin
TI Incubation of Methamphetamine Craving Is Associated with Selective
Increases in Expression of Bdnf and Trkb, Glutamate Receptors, and
Epigenetic Enzymes in Cue-Activated Fos-Expressing Dorsal Striatal
Neurons
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE dorsal striatum; epigenetics; FACS; glutamate; methamphetamine; relapse
ID CONTEXT-INDUCED REINSTATEMENT; ANXIOGENIC DRUG YOHIMBINE; VENTRAL
TEGMENTAL AREA; COCAINE-SEEKING; NUCLEUS-ACCUMBENS; PREFRONTAL CORTEX;
DORSOLATERAL STRIATUM; NEUROTROPHIC FACTOR; MOLECULAR ALTERATIONS;
INDUCED RELAPSE
AB Cue-induced methamphetamine seeking progressively increases after withdrawal (incubation of methamphetamine craving), but the underlying mechanisms are largely unknown. We determined whether this incubation is associated with alterations in candidate genes in dorsal striatum (DS), a brain area implicated in cue-and context-induced drug relapse. We first measured mRNA expression of 24 candidate genes in whole DS extracts after short (2 d) or prolonged (1 month) withdrawal in rats following extended-access methamphetamine or saline (control condition) self-administration (9 h/d, 10 d). We found minimal changes. Next, using fluorescence-activated cell sorting, we compared gene expression in Fos-positive dorsal striatal neurons, which were activated during "incubated" cue-induced drug-seeking tests after prolonged withdrawal, with nonactivated Fos-negative neurons. We found significant increases in mRNA expression of immediate early genes (Arc, Egr1), Bdnf and its receptor (Trkb), glutamate receptor subunits (Gria1, Gria3, Grm1), and epigenetic enzymes (Hdac3, Hdac4, Hdac5, GLP, Dnmt3a, Kdm1a) in the Fos-positive neurons only. Using RNA scope to determine striatal subregion and cell-type specificity of the activated neurons, we measured colabeling of Fos with Drd1 and Drd2 in three DS subregions. Fos expression was neither subregion nor cell-type specific (52.5 and 39.2% of Fos expression colabeled with Drd1 and Drd2, respectively). Finally, we found that DS injections of SCH23390 (C17H18ClNO), a D1-family receptor antagonist known to block cue-induced Fos induction, decreased incubated cue-induced methamphetamine seeking after prolonged withdrawal. Results demonstrate a critical role of DS in incubation of methamphetamine craving and that this incubation is associated with selective gene-expression alterations in cue-activated D1- and D2-expressing DS neurons.
C1 [Li, Xuan; Rubio, F. Javier; Zeric, Tamara; Bossert, Jennifer M.; Kambhampati, Sarita; Liu, Qing-Rong; Hope, Bruce T.; Shaham, Yavin] US Dept Hlth & Human Serv, Behav Neurosci Res Branch, Intramural Res Program, NIDA,NIH, Baltimore, MD 21224 USA.
[Cates, Hannah M.; Nestler, Eric J.] Icahn Sch Med Mt Sinai, Fishberg Dept Neurosci, New York, NY 10029 USA.
[Cates, Hannah M.; Nestler, Eric J.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA.
[Kennedy, Pamela J.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA.
[Cimbro, Raffaello] Johns Hopkins Univ, Sch Med, Div Rheumatol, Baltimore, MD 21224 USA.
RP Li, X (reprint author), US Dept Hlth & Human Serv, Behav Neurosci Res Branch, Intramural Res Program, NIDA,NIH, Baltimore, MD 21224 USA.
EM anna.li@nih.gov; yavin.shaham@nih.gov
RI Hope, Bruce/A-9223-2010; Liu, Qing-Rong/A-3059-2012;
OI Hope, Bruce/0000-0001-5804-7061; Liu, Qing-Rong/0000-0001-8477-6452;
Cates, Hannah/0000-0002-9413-0847; Cimbro, Raffaello/0000-0002-6251-5160
FU NIDA [P01DA008227]; NIDA Intramural Research Program; National
Institutes of Health; Becas-Chile scholarship; Universidad de los Andes,
Santiago, Chile; National Institute of Arthritis and Musculoskeletal and
Skin Diseases of the National Institute of Health [P30AR053503]
FX This work was supported by the intramural (Y.S., B.T.H.) and extramural
(P01DA008227; E.J.N.) divisions of the NIDA, and an
intramural-extramural award from the NIDA Intramural Research Program
(Y.S., X.L., E.J.N.). F.J.R. was supported by an appointment to the NIDA
Research Participation Program sponsored by the National Institutes of
Health and administered by the Oak Ridge Institute for Science and
Education, and received additional financial support from a Becas-Chile
scholarship managed by CONICYT and the Universidad de los Andes,
Santiago, Chile. The Johns Hopkins FACS Core facility was supported by
Award P30AR053503 from the National Institute of Arthritis and
Musculoskeletal and Skin Diseases of the National Institute of Health.
NR 70
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U1 2
U2 7
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 MAY 27
PY 2015
VL 35
IS 21
BP 8232
EP 8244
DI 10.1523/JNEUROSCI.1022-15.2015
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA CL1AB
UT WOS:000356673100017
PM 26019338
ER
PT J
AU Shalaeva, DN
Dibrova, DV
Galperin, MY
Mulkidjanian, AY
AF Shalaeva, Daria N.
Dibrova, Daria V.
Galperin, Michael Y.
Mulkidjanian, Armen Y.
TI Modeling of interaction between cytochrome c and the WD domains of
Apaf-1: bifurcated salt bridges underlying apoptosome assembly
SO BIOLOGY DIRECT
LA English
DT Article
DE Apoptosis; WD40 domains; Hydrogen bond; Salt bridge; Apoptosis;
Protein-protein interactions; Caspase; Molecular dynamics simulations;
Sequence analysis; Evolution
ID ELECTRON-TRANSFER; CRYSTAL-STRUCTURE; CELL-DEATH; MITOCHONDRIAL PATHWAY;
GLOBULAR-PROTEINS; WD40-REPEAT PROTEINS; APOPTOTIC ACTIVITY; BC(1)
COMPLEX; PREDICTION; BINDING
AB Background: Binding of cytochrome c, released from the damaged mitochondria, to the apoptotic protease activating factor 1 (Apaf-1) is a key event in the apoptotic signaling cascade. The binding triggers a major domain rearrangement in Apaf-1, which leads to oligomerization of Apaf-1/cytochrome c complexes into an apoptosome. Despite the availability of crystal structures of cytochrome c and Apaf-1 and cryo-electron microscopy models of the entire apoptosome, the binding mode of cytochrome c to Apaf-1, as well as the nature of the amino acid residues of Apaf-1 involved remain obscure.
Results: We investigated the interaction between cytochrome c and Apaf-1 by combining several modeling approaches. We have applied protein-protein docking and energy minimization, evaluated the resulting models of the Apaf-1/cytochrome c complex, and carried out a further analysis by means of molecular dynamics simulations. We ended up with a single model structure where all the lysine residues of cytochrome c that are known as functionally-relevant were involved in forming salt bridges with acidic residues of Apaf-1. This model has revealed three distinctive bifurcated salt bridges, each involving a single lysine residue of cytochrome c and two neighboring acidic resides of Apaf-1. Salt bridge-forming amino acids of Apaf-1 showed a clear evolutionary pattern within Metazoa, with pairs of acidic residues of Apaf-1, involved in bifurcated salt bridges, reaching their highest numbers in the sequences of vertebrates, in which the cytochrome c-mediated mechanism of apoptosome formation seems to be typical.
Conclusions: The reported model of an Apaf-1/cytochrome c complex provides insights in the nature of protein-protein interactions which are hard to observe in crystallographic or electron microscopy studies. Bifurcated salt bridges can be expected to be stronger than simple salt bridges, and their formation might promote the conformational change of Apaf-1, leading to the formation of an apoptosome. Combination of structural and sequence analyses provides hints on the evolution of the cytochrome c-mediated apoptosis.
C1 [Shalaeva, Daria N.; Mulkidjanian, Armen Y.] Univ Osnabruck, Sch Phys, D-49069 Osnabruck, Germany.
[Shalaeva, Daria N.; Mulkidjanian, Armen Y.] Sch Bioengn & Bioinformat, Moscow 117999, Russia.
[Dibrova, Daria V.; Mulkidjanian, Armen Y.] Moscow MV Lomonosov State Univ, AN Belozersky Inst Physico Chem Biol, Moscow 117999, Russia.
[Galperin, Michael Y.] Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Mulkidjanian, AY (reprint author), Univ Osnabruck, Sch Phys, D-49069 Osnabruck, Germany.
EM amulkid@uos.de
RI Mulkidjanian, Armen/J-8086-2013
OI Mulkidjanian, Armen/0000-0001-5844-3064
FU Osnabrueck University, Germany; German Academic Exchange Service;
Russian Science Foundation [14-14-00592, 14-50-00029]; Development
Program of the Lomonosov Moscow State University, Russia; Intramural
Research Program of the National Institutes of Health at the National
Library of Medicine, USA
FX The authors are grateful to Prof. V.P. Skulachev for drawing their
attention to the potential key role of the residues of Apaf-1 in the
formation of an apoptosome. The research of the authors was supported in
part by the Osnabrueck University, Germany and a fellowship from the
German Academic Exchange Service (DNS), grants from the Russian Science
Foundation (14-14-00592, AYM, molecular modeling of apoptosome
formation, and 14-50-00029, DVD, AYM, phylogenomic analysis of
cytochrome c), by the Development Program of the Lomonosov Moscow State
University, Russia (access to the supercomputer facility), and by the
Intramural Research Program of the National Institutes of Health at the
National Library of Medicine, USA (MYG).
NR 96
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U1 1
U2 14
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6150
J9 BIOL DIRECT
JI Biol. Direct
PD MAY 27
PY 2015
VL 10
AR 29
DI 10.1186/s13062-015-0059-4
PG 28
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA CJ0JH
UT WOS:000355161100001
PM 26014357
ER
PT J
AU Thomas, A
Chen, YB
Yu, TH
Jakopovic, M
Giaccone, G
AF Thomas, Anish
Chen, Yuanbin
Yu, Tinghui
Jakopovic, Marko
Giaccone, Giuseppe
TI Trends and characteristics of young non-small cell lung cancer patients
in the United States
SO FRONTIERS IN ONCOLOGY
LA English
DT Article
DE non-small cell lung cancer; SEER; young; population-based studies;
disparities
ID AGE; SMOKING; EPIDEMIOLOGY; SURVEILLANCE; CARCINOMA; DIAGNOSIS;
OUTCOMES; ADULTS; TUMORS; RATES
AB Background: Although the median age at diagnosis of non-small cell lung cancer (NSCLC) is 70 years, a subset of patients with NSCLC present at a younger age (<40 years). Little is known about the time-trends in incidence of NSCLC in the young, their characteristics and outcomes.
Methods: The surveillance, epidemiology, and end results database was used to extract NSCLC cases from 1978 to 2010. Yearly incidence rates in various age groups, race, site of disease, histology, treatment patterns, and outcomes were assessed. We modeled Kaplan Meyer survival curves stratified by age of presentation.
Results: Young patients represented 0.6% of incident NSCLC from 1978 to 2010. The incidence of young NSCLC declined significantly during this time-period. Young NSCLCs had a higher proportion of women (51%), Asians or Pacific Islanders (14%), adenocarcinoma histology (59%) and were more likely to present with distant metastases (68%). The young had better all cause and lung cancer-specific survival than the older patients (median survival for localized, regional, and distant disease: not reached, 28, 9 vs. 46, 17, 5 months; p <0.001 for all groups). Male sex, non-adenocarcinoma histology, and main bronchial primary were independent negative prognostic factors among the young. In contrast to the overall population, black race was a poor prognostic factor among the young.
Conclusion: The incidence of NSCLC in the young decreased from 1978 to 2010. The clinical characteristics of NSCLC in the young, including demographic distribution, treatment, and outcomes are different from those observed in the older patients.
C1 [Thomas, Anish; Chen, Yuanbin] NCI, Natl Inst Hlth, Med Oncol Branch, Bethesda, MD 20892 USA.
[Yu, Tinghui] Fed Drug Adm, Off Surveillance & Biometr Devices & Radiol, Silver Spring, MD USA.
[Jakopovic, Marko] Univ Zagreb, Univ Hosp Ctr Zagreb, Sch Med, Dept Resp Dis, Zagreb 41000, Croatia.
[Giaccone, Giuseppe] Georgetown Univ, Lombardi Canc Ctr, Washington, DC 20057 USA.
RP Giaccone, G (reprint author), Georgetown Univ, Lombardi Canc Ctr, Res Bldg RoomW503,3970Reservoir Rd NW, Washington, DC 20057 USA.
EM gg496@georgetown.edu
RI Giaccone, Giuseppe/E-8297-2017;
OI Giaccone, Giuseppe/0000-0002-5023-7562; Thomas,
Anish/0000-0003-3293-3115
NR 37
TC 9
Z9 10
U1 1
U2 2
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 2234-943X
J9 FRONT ONCOL
JI Front. Oncol.
PD MAY 26
PY 2015
VL 5
AR 113
DI 10.3389/fonc.2015.00113
PG 7
WC Oncology
SC Oncology
GA CO4OE
UT WOS:000359139500001
PM 26075181
ER
PT J
AU Cheng, Y
Lu, F
Lee, SK
Kong, DH
Ha, KS
Wang, B
Sattabongkot, J
Tsuboi, T
Han, ET
AF Cheng, Yang
Lu, Feng
Lee, Seong-Kyun
Kong, Deok-Hoon
Ha, Kwon-Soo
Wang, Bo
Sattabongkot, Jetsumon
Tsuboi, Takafumi
Han, Eun-Taek
TI Characterization of Plasmodium vivax Early Transcribed Membrane Protein
11.2 and Exported Protein 1
SO PLOS ONE
LA English
DT Article
ID HOST-CELL CYTOPLASM; MALARIA PARASITE; ERYTHROCYTE-MEMBRANE; VACUOLAR
MEMBRANE; FALCIPARUM; INVASION; FAMILY; INFECTION; ANTIGEN; RHOPTRY
AB In Plasmodium, the membrane of intracellular parasites is initially formed during invasion as an invagination of the red blood cell surface, which forms a barrier between the parasite and infected red blood cells in asexual blood stage parasites. The membrane proteins of intracellular parasites of Plasmodium species have been identified such as early-transcribed membrane proteins (ETRAMPs) and exported proteins (EXPs). However, there is little or no information regarding the intracellular parasite membrane in Plasmodium vivax. In the present study, recombinant PvETRAMP11.2 (PVX_003565) and PvEXP1 (PVX_091700) were expressed and evaluated antigenicity tests using sera from P. vivax-infected patients. A large proportion of infected individuals presented with IgG antibody responses against PvETRAMP11.2 (76.8%) and PvEXP1 (69.6%). Both of the recombinant proteins elicited high antibody titers capable of recognizing parasites of vivax malaria patients. PvETRAMP11.2 partially co-localized with PvEXP1 on the intracellular membranes of immature schizont. Moreover, they were also detected at the apical organelles of newly formed merozoites of mature schizont. We first proposed that these proteins might be synthesized in the preceding schizont stage, localized on the parasite membranes and apical organelles of infected erythrocytes, and induced high IgG antibody responses in patients.
C1 [Cheng, Yang; Lu, Feng; Lee, Seong-Kyun; Wang, Bo; Han, Eun-Taek] Kangwon Natl Univ, Sch Med, Dept Med Environm Biol & Trop Med, Chunchon, Gangwon Do, South Korea.
[Cheng, Yang] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Lu, Feng] Jiangsu Inst Parasit Dis, Minist Hlth, Key Lab Parasit Dis Control & Prevent, Wuxi, Jiangsu, Peoples R China.
[Lu, Feng] Jiangsu Inst Parasit Dis, Jiangsu Prov Key Lab Parasite Mol Biol, Wuxi, Jiangsu, Peoples R China.
[Kong, Deok-Hoon; Ha, Kwon-Soo] Kangwon Natl Univ, Sch Med, Dept Mol & Cellular Biochem, Chunchon, Gangwon Do, South Korea.
[Wang, Bo] Anhui Med Univ, Affiliated Hosp 1, Dept Clin Lab, Hefei, Anhui, Peoples R China.
[Sattabongkot, Jetsumon] Mahidol Univ, Fac Trop Med, Mahidol Vivax Res Unit, Bangkok 10700, Thailand.
[Tsuboi, Takafumi] Ehime Univ, Proteosci Ctr, Div Malaria Res, Matsuyama, Ehime, Japan.
RP Tsuboi, T (reprint author), Ehime Univ, Proteosci Ctr, Div Malaria Res, Matsuyama, Ehime, Japan.
EM tsuboi.takafumi.mb@ehime-u.ac.jp; ethan@kangwon.ac.kr
FU National Research Foundation (NRF) of Korea Grant - Korean government
(MEST) [2011-0016401]; Korea Health technology R&D Project, Ministry of
Health & Welfare, Republic of Korea [A121180]; MEXT KAKENHI [23117008];
JSPS KAKENHI in Japan [23406007]
FX This work was supported by National Research Foundation (NRF) of Korea
Grant funded by the Korean government (MEST) (2011-0016401) and a grant
from the Korea Health technology R&D Project, Ministry of Health &
Welfare, Republic of Korea (A121180). This work was also supported in
part by MEXT KAKENHI (23117008) and JSPS KAKENHI (23406007) in Japan.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 35
TC 0
Z9 0
U1 1
U2 3
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 MAY 26
PY 2015
VL 10
IS 5
AR e0127500
DI 10.1371/journal.pone.0127500
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CJ0QZ
UT WOS:000355183900099
ER
PT J
AU Fujita, R
Otake, K
Arimura, Y
Horikoshi, N
Miya, Y
Shiga, T
Osakabe, A
Tachiwana, H
Ohzeki, J
Larionov, V
Masumoto, H
Kurumizaka, H
AF Fujita, Risa
Otake, Koichiro
Arimura, Yasuhiro
Horikoshi, Naoki
Miya, Yuta
Shiga, Tatsuya
Osakabe, Akihisa
Tachiwana, Hiroaki
Ohzeki, Jun-ichirou
Larionov, Vladimir
Masumoto, Hiroshi
Kurumizaka, Hitoshi
TI Stable complex formation of CENP-B with the CENP-A nucleosome
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID HUMAN CENTROMERE PROTEIN; CELL-CYCLE; CRYSTAL-STRUCTURE; DNA-BINDING;
MOLECULAR ARCHITECTURE; CHROMOSOME SEGREGATION; OUTER KINETOCHORE;
HISTONE VARIANT; BUDDING YEAST; ALPHOID DNA
AB CENP-A and CENP-B are major components of centromeric chromatin. CENP-A is the histone H3 variant, which forms the centromere-specific nucleosome. CENP-B specifically binds to the CENP-B box DNA sequence on the centromere-specific repetitive DNA. In the present study, we found that the CENP-A nucleosome more stably retains human CENP-B than the H3.1 nucleosome in vitro. Specifically, CENP-B forms a stable complex with the CENP-A nucleosome, when the CENP-B box sequence is located at the proximal edge of the nucleosome. Surprisingly, the CENP-B binding was weaker when the CENP-B box sequence was located in the distal linker region of the nucleosome. This difference in CENP-B binding, depending on the CENP-B box location, was not observed with the H3.1 nucleosome. Consistently, we found that the DNA-binding domain of CENP-B specifically interacted with the CENP-A-H4 complex, but not with the H3.1-H4 complex, in vitro. These results suggested that CENP-B forms a more stable complex with the CENP-A nucleosome through specific interactions with CENP-A, if the CENP-B box is located proximal to the CENP-A nucleosome. Our in vivo assay also revealed that CENP-B binding in the vicinity of the CENP-A nucleosome substantially stabilizes the CENP-A nucleosome on alphoid DNA in human cells.
C1 [Fujita, Risa; Arimura, Yasuhiro; Horikoshi, Naoki; Miya, Yuta; Shiga, Tatsuya; Osakabe, Akihisa; Tachiwana, Hiroaki; Kurumizaka, Hitoshi] Waseda Univ, Grad Sch Adv Sci & Engn, Lab Struct Biol, Shinjuku Ku, Tokyo 1628480, Japan.
[Otake, Koichiro; Ohzeki, Jun-ichirou; Masumoto, Hiroshi] Kazusa DNA Res Inst, Dept Frontier Res, Lab Cell Engn, Kisarazu, Chiba 2920818, Japan.
[Larionov, Vladimir] NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
RP Kurumizaka, H (reprint author), Waseda Univ, Grad Sch Adv Sci & Engn, Lab Struct Biol, Shinjuku Ku, 2-2 Wakamatsu Cho, Tokyo 1628480, Japan.
EM kurumizaka@waseda.jp
OI Horikoshi, Naoki/0000-0003-1842-6934
FU MEXT KAKENHI [25116002, 23247030, 23114008]; MEXT, Japan; Waseda
Research Institute for Science and Engineering; Uehara Foundation; Naito
Foundation; Japan Society for the Promotion of Science [25-3931]; Kazusa
DNA Research Institute Foundation; Intramural Research Program of the
NIH, NCI, CCR
FX MEXT KAKENHI [25116002 to H.K., 23247030 and 23114008 to H.M.]; Platform
for Drug Discovery, Informatics and Structural Life Science from MEXT,
Japan [to H.K.]. H.K. was also supported by the Waseda Research
Institute for Science and Engineering, and by the Uehara Foundation and
the Naito Foundation. Y.A. was supported by Research Fellowships of the
Japan Society for the Promotion of Science for Young Scientists
[25-3931]. H.M. was also supported by the Kazusa DNA Research Institute
Foundation. V.L. received support from the Intramural Research Program
of the NIH, NCI, CCR. Funding for open access charge: Waseda University.
NR 70
TC 7
Z9 7
U1 5
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD MAY 26
PY 2015
VL 43
IS 10
BP 4909
EP 4922
DI 10.1093/nar/gkv405
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CK0XO
UT WOS:000355929200017
PM 25916850
ER
PT J
AU Zong, DL
Callen, E
Pegoraro, G
Lukas, C
Lukas, J
Nussenzweig, A
AF Zong, Dali
Callen, Elsa
Pegoraro, Gianluca
Lukas, Claudia
Lukas, Jiri
Nussenzweig, Andre
TI Ectopic expression of RNF168 and 53BP1 increases mutagenic but not
physiological non-homologous end joining
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID CLASS-SWITCH RECOMBINATION; DOUBLE-STRAND BREAKS; DNA-DAMAGE-RESPONSE;
HOMOLOGOUS RECOMBINATION; UBIQUITIN LIGASE; SOMATIC HYPERMUTATION;
OVARIAN-CARCINOMA; BRCA1 DEFICIENCY; CANCER GENOMICS; REPAIR PROTEINS
AB DNA double strand breaks (DSBs) formed during S phase are preferentially repaired by homologous recombination (HR), whereas G(1) DSBs, such as those occurring during immunoglobulin class switch recombination (CSR), are repaired by non-homologous end joining (NHEJ). The DNA damage response proteins 53BP1 and BRCA1 regulate the balance between NHEJ and HR. 53BP1 promotes CSR in part by mediating synapsis of distal DNA ends, and in addition, inhibits 5' end resection. BRCA1 antagonizes 53BP1 dependent DNA end-blocking activity during S phase, which would otherwise promote mutagenic NHEJ and genome instability. Recently, it was shown that supra-physiological levels of the E3 ubiquitin ligase RNF168 results in the hyper-accumulation of 53BP1/BRCA1 which accelerates DSB repair. Here, we ask whether increased expression of RNF168 or 53BP1 impacts physiological versus mutagenic NHEJ. We find that the anti-resection activities of 53BP1 are rate-limiting for mutagenic NHEJ but not for physiological CSR. As heterogeneity in the expression of RNF168 and 53BP1 is found in human tumors, our results suggest that deregulation of the RNF168/53BP1 pathway could alter the chemosensitivity of BRCA1 deficient tumors.
C1 [Zong, Dali; Callen, Elsa; Nussenzweig, Andre] NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA.
[Pegoraro, Gianluca] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Lukas, Claudia; Lukas, Jiri] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Prot Res, DK-2200 Copenhagen, Denmark.
RP Nussenzweig, A (reprint author), NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA.
EM andre_nussenzweig@nih.gov
OI Pegoraro, Gianluca/0000-0003-2843-9464
FU Intramural Research Program of the National Institutes of Health;
Department of Defense grant [BCRP DOD Idea Expansion Award] [11557134];
Novo Nordisk Foundation [NNF14CC0001]; National Cancer Institute; Center
for Cancer Research
FX Intramural Research Program of the National Institutes of Health, the
National Cancer Institute, the Center for Cancer Research; Department of
Defense grant [BCRP DOD Idea Expansion Award, 11557134 to A.N.]; Novo
Nordisk Foundation [NNF14CC0001 to J.L. and C.L.]. Funding for open
access charge: NIH Intramural Research Program.
NR 58
TC 4
Z9 4
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD MAY 26
PY 2015
VL 43
IS 10
BP 4950
EP 4961
DI 10.1093/nar/gkv336
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CK0XO
UT WOS:000355929200020
PM 25916843
ER
PT J
AU Billioux, A
Nakigozi, G
Newell, K
Chang, LW
Quinn, TC
Gray, RH
Ndyanabo, A
Galiwango, R
Kiggundu, V
Serwadda, D
Reynolds, SJ
AF Billioux, Alexander
Nakigozi, Gertrude
Newell, Kevin
Chang, Larry W.
Quinn, Thomas C.
Gray, Ron H.
Ndyanabo, Anthony
Galiwango, Ronald
Kiggundu, Valerian
Serwadda, David
Reynolds, Steven J.
TI Durable Suppression of HIV-1 after Virologic Monitoring-Based
Antiretroviral Adherence Counseling in Rakai, Uganda
SO PLOS ONE
LA English
DT Article
ID SUB-SAHARAN AFRICA; VIRAL LOAD; SOUTH-AFRICA; THERAPY; INFECTION;
OUTCOMES; COHORT; ADULTS; METAANALYSIS; PREDICTORS
AB Objectives
HIV viral load is recommended for monitoring antiretroviral treatment and identifying treatment failure. We assessed the durability of viral suppression after viral load-triggered adherence counseling among patients with HIV viremia 6 months after ART initiation.
Design
Observational cohort enrolled in an antiretroviral treatment program in rural Uganda.
Methods
Participants who underwent routine viral load determination every 24 weeks and had at least 48 weeks of follow-up were included in this analysis. Patients with viral loads > 400 copies/ml at 24 weeks of treatment were given additional adherence counseling, and all patients were followed to assess the duration of viral suppression and development of virologic failure.
Results
1,841 participants initiating antiretroviral therapy were enrolled in the Rakai Health Sciences Program between June 2005 and June 2011 and were followed with viral load monitoring every 24 weeks. 148 (8%) of patients did not achieve viral suppression at 24 weeks and were given additional adherence counseling. 85 (60%) of these patients had undetectable viral loads at 48 weeks, with a median duration of viral suppression of 240 weeks (IQR 193-288 weeks). Failure to achieve an undetectable viral load at 48 weeks was associated with age < 30 years and 24 week viral load > 2,000 copies/ml in multivariate logistic regression analysis.
Conclusions
The majority of patients with persistent viremia who were provided adherence counseling achieved robust viral suppression for a median 4.6 years. Access to virologic monitoring and adherence counseling is a priority in resource-limited settings.
C1 [Billioux, Alexander; Chang, Larry W.; Quinn, Thomas C.; Reynolds, Steven J.] Johns Hopkins Sch Med, Baltimore, MD 21205 USA.
[Billioux, Alexander; Nakigozi, Gertrude; Chang, Larry W.; Quinn, Thomas C.; Ndyanabo, Anthony; Galiwango, Ronald; Kiggundu, Valerian; Serwadda, David; Reynolds, Steven J.] Rakai Hlth Sci Program, Rakai, Uganda.
[Newell, Kevin] Leidos Biomed Res Inc, Clin Monitoring Res Program, Clin Res Directorate, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Quinn, Thomas C.; Reynolds, Steven J.] NIAID, NIH, Bethesda, MD 20892 USA.
[Chang, Larry W.; Gray, Ron H.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Serwadda, David] Makerere Univ, Coll Hlth Sci, Sch Publ Hlth, Kampala, Uganda.
RP Reynolds, SJ (reprint author), Johns Hopkins Sch Med, Baltimore, MD 21205 USA.
EM sjr@jhmi.edu
FU National Cancer Institute [HHSN261200800001E]; National Institute of
Mental Health [K23MH086338]; Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health; Leidos Biomedical Research, Inc.
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute under Contract No. HHSN261200800001E, the
National Institute of Mental Health under contract K23MH086338, and by
the Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, 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, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. Government. Leidos Biomedical Research, Inc., provided support in
the form of a salary for author KN, but did not have any additional role
in the study design, data collection and analysis, decision to publish,
or preparation of the manuscript. The specific roles of this author are
articulated in the 'author contributions' section.
NR 29
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 MAY 26
PY 2015
VL 10
IS 5
AR e0127235
DI 10.1371/journal.pone.0127235
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CJ0QZ
UT WOS:000355183900074
PM 26011158
ER
PT J
AU Gross, JA
Bureau, A
Croteau, J
Galfalvy, H
Oquendo, MA
Haghighi, F
Merette, C
Giegling, I
Hodgkinson, C
Goldman, D
Rujescu, D
Mann, JJ
Turecki, G
AF Gross, Jeffrey A.
Bureau, Alexandre
Croteau, Jordie
Galfalvy, Hanga
Oquendo, Maria A.
Haghighi, Fatemeh
Merette, Chantal
Giegling, Ina
Hodgkinson, Colin
Goldman, David
Rujescu, Dan
Mann, J. John
Turecki, Gustavo
TI A Genome-Wide Copy Number Variant Study of Suicidal Behavior
SO PLOS ONE
LA English
DT Article
ID BIPOLAR DISORDER; PARKINSONS-DISEASE; LRRK2; POPULATION;
PHOSPHORYLATION; RESOLUTION; MUTATIONS; LINKAGE; RISK; CNVS
AB Suicide and suicide attempts are complex behaviors that result from the interaction of different factors, including genetic variants that increase the predisposition to suicidal behaviors. Copy number variations (CNVs) are deletions or duplications of a segment of DNA usually larger than one kilobase. These structural genetic changes, although quite rare, have been associated with genetic liability to mental disorders, such as autism, schizophrenia, and bipolar disorder. No genome-wide level studies have been published investigating the potential role of CNVs in suicidal behaviors. Based on single-nucleotide polymorphism array data, we followed the Penn-CNV standards to detect CNVs in 1,608 subjects, comprising 475 suicide and suicide attempt cases and 1,133 controls. Although the initial algorithms determined the presence of CNVs on chromosomes 6 and 12 in seven and eight cases, respectively, compared with none of the controls, visual inspection of the raw data did not support this finding. Furthermore we were unable to validate these findings by CNV-specific real-time polymerase chain reaction. Additionally, rare CNV burden analysis did not find an association between the frequency or length of rare CNVs and suicidal behavior in our sample population. Although our findings suggest CNVs do not play an important role in the etiology of suicidal behaviors, they are not inconsistent with the strong evidence from the literature suggesting that other genetic variants account for a portion of the total phenotypic variability in suicidal behavior.
C1 [Gross, Jeffrey A.; Turecki, Gustavo] Douglas Mental Hlth Univ Inst, McGill Grp Suicide Studies, Montreal, PQ, Canada.
[Bureau, Alexandre; Croteau, Jordie; Merette, Chantal] Univ Laval, Inst Univ Sante Mentale Quebec, Ctr Rech, Quebec City, PQ, Canada.
[Galfalvy, Hanga; Haghighi, Fatemeh] Columbia Univ, Dept Psychiat, Div Biostat, New York, NY USA.
[Oquendo, Maria A.; Mann, J. John] Columbia Univ, Dept Psychiat, Mol Imaging & Neuropathol Div, New York, NY USA.
[Hodgkinson, Colin; Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA.
[Giegling, Ina; Rujescu, Dan] Univ Halle Wittenberg, Psychiat Clin, D-06108 Halle, Saxony Anhalt, Germany.
RP Turecki, G (reprint author), Douglas Mental Hlth Univ Inst, McGill Grp Suicide Studies, Montreal, PQ, Canada.
EM gustavo.turecki@mcgill.ca
RI Goldman, David/F-9772-2010;
OI Goldman, David/0000-0002-1724-5405; Bureau,
Alexandre/0000-0001-8220-9999
FU NIH [R01MH082188]
FX Support was provided by NIH grant R01MH082188 to GT, JJM, and DR
(http://projectreporter.nih.gov/project_info_description.cfm?aid=7527841
&icde=21862620&ddparam=&ddvalue=&ddsub=&cr=5&csb=default&cs=ASC).
NR 38
TC 4
Z9 4
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 MAY 26
PY 2015
VL 10
IS 5
AR e0128369
DI 10.1371/journal.pone.0128369
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CJ0QZ
UT WOS:000355183900230
PM 26010658
ER
PT J
AU Navarathna, DHMLP
Stein, EV
Lessey-Morillon, EC
Nayak, D
Martin-Manso, G
Roberts, DD
AF Navarathna, Dhammika H. M. L. P.
Stein, Erica V.
Lessey-Morillon, Elizabeth C.
Nayak, Debasis
Martin-Manso, Gema
Roberts, David D.
TI CD47 Promotes Protective Innate and Adaptive Immunity in a Mouse Model
of Disseminated Candidiasis
SO PLOS ONE
LA English
DT Article
ID T-CELL-ACTIVATION; DENDRITIC CELLS; SIRP-ALPHA; NEUTROPHIL
TRANSMIGRATION; CYTOKINE EXPRESSION; FUNGAL-INFECTIONS; IN-VIVO;
ALBICANS; RESPONSES; THROMBOSPONDIN-1
AB CD47 is a widely expressed receptor that regulates immunity by engaging its counter-receptor SIRP alpha on phagocytes and its secreted ligand thrombospondin-1. Mice lacking CD47 can exhibit enhanced or impaired host responses to bacterial pathogens, but its role in fungal immunity has not been examined. cd47(-/-) mice on a C57BL/6 background showed significantly increased morbidity and mortality following Candida albicans infection when compared with wild-type mice. Despite normal fungal colonization at earlier times, cd47(-/-) mice at four days post-infection had increased colonization of brain and kidneys accompanied by stronger inflammatory reactions. Neutrophil and macrophage numbers were significantly elevated in kidneys and neutrophils in the brains of infected cd47(-/-) mice. However, no defect in phagocytic activity towards C. albicans was observed in cd47(-/-) bone-marrow-derived macrophages, and neutrophil and macrophage killing of C. albicans was not impaired. CD47-deficiency did not alter the early humoral immune response to C. albicans. Th1, Th2, and Th17 population of CD4(+) T cells were expanded in the spleen, and gene expression profiles of spleen and kidney showed stronger pro-inflammatory signaling in infected cd47(-/-) mice. The chemoattractant chemokines MIP-2 alpha and MIP-2 beta were highly expressed in infected spleens of cd47(-/-) mice. G-CSF, GM-CSF, and the inflammasome component NLRP3 were more highly expressed in infected cd47(-/-) kidneys than in infected wild-type controls. Circulating pro-(TNF-alpha, IL-6) and anti-inflammatory cytokines (IL-10) were significantly elevated, but IL-17 was decreased. These data indicate that CD47 plays protective roles against disseminated candidiasis and alters pro-inflammatory and immunosuppressive pathways known to regulate innate and T cell immunity.
C1 [Navarathna, Dhammika H. M. L. P.; Stein, Erica V.; Lessey-Morillon, Elizabeth C.; Martin-Manso, Gema; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Nayak, Debasis] NINDS, NIH, Bethesda, MD 20892 USA.
[Stein, Erica V.] George Washington Univ, Microbiol & Immunol Program, Inst Biomed Sci, Dept Microbiol, Washington, DC 20037 USA.
[Stein, Erica V.] George Washington Univ, Microbiol & Immunol Program, Inst Biomed Sci, Dept Immunol, Washington, DC 20037 USA.
[Nayak, Debasis] George Washington Univ, Microbiol & Immunol Program, Inst Biomed Sci, Dept Trop Med, Washington, DC 20037 USA.
RP Roberts, DD (reprint author), NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
EM droberts@helix.nih.gov
RI Roberts, David/A-9699-2008
OI Roberts, David/0000-0002-2481-2981
FU NIH, National Cancer Institute, Center for Cancer Research; National
Institute of Neurological Disorders and Stroke
FX This work was supported by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research (DDR) and the
National Institute of Neurological Disorders and Stroke (DN).
NR 73
TC 3
Z9 3
U1 1
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 MAY 26
PY 2015
VL 10
IS 5
AR e0128220
DI 10.1371/journal.pone.0128220
PG 24
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CJ0QZ
UT WOS:000355183900208
PM 26010544
ER
PT J
AU Sepanlou, SG
Malekzadeh, R
Poustchi, H
Sharafkhah, M
Ghodsi, S
Malekzadeh, F
Etemadi, A
Pourshams, A
Pharoah, PD
Abnet, CC
Brennan, P
Boffetta, P
Dawsey, SM
Kamangar, F
AF Sepanlou, Sadaf G.
Malekzadeh, Reza
Poustchi, Hossein
Sharafkhah, Maryam
Ghodsi, Saeed
Malekzadeh, Fatemeh
Etemadi, Arash
Pourshams, Akram
Pharoah, Paul D.
Abnet, Christian C.
Brennan, Paul
Boffetta, Paolo
Dawsey, Sanford M.
Kamangar, Farin
TI The Clinical Performance of an Office-Based Risk Scoring System for
Fatal Cardiovascular Diseases in North-East of Iran
SO PLOS ONE
LA English
DT Article
ID CORONARY-HEART-DISEASE; GLOBAL BURDEN; PRIMARY PREVENTION; GOLESTAN
COHORT; PREDICTION; POPULATION; PROFILE; VALIDATION; HEALTH; MORTALITY
AB Background
Cardiovascular diseases (CVD) are becoming major causes of death in developing countries. Risk scoring systems for CVD are needed to prioritize allocation of limited resources. Most of these risk score algorithms have been based on a long array of risk factors including blood markers of lipids. However, risk scoring systems that solely use office-based data, not including laboratory markers, may be advantageous. In the current analysis, we validated the office-based Framingham risk scoring system in Iran.
Methods
The study used data from the Golestan Cohort in North-East of Iran. The following risk factors were used in the development of the risk scoring method: sex, age, body mass index, systolic blood pressure, hypertension treatment, current smoking, and diabetes. Cardiovascular risk functions for prediction of 10-year risk of fatal CVDs were developed.
Results
A total of 46,674 participants free of CVD at baseline were included. Predictive value of estimated risks was examined. The resulting Area Under the ROC Curve (AUC) was 0.774 (95% CI: 0.762-0.787) in all participants, 0.772 (95% CI: 0.753-0.791) in women, and 0.763 (95% CI: 0.747-0.779) in men. AUC was higher in urban areas (0.790, 95% CI: 0.766-0.815). The predicted and observed risks of fatal CVD were similar in women. However, in men, predicted probabilities were higher than observed.
Conclusion
The AUC in the current study is comparable to results of previous studies while lipid profile was replaced by body mass index to develop an office-based scoring system. This scoring algorithm is capable of discriminating individuals at high risk versus low risk of fatal CVD.
C1 [Sepanlou, Sadaf G.; Malekzadeh, Reza; Poustchi, Hossein; Sharafkhah, Maryam; Ghodsi, Saeed; Malekzadeh, Fatemeh; Etemadi, Arash; Pourshams, Akram; Kamangar, Farin] Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Inst, Tehran, Iran.
[Etemadi, Arash; Abnet, Christian C.; Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Pharoah, Paul D.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France.
[Boffetta, Paolo] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
[Boffetta, Paolo] Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA.
[Kamangar, Farin] Morgan State Univ, Sch Community Hlth & Policy, Dept Publ Hlth Anal, Baltimore, MD 21239 USA.
RP Malekzadeh, R (reprint author), Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Inst, Tehran, Iran.
EM malek@ams.ac.ir
RI Abnet, Christian/C-4111-2015; Etemadi, Arash/C-1386-2016; Sepanlou,
Sadaf/H-9343-2016
OI Abnet, Christian/0000-0002-3008-7843; Etemadi,
Arash/0000-0002-3458-1072; Sepanlou, Sadaf/0000-0002-3669-5129
FU Division of Cancer Epidemiology and Genetics of the National Cancer
Institute, NIH; Digestive Disease Research Institute of Tehran
University of Medical Sciences [82-603]; Cancer Research UK (CRUK);
International Agency for Research on Cancer
FX This study was supported in part by the intramural research program of
the Division of Cancer Epidemiology and Genetics of the National Cancer
Institute, NIH, by the Digestive Disease Research Institute of Tehran
University of Medical Sciences (grant No 82-603), by Cancer Research UK
(CRUK), and by the International Agency for Research on Cancer. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 34
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U1 1
U2 3
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 MAY 26
PY 2015
VL 10
IS 5
AR e0126779
DI 10.1371/journal.pone.0126779
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CJ0QZ
UT WOS:000355183900041
PM 26011607
ER
PT J
AU Wang, LM
Lu, HB
Brown, PL
Rea, W
Vaupel, B
Yang, YH
Stein, E
Shepard, PD
AF Wang, Leiming
Lu, Hanbing
Brown, P. Leon
Rea, William
Vaupel, Bruce
Yang, Yihong
Stein, Elliot
Shepard, Paul D.
TI Manganese-Enhanced MRI Reflects Both Activity-Independent and
Activity-Dependent Uptake within the Rat Habenulomesencephalic Pathway
SO PLOS ONE
LA English
DT Article
ID CEREBRAL GLUCOSE-UTILIZATION; RESONANCE-IMAGING MEMRI;
HABENULO-INTERPEDUNCULAR PATHWAY; IN-VIVO; GLUTAMATE RECEPTORS;
CALCIUM-CHANNELS; TRANSFERRIN RECEPTOR; CA2+ PERMEABILITY;
NEURONAL-ACTIVITY; BRAIN ACTIVATION
AB Manganese-enhanced magnetic resonance imaging (MEMRI) is a powerful technique for assessing the functional connectivity of neurons within the central nervous system. Despite the widely held proposition that MEMRI signal is dependent on neuronal activity, few studies have directly tested this implicit hypothesis. In the present series of experiments, MnCl2 was injected into the habenula of urethane-anesthetized rats alone or in combination with drugs known to alter neuronal activity by modulating specific voltage-and/or ligand-gated ion channels. Continuous quantitative T1 mapping was used to measure Mn2+ accumulation in the interpeduncular nucleus, a midline structure in which efferents from the medial habenula terminate. Microinjection of MnCl2 into the habenular complex using a protocol that maintained spontaneous neuronal activity resulted in a time-dependent increase in MEMRI signal intensity in the interpeduncular nucleus consistent with fast axonal transport of Mn2+ between these structures. Co-injection of the excitatory amino-acid agonist AMPA, increased the Mn2+-enhanced signal intensity within the interpeduncular nucleus. AMPA-induced increases in MEMRI signal were attenuated by co-injection of either the sodium channel blocker, TTX, or broad-spectrum Ca2+ channel blocker, Ni2+, and were occluded in the presence of both channel blockers. However, neither Ni2+ nor TTX, alone or in combination, attenuated the increase in signal intensity following injection of Mn2+ into the habenula. These results support the premise that changes in neuronal excitability are reflected by corresponding changes in MEMRI signal intensity. However, they also suggest that basal rates of Mn2+ uptake by neurons in the medial habenula may also occur via activity-independent mechanisms.
C1 [Wang, Leiming; Lu, Hanbing; Rea, William; Vaupel, Bruce; Yang, Yihong; Stein, Elliot] Natl Inst Drug Abuse, Neuroimaging Res Branch, IRP, Baltimore, MD 21224 USA.
[Wang, Leiming; Brown, P. Leon; Shepard, Paul D.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21228 USA.
[Wang, Leiming; Brown, P. Leon; Shepard, Paul D.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA.
RP Shepard, PD (reprint author), Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21228 USA.
EM shepard.paul@gmail.com
FU Intramural Research Program of the National Institute on Drug Abuse,
NIDA Residential Research Support Services [N01DA-5-9909]; National
Institute of Mental Health [MH-094489]
FX This work was supported in part by the Intramural Research Program of
the National Institute on Drug Abuse, NIDA Residential Research Support
Services Contract N01DA-5-9909 and a grant from the National Institute
of Mental Health (MH-094489).
NR 62
TC 1
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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 MAY 26
PY 2015
VL 10
IS 5
AR e0127773
DI 10.1371/journal.pone.0127773
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CJ0QZ
UT WOS:000355183900142
PM 26009889
ER
PT J
AU Williams, RJ
Tse, T
DiPiazza, K
Zarin, DA
AF Williams, Rebecca J.
Tse, Tony
DiPiazza, Katelyn
Zarin, Deborah A.
TI Terminated Trials in the ClinicalTrials.gov Results Database: Evaluation
of Availability of Primary Outcome Data and Reasons for Termination
SO PLOS ONE
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIALS; CLINICAL-TRIALS; PUBLICATION;
REGISTRATION; PREVALENCE; INSTITUTE; BENEFIT; UPDATE; IMPACT; ISSUES
AB Background
Clinical trials that end prematurely (or "terminate") raise financial, ethical, and scientific concerns. The extent to which the results of such trials are disseminated and the reasons for termination have not been well characterized.
Methods and Findings
A cross-sectional, descriptive study of terminated clinical trials posted on the ClinicalTrials.gov results database as of February 2013 was conducted. The main outcomes were to characterize the availability of primary outcome data on ClinicalTrials.gov and in the published literature and to identify the reasons for trial termination. Approximately 12% of trials with results posted on the ClinicalTrials. gov results database (905/7,646) were terminated. Most trials were terminated for reasons other than accumulated data from the trial (68%; 619/905), with an insufficient rate of accrual being the lead reason for termination among these trials (57%; 350/619). Of the remaining trials, 21% (193/905) were terminated based on data from the trial (findings of efficacy or toxicity) and 10% (93/905) did not specify a reason. Overall, data for a primary outcome measure were available on ClinicalTrials. gov and in the published literature for 72% (648/905) and 22% (198/905) of trials, respectively. Primary outcome data were reported on the ClinicalTrials. gov results database and in the published literature more frequently (91% and 46%, respectively) when the decision to terminate was based on data from the trial.
Conclusions
Trials terminate for a variety of reasons, not all of which reflect failures in the process or an inability to achieve the intended goals. Primary outcome data were reported most often when termination was based on data from the trial. Further research is needed to identify best practices for disseminating the experience and data resulting from terminated trials in order to help ensure maximal societal benefit from the investments of trial participants and others involved with the study.
C1 [Williams, Rebecca J.; Tse, Tony; Zarin, Deborah A.] NIH, Natl Lib Med, DHHS, Bethesda, MD 20892 USA.
[DiPiazza, Katelyn] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
RP Williams, RJ (reprint author), NIH, Natl Lib Med, DHHS, Bldg 10, Bethesda, MD 20892 USA.
EM williamsre@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH),
National Library of Medicine (NLM)
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Library of Medicine (NLM).
The views expressed in this article are those of the authors and do not
necessarily reflect the positions of the NIH. NLM had no role in the
design and conduct of the study; collection, management, analysis, and
interpretation of the data; preparation of the manuscript and decision
to submit the manuscript for publication. NLM reviewed and approved the
manuscript prior to publication.
NR 40
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U1 4
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 MAY 26
PY 2015
VL 10
IS 5
AR e0127242
DI 10.1371/journal.pone.0127242
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CJ0QZ
UT WOS:000355183900075
PM 26011295
ER
PT J
AU Yang, Z
Li, JJ
Liu, QS
Yuan, TT
Zhang, YY
Chen, LQ
Lou, Q
Sun, ZH
Ying, HZ
Xu, JQ
Dimitrov, DS
Zhang, MY
AF Yang, Zheng
Li, Jingjing
Liu, Qingsheng
Yuan, Tingting
Zhang, Yanyu
Chen, Li-Qing
Lou, Qi
Sun, Zehua
Ying, Huazhong
Xu, Jianqing
Dimitrov, Dimiter S.
Zhang, Mei-Yun
TI Identification of Non-HIV Immunogens That Bind to Germline b12
Predecessors and Prime for Elicitation of Cross-clade Neutralizing HIV-1
Antibodies
SO PLOS ONE
LA English
DT Article
ID B-CELL RECEPTORS; POTENT NEUTRALIZATION; MONOCLONAL-ANTIBODIES;
CRYSTAL-STRUCTURE; VACCINE DESIGN; BROAD; GP120; ANTIGEN; VIRUS; EPITOPE
AB A fundamental challenge for developing an effective and safe HIV-1 vaccine is to identify vaccine immunogens that can initiate and maintain immune responses leading to elicitation of broadly neutralizing HIV-1 antibodies (bnAbs) through complex maturation pathways. We have previously found that HIV-1 envelope glycoproteins (Env) lack measurable binding to putative germline predecessors of known bnAbs and proposed to search for non-HIV immunogens that could initiate their somatic maturation. Using bnAb b12 as a model bnAb and yeast display technology, we isolated five (poly) peptides from plant leaves, insects, E. coli strains, and sea water microbes that bind to b12 putative germline and intermediate antibodies. Rabbit immunization with the (poly) peptides alone induced high titers of cross-reactive antibodies that neutralized HIV-1 isolates SF162 and JRFL. Priming rabbits with the (poly) peptides followed by boosts with trimeric gp140(SF162) and then resurfaced Env (RSC3) induced antibodies that competed with mature b12 and neutralized tier 1 and 2 viruses from clade B, C and E, while control rabbits without (poly) peptide priming induced antibodies that did not compete with mature b12 and neutralized fewer isolates. The degree of competition with mature b12 for binding to gp140SF162 correlated with the neutralizing activity of the rabbit IgG. Reversing the order of the two boosting immunogens significantly affected the binding profile and neutralization potency of the rabbit IgG. Our study is the first to provide evidence that appears to support the concept that non-HIV immunogens may initiate immune responses leading to elicitation of cross-clade neutralizing antibodies.
