FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Afonin, KA
Bindewald, E
Yaghoubian, AJ
Voss, N
Jacovetty, E
Shapiro, BA
Jaeger, L
AF Afonin, Kirill A.
Bindewald, Eckart
Yaghoubian, Alan J.
Voss, Neil
Jacovetty, Erica
Shapiro, Bruce A.
Jaeger, Luc
TI In vitro assembly of cubic RNA-based scaffolds designed in silico
SO NATURE NANOTECHNOLOGY
LA English
DT Article
ID THERMODYNAMIC PARAMETERS; STRUCTURAL-ANALYSIS; DNA NANOSTRUCTURES;
NANOSCALE SHAPES; STRANDED-DNA; FOLDING DNA; NANOTECHNOLOGY;
NANOPARTICLES; STRATEGIES; PREDICTION
AB The organization of biological materials into versatile three-dimensional assemblies could be used to build multifunctional therapeutic scaffolds for use in nanomedicine. Here, we report a strategy to design three-dimensional nanoscale scaffolds that can be self-assembled from RNA with precise control over their shape, size and composition. These cubic nanoscaffolds are only similar to 13 nm in diameter and are composed of short oligonucleotides, making them amenable to chemical synthesis, point modifications and further functionalization. Nanocube assembly is verified by gel assays, dynamic light scattering and cryogenic electron microscopy. Formation of functional RNA nanocubes is also demonstrated by incorporation of a light-up fluorescent RNA aptamer that is optimally active only upon full RNA assembly. Moreover, we show that the RNA nanoscaffolds can self-assemble in isothermal conditions (37 degrees C) during in vitro transcription, which opens a route towards the construction of sensors, programmable packaging and cargo delivery systems for biomedical applications.
C1 [Afonin, Kirill A.; Yaghoubian, Alan J.; Jaeger, Luc] Univ Calif Santa Barbara, Dept Chem & Biochem, Biomol Sci & Engn Program, Santa Barbara, CA 93106 USA.
[Bindewald, Eckart] NCI, Basic Sci Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Voss, Neil; Jacovetty, Erica] Scripps Res Inst, Automated Mol Imaging Grp, Dept Cell Biol, La Jolla, CA 92037 USA.
[Shapiro, Bruce A.] NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA.
RP Afonin, KA (reprint author), Univ Calif Santa Barbara, Dept Chem & Biochem, Biomol Sci & Engn Program, Santa Barbara, CA 93106 USA.
EM shapirbr@mail.nih.gov; jaeger@chem.ucsb.edu
RI Voss, Neil/K-6244-2012
FU National Institutes of Health (NIH) [RR17573, R01 GM079604]; Center for
Cancer Research; National Cancer Institute, NIH [HHSN261200800001E]
FX The authors thank V. A. Piunova for assistance with DLS, K. Kahn for
helping with Kd curve analysis, and C. Potter and B.
Carragher for their invaluable scientific input regarding cryo-EM and
single-particle reconstruction. Cryo-EM imaging was performed at
National Resources for Automated Molecular Microscopy, which is
supported by the National Institutes of Health (NIH) through the
National Center for Research Resources P41 program (RR17573). This
research was supported (in part) by the Intramural Research Program of
the NIH, the National Cancer Institute, the Center for Cancer Research
(B. A. S.) and by NIH R01 GM079604 (L.J.). This project has been funded
in whole or in part with federal funds from the National Cancer
Institute, NIH, 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 any mention of trade
names, commercial products or organizations imply endorsement by the US
government. K. A. and L.J. wish to dedicate this work to Sts. Cyril and
Methodius.
NR 51
TC 117
Z9 118
U1 7
U2 55
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1748-3387
J9 NAT NANOTECHNOL
JI Nat. Nanotechnol.
PD SEP
PY 2010
VL 5
IS 9
BP 676
EP 682
DI 10.1038/NNANO.2010.160
PG 7
WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary
SC Science & Technology - Other Topics; Materials Science
GA 647FO
UT WOS:000281603400015
PM 20802494
ER
PT J
AU Chang, MC
Park, JM
Pelkey, KA
Grabenstatter, HL
Xu, DS
Linden, DJ
Sutula, TP
McBain, CJ
Worley, PF
AF Chang, Michael C.
Park, Joo Min
Pelkey, Kenneth A.
Grabenstatter, Heidi L.
Xu, Desheng
Linden, David J.
Sutula, Thomas P.
McBain, Chris J.
Worley, Paul F.
TI Narp regulates homeostatic scaling of excitatory synapses on
parvalbumin-expressing interneurons
SO NATURE NEUROSCIENCE
LA English
DT Article
ID FAST-SPIKING CELLS; AMPA RECEPTORS; SYNAPTIC PLASTICITY; MESSENGER-RNAS;
RAT-BRAIN; NEURONS; PENTRAXIN; INHIBITION; SUBUNIT; SYSTEM
AB Homeostatic synaptic scaling alters the strength of synapses to compensate for prolonged changes in network activity and involves both excitatory and inhibitory neurons. The immediate-early gene Narp (neuronal activity-regulated pentraxin) encodes a secreted synaptic protein that can bind to and induce clustering of AMPA receptors (AMPARs). We found that Narp prominently accumulated at excitatory synapses on parvalbumin-expressing interneurons (PV-INs). Increasing network activity resulted in a homeostatic increase of excitatory synaptic strength onto PV-INs that increased inhibitory drive and this response was absent in neurons cultured from Narp(-/-) mice. Activity-dependent changes in the strength of excitatory inputs on PV-INs in acute hippocampal slices were also dependent on Narp and Narp(-/-) mice had increased sensitivity to kindling-induced seizures. We propose that Narp recruits AMPARs at excitatory synapses onto PV-INs to rebalance network excitation/inhibition dynamics following episodes of increased circuit activity.
C1 [Chang, Michael C.; Park, Joo Min; Xu, Desheng; Linden, David J.; Worley, Paul F.] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21218 USA.
[Pelkey, Kenneth A.; McBain, Chris J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD USA.
[Grabenstatter, Heidi L.; Sutula, Thomas P.] Univ Wisconsin, Dept Neurol, Madison, WI 53706 USA.
[Worley, Paul F.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
RP Worley, PF (reprint author), Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21218 USA.
EM pworley@jhmi.edu
FU US National Institutes of Health [PAR-02-059, NS 39156]
FX We thank M.S. Perin for the Narp-/- mouse, R.L. Huganir
(Johns Hopkins University) for antibodies to GluR1, M. Dehoff and P.
Chuang for animal care, M. Papapavlou for administrative assistance and
X. Yuan and B. Jeffries for technical assistance. Work in the laboratory
of C.J.M. is supported by a US National Institutes of Health intramural
award. Work in the laboratory of P.F.W. is supported by US National
Institutes of Health grants PAR-02-059 and NS 39156.
NR 46
TC 83
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U1 1
U2 12
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD SEP
PY 2010
VL 13
IS 9
BP 1090
EP U83
DI 10.1038/nn.2621
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 643XC
UT WOS:000281332600014
PM 20729843
ER
PT J
AU Smith, JF
Pillai, A
Chen, KW
Horwitz, B
AF Smith, Jason F.
Pillai, Ajay
Chen, Kewei
Horwitz, Barry
TI Identification and validation of effective connectivity networks in
functional magnetic resonance imaging using switching linear dynamic
systems
SO NEUROIMAGE
LA English
DT Article
DE Dynamic systems; fMRI; Effective connectivity; Motor systems;
Computational modeling
ID FISHER INFORMATION MATRIX; BOLD HEMODYNAMIC-RESPONSES; STATE-SPACE
MODELS; LARGE-SCALE MODEL; GRANGER CAUSALITY; MOTOR CORTEX; TIME-SERIES;
NEURONAL DYNAMICS; FMRI; ACTIVATION
AB Dynamic connectivity networks identify directed interregional interactions between modeled brain regions in neuroimaging. However, problems arise when the regions involved in a task and their interconnections are not fully known a priori. Objective measures of model adequacy are necessary to validate such models. We present a connectivity formalism, the Switching Linear Dynamic System (SLDS), that is capable of identifying both Granger-Geweke and instantaneous connectivity that vary according to experimental conditions. SLDS explicitly models the task condition as a Markov random variable. The series of task conditions can be estimated from new data given an identified model providing a means to validate connectivity patterns. We use SLDS to model functional magnetic resonance imaging data from five regions during a finger alternation task. Using interregional connectivity alone, the identified model predicted the task condition vector from a different subject with a different task ordering with high accuracy. In addition, important regions excluded from a model can be identified by augmenting the model state space. A motor task model excluding primary motor cortices was augmented with a new neural state constrained by its connectivity with the included regions. The augmented variable time series, convolved with a hemodynamic kernel, was compared to all brain voxels. The right primary motor cortex was identified as the best region to add to the model. Our results suggest that the SLDS model framework is an effective means to address several problems with modeling connectivity including measuring overall model adequacy and identifying important regions missing from models. Published by Elsevier Inc.
C1 [Smith, Jason F.; Pillai, Ajay; Horwitz, Barry] Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, NIH, Bethesda, MD USA.
[Chen, Kewei] Arizona State Univ, Dept Math & Stat, Tempe, AZ USA.
[Chen, Kewei] Banner Good Samaritan Med Ctr, Positron Emiss Tomog Ctr, Phoenix, AZ USA.
[Chen, Kewei] Banner Good Samaritan Med Ctr, Banner Alzheimers Dis Inst, Phoenix, AZ USA.
[Chen, Kewei] Arizona Alzheimers Dis Consortium, Phoenix, AZ USA.
RP Smith, JF (reprint author), Rm 8S2358,10 Ctr Dr, Bethesda, MD 20892 USA.
EM smithjas@nidcd.nih.gov
RI Chen, kewei/P-6304-2015
OI Chen, kewei/0000-0001-8497-3069
FU National Institute on Deafness and Other Communication Disorders;
National Institutes of Health; National Institute on Aging [AG19610
AG025526]; Evelyn F. McKnight Brain Institute; State of Arizona
FX This work was supported by the intramural program of the National
Institute on Deafness and Other Communication Disorders, the National
Institutes of Health, and a National Institutes of Health Intramural
Research Training Award to JFS. The authors would also like to
acknowledge support from the National Institute on Aging (AG19610
AG025526 [GEA]), the Evelyn F. McKnight Brain Institute [GEA], and the
State of Arizona [GEA, KC].
NR 80
TC 21
Z9 21
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 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD SEP
PY 2010
VL 52
IS 3
BP 1027
EP 1040
DI 10.1016/j.neuroimage.2009.11.081
PG 14
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 629FY
UT WOS:000280181800025
PM 19969092
ER
PT J
AU Mattson, MP
AF Mattson, Mark P.
TI Acetylation Unleashes Protein Demons of Dementia
SO NEURON
LA English
DT Editorial Material
ID ALZHEIMER-DISEASE; ENERGY-INTAKE; MOUSE MODEL; PLASTICITY; SIRT1; AGE;
TAU; RESTRICTION
AB Aberrant posttranslational modifications of proteins can impair synaptic plasticity and may render neurons vulnerable to degeneration during aging. In this issue of Neuron, Min et al. show that acetylation of the amino acid lysine in the microtubule-associated protein tau prevents its ubiquitin-mediated degradation, resulting in "tau tangles" similar to those of dementias. Other recent studies suggest that lysine hyperacetylation contributes to the accumulation of amyloid beta-peptide in Alzheimer's disease and to impaired cognitive function resulting from a trophic factor deficit.
C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
EM mattsonm@grc.nia.nih.gov
RI Mattson, Mark/F-6038-2012
NR 16
TC 2
Z9 2
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD SEP
PY 2010
VL 67
IS 6
BP 900
EP 902
DI 10.1016/j.neuron.2010.09.010
PG 3
WC Neurosciences
SC Neurosciences & Neurology
GA 662IN
UT WOS:000282801100002
PM 20869587
ER
PT J
AU Nedelsky, NB
Pennuto, M
Smith, RB
Palazzolo, I
Moore, J
Nie, ZP
Neale, G
Taylor, JP
AF Nedelsky, Natalia B.
Pennuto, Maria
Smith, Rebecca B.
Palazzolo, Isabella
Moore, Jennifer
Nie, Zhiping
Neale, Geoffrey
Taylor, J. Paul
TI Native Functions of the Androgen Receptor Are Essential to Pathogenesis
in a Drosophila Model of Spinobulbar Muscular Atrophy
SO NEURON
LA English
DT Article
ID HISTONE ACETYLTRANSFERASE ACTIVITY; POLYGLUTAMINE-INDUCED DISEASE;
MOTOR-NEURON DEGENERATION; TRANSGENIC MOUSE MODEL; PROSTATE-CANCER
CELLS; FAST AXONAL-TRANSPORT; ACTIVATION FUNCTION 2; TUMOR-SUPPRESSOR;
MEDIATED TRANSACTIVATION; NH2-TERMINAL DOMAIN
AB Spinobulbar muscular atrophy (SBMA) is a neurodegenerative disease caused by expansion of a polyglutamine tract in the androgen receptor (AR). This mutation confers toxic function to AR through unknown mechanisms. Mutant AR toxicity requires binding of its hormone ligand, suggesting that pathogenesis involves ligand-induced changes in AR. However, whether toxicity is mediated by native AR function or a novel AR function is unknown. We systematically investigated events downstream of ligand-dependent AR activation in a Drosophila model of SBMA. We show that nuclear translocation of AR is necessary, but not sufficient, for toxicity and that DNA binding by AR is necessary for toxicity. Mutagenesis studies demonstrated that a functional AF-2 domain is essential for toxicity, a finding corroborated by a genetic screen that identified AF-2 interactors as dominant modifiers of degeneration. These findings indicate that SBMA pathogenesis is mediated by misappropriation of native protein function, a mechanism that may apply broadly to polyglutamine diseases.
C1 [Nedelsky, Natalia B.; Smith, Rebecca B.; Moore, Jennifer; Taylor, J. Paul] St Jude Childrens Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA.
[Neale, Geoffrey] St Jude Childrens Hosp, Hartwell Ctr Bioinformat & Biotechnol, Memphis, TN 38105 USA.
[Nedelsky, Natalia B.] Univ Penn, Sch Med, Neurosci Grad Grp, Philadelphia, PA 19104 USA.
[Nie, Zhiping] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA.
[Pennuto, Maria] Italian Inst Technol, Dept Neurosci, I-16163 Genoa, Italy.
[Palazzolo, Isabella] Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
RP Taylor, JP (reprint author), St Jude Childrens Hosp, Dept Dev Neurobiol, 332 N Lauderdale St, Memphis, TN 38105 USA.
EM jpaul.taylor@stjude.org
OI Pennuto, Maria/0000-0001-8634-0767
FU Muscular Dystrophy Association; Kennedy's Disease Association; NIH
[NS053825]; ALSAC (American Lebanese Syrian Associated Charities)
FX We thank Eric Baehrecke, Christina McPhee, Yakup Batlevi, and Kevin Cook
for technical advice and reagents. Drosophila anti-lamin antibody
(mAb-ADL 84) was a gift from Paul Fisher (SUNY Stonybrook). FLAG-FHL2
DNA was a gift from Christopher Mack (University of North Carolina).
NLS-AR24Q was a gift from Bryce Paschal (University of Virginia). We
thank Andrew Lieberman for KK/AA DNA. We also thank Rita Balice-Gordon,
Thomas Jongens, Robert Kalb, and Taylor lab members for helpful
comments. Financial support was provided by the Muscular Dystrophy
Association, the Kennedy's Disease Association, NIH grant NS053825, and
ALSAC (American Lebanese Syrian Associated Charities).
NR 74
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U1 0
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD SEP
PY 2010
VL 67
IS 6
BP 936
EP 952
DI 10.1016/j.neuron.2010.08.034
PG 17
WC Neurosciences
SC Neurosciences & Neurology
GA 662IN
UT WOS:000282801100007
PM 20869592
ER
PT J
AU Sanz-Clemente, A
Matta, JA
Isaac, JTR
Roche, KW
AF Sanz-Clemente, Antonio
Matta, Jose A.
Isaac, John T. R.
Roche, Katherine W.
TI Casein Kinase 2 Regulates the NR2 Subunit Composition of Synaptic NMDA
Receptors
SO NEURON
LA English
DT Article
ID D-ASPARTATE RECEPTORS; DEPENDENT PROTEIN-KINASE; SURFACE EXPRESSION;
RAT-BRAIN; HIPPOCAMPAL SYNAPSES; VISUAL-CORTEX; CROSS-TALK;
PHOSPHORYLATION; CK2; TRAFFICKING
AB N-methyl-D-aspartate (NMDA) receptors (NMDARs) play a central role in development, synaptic plasticity, and neurological disease. NMDAR subunit composition defines their biophysical properties and downstream signaling. Casein kinase 2 (CK2) phosphorylates the NR2B subunit within its PDZ-binding domain; however, the consequences for NMDAR localization and function are unclear. Here we show that CK2 phosphorylation of NR2B regulates synaptic NR2B and NR2A in response to activity. We find that CK2 phosphorylates NR2B, but not NR2A, to drive NR2B-endocytosis and remove NR2B from synapses resulting in an increase in synaptic NR2A expression. During development there is an activity-dependent switch from NR2B to NR2A at cortical synapses. We observe an increase in CK2 expression and NR2B phosphorylation over this same critical period and show that the acute activity-dependent switch in NR2 subunit composition at developing hippocampal synapses requires CK2 activity. Thus, CK2 plays a central role in determining the NR2 subunit content of synaptic NMDARs.
C1 [Sanz-Clemente, Antonio; Roche, Katherine W.] Natl Inst Neurol Disorders & Stroke, Receptor Biol Sect, NIH, Bethesda, MD 20892 USA.
[Matta, Jose A.; Isaac, John T. R.] Natl Inst Neurol Disorders & Stroke, Synapt Plast Sect, NIH, Bethesda, MD 20892 USA.
RP Roche, KW (reprint author), Natl Inst Neurol Disorders & Stroke, Receptor Biol Sect, NIH, Bethesda, MD 20892 USA.
EM rochek@ninds.nih.gov
OI Roche, Katherine/0000-0001-7282-6539
FU NINDS; NIGMS
FX We thank John D. Badger II for technical assistance. We also thank the
NINDS sequencing facility and light imaging facility for expertise and
advice. This research was supported by the NINDS Intramural Research
Program (A.S-C.; K.W.R.; J.T.R.I) and the Pharmacology Research
Associate (PRAT) Program, NIGMS (J.A.M).
NR 68
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U1 1
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD SEP
PY 2010
VL 67
IS 6
BP 984
EP 996
DI 10.1016/j.neuron.2010.08.011
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 662IN
UT WOS:000282801100010
PM 20869595
ER
PT J
AU Longenecker, J
Kohn, P
Liu, S
Zoltick, B
Weinberger, DR
Elvevag, B
AF Longenecker, Julia
Kohn, Philip
Liu, Stanley
Zoltick, Brad
Weinberger, Daniel R.
Elvevag, Brita
TI Data-Driven Methodology Illustrating Mechanisms Underlying Word List
Recall: Applications to Clinical Research
SO NEUROPSYCHOLOGY
LA English
DT Article
DE schizophrenia; verbal memory; semantic; retrieval strategy; CVLT
ID VERBAL MEMORY; EPISODIC MEMORY; SERIAL-RECALL; TERM-MEMORY;
SCHIZOPHRENIA; DEFICITS; ORGANIZATION; IMPAIRMENTS; STRATEGY; TASKS
AB Objective: Word list learning tasks such as the California Verbal Learning Test (CVLT; Delis, Kramer, Kaplan, & Ober, 1987) are widely used to investigate recall strategies. Participants who recall the most words generally employ semantic techniques, whereas those with poor recall (e.g., patients with schizophrenia) rely on serial techniques. However, these conclusions are based on formulas that assume that categories reflect semantic associations, bind strategy to overall performance, and neglect strategy changes over 5 trials. Therefore, we derived novel measures independent of recall performance-to compute strategies across trials and identify whether diagnosis predicts recall strategy. Method: Participants were included on the basis of performance on the CVLT (i.e., total words recalled over 5 trials). The 50 highest and 50 lowest performers among healthy volunteers (n = 100) and patients with schizophrenia (n = 100) were selected. Novel measures of recall and transition probability were calculated and analyzed by permutation tests. Results: Recall patterns and strategies of patients resembled those of controls with similar performance levels: Regardless of diagnosis, low performers were more likely to recall the first 2 and last 4 items from the list; high performers increased engagement of semantically based transitions across the 5 trials, whereas low performers did not. Conclusions: Cognitive strategy must be considered independent of overall performance before attributing poor performance to degraded learning processes. Our results demonstrate the importance of departing from global scoring techniques, especially when working with clinical populations such as patients with schizophrenia for whom episodic memory deficits are a hallmark feature.
C1 [Longenecker, Julia; Kohn, Philip; Liu, Stanley; Zoltick, Brad; Weinberger, Daniel R.; Elvevag, Brita] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
RP Elvevag, B (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Room 3C104,Bldg 10CRC,MSC 1379, Bethesda, MD 20892 USA.
EM brita@elvevaag.net
FU National Institute of Mental Health
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health.
NR 44
TC 6
Z9 6
U1 4
U2 4
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0894-4105
J9 NEUROPSYCHOLOGY
JI Neuropsychology
PD SEP
PY 2010
VL 24
IS 5
BP 625
EP 636
DI 10.1037/a0019368
PG 12
WC Psychology, Clinical; Neurosciences; Psychology
SC Psychology; Neurosciences & Neurology
GA 643YV
UT WOS:000281338200009
PM 20804251
ER
PT J
AU Harms, MB
Martin, A
Wallace, GL
AF Harms, Madeline B.
Martin, Alex
Wallace, Gregory L.
TI Facial Emotion Recognition in Autism Spectrum Disorders: A Review of
Behavioral and Neuroimaging Studies
SO NEUROPSYCHOLOGY REVIEW
LA English
DT Review
DE Autism; Face perception; Emotion; Neuroimaging; Eye-tracking;
Electrophysiology
ID HIGH-FUNCTIONING AUTISM; PERVASIVE DEVELOPMENTAL DISORDERS; FUSIFORM
FACE AREA; ASPERGER-SYNDROME; EXPRESSION RECOGNITION; UNDERSTANDING
EMOTIONS; IMPAIRED RECOGNITION; ABNORMAL ACTIVATION; NEURAL CIRCUITRY;
COMPLEX EMOTIONS
AB Behavioral studies of facial emotion recognition (FER) in autism spectrum disorders (ASD) have yielded mixed results. Here we address demographic and experiment-related factors that may account for these inconsistent findings. We also discuss the possibility that compensatory mechanisms might enable some individuals with ASD to perform well on certain types of FER tasks in spite of atypical processing of the stimuli, and difficulties with real-life emotion recognition. Evidence for such mechanisms comes in part from eye-tracking, electrophysiological, and brain imaging studies, which often show abnormal eye gaze patterns, delayed event-related-potential components in response to face stimuli, and anomalous activity in emotion-processing circuitry in ASD, in spite of intact behavioral performance during FER tasks. We suggest that future studies of FER in ASD: 1) incorporate longitudinal (or cross-sectional) designs to examine the developmental trajectory of (or age-related changes in) FER in ASD and 2) employ behavioral and brain imaging paradigms that can identify and characterize compensatory mechanisms or atypical processing styles in these individuals.
C1 [Harms, Madeline B.; Martin, Alex; Wallace, Gregory L.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA.
RP Wallace, GL (reprint author), NIMH, Lab Brain & Cognit, 10 Ctr Dr,Room 4C104,MSC 1366, Bethesda, MD 20892 USA.
EM gregwallace@mail.nih.gov
RI martin, alex/B-6176-2009;
OI Wallace, Gregory/0000-0003-0329-5054
FU NIH, National Institute of Mental Health
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Mental Health.
NR 121
TC 235
Z9 241
U1 31
U2 181
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1040-7308
EI 1573-6660
J9 NEUROPSYCHOL REV
JI Neuropsychol. Rev.
PD SEP
PY 2010
VL 20
IS 3
BP 290
EP 322
DI 10.1007/s11065-010-9138-6
PG 33
WC Psychology, Clinical; Neurosciences
SC Psychology; Neurosciences & Neurology
GA 649SA
UT WOS:000281792300007
PM 20809200
ER
PT J
AU Rasetti, R
Mattay, VS
Stankevich, B
Skjei, K
Blasi, G
Sambataro, F
Arrillaga-Romany, IC
Goldberg, TE
Callicott, JH
Apud, JA
Weinberger, DR
AF Rasetti, Roberta
Mattay, Venkata S.
Stankevich, Beth
Skjei, Kelsey
Blasi, Giuseppe
Sambataro, Fabio
Arrillaga-Romany, Isabel C.
Goldberg, Terry E.
Callicott, Joseph H.
Apud, Jose A.
Weinberger, Daniel R.
TI Modulatory Effects of Modafinil on Neural Circuits Regulating Emotion
and Cognition
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE modafinil; fMRI; emotion; amygdala; cognitive processing; healthy
volunteers
ID DOPAMINE-RECEPTOR AGONIST; WAKE-PROMOTING AGENTS; COMPONENT PROCESSES;
PARKINSONS-DISEASE; DAYTIME SLEEPINESS; HEALTHY-VOLUNTEERS; PREFRONTAL
CORTEX; CORTICAL FUNCTION; CROSSOVER TRIAL; WORKING-MEMORY
AB Modafinil differs from other arousal-enhancing agents in chemical structure, neurochemical profile, and behavioral effects. Most functional neuroimaging studies to date examined the effect of modafinil only on information processing underlying executive cognition, but cognitive enhancers in general have been shown to have pronounced effects on emotional behavior, too. We examined the effect of modafinil on neural circuits underlying affective processing and cognitive functions. Healthy volunteers were enrolled in this double-blinded placebo-controlled trial (100 mg/day for 7 days). They underwent BOLD fMRI while performing an emotion information-processing task that activates the amygdala and two prefrontally dependent cognitive tasks-a working memory (WM) task and a variable attentional control (VAC) task. A clinical assessment that included measurement of blood pressure, heart rate, the Hamilton anxiety scale, and the profile of mood state (POMS) questionnaire was also performed on each test day. BOLD fMRI revealed significantly decreased amygdala reactivity to fearful stimuli on modafinil compared with the placebo condition. During executive cognition tasks, a WM task and a VAC task, modafinil reduced BOLD signal in the prefrontal cortex and anterior cingulate. Although not statistically significant, there were trends for reduced anxiety, for decreased fatigue-inertia and increased vigor-activity, as well as decreased anger-hostility on modafinil. Modafinil in low doses has a unique physiologic profile compared with stimulant drugs: it enhances the efficiency of prefrontal cortical cognitive information processing, while dampening reactivity to threatening stimuli in the amygdala, a brain region implicated in anxiety. Neuropsychopharmacology (2010) 35, 2101-2109; doi:10.1038/npp.2010.83; published online 16 June 2010
C1 [Rasetti, Roberta; Mattay, Venkata S.; Stankevich, Beth; Skjei, Kelsey; Blasi, Giuseppe; Sambataro, Fabio; Arrillaga-Romany, Isabel C.; Goldberg, Terry E.; Callicott, Joseph H.; Apud, Jose A.; Weinberger, Daniel R.] NIMH, Genes Cognit & Psychosis Program, IRP, NIH,Clin Brain Disorders Branch, Bethesda, MD 20892 USA.