C1 [Yang, Zheng; Li, Jingjing; Liu, Qingsheng; Yuan, Tingting; Zhang, Yanyu; Sun, Zehua; Zhang, Mei-Yun] Univ Hong Kong, Li Ka Shing Fac Med, AIDS Inst, Dept Microbiol, Pok Fu Lam, Hong Kong, Peoples R China.
[Chen, Li-Qing; Lou, Qi; Ying, Huazhong] Zhejiang Acad Med Sci, Ctr Lab Anim, Shanghai, Zhejiang, Peoples R China.
[Xu, Jianqing] Fudan Univ, Shanghai Publ Hlth Clin Ctr, Inst Biomed Sci, Shanghai 201508, Peoples R China.
[Dimitrov, Dimiter S.] NCI, Prot Interact Grp, Immunol Lab, Canc & Inflammat Program,Ctr Canc Res,NIH, Frederick, MD 21701 USA.
[Zhang, Mei-Yun] Shenzhen Third Peoples Hosp, Liver Dis Inst, Shenzhen 518112, Peoples R China.
RP Zhang, MY (reprint author), Univ Hong Kong, Li Ka Shing Fac Med, AIDS Inst, Dept Microbiol, Pok Fu Lam, Hong Kong, Peoples R China.
EM zhangmy2014@hotmail.com
OI Yang, Zheng/0000-0003-0217-6694
FU General Research Fund (GRF) from Hong Kong Research Grants Consuls (RGC)
[785112]; China 12th 5-year Mega project for HIV/AIDS [2012ZX10001006]
FX This work was supported by a General Research Fund (GRF) (#785112) from
Hong Kong Research Grants Consuls (RGC)
(http://www.ugc.edu.hk/eng/rgc/index.htm) and the China 12th 5-year Mega
project for HIV/AIDS (#2012ZX10001006)
(http://www.most.gov.cn/tztg/index.htm) to M-Y Z. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 43
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U1 1
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 MAY 26
PY 2015
VL 10
IS 5
AR e0126428
DI 10.1371/journal.pone.0126428
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CJ0QZ
UT WOS:000355183900028
PM 26010511
ER
PT J
AU Qian, X
Brinton, LA
Schairer, C
Matthews, CE
AF Qian, X.
Brinton, L. A.
Schairer, C.
Matthews, C. E.
TI Reply to 'Sleep duration and breast cancer risk in the breast cancer
detection demonstration project follow-up cohort: true associations or
bias?'
SO BRITISH JOURNAL OF CANCER
LA English
DT Letter
C1 [Qian, X.; Matthews, C. E.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA.
[Brinton, L. A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Schairer, C.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
RP Qian, X (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA.
EM qian.xiao@nih.gov
RI Brinton, Louise/G-7486-2015
OI Brinton, Louise/0000-0003-3853-8562
NR 7
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD MAY 26
PY 2015
VL 112
IS 11
BP 1839
EP 1840
DI 10.1038/bjc.2015.131
PG 4
WC Oncology
SC Oncology
GA CJ0EQ
UT WOS:000355148100025
PM 25897672
ER
PT J
AU Blum, MR
Bauer, DC
Collet, TH
Fink, HA
Cappola, AR
da Costa, BR
Wirth, CD
Peeters, RP
Asvold, BO
den Elzen, WPJ
Luben, RN
Imaizumi, M
Bremner, AP
Gogakos, A
Eastell, R
Kearney, PM
Strotmeyer, ES
Wallace, ER
Hoff, M
Ceresini, G
Rivadeneira, F
Uitterlinden, AG
Stott, DJ
Westendorp, RGJ
Khaw, KT
Langhammer, A
Ferrucci, L
Gussekloo, J
Williams, GR
Walsh, JP
Juni, P
Aujesky, D
Rodondi, N
AF Blum, Manuel R.
Bauer, Douglas C.
Collet, Tinh-Hai
Fink, Howard A.
Cappola, Anne R.
da Costa, Bruno R.
Wirth, Christina D.
Peeters, Robin P.
Asvold, Bjorn O.
den Elzen, Wendy P. J.
Luben, Robert N.
Imaizumi, Misa
Bremner, Alexandra P.
Gogakos, Apostolos
Eastell, Richard
Kearney, Patricia M.
Strotmeyer, Elsa S.
Wallace, Erin R.
Hoff, Mari
Ceresini, Graziano
Rivadeneira, Fernando
Uitterlinden, Andre G.
Stott, David J.
Westendorp, Rudi G. J.
Khaw, Kay-Tee
Langhammer, Arnuf
Ferrucci, Luigi
Gussekloo, Jacobijn
Williams, Graham R.
Walsh, John P.
Jueni, Peter
Aujesky, Drahomir
Rodondi, Nicolas
CA Thyroid Studies Collaboration
TI Subclinical Thyroid Dysfunction and Fracture Risk A Meta-analysis
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID CORONARY-HEART-DISEASE; PARTICIPANT DATA-ANALYSIS; BONE-MINERAL DENSITY;
POSTMENOPAUSAL WOMEN; CARDIOVASCULAR-DISEASE; STIMULATING HORMONE;
SYSTEMATIC REVIEWS; RANDOMIZED-TRIALS; FOLLOW-UP; HYPERTHYROIDISM
AB IMPORTANCE Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking.
OBJECTIVE To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures.
DATA SOURCES AND STUDY SELECTION The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures.
DATA EXTRACTION Individual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH <0.45 mIU/L), and subclinical hypothyroidism (TSH >= 4.50-19.99 mIU/L) with normal thyroxine concentrations.
MAIN OUTCOME AND MEASURES The primary outcome was hip fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes.
RESULTS Among 70 298 participants, 4092 (5.8%) had subclinical hypothyroidism and 2219 (3.2%) had subclinical hyperthyroidism. During 762 401 person-years of follow-up, hip fracture occurred in 2975 participants (4.6%; 12 studies), any fracture in 2528 participants (9.0%; 8 studies), nonspine fracture in 2018 participants (8.4%; 8 studies), and spine fracture in 296 participants (1.3%; 6 studies). In age-and sex-adjusted analyses, the hazard ratio (HR) for subclinical hyperthyroidism vs euthyroidismwas 1.36 for hip fracture (95% CI, 1.13-1.64; 146 events in 2082 participants vs 2534 in 56 471); for any fracture, HRwas 1.28 (95% CI, 1.06-1.53; 121 events in 888 participants vs 2203 in 25 901); for nonspine fracture, HRwas 1.16 (95% CI, 0.95-1.41; 107 events in 946 participants vs 1745 in 21 722); and for spine fracture, HRwas 1.51 (95% CI, 0.93-2.45; 17 events in 732 participants vs 255 in 20 328). Lower TSHwas associated with higher fracture rates: for TSH of less than 0.10 mIU/L, HRwas 1.61 for hip fracture (95% CI, 1.21-2.15; 47 events in 510 participants); for any fracture, HRwas 1.98 (95% CI, 1.41-2.78; 44 events in 212 participants); for nonspine fracture, HRwas 1.61 (95% CI, 0.96-2.71; 32 events in 185 participants); and for spine fracture, HRwas 3.57 (95% CI, 1.88-6.78; 8 events in 162 participants). Risks were similar after adjustment for other fracture risk factors. Endogenous subclinical hyperthyroidism (excluding thyroid medication users) was associated with HRs of 1.52 (95% CI, 1.19-1.93) for hip fracture, 1.42 (95% CI, 1.16-1.74) for any fracture, and 1.74 (95% CI, 1.01-2.99) for spine fracture. No association was found between subclinical hypothyroidism and fracture risk.
CONCLUSIONS AND RELEVANCE Subclinical hyperthyroidism was associated with an increased risk of hip and other fractures, particularly among those with TSH levels of less than 0.10 mIU/L and those with endogenous subclinical hyperthyroidism. Further study is needed to determine whether treating subclinical hyperthyroidism can prevent fractures.
C1 [Blum, Manuel R.; Wirth, Christina D.; Aujesky, Drahomir; Rodondi, Nicolas] Univ Hosp Bern, Inselspital, Dept Gen Internal Med, CH-3010 Bern, Switzerland.
[Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Bauer, Douglas C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Collet, Tinh-Hai] Univ Lausanne Hosp, Serv Endocrinol Diabet & Metab, Lausanne, Switzerland.
[Fink, Howard A.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA.
[Fink, Howard A.] VA Med Ctr, Geriatr Res Educ & Clin Ctr, Minneapolis, MN USA.
[Cappola, Anne R.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[da Costa, Bruno R.] Florida Int Univ, Nicole Wertheim Coll Nursing & Hlth Sci, Dept Phys Therapy, Miami, FL 33199 USA.
[Peeters, Robin P.; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Peeters, Robin P.; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Asvold, Bjorn O.; Hoff, Mari; Langhammer, Arnuf] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, N-7034 Trondheim, Norway.
[Asvold, Bjorn O.] Univ Trondheim Hosp, St Olavs Hosp, Dept Endocrinol, Trondheim, Norway.
[den Elzen, Wendy P. J.; Gussekloo, Jacobijn] Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands.
[Luben, Robert N.; Khaw, Kay-Tee] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Imaizumi, Misa] Radiat Effects Res Fdn, Nagasaki, Japan.
[Bremner, Alexandra P.] Univ Western Australia, Sch Populat Hlth, Crawley, WA, Australia.
[Gogakos, Apostolos; Williams, Graham R.] Univ London Imperial Coll Sci Technol & Med, Dept Med, London, England.
[Eastell, Richard] Univ Sheffield, Dept Human Metab, Sheffield, S Yorkshire, England.
[Kearney, Patricia M.] Natl Univ Ireland Univ Coll Cork, Dept Epidemiol & Publ Hlth, Cork, Ireland.
[Strotmeyer, Elsa S.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Wallace, Erin R.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Hoff, Mari] Nord Trondelag Hosp Trust, Levanger Hosp, Levanger, Norway.
[Ceresini, Graziano] Univ Hosp Parma, Dept Clin & Expt Med, Geriatr Endocrine Unit, Parma, Italy.
[Stott, David J.] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow G12 8QQ, Lanark, Scotland.
[Westendorp, Rudi G. J.] Univ Copenhagen, Dept Publ Hlth, Copenhagen, Denmark.
[Ferrucci, Luigi] NIA, NIH, Baltimore, MD 21224 USA.
[Walsh, John P.] Univ Western Australia, Crawley, WA, Australia.
[Walsh, John P.] Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Nedlands, WA 6009, Australia.
[Jueni, Peter] Univ Bern, Inst Social & Prevent Med, Bern, Switzerland.
RP Rodondi, N (reprint author), Univ Bern, Inselspital, Dept Gen Internal Med, CH-3010 Bern, Switzerland.
EM nicolas.rodondi@insel.ch
RI Rivadeneira, Fernando/O-5385-2015;
OI Rivadeneira, Fernando/0000-0001-9435-9441; Schmidt, Christina
Doris/0000-0003-2604-6253; Strotmeyer, Elsa/0000-0002-4093-6036; Luben,
Robert/0000-0002-5088-6343; Blum, Manuel/0000-0003-4638-775X; R. da
Costa, Bruno/0000-0002-1786-6332; Collet, Tinh-Hai/0000-0002-3243-1222
FU Swiss National Science Foundation [SNSF 320030-138267, 320030-150025];
Swiss Heart Foundation; National Heart, Lung, and Blood Institute
(NHLBI) [HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079,
N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086,
U01HL080295]; National Institute of Neurological Disorders and Stroke
(NINDS); NIA [R01AG023629, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106,
R01-AG028050]; American Heart Association; NINR [R01-NR012459]; Medical
Research Council UK; Cancer Research UK; NIH; National Institute of
Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Center
for Advancing Translational Sciences (NCATS); NIH Roadmap for Medical
Research [U01AG027810, U01AG042124, U01AG042139, U01AG042140,
U01AG042143, U01AG042145, U01AG042168, U01AR066160, UL1TR000128]; Wallac
Oy (Turku, Finland); Dutch Ministry of Health, Welfare and Sports;
Bristol-Myers Squibb; Erasmus MC; Erasmus University, Rotterdam, the
Netherlands; Netherlands Organisation for Scientific Research (NWO);
Netherlands Organisation for the Health Research and Development
(ZonMw); Research Institute for Diseases in the Elderly (RIDE); Ministry
of Education, Culture and Science; Dutch Ministry for Health, Welfare
and Sports; European Commission (DG XII); Municipality of Rotterdam;
sanofi-aventis; Eli Lilly; Novartis; Pfizer; Procter & Gamble
Pharmaceuticals; Roche; Netherlands Organization for Scientific Research
[NGI/NWO 911-03-016]; Swiss National Science Foundation; Swiss
Foundation for Grants in Biology and Medicine [PBLAP3-145870,
P3SMP3-155318]
FX This project was supported by grants from the Swiss National Science
Foundation (SNSF 320030-138267 and 320030-150025) and partially
supported by a grant from the Swiss Heart Foundation (Dr Rodondi). The
Cardiovascular Health Study was supported by contracts from the National
Heart, Lung, and Blood Institute (NHLBI) (HHSN268201200036C,
HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081,
N01HC85082, N01HC85083, N01HC85086; and grant U01HL080295) with an
additional contribution from the National Institute of Neurological
Disorders and Stroke (NINDS). Additional support was provided by the NIA
(R01AG023629). The thyroid measurements in the Cardiovascular Health
Study were supported by an American Heart Association Grant-in-Aid (Dr
Fried). The Health, Aging, and Body Composition Study was supported by
the NIA (contract numbers: N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106;
and grant R01-AG028050); and an NINR grant (R01-NR012459). The NIA
funded the Health, Aging, and Body Composition Study, reviewed the
manuscript, and approved its publication. This research was supported in
part by the NIA. The EPIC (European Prospective Investigation of
Cancer)-Norfolk Study was supported by research grants from the Medical
Research Council UK and Cancer Research UK. The Osteoporotic Fractures
in Men (MrOS) Study is supported by NIH funding. The following
institutes provided support: the NIA, the National Institute of
Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National
Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for
Medical Research (grant numbers: U01AG027810, U01AG042124, U01AG042139,
U01AG042140, U01AG042143, U01AG042145, U01AG042168, U01AR066160, and
UL1TR000128). The Nord-Trondelag Health Study (HUNT Study) is a
collaborative effort of the Faculty of Medicine, Norwegian University of
Science and Technology; the Norwegian Institute of Public Health; and
the Nord-Trondelag County Council. Thyroid function testing in the HUNT
Study was financially supported by Wallac Oy (Turku, Finland). The
Leiden 85-plus Study was partly funded by the Dutch Ministry of Health,
Welfare and Sports. The original PROSPER study was supported by an
unrestricted, investigator-initiated grant from Bristol-Myers Squibb.
The Rotterdam Study is funded by Erasmus MC and Erasmus University,
Rotterdam, the Netherlands; the Netherlands Organisation for Scientific
Research (NWO); the Netherlands Organisation for the Health Research and
Development (ZonMw); the Research Institute for Diseases in the Elderly
(RIDE); the Ministry of Education, Culture and Science; the Dutch
Ministry for Health, Welfare and Sports; the European Commission (DG
XII); and the Municipality of Rotterdam. The original OPUS study was
supported by sanofi-aventis, Eli Lilly, Novartis, Pfizer, Procter &
Gamble Pharmaceuticals, and Roche. Dr Westendorp is supported by the
Netherlands Organization for Scientific Research (NGI/NWO 911-03-016).
Dr Collet reports receipt of research support from grants from the Swiss
National Science Foundation and the Swiss Foundation for Grants in
Biology and Medicine (PBLAP3-145870, P3SMP3-155318).
NR 59
TC 30
Z9 30
U1 3
U2 11
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 MAY 26
PY 2015
VL 313
IS 20
BP 2055
EP 2065
DI 10.1001/jama.2015.5161
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA CJ0DC
UT WOS:000355142400019
PM 26010634
ER
PT J
AU Nogueira, L
Foerster, C
Groopman, J
Egner, P
Koshiol, J
Ferreccio, C
AF Nogueira, Leticia
Foerster, Claudia
Groopman, John
Egner, Patricia
Koshiol, Jill
Ferreccio, Catterina
CA Gallbladder Canc Chile Working Grp
TI Association of Aflatoxin With Gallbladder Cancer in Chile
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
ID B-1
C1 [Nogueira, Leticia; Koshiol, Jill] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Foerster, Claudia; Ferreccio, Catterina] Pontificia Univ Catolica Chile, Sch Med, Santiago, Chile.
[Groopman, John; Egner, Patricia] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA.
RP Ferreccio, C (reprint author), Pontificia Univ Catolica Chile, Fac Med, Dept Publ Hlth, Marcoleta 434, Santiago, Chile.
EM catferre@gmail.com
RI Hildesheim, Allan/B-9760-2015
OI Hildesheim, Allan/0000-0003-0257-2363
FU Intramural NIH HHS
NR 6
TC 10
Z9 10
U1 1
U2 6
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 MAY 26
PY 2015
VL 313
IS 20
BP 2075
EP 2077
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA CJ0DC
UT WOS:000355142400023
PM 26010638
ER
PT J
AU Liu, R
Umbach, DM
Peddada, SD
Xu, ZL
Troster, AI
Huang, XM
Chen, HL
AF Liu, Rui
Umbach, David M.
Peddada, Shyamal D.
Xu, Zongli
Troester, Alexander I.
Huang, Xuemei
Chen, Honglei
TI Potential sex differences in nonmotor symptoms in early drug-naive
Parkinson disease
SO NEUROLOGY
LA English
DT Article
ID MILD COGNITIVE IMPAIRMENT; GENDER-DIFFERENCES; DE-NOVO; RISK; MOTOR;
FEATURES; COHORT; HETEROGENEITY; MULTICENTER; CONSUMPTION
AB Objective:To examine potential sex differences in nonmotor symptoms (NMS) among drug-naive patients with Parkinson disease (PD), and to identify NMS that can best differentiate patients with early PD from controls.Methods:Our cross-sectional analysis included 414 newly diagnosed, untreated patients with PD (269 men and 145 women) and 188 healthy controls (121 men and 67 women) in the Parkinson's Progression Markers Initiative Study. NMS were measured using well-validated instruments covering sleep, olfactory, neurobehavioral, autonomic, and neuropsychological domains.Results:Male and female patients with PD were fairly comparable on motor presentations but differed on several nonmotor features. Male patients with PD had significantly more pronounced deficits in olfaction (p = 0.02) and in certain cognitive measurements (all p < 0.01) than female patients, whereas female cases experienced higher trait anxiety (p = 0.02). Multiple stepwise logistic regression analysis showed that the combination of NMS measuresUniversity of Pennsylvania Smell Identification Test (UPSIT), Montreal Cognitive Assessment (MoCA), Scales for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT), and state anxiety from the State-Trait Anxiety Inventoryeffectively differentiated patients with PD from controls with an area under the receiver operating characteristic curve (AUC) of 0.913 (95% confidence interval [CI]: 0.89-0.94). UPSIT, MoCA, and SCOPA-AUT were the most predictive NMS measurements in men (AUC = 0.919; 95% CI: 0.89-0.95) as compared to UPSIT, MoCA, and REM Sleep Behavior Disorder Screening Questionnaire in women (AUC = 0.903; 95% CI: 0.86-0.95).Conclusions:Our analysis revealed notable sex differences in several nonmotor features of patients with de novo PD. Furthermore, we found a parsimonious NMS combination that could effectively differentiate de novo cases from healthy controls.
C1 [Liu, Rui; Xu, Zongli; Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Umbach, David M.; Peddada, Shyamal D.] NIEHS, Biostat & Computat Biol Branch, Res Triangle Pk, NC 27709 USA.
[Troester, Alexander I.] Barrow Neurol Inst, Phoenix, AZ 85013 USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA.
RP Liu, R (reprint author), NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
EM liur2@niehs.nih.gov
OI xu, zongli/0000-0002-9034-8902; Chen, Honglei/0000-0003-3446-7779
FU Michael J. Fox Foundation for Parkinson's Research; AbbVie; Avid
Radiopharmaceuticals; Biogen Idec; Bristol-Myers Squibb; Covance; Elan;
GE Healthcare; Genentech; GSK-GlaxoSmithKline; Lilly; Merck; MSD-Meso
Scale Discovery; Piramal; Pfizer; Roche; UCB; Intramural Research
Program of the NIH, the National Institute of Environmental Health
Sciences [Z01-ES-101986]; NIH [NS060722, ES019672, NS08215]
FX Parkinson's Progression Markers Initiative, a public-private
partnership, is funded by the Michael J. Fox Foundation for Parkinson's
Research and funding partners, including AbbVie, Avid
Radiopharmaceuticals, Biogen Idec, Bristol-Myers Squibb, Covance, Elan,
GE Healthcare, Genentech, GSK-GlaxoSmithKline, Lilly, Merck, MSD-Meso
Scale Discovery, Piramal, Pfizer, Roche, and UCB
(www.ppmi-info.org/fundingpartners). R.L., D.M.U., S.D.P., Z.X., and
H.C. are supported by the Intramural Research Program of the NIH, the
National Institute of Environmental Health Sciences (Z01-ES-101986).
H.X. is supported by NIH grants NS060722, ES019672, and NS08215.
NR 40
TC 14
Z9 14
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD MAY 26
PY 2015
VL 84
IS 21
BP 2107
EP 2115
DI 10.1212/WNL.0000000000001609
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA CJ2LT
UT WOS:000355317000008
PM 25925983
ER
PT J
AU Tsai, SYA
Pokrass, MJ
Klauer, NR
Nohara, H
Su, TP
AF Tsai, Shang-Yi A.
Pokrass, Michael J.
Klauer, Neal R.
Nohara, Hiroshi
Su, Tsung-Ping
TI Sigma-1 receptor regulates Tau phosphorylation and axon extension by
shaping p35 turnover via myristic acid
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE sigma-1 receptor; p35; myristic acid; axon growth; cdk5
ID CYCLIN-DEPENDENT KINASE-5; ALZHEIMERS-DISEASE; CDK5 ACTIVATOR;
BRAIN-DEVELOPMENT; MICE; CHAPERONES; P25; NEURODEGENERATION; GUIDANCE;
CLEAVAGE
AB Dysregulation of cyclin-dependent kinase 5 (cdk5) per relative concentrations of its activators p35 and p25 is implicated in neurodegenerative diseases. P35 has a short t(1/2) and undergoes rapid proteasomal degradation in its membrane-bound myristoylated form. P35 is converted by calpain to p25, which, along with an extended t(1/2), promotes aberrant activation of cdk5 and causes abnormal hyperphosphorylation of tau, thus leading to the formation of neurofibrillary tangles. The sigma-1 receptor (Sig-1R) is an endoplasmic reticulum chaperone that is implicated in neuronal survival. However, the specific role of the Sig-1R in neurodegeneration is unclear. Here we found that Sig-1Rs regulate proper tau phosphorylation and axon extension by promoting p35 turnover through the receptor's interaction with myristic acid. In Sig-1R-KO neurons, a greater accumulation of p35 is seen, which results from neither elevated transcription of p35 nor disrupted calpain activity, but rather to the slower degradation of p35. In contrast, Sig-1R overexpression causes a decrease of p35. Sig-1R-KO neurons exhibit shorter axons with lower densities. Myristic acid is found here to bind Sig-1R as an agonist that causes the dissociation of Sig-1R from its cognate partner binding immunoglobulin protein. Remarkably, treatment of Sig-1R-KO neurons with exogenous myristic acid mitigates p35 accumulation, diminishes tau phosphorylation, and restores axon elongation. Our results define the involvement of Sig-1Rs in neurodegeneration and provide a mechanistic explanation that Sig-1Rs help maintain proper tau phosphorylation by potentially carrying and providing myristic acid to p35 for enhanced p35 degradation to circumvent the formation of overreactive cdk5/p25.
C1 [Tsai, Shang-Yi A.; Pokrass, Michael J.; Klauer, Neal R.; Nohara, Hiroshi; Su, Tsung-Ping] NIDA, Cellular Pathobiol Sect, Integrat Neurosci Res Branch, Intramural Res Program,NIH,US Dept HHS, Baltimore, MD 21224 USA.
RP Tsai, SYA (reprint author), NIDA, Cellular Pathobiol Sect, Integrat Neurosci Res Branch, Intramural Res Program,NIH,US Dept HHS, Baltimore, MD 21224 USA.
EM stsai@intra.nida.nih.gov; tsu@intra.nida.nih.gov
FU Intramural Research Program of the National Institute on Drug Abuse,
National Institutes of Health, US Department of Health and Human
Services
FX We thank Dr. Li-Huei Tsai for providing p35 plasmid and Dr. Peter Davies
for providing mouse MC-1 and mouse PHF-1 antibodies. This work was
supported by the Intramural Research Program of the National Institute
on Drug Abuse, National Institutes of Health, US Department of Health
and Human Services.
NR 59
TC 12
Z9 13
U1 1
U2 2
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 MAY 26
PY 2015
VL 112
IS 21
BP 6742
EP 6747
DI 10.1073/pnas.1422001112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CJ1AJ
UT WOS:000355213200062
PM 25964330
ER
PT J
AU Reveley, C
Seth, AK
Pierpaoli, C
Silva, AC
Yu, D
Saunders, RC
Leopold, DA
Ye, FQ
AF Reveley, Colin
Seth, Anil K.
Pierpaoli, Carlo
Silva, Afonso C.
Yu, David
Saunders, Richard C.
Leopold, David A.
Ye, Frank Q.
TI Superficial white matter fiber systems impede detection of long-range
cortical connections in diffusion MR tractography
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE diffusion MRI; tractography; neuroanatomy; white matter; connectome
ID MACAQUE MONKEY; HUMAN BRAIN; CEREBRAL-CORTEX; PATHWAYS; TISSUE; AREAS;
RECONSTRUCTION; NEUROANATOMY; VALIDATION; PRINCIPLES
AB In vivo tractography based on diffusion magnetic resonance imaging (dMRI) has opened new doors to study structure-function relationships in the human brain. Initially developed to map the trajectory of major white matter tracts, dMRI is used increasingly to infer long-range anatomical connections of the cortex. Because axonal projections originate and terminate in the gray matter but travel mainly through the deep white matter, the success of tractography hinges on the capacity to follow fibers across this transition. Here we demonstrate that the complex arrangement of white matter fibers residing just under the cortical sheet poses severe challenges for long-range tractography over roughly half of the brain. We investigate this issue by comparing dMRI from very-high-resolution ex vivo macaque brain specimens with histological analysis of the same tissue. Using probabilistic tracking from pure gray and white matter seeds, we found that similar to 50% of the cortical surface was effectively inaccessible for long-range diffusion tracking because of dense white matter zones just beneath the infragranular layers of the cortex. Analysis of the corresponding myelin-stained sections revealed that these zones colocalized with dense and uniform sheets of axons running mostly parallel to the cortical surface, most often in sulcal regions but also in many gyral crowns. Tracer injection into the sulcal cortex demonstrated that at least some axonal fibers pass directly through these fiber systems. Current and future high-resolution dMRI studies of the human brain will need to develop methods to overcome the challenges posed by superficial white matter systems to determine long-range anatomical connections accurately.
C1 [Reveley, Colin; Seth, Anil K.] Univ Sussex, Sch Engn & Informat, Sackler Ctr Consciousness Sci, Brighton BN1 9QJ, E Sussex, England.
[Pierpaoli, Carlo] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Pediat Imaging & Tissue Sci, NIH, Bethesda, MD 20892 USA.
[Silva, Afonso C.] NINDS, Cerebral Microcirculat Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
[Yu, David; Leopold, David A.; Ye, Frank Q.] NINDS, Neurophysiol Imaging Facil, NIMH, Bethesda, MD 20892 USA.
[Yu, David; Leopold, David A.; Ye, Frank Q.] NEI, NIH, Bethesda, MD 20892 USA.
[Saunders, Richard C.; Leopold, David A.] NIMH, Lab Neuropsychol, NIH, Bethesda, MD 20892 USA.
RP Leopold, DA (reprint author), NINDS, Neurophysiol Imaging Facil, NIMH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM LeopoldD@mail.nih.gov
OI Leopold, David/0000-0002-1345-6360
FU National Institute of Mental Health; National Institute of Neurological
Disorders and Stroke; National Eye Institute; School of Informatics at
the University of Sussex; Dr. Mortimer and Theresa Sackler Foundation
FX We thank Dr. Cibu Thomas for critical comments on the manuscript and
Drs. Donna Dierker, Tim Coalson, and Matt Glasser for advice and
discussion, and Drs. Hellmut Merkle, Daniel Papoti, and Charles Zhu for
technical assistance. This work was supported by the Intramural Research
Programs of the National Institute of Mental Health, National Institute
of Neurological Disorders and Stroke, and the National Eye Institute.
C.R. and A.K.S. received support from the School of Informatics at the
University of Sussex and the Dr. Mortimer and Theresa Sackler
Foundation.
NR 57
TC 42
Z9 42
U1 3
U2 6
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 MAY 26
PY 2015
VL 112
IS 21
BP E2820
EP E2828
DI 10.1073/pnas.1418198112
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CJ1AJ
UT WOS:000355213200014
PM 25964365
ER
PT J
AU Murley, A
Sarsam, RD
Toulmay, A
Yamada, J
Prinz, WA
Nunnari, J
AF Murley, Andrew
Sarsam, Reta D.
Toulmay, Alexandre
Yamada, Justin
Prinz, William A.
Nunnari, Jodi
TI Ltc1 is an ER-localized sterol transporter and a component of
ER-mitochondria and ER-vacuole contacts
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID SACCHAROMYCES-CEREVISIAE; CRYSTAL-STRUCTURE; REPEAT PROTEINS; YEAST;
COMPLEX; IMPORT; VAC8P; INHERITANCE; RECEPTOR; BINDING
AB Organelle contact sites perform fundamental functions in cells, including lipid and ion homeostasis, membrane dynamics, and signaling. Using a forward proteomics approach in yeast, we identified new ER-mitochondria and ER-vacuole contacts specified by an uncharacterized protein, Ylr072w. Ylr072w is a conserved protein with GRAM and VASt domains that selectively transports sterols and is thus termed Ltc1, for Lipid transfer at contact site 1. Ltc1 localized to ER-mitochondria and ER-vacuole contacts via the mitochondrial import receptors Tom70/71 and the vacuolar protein Vac8, respectively. At mitochondria, Ltc1 was required for cell viability in the absence of Mdm34, a subunit of the ER -mitochondria encounter structure. At vacuoles, Ltc1 was required for sterol-enriched membrane domain formation in response to stress. Increasing the proportion of Ltc1 at vacuoles was sufficient to induce sterol-enriched vacuolar domains without stress. Thus, our data support a model in which Ltc1 is a sterol-dependent regulator of organelle and cellular homeostasis via its dual localization to ER- mitochondria and ER-vacuole contact sites.
C1 [Murley, Andrew; Sarsam, Reta D.; Yamada, Justin; Nunnari, Jodi] Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA.
[Toulmay, Alexandre; Prinz, William A.] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Nunnari, J (reprint author), Univ Calif Davis, Dept Mol & Cellular Biol, Davis, CA 95616 USA.
EM jmnunnari@ucdavis.edu
FU National Institutes of Health (NIH) [5T32GM007377-34]; NIH [R01GM062942,
R01GM097432, R01GM106019]
FX A. Murley was supported by National Institutes of Health (NIH) training
grant 5T32GM007377-34; J. Nunnari is supported by NIH grants
R01GM062942, R01GM097432, and R01GM106019.
NR 53
TC 32
Z9 35
U1 2
U2 7
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0021-9525
EI 1540-8140
J9 J CELL BIOL
JI J. Cell Biol.
PD MAY 25
PY 2015
VL 209
IS 4
BP 539
EP 548
DI 10.1083/jcb.201502033
PG 10
WC Cell Biology
SC Cell Biology
GA CJ6ZO
UT WOS:000355643900011
PM 25987606
ER
PT J
AU Carvalheiro, T
Gomes, D
Pinto, LA
Ines, L
Lopes, A
Henriques, A
Pedreiro, S
Martinho, A
Trindade, H
Young, HA
da Silva, JAP
Paiva, A
AF Carvalheiro, Tiago
Gomes, Diane
Pinto, Ligia A.
Ines, Luis
Lopes, Ana
Henriques, Ana
Pedreiro, Susana
Martinho, Antonio
Trindade, Helder
Young, Howard A.
Pereira da Silva, Jose Antonio
Paiva, Artur
TI Sera from patients with active systemic lupus erythematosus patients
enhance the toll-like receptor 4 response in monocyte subsets
SO JOURNAL OF INFLAMMATION-LONDON
LA English
DT Article
DE Systemic lupus erythematosus; Serum; Cytokines; Toll like receptor 4;
Classical monocytes; Non-classical monocytes; Myeloid dendritic cells
ID DISEASE-ACTIVITY INDEX; BLOOD DENDRITIC CELLS; MONONUCLEAR-CELLS; IGG;
PATHOGENESIS; ACTIVATION; COMPLEXES; TNF; DIFFERENTIATION;
MICROPARTICLES
AB Background: Systemic Lupus Erythematosus (SLE) is an auto-immune disease whose complex pathogenesis remains unraveled. Here we aim to explore the inflammatory ability of SLE patients' sera upon peripheral blood (PB) monocyte subsets and myeloid dendritic cells (mDCs) obtained from healthy donors.
Methods: In this study we included 11 SLE patients with active disease (ASLE), 11 with inactive disease (ISLE) and 10 healthy controls (HC). PB from healthy donors was stimulated with patients' sera, toll-like receptor (TLR) 4 ligand lipopolysaccharide or both. The intracellular production of TNF-alpha was evaluated in classical, non-classical monocytes and mDCs, using flow cytometry. TNF-alpha mRNA expression was assessed in all these purified cells, after sera treatment.
Results: We found that sera of SLE patients did not change spontaneous TNF-alpha production by monocytes or dendritic cells. However, upon stimulation of TLR4, the presence of sera from ASLE patients, but not ISLE, significantly increased the intracellular expression of TNF-alpha in classical and non-classical monocytes. This ability was related to titers anti-double stranded DNA antibodies in the serum. High levels of anti-TNF-alpha in the patients' sera were associated with increased TNF-alpha expression by co-cultured mDCs. No relationship was found with the levels of a wide variety of other pro-inflammatory cytokines. A slight increase of TNF-alpha mRNA expression was observed in these purified cells when they were cultured only in the presence of SLE serum.
Conclusions: Our data suggest that SLE sera induce an abnormal in vitro TLR4 response in classical and non-classical monocytes, reflected by a higher TNF-alpha intracellular expression. These effects may be operative in the pathogenesis of SLE.
C1 [Carvalheiro, Tiago; Lopes, Ana; Pedreiro, Susana; Martinho, Antonio; Trindade, Helder; Paiva, Artur] Portuguese Inst Blood & Transplantat, Blood & Transplantat Ctr Coimbra, P-3041861 Coimbra, Portugal.
[Gomes, Diane; Paiva, Artur] Coll Hlth Technol Coimbra, P-3046854 Coimbra, Portugal.
[Pinto, Ligia A.] Frederick Natl Lab Canc Res, HPV Immunol Lab, Frederick, MD 21702 USA.
[Ines, Luis; Pereira da Silva, Jose Antonio] Ctr Hosp & Univ Coimbra, Dept Rheumatol, P-3000075 Coimbra, Portugal.
[Ines, Luis; Henriques, Ana; Pereira da Silva, Jose Antonio] Univ Coimbra, Fac Med, P-3000548 Coimbra, Portugal.
[Ines, Luis] Univ Beira Interior, Sch Hlth Sci, P-6200506 Covilha, Portugal.
[Young, Howard A.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA.
RP Paiva, A (reprint author), Portuguese Inst Blood & Transplantat, Blood & Transplantat Ctr Coimbra, P-3041861 Coimbra, Portugal.
EM artur.paiva@ipst.min-saude.pt
OI Henriques, Ana/0000-0002-5096-791X; Da Silva, Jose/0000-0002-2782-6780
FU Portuguese Society of Rheumatology (SPR): "Bolsa de Investigacao na area
das Doencas Reumaticas Inflamatorias - Bolsa SPR/MSD"; Intramural
Research Program of the NIH, National Cancer Institute
FX This work was partially supported by research grant from the Portuguese
Society of Rheumatology (SPR): "Bolsa de Investigacao na area das
Doencas Reumaticas Inflamatorias - Bolsa SPR/MSD 2014" and by the
Intramural Research Program of the NIH, National Cancer Institute.
NR 46
TC 1
Z9 1
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-9255
J9 J INFLAMM-LOND
JI J. Inflamm.-Lond.
PD MAY 23
PY 2015
VL 12
AR 38
DI 10.1186/s12950-015-0083-2
PG 9
WC Immunology
SC Immunology
GA CJ3QJ
UT WOS:000355398600001
PM 26038677
ER
PT J
AU Russ, DE
Ho, KY
Longo, NS
AF Russ, Daniel E.
Kwan-Yuet Ho
Longo, Nancy S.
TI HTJoinSolver: Human immunoglobulin VDJ partitioning using approximate
dynamic programming constrained by conserved motifs
SO BMC BIOINFORMATICS
LA English
DT Article
ID MEMORY B-CELLS; SOMATIC HYPERMUTATION; HUMAN-ANTIBODY; SEQUENCES;
IDENTIFICATION; ALGORITHM; ALIGNMENT; DATABASE; HIV-1
AB Background: Partitioning the human immunoglobulin variable region into variable (V), diversity (D), and joining (J) segments is a common sequence analysis step. We introduce a novel approximate dynamic programming method that uses conserved immunoglobulin gene motifs to improve performance of aligning V-segments of rearranged immunoglobulin (Ig) genes. Our new algorithm enhances the former JOINSOLVER algorithm by processing sequences with insertions and/or deletions (indels) and improves the efficiency for large datasets provided by high throughput sequencing.
Results: In our simulations, which include rearrangements with indels, the V-matching success rate improved from 61% for partial alignments of sequences with indels in the original algorithm to over 99% in the approximate algorithm. An improvement in the alignment of human VDJ rearrangements over the initial JOINSOLVER algorithm was also seen when compared to the Stanford. S22 human Ig dataset with an online VDJ partitioning software evaluation tool.
Conclusions: HTJoinSolver can rapidly identify V- and J-segments with indels to high accuracy for mutated sequences when the mutation probability is around 30% and 20% respectively. The D-segment is much harder to fit even at 20% mutation probability. For all segments, the probability of correctly matching V, D, and J increases with our alignment score.
C1 [Russ, Daniel E.; Kwan-Yuet Ho] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Longo, Nancy S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Russ, DE (reprint author), NIH, Div Computat Biosci, Ctr Informat Technol, 12 South Dr, Bethesda, MD 20892 USA.
EM druss@mail.nih.gov
OI Russ, Daniel/0000-0003-4040-4416
FU Intramural Research Programs of the Center for Information Technology;
National Institutes of Health; Vaccine Research Center, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health
FX The authors wish to thank Dr. John Mascola for the opportunity to
develop HTJoinSolver. This work was supported by the Intramural Research
Programs of the Center for Information Technology [DER, K-YH], National
Institutes of Health and the Vaccine Research Center, National Institute
of Allergy and Infectious Diseases, National Institutes of Health [NSL].
NR 21
TC 2
Z9 2
U1 1
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD MAY 23
PY 2015
VL 16
AR 170
DI 10.1186/s12859-015-0589-x
PG 11
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA CI7GH
UT WOS:000354930500001
PM 26001675
ER
PT J
AU Khor, B
Gagnon, JD
Goel, G
Roche, MI
Conway, KL
Tran, K
Aldrich, LN
Sundberg, TB
Paterson, AM
Mordecai, S
Dombkowski, D
Schirmer, M
Tan, PH
Bhan, AK
Roychoudhuri, R
Restifo, NP
O'Shea, JJ
Medoff, BD
Shamji, AF
Schreiber, SL
Sharpe, AH
Shaw, SY
Xavier, RJ
AF Khor, Bernard
Gagnon, John D.
Goel, Gautam
Roche, Marly I.
Conway, Kara L.
Tran, Khoa
Aldrich, Leslie N.
Sundberg, Thomas B.
Paterson, Alison M.
Mordecai, Scott
Dombkowski, David
Schirmer, Melanie
Tan, Pauline H.
Bhan, Atul K.
Roychoudhuri, Rahul
Restifo, Nicholas P.
O'Shea, John J.
Medoff, Benjamin D.
Shamji, Alykhan F.
Schreiber, Stuart L.
Sharpe, Arlene H.
Shaw, Stanley Y.
Xavier, Ramnik J.
TI The kinase DYRK1A reciprocally regulates the differentiation of Th17 and
regulatory T cells
SO ELIFE
LA English
DT Article
ID INFLAMMATORY-BOWEL-DISEASE; PATHOGENIC T(H)17 CELLS; RETINOIC-ACID;
TRANSCRIPTIONAL SIGNATURE; FOXP3 EXPRESSION; GENE-EXPRESSION; SMALL
MOLECULES; NUCLEAR FACTOR; DOWN-SYNDROME; REG-CELLS
AB The balance between Th17 and T regulatory (T-reg) cells critically modulates immune homeostasis, with an inadequate Treg response contributing to inflammatory disease. Using an unbiased chemical biology approach, we identified a novel role for the dual specificity tyrosinephosphorylation-regulated kinase DYRK1A in regulating this balance. Inhibition of DYRK1A enhances Treg differentiation and impairs Th17 differentiation without affecting known pathways of T-reg/Th17 differentiation. Thus, DYRK1A represents a novel mechanistic node at the branch point between commitment to either Treg or Th17 lineages. Importantly, both Treg cells generated using the DYRK1A inhibitor harmine and direct administration of harmine itself potently attenuate inflammation in multiple experimental models of systemic autoimmunity and mucosal inflammation. Our results identify DYRK1A as a physiologically relevant regulator of T-reg cell differentiation and suggest a broader role for other DYRK family members in immune homeostasis. These results are discussed in the context of human diseases associated with dysregulated DYRK activity.
C1 [Khor, Bernard; Conway, Kara L.; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA.
[Khor, Bernard; Conway, Kara L.; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA USA.
[Khor, Bernard; Goel, Gautam; Conway, Kara L.; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA.
[Khor, Bernard; Gagnon, John D.; Conway, Kara L.; Aldrich, Leslie N.; Sundberg, Thomas B.; Schirmer, Melanie; Shamji, Alykhan F.; Schreiber, Stuart L.; Xavier, Ramnik J.] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Khor, Bernard; Mordecai, Scott; Dombkowski, David; Bhan, Atul K.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA.
[Roche, Marly I.; Medoff, Benjamin D.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA.
[Tran, Khoa; Tan, Pauline H.; Shaw, Stanley Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA.
[Aldrich, Leslie N.; Schreiber, Stuart L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
[Paterson, Alison M.; Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA.
[Paterson, Alison M.; Sharpe, Arlene H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Roychoudhuri, Rahul; Restifo, Nicholas P.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
RP Xavier, RJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA.
EM xavier@molbio.mgh.harvard.edu
RI Roychoudhuri, Rahul/A-7442-2010;
OI Roychoudhuri, Rahul/0000-0002-5392-1853; Gagnon,
John/0000-0001-6208-5781; Schirmer, Melanie/0000-0001-6456-3679; Khor,
Bernard/0000-0003-4689-5092; Restifo, Nicholas P./0000-0003-4229-4580
NR 84
TC 5
Z9 5
U1 0
U2 0
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD MAY 22
PY 2015
VL 4
AR e05920
DI 10.7554/eLife.05920
PG 27
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DJ5QI
UT WOS:000374264300001
ER
PT J
AU Newman, DJ
Cragg, GM
AF Newman, David J.
Cragg, Gordon M.
TI Endophytic and epiphytic microbes as "sources" of bioactive agents
SO FRONTIERS IN CHEMISTRY
LA English
DT Review
DE endophyte; epiphyte; natural product sources; ultured microbes; novel
sources
ID TUNICATE ECTEINASCIDIA-TURBINATA; FUNGUS RHIZOPUS-MICROSPORUS;
NATURAL-PRODUCTS; HUPERZIA-SERRATA; BACTERIAL ENDOSYMBIONT; ALKALOID
SWAINSONINE; ANTICANCER AGENTS; GENE-CLUSTER; SAFRAMYCIN-A; DIDEMNIN-B
AB Beginning with the report by Stierle and Strobel in 1993 on taxol(R) production by an endophytic fungus (Stierle et al., 1993), it is possible that a number of the agents now used as leads to treatments of diseases in man, are not produced by the plant or invertebrate host from which they were first isolated and identified. They are probably the product of a microbe in, on or around the macroorganism. At times there is an intricate "dance" between a precursor produced by a microbe, and interactions within the macroorganism, or in certain cases, a fungus, that ends up with the production of a novel agent that has potential as a treatment for a human disease. This report will give examples from insects, plants, and marine invertebrates.
C1 [Newman, David J.; Cragg, Gordon M.] NCI, Nat Prod Branch, Frederick, MD 21701 USA.
EM djnewman664@verizon.net
NR 87
TC 10
Z9 10
U1 17
U2 41
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
EI 2296-2646
J9 FRONT CHEM
JI Front. Chem.
PD MAY 22
PY 2015
VL 3
AR 34
DI 10.3389/fchem.2015.00034
PG 13
WC Chemistry, Multidisciplinary
SC Chemistry
GA DI2WL
UT WOS:000373359700001
PM 26052511
ER
PT J
AU Earl, J
Rico, D
Carrillo-de-Santa-Pau, E
Rodriguez-Santiago, B
Mendez-Pertuz, M
Auer, H
Gomez, G
Grossman, HB
Pisano, DG
Schulz, WA
Perez-Jurado, LA
Carrato, A
Theodorescu, D
Chanock, S
Valencia, A
Real, FX
AF Earl, Julie
Rico, Daniel
Carrillo-de-Santa-Pau, Enrique
Rodriguez-Santiago, Benjamin
Mendez-Pertuz, Marinela
Auer, Herbert
Gomez, Gonzalo
Grossman, Herbert Barton
Pisano, David G.
Schulz, Wolfgang A.
Perez-Jurado, Luis A.
Carrato, Alfredo
Theodorescu, Dan
Chanock, Stephen
Valencia, Alfonso
Real, Francisco X.
TI The UBC-40 Urothelial Bladder Cancer cell line index: a genomic resource
for functional studies
SO BMC GENOMICS
LA English
DT Article
DE Urothelial bladder cancer; Cell line; Genomics; Mutation; Oncogene;
Tumor suppressor
ID COPY NUMBER ALTERATIONS; FGFR3 MUTATIONS; IN-VIVO; CARCINOMA; P53;
EXPRESSION; HYBRIDIZATION; PROGRESSION; PROMOTER; VARIANTS
AB Background: Urothelial bladder cancer is a highly heterogeneous disease. Cancer cell lines are useful tools for its study. This is a comprehensive genomic characterization of 40 urothelial bladder carcinoma (UBC) cell lines including information on origin, mutation status of genes implicated in bladder cancer (FGFR3, PIK3CA, TP53, and RAS), copy number alterations assessed using high density SNP arrays, uniparental disomy (UPD) events, and gene expression.
Results: Based on gene mutation patterns and genomic changes we identify lines representative of the FGFR3-driven tumor pathway and of the TP53/RB tumor suppressor-driven pathway. High-density array copy number analysis identified significant focal gains (1q32, 5p13.1 12, 7q11, and 7q33) and losses (i.e. 6p22.1) in regions altered in tumors but not previously described as affected in bladder cell lines. We also identify new evidence for frequent regions of UPD, often coinciding with regions reported to be lost in tumors. Previously undescribed chromosome X losses found in UBC lines also point to potential tumor suppressor genes. Cell lines representative of the FGFR3-driven pathway showed a lower number of UPD events.
Conclusions: Overall, there is a predominance of more aggressive tumor subtypes among the cell lines. We provide a cell line classification that establishes their relatedness to the major molecularly-defined bladder tumor subtypes. The compiled information should serve as a useful reference to the bladder cancer research community and should help to select cell lines appropriate for the functional analysis of bladder cancer genes, for example those being identified through massive parallel sequencing.
C1 [Earl, Julie; Carrillo-de-Santa-Pau, Enrique; Mendez-Pertuz, Marinela; Real, Francisco X.] Spanish Natl Canc Res Ctr, CNIO, F BBVA Canc Cell Biol Programme, Epithelial Carcinogenesis Grp, Madrid, Spain.
[Earl, Julie; Valencia, Alfonso] Hosp Ramon & Cajal, Med Oncol Serv, E-28034 Madrid, Spain.
[Rico, Daniel; Valencia, Alfonso] Spanish Natl Canc Res Ctr, CNIO, Struct Biol & Biocomp Programme, Struct Computat Biol Grp, Madrid, Spain.
[Rodriguez-Santiago, Benjamin] qGenomics, Quantitat Genom Med Lab, Barcelona, Spain.
[Rodriguez-Santiago, Benjamin; Perez-Jurado, Luis A.; Real, Francisco X.] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain.
[Rodriguez-Santiago, Benjamin; Perez-Jurado, Luis A.] Ctr Invest Biomed Red Enfermedades Raras, Barcelona, Spain.
[Auer, Herbert] Parc Cient Barcelona, Inst Recerca Biomed Barcelona, Barcelona, Spain.
[Gomez, Gonzalo; Pisano, David G.] Spanish Natl Canc Res Ctr, CNIO, Struct Biol & Biocomp Programme, Bioinformat Unit, Madrid, Spain.
[Grossman, Herbert Barton] Univ Texas Houston, MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA.
[Schulz, Wolfgang A.] Univ Dusseldorf, Dept Urol, Dusseldorf, Germany.
[Theodorescu, Dan] Univ Colorado, Ctr Comprehens Canc, Aurora, CO 80045 USA.
[Chanock, Stephen] NCI, Translat Genom Lab, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Real, Francisco X.] Ctr Nacl Invest Oncol, Canc Cell Biol Programme, Madrid 28029, Spain.
RP Real, FX (reprint author), Spanish Natl Canc Res Ctr, CNIO, F BBVA Canc Cell Biol Programme, Epithelial Carcinogenesis Grp, Madrid, Spain.
EM preal@cnio.es
RI Valencia, Alfonso/I-3127-2015; Perez Jurado, Luis Alberto/M-7706-2015;
Gomez-Lopez, Gonzalo/D-9123-2016; Pisano, David/N-5817-2014;
OI Valencia, Alfonso/0000-0002-8937-6789; Gomez-Lopez,
Gonzalo/0000-0002-4146-0551; Pisano, David/0000-0002-4895-4124;
Rodriguez-Santiago, Benjamin/0000-0003-1167-3852; Rico,
Daniel/0000-0002-6561-2310
FU Consolider ONCOBIO, Red Tematica de Investigacion Cooperativa en Cancer
(RTICC) [SAF2011-15934-E]; Asociacion Espanola Contra el Cancer; NIH
[CA089715]; National Institutes of Health [CA075115, CA104106];
[EU-FP7-201663]
FX This work was supported, in part, by grants Consolider ONCOBIO,
SAF2011-15934-E, Red Tematica de Investigacion Cooperativa en Cancer
(RTICC)]; Asociacion Espanola Contra el Cancer, EU-FP7-201663, and NIH
RO-1 (CA089715); and National Institutes of Health grants CA075115 and
CA104106 (to D.T.).
NR 49
TC 13
Z9 13
U1 0
U2 5
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 MAY 22
PY 2015
VL 16
AR 403
DI 10.1186/s12864-015-1450-3
PG 16
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA CK7IH
UT WOS:000356405500001
PM 25997541
ER
PT J
AU Kirtland, KA
Saaddine, JB
Geiss, LS
Thompson, TJ
Cotch, MF
Lee, PP
AF Kirtland, Karen A.
Saaddine, Jinan B.
Geiss, Linda S.
Thompson, Ted J.
Cotch, Mary F.
Lee, Paul P.
TI Geographic Disparity of Severe Vision Loss - United States, 2009-2013
SO MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT
LA English
DT Article
ID VISUAL IMPAIRMENT; US ADULTS; HEALTH
C1 [Kirtland, Karen A.; Saaddine, Jinan B.; Geiss, Linda S.; Thompson, Ted J.] CDC, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA.
[Cotch, Mary F.] NEI, NIH, Bethesda, MD USA.
[Lee, Paul P.] Univ Michigan, Sch Med, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA.
RP Kirtland, KA (reprint author), CDC, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA.
EM kkirtland@cdc.gov
FU Intramural NIH HHS [Z99 EY999999]
NR 10
TC 1
Z9 1
U1 1
U2 3
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 0149-2195
EI 1545-861X
J9 MMWR-MORBID MORTAL W
JI MMWR-Morb. Mortal. Wkly. Rep.
PD MAY 22
PY 2015
VL 64
IS 19
BP 513
EP 517
PG 5
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CI7PV
UT WOS:000354957300002
PM 25996092
ER
PT J
AU Finkel, T
Menazza, S
Holmstrom, KM
Parks, RJ
Liu, JL
Sun, JH
Liu, J
Pan, X
Murphy, E
AF Finkel, Toren
Menazza, Sara
Holmstroem, Kira M.
Parks, Randi J.
Liu, Julia
Sun, Junhui
Liu, Jie
Pan, Xin
Murphy, Elizabeth
TI The Ins and Outs of Mitochondrial Calcium
SO CIRCULATION RESEARCH
LA English
DT Review
DE calcium signaling; cell death; mitochondria
ID PERMEABILITY TRANSITION PORE; CYTOSOLIC FREE CALCIUM; MEDIATED
CELL-DEATH; CA2+ UPTAKE; HEART-MITOCHONDRIA; OXIDATIVE-PHOSPHORYLATION;
ESSENTIAL COMPONENT; CYCLOSPORINE-A; ISCHEMIA/REPERFUSION INJURY;
CARDIAC MITOCHONDRIA
AB Calcium is thought to play an important role in regulating mitochondrial function. Evidence suggests that an increase in mitochondrial calcium can augment ATP production by altering the activity of calcium-sensitive mitochondrial matrix enzymes. In contrast, the entry of large amounts of mitochondrial calcium in the setting of ischemia-reperfusion injury is thought to be a critical event in triggering cellular necrosis. For many decades, the details of how calcium entered the mitochondria remained a biological mystery. In the past few years, significant progress has been made in identifying the molecular components of the mitochondrial calcium uniporter complex. Here, we review how calcium enters and leaves the mitochondria, the growing insight into the topology, stoichiometry and function of the uniporter complex, and the early lessons learned from some initial mouse models that genetically perturb mitochondrial calcium homeostasis.
C1 [Finkel, Toren; Holmstroem, Kira M.; Liu, Julia; Liu, Jie] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
[Menazza, Sara; Parks, Randi J.; Sun, Junhui; Murphy, Elizabeth] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Pan, Xin] Natl Ctr Biomed Anal, Cell Biol Lab, Beijing, Peoples R China.
RP Finkel, T (reprint author), 10 Ctr Dr,Bldg 10 CRC 5-3330, Bethesda, MD 20892 USA.
EM finkelt@nih.gov; murphy1@mail.nih.gov
OI Holmstrom, Kira/0000-0001-6434-7909
FU NHLBI; Leducq Foundation
FX This work was supported by NHLBI Intramural funds and a grant from the
Leducq Foundation.
NR 79
TC 23
Z9 23
U1 3
U2 18
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7330
EI 1524-4571
J9 CIRC RES
JI Circ.Res.
PD MAY 22
PY 2015
VL 116
IS 11
BP 1810
EP 1819
DI 10.1161/CIRCRESAHA.116.305484
PG 10
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA CI6IE
UT WOS:000354861500013
PM 25999421
ER
PT J
AU Lungu, C
Muegge, K
Jeltsch, A
Jurkowska, RZ
AF Lungu, Cristiana
Muegge, Kathrin
Jeltsch, Albert
Jurkowska, Renate Z.
TI An ATPase-Deficient Variant of the SNF2 Family Member HELLS Shows
Altered Dynamics at Pericentromeric Heterochromatin
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
ID DNA METHYLATION; CELLULAR PROLIFERATION; HISTONE METHYLATION; MOLECULAR
MACHINES; SILENT CHROMATIN; MAMMALIAN-CELLS; REPEAT ELEMENTS;
GENE-EXPRESSION; SNF2-LIKE GENE; NUCLEAR-MATRIX
AB The HELLS (helicase, lymphoid specific, also known as lymphoid-specific helicase) protein is related to the SNF2 (sucrose non-fermentable 2) family of chromatin remodeling ATPases. It is required for efficient DNA methylation in mammals, particularly at heterochromatin-located repetitive sequences. In this study, we investigated the interaction of HELLS with chromatin and used an ATPase-deficient HELLS variant to address the role of ATP hydrolysis in this process. Chromatin fractionation experiments demonstrated that, in the absence of the ATPase activity, HELLS is retained at the nuclear matrix compartment, defined in part by lamin B1. Microscopy studies revealed a stronger association of the ATPase-deficient mutant with heterochromatin. These results were further supported by fluorescence recovery after photobleaching measurements, which showed that, at heterochromatic sites, wild-type HELLS is very dynamic, with a recovery half-time of 0.8 s and a mobile protein fraction of 61%. In contrast, the ATPase-deficient mutant displayed 4.5-s recovery half-time and a reduction in the mobile fraction to 30%. We also present evidence suggesting that, in addition to the ATPase activity, a functional H3K9me3 signaling pathway contributes to an efficient release of HELLS from pericentromeric chromatin. Overall, our results show that a functional ATPase activity is not required for the recruitment of HELLS to heterochromatin, but it is important for the release of the enzyme from these sites. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Lungu, Cristiana; Jeltsch, Albert; Jurkowska, Renate Z.] Univ Stuttgart, Inst Biochem, D-70569 Stuttgart, Germany.
[Muegge, Kathrin] NCI, Mouse Canc Genet Program, Basic Sci Program, Leidos Biomed Res Inc, Frederick, MD 21702 USA.
RP Jurkowska, RZ (reprint author), Univ Stuttgart, Inst Biochem, Pfaffenwaldring 55, D-70569 Stuttgart, Germany.
EM renata.jurkowska@ibc.uni-stuttgart.de
RI Jeltsch, Albert/O-7404-2014
OI Jeltsch, Albert/0000-0001-6113-9290
FU Carl Zeiss foundation; Frederick National Laboratory for Cancer
Research, National Institutes of Health [HHSN261200800001E]
FX C.L. and R.Z.J. have been financed by fellowships from the Carl Zeiss
foundation. K.M. has been funded in part with federal funds from the
Frederick National Laboratory for Cancer Research, National Institutes
of Health, under contract 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.
NR 62
TC 1
Z9 1
U1 1
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
EI 1089-8638
J9 J MOL BIOL
JI J. Mol. Biol.
PD MAY 22
PY 2015
VL 427
IS 10
BP 1903
EP 1915
DI 10.1016/j.jmb.2015.03.014
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CH6KH
UT WOS:000354145000005
PM 25823553
ER
PT J
AU Dey, S
Scullen, T
Noguchi, CT
AF Dey, Soumyadeep
Scullen, Tyler
Noguchi, Constance Toni
TI Erythropoietin negatively regulates pituitary ACTH secretion
SO BRAIN RESEARCH
LA English
DT Article
DE Erythropoietin; Adrenocorticotropic hormone; Pituitary gland
ID CORTISOL METABOLISM; HEMODIALYZED PATIENTS; MESSENGER-RNA; HUMAN
OBESITY; ADRENAL AXIS; RECEPTOR; EXPRESSION; STRESS; BRAIN; CELLS
AB Erythropoietin (Epo) and Epo-receptor (EpoR) signaling, in addition to its classical role in erythropoiesis, exhibit a protective response in non-hematopoietic tissues. Mice with EpoR expression restricted to only hematopoietic tissues (Delta EpoR(E)), become obese, have low energy expenditure, and are glucose intolerant and insulin resistant. In the arcuate nucleus of the mouse hypothalamus, EpoR expression co-localizes in proopiomelanocortin (POMC) neurons. In vivo high-dose Epo treatment increases hypothalamus POMC, reduces food intake and fat mass accumulation. Here we report that Epo treatment also decreases plasma concentration of the pituitary derived POMC peptide, adrenocorticotropic hormone (ACTH). Conversely, Delta EpoR(E) mice show reduced hypothalamus POMC and high plasma concentrations of ACTH. In the pituitary, POMC is synthesized in the corticotroph cells, and here we examine Epo effect on pituitary POMC expression using the AtT-20 mouse corticotroph pituitary cell line. In AtT-20 cells, enzyme immunoassay analysis showed that Epo inhibits ACTH secretion. This effect is post-translational, as Epo treatment did not affect POMC mRNA expression but increased intracellular levels of ACTH peptide. Moreover, Epo reduced the basal intracellular calcium (Ca2+) levels, suggesting an effect in the Ca2+-signaling pathway. In summary, our studies suggest a novel regulatory pathway of ACTH secretion in the pituitary via EpoR-signaling. The higher plasma ACTH level in Delta EpoR(E) mice also suggests a possible mechanism of deregulated pituitary function with loss of Epo-signaling. Published by Elsevier B.V.
C1 [Dey, Soumyadeep; Scullen, Tyler; Noguchi, Constance Toni] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
RP Noguchi, CT (reprint author), Mol Med Branch, 10 Ctr Dr,Room 9N319,MSC-1822, Bethesda, MD 20892 USA.
EM cnoguchi@helix.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases at the
National Institutes of Health [ZIA DK025061, ZIA DK025102]
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases (ZIA
DK025061 and ZIA DK025102) at the National Institutes of Health.
NR 37
TC 1
Z9 2
U1 2
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
EI 1872-6240
J9 BRAIN RES
JI Brain Res.
PD MAY 22
PY 2015
VL 1608
BP 14
EP 20
DI 10.1016/j.brainres.2015.02.052
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA CG8YH
UT WOS:000353601100002
PM 25765155
ER
PT J
AU Zhao, HY
Ghirlando, R
Alfonso, C
Arisaka, F
Attali, I
Bain, DL
Bakhtina, MM
Becker, DF
Bedwell, GJ
Bekdemir, A
Besong, TMD
Birck, C
Brautigam, CA
Brennerman, W
Byron, O
Bzowska, A
Chaires, JB
Chaton, CT
Colfen, H
Connaghan, KD
Crowley, KA
Curth, U
Daviter, T
Dean, WL
Diez, AI
Ebel, C
Eckert, DM
Eisele, LE
Eisenstein, E
England, P
Escalante, C
Fagan, JA
Fairman, R
Finn, RM
Fischle, W
de la Torre, JG
Gor, J
Gustafsson, H
Hall, D
Harding, SE
Cifre, JGH
Herr, AB
Howell, EE
Isaac, RS
Jao, SC
Jose, D
Kim, SJ
Kokona, B
Kornblatt, JA
Kosek, D
Krayukhina, E
Krzizike, D
Kusznir, EA
Kwon, H
Larson, A
Laue, TM
Le Roy, A
Leech, AP
Lilie, H
Luger, K
Luque-Ortega, JR
Ma, J
May, CA
Maynard, EL
Modrak-Wojcik, A
Mok, YF
Mucke, N
Nagel-Steger, L
Narlikar, GJ
Noda, M
Nourse, A
Obsil, T
Park, CK
Park, JK
Pawelek, PD
Perdue, EE
Perkins, SJ
Perugini, MA
Peterson, CL
Peverelli, MG
Piszczek, G
Prag, G
Prevelige, PE
Raynal, BDE
Rezabkova, L
Richter, K
Ringel, AE
Rosenberg, R
Rowe, AJ
Rufer, AC
Scott, DJ
Seravalli, JG
Solovyova, AS
Song, RJ
Staunton, D
Stoddard, C
Stott, K
Strauss, HM
Streicher, WW
Sumida, JP
Swygert, SG
Szczepanowski, RH
Tessmer, I
Toth, RT
Tripathy, A
Uchiyama, S
Uebel, SFW
Unzai, S
Gruber, AV
von Hippel, PH
Wandrey, C
Wang, SH
Weitzel, SE
Wielgus-Kutrowska, B
Wolberger, C
Wolff, M
Wright, E
Wu, YS
Wubben, JM
Schuck, P
AF Zhao, Huaying
Ghirlando, Rodolfo
Alfonso, Carlos
Arisaka, Fumio
Attali, Ilan
Bain, David L.
Bakhtina, Marina M.
Becker, Donald F.
Bedwell, Gregory J.
Bekdemir, Ahmet
Besong, Tabot M. D.
Birck, Catherine
Brautigam, Chad A.
Brennerman, William
Byron, Olwyn
Bzowska, Agnieszka
Chaires, Jonathan B.
Chaton, Catherine T.
Coelfen, Helmut
Connaghan, Keith D.
Crowley, Kimberly A.
Curth, Ute
Daviter, Tina
Dean, William L.
Diez, Ana I.
Ebel, Christine
Eckert, Debra M.
Eisele, Leslie E.
Eisenstein, Edward
England, Patrick
Escalante, Carlos
Fagan, Jeffrey A.
Fairman, Robert
Finn, Ron M.
Fischle, Wolfgang
Garcia de la Torre, Jose
Gor, Jayesh
Gustafsson, Henning
Hall, Damien
Harding, Stephen E.
Hernandez Cifre, Jose G.
Herr, Andrew B.
Howell, Elizabeth E.
Isaac, Richard S.
Jao, Shu-Chuan
Jose, Davis
Kim, Soon-Jong
Kokona, Bashkim
Kornblatt, Jack A.
Kosek, Dalibor
Krayukhina, Elena
Krzizike, Daniel
Kusznir, Eric A.
Kwon, Hyewon
Larson, Adam
Laue, Thomas M.
Le Roy, Aline
Leech, Andrew P.
Lilie, Hauke
Luger, Karolin
Luque-Ortega, Juan R.
Ma, Jia
May, Carrie A.
Maynard, Ernest L.
Modrak-Wojcik, Anna
Mok, Yee-Foong
Muecke, Norbert
Nagel-Steger, Luitgard
Narlikar, Geeta J.
Noda, Masanori
Nourse, Amanda
Obsil, Tomas
Park, Chad K.
Park, Jin-Ku
Pawelek, Peter D.
Perdue, Erby E.
Perkins, Stephen J.
Perugini, Matthew A.
Peterson, Craig L.
Peverelli, Martin G.
Piszczek, Grzegorz
Prag, Gali
Prevelige, Peter E.
Raynal, Bertrand D. E.
Rezabkova, Lenka
Richter, Klaus
Ringel, Alison E.
Rosenberg, Rose
Rowe, Arthur J.
Rufer, Arne C.
Scott, David J.
Seravalli, Javier G.
Solovyova, Alexandra S.
Song, Renjie
Staunton, David
Stoddard, Caitlin
Stott, Katherine
Strauss, Holger M.
Streicher, Werner W.
Sumida, John P.
Swygert, Sarah G.
Szczepanowski, Roman H.
Tessmer, Ingrid
Toth, Ronald T.
Tripathy, Ashutosh
Uchiyama, Susumu
Uebel, Stephan F. W.
Unzai, Satoru
Gruber, Anna Vitlin
von Hippel, Peter H.
Wandrey, Christine
Wang, Szu-Huan
Weitzel, Steven E.
Wielgus-Kutrowska, Beata
Wolberger, Cynthia
Wolff, Martin
Wright, Edward
Wu, Yu-Sung
Wubben, Jacinta M.
Schuck, Peter
TI A Multilaboratory Comparison of Calibration Accuracy and the Performance
of External References in Analytical Ultracentrifugation
SO PLOS ONE
LA English
DT Article
ID FLUORESCENCE-DETECTED SEDIMENTATION; SIZE-EXCLUSION CHROMATOGRAPHY;
FIELD-FLOW FRACTIONATION; SPINCO ULTRACENTRIFUGE; BEAD MODELS; VELOCITY;
AGGREGATION; PROTEINS; BIOPHARMACEUTICALS; HYDRODYNAMICS
AB Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 +/- 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of +/- 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies.
C1 [Zhao, Huaying; Ma, Jia; Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, Lab Cellular Imaging & Macromol Biophys, Dynam Macromol Assembly Sect, NIH, Bethesda, MD 20892 USA.
[Ghirlando, Rodolfo] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Alfonso, Carlos; Luque-Ortega, Juan R.] CSIC, Ctr Invest Biol, Analyt Ultracentrifugac & Light Scattering Facil, E-28040 Madrid, Spain.
[Arisaka, Fumio] Nihon Univ, Life Sci Res Ctr, Coll Bioresource Sci, Fujisawa, Kanagawa 2520880, Japan.
[Attali, Ilan; Prag, Gali; Gruber, Anna Vitlin] Tel Aviv Univ, Dept Biochem & Mol Biol, IL-69978 Tel Aviv, Israel.
[Bain, David L.; Connaghan, Keith D.] Univ Colorado Denver, Dept Pharmaceut Sci, Aurora, CO 80045 USA.
[Bakhtina, Marina M.] Ohio State Univ, Ctr Retrovirus Res, Dept Chem & Biochem, Columbus, OH 43210 USA.
[Bakhtina, Marina M.] Ohio State Univ, Ctr RNA Biol, Columbus, OH 43210 USA.
[Becker, Donald F.; Seravalli, Javier G.] Univ Nebraska, Redox Biol Ctr, Lincoln, NE 68588 USA.
[Bedwell, Gregory J.; Prevelige, Peter E.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA.
[Bekdemir, Ahmet] Ecole Polytech Fed Lausanne, Inst Mat, Supramol Nanomat & Interfaces Lab, CH-1015 Lausanne, Switzerland.
[Besong, Tabot M. D.; Harding, Stephen E.; Rowe, Arthur J.] Univ Nottingham, Sch Biosci, Natl Ctr Macromol Hydrodynam, Loughborough LE12 5RD, Leics, England.
[Birck, Catherine] Struct Biol Platform IGBMC, F-67400 Illkirch Graffenstaden, France.
[Brautigam, Chad A.] Univ Texas SW Med Ctr Dallas, Dept Biophys, Dallas, TX 75390 USA.
[Brennerman, William; Perdue, Erby E.] Beckman Coulter Inc, Div Life Sci, Indianapolis, IN 46268 USA.
[Byron, Olwyn] Univ Glasgow, Sch Life Sci, Glasgow G37 TT, Lanark, Scotland.
[Bzowska, Agnieszka; Modrak-Wojcik, Anna; Wielgus-Kutrowska, Beata] Univ Warsaw, Inst Expt Phys, Fac Phys, Div Biophys, PL-02089 Warsaw, Poland.
[Chaires, Jonathan B.; Dean, William L.] Univ Louisville, JG Brown Canc Ctr, Louisville, KY 40202 USA.
[Chaton, Catherine T.; Herr, Andrew B.] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA.
[Coelfen, Helmut; Rosenberg, Rose] Univ Konstanz, Phys Chem, D-78457 Constance, Germany.
[Crowley, Kimberly A.; Peterson, Craig L.; Swygert, Sarah G.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA.
[Curth, Ute] Hannover Med Sch, Inst Biophys Chem, D-30625 Hannover, Germany.
[Daviter, Tina] Univ London, Biol Biophys Ctr, Inst Struct & Mol, London WC1E 7HX, England.
[Daviter, Tina] UCL, London WC1E 7HX, England.
[Diez, Ana I.; Garcia de la Torre, Jose; Hernandez Cifre, Jose G.] Univ Murcia, Dept Phys Chem, Murcia 30071, Spain.
[Ebel, Christine; Le Roy, Aline] Univ Grenoble Alpes, IBS, F-38044 Grenoble, France.
[Ebel, Christine; Le Roy, Aline] CNRS, IBS, F-38044 Grenoble, France.
[Ebel, Christine; Le Roy, Aline] CEA, IBS, F-38044 Grenoble, France.
[Eckert, Debra M.] Univ Utah, Sch Med, Dept Biochem, Prot Interact Core, Salt Lake City, UT 84112 USA.
[Eisele, Leslie E.; Song, Renjie] New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12208 USA.
[Eisenstein, Edward] Univ Maryland, Fischell Dept Bioengn, Inst Biosci & Biotechnol Res, Rockville, MD 20850 USA.
[England, Patrick; Raynal, Bertrand D. E.] Inst Pasteur, Ctr Biophys Macromol & Interact, F-75724 Paris, France.
[Escalante, Carlos] Virginia Commonwealth Univ, Sch Med, Dept Physiol & Biophys, Richmond, VA 23220 USA.
[Fagan, Jeffrey A.] Natl Inst Stand & Technol, Mat Sci & Engn Lab, Gaithersburg, MD 20899 USA.
[Fairman, Robert; Kokona, Bashkim] Haverford Coll, Dept Biol, Haverford, PA 19041 USA.
[Finn, Ron M.; Fischle, Wolfgang] Max Planck Inst Biophys Chem, Lab Chromatin Biochem, D-37077 Gottingen, Germany.
[Gor, Jayesh; Perkins, Stephen J.] UCL, Dept Struct & Mol Biol, London WC1E 6BT, England.
[Gustafsson, Henning; Strauss, Holger M.] Novo Nordisk AS, Diabet Biophys, DK-2760 Malov, Denmark.
[Hall, Damien] Australian Natl Univ, Sect Biol Chem, Res Sch Chem, Acton, ACT 0200, Australia.
[Howell, Elizabeth E.; Wright, Edward] Univ Tennessee, Biochem Cell & Mol Biol Dept, Knoxville, TN 37996 USA.
[Isaac, Richard S.; Larson, Adam; Narlikar, Geeta J.; Stoddard, Caitlin] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA.
[Isaac, Richard S.; Larson, Adam; Stoddard, Caitlin] Univ Calif San Francisco, Tetrad Grad Program, San Francisco, CA 94158 USA.
[Jao, Shu-Chuan] Acad Sinica, Inst Biol Chem, Taipei 115, Taiwan.
[Jao, Shu-Chuan; Wang, Szu-Huan] Acad Sinica, Sci Instrument Ctr, Biophys Core Facil, Taipei 115, Taiwan.
[Jose, Davis; von Hippel, Peter H.; Weitzel, Steven E.] Univ Oregon, Inst Mol Biol, Eugene, OR 97403 USA.
[Jose, Davis; von Hippel, Peter H.; Weitzel, Steven E.] Univ Oregon, Dept Chem & Biochem, Eugene, OR 97403 USA.
[Kim, Soon-Jong] Mokpo Natl Univ, Dept Chem, Muan 534729, South Korea.
[Kornblatt, Jack A.] Concordia Univ, Enzyme Res Grp, Montreal, PQ H4B 1R6, Canada.
[Kosek, Dalibor; Obsil, Tomas] Charles Univ Prague, Fac Sci, Dept Phys & Macromol Chem, Prague 12843, Czech Republic.
[Krayukhina, Elena; Noda, Masanori; Uchiyama, Susumu] Osaka Univ, Grad Sch Engn, Dept Biotechnol, Suita, Osaka 5650871, Japan.
[Krzizike, Daniel; Luger, Karolin] Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA.
[Kusznir, Eric A.; Rufer, Arne C.] F Hoffmann LaRoche Ltd, Roche Innovat Ctr Basel, Pharma Res & Early Dev, CH-4070 Basel, Switzerland.
[Kwon, Hyewon; Sumida, John P.] Univ Washington, Analyt Biopharm Core, Seattle, WA 98195 USA.
[Laue, Thomas M.; May, Carrie A.] Univ New Hampshire, Dept Biochem, Durham, NH 03824 USA.
[Leech, Andrew P.] Univ York, Dept Biol, Technol Facil, York YO10 5DD, N Yorkshire, England.
[Lilie, Hauke] Univ Halle Wittenberg, Inst Biochem & Biotechnol, D-06120 Halle, Germany.
[Maynard, Ernest L.] Uniformed Serv Univ Hlth Sci, Dept Biochem, Bethesda, MD 20814 USA.
[Mok, Yee-Foong] Univ Melbourne, Dept Biochem & Mol Biol Inst Mol Sci & Biotechnol, Parkville, Vic 3010, Australia.
[Muecke, Norbert] German Canc Res Ctr, Biophys Macromol, D-69120 Heidelberg, Germany.
[Nagel-Steger, Luitgard; Wolff, Martin] Res Ctr Juelich, ICS 6, Struct Biochem, D-52428 Julich, Germany.
[Nourse, Amanda] St Jude Childrens Res Hosp, Mol Interact Anal Shared Resource, Memphis, TN 38105 USA.
[Park, Chad K.] Univ Arizona, Dept Chem & Biochem, Analyt Biophys & Mat Characterizat, Tucson, AZ 85721 USA.
[Park, Jin-Ku] Mokpo Natl Univ, Cent Instrument Ctr, Muan 534729, South Korea.
[Pawelek, Peter D.] Concordia Univ, Dept Chem & Biochem, Montreal, PQ H4B 1R6, Canada.
[Perugini, Matthew A.; Peverelli, Martin G.; Wubben, Jacinta M.] La Trobe Univ, La Trobe Inst Mol Sci, Dept Biochem, Melbourne, Vic 3086, Australia.
[Piszczek, Grzegorz] NHLBI, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
[Rezabkova, Lenka] Paul Scherrer Inst, Dept Biol & Chem, Lab Biomol Res, CH-5232 Villigen, Switzerland.
[Richter, Klaus] Tech Univ Munich, Dept Chem, D-85748 Garching, Germany.
[Richter, Klaus] Tech Univ Munich, Ctr Integrated Prot Sci, D-85748 Garching, Germany.
[Ringel, Alison E.; Wolberger, Cynthia] Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA.
[Scott, David J.] Rutherford Appleton Lab, Didcot OX11 0FA, Oxon, England.
[Solovyova, Alexandra S.] Newcastle Univ, Proteome & Prot Anal, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Staunton, David] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England.
[Stott, Katherine] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England.
[Streicher, Werner W.] Novo Nordisk Fdn Ctr Prot Res, Prot Funct & Interact, DK-2200 Copenhagen, Denmark.
[Szczepanowski, Roman H.] Int Inst Mol & Cell Biol, Core Facil, PL-02109 Warsaw, Poland.
[Tessmer, Ingrid] Univ Wurzburg, Rudolf Virchow Ctr Expt Biomed, D-97080 Wurzburg, Germany.
[Toth, Ronald T.] Univ Kansas, Macromol & Vaccine Stabilizat Ctr, Lawrence, KS 66047 USA.
[Tripathy, Ashutosh] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
[Uebel, Stephan F. W.] Max Planck Inst Biochem, Biochem Core Facil, D-82152 Martinsried, Germany.
[Unzai, Satoru] Yokohama City Univ, Grad Sch Med Life Sci, Drug Design Lab, Yokohama, Kanagawa 2300045, Japan.
[Wandrey, Christine] Ecole Polytech Fed Lausanne, Lab Med Regenerat & Pharmacobiol, CH-1015 Lausanne, Switzerland.
[Wu, Yu-Sung] Univ Delaware, Dept Chem & Biomol Engn, Newark, DE 19716 USA.
RP Schuck, P (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Cellular Imaging & Macromol Biophys, Dynam Macromol Assembly Sect, NIH, Bethesda, MD 20892 USA.
EM schuckp@mail.nih.gov
RI Alfonso, Carlos/K-1316-2014; Obsil, Tomas/B-7142-2012; Richter,
Klaus/A-2673-2010; Hall, Damien/D-9927-2012; Nagel-Steger,
Luitgard/H-6415-2013;
OI Perugini, Matthew/0000-0001-8052-5584; Fagan,
Jeffrey/0000-0003-1483-5554; Alfonso, Carlos/0000-0001-7165-4800; Obsil,
Tomas/0000-0003-4602-1272; Hall, Damien/0000-0003-1538-7618;
Nagel-Steger, Luitgard/0000-0001-5232-2149; Schuck,
Peter/0000-0002-8859-6966; kornblatt, jack/0000-0002-9802-8321; Herr,
Andrew/0000-0002-3598-3399; Harding, Stephen E./0000-0002-7798-9692
FU Intramural Research Programs of the National Institute of Biomedical
Imaging and Bioengineering; National Heart, Lung, and Blood Institute;
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health; Max Planck Society; Rudolf Virchow Center
for Experimental Biomedicine - German Research Council (Deutsche
Forschungsgemeinschaft, DFG) [FZ 82]; National Cancer Institute
[CA35635]; National Institute of General Medical Sciences [GM 095822, GM
109102, GM 094363, P30GM103519]; MINECO-Spain/FEDER [CTQ2012-33717];
Centre for Preclinical Research and Technology (CePT) - European Union
[POIG.02.02.00-14-024/08-00]; FRISBI [ANR-10-INSB-05-02]; GRAL within
the Grenoble Partnership for Structural Biology (PSB)
[ANR-10-LABX-49-01]; NIH [GM-15792, GM-29158, GM82545, GM067777,
F31GM105363]; NSF; French Infrastructure for Integrated Structural
Biology (FRISBI) [ANR-10-INSB-05-01]; Instruct, European Strategy Forum
on Research Infrastructures (ESFRI); European Regional Development Fund
within the Innovation Economy Operational Program
[POIG.02.02.00-00025/09]; National Research Foundation of Korea
[2011-0010437]; EMBO long-term fellowship; Marie Curie IEF fellowship;
A.N.U. Senior Research Fellowship
FX This work was supported by the Intramural Research Programs of the
National Institute of Biomedical Imaging and Bioengineering, the
National Heart, Lung, and Blood Institute, and the National Institute of
Diabetes and Digestive and Kidney Diseases National Institutes of
Health; the Max Planck Society; and the Rudolf Virchow Center for
Experimental Biomedicine by the German Research Council (Deutsche
Forschungsgemeinschaft, DFG) FZ 82. Further, this work was supported by
National Cancer Institute grant CA35635, grants from the National
Institute of General Medical Sciences (GM 095822, GM 109102, GM 094363,
and P30GM103519), and by grant CTQ2012-33717 from MINECO-Spain/FEDER.
The purchase of the XL-I AUC instrument for IIMCB Warsaw was supported
by Centre for Preclinical Research and Technology (CePT) - European
Union POIG.02.02.00-14-024/08-00 project. This work used the platforms
of the Grenoble Instruct centre (ISBG; UMS 3518 CNRS-CEA-UJF-EMBL) with
support from FRISBI (ANR-10-INSB-05-02) and GRAL (ANR-10-LABX-49-01)
within the Grenoble Partnership for Structural Biology (PSB). This work
was supported in part by NIH research grants GM-15792 and GM-29158 and
by a Shared Instrument Proposal grant from NSF (P. H. von Hippel,
Principle Investigator). The work in the Strasbourg centre was supported
by the French Infrastructure for Integrated Structural Biology (FRISBI)
ANR-10-INSB-05-01, and Instruct as part of the European Strategy Forum
on Research Infrastructures (ESFRI). Some of the experiments in the
present study were performed in the NanoFun laboratories co-financed by
the European Regional Development Fund within the Innovation Economy
Operational Program, Project No. POIG.02.02.00-00025/09. S-JK
acknowledges support from National Research Foundation of Korea
(2011-0010437). LR acknowledges the receipt of EMBO long-term and Marie
Curie IEF fellowships. DH acknowledges the receipt of an A.N.U. Senior
Research Fellowship. DME and the University of Utah Protein Interaction
Core Facility are supported by NIH Grant GM82545. KL acknowledges NIH
grant GM067777, and DK acknowledges NIH grant F31GM105363. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 41
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U1 4
U2 35
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 MAY 21
PY 2015
VL 10
IS 5
AR e0126420
DI 10.1371/journal.pone.0126420
PG 30
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CK7VW
UT WOS:000356444000024
PM 25997164
ER
PT J
AU Jin, DJ
Cagliero, C
Martin, CM
Izard, J
Zhou, YN
AF Jin, Ding J.
Cagliero, Cedric
Martin, Carmen M.
Izard, Jerome
Zhou, Yan N.
TI The dynamic nature and territory of transcriptional machinery in the
bacterial chromosome
SO FRONTIERS IN MICROBIOLOGY
LA English
DT Review
DE RNA polymerase; bacterial nucleolus; replisome; chromosome territories;
growth rate regulation; stress responses; superresolution imaging; E.
coli
ID ESCHERICHIA-COLI CHROMOSOME; RIBOSOMAL-RNA TRANSCRIPTION;
NUCLEOID-ASSOCIATED PROTEINS; SALMONELLA-TYPHIMURIUM; ACTIVE
TRANSCRIPTION; SPATIAL-ORGANIZATION; STRINGENT RESPONSE;
DNA-REPLICATION; BALANCED GROWTH; SEQA PROTEIN
AB Our knowledge of the regulation of genes involved in bacterial growth and stress responses is extensive; however, we have only recently begun to understand how environmental cues influence the dynamic, three-dimensional distribution of RNA polymerase (RNAP) in Escherichia coli on the level of single cell, using wide-field fluorescence microscopy and state-of-the-art imaging techniques. Live-cell imaging using either an agarose-embedding procedure or a microfluidic system further underscores the dynamic nature of the distribution of RNAP in response to changes in the environment and highlights the challenges in the study. A general agreement between live-cell and fixed-cell images has validated the formaldehyde-fixing procedure, which is a technical breakthrough in the study of the cell biology of RNAP. In this review we use a systems biology perspective to summarize the advances in the cell biology of RNAP in E. coli, including the discoveries of the bacterial nucleolus, the spatial compartmentalization of the transcription machinery at the periphery of the nucleoid, and the segregation of the chromosome territories for the two major cellular functions of transcription and replication in fast-growing cells. Our understanding of the coupling of transcription and bacterial chromosome (or nucleoid) structure is also summarized. Using E. coli as a simple model system, co-imaging of RNAP with DNA and other factors during growth and stress responses will continue to be a useful tool for studying bacterial growth and adaptation in changing environment.
C1 [Jin, Ding J.; Cagliero, Cedric; Martin, Carmen M.; Izard, Jerome; Zhou, Yan N.] NCI, Transcript Control Sect, Gene Regulat & Chromosome Biol Lab, NIH, Frederick, MD 21702 USA.
RP Jin, DJ (reprint author), NCI, Transcript Control Sect, Gene Regulat & Chromosome Biol Lab, POB B, Frederick, MD 21702 USA.
EM jind@mail.nih.gov
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. DJJ would
like to thank the four reviewers and the editor for critical reading of
the manuscript and productive interactions in the reviewing process.
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PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1664-302X
J9 FRONT MICROBIOL
JI Front. Microbiol.
PD MAY 21
PY 2015
VL 6
AR 497
DI 10.3389/fmicb.2015.00497
PG 14
WC Microbiology
SC Microbiology
GA CK5MC
UT WOS:000356267800001
PM 26052320
ER
PT J
AU Barrett, AJ
Ito, S
AF Barrett, A. John
Ito, Sawa
TI The role of stem cell transplantation for chronic myelogenous leukemia
in the 21st century
SO BLOOD
LA English
DT Article
ID CHRONIC MYELOID-LEUKEMIA; CHRONIC GRANULOCYTIC-LEUKEMIA;
BONE-MARROW-TRANSPLANTATION; BCR-ABL TRANSCRIPTS; VERSUS-HOST-DISEASE;
1ST CHRONIC PHASE; CRYOPRESERVED AUTOLOGOUS MARROW; CHROMOSOME-POSITIVE
LEUKEMIA; DONOR LEUKOCYTE TRANSFUSIONS; IMATINIB MESYLATE TREATMENT
AB The introduction of tyrosine kinase inhibitors (TKIs), a treatment of chronic myelogenous leukemia (CML), has largely replaced curative strategies based on allogeneic stem cell transplantation (SCT). Nevertheless, SCT still remains an option for accelerated/blastic-phase and selected chronic-phase CML. Transplant outcomes can be optimized by peritransplant TKIs, conditioning regimen, BCR-ABL monitoring, and relapse management. Controversies exist in transplant timing, pediatric CML, alternative donors, and economics. SCT continues to serve as a platform of "operational cure" for CML with TKIs and immunotherapies.
C1 [Barrett, A. John; Ito, Sawa] NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Barrett, AJ (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM barrettj@nhlbi.nih.gov
FU National Institutes of Health Intramural Research Program at the
National Heart, Lung, and Blood Institute
FX This study was supported by the National Institutes of Health Intramural
Research Program at the National Heart, Lung, and Blood Institute.
NR 93
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U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD MAY 21
PY 2015
VL 125
IS 21
BP 3230
EP 3235
DI 10.1182/blood-2014-10-567784
PG 6
WC Hematology
SC Hematology
GA CJ7QF
UT WOS:000355691700006
PM 25852053
ER
PT J
AU Garnham, CP
Vemu, A
Wilson-Kubalek, EM
Yu, I
Szyk, A
Lander, GC
Milligan, RA
Roll-Mecak, A
AF Garnham, Christopher P.
Vemu, Annapurna
Wilson-Kubalek, Elizabeth M.
Yu, Ian
Szyk, Agnieszka
Lander, Gabriel C.
Milligan, Ronald A.
Roll-Mecak, Antonina
TI Multivalent Microtubule Recognition by Tubulin Tyrosine Ligase-like
Family Glutamylases
SO CELL
LA English
DT Article
ID ALPHA-BETA-TUBULIN; STRUCTURAL BASIS; IN-VITRO; POSTTRANSLATIONAL
MODIFICATIONS; POLYGLUTAMYLATION; PROTEIN; MOTILITY; BINDING;
RESOLUTION; BRAIN
AB Glutamylation, the most prevalent tubulin posttranslational modification, marks stable microtubules and regulates recruitment and activity of microtubule-interacting proteins. Nine enzymes of the tubulin tyrosine ligase-like (TTLL) family catalyze glutamylation. TTLL7, the most abundant neuronal glutamylase, adds glutamates preferentially to the beta-tubulin tail. Coupled with ensemble and single-molecule biochemistry, our hybrid X-ray and cryo-electron microscopy structure of TTLL7 bound to the microtubule delineates a tripartite microtubule recognition strategy. The enzyme uses its core to engage the disordered anionic tails of alpha-and beta-tubulin, and a flexible cationic domain to bind the microtubule and position itself for beta-tail modification. Furthermore, we demonstrate that all single-chain TTLLs with known glutamylase activity utilize a cationic microtubule-binding domain analogous to that of TTLL7. Therefore, our work reveals the combined use of folded and intrinsically disordered substrate recognition elements as the molecular basis for specificity among the enzymes primarily responsible for chemically diversifying cellular microtubules.
C1 [Garnham, Christopher P.; Vemu, Annapurna; Yu, Ian; Szyk, Agnieszka; Roll-Mecak, Antonina] NINDS, Cell Biol & Biophys Unit, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA.
[Wilson-Kubalek, Elizabeth M.; Lander, Gabriel C.; Milligan, Ronald A.] Scripps Res Inst, La Jolla, CA 92037 USA.
[Roll-Mecak, Antonina] NHLBI, Bethesda, MD 20892 USA.
RP Roll-Mecak, A (reprint author), NINDS, Cell Biol & Biophys Unit, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA.
EM antonina@mail.nih.gov
FU NIGMS [P41 GM103310]; NINDS postdoctoral fellowship; Damon Runyon Cancer
Research Foundation (DFS) [07-13]; Pew Scholars program; Searle Scholars
program; NIH [DP2 EB020402, GM-052468, GM095573]; Searle Scholar
program; National Institute of Neurological Disorders and Stroke;
National Heart, Lung and Blood Institute
FX We thank staff at beamlines 24-ID (Advanced Photon Source) and 5.0.1 and
5.0.2 (Advanced Light Source) for support, D.-Y. Lee for access to mass
spectrometers, and A. Ferre-D'Amare, E. Giniger, and S. Gottesman for
critical reading of the manuscript. TEM studies were conducted at the
National Resource for Automated Molecular Microscopy, supported by NIGMS
(P41 GM103310). C.P.G. is supported by an NINDS postdoctoral fellowship.
G.C.L. is supported by the Damon Runyon Cancer Research Foundation
(DFS-#07-13), the Pew Scholars program, the Searle Scholars program, and
NIH (DP2 EB020402). R.A.M. is supported by NIH (GM-052468). E.M.W.-K is
partly supported by NIH (GM095573). A.R.-M. is supported by the Searle
Scholar program and the intramural programs of the National Institute of
Neurological Disorders and Stroke and National Heart, Lung and Blood
Institute.
NR 53
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Z9 15
U1 2
U2 26
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 MAY 21
PY 2015
VL 161
IS 5
BP 1112
EP 1123
DI 10.1016/j.cell.2015.04.003
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CJ0GA
UT WOS:000355152600018
PM 25959773
ER
PT J
AU Canela, A
Stanlie, A
Nussenzweig, A
AF Canela, Andres
Stanlie, Andre
Nussenzweig, Andre
TI Collateral DNA Damage Produced by Genome-Editing Drones: Exception or
Rule?
SO MOLECULAR CELL
LA English
DT Editorial Material
ID OFF-TARGET CLEAVAGE; CHROMOSOMAL TRANSLOCATIONS; SEQUENCING REVEALS;
REARRANGEMENTS; NUCLEASES; BREAKS; CELLS
AB In the recent issue of Nature Biotechnology, Frock et al. (2015) developed an elegant technique to capture translocation partners that can be utilized to determine off-target regions of genome-editing endonucleases as well as endogenous mutators at nucleotide resolution.
C1 [Canela, Andres; Stanlie, Andre; Nussenzweig, Andre] NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA.
RP Nussenzweig, A (reprint author), NCI, Lab Genome Integr, NIH, Bethesda, MD 20892 USA.
EM andre_nussenzweig@nih.gov
NR 10
TC 0
Z9 0
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD MAY 21
PY 2015
VL 58
IS 4
BP 565
EP 567
DI 10.1016/j.molcel.2015.05.012
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CJ0GO
UT WOS:000355154000004
PM 26000841
ER
PT J
AU Zhang, YF
Phung, Y
Gao, W
Kawa, S
Hassan, R
Pastan, I
Ho, M
AF Zhang, Yi-Fan
Phung, Yen
Gao, Wei
Kawa, Seiji
Hassan, Raffit
Pastan, Ira
Ho, Mitchell
TI New High Affinity Monoclonal Antibodies Recognize Non-Overlapping
Epitopes On Mesothelin For Monitoring And Treating Mesothelioma
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MALIGNANT PLEURAL MESOTHELIOMA; ANTIMESOTHELIN IMMUNOTOXIN SS1P;
OVARIAN-CANCER PATIENTS; SERUM MESOTHELIN; POTENTIATING FACTOR;
CELL-SURFACE; IMMUNOTHERAPY; COMBINATION; DIAGNOSIS; THERAPY
AB Mesothelin is an emerging cell surface target in mesothelioma and other solid tumors. Most antibody drug candidates recognize highly immunogenic Region I (296-390) on mesothelin. Here, we report a group of high-affinity non-Region I rabbit monoclonal antibodies. These antibodies do not compete for mesothelin binding with the immunotoxin SS1P that binds Region I of mesothelin. One pair of antibodies (YP218 and YP223) is suitable to detect soluble mesothelin in a sandwich ELISA with high sensitivity. The new assay can also be used to measure serum mesothelin concentration in mesothelioma patients, indicating its potential use for monitoring patients treated with current antibody therapies targeting Region I. The antibodies are highly specific and sensitive in immunostaining of mesothelioma. To explore their use in tumor therapy, we have generated the immunotoxins based on the Fv of these antibodies. One immunotoxin (YP218 Fv-PE38) exhibits potent anti-tumor cytotoxicity towards primary mesothelioma cell lines in vitro and an NCI-H226 xenograft tumor in mice. Furthermore, we have engineered a humanized YP218 Fv that retains full binding affinity for mesothelin-expressing cancer cells. In conclusion, with their unique binding properties, these antibodies may be promising candidates for monitoring and treating mesothelioma and other mesothelin-expressing cancers.
C1 [Zhang, Yi-Fan; Phung, Yen; Gao, Wei; Kawa, Seiji; Pastan, Ira; Ho, Mitchell] Natl Canc Inst, Ctr Canc Res, Mol Biol Lab, Bethesda, MD 20892 USA.
[Hassan, Raffit] Natl Canc Inst, Ctr Canc Res, Thorac & Gastrointestinal Oncol Branch, Bethesda, MD 20892 USA.
RP Ho, M (reprint author), Natl Canc Inst, Ctr Canc Res, Mol Biol Lab, Bethesda, MD 20892 USA.
EM homi@mail.nih.gov
RI Zhang, Yifan/O-9621-2015
OI Zhang, Yifan/0000-0002-0629-0200
FU Intramural Research Program of the National Institutes of Health (NIH);
National Cancer Institute (NCI); Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Cancer Institute (NCI),
Center for Cancer Research. This work was also possible by the
Mesothelioma Applied Research Foundation Craig Kozicki Memorial Grant to
M Ho. 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. We thank Miriam Anver and the staff in
Pathology/Histotechnology Laboratory, SAIC (Frederick, MD), for helping
with in vivo toxicity test and immunohistochemistry analysis and Jingli
Zhang (NCI) for helping with the cytotoxicity assays using primary
patient cell lines. We also thank the NIH Fellows Editorial Board for
editorial assistance. The vehicle and SS1P groups used as control groups
in the study (Fig. 7B) have been previously published in: Kim H, Gao W,
Ho M. Novel immunocytokine IL12-SS1 (Fv) inhibits mesothelioma tumor
growth in nude mice.