RP Weinberger, DR (reprint author), NIMH, Genes Cognit & Psychosis Program, IRP, NIH,Clin Brain Disorders Branch, Rm 4S-235,10 Ctr Dr, Bethesda, MD 20892 USA.
EM daniel.weinberger@mail.nih.gov
RI Sambataro, Fabio/E-3426-2010;
OI Sambataro, Fabio/0000-0003-2102-416X; Callicott,
Joseph/0000-0003-1298-3334
FU National Institute of Mental Health; National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health. We
thank Saumitra Das, MA, Guilna Alce, BS, Ajay Premkumar, Alan Lazerow,
BA, and Natkai Akbar, BS, for their invaluable research assistance. We
thank Steven H Gorman, BS, and Alexander Kogan, BS, Cephalon, Inc., for
information related to measurement of plasma modafinil levels, and
Cephalon, Inc., for the measurement of plasma modafinil levels.
NR 51
TC 33
Z9 34
U1 3
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD SEP
PY 2010
VL 35
IS 10
BP 2101
EP 2109
DI 10.1038/npp.2010.83
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 639UU
UT WOS:000281001000009
PM 20555311
ER
PT J
AU Wong, J
Hyde, TM
Cassano, HL
Deep-Soboslay, A
Kleinman, JE
Weickert, CS
AF Wong, J.
Hyde, T. M.
Cassano, H. L.
Deep-Soboslay, A.
Kleinman, J. E.
Weickert, C. Shannon
TI PROMOTER SPECIFIC ALTERATIONS OF BRAIN-DERIVED NEUROTROPHIC FACTOR mRNA
IN SCHIZOPHRENIA
SO NEUROSCIENCE
LA English
DT Article
DE brain-derived neurotrophic factor; postmortem; DLPFC; antidepressant;
schizophrenic; interneurons
ID ANTIDEPRESSANT DRUG TREATMENTS; PREFRONTAL CORTEX; GENE-EXPRESSION; RAT
HIPPOCAMPUS; BDNF-GENE; DIFFERENTIAL REGULATION; ATYPICAL
ANTIPSYCHOTICS; NEURONAL-ACTIVITY; TRANSGENIC MICE; VISUAL-CORTEX
AB The brain-derived neurotrophic factor (BDNF) gene contains multiple 5' promoters which generate alternate transcripts. Previously, we found that pan-BDNF mRNA and protein are reduced in the dorsolateral prefrontal cortex (DLPFC) from patients with schizophrenia. In this study, we determined which of the four most abundant and best characterized BDNF alternate transcripts, I-IX, II-IX, IV-IX, and VI-IX are altered in schizophrenia. Using a cohort from the NIMH, USA, we found that BDNF II-IX mRNA was significantly reduced in the DLPFC of patients with schizophrenia, and we replicated this finding using a second cohort from Sydney, Australia. Moreover, we show that BDNF protein expression [including prepro (similar to 32 kDa), pro (similar to 28 kDa) and mature (similar to 14 kDa) BDNF] is reduced in the DLPFC of patients with schizophrenia. We next determined the regional specificity of the BDNF mRNA reduction by measuring BDNF transcripts in the parietal cortex and hippocampus and found no significant changes. The effect of antipsychotics on BDNF alternate transcript expression was also examined and we found no relationship between BDNF mRNA expression and antipsychotic use. As schizophrenic patients are often prescribed antidepressants which can up-regulate expression of BDNF, we investigated the relationship between antidepressant treatment and BDNF transcript expression. All four BDNF transcripts were significantly up-regulated in schizophrenic patients treated with antidepressants. Moreover, we found significant reductions in BDNF transcripts II-IX and IV-IX in the parietal cortex and VI-IX in the hippocampus of patients with schizophrenia who did not have a history of treatment with antidepressants. This suggests that down-regulation of at least one out of four major BDNF transcripts occurs in various brain regions of patients with schizophrenia, particularly in the DLPFC which appears to have the most robust BDNF deficit in schizophrenia. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
C1 [Wong, J.; Weickert, C. Shannon] Schizophrenia Res Inst, Sydney, NSW, Australia.
[Wong, J.; Weickert, C. Shannon] Schizophrenia Res Lab, Randwick, NSW 2031, Australia.
[Wong, J.] Univ New S Wales, Fac Med, Sch Med Sci, Sydney, NSW 2052, Australia.
[Hyde, T. M.; Cassano, H. L.; Deep-Soboslay, A.; Kleinman, J. E.; Weickert, C. Shannon] NIMH, Sect Neuropathol,Clin Brain Disorders Branch, Genes Cognit & Pychosis Program, Intramural Res Program,Natl Inst Hlth, Bethesda, MD 20892 USA.
[Weickert, C. Shannon] Univ New S Wales, Fac Med, Sch Psychiat, Sydney, NSW 2052, Australia.
RP Weickert, CS (reprint author), Univ New S Wales, Macquarie Bank Fdn Chair Schizophrenia Res, Dept Psychiat, Prince Wales Med Res Inst, Barker St, Sydney, NSW 2031, Australia.
EM c.weickert@powmri.edu.au
RI Shannon Weickert, Cynthia/G-3171-2011
FU NIMH IRP; Schizophrenia Research Institute; New South Wales Health;
Macquarie Group Foundation; Neuroscience Research Australia; University
of New South Wales; National Health and Medical Research Council
[568884]
FX We thank Debora Rothmond, Shan Yuan-Tsai, Duncan Sinclair, Alice
Rothwell and Heng Giap Woon for advice and technical support; Dr Barbara
Lipska and Dr Mary Herman for their contribution. This work was
supported by the NIMH IRP, Schizophrenia Research Institute, utilizing
infrastructure funding from New South Wales Health and the Macquarie
Group Foundation, Neuroscience Research Australia (formerly the Prince
of Wales Medical Research Institute), and the University of New South
Wales. JW is supported by the National Health and Medical Research
Council Postdoctoral Training Fellowship (568884).
NR 96
TC 55
Z9 56
U1 3
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
J9 NEUROSCIENCE
JI Neuroscience
PD SEP 1
PY 2010
VL 169
IS 3
BP 1071
EP 1084
DI 10.1016/j.neuroscience.2010.05.037
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 641FC
UT WOS:000281109200012
PM 20553817
ER
PT J
AU Bagley, JA
Belluscio, L
AF Bagley, J. A.
Belluscio, L.
TI DYNAMIC IMAGING REVEALS THAT BRAIN-DERIVED NEUROTROPHIC FACTOR CAN
INDEPENDENTLY REGULATE MOTILITY AND DIRECTION OF NEUROBLASTS WITHIN THE
ROSTRAL MIGRATORY STREAM
SO NEUROSCIENCE
LA English
DT Article
DE RMS; BDNF; SVZ; imaging; neuroblast; motility
ID POSTNATAL SUBVENTRICULAR ZONE; ADULT OLFACTORY-BULB; NEURONAL MIGRATION;
CELL-MIGRATION; CORTICAL INTERNEURONS; PROGENITOR CELLS; PRECURSOR
CELLS; NERVOUS-SYSTEM; DEVELOPING RAT; STEM-CELLS
AB Neuronal precursors generated in the subventricular zone (SVZ) migrate through the rostral migratory stream (RMS) to the olfactory bulb (OB). Although, the mechanisms regulating this migration remain largely unknown. Studies have shown that molecular factors, such as brain-derived neurotrophic factor (BDNF) emanating from the OB, may function as chemoattractants drawing neuroblasts toward their target. To better understand the role of BDNF in RMS migration, we used an acute slice preparation from early postnatal mice to track the tangential migration of GAD65-GFP labeled RMS neuroblasts with confocal time-lapse imaging. By quantifying the cell dynamics using specific directional and motility criteria, our results showed that removal of the OB did not alter the overall directional trajectory of neuroblasts, but did reduce their motility. This suggested that additional guidance factors present locally within the RMS region also contribute to this migration. Here we report that BDNF and its high affinity receptor, tyrosine kinase receptor type 2 (TrkB), are indeed heterogeneously expressed within the RMS at postnatal day 7. By altering BDNF levels within the entire pathway, we showed that reduced BDNF signaling changes both neuroblast motility and direction, while increased BDNF levels changes only motility. Together these data reveal that during this early postnatal period BDNF plays a complex role in regulating both the motility and direction of RMS flow, and that BDNF comes from sources within the RMS itself, as well as from the olfactory bulb. Published by Elsevier Ltd on behalf of IBRO.
C1 [Bagley, J. A.; Belluscio, L.] NINDS, Dev Neural Plast Unit, NIH, Bethesda, MD 20892 USA.
RP Belluscio, L (reprint author), NINDS, Dev Neural Plast Unit, NIH, Bethesda, MD 20892 USA.
EM belluscl@ninds.nih.gov
FU National Institutes of Health, National Institute of Neurological
Disorders and Stroke
FX The authors wish to thank Stefano Vicini for the Gad65-GFP mice and Kai
Cheng for help with in-situ hybridizations. We would also like to thank
Beth Belluscio, Ron McKay and the members of the Belluscio lab for
helpful discussions and critical review of the manuscript. This research
was supported by the Intramural Research Program of the National
Institutes of Health, National Institute of Neurological Disorders and
Stroke.
NR 48
TC 17
Z9 18
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
J9 NEUROSCIENCE
JI Neuroscience
PD SEP 1
PY 2010
VL 169
IS 3
BP 1449
EP 1461
DI 10.1016/j.neuroscience.2010.05.075
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 641FC
UT WOS:000281109200046
PM 20538046
ER
PT J
AU Votinov, M
Mima, T
Aso, T
Abe, M
Sawamoto, N
Shinozaki, J
Fukuyama, H
AF Votinov, Mikhail
Mima, Tatsuya
Aso, Toshihiko
Abe, Mitsunari
Sawamoto, Nobukatsu
Shinozaki, Jun
Fukuyama, Hidenao
TI The neural correlates of endowment effect without economic transaction
SO NEUROSCIENCE RESEARCH
LA English
DT Article
DE Loss aversion; Endowment effect; Reward; Decision-making; fMRI; VBM;
IFG; Insula
ID MEDIAL PREFRONTAL CORTEX; HUMAN ORBITOFRONTAL CORTEX; DECISION-MAKING;
HUMAN BRAIN; CORTICAL THICKNESS; RHESUS-MONKEY; FUNCTIONAL NEUROANATOMY;
MACAQUE MONKEYS; FRONTAL-CORTEX; BASAL GANGLIA
AB People always concern about what they have and what they might lose even it is just imaginary property. According to Prospect Theory, the losses might be weighted by subjects higher than gain, which would cause the disparity between the willingness to accept (WTA) and willingness to pay (WTP) compensation in economic valuation. Using functional MRI, we investigated neural correlates of this inconsistent value estimation, known as the endowment effect, during a simple pricing task without economic transaction Brain activation associated with this price discrepancy was observed in the right inferior frontal gyrus (IFG). where voxel-based morphometry of MRI revealed the positive correlation between gray matter concentration and WTA/WTP ratio These findings suggest the functional relevance of IFG in WTA/WTP discrepancy for pricing without any actual gain and loss, where an integration of loss aversion-related signals from insula and expected value signals may occur. (C) 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society All rights reserved.
C1 [Votinov, Mikhail; Mima, Tatsuya; Aso, Toshihiko; Sawamoto, Nobukatsu; Fukuyama, Hidenao] Kyoto Univ, Grad Sch Med, Human Brain Res Ctr, Sakyo Ku, Kyoto 6068507, Japan.
[Abe, Mitsunari] NIH, Human Cort Physiol & Stroke Neurorehabil Sect, Bethesda, MD 20892 USA.
[Shinozaki, Jun] Sapporo Med Univ, Sch Med, Dept Syst Neurosci, Sapporo, Hokkaido, Japan.
RP Fukuyama, H (reprint author), Kyoto Univ, Grad Sch Med, Human Brain Res Ctr, Sakyo Ku, Shogoin Kawahara Cho 54, Kyoto 6068507, Japan.
RI Abe, Mitsunari/F-1373-2014;
OI Abe, Mitsunari/0000-0002-3913-2292; Votinov,
Mikhail/0000-0003-3722-4406; Votinov, Mikhail/0000-0001-6970-6093; Mima,
Tatsuya/0000-0001-7787-4855
FU MEXT of Japan [20019023]; Japan Society for the Promotion of Science
[21613003]
FX This study is partly supported by the Grants-in-Aid for Scientific
Research on Priority Areas (Integrative Brain Research) for T.M.
(20019023) and Strategic Research Program for Brain Sciences (SRPBS) for
TM from the MEXT of Japan, and Grant-in-Aid for Scientific Research (C)
21613003 for T.M. from Japan Society for the Promotion of Science.
NR 82
TC 7
Z9 8
U1 4
U2 9
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0168-0102
J9 NEUROSCI RES
JI Neurosci. Res.
PD SEP
PY 2010
VL 68
IS 1
BP 59
EP 65
DI 10.1016/j.neures.2010.05.006
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 643YW
UT WOS:000281338300008
PM 20538022
ER
PT J
AU Schatlo, B
Dreier, JP
Glasker, S
Fathi, AR
Moncrief, T
Oldfield, EH
Vortmeyer, AO
Pluta, RM
AF Schatlo, Bawarjan
Dreier, Jens P.
Glaesker, Sven
Fathi, Ali-Reza
Moncrief, Travis
Oldfield, Edward H.
Vortmeyer, Alexander O.
Pluta, Ryszard M.
TI Report of Selective Cortical Infarcts in the Primate Clot Model of
Vasospasm After Subarachnoid Hemorrhage
SO NEUROSURGERY
LA English
DT Article
DE Cortical laminar necrosis; Cortical spreading ischemia; Delayed
neurological deficit; Subarachnoid hemorrhage; Vasospasm
ID ISCHEMIC NEUROLOGICAL DEFICITS; DELAYED CEREBRAL-ISCHEMIA; DOUBLE-BLIND;
SPREADING ISCHEMIA; BRAIN; CORTEX; DAMAGE; RATS; DEPOLARIZATIONS;
CLAZOSENTAN
AB BACKGROUND: In human autopsy studies, 70% to 80% of patients with aneurysmal subarachnoid hemorrhage (SAH) showed infarcts in cerebral cortex covered by subarachnoid blood. Thus far, no animal model of SAH is known to produce this peculiar infarct pattern, and its pathogenesis remains enigmatic.
OBJECTIVE: To investigate whether such infarcts occur in the clot model of SAH in primates.
METHODS: We performed a retrospective pathological review of 16 primate brains. In 13 cynomolgus monkeys, a blood clot was placed around the middle cerebral artery after additional removal of the arachnoid membrane from the basal surface of the frontal and temporal cortexes. Three animals underwent sham surgery without placement of a blood clot (controls). The brains were harvested between days 1 and 28 after SAH and examined by a neuropathologist blinded to study group.
RESULTS: We identified 2 types of cortical infarcts. A band of selective cortical laminar necrosis parallel to the cortical surface ("horizontal") was found in 5 animals. The second category of cortical lesions had a "vertical" extension. It included wedge-shaped (n = 2) or pillarlike (n = 2) necrosis. Both horizontal and vertical infarcts were located exclusively in areas adjacent to subarachnoid blood. The presence of a cortical infarct did not correlate with the degree of middle cerebral artery vasospasm (r(2) = .24, P = .13).
CONCLUSION: The presence of cortical infarcts suggests that a modified nonhuman primate model of SAH is suitable to examine the pathogenesis of proximal vasospasm and permits investigation of cortical lesions similar to those reported in patients after SAH. Furthermore, it indicates that direct effects of the blood clot on the brain and microcirculation contribute to the development of cortical infarcts after SAH.
C1 [Schatlo, Bawarjan; Fathi, Ali-Reza; Moncrief, Travis; Oldfield, Edward H.; Vortmeyer, Alexander O.; Pluta, Ryszard M.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Schatlo, Bawarjan; Dreier, Jens P.] Charite, Ctr Stroke Res Berlin, D-13353 Berlin, Germany.
[Schatlo, Bawarjan] Univ Hosp Geneva, Dept Neurosurg, Geneva, Switzerland.
[Glaesker, Sven] Univ Hosp Freiburg, Dept Neurosurg, Freiburg, Germany.
[Fathi, Ali-Reza] Kantonsspital Aarau, Dept Neurosurg, Aarau, Switzerland.
[Oldfield, Edward H.] Univ Virginia, Dept Neurosurg, Charlottesville, VA USA.
[Vortmeyer, Alexander O.] Yale Univ, Sch Med, Dept Neuropathol, New Haven, CT USA.
RP Pluta, RM (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Room 3D20, Bethesda, MD 20892 USA.
EM Ryszard.Pluta@jama-archives.org
RI SCHATLO, Bawarjan/F-4285-2010;
OI Dreier, Jens/0000-0001-7459-2828
FU National Institutes of Health, National Institute of Neurological
Disorders and Stroke; German Research Society [DFG DR 323/3-1];
Boehringer Ingelheim Foundation
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, National Institute of Neurological
Disorders and Stroke and by grants from the German Research Society to
Dr Dreier (DFG DR 323/3-1 and Kompetenznetz Schlaganfall). Dr Schatlo
was supported by a scholarship from the Boehringer Ingelheim Foundation.
Dr Glasker was supported by a research grant from the German Research
Society. The other authors have no personal financial or institutional
interest in any of the drugs, materials, or devices described in this
article.
NR 46
TC 7
Z9 7
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-396X
J9 NEUROSURGERY
JI Neurosurgery
PD SEP
PY 2010
VL 67
IS 3
BP 721
EP 729
DI 10.1227/01.NEU.0000378024.70848.8F
PG 9
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 641TS
UT WOS:000281153200021
PM 20651629
ER
PT J
AU Leischow, SJ
Luke, DA
Mueller, N
Harris, JK
Ponder, P
Marcus, S
Clark, PI
AF Leischow, Scott J.
Luke, Douglas A.
Mueller, Nancy
Harris, Jenine K.
Ponder, Paris
Marcus, Stephen
Clark, Pamela I.
TI Mapping US government tobacco control leadership: Networked for success?
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Article
ID MENTAL-HEALTH; SOCIAL NETWORKS; HIV-AIDS; SERVICES; SYSTEMS; CARE
AB In order to better understand how tobacco control efforts are coordinated across agencies of the Department of Health and Human Services (DHHS), we assessed tobacco control-related communication between tobacco control leaders across DHHS.
Cross-sectional surveys were collected from individuals representing 11 DHHS agencies, and social network analyses were used to assess linkages and map agencies' tobacco control communication.
Individuals within the Office of the Secretary and Centers for Disease Control and Prevention (CDC) were most central to the network, and those of highest rank were most likely to be central to the network (F = 4.03, p = .024). The Centers for Medicare and Medicaid Services, Food and Drug Administration, Health Resources and Services Administration, and Substance Abuse and Mental Health Services Administration had no or almost no contact with other agencies. There was considerable between-agency contact variability, and the CDC was the most central agency.
Tobacco control communication across DHHS agencies was present but extremely variable. This inconsistency may compromise the ability of the DHHS to address tobacco use, a critical public health problem, in a coordinated and efficient fashion. In light of the new leadership at DHHS, this analysis describes a systems approach that can be reimplemented as a means of understanding and improving communication and collaboration to improve public health.
C1 [Leischow, Scott J.] Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA.
[Leischow, Scott J.; Ponder, Paris; Marcus, Stephen; Clark, Pamela I.] NCI, Tobacco Control Res Branch, Rockville, MD USA.
[Luke, Douglas A.; Mueller, Nancy; Harris, Jenine K.] St Louis Univ, Sch Publ Hlth, St Louis, MO 63103 USA.
[Luke, Douglas A.; Mueller, Nancy] Washington Univ, Ctr Tobacco Policy Res, St Louis, MO USA.
[Ponder, Paris] Ctr Dis Control & Prevent, Healthy Homes Lead Poisoning Prevent Branch, Atlanta, GA USA.
[Marcus, Stephen] Natl Inst Gen Med Sci, Ctr Bioinformat & Computat Biol, Rockville, MD USA.
[Clark, Pamela I.] Univ Maryland, Dept Publ & Community Hlth, College Pk, MD 20742 USA.
RP Leischow, SJ (reprint author), Univ Arizona, Arizona Canc Ctr, POB 245024, Tucson, AZ 85724 USA.
EM sleischow@azcc.arizona.edu
OI Luke, Douglas/0000-0003-1332-8569
FU National Cancer Institute
FX All financial support for this study came from the National Cancer
Institute.
NR 19
TC 12
Z9 12
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-2203
J9 NICOTINE TOB RES
JI Nicotine Tob. Res.
PD SEP
PY 2010
VL 12
IS 9
BP 888
EP 894
DI 10.1093/ntr/ntq112
PG 7
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA 644BS
UT WOS:000281346000003
PM 20688869
ER
PT J
AU Iyer, LM
Abhiman, S
de Souza, RF
Aravind, L
AF Iyer, Lakshminarayan M.
Abhiman, Saraswathi
de Souza, Robson F.
Aravind, L.
TI Origin and evolution of peptide-modifying dioxygenases and
identification of the wybutosine hydroxylase/hydroperoxidase
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID TRANSFER-RNA MODIFICATION; MULTIPLE SEQUENCE ALIGNMENT; PHENYLALANINE
TRANSFER-RNA; BIOSYNTHETIC GENE-CLUSTER; CRYSTAL-STRUCTURE; Y-BASE;
HISTONE DEMETHYLATION; TRANSCRIPTION FACTORS; COMPARATIVE GENOMICS;
STRUCTURE PREDICTION
AB Unlike classical 2-oxoglutarate and iron-dependent dioxygenases, which include several nucleic acid modifiers, the structurally similar jumonji-related dioxygenase superfamily was only known to catalyze peptide modifications. Using comparative genomics methods, we predict that a family of jumonji-related enzymes catalyzes wybutosine hydroxylation/peroxidation at position 37 of eukaryotic tRNAPhe. Identification of this enzyme raised questions regarding the emergence of protein- and nucleic acid-modifying activities among jumonji-related domains. We addressed these with a natural classification of DSBH domains and reconstructed the precursor of the dioxygenases as a sugar-binding domain. This precursor gave rise to sugar epimerases and metal-binding sugar isomerases. The sugar isomerase active site was exapted for catalysis of oxygenation, with a radiation of these enzymes in bacteria, probably due to impetus from the primary oxygenation event in Earth's history. 2-Oxoglutarate-dependent versions appear to have further expanded with rise of the tricarboxylic acid cycle. We identify previously under-appreciated aspects of their active site and multiple independent innovations of 2-oxoacid-binding basic residues among these superfamilies. We show that double-stranded beta-helix dioxygenases diversified extensively in biosynthesis and modification of halogenated siderophores, antibiotics, peptide secondary metabolites and glycine-rich collagen-like proteins in bacteria. Jumonji-related domains diversified into three distinct lineages in bacterial secondary metabolism systems and these were precursors of the three major clades of eukaryotic enzymes. The specificity of wybutosine hydroxylase/peroxidase probably relates to the structural similarity of the modified moiety to the ancestral amino acid substrate of this superfamily.
C1 [Iyer, Lakshminarayan M.; Abhiman, Saraswathi; de Souza, Robson F.; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM aravind@mail.nih.gov
FU National Library of Medicine at the National Institutes of Health, USA;
National Institutes of Health, USA
FX Intramural funds of the National Library of Medicine at the National
Institutes of Health, USA. Funding for open access charge: National
Institutes of Health, USA.
NR 92
TC 32
Z9 32
U1 1
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD SEP
PY 2010
VL 38
IS 16
BP 5261
EP 5279
DI 10.1093/nar/gkq265
PG 19
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 648US
UT WOS:000281720500008
PM 20423905
ER
PT J
AU Bebenek, K
Garcia-Diaz, M
Zhou, RZ
Povirk, LF
Kunkel, TA
AF Bebenek, Katarzyna
Garcia-Diaz, Miguel
Zhou, Rui-Zhe
Povirk, Lawrence F.
Kunkel, Thomas A.
TI Loop 1 modulates the fidelity of DNA polymerase lambda
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID DOUBLE-STRAND BREAK; BASE EXCISION-REPAIR; HUMAN NUCLEAR EXTRACTS;
TERMINAL DEOXYNUCLEOTIDYLTRANSFERASE; V(D)J RECOMBINATION; LYASE
ACTIVITY; POL-MU; BETA; MECHANISM; EFFICIENCY
AB Differences in the substrate specificity of mammalian family X DNA polymerases are proposed to partly depend on a loop (loop 1) upstream of the polymerase active site. To examine if this is the case in DNA polymerase lambda (pol lambda), here we characterize a variant of the human polymerase in which nine residues of loop 1 are replaced with four residues from the equivalent position in pol beta. Crystal structures of the mutant enzyme bound to gapped DNA with and without a correct dNTP reveal that the change in loop 1 does not affect the overall structure of the protein. Consistent with these structural data, the mutant enzyme has relatively normal catalytic efficiency for correct incorporation, and it efficiently participates in non-homologous end joining of double-strand DNA breaks. However, DNA junctions recovered from end-joining reactions are more diverse than normal, and the mutant enzyme is substantially less accurate than wild-type pol lambda in three different biochemical assays. Comparisons of the binary and ternary complex crystal structures of mutant and wild-type pol lambda suggest that loop 1 modulates pol lambda's fidelity by controlling dNTP-induced movements of the template strand and the primer-terminal 3'-OH as the enzyme transitions from an inactive to an active conformation.