NR 38
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 MAY 21
PY 2015
VL 5
AR 09928
DI 10.1038/srep09928
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CJ5BL
UT WOS:000355502300001
PM 25996440
ER
PT J
AU Contijoch, F
Witschey, WRT
Rogers, K
Rears, H
Hansen, M
Yushkevich, P
Gorman, J
Gorman, RC
Han, YC
AF Contijoch, Francisco
Witschey, Walter R. T.
Rogers, Kelly
Rears, Hannah
Hansen, Michael
Yushkevich, Paul
Gorman, Joseph, III
Gorman, Robert C.
Han, Yuchi
TI User-initialized active contour segmentation and golden-angle real-time
cardiovascular magnetic resonance enable accurate assessment of LV
function in patients with sinus rhythm and arrhythmias
SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
LA English
DT Article
DE Real-time CMR; Arrhythmia; Temporal resolution
ID NONLINEAR INVERSE RECONSTRUCTION; LEFT-VENTRICULAR FUNCTION; K-SPACE;
RADIAL FLASH; TEMPORAL RESOLUTION; BALANCED SSFP; CARDIAC MRI; T SENSE;
TRAJECTORIES; EXERCISE
AB Background: Data obtained during arrhythmia is retained in real-time cardiovascular magnetic resonance (rt-CMR), but there is limited and inconsistent evidence to show that rt-CMR can accurately assess beat-to-beat variation in left ventricular (LV) function or during an arrhythmia.
Methods: Multi-slice, short axis cine and real-time golden-angle radial CMR data was collected in 22 clinical patients (18 in sinus rhythm and 4 patients with arrhythmia). A user-initialized active contour segmentation (ACS) software was validated via comparison to manual segmentation on clinically accepted software. For each image in the 2D acquisitions, slice volume was calculated and global LV volumes were estimated via summation across the LV using multiple slices. Real-time imaging data was reconstructed using different image exposure times and frame rates to evaluate the effect of temporal resolution on measured function in each slice via ACS. Finally, global volumetric function of ectopic and non-ectopic beats was measured using ACS in patients with arrhythmias.
Results: ACS provides global LV volume measurements that are not significantly different from manual quantification of retrospectively gated cine images in sinus rhythm patients. With an exposure time of 95.2 ms and a frame rate of > 89 frames per second, golden-angle real-time imaging accurately captures hemodynamic function over a range of patient heart rates. In four patients with frequent ectopic contractions, initial quantification of the impact of ectopic beats on hemodynamic function was demonstrated.
Conclusion: User-initialized active contours and golden-angle real-time radial CMR can be used to determine time-varying LV function in patients. These methods will be very useful for the assessment of LV function in patients with frequent arrhythmias.
C1 [Contijoch, Francisco] Univ Penn, Smilow Ctr Translat Res, Dept Bioengn, Philadelphia, PA 19104 USA.
[Witschey, Walter R. T.; Rears, Hannah; Yushkevich, Paul] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
[Rogers, Kelly; Han, Yuchi] Univ Penn, Dept Med, Div Cardiovasc, Philadelphia, PA 19104 USA.
[Hansen, Michael] NHLBI, NIH, Bethesda, MD 20892 USA.
[Gorman, Joseph, III; Gorman, Robert C.] Univ Penn, Dept Surg, Philadelphia, PA USA.
RP Contijoch, F (reprint author), Univ Penn, Smilow Ctr Translat Res, Dept Bioengn, 3400 Civ Ctr Blvd,Bldg 421,7th Floor,Rm 103, Philadelphia, PA 19104 USA.
EM fcont@seas.upenn.edu
RI Hansen, Michael/J-5391-2015;
OI Hansen, Michael/0000-0002-8087-8731; Contijoch,
Francisco/0000-0001-9616-3274
FU National Institutes of Health [F31-HL120580, R00-HL108157, R01-EB014346,
R01-HL103723, R01-HL63954, T32-HL007954, T32-EB009384]
FX We would like to acknowledge the National Institutes of Health for
support through grants: F31-HL120580, R00-HL108157, R01-EB014346,
R01-HL103723, R01-HL63954, T32-HL007954, T32-EB009384.
NR 28
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U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1097-6647
EI 1532-429X
J9 J CARDIOVASC MAGN R
JI J. Cardiov. Magn. Reson.
PD MAY 21
PY 2015
VL 17
AR 37
DI 10.1186/s12968-015-0146-9
PG 12
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA CI7JU
UT WOS:000354940300001
PM 25994390
ER
PT J
AU Klein, HG
Cortes-Puch, I
Natanson, C
AF Klein, Harvey G.
Cortes-Puch, Irene
Natanson, Charles
TI Blood-transfusion decisions not simple
SO NATURE
LA English
DT Letter
C1 [Klein, Harvey G.; Cortes-Puch, Irene; Natanson, Charles] NIH, Bethesda, MD 20892 USA.
RP Klein, HG (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM hklein@dtm.cc.nih.gov
NR 3
TC 2
Z9 2
U1 3
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 21
PY 2015
VL 521
IS 7552
BP 289
EP 289
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CI5RM
UT WOS:000354816500035
PM 25993950
ER
PT J
AU Chen, ZS
Shojaee, S
Buchner, M
Geng, HM
Lee, J
Klemm, L
Titz, B
Graeber, TG
Park, E
Tan, YX
Satterthwaite, A
Paietta, E
Hunger, SP
Willman, CL
Melnick, A
Loh, ML
Jung, JU
Coligan, JE
Bolland, S
Mak, TW
Limnander, A
Jumaa, H
Reth, M
Weiss, A
Lowell, CA
Muschen, M
AF Chen, Zhengshan
Shojaee, Seyedmehdi
Buchner, Maike
Geng, Huimin
Lee, JaeWoong
Klemm, Lars
Titz, Boern
Graeber, Thomas G.
Park, Eugene
Tan, Ying Xim
Satterthwaite, Anne
Paietta, Elisabeth
Hunger, Stephen P.
Willman, Cheryl L.
Melnick, Ari
Loh, Mignon L.
Jung, Jae U.
Coligan, John E.
Bolland, Silvia
Mak, Tak W.
Limnander, Andre
Jumaa, Hassan
Reth, Michael
Weiss, Arthur
Lowell, Clifford A.
Mueschen, Markus
TI Signalling thresholds and negative B-cell selection in acute
lymphoblastic leukaemia
SO NATURE
LA English
DT Article
ID IN-VIVO; RECEPTOR; DELETION; ACTIVATION; MOTIFS
AB B cells are selected for an intermediate level of B-cell antigen receptor (BCR) signalling strength: attenuation below minimum(for example, non-functional BCR)(1) or hyperactivation above maximum (for example, self-reactive BCR)(2,3) thresholds of signalling strength causes negative selection. In similar to 25% of cases, acute lymphoblastic leukaemia (ALL) cells carry the oncogenic BCR-ABL1 tyrosine kinase (Philadelphia chromosome positive), which mimics constitutively active pre-BCR signalling(4,5). Current therapeutic approaches are largely focused on the development of more potent tyrosine kinase inhibitors to suppress oncogenic signalling below a minimum threshold for survival(6). We tested the hypothesis that targeted hyperactivation-above a maximum threshold-will engage a deletional checkpoint for removal of self-reactive B cells and selectively kill ALL cells. Here we find, by testing various components of proximal pre-BCR signalling in mouse BCR-ABL1 cells, that an incremental increase of Syk tyrosine kinase activity was required and sufficient to induce cell death. Hyperactive Syk was functionally equivalent to acute activation of a self-reactive BCR on ALL cells. Despite oncogenic transformation, this basic mechanism of negative selection was still functional in ALL cells. Unlike normal pre-B cells, patient-derived ALL cells express the inhibitory receptors PECAM1, CD300A and LAIR1 at high levels. Genetic studies revealed that Pecam1, Cd300a and Lair1 are critical to calibrate oncogenic signalling strength through recruitment of the inhibitory phosphatases Ptpn6 (ref. 7) and Inpp5d (ref. 8). Using a novel small-molecule inhibitor of INPP5D (also known as SHIP1)(9), we demonstrated that pharmacological hyperactivation of SYK and engagement of negative B-cell selection represents a promising new strategy to overcome drug resistance in human ALL.
C1 [Chen, Zhengshan; Shojaee, Seyedmehdi; Buchner, Maike; Geng, Huimin; Lee, JaeWoong; Klemm, Lars; Park, Eugene; Lowell, Clifford A.; Mueschen, Markus] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
[Titz, Boern; Graeber, Thomas G.] Univ Calif Los Angeles, Crump Inst Mol Imaging, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA.
[Tan, Ying Xim; Weiss, Arthur] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Med,Div Rheumatol, Rosalind Russell Ephraim P Engleman Med Res Ctr A, San Francisco, CA 94143 USA.
[Satterthwaite, Anne] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
[Paietta, Elisabeth] Albert Einstein Coll Med, Dept Med, Bronx, NY 10466 USA.
[Hunger, Stephen P.] Childrens Hosp Philadelphia, Div Pediat Oncol, Philadelphia, PA 19104 USA.
[Hunger, Stephen P.] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA.
[Willman, Cheryl L.] Univ New Mexico, Ctr Canc, Albuquerque, NM 87102 USA.
[Melnick, Ari] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA.
[Melnick, Ari] Weill Cornell Med Coll, Dept Pharmacol, New York, NY 10065 USA.
[Loh, Mignon L.] Univ Calif San Francisco, Pediat Hematol Oncol, San Francisco, CA 94143 USA.
[Jung, Jae U.] Univ So Calif, Dept Mol Microbiol & Immunol, Los Angeles, CA 90033 USA.
[Coligan, John E.] NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Bolland, Silvia] NIAID, Autoimmun & Funct Genom Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Mak, Tak W.] Univ Hlth Network, Campbell Family Inst Breast Canc Res, Toronto, ON M5G 2M9, Canada.
[Limnander, Andre] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA.
[Jumaa, Hassan] Univ Clin Ulm, Inst Immunol, D-89081 Ulm, Germany.
[Reth, Michael] Univ Freiburg, BIOSS Ctr Biol Signalling Studies, D-79104 Freiburg, Germany.
[Reth, Michael] Univ Freiburg, Fac Biol, D-79104 Freiburg, Germany.
[Reth, Michael] MPI Immunbiol & Epigenet, D-79104 Freiburg, Germany.
RP Muschen, M (reprint author), Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
EM markus.muschen@ucsf.edu
OI Titz, Bjoern/0000-0003-4414-4105; Graeber, Thomas/0000-0001-8574-9181
FU National Institutes of Health/National Cancer Institute [R01CA137060,
R01CA139032, R01CA169458, R01CA172558, R01CA157644]; ECOG-ACRIN
[CA180820, CA180794]; Leukemia and Lymphoma Society; California
Institute for Regenerative Medicine [TR02-1816]; William Lawrence and
Blanche Hughes Foundation; DFG [EXC294, TRR130, SFB746]
FX We thank R. W. Hendriks for encouragement and critical discussions, A.
Park and C. Lin and all the members of the Muschen laboratory, L. Tian
and B. Scott for their support. This work is supported by grants from
the National Institutes of Health/National Cancer Institute through
R01CA137060, R01CA139032, R01CA169458, R01CA172558 and R01CA157644 (to
M.M.), ECOG-ACRIN grants CA180820 and CA180794 (to E.P.), grants from
the Leukemia and Lymphoma Society (to M.M.), the California Institute
for Regenerative Medicine through TR02-1816 (M.M.), and the William
Lawrence and Blanche Hughes Foundation. M.M. is a Scholar of The
Leukemia and Lymphoma Society and a Senior Investigator of the Wellcome
Trust. M.R. is supported by the DFG through EXC294, TRR130 and SFB746.
NR 22
TC 24
Z9 24
U1 3
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD MAY 21
PY 2015
VL 521
IS 7552
BP 357
EP +
DI 10.1038/nature14231
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CI5RM
UT WOS:000354816500057
PM 25799995
ER
PT J
AU Xu, H
Rahimpour, S
Nesvick, CL
Zhang, X
Ma, JY
Zhang, M
Zhang, G
Wang, L
Yang, C
Hong, CS
Germanwala, AV
Elder, JB
Ray-Chaudhury, A
Yao, Y
Gilbert, MR
Lonser, RR
Heiss, JD
Brady, RO
Mao, Y
Qin, JH
Zhuang, ZP
AF Xu, Hui
Rahimpour, Shervin
Nesvick, Cody L.
Zhang, Xu
Ma, Jingyun
Zhang, Min
Zhang, Ge
Wang, Li
Yang, Chunzhang
Hong, Christopher S.
Germanwala, Anand V.
Elder, J. Bradley
Ray-Chaudhury, Abhik
Yao, Yu
Gilbert, Mark R.
Lonser, Russell R.
Heiss, John D.
Brady, Roscoe O.
Mao, Ying
Qin, Jianhua
Zhuang, Zhengping
TI Activation of hypoxia signaling induces phenotypic transformation of
glioma cells: implications for bevacizumab antiangiogenic therapy
SO ONCOTARGET
LA English
DT Article
DE glioblastoma; bevacizumab; epithelial-mesenchymal transition; pathologic
angiogenesis; hypoxia-inducible factor
ID ENDOTHELIAL GROWTH-FACTOR; EPITHELIAL-MESENCHYMAL TRANSITION; RECURRENT
MALIGNANT GLIOMA; RECEPTOR INHIBITOR SU5416; ANTI-ANGIOGENIC THERAPY;
INDUCIBLE FACTOR-I; STEM-CELLS; PHASE-II; GLIOBLASTOMA-MULTIFORME; TUMOR
PROGRESSION
AB Glioblastoma (GBM) is the most common and deadly primary brain tumor in adults. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), can attenuate tumor-associated edema and improve patient symptoms but based on magnetic resonance imaging, is associated with non-enhancing tumor progression and possibly gliosarcoma differentiation. To gain insight into these findings, we investigated the role of hypoxia and epithelial-mesenchymal transition (EMT)-associated proteins in GBM. Tumor markers of hypoxia and EMT were upregulated in bevacizumab-treated tumors from GBM patients compared to untreated counterparts. Exposure of glioma cells to 1% oxygen tension increased cell proliferation, expression of EMT-associated proteins and enhanced cell migration in vitro. These phenotypic changes were significantly attenuated by pharmacologic knockdown of hypoxia-inducible Factor 1 alpha (HIF1 alpha) or HIF2 alpha, indicating that HIFs represent a therapeutic target for mesenchymal GBM cells. These findings provide insights into potential development of novel therapeutic targeting of angiogenesis-specific pathways in GBM.
C1 [Xu, Hui; Zhang, Xu; Ma, Jingyun; Zhang, Min; Wang, Li; Qin, Jianhua] Chinese Acad Sci, Dalian Inst Chem Phys, Div Biotechnol, Dalian, Peoples R China.
[Rahimpour, Shervin; Nesvick, Cody L.; Yang, Chunzhang; Hong, Christopher S.; Ray-Chaudhury, Abhik; Heiss, John D.; Brady, Roscoe O.; Zhuang, Zhengping] NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA.
[Zhang, Ge] Dalian Med Univ, Dept Immunol, Dalian, Peoples R China.
[Germanwala, Anand V.] Loyola Univ, Med Ctr, Dept Neurol Surg, Chicago, IL 60611 USA.
[Elder, J. Bradley; Lonser, Russell R.] Ohio State Univ, Med Ctr, Dept Neurol Surg, Columbus, OH 43210 USA.
[Yao, Yu; Mao, Ying] Fudan Univ, Dept Neurosurg, Huashan Hosp, Shanghai Med Coll, Shanghai 200433, Peoples R China.
[Gilbert, Mark R.] Univ Texas MD Anderson Canc Ctr, Dept Neuro Oncol, Div Canc Med, Houston, TX 77030 USA.
RP Mao, Y (reprint author), Fudan Univ, Dept Neurosurg, Huashan Hosp, Shanghai Med Coll, Shanghai 200433, Peoples R China.
EM yingmao168@hotmail.com; jhqin@dicp.ac.cn; zhuangp@ninds.nih.gov
RI Gilbert, Mark/J-7494-2016
OI Gilbert, Mark/0000-0003-2556-9722
FU National Nature Science Foundation of China [11161160552, 91227123]; Key
Projects in the National Science & Technology Pillar Program in the
Twelfth Five-Year Plan Period of China [2012BAK02B00, 2012BAK02B03];
Intramural Research Program at the National Institutes of Health (NIH),
National Cancer Institute; NIH Medical Research Scholars Program - NIH
FX This work was supported by the National Nature Science Foundation of
China (grant nos. 91227123 and 11161160552), Key Projects in the
National Science & Technology Pillar Program in the Twelfth Five-Year
Plan Period of China (grant nos. 2012BAK02B00 and 2012BAK02B03),
Intramural Research Program at the National Institutes of Health (NIH),
National Cancer Institute, and the NIH Medical Research Scholars
Program, a public-private partnership supported jointly by the NIH and
generous contributions to the Foundation for the NIH through Pfizer,
Inc., The Doris Duke Charitable Foundation, The Alexandria Real Estate
Equities, Inc. and Mr. and Mrs. Joel S. Marcus, and the Howard Hughes
Medical Institute, as well as other private donors. For a complete list,
please visit the Foundation website at:
http://fnih.org/work/education-training-0/medical-research-scholars-prog
ram.
NR 49
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U1 3
U2 10
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD MAY 20
PY 2015
VL 6
IS 14
BP 11882
EP 11893
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA CO2SZ
UT WOS:000359008200013
PM 25957416
ER
PT J
AU Castro, NP
Fedorova-Abrams, ND
Merchant, AS
Rangel, MC
Nagaoka, T
Karasawa, H
Klauzinska, M
Hewitt, SM
Biswas, K
Sharan, SK
Salomon, DS
AF Castro, Nadia P.
Fedorova-Abrams, Natalie D.
Merchant, Anand S.
Rangel, Maria Cristina
Nagaoka, Tadahiro
Karasawa, Hideaki
Klauzinska, Malgorzata
Hewitt, Stephen M.
Biswas, Kajal
Sharan, Shyam K.
Salomon, David S.
TI Cripto-1 as a novel therapeutic target for triple negative breast cancer
SO ONCOTARGET
LA English
DT Article
DE cripto-1; notch4; epithelial-mesenchymal plasticity; mouse model;
triple-negative breast cancer
ID EPITHELIAL-MESENCHYMAL TRANSITION; GAMMA-SECRETASE INHIBITORS;
GENE-EXPRESSION; STEM-CELLS; CARCINOMA; PROGRESSION; METASTASIS; TUMORS;
NOTCH; MOUSE
AB Triple-negative breast cancer (TNBC) presents the poorest prognosis among the breast cancer subtypes and no current standard therapy. Here, we performed an in-depth molecular analysis of a mouse model that establishes spontaneous lung metastasis from JygMC(A) cells. These primary tumors resembled the triple-negative breast cancer (TNBC) both phenotypically and molecularly. Morphologically, primary tumors presented both epithelial and spindle-like cells but displayed only adenocarcinoma-like features in lung parenchyma. The use of laser-capture microdissection combined with Nanostring mRNA and microRNA analysis revealed overexpression of either epithelial and miRNA-200 family or mesenchymal markers in adenocarcinoma and mesenchymal regions, respectively. Cripto-1, an embryonic stem cell marker, was present in spindle-like areas and its promoter showed activity in primary tumors. Cripto-1 knockout by the CRISPR-Cas9 system inhibited tumor growth and pulmonary metastasis. Our findings show characterization of a novel mouse model that mimics the TNBC and reveal Cripto-1 as a TNBC target hence may offer alternative treatment strategies for TNBC.
C1 [Castro, Nadia P.; Rangel, Maria Cristina; Nagaoka, Tadahiro; Karasawa, Hideaki; Klauzinska, Malgorzata; Salomon, David S.] NIH, Tumor Growth Factor Sect, Mouse Canc Genet Program, Frederick, MD 20892 USA.
[Fedorova-Abrams, Natalie D.; Merchant, Anand S.] NIH, CCRIFX Bioinformat Core, Bethesda, MD 20892 USA.
[Hewitt, Stephen M.] NIH, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Biswas, Kajal; Sharan, Shyam K.] NIH, Genet Canc Susceptibil Sect, Mouse Canc Genet Program, Frederick, MD USA.
RP Salomon, DS (reprint author), NIH, Tumor Growth Factor Sect, Mouse Canc Genet Program, Frederick, MD 20892 USA.
EM castron2@mail.nih.gov; salomond@mail.nih.gov
RI Rangel, Maria Cristina/P-7216-2014; Abrams, Natalie/F-4845-2011;
OI Rangel, Maria Cristina/0000-0002-8002-9617; Abrams,
Natalie/0000-0001-9698-2819; Hewitt, Stephen/0000-0001-8283-1788
FU Intramural Research Program of the NIH, National Cancer Institute
FX The study was supported by the Intramural Research Program of the NIH,
National Cancer Institute.
NR 53
TC 8
Z9 9
U1 1
U2 5
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD MAY 20
PY 2015
VL 6
IS 14
BP 11910
EP 11929
PG 20
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA CO2SZ
UT WOS:000359008200015
PM 26059540
ER
PT J
AU Terry, S
El-Sayed, IY
Destouches, D
Maille, P
Nicolaiew, N
Ploussard, G
Semprez, F
Pimpie, C
Beltran, H
Londono-Vallejo, A
Allory, Y
de la Taille, A
Salomon, DS
Vacherot, F
AF Terry, Stephane
El-Sayed, Ihsan Y.
Destouches, Damien
Maille, Pascale
Nicolaiew, Nathalie
Ploussard, Guillaume
Semprez, Fannie
Pimpie, Cynthia
Beltran, Himisha
Londono-Vallejo, Arturo
Allory, Yves
de la Taille, Alexandre
Salomon, David S.
Vacherot, Francis
TI CRIPTO overexpression promotes mesenchymal differentiation in prostate
carcinoma cells through parallel regulation of AKT and FGFR activities
SO ONCOTARGET
LA English
DT Article
DE prostate cancer; CRIPTO; mesenchymal-like cancer cells; EMT; FGFR; AKT
ID MAMMARY EPITHELIAL-CELLS; CANCER STEM-CELLS; SIGNALING PATHWAY; TUMOR
PROGRESSION; BREAST-CANCER; GENE FUSIONS; TRANSITION; EXPRESSION;
RECEPTOR; MORPHOGENESIS
AB Members of the EGF-CFC (Cripto, FRL-1, Cryptic) protein family are increasingly recognized as key mediators of cell movement and cell differentiation during vertebrate embryogenesis. The founding member of this protein family, CRIPTO, is overexpressed in various human carcinomas. Yet, the biological role of CRIPTO in this setting remains unclear. Here, we find CRIPTO expression as especially high in a subgroup of primary prostate carcinomas with poorer outcome, wherein resides cancer cell clones with mesenchymal traits. Experimental studies in PCa models showed that one notable function of CRIPTO expression in prostate carcinoma cells may be to augment PI3K/AKT and FGFR1 signaling, which promotes epithelial-mesenchymal transition and sustains a mesenchymal state. In the observed signaling events, FGFR1 appears to function parallel to AKT, and the two pathways act cooperatively to enhance migratory, invasive and transformation properties specifically in the CRIPTO overexpressing cells. Collectively, these findings suggest a novel molecular network, involving CRIPTO, AKT, and FGFR signaling, in favor of the emergence of mesenchymal-like cancer cells during the development of aggressive prostate tumors.
C1 [Terry, Stephane; El-Sayed, Ihsan Y.; Destouches, Damien; Nicolaiew, Nathalie; Ploussard, Guillaume; Semprez, Fannie; Pimpie, Cynthia; Allory, Yves; de la Taille, Alexandre; Vacherot, Francis] Inserm, U955, Equipe 7, Creteil, France.
[Terry, Stephane; El-Sayed, Ihsan Y.; Destouches, Damien; Nicolaiew, Nathalie; Semprez, Fannie; Pimpie, Cynthia; Allory, Yves; de la Taille, Alexandre; Vacherot, Francis] Univ Paris Est, UMR S955, UPEC, F-94000 Creteil, France.
[Terry, Stephane; Londono-Vallejo, Arturo] CNRS, Inst Curie, Ctr Rech, UMR 3244, F-75248 Paris, France.
[Terry, Stephane] Inserm, U753, Inst Cancerol Gustave Roussy, F-94805 Villejuif, France.
[El-Sayed, Ihsan Y.] Univ Libanaise, EDST PRASE, Fac Sci, Beirut, Lebanon.
[Destouches, Damien] CNRS, Lab Rech Croissance Cellulaire, Reparat & Regenerat Tissulaires CRRET, F-94010 Creteil, France.
[Maille, Pascale; Allory, Yves] Hop Henri Mondor, AP HP, Dept pathol, F-94000 Creteil, France.
[Beltran, Himisha] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA.
[Ploussard, Guillaume; Vacherot, Francis] Hop Henri Mondor, AP HP, Serv Urol, F-94000 Creteil, France.
[Salomon, David S.] Frederick Natl Lab Canc Res, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA.
RP Terry, S (reprint author), Inserm, U955, Equipe 7, Creteil, France.
EM stephane.terry@gmail.com
RI Terry, Stephane/K-5351-2013;
OI Terry, Stephane/0000-0003-3089-7886; Londono Vallejo,
Arturo/0000-0003-3535-7563
FU INSERM; CNRS; Association pour la Recherche sur les Tumeurs de la
Prostate; Institut National du Cancer
FX We are grateful to Caterina Bianco, Alyson Baker, Sylvain Loric, Ahmad
Daher, Laurent Salomon, Bruno Goud for providing material and/or advice,
and to Laurence Kheuang, Pascale Soyeux and Vianney Barris for technical
assistance. We appreciate the contribution of Sandy Azoulay, Corine
Matar, Nanor Sirab, Philippe Fontanges, Rachid Souktani, Eric Huet and
Raquel Esgueva for their input in the preliminary work. This work was
supported by INSERM and CNRS intramural fundings and in part by grants
from "Association pour la Recherche sur les Tumeurs de la Prostate" (to
ST) and "Institut National du Cancer" (to ALV and YA)
NR 66
TC 3
Z9 3
U1 1
U2 4
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD MAY 20
PY 2015
VL 6
IS 14
BP 11994
EP 12008
PG 15
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA CO2SZ
UT WOS:000359008200020
PM 25596738
ER
PT J
AU Butz, H
Szabo, PM
Khella, HWZ
Nofech-Mozes, R
Patocs, A
Yousef, GM
AF Butz, Henriett
Szabo, Peter M.
Khella, Heba W. Z.
Nofech-Mozes, Roy
Patocs, Attila
Yousef, George M.
TI miRNA-target network reveals miR-124as a key miRNA contributing to clear
cell renal cell carcinoma aggressive behaviour by targeting CAV1 and
FLOT1
SO ONCOTARGET
LA English
DT Article
DE renal cell carcinoma; miR-124-3p; integrated analysis; CAV1; FLOT1
ID BREAST-CANCER; TUMOR PROGRESSION; GENE-EXPRESSION; PROSTATE-CANCER;
DOWN-REGULATION; MESSENGER-RNA; UP-REGULATION; CAVEOLIN-1;
PROLIFERATION; METASTASIS
AB Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor with frequent metastatic rate and poor survival. Integrated analyses allow understanding the interplay between different levels of molecular alterations.
We integrated miRNA and gene expression data from 458 ccRCC and 254 normal kidney specimens to construct a miRNA-target interaction network.
We identified the downregulated miR-124-3p, -30a-5p and -200c-3p as the most influential miRNAs in RCC pathogenesis. miR-124-3p and miR-200c-3p expression showed association with patient survival, miR-30a-5p was downregulated in metastases compared to primary tumors. We used an independent set of 87 matched samples for validation. We confirmed the functional impact of these miRNAs by in vitro assays. Restoration of these miRNAs reduced migration, invasion and proliferation. miR-124-3p decreased the S phase of cell cycle, as well. We compared transcriptome profiling before and after miRNA overexpression, and validated CAV1 and FLOT1 as miR-124-3p targets. Patients with higher CAV1 and FLOT1 had lower miR-124-3p expression and shorter overall survival.
We hypothesize that these three miRNAs are fundamental contributing to ccRCC aggressive/metastatic behavior; and miR-124-3p especially has a key role through regulating CAV1 and FLOT1 expression. Restoration of the levels of these miRNAs could be considered as a potential therapeutic strategy for ccRCC.
C1 [Butz, Henriett; Khella, Heba W. Z.; Nofech-Mozes, Roy; Yousef, George M.] St Michaels Hosp, Dept Lab Med, Toronto, ON M5B 1W8, Canada.
[Butz, Henriett; Khella, Heba W. Z.; Nofech-Mozes, Roy; Yousef, George M.] St Michaels Hosp, Keenan Res Ctr Biomed Sci, Toronto, ON M5B 1W8, Canada.
[Butz, Henriett; Khella, Heba W. Z.; Yousef, George M.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada.
[Szabo, Peter M.] NCI, NIH, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Patocs, Attila] Hungarian Acad Sci, HAS SE Lendulet Hereditary Endocrine Tumors Res G, H-1051 Budapest, Hungary.
RP Yousef, GM (reprint author), St Michaels Hosp, Dept Lab Med, 30 Bond St, Toronto, ON M5B 1W8, Canada.
EM yousefg@smh.ca
FU Canadian Institute of Health Research [MOP 119606]; Kidney Foundation of
Canada [KFOC130030]; Kidney Cancer Research Network of Canada; Prostate
Cancer Canada Movember Discovery Grants [D2013-39]
FX GMY is supported by grants from Canadian Institute of Health Research
(MOP 119606), Kidney Foundation of Canada (KFOC130030), the Kidney
Cancer Research Network of Canada, and Prostate Cancer Canada Movember
Discovery Grants (D2013-39).
NR 50
TC 8
Z9 9
U1 1
U2 4
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD MAY 20
PY 2015
VL 6
IS 14
BP 12543
EP 12557
PG 15
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA CO2SZ
UT WOS:000359008200059
PM 26002553
ER
PT J
AU Albiges, L
Murray, B
Brooks, A
Cherniack, A
Berger, A
Creighton, CJ
Ricketts, C
Bottaro, DP
Srinivasan, R
Schmidt, LS
Meyerson, M
Spellman, P
Linehan, WM
Choueiri, TK
AF Albiges, Laurence
Murray, Bradley
Brooks, Angela
Cherniack, Andrew
Berger, Alice
Creighton, Chad J.
Ricketts, Christopher
Bottaro, Donald P.
Srinivasan, Ramaprasad
Schmidt, Laura S.
Meyerson, Matthew
Spellman, Paul
Linehan, W. Marston
Choueiri, Toni K.
CA Canc Genome Atlas TCGA Kidney
TI Distinct MET alterations to induce a common phenotype and to define a
MET-driven subset of papillary RCC: Results from the Cancer Genome Atlas
(TCGA) Kidney Renal Papillary (KIRP) Working Group
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA.
Broad Inst, Boston, MA USA.
Broad Inst, Cambridge, MA USA.
Baylor Coll Med, Houston, TX 77030 USA.
NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
NIH, Bethesda, MD 20892 USA.
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dana Farber Canc Inst,Brigham & Womens Hosp,Broad, Boston, MA USA.
Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
NCI, NIH, Bethesda, MD 20892 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 4521
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900989
ER
PT J
AU Allette, K
Pattanayak, P
Steinberg, SM
Parnes, H
Jackson, G
Francis, D
Lamping, E
Folio, L
Apolo, AB
AF Allette, Kimaada
Pattanayak, Puskar
Steinberg, Seth M.
Parnes, Howard
Jackson, Gloria
Francis, Deneise
Lamping, Elizabeth
Folio, Les
Apolo, Andrea Borghese
TI Assessment of treatment response using Computed Tomography (CT) tumor
volume measurements and lesion number in metastatic urothelial carcinoma
(mUC) patients (pts) receiving cabozantinib.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, NIH, Bethesda, MD 20892 USA.
NIH, Radiol & Imaging Sci, Bethesda, MD 20892 USA.
NCI, Rockville, MD USA.
NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA.
NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e15503
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036903053
ER
PT J
AU Apolo, AB
Lee, MJ
Tomita, Y
Lee, S
Agarwal, PK
Jackson, G
Francis, DC
Lamping, E
Buford, L
Tomita, S
Mackall, K
Parnes, HL
Dahut, WL
Gulley, JL
Trepel, JB
AF Apolo, Andrea Borghese
Lee, Min-Jung
Tomita, Yusuke
Lee, Sunmin
Agarwal, Piyush K.
Jackson, Gloria
Francis, Deneise C.
Lamping, Elizabeth
Buford, Lauren
Tomita, Saori
Mackall, Katherine
Parnes, Howard L.
Dahut, William L.
Gulley, James L.
Trepel, Jane B.
TI Evaluation of a new circulating tumor cell (CTC) platform to predict
response and survival in metastatic urothelial carcinoma (UC) patients
receiving cabozantinib (cabo).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, NIH, Bethesda, MD 20892 USA.
NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA.
NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e15501
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036903052
ER
PT J
AU Aren, OR
Silva, R
Cerda, H
Arancibia, JM
Rojas, C
Reyes, M
Ascui, RA
Banchero, P
Pichun, MEB
AF Aren, Osvaldo Rudy
Silva, Ricardo
Cerda, Humberto
Arancibia, Jorge M.
Rojas, Carlos
Reyes, Mauricio
Ascui, Rodrigo Andres
Banchero, Patricia
Pichun, Mauricio Emmanuel Burotto
TI Single institution experience with 75 mg dose of erlotinib in Latin
American patients with mutated metastatic non-small cell lung cancer.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Ctr Int Estudios Clin, Santiago, Chile.
Inst Nacl Canc, Santiago, Chile.
Hosp Reg Concepcion, Concepcion, Chile.
Univ Chile, Santiago, Chile.
NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 8075
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901787
ER
PT J
AU Bates, SE
Lindenberg, ML
Bryla, C
Pichun, MEB
Patronas, N
Amiri-Kordestani, L
Gonzalez, EM
Fojo, T
Balasubramaniam, S
Choyke, PL
AF Bates, Susan Elaine
Lindenberg, Maria Liza
Bryla, Christine
Pichun, Mauricio Emmanuel Burotto
Patronas, Nicholas
Amiri-Kordestani, Laleh
Gonzalez, Esther Mena
Fojo, Tito
Balasubramaniam, Sanjeeve
Choyke, Peter L.
TI ANG1005 for brain metastases from breast cancer: 18F-FLT-PET and MRI as
complementary approaches to response assessment.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
NIH, Dept Radiol, Bethesda, MD 20892 USA.
US FDA, Bethesda, MD 20014 USA.
Johns Hopkins Univ, Div Nucl Med, Baltimore, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 4
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 2552
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900585
ER
PT J
AU Bell-McGuinn, KM
Brady, WE
Schilder, RJ
Fracasso, PM
Moore, KN
Walker, JL
Duska, LR
Mathews, CA
Chen, A
Shepherd, SP
Giranda, VL
Aghajanian, C
AF Bell-McGuinn, Katherine M. y
Brady, William E.
Schilder, Russell J.
Fracasso, Paula M.
Moore, Kathleen N.
Walker, Joan L.
Duska, Linda R.
Mathews, Cara Amanda
Chen, Alice
Shepherd, Stacie Peacock
Giranda, Vincent L.
Aghajanian, Carol
TI A phase I study of continuous veliparib in combination with IV
carboplatin/paclitaxel or IV/IP paclitaxel/cisplatin and bevacizumab in
newly diagnosed patients with previously untreated epithelial ovarian,
fallopian tube, or primary peritoneal cancer: An NRG
Oncology/Gynecologic Oncology Group study.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Weill Cornell Med Coll, New York, NY USA.
Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
Univ Virginia, Sch Med, Charlottesville, VA 22908 USA.
Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
OUHSC, Stephenson Canc Ctr, Oklahoma City, OK USA.
Univ Virginia Hlth Syst, Charlottesville, VA USA.
Women & Infants Hosp Rhode Isl, Providence, RI 02908 USA.
NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
AbbVie, N Chicago, IL USA.
NR 0
TC 3
Z9 3
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 5507
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901165
ER
PT J
AU Bhaumik, S
Stewart, D
Pemov, A
Choyke, PL
Dombi, E
Glod, J
Miettinen, M
Khan, J
Steinberg, SM
Goodwin, A
Baldwin, A
Widemann, BC
AF Bhaumik, Sucharita
Stewart, Douglas
Pemov, Alexander
Choyke, Peter L.
Dombi, Eva
Glod, John
Miettinen, Markku
Khan, Javed
Steinberg, Seth M.
Goodwin, Anne
Baldwin, Andrea
Widemann, Brigitte C.
TI Early detection of transformation of plexiform neurofibromas to
malignant peripheral nerve sheath tumors in neurofibromatosis type 1.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Childrens Natl Med Ctr, Washington, DC 20010 USA.
NCI, Bethesda, MD 20892 USA.
NCI, Clin Genet Branch, Rockville, MD USA.
NCI, NIH, Bethesda, MD 20892 USA.
NCI, Rockville, MD USA.
NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RI Khan, Javed/P-9157-2014
OI Khan, Javed/0000-0002-5858-0488
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA TPS10083
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036904650
ER
PT J
AU Blakeslee, SB
Parker, PA
Gunn, CM
Bandos, H
Bevers, TB
Battaglia, TA
Fagerlin, A
McCaskill-Stevens, WJ
Holmberg, C
AF Blakeslee, Sarah B.
Parker, Patricia A.
Gunn, Christine M.
Bandos, Hanna
Bevers, Therese Bartholomew
Battaglia, Tracy Ann
Fagerlin, Angela
McCaskill-Stevens, Worta J.
Holmberg, Christine
TI Decision-making in breast cancer risk reduction: Results from a nested
qualitative study from NRG Oncology/NSABP protocol DMP-1
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Charite, Berlin Sch Publ Hlth, D-13353 Berlin, Germany.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
NRG Oncol NSABP, Boston, MA USA.
Boston Univ, Med Ctr, Boston, MA USA.
NRG Oncol, Pittsburgh, PA USA.
Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
NRG Oncol NSABP, Houston, TX USA.
Boston Med Ctr, Boston, MA USA.
Boston Univ, Sch Med, Boston, MA 02118 USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
Ann Arbor VA Healthcare Syst, Ann Arbor, MI USA.
NCI, Rockville, MD USA.
Charite, Berlin Sch Publ Hlth, D-13353 Berlin, Germany.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e17569
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036903537
ER
PT J
AU Bot, A
Kochenderfer, J
Mardiros, A
Perez, A
Navale, L
Chang, R
Yueh, WS
Yoder, S
Jia, XC
Rosenberg, SA
Go, WY
Wiezorek, JS
Roberts, M
Chang, DD
AF Bot, Adrian
Kochenderfer, James
Mardiros, Armen
Perez, Arianne
Navale, Lynn
Chang, Richard
Yueh Wei-Shen
Yoder, Sean
Jia Xiao-Chi
Rosenberg, Steven A.
Go, William Y.
Wiezorek, Jeffrey S.
Roberts, Margo
Chang, David D.
TI Biomarker analysis of patients treated with anti-CD19 chimeric antigen
receptor (CAR) T cells.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Kite Pharma Inc, Santa Monica, CA USA.
NCI, Bethesda, MD 20892 USA.
Kite Pharma, Santa Monica, CA USA.
NR 0
TC 0
Z9 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 3028
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900662
ER
PT J
AU Bottaro, DP
Lee, YH
Wright, CE
Wong, TK
Agarwal, PK
Apolo, AB
AF Bottaro, Donald P.
Lee, Young H.
Wright, Cara E.
Wong, Tiffany K.
Agarwal, Piyush K.
Apolo, Andrea Borghese
TI Signaling by Met and related receptor tyrosine kinases in urothelial
carcinoma of the bladder.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Bethesda, MD 20892 USA.
NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e15511
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036903061
ER
PT J
AU Burris, HA
Giaccone, G
Im, SA
Bauer, TM
Oh, DY
Jones, SF
Nordstrom, JL
Li, H
Carlin, DA
Baughman, JE
Lechleider, RJ
Bang, YJ
AF Burris, Howard A.
Giaccone, Giuseppe
Im, Seock-Ah
Bauer, Todd Michael
Oh, Do-Youn
Jones, Suzanne Fields
Nordstrom, Jeffrey L.
Li, Hua
Carlin, David A.
Baughman, Jan E.
Lechleider, Robert Joseph
Bang, Yung-Jue
TI Updated findings of a first-in-human, phase I study of margetuximab (M),
an Fc-optimized chimeric monoclonal antibody (MAb), in patients (pts)
with HER2-positive advanced solid tumors.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Tennessee Oncol PLLC, Sarah Cannon Res Inst, Nashville, TN USA.
NCI, NIH, Bethesda, MD 20892 USA.
Seoul Natl Univ, Coll Med, Seoul, South Korea.
Tennessee Oncol PLLC, Sarah Cannon Res Inst, Nashville, TN USA.
Seoul Natl Univ Hosp, Dept Internal Med, Seoul 110744, South Korea.
MacroGenics Inc, Rockville, MD USA.
MacroGenics Inc, San Francisco, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 523
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901130
ER
PT J
AU Chavez-Mac Gregor, M
Barlow, WE
Pusztai, L
Goetz, MP
Rastogi, P
Ganz, PA
Mamounas, EP
Paik, S
Bandos, H
Gralow, J
Lew, DL
Hortobagyi, GN
AF Chavez-Mac Gregor, Mariana
Barlow, William E.
Pusztai, Lajos
Goetz, Matthew P.
Rastogi, Priya
Ganz, Patricia A.
Mamounas, Eleftherios P.
Paik, Soonmyung
Bandos, Hanna
Gralow, Julie
Lew, Danika L.
Hortobagyi, Gabriel N.
TI Phase III randomized, placebo-controlled clinical trial evaluating the
use of adjuvant endocrine therapy plus /- one year of everolimus in
patients with high-risk, hormone receptor (HR) positive and
HER2-negative breast cancer (BC): SWOG/NRG/Alliance S1207 (NCT01674140).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Canc Rsrch & Biostats, Seattle, WA USA.
Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT USA.
Mayo Clin, Rochester, MN USA.
NRG Oncol NSABP, Pittsburgh, PA USA.
UPMC Canc Ctr, Pittsburgh, PA USA.
UCLA Jonsson Comprehens Canc Ctr, Los Angeles, CA USA.
Natl Surg Adjuvant Breast & Bowel Project, Orlando, FL USA.
UF Hlth Canc Ctr Orlando Hlth, Orlando, FL USA.
Yonsei Univ, Coll Med, NRG Oncol NSABP, Pittsburgh, PA USA.
NRG Oncol NSABP, Pittsburgh, PA USA.
Severance BioMed Sci Inst, Pittsburgh, PA USA.
Yonsei Univ, Coll Med, Pittsburgh, PA USA.
NRG Oncol, Pittsburgh, PA USA.
Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA.
SWOG Stat Ctr, Seattle, WA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA TPS637
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036904829
ER
PT J
AU Chiou, VL
Kohn, EC
Annunziata, CM
Minasian, LM
Lipkowitz, S
Yu, M
Gordon, N
Houston, ND
Lee, JM
AF Chiou, Victoria L.
Kohn, Elise C.
Annunziata, Christina M.
Minasian, Lori M.
Lipkowitz, Stan
Yu, Minshu
Gordon, Nicolas
Houston, Nicole D.
Lee, Jung-min
TI Phase I/Ib study of the PARP inhibitor (PARPi) olaparib (O) with
carboplatin (C) in heavily pretreated high-grade serous ovarian cancer
(HGSOC) at low genetic risk (NCT01445418).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Bethesda, MD 20892 USA.
NCI, Rockville, MD USA.
NCI, NIH, Bethesda, MD 20892 USA.
NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
NIH, Bethesda, MD 20892 USA.
RI Annunziata, Christina/L-3219-2016
OI Annunziata, Christina/0000-0003-2033-6532
NR 0
TC 1
Z9 1
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 5514
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901173
ER
PT J
AU Chun, D
Lynch, JA
DuVall, SL
Filipski, KK
Kelley, MJ
Berse, B
Venne, V
AF Chun, Danielle
Lynch, Julie Ann
DuVall, Scott L.
Filipski, Kelly Kristin
Kelley, Michael J.
Berse, Brygida
Venne, Vickie
TI Utilization of BRCA1/BRCA2 testing in Veterans Health Administration.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Utah, Sch Med, Salt Lake City, UT USA.
Vet Healthcare Adm, Lincoln, MA USA.
NCI, Bethesda, MD 20892 USA.
Duke Univ, Chapel Hill, NC USA.
Boston Univ, Sch Med, Boston, MA 02118 USA.
Vet Healthcare Adm, Salt Lake City, UT USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e17510
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036903484
ER
PT J
AU Connolly, RM
Zhao, FM
Miller, K
Tevaarwerk, A
Wagner, LI
Lee, MJ
Murray, J
Gray, RJ
Piekarz, R
Zujewski, JA
Sparano, JA
AF Connolly, Roisin M.
Zhao, Fengmin
Miller, Kathy
Tevaarwerk, Amye
Wagner, Lynne I.
Lee, Min-Jung
Murray, Judy
Gray, Robert James
Piekarz, Richard
Zujewski, Jo Anne
Sparano, Joseph A.
TI E2112: Randomized phase III trial of endocrine therapy plus
entinostat/placebo in patients with hormone receptor-positive advanced
breast cancer.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
Dana Farber Canc Inst, Malden, MA USA.
Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA.
Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA.
Northwestern Univ, Feinberg Sch, Chicago, IL 60611 USA.
NIH, Bethesda, MD 20892 USA.
Johns Hopkins Univ, Baltimore, MD USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
Montefiore Med Ctr, Bronx, NY 10467 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA TPS636
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036904828
ER
PT J
AU Couvillon, A
Turkbey, B
Lindenberg, ML
Choyke, PL
Kaushal, A
Citrin, DE
Krauze, AV
McNally, D
McKinney, Y
Martinez, M
Han, H
Karzai, F
Parnes, HL
Pinto, PA
Gulley, JL
Dahut, WL
Madan, RA
AF Couvillon, Anna
Turkbey, Baris
Lindenberg, Maria Liza
Choyke, Peter L.
Kaushal, Aradhana
Citrin, Deborah E.
Krauze, Andra V.
McNally, Deborah
McKinney, Yolanda
Martinez, Mirna
Han, Hui
Karzai, Fatima
Parnes, Howard L.
Pinto, Peter A.
Gulley, James L.
Dahut, William L.
Madan, Ravi Amrit
TI Association of NaF PET/CT findings with PSA and alkaline phosphatase in
untreated castration-sensitive prostate cancer.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA.
NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
Ctr Canc Res, Mol Imaging Program, Bethesda, MD USA.
NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e16118
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036903283
ER
PT J
AU Coyne, GHO
Kummar, S
Do, KT
Holbeck, S
Hollingshead, MG
Horneffer, Y
Juwara, L
Srivastava, AK
Rubinstein, L
Piekarz, R
Sharon, E
Streicher, H
Conley, BA
Antony, R
Collins, JM
Chen, A
Doroshow, JH
AF Coyne, Geraldine Helen O'Sullivan
Kummar, Shivaani
Khanh Tu Do
Holbeck, Susan
Hollingshead, Melinda G.
Horneffer, Yvonne
Juwara, Lamin
Srivastava, Apurva K.
Rubinstein, Larry
Piekarz, Richard
Sharon, Elad
Streicher, Howard
Conley, Barbara A.
Antony, Ramya
Collins, Jerry M.
Chen, Alice
Doroshow, James H.
TI Phase I trial of the combination of bortezomib and clofarabine in adults
with refractory solid tumors.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Early Clin Trials Dev Program, Bethesda, MD USA.
Stanford Univ, Sch Med, Phase Clin Res Program 1, Stanford, CA 94305 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
NCI, Div Canc Treatment & Diag, NIH, Frederick, MD 21701 USA.
NCI, Bethesda, MD 20892 USA.
Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
Div Canc Treatment & Diag, Bethesda, MD USA.
NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA.
NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
NCI, Rockville, MD USA.
Leidos Biomed Res Inc, Frederick, MD USA.
NCI, DCTD, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 6
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA TPS2614
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036904692
ER
PT J
AU Deeken, JF
Wang, HK
Smaglo, BG
Hwang, JJ
He, AR
Weiner, LM
Marshall, J
Giaccone, G
Liu, SV
Luecht, J
Urso, C
Spiegel, JY
Cheema, A
Pishvaian, MJ
AF Deeken, John F.
Wang, Hongkun
Smaglo, Brandon George
Hwang, Jimmy J.
He, Aiwu Ruth
Weiner, Louis M.
Marshall, John
Giaccone, Giuseppe
Liu, Stephen V.
Luecht, Jim
Urso, Christina
Spiegel, Jay Y.
Cheema, Amrita
Pishvaian, Michael J.
TI A phase I study of intravenous artesunate (IV AS) in patients with solid
tumors.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Inova Comprehens Canc & Res Inst, Mclean, VA USA.
Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Med & Oncol, Washington, DC USA.
Georgetown Univ, Lombardi Comprehens Canc Ctr, Innovat Ctr Biomed Informat, Washington, DC USA.
NCI, NIH, Bethesda, MD 20892 USA.
Georgetown Univ Hosp, Washington, DC 20007 USA.
Georgetown Univ, Med Ctr, Washington, DC 20007 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 2535
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900568
ER
PT J
AU Denicoff, A
Massett, HA
Mishkin, GE
Bangs, R
Berlin, J
Bischoff, MB
DeSanto, F
Duli, A
Horvath, LE
Katz, MS
Lambersky, R
Mann, BS
McCaskill-Stevens, WJ
Seibel, N
Stine, SH
Williams, W
Mooney, MM
Abrams, JS
AF Denicoff, Andrea
Massett, Holly A.
Mishkin, Grace E.
Bangs, Rick
Berlin, Jordan
Bischoff, Miriam B.
DeSanto, Frank
Duli, Anne
Horvath, Laura E.
Katz, Michael S.
Lambersky, Ruth
Mann, Bhupinder Singh
McCaskill-Stevens, Worta J.
Seibel, Nita
Stine, Sharon Hartson
Williams, Wade
Mooney, Margaret M.
Abrams, Jeffrey S.
TI Creating a national collaborative strategy to enhance trial accrual in
NCI's National Clinical Trials Network (NCTN) in the era of precision
medicine
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Bethesda, MD 20892 USA.
SWOG, San Antonio, TX USA.
Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
Stanford Canc Ctr, Stanford, CA USA.
SWOG, Ann Arbor, MI USA.
Case Comprehens Canc Ctr, Cleveland, OH USA.
Alliance Clin Trials Oncol, Naperville, IL USA.
ECOG ACRIN, North Hollywood, CA USA.
ECOG ACRIN, Philadelphia, PA USA.
NCI, Rockville, MD USA.
NRG Oncol, Merchantville, NJ USA.
Univ Oklahoma, Hlth Sci Ctr, Stephenson Canc Ctr, Oklahoma City, OK USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 6589
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901503
ER
PT J
AU Disis, ML
Patel, MR
Pant, S
Infante, JR
Lockhart, AC
Kelly, K
Beck, JT
Gordon, MS
Weiss, GJ
Ejadi, S
Taylor, MH
von Heydebreck, A
Chin, KM
Cuillerot, JM
Gulley, JL
AF Disis, Mary L.
Patel, Manish R.
Pant, Shubham
Infante, Jeffrey R.
Lockhart, A. Craig
Kelly, Karen
Beck, Joseph Thaddeus
Gordon, Michael S.
Weiss, Glen J.
Ejadi, Samuel
Taylor, Matthew Hiram
von Heydebreck, Anja
Chin, Kevin M.
Cuillerot, Jean-Marie
Gulley, James L.
TI Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with
previously treated, recurrent or refractory ovarian cancer: A phase Ib,
open-label expansion trial.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Washington, Sch Med, Seattle, WA USA.
Florida Canc Specialists, Sarah Cannon Res Inst, Sarasota, FL USA.
Peggy & Charles Stephenson Oklahoma Canc Ctr, Oklahoma City, OK USA.
Sarah Cannon Res Inst Tennessee Oncol, Nashville, TN USA.
Washington Univ, Sch Med, St Louis, MO USA.
UC Davis Comprehens Canc Ctr, Sacramento, CA USA.
Highlands Oncol Grp, Rogers, AR USA.
Pinnacle Oncol Hematol, Scottsdale, AZ USA.
Canc Treatment Centers Amer, Western Reg Med Ctr, Goodyear, AZ USA.
Virginia G Piper Canc Ctr, Scottsdale, AZ USA.
Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
Merck KGaA, Darmstadt, Germany.
EMD Serono, Billerica, MA USA.
NCI, NIH, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 6
Z9 6
U1 5
U2 11
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 5509
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901167
ER
PT J
AU Dix, DB
Gratias, EJ
Seibel, N
Anderson, JR
Mullen, EA
Geller, JI
Khanna, G
Kalapurakal, JA
Perlman, EJ
Ehrlich, PF
Malogolowkin, MH
Grundy, PE
Dome, JS
AF Dix, David B.
Gratias, Eric J.
Seibel, Nita
Anderson, James Robert
Mullen, Elizabeth Anne
Geller, James I.
Khanna, Geetika
Kalapurakal, John A.
Perlman, Elizabeth Jones
Ehrlich, Peter F.
Malogolowkin, Marcio H.
Grundy, Paul Edward
Dome, Jeffrey S.
TI Omission of lung radiation in patients with stage IV favorable histology
Wilms Tumor (FHWT) showing complete lung nodule response after
chemotherapy: A report from Children's Oncology Group study AREN0533.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 British Columbia Childrens Hosp, Vancouver, BC V6H 3V4, Canada.
TC Thompson Childrens Hosp, Chattanooga, TN USA.
NCI, Bethesda, MD 20892 USA.
Frontier Sci Madison, Madison, WI USA.
Dana Farber Boston Childrens Canc & Blood Disorde, Boston, MA USA.
Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
Washington Univ, Sch Med St Louis, St Louis, MO USA.
Northwestern Univ, Lurie Comp Canc Ctr, Chicago, IL 60611 USA.
Northwestern Univ, Feinberg Sch Med, Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA.
Alberta Hlth Svcs, Edmonton, AB, Canada.
Childrens Natl Med Ctr, Washington, DC 20010 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 10011
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900015
ER
PT J
AU Dix, DB
Fernandez, CV
Chi, YY
Anderson, JR
Mullen, EA
Geller, JI
Gratias, EJ
Khanna, G
Kalapurakal, JA
Perlman, EJ
Seibel, N
Ehrlich, PF
Malogolowkin, MH
Gow, KW
Hamilton, TE
Grundy, PE
Dome, J
AF Dix, David B.
Fernandez, Conrad Vincent
Chi, Yueh-Yun
Anderson, James Robert
Mullen, Elizabeth Anne
Geller, James I.
Gratias, Eric J.
Khanna, Geetika
Kalapurakal, John A.
Perlman, Elizabeth Jones
Seibel, Nita
Ehrlich, Peter F.
Malogolowkin, Marcio H.
Gow, Kenneth William
Hamilton, Thomas Edward
Grundy, Paul Edward
Dome, Jeffrey
TI Augmentation of therapy for favorable-histology Wilms Tumor with
combined loss of heterozygosity of chromosomes 1p and 16q: A report from
the Children's Oncology Group studies AREN0532 and AREN0533.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 British Columbia Childrens Hosp, Vancouver, BC V6H 3V4, Canada.
IWK Hlth Ctr, Halifax, NS, Canada.
Dept Biostat, Gainesville, FL USA.
Frontier Sci Madison, Madison, WI USA.
Dana Farber Boston Childrens Canc & Blood Disorde, Boston, MA USA.
Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
TC Thompson Childrens Hosp, Chattanooga, TN USA.
Washington Univ, Sch Med, St Louis, MO USA.
Northwestern Univ, Lurie Comp Canc Ctr, Chicago, IL 60611 USA.
Northwestern Univ, Feinberg Sch Med, Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA.
NCI, Bethesda, MD 20892 USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA.
Seattle Childrens Hosp, Seattle, WA USA.
Boston Childrens Hosp, Boston, MA USA.
Alberta Hlth Svcs, Edmonton, AB, Canada.
Childrens Natl Med Ctr, Washington, DC USA.
NR 0
TC 1
Z9 1
U1 2
U2 2
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 10009
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900012
ER
PT J
AU Doros, LA
Turner, J
Williams, GM
Rossi, C
Schultz, KAP
Stewart, D
Dehner, LP
Messinger, YH
Hill, DA
AF Doros, Leslie Ann
Turner, Joyce
Williams, Gretchen M.
Rossi, Christopher
Schultz, Kris Ann Pinekenstein
Stewart, Douglas
Dehner, Louis P.
Messinger, Yoav H.
Hill, D. Ashley
TI The DICER1 syndrome: Genotype-phenotype correlation in PPB patients.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Childrens Natl Med Ctr, Arlington, VA USA.
Childrens Natl Med Ctr, Washington, DC 20010 USA.
Childrens Hosp & Clin Minnesota, Minneapolis, MN USA.
NCI, Bethesda, MD 20892 USA.
Washington Univ, Sch Med, St Louis, MO USA.
Childrens Hosp & Clin, Minneapolis, MN USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 10022
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900027
ER
PT J
AU Drilon, AE
Eaton, A
Schindler, K
Gounder, MM
Smith, GL
Vulih, D
Harris, PJ
Spriggs, DR
Ivy, P
Iasonos, A
Lacouture, ME
Hyman, DM
AF Drilon, Alexander E.
Eaton, Anne
Schindler, Katja
Gounder, Mrinal M.
Smith, Gary L.
Vulih, Diana
Harris, Pamela Jo
Spriggs, David R.
Ivy, Percy
Iasonos, Alexia
Lacouture, Mario E.
Hyman, David Michael
TI Dermatologic toxicities of 3,517 solid tumor patients on phase I
clinical trials of the National Institutes of Health Cancer Therapy
Evaluation Program (CTEP).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Med Univ Vienna, Vienna, Austria.
NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
Theradex Syst Inc, Princeton, NJ USA.
NCI, Canc Therapeut Evaluat Program, Bethesda, MD 20892 USA.
Weill Cornell Med Coll, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 2546
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900579
ER
PT J
AU Duffy, AG
Makarova-Rusher, OV
Kerkar, SP
Kleiner, DE
Fioravanti, S
Walker, M
Carey, S
Figg, WD
Steinberg, SM
Anderson, V
Abi-Jaoudeh, N
Levi, E
Wood, BJ
Greten, TF
AF Duffy, Austin G.
Makarova-Rusher, Oxana V.
Kerkar, Sid P.
Kleiner, David E.
Fioravanti, Suzanne
Walker, Melissa
Carey, Stephanie
Figg, William Douglas
Steinberg, Seth M.
Anderson, Victoria
Abi-Jaoudeh, Nadine
Levi, Elliot
Wood, Bradford J.
Greten, Tim F.
TI A pilot study of tremelimumab - a monoclonal antibody against CTLA-4-in
combination with either trans catheter arterial chemoembolization (TACE)
or radiofrequency ablation (RFA) in patients with hepatocellular
carcinoma (HCC).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, NIH, Bethesda, MD 20892 USA.
NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, Gastrointestinal Malignancies Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, Clin Pharmacol Program, NIH, Bethesda, MD 20892 USA.
NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.
NIH, Radiol & Imaging Sci, Ctr Canc Res, Bethesda, MD 20892 USA.
NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, Ctr Intervent Oncol, NIH, Bethesda, MD USA.
RI Figg Sr, William/M-2411-2016
NR 0
TC 1
Z9 2
U1 0
U2 2
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 4081
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900919
ER
PT J
AU Duffy, AG
Ma, C
Ulahannan, SV
Makarova-Rusher, OV
Fioravanti, S
Walker, M
Turkbey, B
Trepel, J
Cao, L
Steinberg, SM
Figg, WD
Greten, TF
AF Duffy, Austin G.
Ma, Chi
Ulahannan, Susanna Varkey
Makarova-Rusher, Oxana V.
Fioravanti, Suzanne
Walker, Melissa
Turkbey, Baris
Trepel, Jane
Cao, Liang
Steinberg, Seth M.
Figg, William Douglas
Greten, Tim F.
TI A phase 1/2 study of TRC105 in combination with sorafenib in
hepatocellular carcinoma (HCC)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, NIH, Bethesda, MD 20892 USA.
Canc & Blood Care PC, Ponca City, OK USA.
NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.
NCI, Clin Pharmacol Program, NIH, Bethesda, MD 20892 USA.
RI Figg Sr, William/M-2411-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 4083
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900921
ER
PT J
AU Eaton, A
Iasonos, A
Gounder, MM
Pamer, E
Drilon, AE
Vulih, D
Smith, GL
Ivy, P
Spriggs, DR
Hyman, DM
AF Eaton, Anne
Iasonos, Alexia
Gounder, Mrinal M.
Pamer, Erika
Drilon, Alexander E.
Vulih, Diana
Smith, Gary L.
Ivy, Percy
Spriggs, David R.
Hyman, David Michael
TI Physician toxicity attribution in phase I trials: Evaluating the effect
of dose on the frequency of 11,909 toxicities.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Theradex Syst Inc, Princeton, NJ USA.
NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
Weill Cornell Med Coll, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e17674
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036903626
ER
PT J
AU Feng, LR
Wolff, BS
Lukkahatai, N
Saligan, LN
AF Feng, Li Rebekah
Wolff, Brian S.
Lukkahatai, Nada
Saligan, Leorey N.
TI Immunological predictors of fatigue outcomes in prostate cancer patients
receiving radiation therapy.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NIH, Bethesda, MD 20892 USA.
Univ Nevada, Las Vegas, NV 89154 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e16130
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036903293
ER
PT J
AU George, A
Hoang, AN
Rais-Bahrami, S
Walton-Diaz, A
Rastinehad, A
Siddiqui, MM
Shakir, NA
Ho, R
Fascelli, M
Abboud, SF
Chelluri, R
Merino, MJ
Choyke, PL
Turkbey, B
Wood, BJ
Pinto, PA
AF George, Arvin
Hoang, Anthony N.
Rais-Bahrami, Soroush
Walton-Diaz, Annerleim
Rastinehad, Ardeshir
Siddiqui, Mohummad Minhaj
Shakir, Nabeel Ahmad
Ho, Richard
Fascelli, Michele
Abboud, Steven F.
Chelluri, Raju
Merino, Maria J.
Choyke, Peter L.
Turkbey, Baris
Wood, Bradford J.
Pinto, Peter A.
TI Magnetic resonance imaging-guided focal laser ablation for prostate
cancer: A phase I trial.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
NIH, Bethesda, MD 20892 USA.
Hofstra North Shore LIJ Sch Med, New Hyde Pk, NY USA.
NIH, Rockville, MD USA.
NCI, NIH, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
NCI, Mol Imaging Program, NIH, Bethesda, MD USA.
NCI, Ctr Intervent Oncol, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e16128
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036903291
ER
PT J
AU Gerber, DE
Oxnard, GR
Mandrekar, SJ
Dahlberg, SE
Malik, SM
Mooney, MM
Abrams, JS
Janne, PA
Li, TH
Ramalingam, SS
Vokes, EE
Govindan, R
AF Gerber, David E.
Oxnard, Geoffrey R.
Mandrekar, Sumithra J.
Dahlberg, Suzanne Eleanor
Malik, Shakun M.
Mooney, Margaret M.
Abrams, Jeffrey S.
Janne, Pasi A.
Li, Tianhong
Ramalingam, Suresh S.
Vokes, Everett E.
Govindan, Ramaswamy
TI ALCHEMIST: a clinical trial platform to bring genomic discovery and
molecularly targeted therapies to early-stage lung cancer.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Mayo Clin, Rochester, MN USA.
Clin Invest Branch CTEP DCTD, Rockville, MD USA.
NCI, Bethesda, MD 20892 USA.
UC Davis Comprehens Canc Ctr, Sacramento, CA USA.
Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
Univ Chicago, Dept Med, Chicago, IL 60637 USA.
Washington Univ, Sch Med, St Louis, MO USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA TPS7583
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036904847
ER
PT J
AU Goey, AKL
Trepel, JB
Sissung, TM
Peer, CJ
Lee, MJ
Tomita, Y
Ehrlich, S
Bryla, C
Berman, AW
Balasubramaniam, S
Piekarz, R
Rajan, A
Steinberg, SM
Giaccone, G
Figg, WD
Bates, SE
AF Goey, Andrew K. L.
Trepel, Jane B.
Sissung, Tristan M.
Peer, Cody J.
Lee, Min-Jung
Tomita, Yusuke
Ehrlich, Sheryl
Bryla, Christine
Berman, Arlene W.
Balasubramaniam, Sanjeeve
Piekarz, Richard
Rajan, Arun
Steinberg, Seth M.
Giaccone, Giuseppe
Figg, William Douglas
Bates, Susan Elaine
TI UGT1A1 genotype effects on PK, PD and toxicities of belinostat
administered by 48 h continuous infusion.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Clin Pharmacol Program, NIH, Bethesda, MD 20892 USA.
NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, Mol Pharmacol Program, NIH, Bethesda, MD 20892 USA.
NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
NCI, Thorac & Gastrointestinal Oncol Branch, NIH, Bethesda, MD 20892 USA.
NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA.
NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
RI Figg Sr, William/M-2411-2016
NR 0
TC 0
Z9 0
U1 0
U2 2
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e13581
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036902574
ER
PT J
AU Goncalves, PH
Soubani, AO
Heilbrun, LK
Smith, DW
Villegas, J
LoRusso, P
AF Goncalves, Priscila Hermont
Soubani, Ayman O.
Heilbrun, Lance K.
Smith, Daryn W.
Villegas, Juan
LoRusso, Patricia
TI Pulmonary function tests (PFT) results in a phase 1 (Ph1) oncology
patient (pt) population.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, NIH, Bethesda, MD 20892 USA.
Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
Mt Sinai Hosp, Chicago, IL USA.
Yale Canc Ctr, New Haven, CT USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e17759
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036903699
ER
PT J
AU Gulley, JL
Giacchino, JL
Breitmeyer, JB
Franzusoff, AJ
Panicali, D
Schlom, J
Kantoff, PW
AF Gulley, James L.
Giacchino, Jeannie Lorraine
Breitmeyer, James Bradley
Franzusoff, Alexis J.
Panicali, Dennis
Schlom, Jeffrey
Kantoff, Philip W.
TI Prospect: A randomized double-blind phase 3 efficacy study of
PROSTVAC-VF immunotherapy in men with asymptomatic/minimally symptomatic
metastatic castration-resistant prostate cancer.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, NIH, Bethesda, MD 20892 USA.
Bavarian Nord AS, Mountain View, CA USA.
Bavarian Nord Inc, Mountain View, CA USA.
Bavarian Nord Inc, Mountain View, CA USA.
NCI, Lab Tumor Immunol & Biol, NIH, Bethesda, MD 20892 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA TPS5081
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036904790
ER
PT J
AU Gulley, JL
Madan, RA
Singh, H
Gray, TE
Trager, JB
Sheikh, NA
Mccoy, C
McNeel, DG
AF Gulley, James L.
Madan, Ravi Amrit
Singh, Harpreet
Gray, Todd E.
Trager, James B.
Sheikh, Nadeem A.
Mccoy, Candice
McNeel, Douglas G.
TI The impact of age on sipuleucel-T-induced immune responses.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, NIH, Bethesda, MD 20892 USA.
NCI, NIH, Washington, DC USA.
Dendreon Corp, Seattle, WA USA.
Univ Wisconsin, Madison, WI USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e16009
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036903186
ER
PT J
AU Gulley, JL
Spigel, D
Kelly, K
Chandler, JC
Rajan, A
Hassan, R
Wong, DJL
Leach, J
Edenfield, WJ
Wang, D
Vrindavanam, N
Weiss, GJ
Gurtler, JS
Grote, HJ
von Heydebreck, A
Chin, KM
Iannotti, N
AF Gulley, James L.
Spigel, David
Kelly, Karen
Chandler, Jason Claud
Rajan, Arun
Hassan, Raffit
Wong, Deborah Jean Lee
Leach, Joseph
Edenfield, William Jeffery
Wang, Ding
Vrindavanam, Nandagopal
Weiss, Glen J.
Gurtler, Jayne S.
Grote, Hans Juergen
von Heydebreck, Anja
Chin, Kevin M.
Iannotti, Nicholas
TI Avelumab (MSB0010718C), an anti-PD-L1 antibody, in advanced NSCLC
patients: A phase 1b, open-label expansion trial in patients progressing
after platinum-based chemotherapy.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, NIH, Bethesda, MD 20892 USA.
Tennessee Oncol PLLC, Sarah Cannon Res Inst, Nashville, TN USA.
UC Davis Comprehens Canc Ctr, Sacramento, CA USA.
West Clin, Memphis, TN USA.
NCI, Thorac & Gastrointestinal Oncol Branch, NIH, Bethesda, MD 20892 USA.
NCI, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res, Bethesda, MD USA.
Univ Calif Los Angeles, Los Angeles, CA USA.
Virginia Piper Canc Inst, Minneapolis, MN USA.
Inst Translat Oncol Res, Greenville, SC USA.
Henry Ford Hlth Syst, Detroit, MI USA.
Signal Point Clin Res Ctr LLC, Middletown, OH USA.
Canc Treatment Ctr Amer, Western Reg Med Ctr, Goodyear, AZ USA.
Metairie Oncologist LLC, Metairie, LA USA.
Merck KGaA, Darmstadt, Germany.
EMD Serono, Billerica, MA USA.
Hematol Oncol Associates Treasure Coast, Port St Lucie, FL USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 2
Z9 2
U1 0
U2 2
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 8034
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901747
ER
PT J
AU Halpern, MT
Urato, M
Schwartz, M
Kent, EE
AF Halpern, Michael T.
Urato, Matthew
Schwartz, Margot
Kent, Erin E.
TI Healthcare plan and provider ratings among cancer survivors.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Arizona, Coll Publ Hlth, Tucson, AZ USA.
RTI Int, Res Triangle Pk, NC USA.
RTI Int, Waltham, MA USA.
NCI, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 9579
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036902074
ER
PT J
AU Hamilton, EP
Birrer, MJ
DiCarlo, BA
Gaillard, S
Martin, LP
Nemunaitis, JJ
Perez, RP
Schilder, RJ
Annunziata, CM
Begley, CG
Hager, SJ
AF Hamilton, Erika Paige
Birrer, Michael J.
DiCarlo, Brian Anthony
Gaillard, Stephanie
Martin, Lainie P.
Nemunaitis, John J.
Perez, Raymond P.
Schilder, Russell J.
Annunziata, Christina M.
Begley, Colin G.
Hager, Steven Jeffrey
TI A phase 1b, open-label, non-randomized multicenter study of birinapant
in combination with conatumumab in subjects with relapsed epithelial
ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Tennessee Oncol PLLC, Sarah Cannon Res Inst, Nashville, TN USA.
Massachusetts Gen Hosp, Dana Farber Canc Ctr, Boston, MA 02114 USA.
Coastal Integrat Canc Care, San Luis Obispo, CA USA.
Duke Canc Inst, Durham, NC USA.
Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
Mary Crowley Canc Res Ctr, Dallas, TX USA.
Univ Kansas, Fairway, KS USA.
Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
NCI, NIH, Bethesda, MD 20892 USA.
TetraLog Pharmaceut, Westlake Village, CA USA.
Calif Canc Associates Res & Excellence, Fresno, CA USA.
RI Annunziata, Christina/L-3219-2016; Perez, Raymond/R-6159-2016
OI Annunziata, Christina/0000-0003-2033-6532; Perez,
Raymond/0000-0002-7432-2411
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 5571
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901236
ER
PT J
AU Hassan, R
Antonia, SJ
Alley, EW
Kindler, HL
Jahan, T
Grous, JJ
Honarmand, S
McDougall, K
Whiting, CC
Nair, N
Lemmens, E
Murphy, AL
Thomas, A
Brockstedt, DG
AF Hassan, Raffit
Antonia, Scott Joseph
Alley, Evan W.
Kindler, Hedy Lee
Jahan, Thierry
Grous, John J.
Honarmand, Somayeh
McDougall, Katherine
Whiting, Chan C.
Nair, Nitya
Lemmens, Ed
Murphy, Aimee L.
Thomas, Anish
Brockstedt, Dirk G.
TI Mesothelin-targeted immunotherapy CRS-207 in combination with standard
of care chemotherapy as treatment for malignant pleural mesothelioma
(MPM).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
Univ Penn, Philadelphia, PA 19104 USA.
Univ Chicago, Chicago, IL 60637 USA.
UC San Francisco, San Francisco, CA USA.
Aduro BioTech Inc, Berkeley, CA USA.
NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
NR 0
TC 2
Z9 2
U1 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 7565
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901695
ER
PT J
AU Heery, CR
Infante, JR
Iannotti, N
Kelly, K
Nikolinakos, P
von Heydebreck, A
Chin, KM
Gulley, JL
AF Heery, Christopher Ryan
Infante, Jeffrey R.
Iannotti, Nicholas
Kelly, Karen
Nikolinakos, Petros
von Heydebreck, Anja
Chin, Kevin M.
Gulley, James L.
TI Phase I expansion cohort trial to investigate the safety and clinical
activity of avelumab (MSB0010718C) in patients with metastatic or
locally advanced solid tumors.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Lab Tumor Immunol & Biol, NIH, Bethesda, MD 20892 USA.
Tennessee Oncol, Sarah Cannon Res Inst, Nashville, TN USA.
Hematol Oncol Associates Treasure Coast, Port St Lucie, FL USA.
UC Davis Comprehens Canc Ctr, Sacramento, CA USA.
Northeast Georgia Canc Care, Athens, GA USA.
Merck KGaA, Darmstadt, Germany.
EMD Serono, Billerica, MA USA.
NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA TPS3101
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036904717
ER
PT J
AU Heery, CR
Coyne, GHO
Marte, JL
Singh, H
Cordes, LM
Madan, RA
Donahue, RN
Grenga, I
Lepone, L
Neuteboom, B
Speit, I
Chin, KM
Schlom, J
Gulley, JL
AF Heery, Christopher Ryan
Coyne, Geraldine Helen O'Sullivan
Marte, Jennifer L.
Singh, Harpreet
Cordes, Lisa M.
Madan, Ravi Amrit
Donahue, Renee Nicole
Grenga, Italia
Lepone, Lauren
Neuteboom, Berend
Speit, Isabell
Chin, Kevin M.
Schlom, Jeffrey
Gulley, James L.
TI Pharmacokinetic profile and receptor occupancy of avelumab
(MSB0010718C), an anti-PD-L1 monoclonal antibody, in a phase I,
open-label, dose escalation trial in patients with advanced solid
tumors.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Lab Tumor Immunol & Biol, NIH, Bethesda, MD 20892 USA.
NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD USA.
NCI, NIH, Washington, DC USA.
NIH, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
Ctr Canc Res, Lab Tumor Immunol & Biol, Bethesda, MD USA.
EMD Serono, Billerica, MA USA.
Merck KGaA, Darmstadt, Germany.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 3055
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900689
ER
PT J
AU Heske, C
Mendoza, A
Yeung, C
Proia, DA
Neckers, L
Helman, LJ
AF Heske, Christine
Mendoza, Arnulfo
Yeung, Choh
Proia, David A.
Neckers, Len
Helman, Lee J.
TI Activity of Hsp90-inhibitor drug conjugate (HDC) STA-12-8666 in
preclinical models of pediatric sarcoma.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
Synta Pharmaceut, Lexington, MA USA.
NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 10025
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900030
ER
PT J
AU Hobday, TJ
Yin, J
Pettinger, A
Strosberg, JR
Reidy, DL
Chen, HX
Erlichman, C
AF Hobday, Timothy J.
Yin, Jun
Pettinger, Adam
Strosberg, Jonathan R.
Reidy, Diane Lauren
Chen, Helen X.
Erlichman, Charles
TI Multicenter prospective phase II trial of bevacizumab (bev) for
progressive pancreatic neuroendocrine tumor (PNET)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Mayo Clin, Coll Med, Dept Oncol, Rochester, MN USA.
Mayo Clin, Rochester, MN USA.
Mayo Clin, Coll Med, Rochester, MN USA.
Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Weill Cornell Med Coll, New York, NY USA.
NCI, Canc Therapy Evaluat Program, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 4096
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900934
ER
PT J
AU Hyman, DM
Sill, M
Cho, JK
Lankes, HA
Piekarz, R
Hensley, ML
AF Hyman, David Michael
Sill, Michael
Cho, Jonathan K.
Lankes, Heather A.
Piekarz, Richard
Hensley, Martee Leigh
TI A phase II study of alisertib (MLN8237) in recurrent or persistent
uterine leiomyosarcoma: An NRG Oncology/Gynecologic Oncology Group Study
(GOG-0231D).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Stat & Data Ctr, Gynecol Oncol Grp, Buffalo, NY USA.
Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
Gyn Onc Grp, Buffalo, NY USA.
NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA.
Weill Cornell Med Coll, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e16512
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036903309
ER
PT J
AU Jacobsen, PB
Rowland, JH
Paskett, ED
Van Leeuwen, F
Moskowitz, CS
Katta, S
Wollins, D
Robison, LL
AF Jacobsen, Paul B.
Rowland, Julia Howe
Paskett, Electra D.
Van Leeuwen, Flora
Moskowitz, Chaya S.
Katta, Sweatha
Wollins, Dana
Robison, Leslie L.
TI Results of the ASCO survey of cancer survivorship research: Summary and
implications.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
NCI, NIH, Bethesda, MD USA.
Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
Netherlands Canc Inst, Dept Psychosocial Oncol & Epidemiol, Amsterdam, Netherlands.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Amer Soc Clin Oncol, Alexandria, VA USA.
St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 9567
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036902062
ER
PT J
AU Jang, S
Zheng, CY
Tsai, HT
Fu, AZ
Barac, A
Atkins, MB
Freeman, AN
Minasian, LM
Potosky, AL
AF Jang, Sekwon
Zheng, Chaoyi
Tsai, Huei-Ting
Fu, Alex Z.
Barac, Ana
Atkins, Michael B.
Freeman, Andrew N.
Minasian, Lori M.
Potosky, Arnold L.
TI Cardiovascular toxicity following anti-angiogenic therapy in persons
over age 65 with advanced renal cell carcinoma.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Inova Comprehens Canc & Res Inst, Fairfax, VA USA.
Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
MedStar Washington Hosp Ctr, Washington, DC USA.
Lombardi Comprehens Canc Ctr, Washington, DC USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 4544
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901015
ER
PT J
AU Ji, JPJ
Zhang, YP
Redon, CE
Chen, A
Holbeck, S
Hollingshead, MG
Parchment, RE
Pommier, Y
Tomaszewski, JE
Doroshow, JH
Bonner, W
AF Ji, Jiuping Jay
Zhang, Yiping
Redon, Christophe E.
Chen, Alice
Holbeck, Susan
Hollingshead, Melinda G.
Parchment, Ralph E.
Pommier, Yves
Tomaszewski, Joseph E.
Doroshow, James H.
Bonner, William
TI Using gamma-H2AX and H2AX quantitative ELISA for monitoring DNA damage
induced by chemotherapeutic agents and irradiation exposure.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Frederick Natl Lab Canc Res, Natl Clin Target Validat Lab, Frederick, MD USA.
NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
NCI, Div Canc Treatment & Diag, NIH, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 2
U2 4
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 2559
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900592
ER
PT J
AU Jochems, C
Kwilas, A
Kim, YS
Brechbiel, MW
Hodge, JW
Newton, RC
Schlom, J
Tsang, KY
AF Jochems, Caroline
Kwilas, Anna
Kim, Young-Seung
Brechbiel, Martin W.
Hodge, James W.
Newton, Robert Charles
Schlom, Jeffrey
Tsang, Kwong-Yok
TI The IDO inhibitor INCB024360 to enhance dendritic cell immunogenicity
and anti-tumor immunity in vitro.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Lab Tumor Immunol & Biol, NIH, Bethesda, MD 20892 USA.
NCI, Lab Tumor Immunol & Biol, CCR, NIH, Bethesda, MD 20892 USA.
NCI, Radioimmune & Chem Sect, CCR, NIH, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
Incyte Corp, Avondale, PA USA.
NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 4
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e14012
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036902603
ER
PT J
AU Karzai, F
Madan, RA
Theoret, MR
Arlen, PM
Strauss, J
Chun, G
Couvillon, A
Harold, N
Chen, C
Dawson, NA
Apolo, AB
Steinberg, SM
Trepel, JB
Wright, JJ
Price, DK
Gulley, JL
Figg, WD
Dahut, WL
AF Karzai, Fatima
Madan, Ravi Amrit
Theoret, Marc Robert
Arlen, Philip M.
Strauss, Julius
Chun, Guinevere
Couvillon, Anna
Harold, Nancy
Chen, Clara
Dawson, Nancy Ann
Apolo, Andrea Borghese
Steinberg, Seth M.
Trepel, Jane B.
Wright, John Joseph
Price, Douglas K.
Gulley, James L.
Figg, William Douglas
Dahut, William L.
TI Overcoming resistance mechanisms in a study of cabozantinib (C) plus
docetaxel (D) and prednisone (P) in metastatic castrate-resistant
prostate cancer (mCRPC).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, NIH, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA.
NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD USA.
Lombardi Comprehens Canc Ctr, Washington, DC USA.
NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.
NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA.
NCI, Clin Pharmacol Program, NIH, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016
OI Gulley, James/0000-0002-6569-2912;
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e16032
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036903207
ER
PT J
AU Kazandjian, DG
Blumenthal, GM
Fernandes, L
Mathieu, LN
Tang, SH
Sridhara, R
Kluetz, PG
Keegan, P
Pazdur, R
AF Kazandjian, Dickran Gano
Blumenthal, Gideon Michael
Fernandes, Laura
Mathieu, Luckson Noe
Tang, Shenghui
Sridhara, Rajeshwari
Kluetz, Paul Gustav
Keegan, Patricia
Pazdur, Richard
TI The relationship of delay in time to deterioration of chest pain, cough
and dyspnea with radiographic response with targeted therapies (TT) and
chemotherapy (CT) in NSCLC.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 US FDA, Rockville, MD 20857 USA.
NIH, Potomac, MD USA.
US FDA, Silver Spring, MD USA.
US FDA, Silver Spring, MD USA.
FDA, Kensington, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e19052
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036903906
ER
PT J
AU Kelly, K
Patel, MR
Infante, JR
Iannotti, N
Nikolinakos, P
Leach, J
Wang, D
Chandler, JC
Jerusalem, GHM
Gurtler, JS
Arkenau, HT
Speit, I
von Heydebreck, A
Chin, KM
Heery, CR
Gulley, JL
AF Kelly, Karen
Patel, Manish R.
Infante, Jeffrey R.
Iannotti, Nicholas
Nikolinakos, Petros
Leach, Joseph
Wang, Ding
Chandler, Jason Claud
Jerusalem, Guy Heinrich Maria
Gurtler, Jayne S.
Arkenau, Hendrik-Tobias
Speit, Isabell
von Heydebreck, Anja
Chin, Kevin M.
Heery, Christopher Ryan
Gulley, James L.
TI Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with
metastatic or locally advanced solid tumors: assessment of safety and
tolerability in a phase I, open-label expansion study.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 UC Davis Comprehens Canc Ctr, Sacramento, CA USA.
Florida Canc Specialists, Sarah Cannon Res Inst, Sarasota, FL USA.
Tennessee Oncol, Sarah Cannon Res Inst, Nashville, TN USA.
Hematol Oncol Associates Treasure Coast, Port St Lucie, FL USA.
Univ Canc & Blood Ctr LLC, Athens, GA USA.
Virginia Piper Canc Inst, Minneapolis, MN USA.
Henry Ford Hlth Syst, Detroit, MI USA.
West Clin, Memphis, TN USA.
Ctr Hosp Univ, Liege, Belgium.
Metairie Oncologist LLC, Metairie, LA USA.
Sarah Cannon Res United Kingdom, London, England.
Merck KGaA, Darmstadt, Germany.
EMD Serono, Billerica, MA USA.
NCI, Lab Tumor Immunol & Biol, NIH, Bethesda, MD 20892 USA.
NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 4
Z9 4
U1 0
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 3044
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900678
ER
PT J
AU Koshkin, VS
Bolejack, V
Schwartz, LH
Zhao, BS
Chugh, R
Wahl, RL
Reinke, DK
Helman, LJ
Patel, S
Schuetze, S
Baker, LH
AF Koshkin, Vadim S.
Bolejack, Vanessa
Schwartz, Lawrence H.
Zhao, Binsheng
Chugh, Rashmi
Wahl, Richard L.
Reinke, Denise K.
Helman, Lee J.
Patel, Shreyaskumar
Schuetze, Scott
Baker, Laurence H.
TI The who and what of imaging in sarcoma and correlation with survival
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Michigan, Ann Arbor, MI 48109 USA.
Canc Res & Biostat, Seattle, WA USA.
Columbia Univ Med Ctr, New York Presbyterian Hosp, New York, NY USA.
Columbia Univ Med Ctr, Dept Radiol, New York, NY USA.
Univ Michigain Hlth Syst, Ann Arbor, MI USA.
Mallinckrodt Inst Rad, St Louis, MO USA.
SARC, Ann Arbor, MI USA.
NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 10511
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900146
ER
PT J
AU Kothari, S
Gustafson, D
Killian, K
Costello, J
Edelman, DC
Walling, J
Meltzer, PS
Theodorescu, D
Apolo, AB
AF Kothari, Shalin
Gustafson, Daniel
Killian, Keith
Costello, James
Edelman, Daniel C.
Walling, Jennifer
Meltzer, Paul S.
Theodorescu, Dan
Apolo, Andrea Borghese
TI COXEN prediction of antineoplastic drug sensitivity in bladder cancer
patients
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 SUNY Upstate Med Univ, Syracuse, NY 13210 USA.
Colorado State Univ, Ft Collins, CO 80523 USA.
NCI, Bethesda, MD 20892 USA.
Univ Colorado, Aurora, CO USA.
Ctr Canc Res, Bethesda, MD USA.
Univ Virginia, Charlottesville, VA USA.
NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e15533
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036903081
ER
PT J
AU Kreitman, RJ
Arons, E
Still, K
Tallman, MS
Stetler-Stevenson, M
Yuan, C
FitzGerald, DJP
Pastan, I
AF Kreitman, Robert J.
Arons, Evgeny
Still, Katherine
Tallman, Martin S.
Stetler-Stevenson, Maryalice
Yuan, Constance
FitzGerald, David J. P.
Pastan, Ira
TI Moxetumomab pasudotox and minimal residual disease in hairy cell
leukemia.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 7079
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901615
ER
PT J
AU Kumar, A
Burton, JK
Suman, VJ
Qin, R
Erlichman, C
Haluska, P
Harris, PJ
Bible, KC
AF Kumar, Aditi
Burton, Jill K.
Suman, Vera J.
Qin, Rui
Erlichman, Charles
Haluska, Paul
Harris, Pamela Jo
Bible, Keith Christopher
TI Effects of pazopanib therapy on mean corpuscular volume in patients
enrolled in MC1112: Analysis of correlation with time to disease
progression in solid tumors.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Mayo Clin, Rochester, MN USA.
Mayo Clin, Alliance Stat & Data Ctr, Rochester, MN USA.
NCI, Canc Therapeut Evaluat Program, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e13596
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036902587
ER
PT J
AU Kumar, NB
Pow-Sang, J
Egan, K
Spiess, PE
Dickinson, SI
Salup, R
Helal, M
McLarty, J
Williams, CR
Schreiber, FJ
Parnes, H
Sebti, S
Kazi, A
Kang, L
Quinn, GP
Smith, T
Yue, BL
Chornokur, G
Crocker, T
Schell, MJ
AF Kumar, Nagi B.
Pow-Sang, Julio
Egan, Kathleen
Spiess, Philippe E.
Dickinson, Shohreh I.
Salup, Raoul
Helal, Mohamed
McLarty, Jerry
Williams, Christopher R.
Schreiber, Fred James
Parnes, Howard
Sebti, Said
Kazi, Aslam
Kang, Loveleen
Quinn, Gwendolyn P.
Smith, Tiffany
Yue, Binglin
Chornokur, Ganna
Crocker, Theresa
Schell, Michael J.
TI Effect of green tea catechins in prostate cancer chemoprevention.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr, Tampa, FL USA.
H Lee Moffitt Canc Ctr & Res Inst, Dept Genitourinary Oncol, Tampa, FL USA.
Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
James A Haley Vet Adm Hosp, Tampa, FL USA.
US Virgin Isl, Tampa Urol, Tampa, FL USA.
Louisiana State Univ, Hlth Sci Ctr, Shreveport, LA 71105 USA.
Univ Florida, Div Urol, Shands Hosptial, Jacksonville, FL USA.
Watson Clin, Lakeland, FL USA.
NIH, Bethesda, MD 20892 USA.
H Lee Moffitt Canc Ctr & Res Inst Inc, Tampa, FL USA.
James A Haley Vet Hosp, Tampa, FL USA.
H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
USF Hlth Byrd Alzheimers Inst, Tampa, FL USA.
NR 0
TC 0
Z9 0
U1 0
U2 9
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 1572
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900439
ER
PT J
AU Kummar, S
Do, KT
Coyne, GHO
Turkbey, B
Meltzer, PS
Polley, E
Horneffer, Y
Juwara, L
Antony, R
Choyke, PL
Mitchell, SA
Helman, LJ
Chen, A
Doroshow, JH
AF Kummar, Shivaani
Do, Khanh Tu
Coyne, Geraldine Helen O'Sullivan
Turkbey, Baris
Meltzer, Paul S.
Polley, Eric
Horneffer, Yvonne
Juwara, Lamin
Antony, Ramya
Choyke, Peter L.
Mitchell, Sandra A.
Helman, Lee J.
Chen, Alice
Doroshow, James H.
TI Phase II trial of PF-03084014 in adults with desmoid tumors/aggressive
fibromatosis.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Stanford Univ, Sch Med, Phase Clin Res Program 1, Stanford, CA 94305 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Early Clin Trials Dev Program, Bethesda, MD USA.
NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
Ctr Canc Res, Bethesda, MD USA.
NCI, Div Canc Treatment & Diag, Rockville, MD USA.
NCI, Bethesda, MD 20892 USA.
Leidos Biomed Res Inc, Frederick, MD USA.
NCI, NIH, Bethesda, MD 20892 USA.
NCI, Rockville, MD USA.
NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
Div Canc Treatment & Diag, Bethesda, MD USA.
NR 0
TC 0
Z9 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 10563
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900203
ER
PT J
AU Lagmay, JP
Krailo, MD
Dang, H
Kim, A
Hawkins, DS
Beaty, O
Widemann, BC
Zwerdling, T
Bomgaars, L
Langevin, AM
Grier, HE
Weigel, B
Blaney, S
Gorlick, RG
Janeway, KA
AF Lagmay, Joanne P.
Krailo, Mark D.
Dang, Ha
Kim, AeRang
Hawkins, Douglas S.
Beaty, Orren
Widemann, Brigitte C.
Zwerdling, Theodore
Bomgaars, Lisa
Langevin, Anne-Marie
Grier, Holcombe E.
Weigel, Brenda
Blaney, Susan
Gorlick, Richard Greg
Janeway, Katherine A.
TI Outcome of recurrent osteosarcoma patients enrolled in seven phase II
trials through CCG, POG, and COG: Learning from the past to move
forward.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Florida, Shands Hosp Children, Gainesville, FL USA.
Childrens Onc Grp, Arcadia, CA USA.
Childrens Oncol Grp, Arcadia, CA USA.
Ctr Canc & Blood Disorders, Washington, DC USA.
Seattle Childrens Hosp, Seattle, WA USA.
Mission Hosp, Fairview, NC USA.
NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
Univ Calif Davis, Sacramento, CA USA.
Texas Childrens Canc Ctr, Houston, TX USA.
Univ Texas Med Hlth Ctr San Antonio, San Antonio, TX USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Univ Minnesota, Minneapolis, MN USA.
Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA.
Childrens Hosp, Bronx, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 10042
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900049
ER
PT J
AU Lai, C
Pittaluga, S
Shovlin, M
Steinberg, SM
Roschewski, MJ
Jaffe, ES
Wilson, WH
Dunleavy, K
AF Lai, Catherine
Pittaluga, Stefania
Shovlin, Margaret
Steinberg, Seth M.
Roschewski, Mark J.
Jaffe, Elaine S.
Wilson, Wyndham Hopkins
Dunleavy, Kieron
TI The outcome of ALK positive and ALK negative anaplastic large cell
lymphoma (ALCL) following DA-EPOCH
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 8564
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901876
ER
PT J
AU Land, SR
Warren, GW
Moinpour, C
Ostroff, JS
Crafts, J
Folz, J
Gulley, JL
Szabo, E
Chollette, V
Brandon, TH
Duffy, S
Hatsukami, DK
Dresler, CM
Gritz, ER
Schnoll, R
Sarna, L
Rigotti, N
Buckner, JC
Mitchell, SA
Toll, B
AF Land, Stephanie R.
Warren, Graham Walter
Moinpour, Carol
Ostroff, Jamie S.
Crafts, Jennifer
Folz, Jasmine
Gulley, James L.
Szabo, Eva
Chollette, Veronica
Brandon, Thomas H.
Duffy, Sonia
Hatsukami, Dorothy K.
Dresler, Carolyn M.
Gritz, Ellen R.
Schnoll, Robert
Sarna, Linda
Rigotti, Nancy
Buckner, Jan C.
Mitchell, Sandra A.
Toll, Benjamin
TI Standardizing measurement of tobacco use in cancer clinical trials
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
Med Univ S Carolina, Charleston, SC 29425 USA.
Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Westat Corp, Rockville, MD USA.
NCI, NIH, Bethesda, MD 20892 USA.
NCI, Potomac, MD USA.
NCI, Rockville, MD USA.
H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
Masonic Canc Ctr, Minneapolis, MN USA.
Tobacco Cessat & Control Subcomm, Rockville, MD USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Univ Penn, Philadelphia, PA 19104 USA.
Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Mayo Clin, Rochester, MN USA.
Yale Univ, New Haven, CT USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 9550
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036902045
ER
PT J
AU Lheureux, S
Weberpals, JI
Hendrickson, AEW
Fleming, GF
Olawaiye, A
Brana, I
Mackay, H
Dhani, NC
Wilson, MK
Rodriguez-Freixinos, V
Martin-Lorente, C
Ward, J
Chang, K
Wang, L
Speers, V
Karakasis, K
Bowering, VL
Chen, A
Brenton, J
Oza, AM
AF Lheureux, Stephanie
Weberpals, Johanne Ingrid
Hendrickson, Andrea Elisabeth Wahner
Fleming, Gini F.
Olawaiye, Alexander
Brana, Irene
Mackay, Helen
Dhani, Neesha C.
Wilson, Michelle K.
Rodriguez-Freixinos, Victor
Martin-Lorente, Cristina
Ward, Jacklyn
Chang, Karen
Wang, Lisa
Speers, Vanessa
Karakasis, Katherine
Bowering, Valerie Lydia
Chen, Alice
Brenton, James
Oza, Amit M.
TI A randomized, placebo-controlled phase II trial comparing gemcitabine
monotherapy to gemcitabine in combination with AZD 1775 (MK 1775) in
women with recurrent, platinum-resistant epithelial ovarian, primary
peritoneal, or Fallopian tube cancers: Trial of Princess Margaret, Mayo,
Chicago, and California consortia.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Princess Margaret Canc Ctr, Toronto, ON, Canada.
Ottawa Gen Hosp, Ottawa, ON K1H 8L6, Canada.
Mayo Clin, Rochester, MN USA.
Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
Massachusetts Gen Hosp, Chestnut Hill, MA USA.
UHN Princess Margaret Hosp, Cambridge, ON, Canada.
Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada.
Univ Toronto, Princess Margaret Canc Ctr, Univ Hlth Network, Div Med Oncol & Hematol,Dept Med, Toronto, ON, Canada.
Princess Margaret Canc Ctr, Dept Biostat, Toronto, ON, Canada.
Univ Hlth Network, Toronto, ON, Canada.
Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge, England.
NR 0
TC 0
Z9 0
U1 2
U2 2
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA TPS5613
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036904802
ER
PT J
AU Lheureux, S
Ledermann, JA
Runswick, S
Hodgson, DR
Timms, K
Lanchbury, JS
Kaye, SB
Gourley, C
Bowtell, D
Kohn, EC
Scott, CL
Matulonis, U
Panzarella, T
Dougherty, BA
Barrett, JC
Lai, ZW
O'Connor, M
Robertson, JD
Ho, TW
Oza, AM
AF Lheureux, Stephanie
Ledermann, Jonathan A.
Runswick, Sarah
Hodgson, Darren R.
Timms, Kirsten
Lanchbury, Jerry S.
Kaye, Stanley B.
Gourley, Charlie
Bowtell, David
Kohn, Elise C.
Scott, Clare L.
Matulonis, Ursula
Panzarella, Tony
Dougherty, Brian Andrew
Barrett, J. Carl
Lai, Zhongwu
O'Connor, Mark
Robertson, Jane D.
Ho, Tony Weishiu
Oza, Amit M.
TI Genomic characterization of long-term responders to olaparib.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Princess Margaret Canc Ctr, Toronto, ON, Canada.
UCL, Inst Canc, London, England.
AstraZeneca, Macclesfield, Cheshire, England.
Myriad Genet Inc, Salt Lake City, UT USA.
Inst Canc Res, London SW3 6JB, England.
Royal Marsden NHS Fdn Trust, London, England.
Univ Edinburgh, Canc Res UK Ctr, Edinburgh, Midlothian, Scotland.
Peter MacCallum Canc Ctr, East Melbourne, Australia.
NIH, NCI, Bethesda, MD 20892 USA.
Royal Melbourne Hosp, Parkville, Vic 3050, Australia.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Princess Margaret Hosp, Dept Biostat, Toronto, ON M4X 1K9, Canada.
Univ Toronto, Toronto, ON, Canada.
AstraZeneca, Waltham, MA USA.
Astra Zeneca, Wilmington, DE USA.
Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 5566
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901230
ER
PT J
AU Lheureux, S
Butler, MO
Clarke, B
Cristea, MC
Martin, LP
Tonkin, KS
Fleming, GF
Tinker, A
Hirte, HW
Tsoref, D
Mackay, H
Dhani, NC
Ghatage, P
Pham, NA
Motta, V
Wang, L
Karakasis, K
Udagani, S
Streicher, H
Oza, AM
AF Lheureux, Stephanie
Butler, Marcus O.