C1 [Bebenek, Katarzyna; Garcia-Diaz, Miguel; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Bebenek, Katarzyna; Garcia-Diaz, Miguel; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Zhou, Rui-Zhe; Povirk, Lawrence F.] Virginia Commonwealth Univ, Massey Canc Ctr, Dept Pharmacol & Toxicol, Richmond, VA USA.
RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
EM kunkel@niehs.nih.gov
FU Division of Intramural Research of the National Institutes of Health,
National Institute of Environmental Health Sciences [Z01 ES065070];
National Institutes of Health, National Cancer Institute [CA40615]
FX Division of Intramural Research of the National Institutes of Health,
National Institute of Environmental Health Sciences (Project Z01
ES065070 to T. A. K, in parts); National Institutes of Health, National
Cancer Institute (CA40615 to L. F. P., in parts). Funding for open
access charge: Division of Intramural Research of the National
Institutes of Health, National Institute of Environmental Health
Sciences Project (Z01 ES065070 to T. A. K.).
NR 46
TC 21
Z9 21
U1 1
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD SEP
PY 2010
VL 38
IS 16
BP 5419
EP 5431
DI 10.1093/nar/gkq261
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 648US
UT WOS:000281720500020
PM 20435673
ER
PT J
AU Grady, PA
AF Grady, Patricia A.
TI Creating a healthier tomorrow through research, practice, and policy
SO NURSING OUTLOOK
LA English
DT News Item
ID RANDOMIZED CLINICAL-TRIAL; TRANSITIONAL CARE; OLDER-ADULTS
C1 NINR, NIH, Bethesda, MD 20892 USA.
RP Grady, PA (reprint author), NINR, NIH, 6701 Democracy Blvd, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [Z99 NR999999]
NR 26
TC 3
Z9 3
U1 3
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0029-6554
J9 NURS OUTLOOK
JI Nurs. Outlook
PD SEP-OCT
PY 2010
VL 58
IS 5
BP 268
EP 271
DI 10.1016/j.outlook.2010.07.007
PG 4
WC Nursing
SC Nursing
GA 669WP
UT WOS:000283381200011
PM 20934082
ER
PT J
AU Tamboli, RA
Hossain, HA
Marks, PA
Eckhauser, AW
Rathmacher, JA
Phillips, SE
Buchowski, MS
Chen, KY
Abumrad, NN
AF Tamboli, Robyn A.
Hossain, H. Ayesha
Marks, Pamela A.
Eckhauser, Aaron W.
Rathmacher, John A.
Phillips, Sharon E.
Buchowski, Maciej S.
Chen, Kong Y.
Abumrad, Naji N.
TI Body Composition and Energy Metabolism Following Roux-en-Y Gastric
Bypass Surgery
SO OBESITY
LA English
DT Article
ID X-RAY ABSORPTIOMETRY; MASSIVE WEIGHT-LOSS; BARIATRIC SURGERY;
BIOELECTRICAL-IMPEDANCE; PROTEIN-METABOLISM; OBESE WOMEN; EXPENDITURE;
3-METHYLHISTIDINE; IMPACT; SUPEROBESITY
AB Roux-en-Y gastric bypass (RYGB) surgery has become an accepted treatment for excessive obesity. We conducted a longitudinal study to assess regional body composition, muscle proteolysis, and energy expenditure before RYGB, and 6 and 12 months after RYGB. Whole-body and regional fat mass (FM) and lean mass (LM) were assessed via dual-energy X-ray absorptiometry (DXA), and myofibrillar protein degradation was estimated by urinary 3-methylhistidine (3-MeH) in 29 subjects. Energy expenditure and substrate oxidation were also determined using a whole-room, indirect calorimeter in 12 of these subjects. LM loss constituted 27.8 +/- 10.2% of total weight loss achieved 12 months postoperatively, with the majority of LM loss (18 +/- 6% of initial LM) occurring in the first 6 months following RYGB. During this period, the trunk region contributed 66% of whole-body LM loss. LM loss occurred in the first 6 months after RYGB despite decreased muscle protein breakdown, as indicated by a decrease in 3-MeH concentrations and muscle fractional breakdown rates. Sleep energy expenditure (SEE) decreased from 2,092 +/- 342 kcal/d at baseline to 1,495 +/- 190 kcal/day at 6 months after RYGB (P < 0.0001). Changes in both LM and FM had an effect on the reduction in SEE (P < 0.001 and P = 0.005, respectively). These studies suggest that loss of LM after RYGB is significant and strategies to maintain LM after surgery should be explored.
C1 [Tamboli, Robyn A.; Marks, Pamela A.; Eckhauser, Aaron W.; Abumrad, Naji N.] Vanderbilt Univ, Sch Med, Dept Surg, Nashville, TN 37212 USA.
[Hossain, H. Ayesha] Case Western Reserve Univ, Sch Med, Dept Ophthalmol, Cleveland, OH USA.
[Rathmacher, John A.] Iowa State Univ, Dept Anim Sci, Ames, IA USA.
[Phillips, Sharon E.] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA.
[Buchowski, Maciej S.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA.
[Chen, Kong Y.] NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
RP Abumrad, NN (reprint author), Vanderbilt Univ, Sch Med, Dept Surg, Nashville, TN 37212 USA.
EM naji.abumrad@vanderbilt.edu
RI Buchowski, Maciej/A-2683-2008;
OI Buchowski, Maciej/0000-0002-0566-1743; Chen, Kong/0000-0002-0306-1904
FU National Institute of Diabetes and Digestive and Kidney Diseases
[RO1-DK070860]; National Center for Research Resources [1 UL1 RR024975];
Vanderbilt Diabetes Research and Training Center [DK20593]; Vanderbilt
Digestive Disease Research Center [DK058404]
FX This work was supported by the following National Institutes of Health
grants: National Institute of Diabetes and Digestive and Kidney Diseases
RO1-DK070860 to N.N.A., the Vanderbilt CTSA grant 1 UL1 RR024975 from
the National Center for Research Resources, DK20593 to the Vanderbilt
Diabetes Research and Training Center, and DK058404 to the Vanderbilt
Digestive Disease Research Center. We thank James M. Isbell and Julia P.
Dunn for their advice on this project.
NR 41
TC 46
Z9 47
U1 2
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD SEP
PY 2010
VL 18
IS 9
BP 1718
EP 1724
DI 10.1038/oby.2010.89
PG 7
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 646CE
UT WOS:000281512400007
PM 20414197
ER
PT J
AU Krakoff, J
Clark, JM
Crandall, JP
Wilson, C
Molitch, ME
Brancati, FL
Edelstein, SL
Knowler, WC
AF Krakoff, Jonathan
Clark, Jeanne M.
Crandall, Jill P.
Wilson, Charlton
Molitch, Mark E.
Brancati, Frederick L.
Edelstein, Sharon L.
Knowler, William C.
CA Diabet Prevention Program Res Grp
TI Effects of Metformin and Weight Loss on Serum Alanine Aminotransferase
Activity in the Diabetes Prevention Program
SO OBESITY
LA English
DT Article
ID FATTY LIVER-DISEASE; NONALCOHOLIC STEATOHEPATITIS; UNITED-STATES;
METABOLIC SYNDROME; INSULIN-RESISTANCE; CONTROLLED-TRIAL;
CLINICAL-TRIAL; PREVALENCE; ASSOCIATION; OVERWEIGHT
AB Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, and impaired glucose tolerance. We investigated whether metformin or changes in metabolic measurements (weight, fasting plasma glucose (FPG), or fasting insulin (FI)) improved serum alanine aminotransferase (ALT) activity, as a marker for NAFLD, in the Diabetes Prevention Program (DPP). From 1996 to 1999, 2,153 participants without marked elevations of serum ALT at baseline were randomized (1,081 to placebo, 1,072 to metformin) and treated for an average of 3.2 years. ALT increased during the first 2 years of the study, and was slightly but significantly lower in the participants randomized to metformin. In regression models adjusted for sex, baseline age, FPG, and FI, these differences remained significant, but disappeared after adjustment for weight, FPG, and FI changes at each examination. The 3-year cumulative incidence for development of abnormal ALT concentrations was not significantly different ((mean +/- s.e.) 21.4 +/- 1.4% and 24.6 +/- 1.4%, P = 0.11) in the metformin vs. placebo groups but was lower in individuals in both groups that lost more weight by the end of year 1 (metformin: 19.4 +/- 2.4% vs. 27.5 +/- 3.7%, for highest vs. lowest quartile of weight loss; placebo: 18.7 +/- 3.4% vs. 28.8 +/- 2.6%). Over 3 years of follow-up in persons at high risk for development of diabetes, serum ALT was consistently lower in those treated with metformin compared with placebo. This effect was mediated by weight loss, indicating that the effects of metformin therapy on ALT is via its effects on weight.
C1 [Krakoff, Jonathan; Knowler, William C.] NIDDKD, Phoenix, AZ USA.
[Clark, Jeanne M.; Brancati, Frederick L.] Johns Hopkins Sch Med, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Crandall, Jill P.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA.
[Wilson, Charlton] Indian Hlth Serv, Phoenix Indian Med Ctr, Phoenix, AZ USA.
[Molitch, Mark E.] Northwestern Univ, Div Endocrinol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Edelstein, Sharon L.] George Washington Univ, Biostat Ctr, Rockville, MD USA.
RP Krakoff, J (reprint author), NIDDKD, Phoenix, AZ USA.
EM dppmail@bsc.gwu.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
of the National Institutes of Health; NIDDK; Indian Health Service;
Office of Research on Minority Health; National Institute of Child
Health and Human Development; National Institute on Aging; Centers for
Disease Control and Prevention; Office of Research on Women's Health;
American Diabetes Association; LifeScan Inc.; Health O Meter; Hoechst
Marion Roussel, Inc.; Merck-Medco Managed Care, Inc.; Merck and Co.;
Nike Sports Marketing; Slim Fast Foods Co.; McKesson BioServices Corp.;
Matthews Media Group, Inc.; Henry M. Jackson Foundation
FX The Investigators gratefully acknowledge the commitment and dedication
of the participants of the DPP. We thank Dr. Jay Hoofnagle for his
advice and editing of the manuscript. The National Institute of Diabetes
and Digestive and Kidney Diseases (NIDDK) of the National Institutes of
Health provided funding to the clinical centers and the Coordinating
Center for the design and conduct of the study; collection, management,
analysis, and interpretation of the data. The Southwestern American
Indian Centers were supported directly by the NIDDK and the Indian
Health Service. The General Clinical Research Center Program, National
Center for Research Resources supported data collection at many of the
clinical centers. Funding for data collection and participant support
was also provided by the Office of Research on Minority Health, the
National Institute of Child Health and Human Development, the National
Institute on Aging, the Centers for Disease Control and Prevention, the
Office of Research on Women's Health, and the American Diabetes
Association. Bristol-Myers Squibb and Parke-Davis provided medication.
This research was also supported, in part, by the intramural research
program of the NIDDK. LifeScan Inc., Health O Meter, Hoechst Marion
Roussel, Inc., Merck-Medco Managed Care, Inc., Merck and Co., Nike
Sports Marketing, Slim Fast Foods Co., and Quaker Oats Co. donated
materials, equipment, or medicines for concomitant conditions. McKesson
BioServices Corp., Matthews Media Group, Inc., and the Henry M. Jackson
Foundation provided support services under subcontract with the
Coordinating Center. The opinions expressed are those of the
investigators and do not necessarily reflect the views of the Indian
Health Service or other funding agencies. A complete list of Centers,
investigators, and staff can be found in ref. 10.
NR 33
TC 24
Z9 24
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD SEP
PY 2010
VL 18
IS 9
BP 1762
EP 1767
DI 10.1038/oby.2010.21
PG 6
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 646CE
UT WOS:000281512400013
PM 20186137
ER
PT J
AU Salihu, HM
Alio, AP
Belogolovkin, V
Aliyu, MH
Wilson, RE
Reddy, UM
Bruder, K
Whiteman, VE
AF Salihu, Hamisu M.
Alio, Amina P.
Belogolovkin, Victoria
Aliyu, Muktar H.
Wilson, Ronee E.
Reddy, Uma M.
Bruder, Karen
Whiteman, Valerie E.
TI Prepregnancy Obesity and Risk of Stillbirth in Viable Twin Gestations
SO OBESITY
LA English
DT Article
ID BODY-MASS INDEX; UNITED-STATES; PRENATAL-CARE; PREGNANCY; MORTALITY;
WEIGHT; FETAL; OUTCOMES; TRENDS; BIRTH
AB We sought to estimate the impact of prepregnancy obesity on demise of one or both fetuses in twin gestations. We performed a retrospective cohort study using the Missouri maternally linked cohort files (years 1989-2005). Prepregnancy obesity was defined as a BMI >= 30. Outcomes of interest were stillbirth (intrauterine fetal death at >= 20 weeks' gestation) and demise of one (partial loss) or both (complete loss) fetuses, regardless of the cause. We used Cox Proportional Hazards with correction for intracluster correlation to obtain risk estimates. The overall stillbirth rate for twin gestations was 15.5/1,000 (18.4/1,000 vs. 14.5/1,000 in obese and normal weight mothers, respectively; P = 0.02). The rate for complete fetal loss was higher in obese mothers (8.3/1,000 vs. 5.6/1,000; P = 0.01) but was comparable for partial fetal loss (19.1/1,000 for obese vs. 16.3/1,000 for normal weight mothers; P = 0.1). Adjusted estimates confirmed these findings (adjusted hazards ratio (AHR) and 95% confidence interval (CI) = 1.31 (1.02-1.68) for stillbirth; AHR = 1.59; CI = 1.01-2.51) for complete loss; and AHR = 1.21; CI = 0.91-1.62) for partial loss. Subanalysis conducted on stillbirth showed that the risk associated with obesity was only elevated for same-sex (AHR = 1.54; CI = 1.15-2.04) but not opposite-sex twins (0.99; CI = 0.56-1.75). Our findings may find utility in counseling of obese women with twin gestations.
C1 [Salihu, Hamisu M.; Belogolovkin, Victoria; Bruder, Karen; Whiteman, Valerie E.] Univ S Florida, Dept Obstet & Gynecol, Tampa, FL 33620 USA.
[Salihu, Hamisu M.; Wilson, Ronee E.] Univ S Florida, Dept Epidemiol & Biostat, Tampa, FL 33620 USA.
[Salihu, Hamisu M.] Univ S Florida, Chiles Ctr Healthy Mothers & Babies, Tampa, FL 33620 USA.
[Alio, Amina P.] Univ S Florida, Dept Community & Family Hlth, Tampa, FL 33620 USA.
[Aliyu, Muktar H.] Vanderbilt Univ, Dept Prevent Med, Inst Global Hlth, Nashville, TN USA.
[Reddy, Uma M.] Funice Kennedy Shriver NICHHD, NIH, Bethesda, MD USA.
RP Salihu, HM (reprint author), Univ S Florida, Dept Obstet & Gynecol, Tampa, FL 33620 USA.
EM hamisu.salihu@gmail.com
OI Aliyu, Muktar/0000-0001-9504-4679
FU Flight Attendant Medical Research Institute (FAMRI)
FX This study was funded by a grant from the Flight Attendant Medical
Research Institute (FAMRI) to the first author (H.M.S.). The funding
agency did not play any role in any aspect of the study. We thank the
Missouri Department of Health and Senior Services for providing the data
files used in this study.
NR 45
TC 3
Z9 3
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD SEP
PY 2010
VL 18
IS 9
BP 1795
EP 1800
DI 10.1038/oby.2009.479
PG 6
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 646CE
UT WOS:000281512400018
PM 20057375
ER
PT J
AU Ewens, KG
Stewart, DR
Ankener, W
Urbanek, M
McAllister, JM
Chen, C
Baig, KM
Parker, SCJ
Margulies, EH
Legro, RS
Dunaif, A
Strauss, JF
Spielman, RS
AF Ewens, Kathryn G.
Stewart, Douglas R.
Ankener, Wendy
Urbanek, Margrit
McAllister, Jan M.
Chen, Chen
Baig, K. Maravet
Parker, Stephen C. J.
Margulies, Elliot H.
Legro, Richard S.
Dunaif, Andrea
Strauss, Jerome F., III
Spielman, Richard S.
TI Family-Based Analysis of Candidate Genes for Polycystic Ovary Syndrome
EDITORIAL COMMENT
SO OBSTETRICAL & GYNECOLOGICAL SURVEY
LA English
DT Editorial Material
C1 [Ewens, Kathryn G.] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA.
Penn State Hershey Med Ctr, Dept Pathol, Hershey, PA USA.
Virginia Commonwealth Univ, Dept Obstet & Gynecol, Richmond, VA USA.
Penn State Hershey Coll Med, Dept Obstet & Gynecol, Hershey, PA USA.
RP Ewens, KG (reprint author), Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7828
J9 OBSTET GYNECOL SURV
JI Obstet. Gynecol. Surv.
PD SEP
PY 2010
VL 65
IS 9
BP 571
EP 572
DI 10.1097/OGX.0b013e3182021dfd
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 694WU
UT WOS:000285332600014
ER
PT J
AU Hauth, JC
Clifton, RG
Roberts, JM
Spong, CY
Myatt, L
Leveno, KJ
Pearson, GD
Varner, MW
Thorp, JM
Mercer, BM
Peaceman, AM
Ramin, SM
Sciscione, A
Harper, M
Tolosa, JE
Saade, G
Sorokin, Y
Anderson, GB
AF Hauth, John C.
Clifton, Rebecca G.
Roberts, James M.
Spong, Catherine Y.
Myatt, Leslie
Leveno, Kenneth J.
Pearson, Gail D.
Varner, Michael W.
Thorp, John M., Jr.
Mercer, Brian M.
Peaceman, Alan M.
Ramin, Susan M.
Sciscione, Anthony
Harper, Margaret
Tolosa, Jorge E.
Saade, George
Sorokin, Yoram
Anderson, Garland B.
CA Eunice Kennedy Shriver Natl Inst C
TI Vitamin C and E Supplementation to Prevent Spontaneous Preterm Birth A
Randomized Controlled Trial
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article; Proceedings Paper
CT 30th Annual Meeting of the Society-for-Maternal-Fetal-Medicine
CY FEB 01-06, 2010
CL Chicago, IL
SP Soc Maternal Fetal Med
ID PREMATURE RUPTURE; MEMBRANES; DELIVERY; WOMEN; RISK
AB OBJECTIVE: To estimate whether maternally administered vitamins C and E lower the risk of spontaneous preterm birth.
METHODS: This is a secondary analysis of a randomized, double-masked, placebo-controlled trial in nulliparous women at low-risk administered 1,000 mg vitamin C and 400 international units vitamin E or placebo daily from 9 to 16 weeks of gestation until delivery. Outcomes include preterm birth attributable to premature rupture of membranes (PROM) and total spontaneous preterm births (spontaneous preterm birth attributable to PROM or spontaneous labor).
RESULTS: Of the 10,154 women randomized, outcome data were available for 9,968 (4,992 vitamin group and 4,976 placebo group). A total of 1,038 women (10.4%) delivered preterm, of whom 698 (7.0%) had spontaneous preterm birth. A spontaneous preterm birth occurred in 356 women (7.1%) assigned to daily vitamin C and E supplementation and in 342 (6.9%) assigned to placebo. There were 253 women (2.5%) who delivered after preterm PROM and 445 (4.5%) after a spontaneous preterm labor. In women supplemented with vitamins C and E, births attributed to preterm PROM were similar at less than 37 and 35 weeks of gestation, but births were less frequent before 32 weeks of gestation (0.3% compared with 0.6%, adjusted odds ratio 0.3-0.9). However, total spontaneous preterm births across gestation in women supplemented with vitamins C and E or a placebo were similar.
CONCLUSION: Maternal supplementation with vitamins C and E beginning at 9 to 16 weeks of gestation in nulliparous women at low risk did not reduce spontaneous preterm births.
C1 [Hauth, John C.] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35249 USA.
Univ Pittsburgh, Pittsburgh, PA USA.
Univ Cincinnati, Cincinnati, OH USA.
Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
Univ Utah, Salt Lake City, UT USA.
Univ N Carolina, Chapel Hill, NC USA.
Case Western Reserve Univ, Cleveland, OH 44106 USA.
Northwestern Univ, Chicago, IL 60611 USA.
Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
Drexel Univ, Philadelphia, PA 19104 USA.
Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
Univ Texas Med Branch, Galveston, TX USA.
Wayne State Univ, Detroit, MI USA.
Univ Texas Med Ctr, Galveston, TX USA.
George Washington Univ, Ctr Biostat, Washington, DC USA.
NHLBI, Bethesda, MD 20892 USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Hauth, JC (reprint author), Univ Alabama, Dept Obstet & Gynecol, 619 19th St S 176F,Suite 10360, Birmingham, AL 35249 USA.
EM jchauth@uab.edu
RI Varner, Michael/K-9890-2013;
OI Varner, Michael/0000-0001-9455-3973; Peaceman, Alan/0000-0002-4515-4850
FU NCRR NIH HHS [M01 RR000080, M01 RR00080, UL1 RR024153, UL1 RR024989];
NICHD NIH HHS [HD40512, HD21410, HD27860, HD27869, HD27915, HD27917,
HD34116, HD34136, HD34208, HD36801, HD40485, HD40500, HD40544, HD40545,
HD40560, HD53097, HD53118, R24 HD050924, U01 HD036801, U10 HD021410, U10
HD027860, U10 HD027869, U10 HD027869-21, U10 HD027915, U10 HD027917, U10
HD034116, U10 HD034136, U10 HD034208, U10 HD036801, U10 HD040485, U10
HD040500, U10 HD040512, U10 HD040544, U10 HD040545, U10 HD040560, U10
HD053097, U10 HD053118, UG1 HD027869, UG1 HD027915, UG1 HD034116, UG1
HD034208, UG1 HD040485, UG1 HD040500, UG1 HD040512, UG1 HD040544, UG1
HD040545, UG1 HD040560, UG1 HD053097]
NR 13
TC 30
Z9 30
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD SEP
PY 2010
VL 116
IS 3
BP 653
EP 658
DI 10.1097/AOG.0b013e3181ed721d
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 642AY
UT WOS:000281176400014
PM 20733448
ER
PT J
AU Zhang, J
Fraser, W
Troendle, J
Sundaram, R
AF Zhang, Jun
Fraser, William
Troendle, James
Sundaram, Rajeshwari
TI The Natural History of the Normal First Stage of Labor Reply
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Letter
C1 [Zhang, Jun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
Univ Montreal, Montreal, PQ, Canada.
RP Zhang, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD SEP
PY 2010
VL 116
IS 3
BP 772
EP 773
DI 10.1097/AOG.0b013e3181ee9ff3
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 642AY
UT WOS:000281176400032
ER
PT J
AU Liu, W
Zabirnyk, O
Wang, H
Shiao, YH
Nickerson, ML
Khalil, S
Anderson, LM
Perantoni, AO
Phang, JM
AF Liu, W.
Zabirnyk, O.
Wang, H.
Shiao, Y-H
Nickerson, M. L.
Khalil, S.
Anderson, L. M.
Perantoni, A. O.
Phang, J. M.
TI miR-23b*targets proline oxidase, a novel tumor suppressor protein in
renal cancer
SO ONCOGENE
LA English
DT Article
DE proline oxidase; miR-23b*; renal cancer; ROS; tumor suppressor
ID TARGET MESSENGER-RNAS; CELL CARCINOMA; MICROPROCESSOR COMPLEX;
MICROARRAY ANALYSIS; DOWN-REGULATION; BREAST-CANCER; MICRORNAS;
EXPRESSION; APOPTOSIS; GENE
AB Proline oxidase (POX) is a novel mitochondrial tumor suppressor that can suppress proliferation and induce apoptosis through the generation of reactive oxygen species (ROS) and decreasing hypoxia-inducible factor (HIF) signaling. Recent studies have shown the absence of expression of POX in human cancer tissues, including renal cancer. However, the mechanism for the loss of POX remains obscure. No genetic or epigenetic variation of POX gene was found. In this study, we identified the upregulated miR-23b* in renal cancer as an important regulator of POX. Ectopic overexpression of miR-23b* in normal renal cells resulted in striking downregulation of POX, whereas POX expression increased markedly when endogenous miR-23b* was knocked down by its antagomirs in renal cancer cells. Consistent with the POX-mediated tumor suppression pathway, these antagomirs induced ROS, inhibited HIF signaling and increased apoptosis. Furthermore, we confirmed the regulation of miR-23b* on POX and its function in the DLD1 Tet-off POX cell system. Using a luciferase reporter system, we verified the direct binding of miR-23b* to the POX mRNA 3'-untranslated region. In addition, pairs of human renal carcinoma and normal tissues showed a negative correlation between miR-23b* and POX protein expression, providing its clinical corroboration. Taken together, our results suggested that miR-23b*, by targeting POX, could function as an oncogene; decreasing miR-23b* expression may prove to be an effective way of inhibiting kidney tumor growth. Oncogene (2010) 29, 4914-4924; doi: 10.1038/onc.2010.237; published online 21 June 2010
C1 [Liu, W.; Zabirnyk, O.; Shiao, Y-H; Khalil, S.; Anderson, L. M.; Phang, J. M.] NCI, Lab Comparat Carcinogenesis, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Wang, H.; Perantoni, A. O.] NCI, Lab Canc & Dev Biol, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Nickerson, M. L.] NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
RP Liu, W (reprint author), NCI, Lab Comparat Carcinogenesis, Ctr Canc Res, NIH, Bldg 538,Room 144, Frederick, MD 21702 USA.
EM liuwei3@mail.nih.gov; phangj@mail.nih.gov
RI liu, wei /E-7340-2012
FU NIH; National Cancer Institute, Center for Cancer Research
FX We thank Dr Anna E Maciag for insightful comments, Dr Matthew J Fivash
for statistical analysis, Dr Miriam R Anver for evaluating POX
immunohistochemical staining and miR-23b* in situ hybridization, Dr
Chang H Kim for his help with the miRNA microarray. This research was
supported (in part) by the Intramural Research Program of the NIH, the
National Cancer Institute, Center for Cancer Research. The content of
this publication does not necessarily reflect the views or policies of
the Department of Health and Human Services, nor does mention of trade
names, commercial products or organizations imply endorsement by the US
Government.
NR 43
TC 60
Z9 63
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD SEP
PY 2010
VL 29
IS 35
BP 4914
EP 4924
DI 10.1038/onc.2010.237
PG 11
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 646XP
UT WOS:000281578700006
PM 20562915
ER
PT J
AU Madan, RA
Gulley, JL
Fojo, T
Dahut, WL
AF Madan, Ravi A.
Gulley, James L.
Fojo, Tito
Dahut, William L.
TI Therapeutic Cancer Vaccines in Prostate Cancer: The Paradox of Improved
Survival Without Changes in Time to Progression
SO ONCOLOGIST
LA English
DT Article
DE Prostate cancer; Therapeutic cancer vaccines; Overall survival;
Progression-free survival; Clinical endpoints
ID CELL LUNG-CANCER; PHASE-I TRIAL; TUMOR-IMMUNOTHERAPY; IMMUNE-RESPONSE;
DENDRITIC CELLS; SIPULEUCEL-T; SOLID TUMORS; COMBINATION; DOCETAXEL;
MITOXANTRONE
AB Therapeutic cancer vaccines represent a new class of agents in the treatment of cancer. Sipuleucel-T is an antigen-presenting cell based vaccine that recently demonstrated a significant 4.8-month improvement in overall survival in advanced prostate cancer patients and was well tolerated. The findings of that study have been met with skepticism, primarily because the agent did not change initial disease progression and yet led to longer survival. Although the commonly accepted treatment paradigm suggests that treatments should initially decrease tumor volume, perhaps vaccines work differently. Vaccines may induce delayed responses not seen in the first few months of therapy or they may initiate a dynamic immune response that ultimately slows the tumor growth rate, resulting in longer survival. Subsequent therapies may also combine with the induced immune response, resulting in a combination that is more effective than conventional treatments alone. Also, other treatments may alter tumor-associated antigen expression, enhancing the immune response. Future trials are currently planned to investigate these hypotheses; however, the results of the sipuleucel-T vaccine in prostate cancer should not be dismissed. Results with another vaccine in prostate cancer are similar, perhaps suggesting a class effect. In a broader context, clinicians may need to reconsider how they measure success. Several agents have been approved that produce superior disease progression results, but do not affect overall survival. Given the toxicity and costs of cancer therapies, perhaps studies should put more weight on long-term survival endpoints than on short-term endpoints that may be less consequential. The Oncologist 2010;15:969-975
C1 [Madan, Ravi A.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Madan, Ravi A.; Gulley, James L.; Fojo, Tito; Dahut, William L.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Gulley, JL (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA.
EM gulleyj@mail.nih.gov
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 66
TC 71
Z9 71
U1 1
U2 2
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
EI 1549-490X
J9 ONCOLOGIST
JI Oncologist
PD SEP
PY 2010
VL 15
IS 9
BP 969
EP 975
DI 10.1634/theoncologist.2010-0129
PG 7
WC Oncology
SC Oncology
GA 659CY
UT WOS:000282545800008
PM 20798195
ER
PT J
AU Kjellstrom, S
Vijayasarathy, C
Ponjavic, V
Sieving, PA
Andreasson, S
AF Kjellstrom, Sten
Vijayasarathy, Camasamudram
Ponjavic, Vesna
Sieving, Paul A.
Andreasson, Sten
TI Long-term 12 year follow-up of X-linked congenital retinoschisis
SO OPHTHALMIC GENETICS
LA English
DT Article
DE XLRS; genotype; phenotype; rate of progression
ID DEEP INTRONIC MUTATION; JUVENILE RETINOSCHISIS; FUNDUS AUTOFLUORESCENCE;
FUNCTIONAL IMPLICATIONS; VISUAL-ACUITY; GENE-THERAPY; MOUSE MODEL; RS1
GENE; EXPRESSION; FAMILIES
AB Purpose: To investigate the retinal structure and function during the progression of X-linked retinoschisis (XLRS) from childhood to adulthood.
Methods: Ten patients clinically diagnosed with XLRS were investigated at 6-15 years of age (mean age 9 years) with a follow-up 8 to 14 years later (mean 12 years). The patients underwent regular ophthalmic examination as well as testing of best corrected visual acuity (BCVA), visual field (VF) and assessment of full-field electroretinography (ERG) during their first visit. During the follow-up, the same clinical protocols were repeated. In addition, macular structure and function was examined with multifocal electroretinography (mfERG) and optical coherence tomography (OCT). The patients were 18-25 years of age (mean age 21 years) at the follow-up examination. All exons and exon-intron boundaries of RS1-gene were sequenced for gene mutations in 9 out of the 10 patients.
Results: Best corrected VA and VF were stable during this follow-up period. No significant progression in cone or rod function could be measured by full-field ERG. Multifocal electroretinography and OCT demonstrated a wide heterogeneity of macular changes in retinal structure and function at the time of follow-up visit. Three different mutations were detected in these nine patients, including a known nonsense mutation in exon 3, a novel insertion in exon 5 and an intronic mutation at 5' splice site of intron 3.
Conclusions: Clinical follow-up (mean 12 years) of ten young XLRS patients (mean age of 9 years) with a typical congenital retinoschisis phenotype revealed no significant decline in retinal function during this time period. MfERG and OCT demonstrated a wide variety of macular changes including structure and dysfunction. The XLRS disease was relatively stable during this period of observation and would afford opportunity for therapy studies to judge benefit against baseline and against the fellow eye.
C1 [Kjellstrom, Sten; Ponjavic, Vesna; Andreasson, Sten] Lund Univ, Dept Ophthalmol, S-22185 Lund, Sweden.
[Vijayasarathy, Camasamudram] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA.
[Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA.
RP Kjellstrom, S (reprint author), Lund Univ, Dept Ophthalmol, S-22185 Lund, Sweden.
EM sten.kjellstrom@med.lu.se
FU Stiftelsen Synframjandets Forskningsfond; Swedish Medical Research
Council [2007-3385]; Foundation Fighting Blindness, Owings Mills,
Maryland, USA; NIH [Z01-DC000065]
FX We thank Ing-Marie Holst and Boel Nilsson for skillful technical
assistance. This study was supported by grants from Stiftelsen
Synframjandets Forskningsfond, the Swedish Medical Research Council
(projects no. 2007-3385), the Foundation Fighting Blindness, Owings
Mills, Maryland, USA and NIH Grant Z01-DC000065
NR 32
TC 10
Z9 13
U1 0
U2 3
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 1381-6810
J9 OPHTHALMIC GENET
JI Ophthalmic Genet.
PD SEP
PY 2010
VL 31
IS 3
BP 114
EP 125
DI 10.3109/13816810.2010.482555
PG 12
WC Genetics & Heredity; Ophthalmology
SC Genetics & Heredity; Ophthalmology
GA 655KE
UT WOS:000282248100003
PM 20569020
ER
PT J
AU Cox, CA
Amaral, J
Salloum, R
Guedez, L
Reid, TW
Jaworski, C
John-Aryankalayil, M
Freedman, KA
Campos, MM
Martinez, A
Becerra, SP
Carper, DA
AF Cox, Constance A.
Amaral, Juan
Salloum, Rita
Guedez, Liliana
Reid, Ted W.
Jaworski, Cindy
John-Aryankalayil, Moly
Freedman, Ken A.
Campos, Mercedes M.
Martinez, Alfredo
Becerra, Susan P.
Carper, Deborah A.
TI Doxycycline's Effect on Ocular Angiogenesis: An In Vivo Analysis
SO OPHTHALMOLOGY
LA English
DT Article
ID EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; MATRIX METALLOPROTEINASES;
GROWTH-FACTOR; MACULAR DEGENERATION; BASAL-CELLS; MOUSE MODEL;
PTERYGIUM; PATHOGENESIS; INHIBITION; RAT
AB Purpose: To determine the in vivo effect of doxycycline on choroidal angiogenesis and pterygium growth by using a choroidal neovascular (CNV) murine model, a directed in vivo angiogenesis assay (DIVAA) and a pterygium murine model.
Design: Experimental study.
Participants: Three murine models were investigated with 4 mice minimum per group and 22 maximum per group.
Methods: Mice received water with or without doxycycline. For the CNV, the neovascular lesion volume was determined in choroid-retinal pigment epithelial flat mounts using confocal microscopy 7 days after laser induction. For DIVAA, silicone capsules containing 10 000 human pterygium epithelial cells were implanted in the flanks of mice subcutaneously. After 11 days, neovascularization (NV) was quantified using spectrofluorometry after murine tail-vein injection of fluorescein isothiocyanate-labeled dextran. A pterygium epithelial cell model was developed by injecting 10 000 human pterygium epithelial cells in the nasal subconjunctival space in athymic nude mice. Doxycycline was started on day 6 at 50 mg/kg per day; corneal lesions that resulted from the injections were compared at days 6 and 15.
Main Outcome Measures: The Student t-test was used to evaluate the data for the CNV and DIVAA models and histologic preparations were used to evaluate pterygia lesions.
Results: There was significantly less NV and lesion volume with doxycycline taken in drinking water versus plain water. With doxycycline treatment, the laser-induced CNV showed a maximal 66% decrease in choroidal blood vessel volume (P <= 0.008) and the DIVAA showed a 30% reduction of blood vessel growth and migration (P<0.004). Histologic preparations demonstrated that pterygium cell lesions regressed when mice were administered doxycycline for 9 days.
Conclusions: Doxycycline significantly inhibited angiogenesis in 3 murine models. The most dramatic effect was found in the CNV model followed by the pterygia epithelial cell DIVAA model. The anterior segment pterygium model also showed regression histologically. This suggests that doxycycline may be successful as an adjunctive treatment for CNV and pterygia in humans; clinical trials would be necessary to determine if there is a benefit.
C1 [Cox, Constance A.; Amaral, Juan; Jaworski, Cindy; Campos, Mercedes M.; Becerra, Susan P.; Carper, Deborah A.] NEI, NIH, Bethesda, MD 20892 USA.
[Salloum, Rita; Guedez, Liliana; John-Aryankalayil, Moly; Martinez, Alfredo] NCI, NIH, Bethesda, MD 20892 USA.
[Reid, Ted W.; Freedman, Ken A.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79409 USA.
RP Cox, CA (reprint author), Univ Hawaii, JABSOM, BSB 222-11,651 Ilalo St, Honolulu, HI 96813 USA.
EM cc6@hawaii.edu
RI Guedez, Liliana/H-4951-2012; Martinez, Alfredo/A-3077-2013
OI Martinez, Alfredo/0000-0003-4882-4044
FU National Eye Institute, National Institutes of Health, in Bethesda,
Maryland
FX Supported by the National Eye Institute, National Institutes of Health
(intramural), in Bethesda, Maryland.
NR 37
TC 24
Z9 24
U1 1
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD SEP
PY 2010
VL 117
IS 9
BP 1782
EP 1791
DI 10.1016/j.ophtha.2010.01.037
PG 10
WC Ophthalmology
SC Ophthalmology
GA 646DY
UT WOS:000281518100018
PM 20605212
ER
PT J
AU Nikitakis, N
Arvanitidou, I
Vlachodimitropoulos, D
Gutkind, JS
Sklavounou, A
AF Nikitakis, N.
Arvanitidou, I.
Vlachodimitropoulos, D.
Gutkind, J. S.
Sklavounou, A.
TI pS6k and ki-67 expression in oral premalignancy: An immunohistochemical
study
SO ORAL DISEASES
LA English
DT Meeting Abstract
C1 [Nikitakis, N.; Arvanitidou, I.] Univ Athens, Sch Dent, Dept Oral Pathol & Med, Athens 11528, Greece.
[Vlachodimitropoulos, D.] Univ Athens, Sch Med, Lab Forens Med & Toxicol, Athens 11528, Greece.
[Gutkind, J. S.] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
RI Gutkind, J. Silvio/A-1053-2009
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1354-523X
J9 ORAL DIS
JI Oral Dis.
PD SEP
PY 2010
VL 16
IS 6
BP 525
EP 525
PG 1
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 643HZ
UT WOS:000281287500051
ER
PT J
AU Tang, JS
Kiyatkin, EA
AF Tang, Jeremy S.
Kiyatkin, Eugene A.
TI Fluctuations in brain temperature induced by lypopolysaccharides Central
and peripheral contributions
SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
LA English
DT Article
DE brain; muscle and skin temperatures; hypothalamus; metabolic activation;
vasoconstriction; vasodilatation; rats
ID BROWN ADIPOSE-TISSUE; INTRAVENOUS LIPOPOLYSACCHARIDE;
AMBIENT-TEMPERATURE; GENE-EXPRESSION; OLD RATS; FEVER; THERMOGENESIS;
MECHANISM; INFECTION; RESPONSES
AB In this study, we examined changes in central (anterior-preoptic hypothalamus) and peripheral (temporal muscle and facial skin) temperatures in freely moving rats following intravenous administration of bacterial lipopolysaccharides (LPS) at low doses (1 and 10 mu g/kg) at thermoneutral conditions (28 degrees C). Recordings were made with high temporal resolution (5-s bin) and the effects of LPS were compared with those induced by a tail-pinch, a standard arousing somato-sensory stimulus. At each dose, LPS moderately elevated brain, muscle and skin temperatures. In contrast to rapid, monophasic and relatively short hyperthermic responses induced by a tail-pinch, LPS-induced increases in brain and muscle temperatures occurred with similar to 40 min onset latencies, showed three not clearly defined phases, were slightly larger with the 10 mu m/kg dose and maintained for the entire 4-hour post-injection recording duration. Based on dynamics of brain-muscle and skin-muscle temperature differentials, it appears that the hyperthermic response induced by LPS at the lowest dose originates from enhanced peripheral heat production, with no evidence of brain metabolic activation and skin vasoconstriction. While peripheral heat production also appears to determine the first phase of brain and body temperature elevation with LPS at 10 mu g/kg, a further prolonged increase in brain-muscle differentials (onset at similar to 100 min) suggests metabolic brain activation as a factor contributing to brain and body hyperthermia. At this dose, skin temperature increase was weaker than in temporal muscle, suggesting vasoconstriction as another contributor to brain/body hyperthermia. Therefore, although both LPS at low doses and salient sensory stimuli moderately increase brain and body temperatures, these hyperthermic responses have important qualitative differences, reflecting unique underlying mechanisms.
C1 [Tang, Jeremy S.; Kiyatkin, Eugene A.] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA.
RP Kiyatkin, EA (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA.
EM ekiyatki@intra.nida.nih.gov
FU NIH, NIDA
FX This research was supported by the Intramural Research Program of the
NIH, NIDA. We thank Drs. Andrey A. Romanovsky and Clark M. Blatteis for
helpful comments on the issues examined and discussed in this report.
NR 45
TC 3
Z9 3
U1 0
U2 2
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1942-0900
J9 OXID MED CELL LONGEV
JI Oxidative Med. Cell. Longev.
PD SEP-OCT
PY 2010
VL 3
IS 5
BP 332
EP 341
DI 10.4161/oxim.3.5.13184
PG 10
WC Cell Biology
SC Cell Biology
GA 716TI
UT WOS:000286996000007
PM 21150339
ER
PT J
AU Whitcomb, BW
Bodach, SD
Mumford, SL
Perkins, NJ
Trevisan, M
Wactawski-Wende, J
Liu, AY
Schisterman, EF
AF Whitcomb, Brian W.
Bodach, Sara D.
Mumford, Sunni L.
Perkins, Neil J.
Trevisan, Maurizio
Wactawski-Wende, Jean
Liu, Aiyi
Schisterman, Enrique F.
TI Ovarian function and cigarette smoking
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE BioCycle Study; smoking; menstrual cycle; sex hormones; oestradiol;
progesterone; SHBG; FSH; luteinising hormone; fertility
ID FOLLICLE-STIMULATING-HORMONE; MENSTRUAL-CYCLE LENGTH; SELF-REPORTED
SMOKING; PREMENOPAUSAL WOMEN; MENOPAUSAL TRANSITION; LONGITUDINAL DATA;
OXIDATIVE STRESS; REPRODUCTIVE-AGE; ESTRADIOL; PREDICTORS
AB P>Whitcomb BW, Bodach SD, Mumford SL, Perkins NJ, Trevisan M, Wactawski-Wende J, Liu A, Schisterman F. Ovarian function and cigarette smoking. Paediatric and Perinatal Epidemiology 2010.
Cigarette smoking has been implicated in reproductive outcomes including delayed conception, but mechanisms underlying these associations remain unclear. One potential mechanism is the effect of cigarette smoking on reproductive hormones; however, studies evaluating associations between smoking and hormone levels are complicated by variability of hormones and timing of specimen collection. We evaluated smoking among women participating in the BioCycle Study, a longitudinal study of menstrual cycle function in healthy, premenopausal, regularly menstruating women (n = 259). Fertility monitors were used to help guide timing of specimen collection. Serum levels of oestradiol, progesterone, follicle-stimulating hormone (FSH), luteinising hormone (LH) and total sex-hormone binding globulin (SHBG) across phases of the menstrual cycle were compared between smokers and non-smokers.
We observed statistically significant phase-specific differences in hormone levels between smokers and non-smokers. Compared with non-smokers, smokers had higher levels of FSH in the early follicular phase and higher LH at menses after adjusting for potential confounding factors of age, race, body mass index, parity, vigorous exercise, and alcohol and caffeine intake through inverse probability of treatment weights. No statistically significant differences were observed for oestradiol, progesterone or SHBG. These phase-specific differences in levels of LH and FSH in healthy, regularly menstruating women who are current smokers compared with non-smokers reflect one mechanism by which smoking may influence fertility and reproductive health.
C1 [Whitcomb, Brian W.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01003 USA.
[Whitcomb, Brian W.; Bodach, Sara D.; Mumford, Sunni L.; Perkins, Neil J.; Liu, Aiyi; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA.
[Bodach, Sara D.] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
[Trevisan, Maurizio; Wactawski-Wende, Jean] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
[Trevisan, Maurizio] Univ Nevada Hlth Sci Syst, Las Vegas, NV USA.
RP Whitcomb, BW (reprint author), 408 Arnold House,715 N Pleasant St, Amherst, MA 01003 USA.
EM bwhitcomb@schoolph.umass.edu
RI Perez , Claudio Alejandro/F-8310-2010;
OI Perez , Claudio Alejandro/0000-0001-9688-184X; Perkins,
Neil/0000-0002-6802-4733; Liu, Aiyi/0000-0002-6618-5082; Schisterman,
Enrique/0000-0003-3757-641X
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health
FX The authors would like to acknowledge the non-author members of the
BioCycle Study team at the University at Buffalo, whose great efforts
were essential to the happiness of the BioCycle Study participants and
to the success of the research. The BioCycle Study, along with this
research, was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health.
NR 45
TC 17
Z9 17
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-5022
EI 1365-3016
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD SEP
PY 2010
VL 24
IS 5
BP 433
EP 440
DI 10.1111/j.1365-3016.2010.01131.x
PG 8
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 632WO
UT WOS:000280460300004
PM 20670224
ER
PT J
AU Schneider, JS
Elm, JJ
Parashos, SA
Ravina, BM
Galpern, WR
AF Schneider, Jay S.
Elm, Jordan J.
Parashos, Sotirios A.
Ravina, Bernard M.
Galpern, Wendy R.
CA NET-PD Invest
TI Predictors of cognitive outcomes in early Parkinson disease patients:
The National Institutes of Health Exploratory Trials in Parkinson
Disease (NET-PD) experience
SO PARKINSONISM & RELATED DISORDERS
LA English
DT Article
DE Cognition; Parkinson's disease; RBANS; FAB
ID FRONTAL ASSESSMENT BATTERY; ALZHEIMERS-DISEASE; WORKING-MEMORY;
CLINICAL-TRIAL; FAB; DYSFUNCTION; IMPAIRMENT; DEMENTIA; OBJECT
AB Cognitive dysfunction is an important aspect of Parkinson disease (PD) and is increasingly being examined in various large scale PD clinical studies. However, the sensitivity of some of the cognitive measures used for detecting change in cognitive status in early PD patients is not known nor is the relationship between cognitive outcome measures and other motor and non-motor disease characteristics and various demographic parameters in early PD patients. The current analysis of the NET-PD cohort (i.e., untreated patients) was undertaken to: 1) assess which (if any) baseline demographic parameters correlate with baseline cognitive measures and any potential change in cognitive measures over the 12-18 months evaluation period; 2) assess the extent to which cognitive measures employed (i.e., Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Frontal Assessment Battery (FAB) and Letter-Number Sequencing) are sensitive to change over time; 3) examine whether initiation of symptomatic therapy is associated with change in cognitive status. At baseline, NET-PD subjects had no significant impairment on the assessments employed. Only education and age were significant predictors of cognitive score at baseline. None of the summary measures were indicative of change in cognitive status over the 12-18 months of study. These results suggest either the cognitive domains examined are not affected in the population examined or that more sensitive measures of cognition than those currently employed may need to be considered for use in a large trial setting in which an early, highly educated PD population is studied. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Schneider, Jay S.] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA.
[Elm, Jordan J.] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA.
[Parashos, Sotirios A.] Struthers Parkinsons Ctr, Golden, MN 55427 USA.
[Ravina, Bernard M.] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA.
[Galpern, Wendy R.] NINDS, Off Clin Res, NIH, Bethesda, MD 20892 USA.
RP Schneider, JS (reprint author), Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, 1020 Locust St,521 JAH, Philadelphia, PA 19107 USA.
EM jay.schneider@jefferson.edu
FU National Institute of Neurological Disorders and Stroke, National
Institutes of Health [U01NS043127, U01NS043128, U10NS44415, 44555]
FX This study was supported by the National Institute of Neurological
Disorders and Stroke, National Institutes of Health (grants U01NS043127,
U01NS043128, and U10NS44415 through 44555). The authors acknowledge the
NET-PD investigators, coordinators and study sites for providing the
data that were analyzed in this study.
NR 30
TC 7
Z9 7
U1 2
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8020
J9 PARKINSONISM RELAT D
JI Parkinsonism Relat. Disord.
PD SEP
PY 2010
VL 16
IS 8
BP 507
EP 512
DI 10.1016/j.parkreldis.2010.06.001
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 665FE
UT WOS:000283019800005
PM 20598621
ER
PT J
AU Okun, MS
Siderowf, A
Nutt, JG
O'Conner, GT
Bloem, BR
Olmstead, EM
Guttman, M
Simuni, T
Cheng, E
Cohen, EV
Parashos, S
Marsh, L
Malaty, IA
Giladi, N
Schmidt, P
Oberdorf, J
AF Okun, Michael S.
Siderowf, Andrew
Nutt, John G.
O'Conner, Gerald T.
Bloem, Bastiaan R.
Olmstead, Elaine M.
Guttman, Mark
Simuni, Tanya
Cheng, Eric
Cohen, Elaine V.
Parashos, Sotirios
Marsh, Laura
Malaty, Irene A.
Giladi, Nir
Schmidt, Peter
Oberdorf, Joyce
TI Piloting the NPF data-driven quality improvement initiative
SO PARKINSONISM & RELATED DISORDERS
LA English
DT Article
DE Parkinson's disease; Care; Treatment; Economic; Database
ID PARKINSONS-DISEASE
AB Objective: To pilot a data-driven quality care program in National Parkinson Foundation (NPF) Centers of Excellence.
Background: Evidence from comparative effectiveness research (CER) can be used to guide decisions regarding health care and to improve quality and efficiency of care. We propose to develop the infrastructure required to conduct CER across an extensive network of NPF Centers of Excellence.
Methods: We present the staged planning for a pilot study which will demonstrate the development and implementation of the infrastructure that will be needed for a large standardized patient-centered, clinical practice database for PD. This database will support CER and drive quality improvement studies.
Results: We describe the infrastructure for the ongoing pilot feasibility testing in a subset of six NPF Centers of Excellence, and we discuss the impact that the data (available in 2010) could have in guiding PD management.
Conclusion: This preliminary experience will facilitate the longitudinal tracking of therapies and of outcomes in PD clinical practice. Further, we are hopeful that the information will provide insight into PD that will extend beyond the clinical trials population (the population included in most available PD databases). This prospective standardized real-world multi-center clinical practice database will aim to identify positive health outcomes associated with treatment approaches, and to identify variations in clinical outcomes that may suggest improvements in best clinical practice patterns. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Okun, Michael S.; Malaty, Irene A.] Univ Florida, Dept Neurol, Natl Parkinson Fdn,Ctr Excellence, Movement Disorders Ctr,McKnight Brain Inst, Gainesville, FL 32611 USA.
[Siderowf, Andrew] Univ Penn, Dept Neurol, Natl Parkinson Fdn,Ctr Excellence, Educ & Clin Ctr,NIH Udall Ctr,VA Parkinson Dis Re, Philadelphia, PA 19104 USA.
[Nutt, John G.] Oregon Hlth & Sci Univ, VA Parkinson Dis Res, Natl Parkinson Fdn,Ctr Excellence, Educ & Clin Ctr, Portland Va, OR USA.
[O'Conner, Gerald T.; Olmstead, Elaine M.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
[Bloem, Bastiaan R.] Radboud Univ Nijmegen, Med Ctr, Natl Parkinson Fdn,Ctr Excellence, Donders Inst Brain Cognit & Behav,Dept Neurol, Nijmegen, Netherlands.
[Guttman, Mark] Univ Toronto, Dept Med, Div Neurol, Natl Parkinson Fdn,Ctr Excellence, Toronto, ON, Canada.