Clarke, Blaise
Cristea, Mihaela C.
Martin, Lainie P.
Tonkin, Katia Sonia
Fleming, Gini F.
Tinker, Anna
Hirte, Hal W.
Tsoref, Daliah
Mackay, Helen
Dhani, Neesha C.
Ghatage, Prafull
Nhu-An Pham
Motta, Vinicius
Wang, Lisa
Karakasis, Katherine
Udagani, Smitha
Streicher, Howard
Oza, Amit M.
TI A phase I/II study of ipilimumab in women with metastatic or recurrent
cervical carcinoma: A study of the Princess Margaret and Chicago N01
Consortia.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Princess Margaret Canc Ctr, Toronto, ON, Canada.
Univ Hlth Network, Dept Pathol & Lab Med, Toronto, ON, Canada.
City Hope Natl Med Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA 91010 USA.
Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada.
Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
Juravinski Canc Ctr, Hamilton, ON, Canada.
Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada.
Univ Toronto, Dept Med, Div Med Oncol & Hematol, Princess Margaret Canc Ctr,Univ Hlth Network, Toronto, ON, Canada.
Tom Baker Canc Clin, Calgary, AB, Canada.
Univ Toronto, Lab Med & Pathobiol, Toronto, ON, Canada.
Princess Margaret Canc Ctr, Dept Biostat, Toronto, ON, Canada.
Univ Hlth Network, Toronto, ON, Canada.
NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 3061
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900695
ER
PT J
AU Liu, J
Lee, JM
Luo, WX
Birrer, MJ
Whalen, C
Houston, ND
Obermayer, E
Spagnoletti, T
Barry, WT
Kohn, EC
Ivy, SP
Matulonis, U
AF Liu, Joyce
Lee, Jung-min
Luo, Weixiu
Birrer, Michael J.
Whalen, Christin
Houston, Nicole D.
Obermayer, Elizabeth
Spagnoletti, Tatum
Barry, William Thomas
Kohn, Elise C.
Ivy, S. Percy
Matulonis, Ursula
TI A phase 1 study optimizing the dosing of olaparib tablet formulation
combined with cediranib in recurrent ovarian cancer.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Dana Farber Canc Inst, Newton, MA USA.
NIH, Bethesda, MD 20892 USA.
Dana Farber Canc Inst, IBCSG Stat Ctr, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Dana Farber Canc Ctr, Boston, MA 02114 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
NCI, CTEP, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 5559
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901222
ER
PT J
AU Liu, SV
Powderly, JD
Camidge, DR
Ready, N
Heist, RS
Hodi, FS
Giaccone, G
Liu, B
Wallin, J
Funke, RP
Waterkamp, D
Gettinger, SN
AF Liu, Stephen V.
Powderly, John D.
Camidge, D. Ross
Ready, Neal
Heist, Rebecca Suk
Hodi, F. Stephen
Giaccone, Giuseppe
Liu, Bo
Wallin, Jeffrey
Funke, Roel Peter
Waterkamp, Daniel
Gettinger, Scott N.
TI Safety and efficacy of MPDL3280A (anti-PDL1) in combination with
platinum-based doublet chemotherapy in patients with advanced non-small
cell lung cancer (NSCLC).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Georgetown Univ Hosp, Washington, DC 20007 USA.
Carolina BioOncol Inst, Huntersville, NC USA.
Univ Colorado, Ctr Canc, Aurora, CO USA.
Duke Univ, Med Ctr, Chapel Hill, NC USA.
Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NCI, NIH, Bethesda, MD 20892 USA.
Genentech Inc, San Francisco, CA 94080 USA.
F Hoffmann La Roche Ltd, Basel, Switzerland.
Yale Sch Med, New Haven, CT USA.
NR 0
TC 20
Z9 20
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 8030
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901743
ER
PT J
AU Lopez-Chavez, A
Evbuomwan, M
Xi, LQ
Chun, G
Vidaurre, T
Arrieta, O
Oblitas, G
Oton, AB
Calvo, AR
Rajan, A
Amarapurkar, P
Raffeld, M
Steinberg, SM
Arze-Aimaretti, L
Giaccone, G
AF Lopez-Chavez, Ariel
Evbuomwan, Moses
Xi, Liqiang
Chun, Guinevere
Vidaurre, Tatiana
Arrieta, Oscar
Oblitas, George
Oton, Ana Belen
Calvo, Alejandro R.
Rajan, Arun
Amarapurkar, Pooja
Raffeld, Mark
Steinberg, Seth M.
Arze-Aimaretti, Lorena
Giaccone, Giuseppe
TI EGFR mutations in Latinos from the United States and Latin America.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL USA.
NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
INEN, Lima, Peru.
Inst Nacl Cancerol INCAN, Mexico City, DF, Mexico.
Hosp Oncol Luis Razetti, Caracas, Venezuela.
Univ Colorado, DHMC, Denver, CO 80202 USA.
Kettering Canc & Blood Spclsts, Kettering, OH USA.
NCI, Thorac & Gastrointestinal Oncol Branch, NIH, Bethesda, MD 20892 USA.
Univ Miami, Miami, FL USA.
NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.
Univ Mayor de San Simon, Cochabamba, Bolivia.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 8070
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901782
ER
PT J
AU Lynch, JA
Berse, B
Filipski, KK
Kulich, S
Freedman, AN
DuVall, SL
Kelley, MJ
AF Lynch, Julie Ann
Berse, Brygida
Filipski, Kelly Kristin
Kulich, Scott
Freedman, Andrew N.
DuVall, Scott L.
Kelley, Michael J.
TI Epidermal growth factor receptor (EGFR) testing among veterans diagnosed
with lung cancer in the VA
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Vet Healthcare Adm, Lincoln, MA USA.
Boston Univ, Sch Med, Boston, MA 02118 USA.
NCI, Bethesda, MD 20892 USA.
Vet Hlth Adm, Pittsburgh, PA USA.
NCI, Epidemiol & Genom Res Program, Bethesda, MD USA.
Univ Utah, Sch Med, Salt Lake City, UT USA.
Duke Univ, Chapel Hill, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e17582
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036903548
ER
PT J
AU Lynch, JA
Berse, B
Filipski, KK
Freedman, AN
DuVall, S
Venne, V
Kelley, MJ
AF Lynch, Julie Ann
Berse, Brygida
Filipski, Kelly Kristin
Freedman, Andrew N.
DuVall, Scott
Venne, Vickie
Kelley, Michael J.
TI Implementation of gene expression testing for breast cancer patients
within the Veterans Health Administration.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Vet Healthcare Adm, Lincoln, MA USA.
Boston Univ, Sch Med, Boston, MA 02118 USA.
NCI, Bethesda, MD 20892 USA.
NCI, Epidemiol & Genom Res Program, Bethesda, MD 20892 USA.
Vet Healthcare Adm, Salt Lake City, UT USA.
Duke Univ, Chapel Hill, NC USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e17511
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036903485
ER
PT J
AU Makarova-Rusher, OV
Erokhina, KA
Duffy, AG
Ulahannan, SV
Greten, TF
AF Makarova-Rusher, Oxana V.
Erokhina, Katerina A.
Duffy, Austin G.
Ulahannan, Susanna Varkey
Greten, Tim F.
TI Racial/ethnic disparities in hepatocellular carcinoma treatment and
survival: Are we making progress?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, NIH, Bethesda, MD 20892 USA.
West Palm Hosp, W Palm Beach, FL USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e17591
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036903557
ER
PT J
AU Malik, SM
Korn, E
Thomas, A
AF Malik, Shakun M.
Korn, Ed
Thomas, Anish
TI Small cell lung cancer: Why has it become an orphan disease?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Clin Invest Branch CTEP DCTD, Rockville, MD USA.
NCI, NIH, Rockville, MD USA.
NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 7578
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901708
ER
PT J
AU Mansfield, AS
Vulih, D
Smith, GL
Harris, PJ
Ivy, SP
AF Mansfield, Aaron Scott
Vulih, Diana
Smith, Gary L.
Harris, Pamela Jo
Ivy, S. Percy
TI Patterns of hepatic impairment in phase I clinical trials.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Mayo Clinc, Rochester, MN USA.
Theradex Syst Inc, Princeton, NJ USA.
NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
NCI, CTEP, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 2567
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900600
ER
PT J
AU Massett, HA
Godwin, E
Rubinstein, L
Ivy, P
DiPiazza, K
Zwiebel, J
Friedman, S
Denicoff, A
Mishkin, GE
Abrams, J
AF Massett, Holly A.
Godwin, Elizabeth
Rubinstein, Lawrence
Ivy, Percy
DiPiazza, Kate
Zwiebel, James
Friedman, Steve
Denicoff, Andrea
Mishkin, Grace E.
Abrams, Jeffrey
TI An analysis of corrective action plans to address slow accruing NCI-held
IND early phase trials
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Bethesda, MD 20892 USA.
Emmes Corp, Rockville, MD USA.
NCI, Rockville, MD USA.
NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 6577
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901491
ER
PT J
AU May, M
Rojas, P
Sequeira, G
Elia, A
Vazquez, PM
Gonzalez, P
Abba, MC
Molinolo, A
Hewitt, SM
Perou, CM
Gass, H
Lanari, C
AF May, Maria
Rojas, Paola
Sequeira, Gonzalo
Elia, Andres
Vazquez, Paula Martinez
Gonzalez, Pedro
Abba, Martin C.
Molinolo, Alfredo
Hewitt, Stephen M.
Perou, Charles M.
Gass, Hugo
Lanari, Claudia
TI Progesterone receptor isoform ratio to define the molecular signature of
luminal breast cancers and their antiprogestin responsiveness.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 IBYME CONICET, Buenos Aires, DF, Argentina.
Hosp Gen Pacheco, Tigre, Argentina.
CINIBA, La Plata, Buenos Aires, Argentina.
NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
Univ N Carolina, Chapel Hill, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 11016
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900275
ER
PT J
AU Merchant, MS
Cristea, MC
Stadtmauer, EA
Tap, WD
D'Angelo, SP
Grupp, SA
Holdich, T
Binder-Scholl, G
Jakobsen, BK
Odunsi, K
Rapoport, A
Mackall, C
AF Merchant, Melinda S.
Cristea, Mihaela C.
Stadtmauer, Edward A.
Tap, William D.
D'Angelo, Sandra P.
Grupp, Stephan A.
Holdich, Tom
Binder-Scholl, Gwendolyn
Jakobsen, Bent K.
Odunsi, Kunle
Rapoport, Aaron
Mackall, Crystal
TI Genetically engineered NY-ESO-1 specific T cells in HLA-A201+patients
with advanced cancers.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Bethesda, MD 20892 USA.
City Hope Natl Med Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA 91010 USA.
Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
Adaptimmune, Abingdon, Oxon, England.
Adaptimmune LLC, Philadelphia, PA USA.
Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
Greenebaum Canc Ctr, Baltimore, MD USA.
NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 2
Z9 2
U1 3
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA TPS3102
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036904718
ER
PT J
AU Naing, A
Fu, SQ
Habra, MA
Chugh, R
Kebebew, E
Russell, J
Welshans, D
Fassnacht, M
Kroiss, M
Goebeler, ME
Ijzerman, M
Plaunt, MR
Mohideen, P
Phillips, M
Smith, DC
AF Naing, Aung
Fu, Siqing
Habra, Mouhammed Amir
Chugh, Rashmi
Kebebew, Electron
Russell, Jeffrey
Welshans, Dawn
Fassnacht, Martin
Kroiss, Matthias
Goebeler, Maria-Elisabeth
Ijzerman, Marian
Plaunt, Marianne R.
Mohideen, Pharis
Phillips, Martin
Smith, David C.
TI ATR-101 phase 1 clinical study for adrenocortical carcinoma.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Phase Program 1, Houston, TX 77030 USA.
Univ Texas MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, Div Internal Med, Houston, TX 77030 USA.
Univ Michigain Hlth Syst, Ann Arbor, MI USA.
NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Head & Neck & Endocrine Oncol, Tampa, FL 33612 USA.
Univ Hosp Wuerzburg, Dept Internal Med 1, Endocrine Unit, Wurzburg, Germany.
Uniklinikum Wurzburg, Dept Endocrinol, Wurzburg, Germany.
Zentrum Innere Med, Med Klin 2, Wurzburg, Germany.
Atterocor Inc, Ann Arbor, MI USA.
Univ Michigan, Dept Internal Med, Div Hematol Oncol, Ann Arbor, MI 48109 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA TPS4585
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036904777
ER
PT J
AU Pahuja, S
Beumer, JH
Appleman, LJ
Tawbi, HAH
Stoller, RG
Lee, JJ
Lin, Y
Ding, F
Yu, J
Belani, CP
Chen, AP
Giranda, VL
Shepherd, SP
Chu, E
Puhalla, S
AF Pahuja, Shalu
Beumer, Jan Hendrik
Appleman, Leonard Joseph
Tawbi, Hussein Abdul-Hassan
Stoller, Ronald G.
Lee, James J.
Lin, Yan
Ding, Fei
Yu, Jing
Belani, Chandra Prakash
Chen, Alice P.
Giranda, Vincent L.
Shepherd, Stacie Peacock
Chu, Edward
Puhalla, Shannon
TI A phase I study of veliparib (ABT-888) in combination with weekly
carboplatin and paclitaxel in advanced solid malignancies and enriched
for triple-negative breast cancer (TNBC)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
Univ Pittsburgh, Pittsburgh, PA USA.
Magee Womens Hosp UPMC, Pittsburgh, PA USA.
Penn State Hershey Canc Inst, Hershey, PA USA.
NCI, Potomac, MD USA.
AbbVie, N Chicago, IL USA.
Abbott, Abbott Pk, IL USA.
Univ Pittsburgh, Med Ctr, Magee Womens Hosp UMPC, Womens Canc Program, Pittsburgh, PA USA.
NR 0
TC 4
Z9 4
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 1015
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900096
ER
PT J
AU Park, JW
Green, JE
Kim, HK
AF Park, Jun Won
Green, Jeffrey E.
Kim, Hark K.
TI Establishment and characterization of Smad4-and p53-null GEM models for
colorectal adenocarcinoma.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Natl Canc Ctr, Biomol Funct Res Branch, Goyang, South Korea.
NCI, Transgen Oncogenesis & Genom Sect, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
Natl Canc Ctr, Goyang, South Korea.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e14697
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036902782
ER
PT J
AU Pichun, MEB
Thomas, A
Wilkerson, J
Hassan, R
Fojo, AT
Giaccone, G
Rajan, A
AF Pichun, Mauricio Emmanuel Burotto
Thomas, Anish
Wilkerson, Julia
Hassan, Raffit
Fojo, Antonio Tito
Giaccone, Giuseppe
Rajan, Arun
TI Effect of treatment on the regression and growth rates of thymic
epithelial tumors (TETs).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, NIH, Bethesda, MD 20892 USA.
NCI, NIH, Rockville, MD USA.
NCI, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
NCI, Thorac & Gastrointestinal Oncol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e18564
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036903865
ER
PT J
AU Piotrowski, AF
Campian, JL
Hakim, F
Rose, J
Yan, XY
Gress, R
Grossman, SA
AF Piotrowski, Anna F.
Campian, Jian Li
Hakim, Frances
Rose, Jeremy
Yan, Xiao-Yi
Gress, Ronald
Grossman, Stuart A.
TI Serial evaluation of lymphocyte subsets in patients with newly diagnosed
high grade gliomas treated with standard radiation and temozolomide
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Johns Hopkins Univ, Ellicott City, MD USA.
Washington Univ, St Louis, MO USA.
NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e22116
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036904502
ER
PT J
AU Purev, E
Srinivasan, R
Aue, G
Stroncek, D
Khuu, H
Ramos, C
Cook, L
Cho, E
Schmitt, M
Childs, RW
AF Purev, Enkhtsetseg
Srinivasan, Ramaprasad
Aue, George
Stroncek, Dave
Khuu, Hahn
Ramos, Caltalina
Cook, Lisa
Cho, Elena
Schmitt, Monica
Childs, Richard W.
TI Outpatient allogeneic hematopoietic cell transplant following
alemtuzumab based reduced intensity conditioning in patients with
advanced mycosis fungoides/Sezary syndrome.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 [Purev, Enkhtsetseg; Srinivasan, Ramaprasad; Aue, George; Stroncek, Dave; Khuu, Hahn; Ramos, Caltalina; Cook, Lisa; Cho, Elena; Schmitt, Monica; Childs, Richard W.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 7089
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901625
ER
PT J
AU Rimando, J
Larrick, S
Fowler, N
Castiello, L
Ali, SA
Sabatino, M
Stroncek, D
Felizardo, T
Fowler, DH
AF Rimando, Joseph
Larrick, Steven
Fowler, Nicholas
Castiello, Luciano
Ali, Syed Abbas
Sabatino, Marianna
Stroncek, Dave
Felizardo, Tania
Fowler, Daniel H.
TI The relationship between HIF family gene expression in allogeneic T-cell
products and acute graft-versus-host disease.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NIH, Bethesda, MD 20892 USA.
NCI, NIH, Columbia, MD USA.
NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 7026
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901562
ER
PT J
AU Rubinstein, MMZ
Gray, RJ
Sparano, JA
Zujewski, J
Whelan, TJ
Albain, KS
Hayes, DF
Geyer, CE
Dees, EC
Perez, EA
Keane, MM
Vallejos, C
Goggins, TF
Mayer, IA
Brufsky, A
Toppmeyer, D
Kaklamani, VG
Atkins, JN
Berenberg, JL
Sledge, GW
AF Rubinstein, Maria M. Zlobinsky
Gray, Robert James
Sparano, Joseph A.
Zujewski, JoAnne
Whelan, Timothy Joseph
Albain, Kathy S.
Hayes, Daniel F.
Geyer, Charles E.
Dees, Elizabeth Claire
Perez, Edith A.
Keane, Maccon M.
Vallejos, Carlos
Goggins, Timothy F.
Mayer, Ingrid A.
Brufsky, Adam
Toppmeyer, Deborah
Kaklamani, Virginia G.
Atkins, James Norman
Berenberg, Jeffrey L.
Sledge, George W.
TI Recurrence score and clinicopathologic characteristics of TAILORx
participants by race and ethnicity.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Montefiore Med Ctr, Bronx, NY 10467 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
NIH, Bethesda, MD 20892 USA.
Canc Care Ontario, Hamilton, ON, Canada.
SWOG, NRG Oncol NSABP, Maywood, IL USA.
Loyola Univ, Chicago Stritch Sch Med, Maywood, IL 60153 USA.
Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA.
Univ N Carolina, Chapel Hill, NC USA.
Mayo Clin, Jacksonville, FL 32224 USA.
West Ireland Canc Ctr, Galway, Ireland.
Inst Nacl Enfermedades Neoplas, Lima, Peru.
Fox Valley Hem Onc, Appleton, WI USA.
Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
NRG Oncol NSABP, Pittsburgh, PA USA.
Magee Womens Hosp, Pittsburgh, PA USA.
Canc Inst New Jersey, New Brunswick, NJ USA.
Northwestern Univ, Div Hematol Oncol, Chicago, IL 60611 USA.
Southeastern Medcl Ctr, Goldsboro, NC USA.
Tripler Army Medcl Ctr, Honolulu, HI USA.
Stanford Univ, Med Ctr, Stanford, CA 94305 USA.
RI Whelan, Timothy/D-3185-2017
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 533
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901140
ER
PT J
AU Rubinstein, WS
Benson, M
Chitipiralla, S
Hoover, J
Kattman, BL
Katz, KS
Maglott, DR
Malheiro, AJ
Tekumalla, R
Lee, JM
AF Rubinstein, Wendy S.
Benson, Mark
Chitipiralla, Shanmuga
Hoover, Jeffrey
Kattman, Brandi L.
Katz, Kenneth S.
Maglott, Donna R.
Malheiro, Adriana J.
Tekumalla, Radhika
Lee, Jennifer M.
TI The NIH Genetic Testing Registry and content tailored for oncologists.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 [Rubinstein, Wendy S.; Benson, Mark; Chitipiralla, Shanmuga; Hoover, Jeffrey; Kattman, Brandi L.; Katz, Kenneth S.; Maglott, Donna R.; Malheiro, Adriana J.; Tekumalla, Radhika; Lee, Jennifer M.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e12543
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036902351
ER
PT J
AU Schultz, KAP
Williams, GM
Stewart, D
Rosenberg, PS
Doros, LA
Dehner, LP
Hill, DA
Messinger, YH
AF Schultz, Kris Ann Pinekenstein
Williams, Gretchen M.
Stewart, Douglas
Rosenberg, Philip S.
Doros, Leslie Ann
Dehner, Louis P.
Hill, D. Ashley
Messinger, Yoav H.
TI Association of recurrent or progressive p of form types II and III
pleuropulmonary blastoma (PPB) with poor outcome: A report from the
international PPB registry.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Childrens Hosp & Clin Minnesota, Minneapolis, MN USA.
NCI, Bethesda, MD 20892 USA.
Childrens Natl Med Ctr, Arlington, VA USA.
Washington Univ, Sch Med St Louis, St Louis, MO USA.
Childrens Natl Med Ctr, Washington, DC 20010 USA.
Childrens Hosp & Clin, Minneapolis, MN USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 10014
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900018
ER
PT J
AU Shirai, K
Day, TA
Szabo, E
Van Waes, C
O'Brien, PE
Matheus, MG
Godwin, K
Sood, AJ
Vick, JA
Martin, D
Vitale-Cross, L
Molinolo, A
Gutkind, JS
AF Shirai, Keisuke
Day, Terry A.
Szabo, Eva
Van Waes, Carter
O'Brien, Paul E.
Matheus, Maria Gisele
Godwin, Kristina
Sood, Amit J.
Vick, Julie A.
Martin, Daniel
Vitale-Cross, Lynn
Molinolo, Alfredo
Gutkind, Jorge Silvio
TI A pilot, single arm, prospective trial using neoadjuvant rapamycin prior
to definitive therapy in head and neck squamous cell carcinoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Med Univ S Carolina, Charleston, SC 29425 USA.
Natl Canc Inst, Potomac, MD USA.
Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA.
Medcl Univ South Carolina, Charleston, SC USA.
Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA.
Rho Inc, Chapel Hill, NC USA.
Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
Natl Inst Dent & Craniofacial Res, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 6071
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901388
ER
PT J
AU Singh, H
Madan, RA
Dahut, WL
Strauss, J
Rauckhorst, M
McMahon, S
Heery, CR
Schlom, J
Gulley, JL
AF Singh, Harpreet
Madan, Ravi Amrit
Dahut, William L.
Strauss, Julius
Rauckhorst, Myrna
McMahon, Sheri
Heery, Christopher Ryan
Schlom, Jeffrey
Gulley, James L.
TI Combining active immunotherapy and immune checkpoint inhibitors in
prostate cancer.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
NCI, Lab Tumor Immunol & Biol, NIH, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e14008
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036902600
ER
PT J
AU Somlo, G
Frankel, PH
Luu, TH
Ma, CX
Arun, B
Garcia, AA
Cigler, T
Cream, L
Harvey, HA
Sparano, JA
Nanda, R
Chew, HK
Moynihan, TJ
Vahdat, LT
Goetz, MP
Hurria, A
Mortimer, JE
Gandara, DR
Chen, AP
Weitzel, JN
AF Somlo, George
Frankel, Paul Henry
Luu, Thehang H.
Ma, Cynthia X.
Arun, Banu
Garcia, Agustin A.
Cigler, Tessa
Cream, Leah
Harvey, Harold A.
Sparano, Joseph A.
Nanda, Rita
Chew, Helen K.
Moynihan, Timothy Jerome
Vahdat, Linda T.
Goetz, Matthew P.
Hurria, Arti
Mortimer, Joanne E.
Gandara, David R.
Chen, Alice P.
Weitzel, Jeffrey N.
TI Efficacy of the PARP inhibitor (PI) ABT-888 (veliparib [vel]) either
with carboplatin (carb) or as a single agent followed by
post-progression therapy in combination with carb in patients (pts) with
BRCA1- or BRCA2-(BRCA)-associated metastatic breast cancer (MBC).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 City Hope Natl Med Ctr, Duarte, CA USA.
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA.
Washington Univ, St Louis, MO USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Univ So Calif, Los Angeles Cty Hosp, Los Angeles, CA USA.
Weill Cornell Breast Ctr, New York, NY USA.
Penn State Coll Med, Hershey, PA USA.
Penn State Milton S Hershey Med Ctr, Hershey, PA USA.
Montefiore Med Ctr, Bronx, NY 10467 USA.
Univ Chicago, Chicago, IL 60637 USA.
Univ Calif Davis, Med Ctr, Sacramento, CA USA.
Mayo Clin, Rochester, MN USA.
Weill Cornell Med Coll, New York, NY USA.
Univ Calif Davis, Ctr Comprehens Canc, Sacramento, CA 95817 USA.
NCI, Potomac, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 520
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901127
ER
PT J
AU Suneja, G
Lin, CC
Simard, EP
Han, XS
Engels, EA
Jemal, A
AF Suneja, Gita
Lin, Chun Chieh
Simard, Edgar P.
Han, Xuesong
Engels, Eric A.
Jemal, Ahmedin
TI Disparities in cancer treatment among HIV-infected individuals
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Huntsman Canc Hosp, Salt Lake City, UT USA.
Amer Canc Soc, Atlanta, GA 30329 USA.
Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
Amer Canc Soc, Atlanta, GA 30329 USA.
NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e17592
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036903558
ER
PT J
AU Tsang, KY
Boyerinas, B
Jochems, C
Fantini, M
Heery, CR
Madan, RA
Gulley, JL
Schlom, J
AF Tsang, Kwong-Yok
Boyerinas, Benjamin
Jochems, Caroline
Fantini, Massimo
Heery, Christopher Ryan
Madan, Ravi Amrit
Gulley, James L.
Schlom, Jeffrey
TI Antibody dependent cellular cytotoxicity activity of a novel anti-PD-L1
antibody, avelumab (MSB0010718C), on human tumor cells.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, Bethesda, MD 20892 USA.
NCI, Lab Tumor Immunol & Biol, NIH, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
NCI, NIH, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 0
Z9 0
U1 1
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 3038
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900672
ER
PT J
AU Tutt, ANJ
Kaufman, B
Gelber, RD
Mc Fadden, E
Goessl, CD
Viale, G
Arahmani, A
Fumagalli, D
Azim, HA
Wu, WT
Grocholewicz, A
Costantino, JP
Rastogi, P
Garber, JE
Geyer, CE
AF Tutt, Andrew Nicholas James
Kaufman, Bella
Gelber, Richard D.
Mc Fadden, Eleanor
Goessl, Carsten Dietrich
Viale, Giuseppe
Arahmani, Amal
Fumagalli, Debora
Azim, Hatem Abdel
Wu, Wenting
Grocholewicz, Anna
Costantino, Joseph P.
Rastogi, Priya
Garber, Judy Ellen
Geyer, Charles E.
TI OlympiA: A randomized phase III trial of olaparib as adjuvant therapy in
patients with high-risk HER2-negative breast cancer (BC) and a germline
BRCA1/2 mutation (gBRCAm).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Kings Coll London, Sch Med, London WC2R 2LS, England.
Chaim Sheba Med Ctr, Ramat Gan, Israel.
Tel Aviv Univ, Sackler Fac Med, Ramat Gan, Israel.
Dana Farber Canc Inst, Boston, MA 02115 USA.
Frontier Sci, Kingussie, Inverness, Scotland.
AstraZeneca, Gaithersburg, MD USA.
European Inst Oncol, Div Pathol, Milan, Italy.
Breast Int Grp, Brussels, Belgium.
Inst Jules Bordet, B-1000 Brussels, Belgium.
AstraZeneca, Gaithersburg, MD USA.
AstraZeneca, Warsaw, Poland.
NRG Oncol, Pittsburgh, PA USA.
Univ Pittsburgh, Pittsburgh, PA USA.
NRG Oncol, NSABP, Pittsburgh, PA USA.
UPMC, Ctr Canc, Pittsburgh, PA USA.
Virginia Commonwealth Univ, Massey Canc Ctr, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA TPS1109
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036904664
ER
PT J
AU Urbanic, JJ
Case, D
Baez-Diaz, L
Brown, DR
Strasser, J
Enevold, G
Naughton, M
Weaver, KE
Baglan, K
Bryant, D
Langefeld, C
Lad, TE
Lee, L
Rine, G
Curtis, AE
Koprowski, CD
Tomlinson, WV
Lesser, GJ
Shaw, EG
Hu, JJ
AF Urbanic, James John
Case, Doug
Baez-Diaz, Luis
Brown, Doris R.
Strasser, Jon
Enevold, Gina
Naughton, Michelle
Weaver, Kathryn E.
Baglan, Kathy
Bryant, David
Langefeld, Carl
Lad, Thomas E.
Lee, Lucille
Rine, Grant
Curtis, Amarinthia E.
Koprowski, Christoper D.
Tomlinson, W. Vic
Lesser, Glenn Jay
Shaw, Edward G.
Hu, Jennifer J.
TI A prospective evaluation of radiotherapy (RT) related skin reactions in
a multi-racial/ethnic population of women with newly diagnosed breast
cancer (BC)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Calif San Diego, Encinitas, CA USA.
Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
Natl Surg Adjuvant Breast & Bowel Project, San Juan, PR USA.
CCOP San Juan, San Juan, PR USA.
Helen F Graham Canc Ctr, Newark, DE USA.
Ohio State Univ, Columbus, OH 43210 USA.
Mercy Hosp Sanit Louis, St Louis, MO USA.
Via Christi Canc Ctr, Wichita, KS USA.
Cook Cty Hosp, Chicago, IL 60612 USA.
North Shore LIJ Canc Inst, Lake Success, NY USA.
Wesley Med Ctr, Wichita, KS USA.
Upstate Carolina CCOP, Spartanburg, SC USA.
Christiana Care Hlth Syst, Helen Graham Canc Ctr, Newark, DE USA.
AnMed Hlth, Anderson, SC USA.
Wake Forest Univ, Winston Salem, NC 27109 USA.
Wake Forest Baptist Hlth, Winston Salem, NC USA.
Univ Miami, Miami, FL USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 6593
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901507
ER
PT J
AU Walcott, FL
Land, SR
Costantino, JP
Midthune, D
Dunn, BK
AF Walcott, Farzana L.
Land, Stephanie R.
Costantino, Joseph P.
Midthune, Doug
Dunn, Barbara Karen
TI Vasomotor symptoms, BMI, and adherence to tamoxifen in the National
Surgical Adjuvant Breast and Bowel Project (NSABP) Breast Cancer
Prevention Trial (P-1)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Rockville, MD USA.
NRG Oncol, Pittsburgh, PA USA.
Univ Pittsburgh, Pittsburgh, PA USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 1501
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036900368
ER
PT J
AU Wallden, B
Ferree, S
Ravi, H
Dowidar, N
Hood, T
Danaher, P
Mashadi-Hossein, A
Wright, G
Schaper, C
Storhoff, JJ
AF Wallden, Brett
Ferree, Sean
Ravi, Harini
Dowidar, Naeem
Hood, Tressa
Danaher, Patrick
Mashadi-Hossein, Afshin
Wright, George
Schaper, Carl
Storhoff, James Justin
TI Development of the molecular diagnostic (MDx) DLBCL Lymphoma Subtyping
Test (LST) on the nCounter Analysis System
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NanoString Technol Inc, Seattle, WA USA.
NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 8536
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901848
ER
PT J
AU Yabroff, KR
Dowling, E
Guy, G
Banegas, M
McNeel, TS
Davidoff, AJ
Chawla, N
Hartigan, DB
Han, XS
Kent, EE
Li, CY
Virgo, KS
Rodriguez, J
de Moor, J
Zheng, ZY
Jemal, A
Ekwueme, DU
AF Yabroff, K. Robin
Dowling, Emily
Guy, Gery
Banegas, Matthew
McNeel, Timothy S.
Davidoff, Amy J.
Chawla, Neetu
Hartigan, Danielle Blanch
Han, Xuesong
Kent, Erin E.
Li, Chunyu
Virgo, Katherine S.
Rodriguez, Juan
de Moor, Janet
Zheng, Zhiyuan
Jemal, Ahmedin
Ekwueme, Donatus U.
TI Financial hardship associated with cancer in the United States
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 NCI, Rockville, MD USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Ctr Dis Control & Prevent, Atlanta, GA USA.
IMS, Rockville, MD USA.
Yale Univ, Sch Publ Hlth, New Haven, CT USA.
Kaiser Permanente No Calif, Oakland, CA USA.
Bentley Univ, Saugus, MA USA.
Amer Canc Soc, Atlanta, GA 30329 USA.
Emory Univ, Atlanta, GA 30322 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 6608
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901522
ER
PT J
AU Yellu, M
Fakhrejahani, F
Ying, J
Mierzwa, M
Malek, E
Haque, S
Sendilnathan, A
Huth, BJ
Morris, JC
Karim, NA
Latif, T
Redmond, KP
Barrett, W
Videtic, GMM
Sadraei, NH
AF Yellu, Mahender
Fakhrejahani, Farhad
Ying, Jun
Mierzwa, Michelle
Malek, Ehsan
Haque, Sulsal
Sendilnathan, Arun
Huth, Bradley Joseph
Morris, John Charles
Karim, Nagla Abdel
Latif, Tahir
Redmond, Kevin P.
Barrett, William
Videtic, Gregory M. M.
Sadraei, Nooshin Hashemi
TI Lymphopenia as a predictor of survival in chemoradiation (CRT)-treated
stage III non-small cell lung cancer (NSCLC).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Univ Cincinnati, Cincinnati, OH USA.
Natl Canc Inst, Potomac, MD USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Univ Cincinnati, Div Hematol & Oncol, Cincinnati, OH USA.
Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
Univ Cincinnati, Barrett Canc Ctr, Cincinnati, OH USA.
Univ Cincinnati, Dept Med, Inst Canc, Div Hematol Oncol, Cincinnati, OH USA.
Univ Cincinnati, Inst Canc, Cincinnati, OH USA.
Univ Hosp, Cincinnati, OH USA.
Cleveland Clin Fdn, Cleveland, OH 44195 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA e18513
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036903821
ER
PT J
AU Yu, HA
Oxnard, GR
Spira, AI
Horn, L
Weiss, J
Feng, Y
West, HJ
Giaccone, G
Evans, TL
Kelly, RJ
Fleege, T
Poondru, S
Jie, F
Aoyama, K
Foley, MA
Whitcomb, D
Keating, AT
Krivoshik, AP
AF Yu, Helena Alexandra
Oxnard, Geoffrey R.
Spira, Alexander I.
Horn, Leora
Weiss, Jared
Feng, Yan
West, Howard Jack
Giaccone, Giuseppe
Evans, Tracey L.
Kelly, Ronan Joseph
Fleege, Tanya
Poondru, Srinivasu
Jie, Fei
Aoyama, Koji
Foley, Margaret A.
Whitcomb, Debbie
Keating, Anne Therese
Krivoshik, Andrew P.
TI Phase I dose escalation study of ASP8273, a mutant-selective
irreversible EGFR inhibitor, in subjects with EGFR mutation positive
NSCLC.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Dana Farber Canc Inst, Boston, MA 02115 USA.
US Oncol Res, Virginia Canc Specialists Res Inst, Fairfax, VA USA.
Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
Case Western Reserve Univ, Univ Hosp, Broadview Hts, OH USA.
Swedish Canc Inst, Seattle, WA USA.
NCI, NIH, Bethesda, MD 20892 USA.
Univ Penn, Wynnewood, PA USA.
Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
Astellas Pharma Global Dev, Northbrook, IL USA.
Astellas Pharma Inc, Northbrook, IL USA.
Astellas Pharma, Tokyo, Japan.
NR 0
TC 0
Z9 0
U1 2
U2 2
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 8083
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901795
ER
PT J
AU Zell, JA
Unger, JM
Anderson, GL
Cook, ED
Krouse, RS
Lance, MP
Minasian, LM
Ford, L
Brown, P
AF Zell, Jason A.
Unger, Joseph M.
Anderson, Garnet L.
Cook, Elise D.
Krouse, Robert S.
Lance, M. Peter
Minasian, Lori M.
Ford, Leslie
Brown, Powel
TI SWOG S0820/PACES (Preventing Adenomas of the Colon with Eflornithine and
Sulindac): A randomized, double-blind, placebo-controlled phase III
clinical trial.
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 UC Irvine Hlth, Chao Family Comprehens Canc Ctr, Orange, CA USA.
Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
Southern Arizona Vet Affairs Hlth Care Syst, Tucson, AZ USA.
Univ Arizona, Tucson, AZ USA.
NCI, Bethesda, MD 20892 USA.
NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA TPS3627
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036904730
ER
PT J
AU Zheng, ZY
Jemal, A
Guy, G
Han, XS
Banegas, M
Li, CY
Ekwueme, DU
Yabroff, KR
AF Zheng, Zhiyuan
Jemal, Ahmedin
Guy, Gery
Han, Xuesong
Banegas, Matthew
Li, Chunyu
Ekwueme, Donatus U.
Yabroff, K. Robin
TI Medical expenditures and productivity loss among colorectal, breast, and
prostate cancer survivors in the US
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 29-JUN 02, 2015
CL Chicago, IL
SP Amer Soc Clin Oncol
C1 Amer Canc Soc, Atlanta, GA 30329 USA.
Ctr Dis Control & Prevent, Atlanta, GA USA.
NCI, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 MAY 20
PY 2015
VL 33
IS 15
SU S
MA 6619
PG 1
WC Oncology
SC Oncology
GA CM9OA
UT WOS:000358036901533
ER
PT J
AU Lu, VB
Ikeda, SR
Puhl, HL
AF Lu, Van B.
Ikeda, Stephen R.
Puhl, Henry L., III
TI A 3.7 kb Fragment of the Mouse Scn10a Gene Promoter Directs Neural Crest
But Not Placodal Lineage EGFP Expression in a Transgenic Animal
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE dorsal root ganglia; nodose ganglion; pain; sodium channels; transgenic
ID SODIUM-CHANNEL NA(V)1.8; GRUENEBERG GANGLION NEURONS; INFLAMMATORY PAIN;
MULTIPLE-SCLEROSIS; CALCIUM-CHANNELS; AFFERENT NEURONS; SENSORY NEURONS;
NA+ CURRENTS; ION CHANNELS; DRG NEURONS
AB Under physiological conditions, the voltage-gated sodium channel Na(v)1.8 is expressed almost exclusively in primary sensory neurons. The mechanism restricting Na(v)1.8 expression is not entirely clear, but we have previously described a 3.7 kb fragment of the Scn10a promoter capable of recapitulating the tissue-specific expression of Na(v)1.8 in transfected neurons and cell lines (Puhl and Ikeda, 2008). To validate these studies in vivo, a transgenic mouse encoding EGFP under the control of this putative sensory neuron specific promoter was generated and characterized in this study. Approximately 45% of dorsal root ganglion neurons of transgenic mice were EGFP-positive (mean diameter = 26.5 mu m). The majority of EGFP-positive neurons bound isolectin B4, although a small percentage (similar to 10%) colabeled with markers of A-fiber neurons. EGFP expression correlated well with the presence of Na(v)1.8 transcript (95%), Na(v)1.8-immunoreactivity (70%), and TTX-R I-Na (100%), although not all Na(v)1.8-expressing neurons expressed EGFP. Several cranial sensory ganglia originating from neurogenic placodes, such as the nodose ganglion, failed to express EGFP, suggesting that additional regulatory elements dictate Scn10a expression in placodal-derived sensory neurons. EGFP was also detected in discrete brain regions of transgenic mice. Quantitative PCR and Na(v)1.8-immunoreactivity confirmed Na(v)1.8 expression in the amygdala, brainstem, globus pallidus, lateral and paraventricular hypothalamus, and olfactory tubercle. TTX-R I-Na recorded from EGFP-positive hypothalamic neurons demonstrate the usefulness of this transgenic line to study novel roles of Na(v)1.8 beyond sensory neurons. Overall, Scn10a-EGFP transgenic mice recapitulate the majority of the Na(v)1.8 expression pattern in neural crest-derived sensory neurons.
C1 [Lu, Van B.; Ikeda, Stephen R.; Puhl, Henry L., III] NIAAA, Sect Transmitter Signaling, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
RP Puhl, HL (reprint author), NIAAA, Lab Mol Physiol, NIH, 5625 Fishers Lane,Room TS-06, Rockville, MD 20852 USA.
EM puhlh@mail.nih.gov
FU Intramural program at the National Institutes of Health, National
Institute on Alcohol Abuse and Alcoholism
FX This work was supported by the Intramural program at the National
Institutes of Health, National Institute on Alcohol Abuse and
Alcoholism. We thank Dr. James Pickel (National Institute of Mental
Health Transgenic Core Facility) for assistance with pronuclear
microinjections and Dr. Margaret Davis (Laboratory for Integrative
Neuroscience/National Institute on Alcohol Abuse and Alcoholism) for
technical assistance with immunohistochemistry experiments.
NR 51
TC 3
Z9 3
U1 6
U2 16
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 MAY 20
PY 2015
VL 35
IS 20
BP 8021
EP 8034
DI 10.1523/JNEUROSCI.0214-15.2015
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA CL0YW
UT WOS:000356670000024
PM 25995484
ER
PT J
AU Land, SR
Marcus, PM
AF Land, Stephanie R.
Marcus, Pamela M.
TI Cancer Screening and Diagnosis: Opportunities for Smoking Cessation
Intervention
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID LUNG-CANCER; UNITED-STATES; MORTALITY; PROGRAM; TOBACCO; TRIAL
C1 [Land, Stephanie R.; Marcus, Pamela M.] NCI, NIH, Bethesda, MD 20892 USA.
RP Land, SR (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM stephanie.land@alumni.stanford.edu
NR 23
TC 6
Z9 6
U1 0
U2 2
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 MAY 20
PY 2015
VL 33
IS 15
BP 1631
EP +
DI 10.1200/JCO.2015.61.2077
PG 4
WC Oncology
SC Oncology
GA CK2RW
UT WOS:000356060500002
PM 25897157
ER
PT J
AU Lynch, C
Zhao, JH
Huang, RL
Xiao, JW
Li, LH
Heyward, S
Xia, MH
Wang, HB
AF Lynch, Caitlin
Zhao, Jinghua
Huang, Ruili
Xiao, Jingwei
Li, Linhao
Heyward, Scott
Xia, Menghang
Wang, Hongbing
TI Quantitative High-Throughput Identification of Drugs as Modulators of
Human Constitutive Androstane Receptor
SO SCIENTIFIC REPORTS
LA English
DT Article
ID PREGNANE-X-RECEPTOR; ORPHAN NUCLEAR RECEPTORS; PRIMARY HUMAN
HEPATOCYTES; STRUCTURAL DETERMINANTS; ENHANCER MODULE; AGONIST LIGAND;
HEPG2 CELLS; CAR; ACTIVATION; METABOLISM
AB The constitutive androstane receptor (CAR, NR1I3) plays a key role in governing the transcription of numerous hepatic genes that involve xenobiotic metabolism/clearance, energy homeostasis, and cell proliferation. Thus, identification of novel human CAR (hCAR) modulators may not only enhance early prediction of drug-drug interactions but also offer potentially novel therapeutics for diseases such as metabolic disorders and cancer. In this study, we have generated a double stable cell line expressing both hCAR and a CYP2B6-driven luciferase reporter for quantitative high-throughput screening (qHTS) of hCAR modulators. Approximately 2800 compounds from the NIH Chemical Genomics Center Pharmaceutical Collection were screened employing both the activation and deactivation modes of the qHTS. Activators (115) and deactivators (152) of hCAR were identified from the primary qHTS, among which 10 agonists and 10 antagonists were further validated in the physiologically relevant human primary hepatocytes for compound-mediated hCAR nuclear translocation and target gene expression. Collectively, our results reveal that hCAR modulators can be efficiently identified through this newly established qHTS assay. Profiling drug collections for hCAR activity would facilitate the prediction of metabolism-based drug-drug interactions, and may lead to the identification of potential novel therapeutics.
C1 [Lynch, Caitlin; Xiao, Jingwei; Li, Linhao; Wang, Hongbing] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA.
[Zhao, Jinghua; Huang, Ruili; Xia, Menghang] NIH, NCATS, Bethesda, MD 20892 USA.
[Heyward, Scott] Bioreclamat IVT, Baltimore, MD USA.
RP Wang, HB (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA.
EM hwang@rx.umaryland.edu
RI Li, Linhao/A-6348-2013
FU National Institutes of Health [DK061652, GM107058]; National Center for
Advancing Translational Sciences, National Institutes of Health
FX This work was supported in part by the National Institutes of Health
Grants (DK061652 and GM107058), and the Intramural Research Program of
the National Center for Advancing Translational Sciences, National
Institutes of Health. We also thank William Hedrich and Bryan Mackowiak
for critical reading of the manuscript.
NR 43
TC 5
Z9 5
U1 1
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 MAY 20
PY 2015
VL 5
AR 10405
DI 10.1038/srep10405
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CJ3PC
UT WOS:000355395300001
PM 25993555
ER
PT J
AU Vardy, E
Robinson, JE
Li, C
Olsen, RHJ
DiBerto, JF
Giguere, PM
Sassano, FM
Huang, XP
Zhu, H
Urban, DJ
White, KL
Rittiner, JE
Crowley, NA
Pleil, KE
Mazzone, CM
Mosier, PD
Song, J
Kash, TL
Malanga, CJ
Krashes, MJ
Roth, BL
AF Vardy, Eyal
Robinson, J. Elliott
Li, Chia
Olsen, Reid H. J.
DiBerto, Jeffrey F.
Giguere, Patrick M.
Sassano, Flori M.
Huang, Xi-Ping
Zhu, Hu
Urban, Daniel J.
White, Kate L.
Rittiner, Joseph E.
Crowley, Nicole A.
Pleil, Kristen E.
Mazzone, Christopher M.
Mosier, Philip D.
Song, Juan
Kash, Thomas L.
Malanga, C. J.
Krashes, Michael J.
Roth, Bryan L.
TI A New DREADD Facilitates the Multiplexed Chemogenetic Interrogation of
Behavior
SO NEURON
LA English
DT Article
ID KAPPA-OPIOID RECEPTOR; PROTEIN-COUPLED RECEPTORS; BETA-CELL FUNCTION;
IN-VIVO; SALVINORIN-A; G(Q)-COUPLED RECEPTOR; FEEDING-BEHAVIOR;
REMOTE-CONTROL; ACTIVATION; LIGANDS
AB DREADDs are chemogenetic tools widely used to remotely control cellular signaling, neuronal activity, and behavior. Here we used a structure-based approach to develop a new Gi-coupled DREADD using the kappa-opioid receptor as a template (KORD) that is activated by the pharmacologically inert ligand salvinorin B (SALB). Activation of virally expressed KORD in several neuronal contexts robustly attenuated neuronal activity and modified behaviors. Additionally, co-expression of the KORD and the Gq-coupled M3-DREADD within the same neuronal population facilitated the sequential and bidirectional remote control of behavior. The availability of DREADDs activated by different ligands provides enhanced opportunities for investigating diverse physiological systems using multiplexed chemogenetic actuators.
C1 [Vardy, Eyal; Olsen, Reid H. J.; Giguere, Patrick M.; Sassano, Flori M.; Huang, Xi-Ping; Zhu, Hu; Urban, Daniel J.; White, Kate L.; Crowley, Nicole A.; Pleil, Kristen E.; Mazzone, Christopher M.; Song, Juan; Kash, Thomas L.; Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27514 USA.
[Vardy, Eyal; Olsen, Reid H. J.; Giguere, Patrick M.; Sassano, Flori M.; Huang, Xi-Ping; Zhu, Hu; Urban, Daniel J.; White, Kate L.; Crowley, Nicole A.; Pleil, Kristen E.; Mazzone, Christopher M.; Song, Juan; Kash, Thomas L.; Roth, Bryan L.] Univ N Carolina, Sch Med, NIMH, PDSP, Chapel Hill, NC 27514 USA.
[Robinson, J. Elliott; DiBerto, Jeffrey F.; Malanga, C. J.] Univ N Carolina, Sch Med, Neurol Dept, Chapel Hill, NC 27514 USA.
[Robinson, J. Elliott; Olsen, Reid H. J.; Rittiner, Joseph E.; Crowley, Nicole A.; Pleil, Kristen E.; Mazzone, Christopher M.; Song, Juan; Kash, Thomas L.; Malanga, C. J.; Roth, Bryan L.] Univ N Carolina, Sch Med, Curriculum Neurobiol, Chapel Hill, NC 27599 USA.
[Robinson, J. Elliott; Crowley, Nicole A.; Pleil, Kristen E.; Mazzone, Christopher M.; Kash, Thomas L.; Malanga, C. J.] Univ N Carolina, Sch Med, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA.
[Li, Chia; Krashes, Michael J.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
[Li, Chia; Krashes, Michael J.] NIDA, Baltimore, MD 21224 USA.
[Mosier, Philip D.] Virginia Commonwealth Univ, Sch Pharm, Dept Med Chem, Richmond, VA 23298 USA.