[Simuni, Tanya] Northwestern Univ, Dept Neurol, Natl Parkinson Fdn,Ctr Excellence, Parkinsons Dis & Movement Disorders Ctr, Chicago, IL USA.
[Cheng, Eric] VA Greater Los Angeles Healthcare Syst, VA Parkinsons Dis Res Educ & Clin Ctr, Los Angeles, CA USA.
[Cohen, Elaine V.] NY Univ, New York Univ Pk, Natl Parkinson Fdn,Ctr Excellence, Dept Neurol, New York, NY USA.
[Cohen, Elaine V.] NY Univ, Movement Disorder Ctr, New York, NY USA.
[Parashos, Sotirios] Struthers Parkinsons Ctr, Natl Parkinson Fdn,Ctr Excellence, Minneapolis, MN USA.
[Marsh, Laura] Menninger Dept Psychiat & Behav Sci, Houston, TX USA.
[Giladi, Nir] Tel Aviv Univ, Sackler Sch Med, Tel Aviv Sourasky Med Ctr, Movement Disorders Unit,Natl Parkinson Fdn,Ctr Ex, IL-69978 Tel Aviv, Israel.
[Schmidt, Peter; Oberdorf, Joyce] Natl Parkinson Fdn, Miami, FL USA.
RP Okun, MS (reprint author), Univ Florida, Dept Neurol, Natl Parkinson Fdn,Ctr Excellence, Movement Disorders Ctr,McKnight Brain Inst, 100 S Newell Dr,Rm L3-101 3rd Floor Neurol, Gainesville, FL 32611 USA.
EM okun@neurology.ufl.edu
RI Bloem, Bastiaan/E-3812-2010; Bloem, B.R./H-8013-2014
OI Okun, Michael/0000-0002-6247-9358;
FU National Parkinson Foundation
FX Funding was provided for this project through the National Parkinson
Foundation, and we thank Sharon Metz for organizational support.
NR 12
TC 15
Z9 15
U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8020
J9 PARKINSONISM RELAT D
JI Parkinsonism Relat. Disord.
PD SEP
PY 2010
VL 16
IS 8
BP 517
EP 521
DI 10.1016/j.parkreldis.2010.06.005
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA 665FE
UT WOS:000283019800007
PM 20609611
ER
PT J
AU Rogers, BB
Momirova, V
Dizon-Townson, D
Wenstrom, K
Samuels, P
Sibai, B
Spong, C
Caritis, SN
Sorokin, Y
Miodovnik, M
O'Sullivan, MJ
Conway, D
Wapner, RJ
AF Rogers, Beverly Barton
Momirova, Valerija
Dizon-Townson, Donna
Wenstrom, Katharine
Samuels, Philip
Sibai, Baha
Spong, Catherine
Caritis, Steve N.
Sorokin, Yoram
Miodovnik, Menachem
O'Sullivan, Mary J.
Conway, Deborah
Wapner, Ronald J.
CA Eunice Kennedy Shriver Natl Inst H
TI Avascular Villi, Increased Syncytial Knots, and Hypervascular Villi Are
Associated with Pregnancies Complicated by Factor V Leiden Mutation
SO PEDIATRIC AND DEVELOPMENTAL PATHOLOGY
LA English
DT Article
DE avascular; chorangiosis; Leiden; pathology; placenta; thrombophilia
ID PLACENTAL REACTION PATTERNS; THROMBOPHILIA; LESIONS; PATHOLOGY;
REPRODUCIBILITY; NOSOLOGY; WOMEN
AB There is controversy about whether pathologic abnormalities are associated with pregnancies complicated by factor V Leiden (FVL) mutation. The purpose of this study was to evaluate 105 placentas delivered to mothers heterozygous for FVL mutation to determine if there are pathologic changes suggestive of hypoxia or thrombosis, which correlate with mutation status. We examined placentas obtained as part of a prospective study of 5188 pregnancies analyzed for the presence of FVL mutation in either the mother or the infant. One hundred five placentas from mothers heterozygous for the mutation were compared with 225 controls matched for maternal age, race, and geographic site. Of the 330 pregnancies, 50 infants were FVL mutation heterozygotes. Maternal FVL heterozygote status was associated with more frequent increased numbers of syncytial knots (13% vs 4%); the difference remained significant after controlling for hypertension, preeclampsia, small-for-gestational-age infants, and delivery prior to 35 weeks of gestation (odds ratio 3.6, 95% confidence interval 1.5-8.7, P = 0.004). Maternal FVL heterozygotes had more hypervascular villi (10% vs 3%), with significance retained controlling for delivery route (odds ratio 3.4, 95% confidence ratio 1.2-9.4, P = 0.018). Placentas from infants heterozygous for FVL mutation had more avascular villi than controls (odds ratio 2.9, 95% confidence interval 1.5-5.6, P = 0.001). Fetal or maternal FVL heterozygosity was not associated with infarcts, small-for-gestational-age placentas, or fetal thrombotic vasculopathy. This analysis demonstrates that pathologic findings associated with placental hypoxia, specifically focal avascular villi, increased numbers of syncytial knots, and hypervascular villi, also correlate with FVL heterozygosity in infants or mothers.
C1 [Rogers, Beverly Barton] Childrens Med Ctr, Dept Pathol, Dallas, TX 75235 USA.
[Momirova, Valerija] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Dizon-Townson, Donna] Univ Utah, Dept Obstet, Salt Lake City, UT USA.
[Dizon-Townson, Donna] Univ Utah, Dept Gynecol, Salt Lake City, UT USA.
[Wenstrom, Katharine] Univ Alabama, Birmingham, AL USA.
[Samuels, Philip] Univ Pittsburgh, Pittsburgh, PA USA.
[Sibai, Baha] Ohio State Univ, Columbus, OH 43210 USA.
[Spong, Catherine] Univ Tennessee, Memphis, TN USA.
[Caritis, Steve N.] Wayne State Univ, Detroit, MI USA.
[Sorokin, Yoram] Univ Cincinnati, Cincinnati, OH USA.
[Miodovnik, Menachem] Univ Miami, Miami, FL USA.
[O'Sullivan, Mary J.] Univ Texas San Antonio, San Antonio, TX USA.
[Conway, Deborah] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
[Wapner, Ronald J.] George Washington Univ, Ctr Biostat, Washington, DC USA.
RP Rogers, BB (reprint author), Childrens Med Ctr, Dept Pathol, Dallas, TX 75235 USA.
EM beverly.rogers@childrens.com
RI Samuels, Philip/E-4011-2011;
OI caritis, steve/0000-0002-2169-0712
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [HD27860, HD36801, HD27917, HD21414, HD27861, HD27869,
HD27905, HD34208, HD34116, HD21410, HD27915, HD34136, HD34122, HD34210]
FX This work was supported by grants from the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (HD27860,
HD36801, HD27917, HD21414, HD27861, HD27869, HD27905, HD34208, HD34116,
HD21410, HD27915, HD34136, HD34122, HD34210).
NR 22
TC 9
Z9 10
U1 0
U2 2
PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS
PI LAWRENCE
PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA
SN 1093-5266
J9 PEDIATR DEVEL PATHOL
JI Pediatr. Dev. Pathol.
PD SEP-OCT
PY 2010
VL 13
IS 5
BP 341
EP 347
DI 10.2350/09-05-0657-OA.1
PG 7
WC Pathology; Pediatrics
SC Pathology; Pediatrics
GA 692XW
UT WOS:000285190200001
PM 20121426
ER
PT J
AU Beaty, O
Berg, S
Blaney, S
Malogolowkin, M
Krailo, M
Knight, R
Schaiquevich, P
Stewart, C
Chen, ZJ
Nelson, M
Voss, S
Ivy, SP
Adamson, PC
AF Beaty, Orren, III
Berg, Stacey
Blaney, Susan
Malogolowkin, Marcio
Krailo, Mark
Knight, Ronald
Schaiquevich, Paula
Stewart, Clinton
Chen, Zhengjia
Nelson, Marvin
Voss, Stephan
Ivy, S. Percy
Adamson, Peter C.
TI A Phase II Trial and Pharmacokinetic Study of Oxaliplatin in Children
With Refractory Solid Tumors: A Children's Oncology Group Study
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE oxaliplatin; pediatric; pharmacokinetics; phase II study; refractory
solid tumor
ID METASTATIC COLORECTAL-CANCER; CARCINOMA CELL-LINES; ANTITUMOR-ACTIVITY;
CARRIER LIGAND; FOLINIC ACID; FLUOROURACIL-LEUCOVORIN; PLATINUM
RESISTANCE; CLINICAL-TRIAL; DNA-ADDUCTS; L-OHP
AB Background. Platinating agents are used in the treatment of a spectrum of childhood cancers. Oxaliplatin, a third generation platinum compound, may provide less toxicity and be more effective. A phase 2 study was performed to estimate the response rate to single agent oxaliplatin in patients with refractory pediatric solid tumors, and to further describe the toxicities and pharmacokinetics of the drug in this population. Patients and Methods. Subjects, <= 21 years of age at original diagnosis, received oxaliplatin (130 mg/m(2)) intravenously every 21 days. Prior platinum exposure was acceptable. Histologies included: Ewing sarcoma/peripheral PNET, osteosarcoma, rhabdomyosarcoma, neuroblastoma, high and low grade astrocytoma, brain stem glioma, ependymoma, hepatoblastoma and selected rare tumors. A two-stage design, enrolling 10 + 10 subjects, was used for each disease stratum. Limited sampling pharmacokinetic studies were performed. Results. Of 124 eligible subjects (75 males), 113 were evaluable for response and 69 (62%) had received platinum previously. Only one objective response was observed, a partial response in a 6-year-old child with ependymoma. An additional 13 subjects with various other solid tumors had stable disease, receiving a median (range) of 13.5 (2-17) cycles. Five subjects completed 17 treatment cycles. Thrombocytopenia was the most common toxicity observed. The median (range) terminal half-life and clearance for ultrafiltrable platinum were 293 (187-662 hr) and 14.0 (1.9-24.9 Uhr/m(2)), respectively (n = 49). Conclusions. Although reasonably well tolerated, oxaliplatin administered as a single agent has limited activity in pediatric patients with relapsed or refractory solid tumors. Pediatr Blood Cancer. (C) 2010;55:440-445. 2010 Wiley-Liss, Inc.
C1 [Beaty, Orren, III] Mission Hosp Inc, Zeis Childrens Canc Ctr, Asheville, NC 28803 USA.
[Berg, Stacey; Blaney, Susan] Texas Childrens Canc Ctr, Houston, TX USA.
[Malogolowkin, Marcio; Nelson, Marvin] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Krailo, Mark; Chen, Zhengjia] Childrens Oncol Grp, Arcadia, CA USA.
[Knight, Ronald] Sanofi Aventis, Bridgewater, MA USA.
[Schaiquevich, Paula; Stewart, Clinton] St Jude Childrens Hosp, Memphis, TN 38105 USA.
[Voss, Stephan] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Voss, Stephan] Childrens Hosp, Boston, MA 02115 USA.
[Ivy, S. Percy] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Adamson, Peter C.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
RP Beaty, O (reprint author), Mission Hosp Inc, Zeis Childrens Canc Ctr, Vanderbilt Pk Dr, Asheville, NC 28803 USA.
EM orren.beaty@msj.org
FU National Cancer Institute [U10 CA98543, U10CA98413]; Sanofi Aventis
FX Grant sponsor: National Cancer Institute Grants; Grant numbers: U10
CA98543, U10CA98413; Grant sponsor: Sanofi Aventis.
NR 40
TC 24
Z9 24
U1 1
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD SEP
PY 2010
VL 55
IS 3
BP 440
EP 445
DI 10.1002/pbc.22544
PG 6
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 632PV
UT WOS:000280438600009
PM 20658614
ER
PT J
AU Shomaker, LB
Tanofsky-Kraff, M
Young-Hyman, D
Han, JC
Yanoff, LB
Brady, SM
Yanovski, SZ
Yanovski, JA
AF Shomaker, Lauren B.
Tanofsky-Kraff, Marian
Young-Hyman, Deborah
Han, Joan C.
Yanoff, Lisa B.
Brady, Sheila M.
Yanovski, Susan Z.
Yanovski, Jack A.
TI Psychological symptoms and insulin sensitivity in adolescents
SO PEDIATRIC DIABETES
LA English
DT Article
DE adolescents; children; depression; general psychopathology; insulin
sensitivity
ID METABOLIC SYNDROME; DEPRESSIVE SYMPTOMS; CARDIOVASCULAR-DISEASE;
GLUCOSE-METABOLISM; PUBERTAL CHANGES; RISK-FACTORS; CHILDREN;
RESISTANCE; PREVALENCE; SECRETION
AB Purpose: Symptoms of psychological distress have been linked to low insulin sensitivity in adults; however, little is known about this relationship in pediatric samples. We therefore examined symptoms of depression and anxiety in relation to insulin sensitivity in adolescents.
Methods: Participants were 136 non-treatment-seeking, healthy adolescents (53.2% female) of all weight strata (BMI-z = 1.08 +/- 1.08) between the ages of 12 and 18 years (M = 15.16,SD = 1.55). Adolescents completed questionnaire measures assessing depression and anxiety symptoms. Fasting blood samples for serum insulin and plasma glucose were obtained to estimate insulin sensitivity with the quantitative insulin sensitivity check index. Fat mass and fat-free mass were measured with air displacement plethysmography or dual-energy X-ray absorptiometry.
Results: Depressive symptoms were associated with higher fasting insulin and decreased insulin sensitivity even after controlling for fat mass, fat-free mass, height, age, pubertal status, race, and sex (p < 0.01).
Conclusions: As has been described for adults, depressive symptoms are associated with low insulin sensitivity among healthy adolescents. Further experimental and prospective studies are required to determine the directionality of this link.
C1 [Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Growth & Obes, Program Dev Endocrinol, Dept Hlth & Human Serv,Hatfield Clin Res Ctr,NIH, Bethesda, MD 20892 USA.
[Shomaker, Lauren B.; Tanofsky-Kraff, Marian] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA.
[Yanovski, Susan Z.] NIDDK, Div Digest Dis & Nutr, DHHS, NIH, Bethesda, MD 20892 USA.
RP Yanovski, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Growth & Obes, Program Dev Endocrinol, Dept Hlth & Human Serv,Hatfield Clin Res Ctr,NIH, 9000 Rockville Pike,Room 1E-3330,MSC 1103, Bethesda, MD 20892 USA.
EM jy15i@nih.gov
OI Yanovski, Jack/0000-0001-8542-1637
FU Intramural NIH HHS [Z99 HD999999, ZIA HD000641-14]
NR 41
TC 20
Z9 21
U1 1
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1399-543X
J9 PEDIATR DIABETES
JI Pediatr. Diabetes
PD SEP
PY 2010
VL 11
IS 6
BP 417
EP 423
DI 10.1111/j.1399-5448.2009.00606.x
PG 7
WC Endocrinology & Metabolism; Pediatrics
SC Endocrinology & Metabolism; Pediatrics
GA 643HG
UT WOS:000281285600008
PM 19912553
ER
PT J
AU Topaloglu, R
Vilboux, T
Tinloy, B
Coskun, T
Gunay-Aygun, M
Jeong, A
Bakkaloglu, A
Besbas, N
Ozen, S
Sivri, S
Kleta, R
Gahl, WA
AF Topaloglu, R.
Vilboux, T.
Tinloy, B.
Coskun, T.
Gunay-Aygun, M.
Jeong, A.
Bakkaloglu, A.
Besbas, N.
Ozen, S.
Sivri, S.
Kleta, R.
Gahl, W. A.
TI Additional Molecular Findings in Turkish Cystinosis Patients
SO PEDIATRIC NEPHROLOGY
LA English
DT Meeting Abstract
C1 [Topaloglu, R.; Coskun, T.; Bakkaloglu, A.; Besbas, N.; Ozen, S.; Sivri, S.] Hacettepe Univ, Fac Med, TR-06100 Ankara, Turkey.
[Vilboux, T.; Tinloy, B.; Gunay-Aygun, M.; Jeong, A.; Gahl, W. A.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Kleta, R.] UCL, Dept Med, London, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0931-041X
J9 PEDIATR NEPHROL
JI Pediatr. Nephrol.
PD SEP
PY 2010
VL 25
IS 9
MA 630
BP 1921
EP 1921
PG 1
WC Pediatrics; Urology & Nephrology
SC Pediatrics; Urology & Nephrology
GA 630BU
UT WOS:000280247200659
ER
PT J
AU Szabo, T
Ambrus, L
Czifra, G
Kedei, N
Blumberg, PM
Biro, T
AF Szabo, T.
Ambrus, Li.
Czifra, G.
Kedei, N.
Blumberg, P. M.
Biro, T.
TI Modulation of Transient Receptor Potential Canoninal-6 (TRPC6) Ion
Channel in Cultured Podocytes
SO PEDIATRIC NEPHROLOGY
LA English
DT Meeting Abstract
C1 [Szabo, T.] Univ Debrecen, Dept Pediat, MHSC, Debrecen, Hungary.
[Ambrus, Li.; Czifra, G.; Biro, T.] Univ Debrecen, Dept Physiol, MHSC, Debrecen, Hungary.
[Kedei, N.; Blumberg, P. M.] Natl Inst Hlth, MMTP, LCBC, NCI, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0931-041X
J9 PEDIATR NEPHROL
JI Pediatr. Nephrol.
PD SEP
PY 2010
VL 25
IS 9
MA 955
BP 1986
EP 1986
PG 1
WC Pediatrics; Urology & Nephrology
SC Pediatrics; Urology & Nephrology
GA 630BU
UT WOS:000280247200984
ER
PT J
AU Donohoe, M
Cintas, H
AF Donohoe, Maureen
Cintas, Holly
TI Ankle Strength and Functional Limitations in Children and Adolescents
With Type I Osteogenesis Imperfecta
SO PEDIATRIC PHYSICAL THERAPY
LA English
DT Editorial Material
C1 [Donohoe, Maureen] Alfred I duPont Hosp Children, Wilmington, DE USA.
[Cintas, Holly] NIH, Bethesda, MD 20892 USA.
RP Donohoe, M (reprint author), Alfred I duPont Hosp Children, Wilmington, DE USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0898-5669
J9 PEDIATR PHYS THER
JI Pediatr. Phys. Ther.
PD FAL
PY 2010
VL 22
IS 3
BP 295
EP 295
DI 10.1097/PEP.0b013e3181eb6d35
PG 1
WC Pediatrics; Rehabilitation
SC Pediatrics; Rehabilitation
GA V21SE
UT WOS:000208226500011
PM 20699779
ER
PT J
AU Stoll, BJ
Hansen, NI
Bell, EF
Shankaran, S
Laptook, AR
Walsh, MC
Hale, EC
Newman, NS
Schibler, K
Carlo, WA
Kennedy, KA
Poindexter, BB
Finer, NN
Ehrenkranz, RA
Duara, S
Sanchez, PJ
O'Shea, TM
Goldberg, RN
Van Meurs, KP
Faix, RG
Phelps, DL
Frantz, ID
Watterberg, KL
Saha, S
Das, A
Higgins, RD
AF Stoll, Barbara J.
Hansen, Nellie I.
Bell, Edward F.
Shankaran, Seetha
Laptook, Abbot R.
Walsh, Michele C.
Hale, Ellen C.
Newman, Nancy S.
Schibler, Kurt
Carlo, Waldemar A.
Kennedy, Kathleen A.
Poindexter, Brenda B.
Finer, Neil N.
Ehrenkranz, Richard A.
Duara, Shahnaz
Sanchez, Pablo J.
O'Shea, T. Michael
Goldberg, Ronald N.
Van Meurs, Krisa P.
Faix, Roger G.
Phelps, Dale L.
Frantz, Ivan D.
Watterberg, Kristi L.
Saha, Shampa
Das, Abhik
Higgins, Rosemary D.
CA Eunice Kennedy Shriver Natl Inst
TI Neonatal Outcomes of Extremely Preterm Infants From the NICHD Neonatal
Research Network
SO PEDIATRICS
LA English
DT Article
DE extremely low gestation; very low birth weight; morbidity; death
ID BIRTH-WEIGHT OUTCOMES; NATIONAL-INSTITUTE; CHILD-HEALTH;
BRONCHOPULMONARY DYSPLASIA; TREATMENT DECISIONS; GESTATIONAL-AGE;
INTENSIVE-CARE; RESOURCE USE; MORBIDITY; MORTALITY
AB OBJECTIVE: This report presents data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network on care of and morbidity and mortality rates for very low birth weight infants, according to gestational age (GA).
METHODS: Perinatal/neonatal data were collected for 9575 infants of extremely low GA (22-28 weeks) and very low birth weight (401-1500 g) who were born at network centers between January 1, 2003, and December 31, 2007.
RESULTS: Rates of survival to discharge increased with increasing GA (6% at 22 weeks and 92% at 28 weeks); 1060 infants died at <= 12 hours, with most early deaths occurring at 22 and 23 weeks (85% and 43%, respectively). Rates of prenatal steroid use (13% and 53%, respectively), cesarean section (7% and 24%, respectively), and delivery room intubation (19% and 68%, respectively) increased markedly between 22 and 23 weeks. Infants at the lowest GAs were at greatest risk for morbidities. Overall, 93% had respiratory distress syndrome, 46% patent ductus arteriosus, 16% severe intraventricular hemorrhage, 11% necrotizing enterocolitis, and 36% late-onset sepsis. The new severity-based definition of bronchopulmonary dysplasia classified more infants as having bronchopulmonary dysplasia than did the traditional definition of supplemental oxygen use at 36 weeks (68%, compared with 42%). More than one-half of infants with extremely low GAs had undetermined retinopathy status at the time of discharge. Center differences in management and outcomes were identified.
CONCLUSION: Although the majority of infants with GAs of >= 24 weeks survive, high rates of morbidity among survivors continue to be observed. Pediatrics 2010; 126: 443-456
C1 [Stoll, Barbara J.; Hale, Ellen C.] Emory Univ, Dept Pediat, Sch Med, Childrens Healthcare Atlanta, Atlanta, GA 30322 USA.
[Hansen, Nellie I.; Saha, Shampa] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
[Bell, Edward F.] Univ Iowa, Dept Pediat, Carver Coll Med, Iowa City, IA 52242 USA.
[Shankaran, Seetha] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA.
[Laptook, Abbot R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA.
[Walsh, Michele C.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
[Schibler, Kurt] Univ Cincinnati, Dept Pediat, Sch Med, Cincinnati, OH 45221 USA.
[Carlo, Waldemar A.] Univ Alabama, Sch Med, Div Neonatol, Birmingham, AL USA.
[Kennedy, Kathleen A.] Univ Texas Houston, Sch Med, Dept Pediat, Houston, TX USA.
[Poindexter, Brenda B.] Indiana Univ, Sch Med, Dept Pediat, Indianapolis, IN 46202 USA.
[Finer, Neil N.] Univ Calif San Diego, Dept Neonatol, Med Ctr, San Diego, CA 92103 USA.
[Ehrenkranz, Richard A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Duara, Shahnaz] Univ Miami, Dept Pediat, Miller Sch Med, Miami, FL 33152 USA.
[Sanchez, Pablo J.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
[O'Shea, T. Michael] Wake Forest Univ, Dept Pediat, Sch Med, Winston Salem, NC 27109 USA.
[Goldberg, Ronald N.] Duke Univ, Dept Pediat, Sch Med, Durham, NC 27706 USA.
[Van Meurs, Krisa P.] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA.
[Faix, Roger G.] Univ Utah, Sch Med, Dept Pediat, Div Neonatol, Salt Lake City, UT USA.
[Phelps, Dale L.] Univ Rochester, Sch Med & Dent, Dept Pediat, Rochester, NY 14642 USA.
[Frantz, Ivan D.] Floating Hosp Children, Div Newborn Med, Dept Pediat, Tufts Med Ctr, Boston, MA USA.
[Watterberg, Kristi L.] Univ New Mexico, Dept Pediat, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
[Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hu, Natl Inst Hlth Bethesda, Bethesda, MD USA.
RP Stoll, BJ (reprint author), Emory Univ, Dept Pediat, Sch Med, Childrens Healthcare Atlanta, Atlanta, GA 30322 USA.
FU National Institutes of Health; National Institutes of Health, National
Center for Research Resources [UL1 RR025008]
FX The National Institutes of Health provided grant support for the NRN
Generic Database Study (Recruitment 2003-2007). This study was supported
in part by PHS grant UL1 RR025008 from the Clinical and Translational
Science Award program, National Institutes of Health, National Center
for Research Resources.
NR 24
TC 729
Z9 775
U1 11
U2 63
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD SEP
PY 2010
VL 126
IS 3
BP 443
EP 456
DI 10.1542/peds.2009-2959
PG 14
WC Pediatrics
SC Pediatrics
GA 646JK
UT WOS:000281535700006
PM 20732945
ER
PT J
AU Miller, FG
Colloca, L
AF Miller, Franklin G.
Colloca, Luana
TI SEMIOTICS AND THE PLACEBO EFFECT
SO PERSPECTIVES IN BIOLOGY AND MEDICINE
LA English
DT Article
AB Despite substantial progress in elucidating its neurobiological mechanisms, theoretical understanding of the placebo effect is poorly developed. Application of the semiotic theory developed by the American philosopher Charles Peirce offers a promising account of placebo effects as involving the apprehension and response to signs. The semiotic approach dovetails with the various psychological mechanisms invoked to account for placebo effects, such as conditioning and expectation, and bridges the biological and cultural dimensions of this fascinating phenomenon.
C1 [Miller, Franklin G.; Colloca, Luana] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Miller, FG (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM fmiller@nih.gov
FU Clinical Center, NIH; National Center for Complementary and Alternative
Medicine
FX The opinions expressed are the views of the authors and do not
necessarily reflect the policy of the National Institutes of Health, the
Public Health Service, or the U.S. Department of Health and Human
Services. This research was supported by the Intramural Research Program
of the Clinical Center, NIH and the National Center for Complementary
and Alternative Medicine.
NR 15
TC 7
Z9 8
U1 1
U2 3
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
21218-4363 USA
SN 0031-5982
J9 PERSPECT BIOL MED
JI Perspect. Biol. Med.
PD FAL
PY 2010
VL 53
IS 4
BP 509
EP 516
PG 8
WC History & Philosophy Of Science; Medicine, Research & Experimental
SC History & Philosophy of Science; Research & Experimental Medicine
GA 662HX
UT WOS:000282799400003
PM 21037405
ER
PT J
AU Piatigorsky, J
AF Piatigorsky, Joram
TI REFLECTIONS ON BASIC SCIENCE
SO PERSPECTIVES IN BIOLOGY AND MEDICINE
LA English
DT Article
ID LENS CRYSTALLINS; CORNEAL CRYSTALLIN; TRANSGENIC MICE; GENE-EXPRESSION;
EYE LENS; EVOLUTION; PROMOTER; RECRUITMENT; NEUROSPORA; PROTEINS
AB After almost 50 years in science, I believe that there is an acceptable, often advantageous chasm between open-ended basic research free exploration without a practical destination and in which the original ideas may fade into new concepts and translational research or clinical research. My basic research on crystallins (proteins conferring the optical properties of the eye lens) led me down paths I never would have considered if I were conducting translational research. My investigations ranged from jellyfish to mice and resulted in the gene-sharing concept, which showed that the same protein can have distinct molecular functions depending upon its expression pattern and, conversely, that different proteins can serve similar functional roles. This essay portrays basic science as a creative narrative, comparable to literary and artistic endeavors. Preserving the autonomy of open-ended basic research and recognizing its artistic, narrative qualities will accelerate the development of innovative concepts, create a rich resource of information feeding translational research, and have a positive impact by attracting creative individuals to science.
C1 NEI, NIH, Mol & Dev Biol Lab, Bethesda, MD 20892 USA.
RP Piatigorsky, J (reprint author), NEI, NIH, Mol & Dev Biol Lab, 5635 Fishers Lane,Room 1127, Bethesda, MD 20892 USA.
EM joramp@nei.nih.gov
NR 37
TC 0
Z9 0
U1 0
U2 3
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
21218-4363 USA
SN 0031-5982
J9 PERSPECT BIOL MED
JI Perspect. Biol. Med.
PD FAL
PY 2010
VL 53
IS 4
BP 571
EP 583
PG 13
WC History & Philosophy Of Science; Medicine, Research & Experimental
SC History & Philosophy of Science; Research & Experimental Medicine
GA 662HX
UT WOS:000282799400008
PM 21037410
ER
PT J
AU Lencz, T
Robinson, DG
Napolitano, B
Sevy, S
Kane, JM
Goldman, D
Malhotra, AK
AF Lencz, Todd
Robinson, Delbert G.
Napolitano, Barbara
Sevy, Serge
Kane, John M.
Goldman, David
Malhotra, Anil K.
TI DRD2 promoter region variation predicts antipsychotic-induced weight
gain in first episode schizophrenia
SO PHARMACOGENETICS AND GENOMICS
LA English
DT Article
DE antipsychotic; dopamine; DRD2; pharmacogenetics; weight gain
ID D2 RECEPTOR GENE; 1ST-EPISODE SCHIZOPHRENIA; DOPAMINE; POLYMORPHISM;
RISPERIDONE; OLANZAPINE
AB Many antipsychotic medications carry a substantial liability for weight gain, and one mechanism common to all antipsychotics is binding to the dopamine D(2) receptor. We therefore examined the relationship between -141C Ins/Del (rs1799732), a functional promoter region polymorphism in DRD2, and antipsychotic-induced weight gain in 58 first episode schizophrenia patients enrolled in a randomized trial of risperidone versus olanzapine. Carriers of the deletion allele (n = 29) were compared with Ins/Ins homozygotes (noncarriers, n = 29) in a mixed model encompassing 10 weight measurements over 16 weeks. Deletion allele carriers showed significantly more weight gain after 6 weeks of treatment regardless of assigned medication. Although deletion carriers were prescribed higher doses of olanzapine (but not risperidone), dose did not seem to account for the genotype effects on weight gain. Given earlier evidence that deletion carriers show reduced symptom response to medication, additional study of appropriate treatment options for these patients seems warranted. Pharmacogenetics and Genomics 20: 569-572 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.
C1 [Lencz, Todd; Robinson, Delbert G.; Sevy, Serge; Kane, John M.; Malhotra, Anil K.] Zucker Hillside Hosp, Div Psychiat Res, Glen Oaks, NY 11004 USA.
[Lencz, Todd; Robinson, Delbert G.; Sevy, Serge; Kane, John M.; Malhotra, Anil K.] Ctr Psychiat Neurosci, Glen Oaks, NY USA.
[Napolitano, Barbara] Feinstein Inst Med Res, Biostat Unit, Glen Oaks, NY USA.
[Lencz, Todd; Robinson, Delbert G.; Sevy, Serge; Kane, John M.; Malhotra, Anil K.] Albert Einstein Coll Med, Dept Psychiat & Behav Sci, Bronx, NY 10467 USA.
[Goldman, David] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA.
RP Lencz, T (reprint author), Zucker Hillside Hosp, Div Psychiat Res, 75-59 263rd St, Glen Oaks, NY 11004 USA.
EM lencz@lij.edu
RI Goldman, David/F-9772-2010; Lencz, Todd/J-3418-2014
OI Goldman, David/0000-0002-1724-5405; Lencz, Todd/0000-0001-8586-338X
FU National Institute of Mental Health [K01 MH65580, R01 MH60004, P30
MH60575, K23 MH01760, P50 MH080173, K23 DA15541]; General Clinical
Research Center from the National Center for Research Resources [M01
RR18535]; NARSAD
FX This study was supported by grants from the National Institute of Mental
Health: K01 MH65580 (Dr Lencz), R01 MH60004 (Dr Robinson), P30 MH60575
(Dr Kane), K23 MH01760 and P50 MH080173 (Dr Malhotra), and K23 DA15541
(Dr Sevy), and by a General Clinical Research Center from the National
Center for Research Resources (M01 RR18535; PI: Kevin Tracey). This
study was also supported by NARSAD (Dr Malhotra).
NR 17
TC 30
Z9 35
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1744-6872
J9 PHARMACOGENET GENOM
JI Pharmacogenet. Genomics
PD SEP
PY 2010
VL 20
IS 9
BP 569
EP 572
DI 10.1097/FPC.0b013e32833ca24b
PG 4
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology
& Pharmacy
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology
& Pharmacy
GA 643KO
UT WOS:000281295500007
PM 20664489
ER
PT J
AU Pitkin, SL
Maguire, JJ
Bonner, TI
Davenport, AP
AF Pitkin, Sarah L.
Maguire, Janet. J.
Bonner, Tom I.
Davenport, Anthony P.
TI International Union of Basic and Clinical Pharmacology. LXXIV. Apelin
Receptor Nomenclature, Distribution, Pharmacology, and Function
SO PHARMACOLOGICAL REVIEWS
LA English
DT Review
ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENDOGENOUS INOTROPE APELIN;
PROTEIN-COUPLED RECEPTOR; ORPHAN 7-TRANSMEMBRANE RECEPTOR; SPONTANEOUSLY
HYPERTENSIVE-RATS; RIBONUCLEIC-ACID EXPRESSION; MESSENGER-RNA
EXPRESSION; MOUSE 3T3-L1 ADIPOCYTES; ISCHEMIC-HEART FAILURE; VASCULAR
SMOOTH-MUSCLE
AB A gene encoding a novel class a G-protein- coupled receptor was discovered in 1993 by homology cloning and was called APJ. It was designated an "orphan" receptor until 1998, when its endogenous ligand was identified and named apelin (for APJ endogenous ligand). Since this pairing, both apelin and its receptor have been found to have a widespread distribution in both the central nervous system and the periphery. A number of physiological and pathophysiological roles for the receptor have emerged, including regulation of cardiovascular function, fluid homeostasis, and the adipoinsular axis. This review outlines the official International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification nomenclature, designating the receptor protein as the apelin receptor, together with current knowledge of its pharmacology, distribution, and functions.
C1 [Pitkin, Sarah L.; Maguire, Janet. J.; Davenport, Anthony P.] Univ Cambridge, Clin Pharmacol Unit, Cambridge CB2 0QQ, England.
[Bonner, Tom I.] NIMH, Sect Funct Neurosci, Bethesda, MD 20892 USA.
RP Davenport, AP (reprint author), Univ Cambridge, Addenbrookes Hosp, Emerging Pharmacol Grp, Clin Pharmacol Unit,NC IUPHAR, Cambridge CB2 0QQ, England.
EM apd10@medschl.cam.ac.uk
OI Maguire, Janet/0000-0002-9254-7040; Davenport, Anthony
Peter/0000-0002-2096-3117
FU British Heart Foundation [PS/02/001, PG/09/050/27734, FS/06/017]
FX This work was supported by the British Heart Foundation [Grants
PS/02/001, PG/09/050/27734, FS/06/017].
NR 150
TC 53
Z9 60
U1 2
U2 7
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0031-6997
J9 PHARMACOL REV
JI Pharmacol. Rev.
PD SEP
PY 2010
VL 62
IS 3
BP 331
EP 342
DI 10.1124/pr.110.002949
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 639VR
UT WOS:000281004000001
PM 20605969
ER
PT J
AU Traynelis, SF
Wollmuth, LP
McBain, CJ
Menniti, FS
Vance, KM
Ogden, KK
Hansen, KB
Yuan, HJ
Myers, SJ
Dingledine, R
AF Traynelis, Stephen F.
Wollmuth, Lonnie P.
McBain, Chris J.
Menniti, Frank S.
Vance, Katie M.
Ogden, Kevin K.
Hansen, Kasper B.
Yuan, Hongjie
Myers, Scott J.
Dingledine, Ray
TI Glutamate Receptor Ion Channels: Structure, Regulation, and Function
SO PHARMACOLOGICAL REVIEWS
LA English
DT Review
ID METHYL-D-ASPARTATE; LIGAND-BINDING DOMAIN; LONG-TERM DEPRESSION;
DEPENDENT PROTEIN-KINASE; RAT HIPPOCAMPAL-NEURONS; EXCITATORY
AMINO-ACID; NR2B-CONTAINING NMDA-RECEPTORS; CA2+-PERMEABLE AMPA
RECEPTORS; GLUR6 KAINATE-RECEPTOR; SUBUNIT MESSENGER-RNAS
AB The mammalian ionotropic glutamate receptor family encodes 18 gene products that coassemble to form ligand-gated ion channels containing an agonist recognition site, a transmembrane ion permeation pathway, and gating elements that couple agonist-induced conformational changes to the opening or closing of the permeation pore. Glutamate receptors mediate fast excitatory synaptic transmission in the central nervous system and are localized on neuronal and non-neuronal cells. These receptors regulate a broad spectrum of processes in the brain, spinal cord, retina, and peripheral nervous system. Glutamate receptors are postulated to play important roles in numerous neurological diseases and have attracted intense scrutiny. The description of glutamate receptor structure, including its transmembrane elements, reveals a complex assembly of multiple semiautonomous extracellular domains linked to a pore-forming element with striking resemblance to an inverted potassium channel. In this review we discuss International Union of Basic and Clinical Pharmacology glutamate receptor nomenclature, structure, assembly, accessory subunits, interacting proteins, gene expression and translation, post-translational modifications, agonist and antagonist pharmacology, allosteric modulation, mechanisms of gating and permeation, roles in normal physiological function, as well as the potential therapeutic use of pharmacological agents acting at glutamate receptors.
C1 [Traynelis, Stephen F.] Emory Univ, Sch Med, Dept Pharmacol, Rollins Res Ctr, Atlanta, GA 30322 USA.
[Wollmuth, Lonnie P.] SUNY Stony Brook, Dept Neurobiol & Behav, Stony Brook, NY 11794 USA.
[Wollmuth, Lonnie P.] SUNY Stony Brook, Ctr Nervous Syst Disorders, Stony Brook, NY 11794 USA.
[Menniti, Frank S.] CyclicM LLC, Mystic, CT USA.
[McBain, Chris J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Traynelis, SF (reprint author), Emory Univ, Sch Med, Dept Pharmacol, Rollins Res Ctr, 1510 Clifton Rd, Atlanta, GA 30322 USA.
EM strayne@emory.edu
RI Hansen, Kasper/C-4062-2008; dingledine, Ray/F-5173-2011; Ogden,
Kevin/F-7118-2012;
OI Hansen, Kasper/0000-0002-3303-4819; Ogden, Kevin/0000-0001-7286-3209;
Menniti, Frank/0000-0003-2612-9534
FU National Institutes of Health National Institute of Neurological
Disorders and Stroke [NS065371, NS036654, NS068464, NS036604]; National
Institutes of Health National Institute of Mental Health [MH066892];
National Institutes of Health National Eye Institute [EY01697905];
National Institutes of Health National Institute of Child Health & Human
Development; National Institutes of Health National Institute of General
Medical Sciences [T32-GM008602]; National Institutes of Health National
Institute on Drug Abuse [T32-DA01504006]; National Institutes of Health
National Institute of Environmental Health Sciences [T32-ES012870];
Michael J. Fox Foundation; Lundbeck Foundation; Villum Kann Rasmussen
Foundation
FX This work was supported by the National Institutes of Health National
Institute of Neurological Disorders and Stroke [Grants NS065371,
NS036654, NS068464 (all to S. F. T.), NS036604 (to R. D.)]; the National
Institutes of Health National Institute of Mental Health [Grant MH066892
(to L. P. W.); the National Institutes of Health National Eye Institute
[Grant EY01697905 (to L. P. W.); the National Institutes of Health
National Institute of Child Health & Human Development [Intramural
Research Award (to C.J.M.)]; the National Institutes of Health National
Institute of General Medical Sciences [Grant T32-GM008602 (to K.K.O.)];
the National Institutes of Health National Institute on Drug Abuse
[Grant T32-DA01504006 (to K. M. V.)]; the National Institutes of Health
National Institute of Environmental Health Sciences [Grant T32-ES012870
(to K. M. V.)]; the Michael J. Fox Foundation (to S. F. T.); the
Lundbeck Foundation (to K. B. H.); and the Villum Kann Rasmussen
Foundation (to K. B. H.). We are grateful to Stefka Gyoneva, Randy Hall,
Richard Huganir, Meag Jenkins, Jon Johnson, John Isaac, Mark Mayer, and
Ken Pelkey for providing critical comments on portions of the
manuscript, as well as the reviewers for their painstaking and careful
reading of the manuscript. We also thank Drs. Howe, Furukawa, Mott,
Rosconi, Sobolevsky, Gouaux, and others for sharing unpublished data and
Polina Lyuboslavsky and Kimberly Vellano for excellent technical
assistance.
NR 1367
TC 1050
Z9 1074
U1 51
U2 328
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0031-6997
EI 1521-0081
J9 PHARMACOL REV
JI Pharmacol. Rev.
PD SEP
PY 2010
VL 62
IS 3
BP 405
EP 496
DI 10.1124/pr.109.002451
PG 92
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 639VR
UT WOS:000281004000004
PM 20716669
ER
PT J
AU Belanger, JM
Raviv, Y
Viard, M
de la Cruz, MJ
Nagashima, K
Blumenthal, R
AF Belanger, Julie M.
Raviv, Yossef
Viard, Mathias
de la Cruz, Michael Jason
Nagashima, Kunio
Blumenthal, Robert
TI Characterization of the Effects of Aryl-azido Compounds and UVA
Irradiation on the Viral Proteins and Infectivity of Human
Immunodeficiency Virus Type 1
SO PHOTOCHEMISTRY AND PHOTOBIOLOGY
LA English
DT Article
ID CROSS-LINKING; FORMALIN INACTIVATION; ENVELOPE GLYCOPROTEIN;
BIOLOGICAL-MEMBRANES; STRUCTURAL INTEGRITY; ERYTHROCYTE-MEMBRANE; HIV-1;
PRESERVATION; BINDING; CELLS
AB Hydrophobic UV-activatable compounds have been shown to partition into the hydrophobic region of biological membranes to selectively label transmembrane proteins, and to inactivate enveloped viruses. Here, we analyze various UV-activatable azido- and iodo-based hydrophobic compounds for their ability to inactivate a model-enveloped virus, human immunodeficiency virus (HIV-1 MN). Treatment of HIV-1 with 1,5-diazidonapthalene (DAN), 1-iodo, 5-azidonaphthalene (INA), 1-azidonaphthalene (AzNAP) or 4,4'-diazidobiphenyl (DABIPH) followed by UVA irradiation for 2 min resulted in complete viral inactivation, whereas treatment using analogous non-azido-containing controls had no effect. Incorporation of an azido moiety within these hydrophobic compounds to promote photoinduced covalent reactions with proteins was found to be the primary mechanism of viral inactivation for this class of compounds. Prolonged UVA irradiation of the virus in the presence of these azido compounds resulted in further modifications of viral proteins, due to the generation of reactive oxygen species, leading to aggregation as visualized via Western blot analysis, providing additional viral modifications that may inhibit viral infectivity. Furthermore, inactivation using these compounds resulted in the preservation of surface antigenic structures (recognized by neutralizing antibodies b12, 2g12 and 4e10), which is favorable for the creation of vaccines from these inactivated virus preparations.
C1 [Belanger, Julie M.; Blumenthal, Robert] NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA.
[Raviv, Yossef; Viard, Mathias] NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21701 USA.
[de la Cruz, Michael Jason; Nagashima, Kunio] NCI, Adv Technol Program, SAIC Frederick, Frederick, MD 21701 USA.
RP Blumenthal, R (reprint author), NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA.
EM blumenthalr@mail.nih.gov
RI Belanger, Julie/A-5734-2009
OI Belanger, Julie/0000-0002-7236-2778
FU Intramural AIDS Targeted Antiviral Program; Intramural Research Program
of the NIH; National Cancer Institute, Center for Cancer Research;
National Cancer Institute, National Institutes of Health
[HHSN26120080001E]; U.S. Government
FX The authors would like to thank Julian W. Bess, Jr. of the AIDS and
Cancer Virus Program, SAIC-Frederick, for many helpful conversations and
his critical reading of this manuscript. We thank ARRRP for reagents,
and Jeff Lifson and Julian W. Bess, Jr. for generously providing
purified virus. This research was supported (in part) by federal funds
from the Intramural AIDS Targeted Antiviral Program and the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research. This project has been funded in whole or in part with
federal funds from the National Cancer Institute, National Institutes of
Health, under contract HHSN26120080001E. The content of this publication
does not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products or organizations imply endorsement by the U.S. Government.
NR 36
TC 4
Z9 4
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0031-8655
J9 PHOTOCHEM PHOTOBIOL
JI Photochem. Photobiol.
PD SEP-OCT
PY 2010
VL 86
IS 5
BP 1099
EP 1108
DI 10.1111/j.1751-1097.2010.00780.x
PG 10
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 647SG
UT WOS:000281638700017
PM 20630026
ER
PT J
AU Paliy, M
Melnik, R
Shapiro, BA
AF Paliy, Maxim
Melnik, Roderick
Shapiro, Bruce A.
TI Coarse-graining RNA nanostructures for molecular dynamics simulations
SO PHYSICAL BIOLOGY
LA English
DT Article
ID STRUCTURE PREDICTION; TERTIARY STRUCTURES; POTENTIALS; MODELS; SEQUENCE;
DNA; REPRESENTATION; PROTEINS; HAIRPINS
AB A series of coarse-grained models have been developed for study of the molecular dynamics of RNA nanostructures. The models in the series have one to three beads per nucleotide and include different amounts of detailed structural information. Such a treatment allows us to reach, for systems of thousands of nucleotides, a time scale of microseconds (i.e. by three orders of magnitude longer than in full atomistic modeling) and thus to enable simulations of large RNA polymers in the context of bionanotechnology. We find that the three-beads-per-nucleotide models, described by a set of just a few universal parameters, are able to describe different RNA conformations and are comparable in structural precision to the models where detailed values of the backbone P-C4' dihedrals taken from a reference structure are included. These findings are discussed in the context of RNA conformation classes.
C1 [Paliy, Maxim; Melnik, Roderick] Wilfrid Laurier Univ, Lab M2NeT, Waterloo, ON N2L 3C5, Canada.
[Paliy, Maxim] Univ Western Ontario, London, ON N6A 5B7, Canada.
[Melnik, Roderick] BCAM, Derio 48160, Spain.
[Shapiro, Bruce A.] NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
RP Paliy, M (reprint author), Wilfrid Laurier Univ, Lab M2NeT, 75 Univ Ave W, Waterloo, ON N2L 3C5, Canada.
EM mpaliy@wlu.ca
FU NSERC CRC; NIH; National Cancer Institute; Center for Cancer Research
FX MP and RM are grateful to the NSERC CRC Program for its support. This
research was supported (in part) by the Intramural Research Program of
the NIH, National Cancer Institute, Center for Cancer Research. This
work was made possible by the facilities of the Shared Hierarchical
Academic Research Computing Network (SHARCNET: www.sharcnet.ca) and
Compute/Calcul Canada. The authors are grateful to Valentina Tozzini for
helpful comments and suggestions.
NR 44
TC 18
Z9 18
U1 1
U2 7
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 1478-3967
J9 PHYS BIOL
JI Phys. Biol.
PD SEP
PY 2010
VL 7
IS 3
AR 036001
DI 10.1088/1478-3975/7/3/036001
PG 12
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 653NA
UT WOS:000282097000003
PM 20577037
ER
PT J
AU Park, HS
Romero, R
Lee, SM
Park, CW
Jun, JK
Yoon, BH
AF Park, H. S.
Romero, R.
Lee, S. M.
Park, C. W.
Jun, J. K.
Yoon, B. H.
TI Histologic Chorioamnionitis is More Common after Spontaneous Labor than
after Induced Labor at Term
SO PLACENTA
LA English
DT Article
DE Placental inflammation; Parturition; Spontaneous onset of labor; Term
pregnancy; Inflammation; Infection
ID PRETERM LABOR; CEREBRAL-PALSY; AMNIOTIC-FLUID; INTRAAMNIOTIC
INFLAMMATION; UREAPLASMA-UREALYTICUM; CLINICAL-SIGNIFICANCE;
PARTURITION; INFECTION; MEMBRANES; EXPRESSION
AB Objective: Inflammation of the chorioamniotic membranes (histologic chorioamnionitis) is a risk factor for adverse neonatal outcome. Labor has many common features with inflammatory processes; therefore, an important question is whether the frequency of histologic chorioamnionitis in spontaneous labor at term is higher than that of women in labor after induction. This study was conducted to address this question.
Study design: The frequency of histologic chorioamnionitis was compared between patients who delivered after the spontaneous onset of labor versus those who delivered after induction of labor at term in singleton gestations (>= 37 weeks). Patients in whom uterotonic agents were used during the latent phase of labor were excluded.
Results: (1) The overall frequency of histologic chorioamnionitis was 20.2% (107/531); (2) histologic chorioamnionitis was significantly more frequent in women who delivered after the spontaneous onset of labor than in those who underwent induction of labor (24.3% [81/333] versus 13.1% [26/198], p < 0.005). This difference remained significant after adjusting for parity, gestational age at delivery, total duration of labor, the interval from rupture of membranes to delivery and the mode of delivery.
Conclusion: Histologic chorioamnionitis is more common in women who delivered after the spontaneous onset of labor than in those who underwent induction of labor at term. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Lee, S. M.; Park, C. W.; Jun, J. K.; Yoon, B. H.] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea.
[Park, H. S.] Dongguk Univ, Grad Sch Med, Dept Obstet & Gynecol, Seoul, South Korea.
[Romero, R.] NICHD, Perinatol Res Branch, DHHS, NIH, Bethesda, MD USA.
[Romero, R.] NICHD, Perinatol Res Branch, DHHS, NIH, Detroit, MI USA.
[Romero, R.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Romero, R.] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
RP Yoon, BH (reprint author), Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea.
EM yoonbh@snu.ac.kr
RI Park, Hyun Soo/D-5728-2012; Jun, Jong Kwan/D-5776-2012; Yoon, Bo
Hyun/H-6344-2011
OI Jun, Jong Kwan/0000-0002-0242-1736;
FU Korea government (MEST) [2009-0080429]
FX This work was supported by the National Research Foundation of Korea
(NRF) grant funded by the Korea government (MEST) (No. 2009-0080429)
NR 23
TC 14
Z9 14
U1 0
U2 4
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0143-4004
J9 PLACENTA
JI Placenta
PD SEP
PY 2010
VL 31
IS 9
BP 792
EP 795
DI 10.1016/j.placenta.2010.06.013
PG 4
WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
GA 654CW
UT WOS:000282147100007
PM 20655108
ER
PT J
AU Wildman, DE
AF Wildman, D. E.
TI FUNCTIONAL PHYLOGENOMIC DATA ELUCIDATE CONSERVED AND DERIVED ASPECTS OF
PLACENTA BIOLOGY
SO PLACENTA
LA English
DT Meeting Abstract
CT International-Federation-of-Placental-Associations Meeting 2010
CY OCT 19-22, 2010
CL Santiago, CHILE
DE transcriptome; evolution; gene gain and loss; phylogeny
C1 [Wildman, D. E.] Wayne State Univ, Detroit, MI 48202 USA.
[Wildman, D. E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0143-4004
J9 PLACENTA
JI Placenta
PD SEP
PY 2010
VL 31
IS 9
BP A9
EP A9
PG 1
WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
GA 654CW
UT WOS:000282147100032
ER
PT J
AU Dalloul, RA
Long, JA
Zimin, AV
Aslam, L
Beal, K
Blomberg, L
Bouffard, P
Burt, DW
Crasta, O
Crooijmans, RPMA
Cooper, K
Coulombe, RA
De, S
Delany, ME
Dodgson, JB
Dong, JJ
Evans, C
Frederickson, KM
Flicek, P
Florea, L
Folkerts, O
Groenen, MAM
Harkins, TT
Herrero, J
Hoffmann, S
Megens, HJ
Jiang, A
de Jong, P
Kaiser, P
Kim, H
Kim, KW
Kim, S
Langenberger, D
Lee, MK
Lee, T
Mane, S
Marcais, G
Marz, M
McElroy, AP
Modise, T
Nefedov, M
Notredame, C
Paton, IR
Payne, WS
Pertea, G
Prickett, D
Puiu, D
Qioa, D
Raineri, E
Ruffier, M
Salzberg, SL
Schatz, MC
Scheuring, C
Schmidt, CJ
Schroeder, S
Searle, SMJ
Smith, EJ
Smith, J
Sonstegard, TS
Stadler, PF
Tafer, H
Tu, ZJ
Van Tassell, CP
Vilella, AJ
Williams, KP
Yorke, JA
Zhang, LQ
Zhang, HB
Zhang, XJ
Zhang, Y
Reed, KM
AF Dalloul, Rami A.