RP Krashes, MJ (reprint author), NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
EM michael.krashes@nih.gov; bryan_roth@med.unc.edu
RI Roth, Bryan/F-3928-2010;
OI Robinson, J. Elliott/0000-0001-9417-3938
FU NIH BRAIN Initiative [UO1MH105892, R01 DA017204, PO1DA035764]; NIH-NIMH
Psychoactive Drug Screening Program; Intramural Research Program of the
NIH, The National Institute of Diabetes and Digestive and Kidney
Diseases - NIDDK [DK075087, DK075089]; NARSAD Young Investigator Award
[R01AA019454, R00AA017668]; [U01AA020911]; [F31AA02228001]; [R01
AA018335]; [F30 AA021312]
FX This work was supported, in whole or in part, by the NIH BRAIN
Initiative Grant UO1MH105892 (B.L.R. and T.L.K.) and by R01 DA017204
(B.L.R.), PO1DA035764 (B.L.R.), and the NIH-NIMH Psychoactive Drug
Screening Program (B.L.R.); the Intramural Research Program of the NIH,
The National Institute of Diabetes and Digestive and Kidney Diseases -
NIDDK; DK075087, DK075089 (M.J.K.); and by R01AA019454, R00AA017668,
NARSAD Young Investigator Award, and U01AA020911 (T.L.K.); and
F31AA02228001 (N.A.C.), R01 AA018335 (C.J.M.), and F30 AA021312
(J.E.R.).
NR 46
TC 41
Z9 41
U1 4
U2 31
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
EI 1097-4199
J9 NEURON
JI Neuron
PD MAY 20
PY 2015
VL 86
IS 4
BP 936
EP 946
DI 10.1016/j.neuron.2015.03.065
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA CI6OB
UT WOS:000354878400009
PM 25937170
ER
PT J
AU Yang, S
Prentice, RL
AF Yang, Song
Prentice, Ross L.
TI Assessing potentially time-dependent treatment effect from clinical
trials and observational studies for survival data, with applications to
the Women's Health Initiative combined hormone therapy trial
SO STATISTICS IN MEDICINE
LA English
DT Article
DE average hazard ratio; censored data; hazard ratio; nonproportional
hazards; semiparametric analysis; simultaneous inference
ID ESTROGEN PLUS PROGESTIN; HAZARD RATIO; TRANSFORMATION MODELS; PROPENSITY
SCORE; CENSORED-DATA; SHORT-TERM; REGRESSION; REDUCTION; INFERENCE;
CHECKING
AB For risk and benefit assessment in clinical trials and observational studies with time-to-event data, the Cox model has usually been the model of choice. When the hazards are possibly non-proportional, a piece-wise Cox model over a partition of the time axis may be considered. Here, we propose to analyze clinical trials or observational studies with time-to-event data using a certain semiparametric model. The model allows for a time-dependent treatment effect. It includes the important proportional hazards model as a sub-model and can accommodate various patterns of time-dependence of the hazard ratio. After estimation of the model parameters using a pseudo-likelihood approach, simultaneous confidence intervals for the hazard ratio function are established using a Monte Carlo method to assess the time-varying pattern of the treatment effect. To assess the overall treatment effect, estimated average hazard ratio and its confidence intervals are also obtained. The proposed methods are applied to data from the Women's Health Initiative. To compare the Women's Health Initiative clinical trial and observational study, we use the propensity score in building the regression model. Compared with the piece-wise Cox model, the proposed model yields a better model fit and does not require partitioning of the time axis. Copyright (c) 2015 John Wiley & Sons, Ltd.
C1 [Yang, Song] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Prentice, Ross L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
RP Yang, S (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr MSC 7913, Bethesda, MD 20892 USA.
EM yangso@nhlbi.nih.gov
FU National Heart, Lung, and Blood Institute [HHSN268201100046C,
HHSN268201100001C, HHSN268201100002C, HHSN268201100003C]; National
Cancer Institute [CA53996]
FX We thank the WHI Publication and Presentation Committee for reviewing
and approving this article. The WHI was sponsored by the National Heart,
Lung, and Blood Institute through contracts HHSN268201100046C,
HHSN268201100001C, HHSN268201100002C, and HHSN268201100003C. This work
was also partially supported by National Cancer Institute grant CA53996.
We would also like to thank Dr. Nancy Geller and Dr. Dong-Yun Kim for
careful reviews and comments that led to the improvement of this
research article.
NR 35
TC 0
Z9 0
U1 1
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD MAY 20
PY 2015
VL 34
IS 11
BP 1801
EP 1817
DI 10.1002/sim.6453
PG 17
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA CF5YL
UT WOS:000352633200001
PM 25689356
ER
PT J
AU Landsman, V
Lou, WYW
Graubard, BI
AF Landsman, V.
Lou, W. Y. W.
Graubard, B. I.
TI Estimating survival probabilities by exposure levels: utilizing vital
statistics and complex survey data with mortality follow-up
SO STATISTICS IN MEDICINE
LA English
DT Article
DE categorical exposure; Cox proportional hazard model; crude hazard rate;
leave-one-out jackknife; linked mortality data; multistage surveys;
Taylor deviates
ID STANDARD ERRORS; UNITED-STATES; SMOKING; HAZARDS; DEATH; RISK
AB We present a two-step approach for estimating hazard rates and, consequently, survival probabilities, by levels of general categorical exposure. The resulting estimator utilizes three sources of data: vital statistics data and census data are used at the first step to estimate the overall hazard rate for a given combination of gender and age group, and cohort data constructed from a nationally representative complex survey with linked mortality records, are used at the second step to divide the overall hazard rate by exposure levels. We present an explicit expression for the resulting estimator and consider two methods for variance estimation that account for complex multistage sample design: (1) the leaving-one-out jackknife method, and (2) the Taylor linearization method, which provides an analytic formula for the variance estimator. The methods are illustrated with smoking and all-cause mortality data from the US National Health Interview Survey Linked Mortality Files, and the proposed estimator is compared with a previously studied crude hazard rate estimator that uses survey data only. The advantages of a two-step approach and possible extensions of the proposed estimator are discussed. Copyright (c) 2015 John Wiley & Sons, Ltd.
C1 [Landsman, V.; Lou, W. Y. W.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5T 3M7, Canada.
[Graubard, B. I.] NCI, Bethesda, MD 20852 USA.
RP Landsman, V (reprint author), Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5T 3M7, Canada.
EM victoria.landsman@utoronto.ca
NR 20
TC 0
Z9 0
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD MAY 20
PY 2015
VL 34
IS 11
BP 1864
EP 1875
DI 10.1002/sim.6455
PG 12
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA CF5YL
UT WOS:000352633200005
PM 25656596
ER
PT J
AU Hu, ZH
Proschan, M
AF Hu, Zonghui
Proschan, Michael
TI Two-part test of vaccine effect
SO STATISTICS IN MEDICINE
LA English
DT Article
DE Fisher's exact test; Lachenbruch's test; local alternative;
randomization test; vaccine
ID TRIALS
AB Vaccine benefit is usually two-folded: (i) prevent a disease or, failing that, (ii) diminish the severity of a disease. To assess vaccine effect, we propose two adaptive tests. The weighted two-part test is a combination of two statistics, one on disease incidence and one on disease severity. More weight is given to the statistic with the larger a priori effect size, and the weights are determined to maximize testing power. The randomized test applies to the scenario where the total number of infections is relatively small. It uses information on disease severity to bolster power while preserving disease incidence as the primary interest. Properties of the proposed tests are explored asymptotically and by numerical studies. Although motivated by vaccine studies, the proposed tests apply to any trials that involve both binary and continuous outcomes for evaluating treatment effect. Published 2015. This article is a US Government work and is in the public domain in the USA.
C1 [Hu, Zonghui; Proschan, Michael] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
RP Hu, ZH (reprint author), NIAID, Biostat Res Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM huzo@niaid.nih.gov
FU Intramural NIH HHS [Z99 AI999999]
NR 6
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD MAY 20
PY 2015
VL 34
IS 11
BP 1904
EP 1911
DI 10.1002/sim.6412
PG 8
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA CF5YL
UT WOS:000352633200008
PM 25630496
ER
PT J
AU Westendorp, WF
Nederkoorn, PJ
Aksentijevich, I
Hak, AE
Lichtenbelt, KD
Braun, KPJ
AF Westendorp, Willeke F.
Nederkoorn, Paul J.
Aksentijevich, Ivona
Hak, A. Elisabeth
Lichtenbelt, Klaske D.
Braun, Kees P. J.
TI UNEXPLAINED EARLY-ONSET LACUNAR STROKE AND INFLAMMATORY SKIN LESIONS:
CONSIDER ADA2 DEFICIENCY
SO NEUROLOGY
LA English
DT Editorial Material
C1 [Westendorp, Willeke F.; Nederkoorn, Paul J.; Hak, A. Elisabeth] Univ Amsterdam, Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
[Aksentijevich, Ivona] NHGRI, NIH, Bethesda, MD 20892 USA.
[Lichtenbelt, Klaske D.; Braun, Kees P. J.] Univ Med Ctr Utrecht, Utrecht, Netherlands.
RP Westendorp, WF (reprint author), Univ Amsterdam, Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
EM w.f.westendorp@amc.nl
NR 2
TC 7
Z9 7
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD MAY 19
PY 2015
VL 84
IS 20
BP 2092
EP 2093
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA DD2NU
UT WOS:000369760100017
PM 25888558
ER
PT J
AU Freeman, ZT
Rice, KA
Soto, PL
Pate, KAM
Weed, MR
Ator, NA
DeLeon, IG
Wong, DF
Zhou, Y
Mankowski, JL
Zink, MC
Adams, RJ
Hutchinson, EK
AF Freeman, Z. T.
Rice, K. A.
Soto, P. L.
Pate, K. A. M.
Weed, M. R.
Ator, N. A.
DeLeon, I. G.
Wong, D. F.
Zhou, Y.
Mankowski, J. L.
Zink, M. C.
Adams, R. J.
Hutchinson, E. K.
TI Neurocognitive dysfunction and pharmacological intervention using
guanfacine in a rhesus macaque model of self-injurious behavior
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
ID LESCH-NYHAN-SYNDROME; BORDERLINE PERSONALITY-DISORDER; AUTISM SPECTRUM
DISORDER; MACACA-MULATTA; PREFRONTAL CORTEX; RETROSPECTIVE ANALYSIS;
DOPAMINE RELEASE; EXTENDED-RELEASE; WORKING-MEMORY; UP-REGULATION
AB Self-injurious behavior (SIB) is a common comorbidity of psychiatric disorders but there is a dearth of information about neurological mechanisms underlying the behavior, and few animal models exist. SIB in humans is characterized by any intentional self-directed behavior that leads to wounds, whereas in macaques it is not always accompanied by wounds. We describe a cohort of rhesus macaques displaying SIB as adults, in which changes within the central nervous system were associated with the SIB. In these macaques, increases in central nervous system striatal dopamine (DA) receptor binding (BPND) measured by positron emission tomography (PET) [11C]raclopride imaging correlated with severity of wounding (r(s) = 0.662, P = 0.014). Furthermore, utilizing standardized cognitive function tests, we showed that impulsivity (stop signal reaction time, SSRT) and deficits in attentional set shifting (intra-/extradimensional shift) were correlated with increased severity of SIB (r(s) = 0.563, P = 0.045 and r(s) = 0.692, P = 0.009, respectively). We also tested the efficacy of guanfacine, an alpha 2A adrenergic agonist that acts to improve postsynaptic transmission of neuronal impulses, in reducing SIB. A subset of these animals were enrolled in a randomized experimenter-blinded study that demonstrated guanfacine decreased the severity of wounding in treated animals compared with vehicle-only-treated controls (P = 0.043), with residual beneficial effects seen for several weeks after cessation of therapy. Animals with the highest severity of SIB that received guanfacine also showed the most significant improvement (r(s) = -0.761, P = 0.009). The elevated PET BPND was likely due to low intrasynaptic DA, which in turn may have been improved by guanfacine. With underlying physiology potentially representative of the human condition and the ability to affect outcome measures of disease using pharmacotherapy, this model represents a unique opportunity to further our understanding of the biology and treatment of SIB in both animals and humans.
C1 [Freeman, Z. T.; Rice, K. A.; Pate, K. A. M.; Mankowski, J. L.; Zink, M. C.; Adams, R. J.] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD USA.
[Rice, K. A.; Hutchinson, E. K.] NIH, Div Vet Resources, Bethesda, MD 21205 USA.
[Soto, P. L.; Weed, M. R.; Ator, N. A.; DeLeon, I. G.; Wong, D. F.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[DeLeon, I. G.] Kennedy Krieger Inst, Dept Behav Psychol, Baltimore, MD USA.
[Wong, D. F.; Zhou, Y.] Johns Hopkins Sch Med, Dept Radiol & Radiol Sci, Baltimore, MD USA.
[Wong, D. F.] Johns Hopkins Sch Med, Dept Neurosci, Baltimore, MD USA.
RP Hutchinson, EK (reprint author), NIH, Div Vet Resources, 9000 Rockville Pike,Bldg 14A, Bethesda, MD 21205 USA.
EM EricHutchinsonDVM@gmail.com
FU Johns Hopkins Research Animal Resources; National Institutes of Health
[U01MH075378, T32OD011089, P40OD013117, P40RR019995]
FX We acknowledge Melanie Albano, Kristy Koenig, Theresa Meade, Caroline
Garrett, Tracey Graham, Nicole Azene, Tori Baxter, Stacey Perry,
Virginia Bogdan and Ray Smith for their valuable contributions in
conducting these experiments. This project was supported by Johns
Hopkins Research Animal Resources and by the following National
Institutes of Health grants U01MH075378, T32OD011089, P40OD013117 and
P40RR019995.
NR 56
TC 3
Z9 3
U1 4
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD MAY 19
PY 2015
VL 5
AR e567
DI 10.1038/tp.2015.61
PG 7
WC Psychiatry
SC Psychiatry
GA DA2WH
UT WOS:000367657300001
PM 25989141
ER
PT J
AU Hurwitz, AA
Lee, S
Knox, S
Kohrt, H
Verdeil, G
Romano, E
Margolin, K
Urba, WJ
Speiser, DE
AF Hurwitz, Arthur A.
Lee, Sylvia
Knox, Susan
Kohrt, Holbrook
Verdeil, Gregory
Romano, Emanuela
Margolin, Kim
Urba, Walter J.
Speiser, Daniel E.
TI 29th Annual meeting of the Society for Immunotherapy of Cancer (SITC)
SO JOURNAL FOR IMMUNOTHERAPY OF CANCER
LA English
DT Article
DE Immunotherapy; Cancer; Adaptive immunity; Innate immunity; Adoptive
immunotherapy; Immune escape; Checkpoint inhibitors; Tumor immunity;
Immune suppression
AB The 29th annual meeting of the Society for Immunotherapy of Cancer (SITC) was held November 7-9, 2014 in National Harbor, MD and was organized by Dr. Arthur A. Hurwitz (National Cancer Institute), Dr. Kim A. Margolin (Stanford University), Dr. Daniel E. Speiser (Ludwig Center for Cancer Research, University of Lausanne) and Dr. Walter J. Urba (Earle A. Chiles Research Institute, Providence Cancer Center). This meeting included over 1,600 registered participants from 28 separate countries, making it the largest SITC meeting held to date. It highlighted significant worldwide progress in the development and application of cancer immunology to the practice of clinical oncology, including advances in diagnosis, prognosis and therapy, utilizing several immunological pathways and mechanisms for a variety of oncologic conditions. Presentations and posters demonstrated that many concepts that had been pursued preclinically in the past are now being translated into clinical practice, with clear benefits for patients.
C1 [Hurwitz, Arthur A.] NCI, Frederick, MD 21701 USA.
[Lee, Sylvia] Univ Washington, Seattle, WA 98195 USA.
[Lee, Sylvia] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Knox, Susan; Margolin, Kim] Stanford Univ, Stanford, CA 94305 USA.
[Kohrt, Holbrook] Stanford Canc Inst, Stanford, CA USA.
[Verdeil, Gregory; Romano, Emanuela; Speiser, Daniel E.] Ludwig Ctr Canc Res, Lausanne, Switzerland.
[Romano, Emanuela] Univ Lausanne, Med Oncol Serv, Lausanne, Switzerland.
[Urba, Walter J.] Providence Canc Ctr, Earle A Chiles Res Inst, Portland, OR 97504 USA.
RP Urba, WJ (reprint author), Providence Canc Ctr, Earle A Chiles Res Inst, Portland, OR 97504 USA.
EM walter.urba@providence.org
OI Verdeil, Gregory/0000-0001-9445-8474
NR 4
TC 0
Z9 0
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2051-1426
J9 J IMMUNOTHER CANCER
JI J. Immunother. Cancer
PD MAY 19
PY 2015
VL 3
AR 17
DI 10.1186/s40425-015-0062-4
PG 14
WC Oncology
SC Oncology
GA CU7SJ
UT WOS:000363741500002
ER
PT J
AU Meir, M
Galanty, Y
Kashani, L
Blank, M
Khosravi, R
Fernandez-Avila, MJ
Cruz-Garcia, A
Star, A
Shochot, L
Thomas, Y
Garrett, LJ
Chamovitz, DA
Bodine, DM
Kurz, T
Huertas, P
Ziv, Y
Shiloh, Y
AF Meir, Michal
Galanty, Yaron
Kashani, Lior
Blank, Michael
Khosravi, Rami
Jesus Fernandez-Avila, Maria
Cruz-Garcia, Andres
Star, Ayelet
Shochot, Lea
Thomas, Yann
Garrett, Lisa J.
Chamovitz, Daniel A.
Bodine, David M.
Kurz, Thimo
Huertas, Pablo
Ziv, Yael
Shiloh, Yosef
TI The COP9 signalosome is vital for timely repair of DNA double-strand
breaks
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID E3 UBIQUITIN LIGASES; CELLULAR-RESPONSE; DAMAGE RESPONSE; END RESECTION;
GENOME STABILITY; PATHWAY CHOICE; ATM; SCF; DYNAMICS; ROLES
AB The DNA damage response is vigorously activated by DNA double-strand breaks (DSBs). The chief mobilizer of the DSB response is the ATM protein kinase. We discovered that the COP9 signalosome (CSN) is a crucial player in the DSB response and an ATM target. CSN is a protein complex that regulates the activity of cullin ring ubiquitin ligase (CRL) complexes by removing the ubiquitin-like protein, NEDD8, from their cullin scaffold. We find that the CSN is physically recruited to DSB sites in a neddylationdependent manner, and is required for timely repair of DSBs, affecting the balance between the two major DSB repair pathways-nonhomologous end-joining and homologous recombination repair (HRR). The CSN is essential for the processivity of deep end-resection-the initial step in HRR. Cullin 4a (CUL4A) is recruited to DSB sites in a CSN- and neddylation-dependent manner, suggesting that CSN partners with CRL4 in this pathway. Furthermore, we found that ATM-mediated phosphorylation of CSN subunit 3 on S410 is critical for proper DSB repair, and that loss of this phosphorylation site alone is sufficient to cause a DDR deficiency phenotype in the mouse. This novel branch of the DSB response thus significantly affects genome stability.
C1 [Meir, Michal; Galanty, Yaron; Kashani, Lior; Blank, Michael; Khosravi, Rami; Star, Ayelet; Shochot, Lea; Ziv, Yael; Shiloh, Yosef] Tel Aviv Univ, George S Wise Fac Life Sci, Sackler Sch Med, David & Inez Myers Lab Canc Res,Dept Human Mol Ge, IL-69978 Tel Aviv, Israel.
[Jesus Fernandez-Avila, Maria; Cruz-Garcia, Andres; Huertas, Pablo] Univ Seville, Ctr Andaluz Biol Mol Med Regenerat CABIMER, Seville 41092, Spain.
[Jesus Fernandez-Avila, Maria; Cruz-Garcia, Andres; Huertas, Pablo] Univ Seville, Dept Genet, Seville 41092, Spain.
[Thomas, Yann; Kurz, Thimo] Univ Dundee, Coll Life Sci, MRC Prot Phosphorylat & Ubiquitylat Unit, Dundee DD1 5EH, Scotland.
[Garrett, Lisa J.; Bodine, David M.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Chamovitz, Daniel A.] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Mol Biol & Ecol Plants, IL-69978 Tel Aviv, Israel.
RP Shiloh, Y (reprint author), Tel Aviv Univ, George S Wise Fac Life Sci, Sackler Sch Med, David & Inez Myers Lab Canc Res,Dept Human Mol Ge, IL-69978 Tel Aviv, Israel.
EM y.galanty@gurdon.cam.ac.uk; yaelz@post.tau.ac.il; yossih@post.tau.ac.il
RI Huertas, Pablo/N-2245-2016;
OI Huertas, Pablo/0000-0002-1756-4449; Chamovitz,
Daniel/0000-0002-2815-2909; Kurz, Thimo/0000-0003-0700-6993
FU Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; Israel
Cancer Research Fund; Israel Science Foundation [1900/12, 998/14];
I-CORE Program of the Planning and Budgeting Committee of the Israel
Ministry of Education; Spanish Ministry of Economy and Competitivity
[SAF2013-43255-P]; ERC Starting Grant (DSBRECA); ERC Starting Grant
(NEDD8andCRLs); Consejo Nacional de Ciencia y Tecnologia (CONACYT),
Mexico
FX Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; Israel
Cancer Research Fund; Israel Science Foundation (grants no. 1900/12 and
998/14); The I-CORE Program of the Planning and Budgeting Committee of
the Israel Ministry of Education, to YS laboratory; Spanish Ministry of
Economy and Competitivity (SAF2013-43255-P) and ERC Starting Grant
(DSBRECA), to PH laboratory; ERC Starting Grant (NEDD8andCRLs) to TK
laboratory; Consejo Nacional de Ciencia y Tecnologia (CONACYT), Mexico,
to A. C.-G. YS is a Research Professor of the Israel Cancer Research
Fund. Funding for open access charge: Donation to our lab.
NR 62
TC 8
Z9 8
U1 1
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD MAY 19
PY 2015
VL 43
IS 9
BP 4517
EP 4530
DI 10.1093/nar/gkv270
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CK0XK
UT WOS:000355928800017
PM 25855810
ER
PT J
AU Sherpa, C
Rausch, JW
Le Grice, SFJ
Hammarskjold, ML
Rekosh, D
AF Sherpa, Chringma
Rausch, Jason W.
Le Grice, Stuart F. J.
Hammarskjold, Marie-Louise
Rekosh, David
TI The HIV-1 Rev response element (RRE) adopts alternative conformations
that promote different rates of virus replication
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID VIRAL MESSENGER-RNA; GENE-EXPRESSION REQUIRES; TARGET SEQUENCE;
FUNCTIONAL-ANALYSIS; ENV EXPRESSION; BINDING-SITE; PROTEIN EXPRESSION;
ACTIVATION DOMAIN; TRANS-ACTIVATOR; NUCLEAR EXPORT
AB The HIV Rev protein forms a complex with a 351 nucleotide sequence present in unspliced and incompletely spliced human immunodeficiency virus (HIV) mRNAs, the Rev response element (RRE), to recruit the cellular nuclear export receptor Crm1 and RanGTP. This complex facilitates nucleo-cytoplasmic export of these mRNAs. The precise secondary structure of the HIV-1 RRE has been controversial, since studies have reported alternative structures comprising either four or five stem-loops. The published structures differ only in regions that lie outside of the primary Rev binding site. Using in-gel SHAPE, we have now determined that the wt NL4-3 RRE exists as a mixture of both structures. To assess functional differences between these RRE 'conformers', we created conformationally locked mutants by site-directed mutagenesis. Using subgenomic reporters, as well as HIV replication assays, we demonstrate that the five stem-loop form of the RRE promotes greater functional Rev/ RRE activity compared to the four stem-loop counterpart.
C1 [Sherpa, Chringma; Hammarskjold, Marie-Louise; Rekosh, David] Univ Virginia, Dept Microbiol Immunol & Canc Biol, Myles H Thaler Ctr AIDS & Human Retrovirus Res, Charlottesville, VA 22908 USA.
[Rausch, Jason W.; Le Grice, Stuart F. J.] NCI, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
RP Rekosh, D (reprint author), Univ Virginia, Dept Microbiol Immunol & Canc Biol, Myles H Thaler Ctr AIDS & Human Retrovirus Res, Charlottesville, VA 22908 USA.
EM mh7g@virginia.edu; dr4u@virginia.edu
FU University of Virginia and National Institute of General Medical
Sciences [GM110009]; Intramural Research Program of the National
Institutes of Health; University of Virginia and National Cancer
Institute
FX Charles H. Ross Jr and Myles H. Thaler Endowments at the University of
Virginia and National Institute of General Medical Sciences [GM110009]
(to M.-L. H. and D.R.); Intramural Research Program of the National
Institutes of Health (to S.L.G. and J.R.). Funding for open access
charge: University of Virginia and National Cancer Institute.
NR 74
TC 14
Z9 14
U1 1
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD MAY 19
PY 2015
VL 43
IS 9
BP 4676
EP 4686
DI 10.1093/nar/gkv313
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CK0XK
UT WOS:000355928800030
PM 25855816
ER
PT J
AU Kononenko, AV
Lee, NCO
Liskovykh, M
Masumoto, H
Earnshaw, WC
Larionov, V
Kouprina, N
AF Kononenko, Artem V.
Lee, Nicholas C. O.
Liskovykh, Mikhail
Masumoto, Hiroshi
Earnshaw, William C.
Larionov, Vladimir
Kouprina, Natalay
TI Generation of a conditionally self-eliminating HAC gene delivery vector
through incorporation of a tTA(VP64) expression cassette
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID HUMAN ARTIFICIAL CHROMOSOMES; TRANSFORMATION-ASSOCIATED RECOMBINATION;
SACCHAROMYCES-CEREVISIAE; GENOMIC LOCI; STEM-CELLS; DNA; YEAST;
CENTROMERE; TRANSGENE; CLONING
AB Human artificial chromosome (HAC)-based vectors represent an alternative technology for gene delivery and expression with a potential to overcome the problems caused by virus-based vectors. The recently developed alphoid(tetO)-HAC has an advantage over other HAC vectors because it can be easily eliminated from cells by inactivation of the HAC kinetochore via binding of chromatin modifiers, tTA or tTS, to its centromeric tetO sequences. This provides a unique control for phenotypes induced by genes loaded into the HAC. The alphoid(tetO)-HAC elimination is highly efficient when a high level of chromatin modifiers as tetR fusion proteins is achieved following transfection of cells by a retrovirus vector. However, such vectors are potentially mutagenic and might want to be avoided under some circumstances. Here, we describe a novel system that allows verification of phenotypic changes attributed to expression of genes from the HAC without a transfection step. We demonstrated that a single copy of tTA(VP64) carrying four tandem repeats of the VP16 domain constitutively expressed from the HAC is capable to generate chromatin changes in the HAC kinetochore that are not compatible with its function. To adopt the alphoid(tetO)-HAC for routine gene function studies, we constructed a new TAR-BRV-tTA(VP64) cloning vector that allows a selective isolation of a gene of interest from genomic DNA in yeast followed by its direct transfer to bacterial cells and subsequent loading into the loxP site of the alphoid(tetO)-HAC in hamster CHO cells from where the HAC may be MMCT-transferred to the recipient human cells.
C1 [Kononenko, Artem V.; Lee, Nicholas C. O.; Liskovykh, Mikhail; Larionov, Vladimir; Kouprina, Natalay] NCI, Dev Therapeut Branch, Bethesda, MD 20892 USA.
[Masumoto, Hiroshi] Kazusa DNA Res Inst, Dept Frontier Res, Lab Cell Engn, Kisarazu, Chiba 2920818, Japan.
[Earnshaw, William C.] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland.
RP Kouprina, N (reprint author), NCI, Dev Therapeut Branch, Bethesda, MD 20892 USA.
EM larionov@mail.nih.gov; kouprinn@mail.nih.gov
RI Lee, Nicholas/F-3668-2015
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research, USA; Kazusa DNA Research Institute
Foundation; Wellcome Trust [073915]; NIH
FX Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research, USA (V.L., N.K.); Kazusa DNA Research
Institute Foundation (H.M.); Wellcome Trust of which W.C.E. is a
Principal Research Fellow [073915]. Funding for open access charge: NIH.
NR 58
TC 2
Z9 2
U1 2
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD MAY 19
PY 2015
VL 43
IS 9
AR e57
DI 10.1093/nar/gkv124
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CK0XK
UT WOS:000355928800001
PM 25712097
ER
PT J
AU Lark, DS
Kang, L
Lustig, ME
Bonner, JS
James, FD
Neufer, PD
Wasserman, DH
AF Lark, Daniel S.
Kang, Li
Lustig, Mary E.
Bonner, Jeffrey S.
James, Freyja D.
Neufer, P. Darrell
Wasserman, David H.
TI Enhanced Mitochondrial Superoxide Scavenging Does Not Improve Muscle
Insulin Action in the High Fat-Fed Mouse
SO PLOS ONE
LA English
DT Article
ID SKELETAL-MUSCLE; GLUCOSE-HOMEOSTASIS; DISMUTASE PROTECTS; CONSCIOUS
MOUSE; TRANSGENIC MICE; H2O2 EMISSION; CELL-DEATH; RESISTANCE;
OVEREXPRESSION; ANTIOXIDANT
AB Improving mitochondrial oxidant scavenging may be a viable strategy for the treatment of insulin resistance and diabetes. Mice overexpressing the mitochondrial matrix isoform of superoxide dismutase (sod2(tg) mice) and/or transgenically expressing catalase within the mitochondrial matrix (mcat(tg) mice) have increased scavenging of O-2(.-) and H2O2, respectively. Furthermore, muscle insulin action is partially preserved in high fat (HF)-fed mcat(tg) mice. The goal of the current study was to test the hypothesis that increased O-2(._) scavenging alone or in combination with increased H2O2 scavenging (mtAO mice) enhances in vivo muscle insulin action in the HF-fed mouse. Insulin action was examined in conscious, unrestrained and unstressed wild type (WT), sod2(tg), mcattg and mtAO mice using hyperinsulinemic-euglycemic clamps (insulin clamps) combined with radioactive glucose tracers following sixteen weeks of normal chow or HF (60% calories from fat) feeding. Glucose infusion rates, whole body glucose disappearance, and muscle glucose uptake during the insulin clamp were similar in chow- and HF-fed WT and sod2(tg) mice. Consistent with our previous work, HF-fed mcat(tg) mice had improved muscle insulin action, however, an additive effect was not seen in mtAO mice. Insulin-stimulated Akt phosphorylation in muscle from clamped mice was consistent with glucose flux measurements. These results demonstrate that increased O-2(._) scavenging does not improve muscle insulin action in the HF-fed mouse alone or when coupled to increased H2O2 scavenging.
C1 [Lark, Daniel S.; Kang, Li; Lustig, Mary E.; Bonner, Jeffrey S.; James, Freyja D.; Wasserman, David H.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37235 USA.
[Neufer, P. Darrell] E Carolina Univ, Dept Physiol, Greenville, NC USA.
[Neufer, P. Darrell] E Carolina Univ, East Carolina Diabet & Obes Inst, Greenville, NC USA.
[Wasserman, David H.] Vanderbilt Univ, Mouse Metab Phenotyping Ctr, Nashville, TN 37235 USA.
RP Lark, DS (reprint author), Vanderbilt Univ, Dept Mol Physiol & Biophys, 221 Kirkland Hall, Nashville, TN 37235 USA.
EM daniel.lark@vanderbilt.edu
OI Lark, Daniel/0000-0001-8386-8478
FU National Institutes of Health [DK054902, DK059637, DK007061, DK073488]
FX This work was supported by National Institutes of Health Grants DK054902
(to D.H.W.), DK059637 (Vanderbilt-NIDDK Mouse Metabolic Phenotyping
Center), DK007061 (to D.S.L.) and DK073488 (to P.D.N.). The authors
would also like to acknowledge the Diabetes Research and Training Center
(DK20593). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 31
TC 2
Z9 2
U1 0
U2 3
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 MAY 19
PY 2015
VL 10
IS 5
AR UNSP e0126732
DI 10.1371/journal.pone.0126732
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CI7BT
UT WOS:000354918600041
PM 25992608
ER
PT J
AU Chang, YH
Chen, SL
Lee, SY
Chen, PS
Wang, TY
Lee, IH
Chen, KC
Yang, YK
Hong, JS
Lu, RB
AF Chang, Yun-Hsuan
Chen, Shiou-Lan
Lee, Sheng-Yu
Chen, Po See
Wang, Tzu-Yun
Lee, I. Hui
Chen, Kao Chin
Yang, Yen Kuang
Hong, Jau-Shyong
Lu, Ru-Band
TI Low-dose add-on memantine treatment may improve cognitive performance
and self-reported health conditions in opioid-dependent patients
undergoing methadone-maintenance-therapy
SO SCIENTIFIC REPORTS
LA English
DT Article
ID OPIATE TREATMENT INDEX; RECEPTOR ANTAGONIST; DISORDERS; BUPRENORPHINE;
METAANALYSIS; AMPHETAMINE; RELIABILITY; DYSFUNCTION; IMPAIRMENT;
DEMENTIA
AB An important interaction between opioid and dopamine systems has been indicated, and using opioids may negatively affect cognitive functioning. Memantine, a medication for Alzheimer's disease, increasingly is being used for several disorders and maybe important for cognitive improvement. Opioid-dependent patients undergoing methadone-maintenance-therapy (MMT) and healthy controls (HCs) were recruited. Patients randomly assigned to the experimental (5 mg/day memantine (MMT+M) or placebo (MMT+P) group: 57 in MMT+M, 77 in MMT+P. Those completed the cognitive tasks at the baseline and after the 12-week treatment were analyzed. Thirty-seven age- and gender-matched HCs, and 42 MMT+P and 39 MMT+M patients were compared. The dropout rates were 49.4% in the MMT+P and 26.3% in the MMT+M. Both patient groups' cognitive performances were significantly worse than that of the HCs. After the treatment, both patient groups showed improved cognitive performance. We also found an interaction between the patient groups and time which indicated that the MMT+M group's post-treatment improvement was better than that of the MMT+P group. Memantine, previously reported as neuroprotective may attenuate chronic opioid-dependence-induced cognitive decline. Using such low dose of memantine as adjuvant treatment for improving cognitive performance in opioid dependents; the dose of memantine might be a worthy topic in future studies.
C1 [Chang, Yun-Hsuan] Asia Univ, Dept Psychol, Taichung, Taiwan.
[Chang, Yun-Hsuan; Lu, Ru-Band] Natl Cheng Kung Univ, Coll Med, Inst Allied Hlth Sci, Div Clin Psychol, Tainan 70101, Taiwan.
[Chang, Yun-Hsuan; Chen, Po See; Wang, Tzu-Yun; Lee, I. Hui; Chen, Kao Chin; Yang, Yen Kuang; Lu, Ru-Band] Natl Cheng Kung Univ, Coll Med, Dept Psychiat, Tainan 70101, Taiwan.
[Yang, Yen Kuang; Lu, Ru-Band] Natl Cheng Kung Univ, Coll Med, Inst Behav Med, Tainan 70101, Taiwan.
[Chen, Po See; Yang, Yen Kuang] Natl Cheng Kung Univ, Coll Med, Addict Res Ctr, Tainan 70101, Taiwan.
[Lee, Sheng-Yu; Chen, Po See; Wang, Tzu-Yun; Lee, I. Hui; Chen, Kao Chin; Yang, Yen Kuang; Lu, Ru-Band] Natl Cheng Kung Univ Hosp, Dept Psychiat, Tainan 70428, Taiwan.
[Lu, Ru-Band] Natl Hlth Res Inst, Ctr Neuropsychiat Res, Zhunan, Miaoli County, Taiwan.
[Lee, I. Hui] Natl Cheng Kung Univ Hosp, Dou Liou Branch, Dept Psychiat, Yunlin, Taiwan.
[Lee, Sheng-Yu] Kaohsiung Vet Gen Hosp, Dept Psychiat, Kaohsiung, Taiwan.
[Chen, Shiou-Lan] Kaohsiung Med Univ, Coll Med, Dept Neurol, Kaohsiung, Taiwan.
[Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, Neurobiol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Lu, RB (reprint author), Natl Cheng Kung Univ, Coll Med, Inst Allied Hlth Sci, Div Clin Psychol, Tainan 70101, Taiwan.
EM rblu@mail.ncku.edu.tw
FU Taiwan National Science Council [NSC 98-2627-B-006-017]; National Cheng
Kung University Project to Promote Academic Excellence and Develop a
World Class Research Center
FX This study was supported in part by grant NSC 98-2627-B-006-017 from the
Taiwan National Science Council (to RBL), and by a grant from the
National Cheng Kung University Project to Promote Academic Excellence
and Develop a World Class Research Center.
NR 48
TC 2
Z9 2
U1 3
U2 4
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 MAY 19
PY 2015
VL 5
AR 9708
DI 10.1038/srep09708
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CJ2CQ
UT WOS:000355292200001
PM 25989606
ER
PT J
AU Lee, SY
Chen, SL
Chang, YH
Chen, PS
Huang, SY
Tzeng, NS
Wang, LJ
Lee, IH
Wang, TY
Chen, KC
Yang, YK
Hong, JS
Lu, RB
AF Lee, Sheng-Yu
Chen, Shiou-Lan
Chang, Yun-Hsuan
Chen, Po See
Huang, San-Yuan
Tzeng, Nian-Sheng
Wang, Liang-Jen
Lee, I. Hui
Wang, Tzu-Yun
Chen, Kao Chin
Yang, Yen Kuang
Hong, Jau-Shyong
Lu, Ru-Band
TI Low-dose memantine attenuated methadone dose in opioid-dependent
patients: a 12-week double-blind randomized controlled trial
SO SCIENTIFIC REPORTS
LA English
DT Article
ID PSYCHIATRIC-DISORDERS; NEUROTROPHIC FACTOR; OPIUM TARYAK; TNF-ALPHA;
MORPHINE; INFLAMMATION; HEROIN; ANTAGONIST; ACTIVATION; MECHANISMS
AB Low-dose memantine might have anti-inflammatory and neurotrophic effects mechanistically remote from an NMDA receptor. We investigated whether add-on memantine reduced cytokine levels and benefitted patients with opioid dependence undergoing methadone maintenance therapy (MMT) in a randomized, double-blind, controlled 12-week study. Patients were randomly assigned to a group: Memantine (5 mg/day) (n = 53) or Placebo (n = 75). The methadone dose required and retention in treatment were monitored. Plasma tumor necrosis factor (TNF)-alpha, C-reactive protein (CRP), interleukin (IL)-6, IL-8, transforming growth factor (TGF)-beta 1, and brain-derived neurotrophic factor (BDNF) levels were examined during weeks 0, 1, 4, 8, and 12. General linear mixed models were used to examine therapeutic effect. After 12 weeks, Memantine-group required a somewhat lower methadone dose than did Placebo-group (P = 0.039). They also had significantly lower plasma TNF-alpha and significantly higher TGF-beta 1 levels. We provide evidence of the benefit of add-on memantine in opioid dependent patients undergoing MMT.
C1 [Lee, Sheng-Yu] Kaohsiung Vet Gen Hosp, Dept Psychiat, Kaohsiung, Taiwan.
[Lee, Sheng-Yu; Chen, Shiou-Lan; Chen, Po See; Lee, I. Hui; Wang, Tzu-Yun; Chen, Kao Chin; Yang, Yen Kuang; Lu, Ru-Band] Natl Cheng Kung Univ, Dept Psychiat, Coll Med & Hosp, Tainan 70101, Taiwan.
[Chen, Shiou-Lan] Kaohsiung Med Univ, Sch Med, Dept Neurol, Kaohsiung, Taiwan.
[Chang, Yun-Hsuan; Lu, Ru-Band] Natl Def Med Ctr, Inst Allied Hlth Sci, Taipei, Taiwan.
[Huang, San-Yuan; Tzeng, Nian-Sheng] Natl Def Med Ctr, Dept Psychiat, Tri Serv Gen Hosp, Taipei, Taiwan.
[Wang, Liang-Jen] Kaohsiung Chang Gung Mem Hosp, Dept Child & Adolescent Psychiat, Kaohsiung, Taiwan.
[Wang, Liang-Jen] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan.
[Hong, Jau-Shyong] NIEHS, Neurobiol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Lu, Ru-Band] Natl Cheng Kung Univ, Inst Behav Med, Coll Med & Hosp, Tainan 70101, Taiwan.
[Lu, Ru-Band] Natl Cheng Kung Univ, Addict Res Ctr, Tainan 70101, Taiwan.
[Lu, Ru-Band] Natl Hlth Res Inst, Ctr Neuropsychiat Res, Miaoli, Taiwan.
RP Lu, RB (reprint author), Natl Cheng Kung Univ, Dept Psychiat, Coll Med & Hosp, Tainan 70101, Taiwan.
EM rblu@mail.ncku.edu.tw
FU Taiwan National Science Council [NSC98-2314-B-006-022-MY3]; Taiwan
Department of Health [DOH 95-TD-M-113-055]; Taiwan National Health
Research Institute [NHRI-EX-97-9738NI]; National Cheng Kung University
Project for Promoting Academic Excellence and Developing World Class
Research Centers
FX We thank Dr Liang-Jen Wang for his statistical advice, and Ms Hong-Yi
Chang for her assistance in preparing this manuscript. This work was
supported in part by grant NSC98-2314-B-006-022-MY3 (to RBL) from the
Taiwan National Science Council, grant DOH 95-TD-M-113-055 (to RBL) from
the Taiwan Department of Health, grant NHRI-EX-97-9738NI (to RBL) from
the Taiwan National Health Research Institute, and the National Cheng
Kung University Project for Promoting Academic Excellence and Developing
World Class Research Centers.
NR 36
TC 1
Z9 1
U1 4
U2 7
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 MAY 19
PY 2015
VL 5
AR 10140
DI 10.1038/srep10140
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CJ2DM
UT WOS:000355294400001
PM 25988317
ER
PT J
AU Fenollar-Ferrer, C
Forster, IC
Patti, M
Knoepfel, T
Werner, A
Forrest, LR
AF Fenollar-Ferrer, Cristina
Forster, Ian C.
Patti, Monica
Knoepfel, Thomas
Werner, Andreas
Forrest, Lucy R.
TI Identification of the First Sodium Binding Site of the Phosphate
Cotransporter NaPi-IIa (SLC34A1)
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID NA+/P-I COTRANSPORTER; DEPENDENT DICARBOXYLATE TRANSPORTER; FUNCTIONALLY
IMPORTANT SITES; SUBSTRATE INTERACTIONS; VOLTAGE-DEPENDENCE;
MEMBRANE-PROTEINS; CATION; ELECTROGENICITY; MECHANISM; RESIDUES
AB Transporters of the SLC34 family (NaPi-IIa,b,c) catalyze uptake of inorganic phosphate (P-i) in renal and intestinal epithelia. The transport cycle requires three Na+ ions and one divalent P-i to bind before a conformational change enables translocation, intracellular release of the substrates, and reorientation of the empty carrier. The electrogenic interaction of the first Na+ ion with NaPi-IIa/b at a postulated Na1 site is accompanied by charge displacement, and Na1 occupancy subsequently facilitates binding of a second Na+ ion at Na2. The voltage dependence of cotransport and presteady-state charge displacements (in the absence of a complete transport cycle) are directly related to the molecular architecture of the Na1 site. The fact that Li+ ions substitute for Na+ at Na1, but not at the other sites (Na2 and Na3), provides an additional tool for investigating Na1 site-specific events. We recently proposed a three-dimensional model of human SLC34a1 (NaPi-IIa) including the binding sites Na2, Na3, and P-i based on the crystal structure of the dicarboxylate transporter VcINDY. Here, we propose nine residues in transmembrane helices (TM2, TM3, and TM5) that potentially contribute to Na1. To verify their roles experimentally, we made single alanine substitutions in the human NaPi-IIa isoform and investigated the kinetic properties of the mutants by voltage clamp and P-32 uptake. Substitutions at five positions in TM2 and one in TM5 resulted in relatively small changes in the substrate apparent affinities, yet at several of these positions, we observed significant hyperpolarizing shifts in the voltage dependence. Importantly, the ability of Li+ ions to substitute for Na+ ions was increased compared with the wild-type. Based on these findings, we adjusted the regions containing Na1 and Na3, resulting in a refined NaPi-IIa model in which five positions (T200, Q206, D209, N227, and S447) contribute directly to cation coordination at Na1.
C1 [Fenollar-Ferrer, Cristina; Forrest, Lucy R.] NINDS, Porter Neurosci Res Ctr, Computat Struct Biol Sect, NIH, Bethesda, MD 20892 USA.
[Forster, Ian C.; Patti, Monica; Knoepfel, Thomas] Univ Zurich, Inst Physiol, Zurich, Switzerland.
[Forster, Ian C.; Patti, Monica; Knoepfel, Thomas] Univ Zurich, Zurich Ctr Integrat Human Physiol, Zurich, Switzerland.
[Werner, Andreas] Newcastle Univ, Epithelial Res Grp, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
RP Forrest, LR (reprint author), NINDS, Porter Neurosci Res Ctr, Computat Struct Biol Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM iforster@access.uzh.ch; andreas.werner@newcastle.ac.uk;
lucy.forrest@nih.gov
FU Dunhill Medical Trust [AW SA10/0210]; Swiss National Science Foundation;
Hartmann Muller Foundation; NIH, National Institute of Neurological
Disorders and Stroke
FX This work was supported by The Dunhill Medical Trust (AW SA10/0210), the
Swiss National Science Foundation (I.C.F.), the Hartmann Muller
Foundation (I.C.F.), and the Intramural Research Program of the NIH,
National Institute of Neurological Disorders and Stroke (L.R.F.).
NR 37
TC 5
Z9 5
U1 0
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD MAY 19
PY 2015
VL 108
IS 10
BP 2465
EP 2480
DI 10.1016/j.bpj.2015.03.054
PG 16
WC Biophysics
SC Biophysics
GA CI5VF
UT WOS:000354827200007
PM 25992725
ER
PT J
AU Norouzi, D
Zhurkin, VB
AF Norouzi, Davood
Zhurkin, Victor B.
TI Topological Polymorphism of the Two-Start Chromatin Fiber
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID HIGHER-ORDER STRUCTURE; NUCLEOSOME CORE PARTICLE; LINKING NUMBER;
MOLECULAR-DYNAMICS; REPEAT LENGTH; LINKER LENGTH; DOUBLE HELIX; DNA;
ORIENTATION; REVEALS
AB Specific details concerning the spatial organization of nucleosomes in 30 nm fibers remain unknown. To investigate this, we analyzed all stereochemically possible configurations of two-start nucleosome fibers with short DNA linkers L = 13-37 bp (nucleosome repeat length (NRL) = 160-184 bp). Four superhelical parameters-inclination of nucleosomes, twist, rise, and diameter-uniquely describe a regular symmetric fiber. The energy of a fiber is defined as the sum of four terms: elastic energy of the linker DNA, steric repulsion, electrostatics, and a phenomenological (H4 tail-acidic patch) interaction between two stacked nucleosomes. By optimizing the fiber energy with respect to the superhelical parameters, we found two types of topological transition in fibers (associated with the change in inclination angle): one caused by an abrupt 360 degrees change in the linker DNA twisting (change in the DNA linking number, Delta Lk = 1), and another caused by overcrossing of the linkers (Delta Lk = 2). To the best of our knowledge, this topological polymorphism of the two-start fibers was not reported in the computations published earlier. Importantly, the optimal configurations of the fibers with linkers L = 10n and 10n + 5 bp are characterized by different values of the DNA linking number-that is, they are topologically different. Our results are consistent with experimental observations, such as the inclination 60 degrees to 70 degrees (the angle between the nucleosomal disks and the fiber axis), helical rise, diameter, and left-handedness of the fibers. In addition, we make several testable predictions, among them different degrees of DNA supercoiling in fibers with L = 10n and 10n + 5 bp, different flexibility of the two types of fibers, and a correlation between the local NRL and the level of transcription in different parts of the yeast genome.
C1 [Norouzi, Davood; Zhurkin, Victor B.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Zhurkin, VB (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM zhurkin@nih.gov
FU NIH Intramural Research Program
FX We are grateful to Wilma Olson and Sergei Grigoryev for sharing their
unpublished observations and valuable discussions and to George Leiman
for text editing. We appreciate constructive critical remarks by
anonymous reviewers. The research was supported by the NIH Intramural
Research Program.
NR 55
TC 9
Z9 10
U1 2
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD MAY 19
PY 2015
VL 108
IS 10
BP 2591
EP 2600
DI 10.1016/j.bpj.2015.04.015
PG 10
WC Biophysics
SC Biophysics
GA CI5VF
UT WOS:000354827200019
PM 25992737
ER
PT J
AU Givertz, MM
Anstrom, KJ
Redfield, MM
Deswal, A
Haddad, H
Butler, J
Tang, WHW
Dunlap, ME
LeWinter, MM
Mann, DL
Felker, GM
O'Connor, CM
Goldsmith, SR
Ofili, EO
Saltzberg, MT
Margulies, KB
Cappola, TP
Konstam, MA
Semigran, MJ
McNulty, SE
Lee, KL
Shah, MR
Hernandez, AF
AF Givertz, Michael M.