Long, Julie A.
Zimin, Aleksey V.
Aslam, Luqman
Beal, Kathryn
Blomberg, Le Ann
Bouffard, Pascal
Burt, David W.
Crasta, Oswald
Crooijmans, Richard P. M. A.
Cooper, Kristal
Coulombe, Roger A.
De, Supriyo
Delany, Mary E.
Dodgson, Jerry B.
Dong, Jennifer J.
Evans, Clive
Frederickson, Karin M.
Flicek, Paul
Florea, Liliana
Folkerts, Otto
Groenen, Martien A. M.
Harkins, Tim T.
Herrero, Javier
Hoffmann, Steve
Megens, Hendrik-Jan
Jiang, Andrew
de Jong, Pieter
Kaiser, Pete
Kim, Heebal
Kim, Kyu-Won
Kim, Sungwon
Langenberger, David
Lee, Mi-Kyung
Lee, Taeheon
Mane, Shrinivasrao
Marcais, Guillaume
Marz, Manja
McElroy, Audrey P.
Modise, Thero
Nefedov, Mikhail
Notredame, Cedric
Paton, Ian R.
Payne, William S.
Pertea, Geo
Prickett, Dennis
Puiu, Daniela
Qioa, Dan
Raineri, Emanuele
Ruffier, Magali
Salzberg, Steven L.
Schatz, Michael C.
Scheuring, Chantel
Schmidt, Carl J.
Schroeder, Steven
Searle, Stephen M. J.
Smith, Edward J.
Smith, Jacqueline
Sonstegard, Tad S.
Stadler, Peter F.
Tafer, Hakim
Tu, Zhijian (Jake)
Van Tassell, Curtis P.
Vilella, Albert J.
Williams, Kelly P.
Yorke, James A.
Zhang, Liqing
Zhang, Hong-Bin
Zhang, Xiaojun
Zhang, Yang
Reed, Kent M.
TI Multi-Platform Next-Generation Sequencing of the Domestic Turkey
(Meleagris gallopavo): Genome Assembly and Analysis
SO PLOS BIOLOGY
LA English
DT Article
ID HIGH-THROUGHPUT; MONODELPHIS-DOMESTICA; MOLECULAR PHYLOGENY; CHICKEN
GENOME; GENE FAMILY; EVOLUTION; IDENTIFICATION; DIVERSITY; BIRDS;
GALLIFORMES
AB A synergistic combination of two next-generation sequencing platforms with a detailed comparative BAC physical contig map provided a cost-effective assembly of the genome sequence of the domestic turkey (Meleagris gallopavo). Heterozygosity of the sequenced source genome allowed discovery of more than 600,000 high quality single nucleotide variants. Despite this heterozygosity, the current genome assembly (similar to 1.1 Gb) includes 917 Mb of sequence assigned to specific turkey chromosomes. Annotation identified nearly 16,000 genes, with 15,093 recognized as protein coding and 611 as non-coding RNA genes. Comparative analysis of the turkey, chicken, and zebra finch genomes, and comparing avian to mammalian species, supports the characteristic stability of avian genomes and identifies genes unique to the avian lineage. Clear differences are seen in number and variety of genes of the avian immune system where expansions and novel genes are less frequent than examples of gene loss. The turkey genome sequence provides resources to further understand the evolution of vertebrate genomes and genetic variation underlying economically important quantitative traits in poultry. This integrated approach may be a model for providing both gene and chromosome level assemblies of other species with agricultural, ecological, and evolutionary interest.
C1 [Dalloul, Rami A.; Kim, Sungwon; McElroy, Audrey P.; Smith, Edward J.] Virginia Tech, Dept Anim & Poultry Sci, Avian Immunobiol Lab, Blacksburg, VA 24061 USA.
[Long, Julie A.; Blomberg, Le Ann] ARS, Anim Biosci & Biotechnol Lab, USDA, Beltsville, MD USA.
[Zimin, Aleksey V.; Marcais, Guillaume; Yorke, James A.] Univ Maryland, Inst Phys Sci & Technol, College Pk, MD 20742 USA.
[Aslam, Luqman; Crooijmans, Richard P. M. A.; Groenen, Martien A. M.; Megens, Hendrik-Jan] Wageningen Univ, Anim Breeding & Genom Ctr, Wageningen, Netherlands.
[Beal, Kathryn; Flicek, Paul; Herrero, Javier; Vilella, Albert J.] European Bioinformat Inst, Cambridge, England.
[Bouffard, Pascal; Frederickson, Karin M.; Harkins, Tim T.] Roche Appl Sci, Indianapolis, IN USA.
[Burt, David W.; Paton, Ian R.; Smith, Jacqueline] Univ Edinburgh, Roslin Inst, Roslin, Midlothian, Scotland.
[Burt, David W.; Paton, Ian R.; Smith, Jacqueline] Univ Edinburgh, Royal Dick Sch Vet Studies, Roslin, Midlothian, Scotland.
[Crasta, Oswald; Cooper, Kristal; Evans, Clive; Folkerts, Otto; Mane, Shrinivasrao; Modise, Thero; Williams, Kelly P.] Virginia Tech, Virginia Bioinformat Inst, Blacksburg, VA USA.
[Crasta, Oswald; Folkerts, Otto] Chromatin Inc, Champaign, IL USA.
[Coulombe, Roger A.] Utah State Univ, Dept Vet Sci, Logan, UT 84322 USA.
[De, Supriyo] NIA, Gene Express & Genom Unit, NIH, Baltimore, MD 21224 USA.
[Delany, Mary E.; Jiang, Andrew] Univ Calif Davis, Dept Anim Sci, Davis, CA 95616 USA.
[Dodgson, Jerry B.; Payne, William S.] Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA.
[Dong, Jennifer J.; Lee, Mi-Kyung; Scheuring, Chantel; Zhang, Hong-Bin; Zhang, Xiaojun; Zhang, Yang] Texas A&M Univ, Dept Soil & Crop Sci, College Stn, TX 77843 USA.
[Hoffmann, Steve; Langenberger, David; Marz, Manja; Stadler, Peter F.; Tafer, Hakim] Univ Leipzig, Interdisciplinary Ctr Bioinformat, Leipzig, Germany.
[Hoffmann, Steve; Langenberger, David; Marz, Manja; Stadler, Peter F.; Tafer, Hakim] Univ Leipzig, Dept Comp Sci, Leipzig, Germany.
[Hoffmann, Steve] Univ Leipzig, LIFE Project, Leipzig, Germany.
[de Jong, Pieter; Nefedov, Mikhail] Childrens Hosp & Res Ctr Oakland, Oakland, CA USA.
[Kaiser, Pete; Prickett, Dennis] Inst Anim Hlth, Compton, Berks, England.
[Kim, Heebal; Kim, Kyu-Won; Lee, Taeheon] Seoul Natl Univ, Dept Agr Biotechnol, Lab Bioinformat & Populat Genet, Seoul, South Korea.
[Marz, Manja] Univ Marburg, Marburg, Germany.
[Notredame, Cedric; Raineri, Emanuele] Univ Pompeus Fabre, Ctr Genom Regulat CRG, Barcelona, Spain.
[Qioa, Dan; Zhang, Liqing] Virginia Tech, Dept Comp Sci, Blacksburg, VA USA.
[Ruffier, Magali; Searle, Stephen M. J.] Wellcome Trust Sanger Inst, Cambridge, England.
[Salzberg, Steven L.; Schatz, Michael C.] Univ Maryland, Dept Comp Sci, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA.
[Schmidt, Carl J.] Univ Delaware, Dept Anim & Food Sci, Newark, DE USA.
[Reed, Kent M.] Univ Minnesota, Coll Vet Med, Dept Vet & Biomed Sci, St Paul, MN 55108 USA.
[Van Tassell, Curtis P.] ARS, Anim Improvement Programs Lab, USDA, Beltsville Agr Res Ctr, Beltsville, MD USA.
[Tu, Zhijian (Jake)] Virginia Tech, Dept Biochem, Blacksburg, VA USA.
[Stadler, Peter F.] Santa Fe Inst, Santa Fe, NM 87501 USA.
[Stadler, Peter F.; Tafer, Hakim] Univ Vienna, Dept Theoret Chem, Vienna, Austria.
[Stadler, Peter F.] Fraunhofer Inst Zelltherapie & Immunol, Leipzig, Germany.
[Stadler, Peter F.] Max Planck Inst Math Sci, Leipzig, Germany.
[Schroeder, Steven; Sonstegard, Tad S.; Van Tassell, Curtis P.] ARS, Bovine Funct Genom Lab, USDA, Beltsville Agr Res Ctr, Beltsville, MD USA.
RP Dalloul, RA (reprint author), Virginia Tech, Dept Anim & Poultry Sci, Avian Immunobiol Lab, Blacksburg, VA 24061 USA.
EM reedx054@umn.edu
RI Megens, Hendrik-Jan/E-9676-2010; Zhang, Yang/A-5460-2011; Groenen,
Martien/D-8408-2012; Crooijmans, Richard/E-2492-2012; Smith,
Jacqueline/C-7719-2013; Langenberger, David/D-4155-2013; Hoffmann,
Steve/E-1438-2013; Aslam, Muhammad/J-5053-2014; Stadler, Peter
F./L-7857-2015; Coulombe, Roger/G-7523-2012; Salzberg,
Steven/F-6162-2011; notredame, cedric/G-3868-2010;
OI Megens, Hendrik-Jan/0000-0002-3619-7533; Groenen,
Martien/0000-0003-0484-4545; Langenberger, David/0000-0001-9424-9701;
Aslam, Muhammad/0000-0001-8812-6887; Stadler, Peter
F./0000-0002-5016-5191; Salzberg, Steven/0000-0002-8859-7432; Dalloul,
Rami/0000-0003-4690-9220; De, Supriyo/0000-0002-2075-7655; Flicek,
Paul/0000-0002-3897-7955; Kim, Heebal/0000-0003-3064-1303; Schatz,
Michael/0000-0002-4118-4446; Ruffier, Magali/0000-0002-8386-1580; Tafer,
Hakim/0000-0002-6252-9802; Schmidt, Carl/0000-0002-8386-4781; Vilella,
Albert/0000-0002-2005-2516; Van Tassell, Curtis/0000-0002-8416-2087;
notredame, cedric/0000-0003-1461-0988; Schroeder,
Steven/0000-0001-9103-5150; Herrero, Javier/0000-0001-7313-717X
FU Roche Applied Science; University of Minnesota (College of Veterinary
Medicine, and College of Food, Agricultural & Natural Resource
Sciences); Utah State University (Center for Integrated Biosystems);
Virginia Bioinformatics Institute Core Lab Facility, Virginia Tech
University (College of Agriculture & Life Sciences, Virginia
Bioinformatics Institute, Fralin Biotechnology Center, Office of Vice
President for Research); USDA; NIH National Institute on Aging; Center
for Genomics regulation; European Community (Barcelona, Spain);
"Landesexzellenzinitiative LIFE'' (Germany); NIH National Human Genome
Research Institute [R01-HG002945]; NIH National Library of Medicine
[R01-LM006845]; National Science Foundation [DMS0616585]; European
Union; Spanish Ministry of Science; Wellcome Trust; USDA National
Institute of Food and Agriculture Animal Genome [2005-35205-15451,
2007-0212704, 2007-35205-17880, 2008-04049, 2008-35205-18720,
2009-35205-05302, 2010-65205-20412]; Ministry of Science & Technology
(Korea Science & Engineering Foundation) of Korea
[R01-2007-000-20456-0]; [USDA-NIFA-NRSP8]
FX Funding for sequencing was supported by Roche Applied Science, the
University of Minnesota (College of Veterinary Medicine, and College of
Food, Agricultural & Natural Resource Sciences), the Utah State
University (Center for Integrated Biosystems), the Virginia
Bioinformatics Institute Core Lab Facility, Virginia Tech University
(College of Agriculture & Life Sciences, Virginia Bioinformatics
Institute, Fralin Biotechnology Center, Office of Vice President for
Research), the Intramural Research Programs of the USDA Agricultural
Research Service and the NIH National Institute on Aging, and
Multi-State Research Support Program (USDA-NIFA-NRSP8). Funding for
assembly, annotation and genomic analyses was provided by The Center for
Genomics regulation and the European Community (Barcelona, Spain),
"Landesstipendium Sachsen'', the Free State of Saxony under the auspices
of the "Landesexzellenzinitiative LIFE'' (Germany), the NIH National
Human Genome Research Institute (#R01-HG002945), the NIH National
Library of Medicine (#R01-LM006845), the National Science Foundation
(#DMS0616585), The Quantomics Project from 7th Framework Programe of the
European Union, the Spanish Ministry of Science, The Wellcome Trust, the
USDA National Institute of Food and Agriculture Animal Genome Program
(#'s 2005-35205-15451; 2007-0212704; 2007-35205-17880; 2008-04049;
2008-35205-18720; 2009-35205-05302; 2010-65205-20412) and Ministry of
Science & Technology (Korea Science & Engineering Foundation) of Korea
(R01-2007-000-20456-0). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 103
TC 176
Z9 181
U1 5
U2 71
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1545-7885
J9 PLOS BIOL
JI PLoS. Biol.
PD SEP
PY 2010
VL 8
IS 9
AR e1000475
DI 10.1371/journal.pbio.1000475
PG 21
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 655UY
UT WOS:000282279200020
ER
PT J
AU Laneri, K
Bhadra, A
Ionides, EL
Bouma, M
Dhiman, RC
Yadav, RS
Pascual, M
AF Laneri, Karina
Bhadra, Anindya
Ionides, Edward L.
Bouma, Menno
Dhiman, Ramesh C.
Yadav, Rajpal S.
Pascual, Mercedes
TI Forcing Versus Feedback: Epidemic Malaria and Monsoon Rains in Northwest
India
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID PLASMODIUM-FALCIPARUM INFECTIONS; NINO-SOUTHERN-OSCILLATION; EARLY
WARNING SYSTEMS; TIME-SERIES DATA; CHOLERA DYNAMICS; EL-NINO; MODELS;
DISEASES; TRANSMISSION; PATTERNS
AB Malaria epidemics in regions with seasonal windows of transmission can vary greatly in size from year to year. A central question has been whether these interannual cycles are driven by climate, are instead generated by the intrinsic dynamics of the disease, or result from the resonance of these two mechanisms. This corresponds to the more general inverse problem of identifying the respective roles of external forcings vs. internal feedbacks from time series for nonlinear and noisy systems. We propose here a quantitative approach to formally compare rival hypotheses on climate vs. disease dynamics, or external forcings vs. internal feedbacks, that combines dynamical models with recently developed, computational inference methods. The interannual patterns of epidemic malaria are investigated here for desert regions of northwest India, with extensive epidemiological records for Plasmodium falciparum malaria for the past two decades. We formulate a dynamical model of malaria transmission that explicitly incorporates rainfall, and we rely on recent advances on parameter estimation for nonlinear and stochastic dynamical systems based on sequential Monte Carlo methods. Results show a significant effect of rainfall in the inter-annual variability of epidemic malaria that involves a threshold in the disease response. The model exhibits high prediction skill for yearly cases in the malaria transmission season following the monsoonal rains. Consideration of a more complex model with clinical immunity demonstrates the robustness of the findings and suggests a role of infected individuals that lack clinical symptoms as a reservoir for transmission. Our results indicate that the nonlinear dynamics of the disease itself play a role at the seasonal, but not the interannual, time scales. They illustrate the feasibility of forecasting malaria epidemics in desert and semi-arid regions of India based on climate variability. This approach should be applicable to malaria in other locations, to other infectious diseases, and to other nonlinear systems under forcing.
C1 [Laneri, Karina; Pascual, Mercedes] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
[Bhadra, Anindya; Ionides, Edward L.] Univ Michigan, Dept Stat, Ann Arbor, MI 48109 USA.
[Ionides, Edward L.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Bouma, Menno] Univ London, Dept Infect & Trop Dis, London Sch Hyg & Trop Med, London, England.
[Dhiman, Ramesh C.; Yadav, Rajpal S.] Natl Inst Malaria Res, Delhi, India.
[Pascual, Mercedes] Univ Michigan, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA.
RP Laneri, K (reprint author), Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
EM pascual@umich.edu
FU Graham Environmental Sustainability Institute (GESI) of the University
of Michigan; National Oceanic and Atmospheric Administration [NA 040 AR
460019]; National Science Foundation [DMS-0805533]; Science & Technology
Directorate, Department of Homeland Security; Fogarty International
Center, National Institutes of Health
FX M.P. acknowledges the support of the Graham Environmental Sustainability
Institute (GESI) of the University of Michigan and the National Oceanic
and Atmospheric Administration (Oceans and Health Program NA 040 AR
460019); and E.I, that of the National Science Foundation (DMS-0805533)
and the RAPIDD program of the Science & Technology Directorate,
Department of Homeland Security, and the Fogarty International Center,
National Institutes of Health. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 60
TC 41
Z9 41
U1 1
U2 28
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-734X
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD SEP
PY 2010
VL 6
IS 9
AR e1000898
DI 10.1371/journal.pcbi.1000898
PG 13
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 656WU
UT WOS:000282372600033
PM 20824122
ER
PT J
AU Chen, GK
Millikan, RC
John, EM
Ambrosone, CB
Bernstein, L
Zheng, W
Hu, JJ
Chanock, SJ
Ziegler, RG
Bandera, EV
Henderson, BE
Haiman, CA
Stram, DO
AF Chen, Gary K.
Millikan, Robert C.
John, Esther M.
Ambrosone, Christine B.
Bernstein, Leslie
Zheng, Wei
Hu, Jennifer J.
Chanock, Stephen J.
Ziegler, Regina G.
Bandera, Elisa V.
Henderson, Brian E.
Haiman, Christopher A.
Stram, Daniel O.
TI The Potential for Enhancing the Power of Genetic Association Studies in
African Americans through the Reuse of Existing Genotype Data
SO PLOS GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; BREAST-CANCER RISK; POPULATION; STRATIFICATION;
POLYMORPHISMS; EPIDEMIOLOGY; SAMPLES; MODEL
AB We consider the feasibility of reusing existing control data obtained in genetic association studies in order to reduce costs for new studies. We discuss controlling for the population differences between cases and controls that are implicit in studies utilizing external control data. We give theoretical calculations of the statistical power of a test due to Bourgain et al (Am J Human Genet 2003), applied to the problem of dealing with case-control differences in genetic ancestry related to population isolation or population admixture. Theoretical results show that there may exist bounds for the non-centrality parameter for a test of association that places limits on study power even if sample sizes can grow arbitrarily large. We apply this method to data from a multi-center, geographically-diverse, genome-wide association study of breast cancer in African-American women. Our analysis of these data shows that admixture proportions differ by center with the average fraction of European admixture ranging from approximately 20% for participants from study sites in the Eastern United States to 25% for participants from West Coast sites. However, these differences in average admixture fraction between sites are largely counterbalanced by considerable diversity in individual admixture proportion within each study site. Our results suggest that statistical correction for admixture differences is feasible for future studies of African-Americans, utilizing the existing controls from the African-American Breast Cancer study, even if case ascertainment for the future studies is not balanced over the same centers or regions that supplied the controls for the current study.
C1 [Chen, Gary K.; Henderson, Brian E.; Haiman, Christopher A.; Stram, Daniel O.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Millikan, Robert C.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Millikan, Robert C.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[John, Esther M.] No Calif Canc Ctr, Fremont, CA USA.
[John, Esther M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[John, Esther M.] Stanford Canc Ctr, Stanford, CA 94305 USA.
[Ambrosone, Christine B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Bernstein, Leslie] Beckman Res Inst, Div Canc Etiol, Dept Populat Sci, City Of Hope, CA USA.
[Zheng, Wei] Vanderbilt Epidemiol Ctr, Dept Med, Div Epidemiol, Nashville, TN USA.
[Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA.
[Hu, Jennifer J.] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA.
[Hu, Jennifer J.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
[Chanock, Stephen J.; Ziegler, Regina G.] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Bandera, Elisa V.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ USA.
RP Chen, GK (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
EM stram@usc.edu
RI Bandera, Elisa/M-4169-2014
OI Bandera, Elisa/0000-0002-8789-2755
FU California Breast Cancer Research Program [15UB-8402]; National Cancer
Institute [P01 CA 017054-30]; Department of Defense; MEC (National
Institutes of Health) [R01-CA63464, R37-CA54281]; CARE (National
Institute for Child Health and Development) [NO1-HD-3-3175]; WCHS (U.S.
Army Medical Research and Material Command (USAMRMC)
[DAMD-17-01-0-0334]; National Institutes of Health [R01-CA100598];
Breast Cancer Research Foundation; SFBC (National Institutes of Health)
[R01-CA77305]; SFBC (United States Army Medical Research)
[DAMD17-96-6071]; NC-BCFR (National Institutes of Health) [U01-CA69417];
CBCS (National Institutes of Health) [P50-CA58223]; Center for
Environmental Health and Susceptibility, National Institute of
Environmental Health Sciences, National Institutes of Health
[P30-ES10126]; National Cancer Institute, National Institutes of Health;
NHBS (National Institutes of Health) [R01-CA100374]; WFBC (National
Institutes of Health) [R01-CA73629]; National Cancer Institute, National
Institutes of Health [CA-06-503]
FX GKC's and DOS's work on the AABC data is funded by grants from the
California Breast Cancer Research Program (15UB-8402) and from the
National Cancer Institute (P01 CA 017054-30). The AABC was supported by
a Department of Defense Breast Cancer Research Program Era of Hope
Scholar Award to Christopher Haiman and the Norris Foundation. The
participating studies were supported by the following grants: MEC
(National Institutes of Health grants R01-CA63464 and R37-CA54281), CARE
(National Institute for Child Health and Development grant
NO1-HD-3-3175), WCHS (U.S. Army Medical Research and Material Command
(USAMRMC) grant DAMD-17-01-0-0334, the National Institutes of Health
grant R01-CA100598, and the Breast Cancer Research Foundation, SFBC
(National Institutes of Health grant R01-CA77305 and United States Army
Medical Research Program grant DAMD17-96-6071), NC-BCFR (National
Institutes of Health grant U01-CA69417), CBCS (National Institutes of
Health Specialized Program of Research Excellence in Breast Cancer,
grant number P50-CA58223, and Center for Environmental Health and
Susceptibility, National Institute of Environmental Health Sciences,
National Institutes of Health, grant number P30-ES10126), PLCO
(Intramural Research Program, National Cancer Institute, National
Institutes of Health), NHBS (National Institutes of Health grant
R01-CA100374), and WFBC (R01-CA73629). The Breast Cancer Family Registry
(BCFR) was supported by the National Cancer Institute, National
Institutes of Health under RFA # CA-06-503 and through cooperative
agreements with members of the Breast Cancer Family Registry and
Principal Investigators. 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 BCFR, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the US Government or the BCFR. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 25
TC 4
Z9 4
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD SEP
PY 2010
VL 6
IS 9
AR e1001096
DI 10.1371/journal.pgen.1001096
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 656VM
UT WOS:000282369200064
PM 20824062
ER
PT J
AU Pelak, K
Shianna, KV
Ge, DL
Maia, JM
Zhu, MF
Smith, JP
Cirulli, ET
Fellay, J
Dickson, SP
Gumbs, CE
Heinzen, EL
Need, AC
Ruzzo, EK
Singh, A
Campbell, CR
Hong, LK
Lornsen, KA
McKenzie, AM
Sobreira, NLM
Hoover-Fong, JE
Milner, JD
Ottman, R
Haynes, BF
Goedert, JJ
Goldstein, DB
AF Pelak, Kimberly
Shianna, Kevin V.
Ge, Dongliang
Maia, Jessica M.
Zhu, Mingfu
Smith, Jason P.
Cirulli, Elizabeth T.
Fellay, Jacques
Dickson, Samuel P.
Gumbs, Curtis E.
Heinzen, Erin L.
Need, Anna C.
Ruzzo, Elizabeth K.
Singh, Abanish
Campbell, C. Ryan
Hong, Linda K.
Lornsen, Katharina A.
McKenzie, Alexander M.
Sobreira, Nara L. M.
Hoover-Fong, Julie E.
Milner, Joshua D.
Ottman, Ruth
Haynes, Barton F.
Goedert, James J.
Goldstein, David B.
TI The Characterization of Twenty Sequenced Human Genomes
SO PLOS GENETICS
LA English
DT Article
ID COPY NUMBER VARIATION; HEMOPHILIA-A; WHOLE; CAPTURE; PATIENT; SNPS
AB We present the analysis of twenty human genomes to evaluate the prospects for identifying rare functional variants that contribute to a phenotype of interest. We sequenced at high coverage ten "case" genomes from individuals with severe hemophilia A and ten "control" genomes. We summarize the number of genetic variants emerging from a study of this magnitude, and provide a proof of concept for the identification of rare and highly-penetrant functional variants by confirming that the cause of hemophilia A is easily recognizable in this data set. We also show that the number of novel single nucleotide variants (SNVs) discovered per genome seems to stabilize at about 144,000 new variants per genome, after the first 15 individuals have been sequenced. Finally, we find that, on average, each genome carries 165 homozygous protein-truncating or stop loss variants in genes representing a diverse set of pathways.
C1 [Pelak, Kimberly; Shianna, Kevin V.; Ge, Dongliang; Maia, Jessica M.; Zhu, Mingfu; Smith, Jason P.; Cirulli, Elizabeth T.; Fellay, Jacques; Dickson, Samuel P.; Gumbs, Curtis E.; Heinzen, Erin L.; Need, Anna C.; Ruzzo, Elizabeth K.; Singh, Abanish; Campbell, C. Ryan; Hong, Linda K.; Lornsen, Katharina A.; McKenzie, Alexander M.; Goldstein, David B.] Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC 27710 USA.