Anstrom, Kevin J.
Redfield, Margaret M.
Deswal, Anita
Haddad, Haissam
Butler, Javed
Tang, W. H. Wilson
Dunlap, Mark E.
LeWinter, Martin M.
Mann, Douglas L.
Felker, G. Michael
O'Connor, Christopher M.
Goldsmith, Steven R.
Ofili, Elizabeth O.
Saltzberg, Mitchell T.
Margulies, Kenneth B.
Cappola, Thomas P.
Konstam, Marvin A.
Semigran, Marc J.
McNulty, Steven E.
Lee, Kerry L.
Shah, Monica R.
Hernandez, Adrian F.
CA NHLBI Heart Failure Clinical Res
TI Effects of Xanthine Oxidase Inhibition in Hyperuricemic Heart Failure
Patients The Xanthine Oxidase Inhibition for Hyperuricemic Heart Failure
Patients (EXACT-HF) Study
SO CIRCULATION
LA English
DT Article
DE allopurinol; clinical trial; heart failure; xanthine oxidase
ID NITROSO-REDOX IMBALANCE; LEFT-VENTRICULAR MASS; URIC-ACID; OXIDATIVE
STRESS; ALLOPURINOL USE; HEALTH-STATUS; OXYPURINOL; SURVIVAL; TRIAL;
CARDIOMYOPATHY
AB Background-Oxidative stress may contribute to heart failure (HF) progression. Inhibiting xanthine oxidase in hyperuricemic HF patients may improve outcomes.
Methods and Results-We randomly assigned 253 patients with symptomatic HF, left ventricular ejection fraction <= 40%, and serum uric acid levels >= 9.5 mg/dL to receive allopurinol (target dose, 600 mg daily) or placebo in a double-blind, multicenter trial. The primary composite end point at 24 weeks was based on survival, worsening HF, and patient global assessment. Secondary end points included change in quality of life, submaximal exercise capacity, and left ventricular ejection fraction. Uric acid levels were significantly reduced with allopurinol in comparison with placebo (treatment difference, -4.2 [-4.9, -3.5] mg/dL and -3.5 [-4.2, -2.7] mg/dL at 12 and 24 weeks, respectively, both P<0.0001). At 24 weeks, there was no significant difference in clinical status between the allopurinol-and placebo-treated patients (worsened 45% versus 46%, unchanged 42% versus 34%, improved 13% versus 19%, respectively; P=0.68). At 12 and 24 weeks, there was no significant difference in change in Kansas City Cardiomyopathy Questionnaire scores or 6-minute walk distances between the 2 groups. At 24 weeks, left ventricular ejection fraction did not change in either group or between groups. Rash occurred more frequently with allopurinol (10% versus 2%, P=0.01), but there was no difference in serious adverse event rates between the groups (20% versus 15%, P=0.36).
Conclusions-In high-risk HF patients with reduced ejection fraction and elevated uric acid levels, xanthine oxidase inhibition with allopurinol failed to improve clinical status, exercise capacity, quality of life, or left ventricular ejection fraction at 24 weeks.
C1 [Givertz, Michael M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Anstrom, Kevin J.; Felker, G. Michael; O'Connor, Christopher M.; McNulty, Steven E.; Lee, Kerry L.; Hernandez, Adrian F.] Duke Univ, Med Ctr, Durham, NC USA.
[Redfield, Margaret M.] Mayo Clin, Rochester, MN USA.
[Deswal, Anita] Baylor Coll Med, Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA.
[Haddad, Haissam] Ottawa Heart Inst, Ottawa, ON, Canada.
[Butler, Javed] Emory Univ, Atlanta, GA 30322 USA.
[Tang, W. H. Wilson] Cleveland Clin, Cleveland, OH USA.
[Dunlap, Mark E.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[LeWinter, Martin M.] Univ Vermont, Burlington, VT 05405 USA.
[Mann, Douglas L.] Washington Univ, St Louis, MO USA.
[Goldsmith, Steven R.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA.
[Ofili, Elizabeth O.] Morehouse Sch Med, Atlanta, GA 30310 USA.
[Saltzberg, Mitchell T.] Christiana Care Hlth Syst, Newark, DE USA.
[Margulies, Kenneth B.; Cappola, Thomas P.] Univ Penn, Philadelphia, PA 19104 USA.
[Konstam, Marvin A.] Tufts Med Ctr, Boston, MA USA.
[Semigran, Marc J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Shah, Monica R.] NHLBI, Bethesda, MD 20892 USA.
RP Givertz, MM (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA.
EM mgivertz@partners.org
RI Hernandez, Adrian F./A-7818-2016
OI Hernandez, Adrian F./0000-0003-3387-9616
FU National Institutes of Health: NHLBI [U10HL084904, U01HL084861,
U10HL110312, U109HL110337, U01HL084889, U01HL084890, U01HL084891,
U10HL110342, U10HL110262, U01HL084931, U10HL110297, U10HL110302, U10
HL110309, U10HL110336, U10HL110338]; National Center for Advancing
Translational Sciences [UL1TR000454, UL1TR000439]; National Institute on
Minority Health and Health Disparities [8 U54 MD007588]
FX This work was supported by grants from the National Institutes of
Health: NHLBI (coordinating center: U10HL084904; regional clinical
centers: U01HL084861, U10HL110312, U109HL110337, U01HL084889,
U01HL084890, U01HL084891, U10HL110342, U10HL110262, U01HL084931,
U10HL110297, U10HL110302, U10 HL110309, U10HL110336, U10HL110338); the
National Center for Advancing Translational Sciences (UL1TR000454,
UL1TR000439); and the National Institute on Minority Health and Health
Disparities (8 U54 MD007588).
NR 41
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PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAY 19
PY 2015
VL 131
IS 20
BP 1763
EP 1771
DI 10.1161/CIRCULATIONAHA.114.014536
PG 9
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CI2XC
UT WOS:000354610300013
PM 25986447
ER
PT J
AU Mitra, S
Ring, AM
Amarnath, S
Spangler, JB
Li, P
Ju, W
Fischer, S
Oh, J
Spolski, R
Weiskopf, K
Kohrt, H
Foley, JE
Rajagopalan, S
Long, EO
Fowler, DH
Waldmann, TA
Garcia, KC
Leonard, WJ
AF Mitra, Suman
Ring, Aaron M.
Amarnath, Shoba
Spangler, Jamie B.
Li, Peng
Ju, Wei
Fischer, Suzanne
Oh, Jangsuk
Spolski, Rosanne
Weiskopf, Kipp
Kohrt, Holbrook
Foley, Jason E.
Rajagopalan, Sumati
Long, Eric O.
Fowler, Daniel H.
Waldmann, Thomas A.
Garcia, K. Christopher
Leonard, Warren J.
TI Interleukin-2 Activity Can Be Fine Tuned with Engineered Receptor
Signaling Clamps
SO IMMUNITY
LA English
DT Article
ID GAMMA-CHAIN; IL-2 RECEPTOR; BETA-CHAIN; CARDIAC TRANSPLANTATION;
CYTOPLASMIC DOMAINS; MONOCLONAL-ANTIBODY; ALPHA-RECEPTOR; T-LYMPHOCYTES;
HOST-DISEASE; CELLS
AB Interleukin-2 (IL-2) regulates lymphocyte function by signaling through heterodimerization of the IL-2R beta and gamma(c) receptor subunits. IL-2 is of considerable therapeutic interest, but harnessing its actions in a controllable manner remains a challenge. Previously, we have engineered an IL-2 "superkine'' with enhanced affinity for IL-2R beta. Here, we describe next-generation IL-2 variants that function as "receptor signaling clamps.'' They retained high affinity for IL-2R beta, inhibiting binding of endogenous IL-2, but their interaction with gamma(c) was weakened, attenuating IL-2R beta-gamma(c) heterodimerization. These IL-2 analogs acted as partial agonists and differentially affected lymphocytes poised at distinct activation thresholds. Moreover, one variant, H9-RETR, antagonized IL-2 and IL-15 better than blocking antibodies against IL-2R alpha or IL-2R beta. Furthermore, this mutein prolonged survival in a model of graft-versus-host disease and blocked spontaneous proliferation of smoldering adult T cell leukemia (ATL) T cells. This receptor-clamping approach might be a general mechanism-based strategy for engineering cytokine partial agonists for therapeutic immunomodulation.
C1 [Mitra, Suman; Li, Peng; Oh, Jangsuk; Spolski, Rosanne; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Mitra, Suman; Li, Peng; Oh, Jangsuk; Spolski, Rosanne; Leonard, Warren J.] NHLBI, Ctr Immunol, NIH, Bethesda, MD 20892 USA.
[Ring, Aaron M.; Spangler, Jamie B.; Fischer, Suzanne; Garcia, K. Christopher] Stanford Univ, Howard Hughes Med Inst, Sch Med, Stanford, CA 94305 USA.
[Ring, Aaron M.; Spangler, Jamie B.; Fischer, Suzanne; Garcia, K. Christopher] Stanford Univ, Dept Mol & Cellular Physiol, Sch Med, Stanford, CA 94305 USA.
[Ring, Aaron M.; Spangler, Jamie B.; Fischer, Suzanne; Garcia, K. Christopher] Stanford Univ, Dept Biol Struct, Sch Med, Stanford, CA 94305 USA.
[Amarnath, Shoba; Foley, Jason E.; Fowler, Daniel H.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Ju, Wei; Waldmann, Thomas A.] NCI, Lymphoid Malignancies Branch, NIH, Bethesda, MD 20892 USA.
[Weiskopf, Kipp; Kohrt, Holbrook] Stanford Univ, Dept Med, Div Oncol, Sch Med, Stanford, CA 94305 USA.
[Rajagopalan, Sumati; Long, Eric O.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Garcia, KC (reprint author), Stanford Univ, Howard Hughes Med Inst, Sch Med, Stanford, CA 94305 USA.
EM kcgarcia@stanford.edu; wjl@helix.nih.gov
FU Divisions of Intramural Research, National Heart, Lung, and Blood
Institute; National Cancer Institute; National Institute of Allergy and
Infectious Diseases; Leukemia & Lymphoma Society; [NIH-R0AI51321];
[NIH-F30DK094541]
FX This work was supported by the Divisions of Intramural Research,
National Heart, Lung, and Blood Institute (S.M., P.L., J.O., R.S., and
W.J.L.), National Cancer Institute (S.M., W.J., D.H.F., and T.A.W.),
National Institute of Allergy and Infectious Diseases (S.R. and E.O.L),
NIH-R0AI51321 (K.C.G.), and NIH-F30DK094541 (A.M.R.). K.C.G. is an
investigator of the Howard Hughes Medical Institute. J.B.S. is the
recipient of a Leukemia & Lymphoma Society Career Development Program
fellowship. We thank Dr. Junji Yodoi, Kyoto University, for YT and YT-1
NK-like cells.
NR 48
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U2 17
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 MAY 19
PY 2015
VL 42
IS 5
BP 826
EP 838
DI 10.1016/j.immuni.2015.04.018
PG 13
WC Immunology
SC Immunology
GA CI5VH
UT WOS:000354827400010
PM 25992859
ER
PT J
AU Ritter, AT
Asano, Y
Stinchcombe, JC
Dieckmann, NMG
Chen, BC
Gawden-Bone, C
van Engelenburg, S
Legant, W
Gao, L
Davidson, MW
Betzig, E
Lippincott-Schwartz, J
Griffiths, GM
AF Ritter, Alex T.
Asano, Yukako
Stinchcombe, Jane C.
Dieckmann, N. M. G.
Chen, Bi-Chang
Gawden-Bone, C.
van Engelenburg, Schuyler
Legant, Wesley
Gao, Liang
Davidson, Michael W.
Betzig, Eric
Lippincott-Schwartz, Jennifer
Griffiths, Gillian M.
TI Actin Depletion Initiates Events Leading to Granule Secretion at the
Immunological Synapse
SO IMMUNITY
LA English
DT Article
ID T-CELL-RECEPTOR; RETROGRADE FLOW; F-ACTIN; ACTIVATION; MICROCLUSTERS;
ADHESION; DOMAIN; POLYMERIZATION; REORIENTATION; ACCUMULATION
AB Cytotoxic T lymphocytes (CTLs) use polarized secretion to rapidly destroy virally infected and tumor cells. To understand the temporal relationships between key events leading to secretion, we used high-resolution 4D imaging. CTLs approached targets with actin-rich projections at the leading edge, creating an initially actin-enriched contact with rearward-flowing actin. Within 1 min, cortical actin reduced across the synapse, T cell receptors (TCRs) clustered centrally to form the central supramolecular activation cluster (cSMAC), and centrosome polarization began. Granules clustered around the moving centrosome within 2.5 min and reached the synapse after 6 min. TCR-bearing intracellular vesicles were delivered to the cSMAC as the centrosome docked. We found that the centrosome and granules were delivered to an area of membrane with reduced cortical actin density and phospholipid PIP2. These data resolve the temporal order of events during synapse maturation in 4D and reveal a critical role for actin depletion in regulating secretion.
C1 [Ritter, Alex T.; Asano, Yukako; Stinchcombe, Jane C.; Dieckmann, N. M. G.; Gawden-Bone, C.; Griffiths, Gillian M.] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 0XY, England.
[Ritter, Alex T.; van Engelenburg, Schuyler; Lippincott-Schwartz, Jennifer] NICHD, NIH, Bethesda, MD 20892 USA.
[Chen, Bi-Chang; Legant, Wesley; Gao, Liang; Betzig, Eric] Howard Hughes Med Inst, Ashburn, VA 20147 USA.
[Davidson, Michael W.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32304 USA.
[Davidson, Michael W.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32304 USA.
RP Lippincott-Schwartz, J (reprint author), NICHD, NIH, Bethesda, MD 20892 USA.
EM lippincj@mail.nih.gov; gg305@cam.ac.uk
RI Chen , Bi-Chang /F-3480-2014;
OI Griffiths, Gillian/0000-0003-0434-5842
FU Wellcome Trust [075880, 103930]; Eunice Shriver National Institute of
Child Health and Human Development; [100140]
FX Funding was provided by the Wellcome Trust through Principal Research
Fellowships (075880 and 103930) to G.M.G. and a Strategic Award (100140)
to the Cambridge Institute for Medical Research (CIMR). A.T.R. is an
NIH-OxCam scholar supported by funding to J.L.-S. from the Eunice
Shriver National Institute of Child Health and Human Development. At the
NIH, we thank Senta Kapnick and Pam Schwartzberg for assistance with CTL
culture and helpful discussion, P. Sengupta for Farnesyl-EGFP, and Erin
Fincher for assistance with the graphic illustration. At the CIMR, we
thank Matthew Gratian and Mark Bowen for support with imaging and Alison
Schuldt and John James for critical reading of the manuscript. The
light-sheet technology used herein is covered by US patent 7,894,136
(issued to E.B. and assigned to Lattice Light LLC of Ashburn, VA), US
patent 8,711,211 (issued to E.B. and assigned to the Howard Hughes
Medical Institute [HHMI]), and US patent application 13/844,405 (filed
by E.B. and assigned to the HHMI).
NR 42
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U2 15
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 MAY 19
PY 2015
VL 42
IS 5
BP 864
EP 876
DI 10.1016/j.immuni.2015.04.013
PG 13
WC Immunology
SC Immunology
GA CI5VH
UT WOS:000354827400013
PM 25992860
ER
PT J
AU Hirahara, K
Onodera, A
Villarino, AV
Bonelli, M
Sciume, G
Laurence, A
Sun, HW
Brooks, SR
Vahedi, G
Shih, HY
Gutierrez-Cruz, G
Iwata, S
Suzuki, R
Mikami, Y
Okamoto, Y
Nakayama, T
Holland, SM
Hunter, CA
Kanno, Y
O'Shea, JJ
AF Hirahara, Kiyoshi
Onodera, Atsushi
Villarino, Alejandro V.
Bonelli, Michael
Sciume, Giuseppe
Laurence, Arian
Sun, Hong-Wei
Brooks, Stephen R.
Vahedi, Golnaz
Shih, Han-Yu
Gutierrez-Cruz, Gustavo
Iwata, Shigeru
Suzuki, Ryo
Mikami, Yohei
Okamoto, Yoshitaka
Nakayama, Toshinori
Holland, Steven M.
Hunter, Christopher A.
Kanno, Yuka
O'Shea, John J.
TI Asymmetric Action of STAT Transcription Factors Drives Transcriptional
Outputs and Cytokine Specificity
SO IMMUNITY
LA English
DT Article
ID CD4(+) T-CELLS; INTERFERON-GAMMA; CUTTING EDGE; TH17 CELLS; IL-27;
INTERLEUKIN-27; ACTIVATION; RECEPTOR; DIFFERENTIATION; INDUCTION
AB Interleukin-6 (IL-6) and IL-27 signal through a shared receptor subunit and employ the same downstream STAT transcription proteins, but yet are ascribed unique and overlapping functions. To evaluate the specificity and redundancy for these cytokines, we quantified their global transcriptomic changes and determined the relative contributions of STAT1 and STAT3 using genetic models and chromatin immunoprecipitation- sequencing (ChIP-seq) approaches. We found an extensive overlap of the transcriptomes induced by IL-6 and IL-27 and few examples in which the cytokines acted in opposition. Using STAT-deficient cells and T cells from patients with gain-of-function STAT1 mutations, we demonstrated that STAT3 is responsible for the overall transcriptional output driven by both cytokines, whereas STAT1 is the principal driver of specificity. STAT1 cannot compensate in the absence of STAT3 and, in fact, much of STAT1 binding to chromatin is STAT3 dependent. Thus, STAT1 shapes the specific cytokine signature superimposed upon STAT3's action.
C1 [Hirahara, Kiyoshi; Villarino, Alejandro V.; Bonelli, Michael; Sciume, Giuseppe; Laurence, Arian; Vahedi, Golnaz; Shih, Han-Yu; Iwata, Shigeru; Mikami, Yohei; Kanno, Yuka; O'Shea, John J.] NIAMS, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
[Sun, Hong-Wei; Brooks, Stephen R.] NIAMS, Biodata Min & Discovery Sect, NIH, Bethesda, MD 20892 USA.
[Gutierrez-Cruz, Gustavo] NIAMS, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA.
[Suzuki, Ryo] NIAMS, Lab Mol Immunogenet, NIH, Bethesda, MD 20892 USA.
[Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Hunter, Christopher A.] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA.
[Hirahara, Kiyoshi] Chiba Univ, Grad Sch Med, Dept Adv Allergol Airway, Chiba 2608670, Japan.
[Onodera, Atsushi; Nakayama, Toshinori] Chiba Univ, Grad Sch Med, Dept Immunol, Chiba 2608670, Japan.
[Okamoto, Yoshitaka] Chiba Univ, Grad Sch Med, Dept Otorhinolaryngol, Chiba 2608670, Japan.
[Nakayama, Toshinori] Core Res Evolut Sci & Technol, Japan Sci & Technol Agcy, Chiba, Chiba 2608670, Japan.
RP Kanno, Y (reprint author), NIAMS, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
EM kannoy@mail.nih.gov; osheaj@arb.niams.nih.gov
RI Laurence, Arian/A-8770-2009; Sciume, Giuseppe/K-8985-2016; Nakayama,
Toshinori/E-1067-2017; Hirahara, Kiyoshi/E-2460-2017; Onodera,
Atsushi/E-3136-2017;
OI Laurence, Arian/0000-0003-0942-8292; Sciume,
Giuseppe/0000-0003-0131-512X; Hirahara, Kiyoshi/0000-0002-9128-9449;
Kanno, Yuka/0000-0001-5668-9319; Villarino,
Alejandro/0000-0001-8068-2176
FU Intramural Research Programs of NIAMS; Ministry of Education, Culture,
Sports, Science and Technology (Japan) [25893032]; Astellas Foundation
for Research on Metabolic Disorders; Uehara Memorial Foundation; Osaka
Foundation for Promotion of Fundamental Medical Research; Kanae
Foundation for the Promotion of Medical Science; Takeda Science
Foundation
FX We thank J. Simone, J. Lay (Flow Cytometry Section, NIAMS), and the
NIAMS LACU staff for their excellent technical support. This study
utilized the high-performance computational capabilities of the Helix
Systems at the NIH. This work was supported by the Intramural Research
Programs of NIAMS, grant from the Ministry of Education, Culture,
Sports, Science and Technology (Japan; Grants-in-Aid for Research
Activity start-up #25893032), The Astellas Foundation for Research on
Metabolic Disorders, The Uehara Memorial Foundation, Osaka Foundation
for Promotion of Fundamental Medical Research, Kanae Foundation for the
Promotion of Medical Science, and Takeda Science Foundation (K.H.).
NR 50
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U2 17
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
EI 1097-4180
J9 IMMUNITY
JI Immunity
PD MAY 19
PY 2015
VL 42
IS 5
BP 877
EP 889
DI 10.1016/j.immuni.2015.04.014
PG 13
WC Immunology
SC Immunology
GA CI5VH
UT WOS:000354827400014
PM 25992861
ER
PT J
AU Butt, D
Chan, TD
Bourne, K
Hermes, JR
Nguyen, A
Statham, A
O'Reilly, LA
Strasser, A
Price, S
Schofield, P
Christ, D
Basten, A
Ma, CS
Tangye, SG
Phan, TG
Rao, VK
Brink, R
AF Butt, Danyal
Chan, Tyani D.
Bourne, Katherine
Hermes, Jana R.
Nguyen, Akira
Statham, Aaron
O'Reilly, Lorraine A.
Strasser, Andreas
Price, Susan
Schofield, Peter
Christ, Daniel
Basten, Antony
Ma, Cindy S.
Tangye, Stuart G.
Tri Giang Phan
Rao, V. Koneti
Brink, Robert
TI FAS Inactivation Releases Unconventional Germinal Center B Cells that
Escape Antigen Control and Drive IgE and Autoantibody Production
SO IMMUNITY
LA English
DT Article
ID AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; SYSTEMIC-LUPUS-ERYTHEMATOSUS;
T-CELLS; GENE-MUTATIONS; IN-VIVO; LIGAND; APOPTOSIS; MICE; DISEASE;
ELIMINATION
AB The mechanistic links between genetic variation and autoantibody production in autoimmune disease remain obscure. Autoimmune lymphoproliferative syndrome (ALPS) is caused by inactivating mutations in FAS or FASL, with autoantibodies thought to arise through failure of FAS-mediated removal of self-reactive germinal center (GC) B cells. Here we show that FAS is in fact not required for this process. Instead, FAS inactivation led to accumulation of a population of unconventional GC B cells that underwent somatic hypermutation, survived despite losing antigen reactivity, and differentiated into a large population of plasma cells that included autoantibody-secreting clones. IgE(+) plasma cell numbers, in particular, increased after FAS inactivation and a major cohort of ALPS-affected patients were found to have hyper-IgE. We propose that these previously unidentified cells, designated "rogue GC B cells,'' are a major driver of autoantibody production and provide a mechanistic explanation for the linked production of IgE and autoantibodies in autoimmune disease.
C1 [Butt, Danyal; Chan, Tyani D.; Bourne, Katherine; Hermes, Jana R.; Nguyen, Akira; Statham, Aaron; Schofield, Peter; Christ, Daniel; Basten, Antony; Ma, Cindy S.; Tangye, Stuart G.; Tri Giang Phan; Brink, Robert] Garvan Inst Med Res, Div Immunol, Darlinghurst, NSW 2010, Australia.
[Butt, Danyal; Chan, Tyani D.; Christ, Daniel; Basten, Antony; Ma, Cindy S.; Tangye, Stuart G.; Tri Giang Phan; Brink, Robert] UNSW Australia, St Vincents Clin Sch, Darlinghurst, NSW 2010, Australia.
[O'Reilly, Lorraine A.; Strasser, Andreas] Walter & Eliza Hall Inst Med Res, Mol Genet Canc Div, Parkville, Vic 3052, Australia.
[O'Reilly, Lorraine A.; Strasser, Andreas] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia.
[Price, Susan; Rao, V. Koneti] NIAID, Mol Dev Sect, Immunol Lab, Div Intramural Res,NIH, Bethesda, MD 20892 USA.
RP Brink, R (reprint author), Garvan Inst Med Res, Div Immunol, 384 Victoria St, Darlinghurst, NSW 2010, Australia.
EM r.brink@garvan.org.au
RI Strasser, Andreas/C-7581-2013;
OI Strasser, Andreas/0000-0002-5020-4891
FU Australian Postgraduate Award; National Health and Medical Research
Council (NHMRC) [1054669, 1020363, 1050146, 1008820, 1042925, 1005097,
1002280]; Asthma Foundation NSW; R.G. Arnott Foundation; NHMRC [1044477,
1016953, 1009145, 1016701]; Leukemia and Lymphoma Society (SCOR) [7413,
7001-13]; National Institute of Allergy and Infectious Diseases; NIH
Clinical Center
FX We thank R. Salomon, C. Brownlee, and Garvan Institute Flow Facility
staff for single-cell sorting and J. Kingham and the staff of Australian
BioResources for animal husbandry. We also thank C. Goodnow, A. Collins,
and J. Davies for their comments on the manuscript. D.B. is supported by
an Australian Postgraduate Award and T.D.C., A. Strasser, D. C., C.S.M.,
S.G.T., T.G.P., and R.B. by National Health and Medical Research Council
(NHMRC) fellowships 1054669, 1020363, 1050146, 1008820, 1042925,
1005097, and 1002280. This work was funded by Asthma Foundation NSW,
R.G. Arnott Foundation, NHMRC Project Grant 1044477, and NHMRC Program
Grant 1016953. Additional support came from NHMRC Project Grant 1009145,
NHMRC Program Grant 1016701, Leukemia and Lymphoma Society (SCOR grants
#7413 and #7001-13), and the Intramural Research Program of the National
Institute of Allergy and Infectious Diseases and the NIH Clinical
Center.
NR 44
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U1 2
U2 9
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 MAY 19
PY 2015
VL 42
IS 5
BP 890
EP 902
DI 10.1016/j.immuni.2015.04.010
PG 13
WC Immunology
SC Immunology
GA CI5VH
UT WOS:000354827400015
PM 25979420
ER
PT J
AU Devanathan, V
Hagedorn, I
Kohler, D
Pexa, K
Cherpokova, D
Kraft, P
Singh, M
Rosenberger, P
Stoll, G
Birnbaumer, L
Piekorz, RP
Beer-Hammer, S
Nieswandt, B
Nurnberg, B
AF Devanathan, Vasudharani
Hagedorn, Ina
Koehler, David
Pexa, Katja
Cherpokova, Deya
Kraft, Peter
Singh, Madhurendra
Rosenberger, Peter
Stoll, Guido
Birnbaumer, Lutz
Piekorz, Roland P.
Beer-Hammer, Sandra
Nieswandt, Bernhard
Nuernberg, Bernd
TI Platelet G(i) protein G alpha(i2) is an essential mediator of
thrombo-inflammatory organ damage in mice
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE G proteins; platelets; ischemia reperfusion injury; P2Y(12) receptor;
thrombosis
ID CARDIOVASCULAR-DISEASE; ARTERIAL THROMBOSIS; REPERFUSION INJURY;
ISCHEMIC-STROKE; FAMILY MEMBERS; BLEEDING-TIME; ACTIVATION; RECEPTOR;
P2Y(12); AGGREGATION
AB Platelets are crucial for hemostasis and thrombosis and exacerbate tissue injury following ischemia and reperfusion. Important regulators of platelet function are G proteins controlled by seven transmembrane receptors. The G(i) protein G alpha(i2) mediates platelet activation in vitro, but its in vivo role in hemostasis, arterial thrombosis, and postischemic infarct progression remains to be determined. Here we show that mice lacking G alpha(i2) exhibit prolonged tail-bleeding times and markedly impaired thrombus formation and stability in different models of arterial thrombosis. We thus generated mice selectively lacking G alpha(i2) in megakaryocytes and platelets (Gnai2(fl/fl)/PF4-Cre mice) and found bleeding defects comparable to those in global G alpha(i2)-deficient mice. To examine the impact of platelet G alpha(i2) in postischemic thrombo-inflammatory infarct progression, Gnai2(fl/fl)/PF4-Cre mice were subjected to experimental models of cerebral and myocardial ischemia/reperfusion injury. In the model of transient middle cerebral artery occlusion stroke Gnai2(fl/fl)/PF4-Cre mice developed significantly smaller brain infarcts and fewer neurological deficits than littermate controls. Following myocardial ischemia, Gnai2(fl/fl)/PF4-Cre mice showed dramatically reduced reperfusion injury which correlated with diminished formation of the ADP-dependent platelet neutrophil complex. In conclusion, our data provide definitive evidence that platelet G alpha(i2) not only controls hemostatic and thrombotic responses but also is critical for the development of ischemia/reperfusion injury in vivo.
C1 [Devanathan, Vasudharani; Beer-Hammer, Sandra; Nuernberg, Bernd] Univ Tubingen, Dept Pharmacol & Expt Therapy, D-72074 Tubingen, Germany.
[Devanathan, Vasudharani; Beer-Hammer, Sandra; Nuernberg, Bernd] Univ Tubingen, Interfac Ctr Pharmacogen & Drug Res, D-72074 Tubingen, Germany.
[Koehler, David; Rosenberger, Peter] Univ Tubingen, Dept Anesthesiol & Intens Care Med, D-72076 Tubingen, Germany.
[Hagedorn, Ina; Cherpokova, Deya; Nieswandt, Bernhard] Univ Wurzburg, Univ Hosp, Dept Expt Biomed, D-97080 Wurzburg, Germany.
[Cherpokova, Deya; Nieswandt, Bernhard] Univ Wurzburg, Rudolf Virchow Ctr, D-97080 Wurzburg, Germany.
[Kraft, Peter; Stoll, Guido] Univ Wurzburg, Dept Neurol, D-97080 Wurzburg, Germany.
[Pexa, Katja; Singh, Madhurendra; Piekorz, Roland P.] Univ Dusseldorf, Inst Biochem & Mol Biol 2, D-40225 Dusseldorf, Germany.
[Birnbaumer, Lutz] NIEHS, Neurobiol Lab, NIH, Res Triangle Pk, NC 27009 USA.
RP Birnbaumer, L (reprint author), NIEHS, Neurobiol Lab, NIH, Res Triangle Pk, NC 27009 USA.
EM birnbau1@gmail.com; bernd.nuernberg@uni-tuebingen.de
FU Deutsche Forschungsgemeinschaft [Sonderforschungsbereich (SFB) 612,
MO2252/1, SFB 688]; Forschungskommission (Medical Faculty) of the
Dusseldorf University [9772327, 9772517]; Dusseldorf Entrepreneurs
Foundation ("Qiagen-Stiftung"); Intramural Research Program of the
National Institutes of Health Grant [Z01-ES101643]
FX We thank Sandra Schwegmann, Michaela Hoch-Gutbrod, and Dr. Claudia
Bernardo de Oliviera Franz for excellent technical assistance and
Christian Harteneck for critical discussions. This work was supported by
Deutsche Forschungsgemeinschaft Grants Sonderforschungsbereich (SFB) 612
(to R.P.P. and B. Nurnberg), MO2252/1 (to D.K.), and SFB 688 (to B.
Nieswandt and G.S.); Forschungskommission (Medical Faculty) of the
Dusseldorf University Grants 9772327 (to R.P.P. and B. Nurnberg) and
9772517 (to R.P.P.); a grant from the Dusseldorf Entrepreneurs
Foundation ("Qiagen-Stiftung") (to K.P.); and the Intramural Research
Program of the National Institutes of Health Grant Z01-ES101643 (to
L.B.).
NR 49
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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 MAY 19
PY 2015
VL 112
IS 20
BP 6491
EP 6496
DI 10.1073/pnas.1505887112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CI4OD
UT WOS:000354729500074
PM 25944935
ER
PT J
AU Jorgenson, LA
Newsome, WT
Anderson, DJ
Bargmann, CI
Brown, EN
Deisseroth, K
Donoghue, JP
Hudson, KL
Ling, GSF
MacLeish, PR
Marder, E
Normann, RA
Sanes, JR
Schnitzer, MJ
Sejnowski, TJ
Tank, DW
Tsien, RY
Ugurbil, K
Wingfield, JC
AF Jorgenson, Lyric A.
Newsome, William T.
Anderson, David J.
Bargmann, Cornelia I.
Brown, Emery N.
Deisseroth, Karl
Donoghue, John P.
Hudson, Kathy L.
Ling, Geoffrey S. F.
MacLeish, Peter R.
Marder, Eve
Normann, Richard A.
Sanes, Joshua R.
Schnitzer, Mark J.
Sejnowski, Terrence J.
Tank, David W.
Tsien, Roger Y.
Ugurbil, Kamil
Wingfield, John C.
TI The BRAIN Initiative: developing technology to catalyse neuroscience
discovery
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Article
DE BRAIN Initiative; neural circuitry; neurotechnology
ID RETINAL CELL-TYPES; NEURAL CIRCUITS; FUNCTIONAL ARCHITECTURE; SENSORY
STIMULATION; CEREBRAL-CORTEX; VISUAL-CORTEX; RESOLUTION; NEURONS;
RECONSTRUCTION; OPTOGENETICS
AB The evolution of the field of neuroscience has been propelled by the advent of novel technological capabilities, and the pace at which these capabilities are being developed has accelerated dramatically in the past decade. Capitalizing on this momentum, the United States launched the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative to develop and apply new tools and technologies for revolutionizing our understanding of the brain. In this article, we review the scientific vision for this initiative set forth by the National Institutes of Health and discuss its implications for the future of neuroscience research. Particular emphasis is given to its potential impact on the mapping and study of neural circuits, and how this knowledge will transform our understanding of the complexity of the human brain and its diverse array of behaviours, perceptions, thoughts and emotions.
C1 [Jorgenson, Lyric A.; Hudson, Kathy L.] NIH, Off Director, Bethesda, MD 20892 USA.
[Newsome, William T.; Deisseroth, Karl; Schnitzer, Mark J.] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA.
[Newsome, William T.] Stanford Univ, Stanford Neurosdences Inst, Stanford, CA 94305 USA.
[Anderson, David J.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA.
[Anderson, David J.] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA.
[Bargmann, Cornelia I.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA.
[Bargmann, Cornelia I.] Rockefeller Univ, Lulu & Anthony Wang Lab Neural Circuits & Behav, New York, NY 10065 USA.
[Brown, Emery N.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA.
[Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
[Brown, Emery N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Deisseroth, Karl] Stanford Univ, Dept Psychiat & Behav Sci, Dept Bioengn, Stanford, CA 94305 USA.
[Donoghue, John P.] Brown Univ, Brown Inst Brain Sci, Providence, RI 02912 USA.
[Ling, Geoffrey S. F.] Def Adv Res Projects Agcy, Biol Technol Off, Arlington, VA 22203 USA.
[MacLeish, Peter R.] Morehouse Sch Med, Neurosci Inst, Dept Neurobiol, Atlanta, GA 30310 USA.
[Marder, Eve] Brandeis Univ, Dept Biol, Waltham, MA 02454 USA.
[Marder, Eve] Brandeis Univ, Volen Ctr, Waltham, MA 02454 USA.
[Normann, Richard A.] Univ Utah, Dept Bioengn, Salt Lake City, UT 84112 USA.
[Sanes, Joshua R.] Harvard Univ, Ctr Brain Sci, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
[Schnitzer, Mark J.] Stanford Univ, James H Clark Ctr Biomed Engn & Sci, CNC Program, Stanford, CA 94305 USA.
[Sejnowski, Terrence J.] Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA 92037 USA.
[Sejnowski, Terrence J.] Salk Inst Biol Studies, Computat Neurobiol Lab, La Jolla, CA 92037 USA.
[Tank, David W.] Princeton Univ, Princeton Neurosci Inst, Bezos Ctr Neural Circuit Dynam, Princeton, NJ 08544 USA.
[Tank, David W.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
[Tsien, Roger Y.] Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA.
[Tsien, Roger Y.] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA.
[Ugurbil, Kamil] Univ Minnesota, Ctr Magnet Resonance Res, Minneapolis, MN 55454 USA.
[Wingfield, John C.] Natl Sci Fdn, Directorate Biol Sci, Arlington, VA 22230 USA.
RP Jorgenson, LA (reprint author), NIH, Off Director, Bldg 10, Bethesda, MD 20892 USA.
EM bnewsome@stanford.edu
OI Bargmann, Cornelia/0000-0002-8484-0618
FU National Institutes of Health; Howard Hughes Medical Institute
FX The authors thank the National Institutes of Health and the Howard
Hughes Medical Institute for supporting the publication of this article.
NR 82
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U1 5
U2 37
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8436
EI 1471-2970
J9 PHILOS T R SOC B
JI Philos. Trans. R. Soc. B-Biol. Sci.
PD MAY 19
PY 2015
VL 370
IS 1668
BP 8
EP 19
AR UNSP 20140164
DI 10.1098/rstb.2014.0164
PG 12
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA CH5JH
UT WOS:000354071400002
ER
PT J
AU Kim, S
Rimando, J
Sandler, DP
AF Kim, Sangmi
Rimando, Joseph
Sandler, Dale P.
TI Fruit and Vegetable Intake and Urinary Levels of Prostaglandin E-2
Metabolite in Postmenopausal Women
SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
LA English
DT Article
ID C-REACTIVE PROTEIN; NUTRITION EXAMINATION SURVEY; TOTAL ANTIOXIDANT
CAPACITY; HEALTHY EATING INDEX; OXIDATIVE STRESS; CANCER RISK;
ENDOTHELIAL ACTIVATION; COLORECTAL-CANCER; DIETARY PATTERNS;
NATIONAL-HEALTH
AB Prostaglandin E-2 (PGE(2)) is an inflammatory mediator that plays key roles in promoting tumor development and progression. Urinary concentration of a major PGE(2) metabolite (PGE-M) has been recently proposed as a promising cancer biomarker. Using dietary intake data from 600 postmenopausal women aged 50-74years, we examined cross-sectional relationships between fruit and vegetable intake and urinary levels of PGE-M, determined using liquid chromatography/tandem mass spectrometry. After multivariable adjustment, increasing consumption of fruits, but not vegetables, was associated with reduced levels of urinary PGE-M (P for linear trend = 0.02), with geometric means of 5.8 [95% confidence interval (CI): 5.2-6.6] in the lowest quintile versus 4.8 (95% CI: 4.3-5.4) in the highest quintile (Q5) of fruit consumption. A better quality diet, indicated by higher scores on the Healthy Eating Index, was also associated with decreased PGE-M (P for linear trend <0.01). The lack of association with vegetable intake may be related to variation in antioxidant capacities of the major dietary sources of fruits and vegetables for the study participants. Our findings suggest that urinary PGE-M may be modifiable by a healthy diet that follows current national dietary guideline. Further studies are warranted to assess potential utility of urinary PGE-M in assessing cancer prevention efficacy.
C1 [Kim, Sangmi; Rimando, Joseph] Georgia Regents Univ, Med Coll Georgia, Ctr Canc, Dept Med,Sect Hematol Oncol, Augusta, GA 30912 USA.
[Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
RP Kim, S (reprint author), Georgia Regents Univ, Med Coll Georgia, Ctr Canc, Dept Med,Sect Hematol Oncol, 1410 Laney Walker Blvd, Augusta, GA 30912 USA.
EM sankim@gru.edu
OI Sandler, Dale/0000-0002-6776-0018
FU Department of Defense Breast Cancer Postdoctoral Fellowship [BC0923202];
NIH, National Institute of Environmental Health Sciences [Z01 ES044005]
FX This work was supported in part by Department of Defense Breast Cancer
Postdoctoral Fellowship BC0923202 and the Intramural Research Program of
the NIH, National Institute of Environmental Health Sciences (Z01
ES044005).
NR 43
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U1 1
U2 2
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 0163-5581
EI 1532-7914
J9 NUTR CANCER
JI Nutr. Cancer
PD MAY 19
PY 2015
VL 67
IS 4
BP 580
EP 586
DI 10.1080/01635581.2015.1011787
PG 7
WC Oncology; Nutrition & Dietetics
SC Oncology; Nutrition & Dietetics
GA CH1HC
UT WOS:000353771000004
PM 25811232
ER
PT J
AU Munoz-Lopez, M
Insausti, R
Mohedano-Moriano, A
Mishkin, M
Saunders, RC
AF Munoz-Lopez, M.
Insausti, R.
Mohedano-Moriano, A.
Mishkin, M.
Saunders, R. C.
TI Anatomical pathways for auditory memory II: information from rostral
superior temporal gyrus to dorsolateral temporal pole and medial
temporal cortex
SO FRONTIERS IN NEUROSCIENCE
LA English
DT Article
DE auditory; memory; superior temporal gyrus; primate; temporal pole;
medial temporal cortex
ID VISUAL RECOGNITION MEMORY; RHESUS-MONKEY; ENTORHINAL CORTEX;
PARAHIPPOCAMPAL CORTICES; PERIRHINAL CORTEX; MACAQUE MONKEY;
CONNECTIONS; REGION; ORGANIZATION; PROJECTIONS
AB Auditory recognition memory in non-human primates differs from recognition memory in other sensory systems. Monkeys learn the rule for visual and tactile delayed matching-to-sample within a few sessions, and then show one-trial recognition memory lasting 10-20 min. In contrast, monkeys require hundreds of sessions to master the rule for auditory recognition, and then show retention lasting no longer than 30-40s. Moreover, unlike the severe effects of rhinal lesions on visual memory, such lesions have no effect on the monkeys' auditory memory performance. The anatomical pathways for auditory memory may differ from those in vision. Long-term visual recognition memory requires anatomical connections from the visual association area TE with areas 35 and 36 of the perirhinal cortex (PRC). We examined whether there is a similar anatomical route for auditory processing, or that poor auditory recognition memory may reflect the lack of such a pathway. Our hypothesis is that an auditory pathway for recognition memory originates in the higher order processing areas of the rostral superior temporal gyrus (rSTG), and then connects via the dorsolateral temporal pole to access the rhinal cortex of the medial temporal lobe. To test this, we placed retrograde (3% FB and 2% DY) and anterograde (10% BDA 10,000 mW) tracer injections in rSTG and the dorsolateral area 38(DL) of the temporal pole. Results showed that area 38(DL) receives dense projections from auditory association areas Ts1, TAa, TPO of the rSTG, from the rostral parabelt and, to a lesser extent, from areas Ts2-3 and PGa. In turn, area 38(DL) projects densely to area 35 of PRC, entorhinal cortex (EC), and to areas TH/TF of the posterior parahippocampal cortex. Significantly, this projection avoids most of area 36r/c of PRC. This anatomical arrangement may contribute to our understanding of the poor auditory memory of rhesus monkeys.
C1 [Munoz-Lopez, M.; Mishkin, M.; Saunders, R. C.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
[Munoz-Lopez, M.; Insausti, R.; Mohedano-Moriano, A.] Univ Castilla La Mancha, Sch Med, Human Neuroanat Lab, Albacete 02006, Spain.
[Munoz-Lopez, M.; Insausti, R.; Mohedano-Moriano, A.] Univ Castilla La Mancha, Sch Med, Reg Ctr Biomed Res CRIB, Albacete 02006, Spain.
RP Munoz-Lopez, M (reprint author), Univ Castilla La Mancha, Sch Med, Ave Almansa 14, Albacete 02006, Spain.
EM monica.munozlopez@uclm.es
RI Mohedano-Moriano, Alicia/L-1121-2016;
OI Mohedano-Moriano, Alicia/0000-0003-4904-6774; Munoz Lopez,
Monica/0000-0002-5530-2394
FU NIMH/IRP [BFI 2003-09581]; Spanish Ministry of Science and Innovation
[BFU 2006-12964]
FX This study was supported by NIMH/IRP grant BFI 2003-09581 and the
Spanish Ministry of Science and Innovation grant BFU 2006-12964. The
Technical support of Elena Hernaez, Marta Fonollosa is greatly
appreciated.
NR 68
TC 7
Z9 7
U1 0
U2 7
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-453X
J9 FRONT NEUROSCI-SWITZ
JI Front. Neurosci.
PD MAY 18
PY 2015
VL 9
AR 158
DI 10.3389/fnins.2015.00158
PG 21
WC Neurosciences
SC Neurosciences & Neurology
GA CS3NM
UT WOS:000361981200001
PM 26041980
ER
PT J
AU Preusch, PC
AF Preusch, Peter C.
TI New grant programs offered by the National Institute of General Medical
Sciences
SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
LA English
DT Meeting Abstract
C1 [Preusch, Peter C.] Natl Inst Gen Med Sci, Div Cell Biol & Biophys, Bethesda, MD 20892 USA.
EM preuschp@nigms.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0739-1102
EI 1538-0254
J9 J BIOMOL STRUCT DYN
JI J. Biomol. Struct. Dyn.
PD MAY 18
PY 2015
VL 33
SU 1
MA 3
BP 1
EP 2
DI 10.1080/07391102.2015.1032629
PG 2
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA CL1FR
UT WOS:000356688600004
PM 26103213
ER
PT J
AU Zhou, BR
Jiang, JS
Wang, R
Feng, HQ
Ghirlando, R
Xiao, TS
Bai, YW
AF Zhou, Bing-Rui
Jiang, Jiansheng
Wang, Rui
Feng, Hanqiao
Ghirlando, Rodolfo
Xiao, T. Sam
Bai, Yawen
TI Structural mechanisms of nucleosome recognition by linker histones
SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
LA English
DT Meeting Abstract
C1 [Zhou, Bing-Rui; Wang, Rui; Feng, Hanqiao; Bai, Yawen] NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Jiang, Jiansheng; Xiao, T. Sam] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Ghirlando, Rodolfo] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM yawen@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0739-1102
EI 1538-0254
J9 J BIOMOL STRUCT DYN
JI J. Biomol. Struct. Dyn.
PD MAY 18
PY 2015
VL 33
SU 1
MA 5
BP 2
EP 3
DI 10.1080/07391102.2015.1032630
PG 2
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA CL1FR
UT WOS:000356688600006
PM 26103215
ER
PT J
AU Shaytan, AK
Armeev, GA
Goncearenco, A
Zhurkin, VB
Landsman, D
Panchenko, AR
AF Shaytan, Alexey K.
Armeev, Grigoriy A.
Goncearenco, Alexander
Zhurkin, Victor B.
Landsman, David
Panchenko, Anna R.
TI Combined influence of linker DNA and histone tails on nucleosome
dynamics as revealed by microsecond molecular dynamics simulations
SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
LA English
DT Meeting Abstract
C1 [Shaytan, Alexey K.; Goncearenco, Alexander; Landsman, David; Panchenko, Anna R.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[Armeev, Grigoriy A.] Moscow MV Lomonosov State Univ, Fac Biol, Moscow 119991, Russia.
[Zhurkin, Victor B.] NCI, Cell Biol Lab, Bethesda, MD 20892 USA.
EM alexey.shaytan@nih.gov
RI Goncearenco, Alexander/M-3946-2015; Shaytan, Alexey/D-7306-2012
OI Goncearenco, Alexander/0000-0002-9738-7146; Shaytan,
Alexey/0000-0003-0312-938X
NR 0
TC 0
Z9 1
U1 2
U2 4
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0739-1102
EI 1538-0254
J9 J BIOMOL STRUCT DYN
JI J. Biomol. Struct. Dyn.
PD MAY 18
PY 2015
VL 33
SU 1
MA 6
BP 3
EP 3
DI 10.1080/07391102.2015.1032631
PG 1
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA CL1FR
UT WOS:000356688600007
PM 26103217
ER
PT J
AU Norouzi, D
Zhurkin, VB
AF Norouzi, Davood
Zhurkin, Victor B.
TI Topological polymorphism of two-start nucleosome fibers
SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
LA English
DT Meeting Abstract
C1 [Norouzi, Davood; Zhurkin, Victor B.] NCI, Cell Biol Lab, Bethesda, MD 20892 USA.
EM davood.norouzi@nih.gov
NR 3
TC 0
Z9 0
U1 1
U2 1
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0739-1102
EI 1538-0254
J9 J BIOMOL STRUCT DYN
JI J. Biomol. Struct. Dyn.
PD MAY 18
PY 2015
VL 33
SU 1
MA 7
BP 4
EP 4
DI 10.1080/07391102.2015.1032631
PG 1
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA CL1FR
UT WOS:000356688600008
PM 26103219
ER
PT J
AU Naufer, MN
Furano, AV
Williams, MC
AF Naufer, M. Nabuan
Furano, Anthony V.
Williams, Mark C.
TI Oligomerization kinetics of ORF1p is correlated with LINE1
retrotransposition
SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
LA English
DT Meeting Abstract
C1 [Naufer, M. Nabuan; Williams, Mark C.] Northeastern Univ, Dept Phys, Boston, MA 02115 USA.
[Furano, Anthony V.] NIDDK, Lab Mol & Cellular Biol, NIH, Bethesda, MD 20892 USA.
EM ma.williams@neu.edu
NR 0
TC 0
Z9 0
U1 0
U2 2
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0739-1102
EI 1538-0254
J9 J BIOMOL STRUCT DYN
JI J. Biomol. Struct. Dyn.
PD MAY 18
PY 2015
VL 33
SU 1
MA 12
BP 7
EP 8
DI 10.1080/07391102.2015.1032553
PG 2
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA CL1FR
UT WOS:000356688600013
PM 26103223
ER
EF