[Sobreira, Nara L. M.; Hoover-Fong, Julie E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Milner, Joshua D.] NIAID, Allerg Inflammat Unit, Lab Allerg Dis, Bethesda, MD 20892 USA.
[Ottman, Ruth] Columbia Univ, GH Sergievsky Ctr, New York, NY USA.
[Ottman, Ruth] Columbia Univ, Dept Epidemiol, New York, NY USA.
[Ottman, Ruth] Columbia Univ, Dept Neurol, New York, NY USA.
[Ottman, Ruth] New York State Psychiat Inst & Hosp, Div Epidemiol, New York, NY 10032 USA.
[Haynes, Barton F.] Duke Univ, Duke Human Vaccine Inst, Durham, NC USA.
[Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
RP Pelak, K (reprint author), Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC 27710 USA.
EM d.goldstein@duke.edu
RI Zhu, Mingfu/F-3217-2011; Sincan, Murat /A-3794-2010; Ottman,
Ruth/O-2371-2013; Fellay, Jacques/A-6681-2009;
OI Zhu, Mingfu/0000-0003-0296-712X; Fellay, Jacques/0000-0002-8240-939X;
Cirulli Rogers, Liz/0000-0001-7808-2809; Need, Anna/0000-0003-3955-8207
FU Bill and Melinda Gates Foundation [157412]; National Institute of
Allergy and Infectious Diseases (NIAID) Center for HIV/AIDS Vaccine
Immunology (CHAVI) [AI067854]; National Institute of Mental Health
[RC2MH089915]; National Institute Of Neurological Disorders And Stroke
[RC2NS070344]; Division of Intramural Research, NIAID, National
Institutes of Health
FX Funding was provided by the Bill and Melinda Gates Foundation grant
157412, with additional funding by the National Institute of Allergy and
Infectious Diseases (NIAID) Center for HIV/AIDS Vaccine Immunology
(CHAVI) grant AI067854. Funding for the collection of control samples
was provided in part by RC2MH089915 from the National Institute of
Mental Health, and Award Number RC2NS070344 from the National Institute
Of Neurological Disorders And Stroke. This research was supported in
part by funding from the Division of Intramural Research, NIAID,
National Institutes of Health. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 36
TC 88
Z9 94
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD SEP
PY 2010
VL 6
IS 9
AR e1001111
DI 10.1371/journal.pgen.1001111
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 656VM
UT WOS:000282369200049
PM 20838461
ER
PT J
AU Shu, XO
Long, JR
Cai, QY
Qi, L
Xiang, YB
Cho, YS
Tai, ES
Li, XY
Lin, X
Chow, WH
Go, MJ
Seielstad, M
Bao, W
Li, HX
Cornelis, MC
Yu, K
Wen, WQ
Shi, JJ
Han, BG
Sim, XL
Liu, LG
Qi, QB
Kim, HL
Ng, DPK
Lee, JY
Kim, YJ
Li, C
Gao, YT
Zheng, W
Hu, FB
AF Shu, Xiao Ou
Long, Jirong
Cai, Qiuyin
Qi, Lu
Xiang, Yong-Bing
Cho, Yoon Shin
Tai, E. Shyong
Li, Xiangyang
Lin, Xu
Chow, Wong-Ho
Go, Min Jin
Seielstad, Mark
Bao, Wei
Li, Huaixing
Cornelis, Marilyn C.
Yu, Kai
Wen, Wanqing
Shi, Jiajun
Han, Bok-Ghee
Sim, Xue Ling
Liu, Liegang
Qi, Qibin
Kim, Hyung-Lae
Ng, Daniel P. K.
Lee, Jong-Young
Kim, Young Jin
Li, Chun
Gao, Yu-Tang
Zheng, Wei
Hu, Frank B.
TI Identification of New Genetic Risk Variants for Type 2 Diabetes
SO PLOS GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SPROUTY PROTEINS; SUSCEPTIBILITY; INFLAMMATION;
LOCI; PATHOPHYSIOLOGY; COMPLICATIONS; REPLICATION; MELLITUS
AB Although more than 20 genetic susceptibility loci have been reported for type 2 diabetes (T2D), most reported variants have small to moderate effects and account for only a small proportion of the heritability of T2D, suggesting that the majority of inter-person genetic variation in this disease remains to be determined. We conducted a multistage, genome-wide association study (GWAS) within the Asian Consortium of Diabetes to search for T2D susceptibility markers. From 590,887 SNPs genotyped in 1,019 T2D cases and 1,710 controls selected from Chinese women in Shanghai, we selected the top 2,100 SNPs that were not in linkage disequilibrium (r(2)<0.2) with known T2D loci for in silico replication in three T2D GWAS conducted among European Americans, Koreans, and Singapore Chinese. The 5 most promising SNPs were genotyped in an independent set of 1,645 cases and 1,649 controls from Shanghai, and 4 of them were further genotyped in 1,487 cases and 3,316 controls from 2 additional Chinese studies. Consistent associations across all studies were found for rs1359790 (13q31.1), rs10906115 (10p13), and rs1436955 (15q22.2) with P-values (per allele OR, 95%CI) of 6.49 x 10(-9) (1.15, 1.10-1.20), 1.45 x 10(-8) (1.13, 1.08-1.18), and 7.14 x 10(-7) (1.13, 1.08-1.19), respectively, in combined analyses of 9,794 cases and 14,615 controls. Our study provides strong evidence for a novel T2D susceptibility locus at 13q31.1 and the presence of new independent risk variants near regions (10p13 and 15q22.2) reported by previous GWAS.
C1 [Shu, Xiao Ou; Long, Jirong; Cai, Qiuyin; Wen, Wanqing; Shi, Jiajun; Zheng, Wei] Vanderbilt Univ, Sch Med, Div Epidemiol, Dept Med,Vanderbilt Epidemiol Ctr,Vanderbilt Ingr, Nashville, TN 37212 USA.
[Qi, Lu; Cornelis, Marilyn C.; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Qi, Lu; Cornelis, Marilyn C.; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Xiang, Yong-Bing; Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Cho, Yoon Shin; Go, Min Jin; Han, Bok-Ghee; Kim, Hyung-Lae; Lee, Jong-Young; Kim, Young Jin] Korea Natl Inst Hlth, Ctr Genome Sci, Seoul, South Korea.
[Tai, E. Shyong] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 117595, Singapore.
[Tai, E. Shyong; Ng, Daniel P. K.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Epidemiol & Publ Hlth, Singapore 117595, Singapore.
[Tai, E. Shyong] Duke Natl Univ Singapore Grad Med Sch, Singapore, Singapore.
[Li, Xiangyang; Bao, Wei; Liu, Liegang] Huazhong Univ Sci & Technol, Dept Nutr & Food Hyg, Tongji Med Coll, Wuhan 430074, Peoples R China.
[Li, Xiangyang; Bao, Wei; Liu, Liegang] Huazhong Univ Sci & Technol, MOE Key Lab Environm & Hlth, Tongji Med Coll, Sch Publ Hlth, Wuhan 430074, Peoples R China.
[Lin, Xu; Li, Huaixing; Qi, Qibin] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Nutr & Metab, Shanghai, Peoples R China.
[Lin, Xu; Li, Huaixing; Qi, Qibin] Chinese Acad Sci, Grad Sch, Shanghai, Peoples R China.
[Chow, Wong-Ho; Yu, Kai] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Seielstad, Mark; Sim, Xue Ling] Genome Inst Singapore, Singapore, Singapore.
[Li, Chun] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA.
RP Shu, XO (reprint author), Vanderbilt Univ, Sch Med, Div Epidemiol, Dept Med,Vanderbilt Epidemiol Ctr,Vanderbilt Ingr, Nashville, TN 37212 USA.
EM xiao-ou.shu@vanderbilt.edu
RI Li, Chun/B-8388-2012; Qi, Qibin/H-9055-2012;
OI Seielstad, Mark/0000-0001-5783-1401; Tai, E Shyong/0000-0003-2929-8966;
Bao, Wei/0000-0002-7301-5786
FU United States National Institutes of Health (NIH) [R01CA124558,
R01CA64277, R37CA70867, R01CA90899, R01CA100374]; NIH [R01 CA118229,
R01CA92585]; Allen Foundation; National Center for Research Resources
(NCRR)/NIH [1 UL1 RR024975]; Department of Defense [BC050791, DK58845,
HG004399]; Vanderbilt-Ingram Cancer Center [P30 CA68485]; [R01CA122756]
FX This research was supported in part by the United States National
Institutes of Health (NIH) grants R01CA124558, R01CA64277, R37CA70867,
R01CA90899 and R01CA100374, as well as Ingram professorship funds and
research award funds to WZ, R01 CA118229, R01CA92585 from the NIH and a
research grant from Allen Foundation Fund to XOS, the Vanderbilt CTSA
grant 1 UL1 RR024975 from the National Center for Research Resources
(NCRR)/NIH to JL, R01CA122756 and Department of Defense Idea Award
BC050791 to QC, and DK58845 and HG004399 to FBH. Sample preparation,
SBCS/SWHS GWAS scanning, and SWHS/SMHS targeted genotyping (Replication
II) were conducted at the Survey and Biospecimen Shared Resources and
Vanderbilt Microarray Shared Resources that are supported in part by the
Vanderbilt-Ingram Cancer Center (P30 CA68485). The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 27
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Z9 103
U1 2
U2 14
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD SEP
PY 2010
VL 6
IS 9
AR e1001127
DI 10.1371/journal.pgen.1001127
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 656VM
UT WOS:000282369200033
PM 20862305
ER
PT J
AU Nechuta, SJ
Shu, XO
Li, HL
Yang, G
Xiang, YB
Cai, H
Chow, WH
Ji, BT
Zhang, XL
Wen, WQ
Gao, YT
Zheng, W
AF Nechuta, Sarah J.
Shu, Xiao-Ou
Li, Hong-Lan
Yang, Gong
Xiang, Yong-Bing
Cai, Hui
Chow, Wong-Ho
Ji, Butian
Zhang, Xianglan
Wen, Wanqing
Gao, Yu-Tang
Zheng, Wei
TI Combined Impact of Lifestyle-Related Factors on Total and Cause-Specific
Mortality among Chinese Women: Prospective Cohort Study
SO PLOS MEDICINE
LA English
DT Article
ID ALL-CAUSE MORTALITY; BODY-MASS INDEX; CARDIOVASCULAR-DISEASE MORTALITY;
PHYSICAL-ACTIVITY; ABDOMINAL ADIPOSITY; JAPANESE POPULATION; HEALTH
BEHAVIORS; PASSIVE SMOKING; ISCHEMIC-STROKE; FOLLOW-UP
AB Background: Although cigarette smoking, excessive alcohol drinking, obesity, and several other well-studied unhealthy lifestyle-related factors each have been linked to the risk of multiple chronic diseases and premature death, little is known about the combined impact on mortality outcomes, in particular among Chinese and other non-Western populations. The objective of this study was to quantify the overall impact of lifestyle-related factors beyond that of active cigarette smoking and alcohol consumption on all-cause and cause-specific mortality in Chinese women.
Methods and Findings: We used data from the Shanghai Women's Health Study, an ongoing population-based prospective cohort study in China. Participants included 71,243 women aged 40 to 70 years enrolled during 1996-2000 who never smoked or drank alcohol regularly. A healthy lifestyle score was created on the basis of five lifestyle-related factors shown to be independently associated with mortality outcomes (normal weight, lower waist-hip ratio, daily exercise, never exposed to spouse's smoking, higher daily fruit and vegetable intake). The score ranged from zero (least healthy) to five (most healthy) points. During an average follow-up of 9 years, 2,860 deaths occurred, including 775 from cardiovascular disease (CVD) and 1,351 from cancer. Adjusted hazard ratios for mortality decreased progressively with an increasing number of healthy lifestyle factors. Compared to women with a score of zero, hazard ratios (95% confidence intervals) for women with four to five factors were 0.57 (0.44-0.74) for total mortality, 0.29 (0.16-0.54) for CVD mortality, and 0.76 (0.54-1.06) for cancer mortality. The inverse association between the healthy lifestyle score and mortality was seen consistently regardless of chronic disease status at baseline. The population attributable risks for not having 4-5 healthy lifestyle factors were 33% for total deaths, 59% for CVD deaths, and 19% for cancer deaths.
Conclusions: In this first study, to our knowledge, to quantify the combined impact of lifestyle-related factors on mortality outcomes in Chinese women, a healthier lifestyle pattern-including being of normal weight, lower central adiposity, participation in physical activity, nonexposure to spousal smoking, and higher fruit and vegetable intake-was associated with reductions in total and cause-specific mortality among lifetime nonsmoking and nondrinking women, supporting the importance of overall lifestyle modification in disease prevention.
C1 [Nechuta, Sarah J.; Shu, Xiao-Ou; Yang, Gong; Cai, Hui; Zhang, Xianglan; Wen, Wanqing; Zheng, Wei] Vanderbilt Univ, Sch Med, Dept Med, Div Epidemiol, Nashville, TN 37212 USA.
[Li, Hong-Lan; Xiang, Yong-Bing; Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Chow, Wong-Ho; Ji, Butian] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
RP Nechuta, SJ (reprint author), Vanderbilt Univ, Sch Med, Dept Med, Div Epidemiol, Nashville, TN 37212 USA.
EM wei.zheng@vanderbilt.edu
FU National Institutes of Health [R37 CA070867]
FX Supported by National Institutes of Health grant R37 CA070867. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 44
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U1 1
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1549-1277
J9 PLOS MED
JI PLos Med.
PD SEP
PY 2010
VL 7
IS 9
AR e1000339
DI 10.1371/journal.pmed.1000339
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 655UQ
UT WOS:000282276900013
ER
PT J
AU Romero, I
Tellez, J
Suarez, Y
Cardona, M
Figueroa, R
Zelazny, A
Saravia, NG
AF Romero, Ibeth
Tellez, Jair
Suarez, Yazmin
Cardona, Maria
Figueroa, Roger
Zelazny, Adrian
Gore Saravia, Nancy
TI Viability and Burden of Leishmania in Extralesional Sites during Human
Dermal Leishmaniasis
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID POLYMERASE-CHAIN-REACTION; REAL-TIME PCR; CUTANEOUS LEISHMANIASIS;
VIANNIA BRAZILIENSIS; CLINICAL CURE; 7SL RNA; PARASITES; QUANTIFICATION;
SCARS; ASSAY
AB Background: The clinical and epidemiological significance of Leishmania DNA in extralesional sites is obscured by uncertainty of whether the DNA derives from viable parasites. To examine dissemination of Leishmania during active disease and the potential participation of human infection in transmission, Leishmania 7SLRNA was exploited to establish viability and estimate parasite burden in extralesional sites of dermal leishmaniasis patients.
Methods: The feasibility of discriminating parasite viability by PCR of Leishmania 7SLRNA was evaluated in relation with luciferase activity of luc transfected intracellular amastigotes in dose-response assays of Glucantime cytotoxicity. Monocytes, tonsil swabs, aspirates of normal skin and lesions of 28 cutaneous and 2 mucocutaneous leishmaniasis patients were screened by kDNA amplification/Southern blot. Positive samples were analyzed by quantitative PCR of Leishmania 7SLRNA genes and transcripts.
Results: 7SLRNA amplification coincided with luciferase activity, confirming discrimination of parasite viability. Of 22 patients presenting kDNA in extralesional samples, Leishmania 7SLRNA genes or transcripts were detected in one or more kDNA positive samples in 100% and 73% of patients, respectively. Gene and transcript copy number amplified from extralesional tissues were comparable to lesions. 7SLRNA transcripts were detected in 13/19 (68%) monocyte samples, 5/12 (42%) tonsil swabs, 4/11 (36%) normal skin aspirates, and 22/25 (88%) lesions; genes were quantifiable in 15/19 (79%) monocyte samples, 12/13 (92%) tonsil swabs, 8/11 (73%) normal skin aspirates.
Conclusion: Viable parasites are present in extralesional sites, including blood monocytes, tonsils and normal skin of dermal leishmaniasis patients. Leishmania 7SLRNA is an informative target for clinical and epidemiologic investigations of human leishmaniasis.
C1 [Romero, Ibeth; Tellez, Jair; Suarez, Yazmin; Cardona, Maria; Figueroa, Roger; Gore Saravia, Nancy] CIDEIM, Cali, Colombia.
[Zelazny, Adrian] NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Romero, I (reprint author), CIDEIM, Cali, Colombia.
EM jaircinio@gmail.com
RI Tellez, Jair/J-2386-2016; Romero, Ibeth/F-3260-2017
OI Tellez, Jair/0000-0001-6646-8069; Romero, Ibeth/0000-0002-0459-8383
FU National Scientific Research Council of Colombia [365-2006]; USNIH
NIAID-ICDR [U19 A1065866]; Fogarty Global Infectious Disease [1D43
TW006589, 2D43 TW006589-06]; COLCIENCIAS [098-2007]
FX This work was supported by National Scientific Research Council of
Colombia (COLCIENCIAS) (Project Code: 365-2006), USNIH NIAID-ICDR, grant
U19 A1065866 and Fogarty Global Infectious Disease Research Training
grants 1D43 TW006589 and 2D43 TW006589-06. MC was supported by an award
from the COLCIENCIAS Young Investigator Program (contract 098-2007). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 24
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Z9 8
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD SEP
PY 2010
VL 4
IS 9
AR e819
DI 10.1371/journal.pntd.0000819
PG 5
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 655TB
UT WOS:000282271300010
ER
PT J
AU Rudicell, RS
Jones, JH
Wroblewski, EE
Learn, GH
Li, YY
Robertson, JD
Greengrass, E
Grossmann, F
Kamenya, S
Pintea, L
Mjungu, DC
Lonsdorf, EV
Mosser, A
Lehman, C
Collins, DA
Keele, BF
Goodall, J
Hahn, BH
Pusey, AE
Wilson, ML
AF Rudicell, Rebecca S.
Jones, James Holland
Wroblewski, Emily E.
Learn, Gerald H.
Li, Yingying
Robertson, Joel D.
Greengrass, Elizabeth
Grossmann, Falk
Kamenya, Shadrack
Pintea, Lilian
Mjungu, Deus C.
Lonsdorf, Elizabeth V.
Mosser, Anna
Lehman, Clarence
Collins, D. Anthony
Keele, Brandon F.
Goodall, Jane
Hahn, Beatrice H.
Pusey, Anne E.
Wilson, Michael L.
TI Impact of Simian Immunodeficiency Virus Infection on Chimpanzee
Population Dynamics
SO PLOS PATHOGENS
LA English
DT Article
ID GOMBE NATIONAL-PARK; PAN-TROGLODYTES-SCHWEINFURTHII; WILD CHIMPANZEES;
GENETIC-MARKERS; COTE-DIVOIRE; MORTALITY; TANZANIA; UGANDA; HIV-1; AIDS
AB Like human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus of chimpanzees (SIVcpz) can cause CD4+ T cell loss and premature death. Here, we used molecular surveillance tools and mathematical modeling to estimate the impact of SIVcpz infection on chimpanzee population dynamics. Habituated (Mitumba and Kasekela) and non-habituated (Kalande) chimpanzees were studied in Gombe National Park, Tanzania. Ape population sizes were determined from demographic records (Mitumba and Kasekela) or individual sightings and genotyping (Kalande), while SIVcpz prevalence rates were monitored using non-invasive methods. Between 2002-2009, the Mitumba and Kasekela communities experienced mean annual growth rates of 1.9% and 2.4%, respectively, while Kalande chimpanzees suffered a significant decline, with a mean growth rate of -6.5% to -7.4%, depending on population estimates. A rapid decline in Kalande was first noted in the 1990s and originally attributed to poaching and reduced food sources. However, between 2002-2009, we found a mean SIVcpz prevalence in Kalande of 46.1%, which was almost four times higher than the prevalence in Mitumba (12.7%) and Kasekela (12.1%). To explore whether SIVcpz contributed to the Kalande decline, we used empirically determined SIVcpz transmission probabilities as well as chimpanzee mortality, mating and migration data to model the effect of viral pathogenicity on chimpanzee population growth. Deterministic calculations indicated that a prevalence of greater than 3.4% would result in negative growth and eventual population extinction, even using conservative mortality estimates. However, stochastic models revealed that in representative populations, SIVcpz, and not its host species, frequently went extinct. High SIVcpz transmission probability and excess mortality reduced population persistence, while intercommunity migration often rescued infected communities, even when immigrating females had a chance of being SIVcpz infected. Together, these results suggest that the decline of the Kalande community was caused, at least in part, by high levels of SIVcpz infection. However, population extinction is not an inevitable consequence of SIVcpz infection, but depends on additional variables, such as migration, that promote survival. These findings are consistent with the uneven distribution of SIVcpz throughout central Africa and explain how chimpanzees in Gombe and elsewhere can be at equipoise with this pathogen.
C1 [Rudicell, Rebecca S.; Hahn, Beatrice H.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA.
[Jones, James Holland] Stanford Univ, Dept Anthropol, Stanford, CA 94305 USA.
[Jones, James Holland] Stanford Univ, Woods Inst Environm, Stanford, CA 94305 USA.
[Wroblewski, Emily E.; Mjungu, Deus C.; Lehman, Clarence; Wilson, Michael L.] Univ Minnesota, Dept Ecol Evolut & Behav, St Paul, MN 55108 USA.
[Learn, Gerald H.; Li, Yingying; Robertson, Joel D.; Hahn, Beatrice H.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Greengrass, Elizabeth] Fauna & Flora Int, Monrovia, Liberia.
[Grossmann, Falk] Wildlife Conservat Soc, Africa Program, Bronx, NY USA.
[Kamenya, Shadrack; Mosser, Anna; Collins, D. Anthony] Gombe Stream Res Ctr, Jane Goodall Inst, Kigoma, Tanzania.
[Pintea, Lilian; Goodall, Jane] Jane Goodall Inst, Arlington, VA USA.
[Lonsdorf, Elizabeth V.] Lester E Fisher Ctr Study & Conservat Apes, Chicago, IL USA.
[Keele, Brandon F.] NCI, SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick, MD 21701 USA.
[Pusey, Anne E.] Duke Univ, Dept Evolutionary Anthropol, Durham, NC USA.
[Wilson, Michael L.] Univ Minnesota, Dept Anthropol, Minneapolis, MN USA.
RP Rudicell, RS (reprint author), Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA.
EM wilso198@umn.edu
OI Jones, James/0000-0003-1680-6757
FU National Institutes of Health [R01 AI50529, R01 AI58715, T32 GM008111,
K01 HD051494]; UAB Center for AIDS Research [P30 AI 27767]; National
Science Foundation [DBS-9021946, SBR-9319909, BSC-0452315, IIS-0431141,
BSC-0648481]; Jane Goodall Institute; Harris Steel Group; University of
Minnesota; American Foundation of AIDS Research (amFAR); National Cancer
Institute [HHSN266200400088C]; Howard Hughes Medical Institute; Leakey
Foundation
FX This work was supported by grants from the National Institutes of Health
(R01 AI50529, R01 AI58715, T32 GM008111, K01 HD051494), the UAB Center
for AIDS Research (P30 AI 27767), the National Science Foundation
(DBS-9021946, SBR-9319909, BSC-0452315, IIS-0431141, BSC-0648481), the
Jane Goodall Institute, the Harris Steel Group, and the University of
Minnesota. B.F.K. was funded by a fellowship by the American Foundation
of AIDS Research (amFAR) and the National Cancer Institute under
contract no. HHSN266200400088C; R. S. R. was funded by a Howard Hughes
Medical Institute Med-into-Grad Fellowship. L. P. was funded by the
Leakey Foundation. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 56
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U1 4
U2 30
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD SEP
PY 2010
VL 6
IS 9
AR e1001116
DI 10.1371/journal.ppat.1001116
PG 17
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 656WY
UT WOS:000282373000015
PM 20886099
ER
PT J
AU Xu, HJ
Caimano, MJ
Lin, T
He, M
Radolf, JD
Norris, SJ
Gheradini, F
Wolfe, AJ
Yang, XF
AF Xu, Haijun
Caimano, Melissa J.
Lin, Tao
He, Ming
Radolf, Justin D.
Norris, Steven J.
Gheradini, Frank
Wolfe, Alan J.
Yang, X. Frank
TI Role of Acetyl-Phosphate in Activation of the Rrp2-RpoN-RpoS Pathway in
Borrelia burgdorferi
SO PLOS PATHOGENS
LA English
DT Article
ID 2-COMPONENT SIGNAL-TRANSDUCTION; LYME-DISEASE SPIROCHETE; OUTER-SURFACE
PROTEIN; RESPONSE REGULATOR PROTEINS; ESCHERICHIA-COLI; MAMMALIAN
INFECTION; CLONAL POPULATIONS; GENE-EXPRESSION; SALIVARY-GLANDS;
IN-VITRO
AB Borrelia burgdorferi, the Lyme disease spirochete, dramatically alters its transcriptome and proteome as it cycles between the arthropod vector and mammalian host. During this enzootic cycle, a novel regulatory network, the Rrp2-RpoN-RpoS pathway (also known as the sigma(54)-sigma(S) sigma factor cascade), plays a central role in modulating the differential expression of more than 10% of all B. burgdorferi genes, including the major virulence genes ospA and ospC. However, the mechanism(s) by which the upstream activator and response regulator Rrp2 is activated remains unclear. Here, we show that none of the histidine kinases present in the B. burgdorferi genome are required for the activation of Rrp2. Instead, we present biochemical and genetic evidence that supports the hypothesis that activation of the Rrp2-RpoN-RpoS pathway occurs via the small, high-energy, phosphoryl-donor acetyl phosphate (acetyl similar to P), the intermediate of the Ack-Pta (acetate kinase-phosphate acetyltransferase) pathway that converts acetate to acetyl-CoA. Supplementation of the growth medium with acetate induced activation of the Rrp2-RpoN-RpoS pathway in a dose-dependent manner. Conversely, the overexpression of Pta virtually abolished acetate-induced activation of this pathway, suggesting that acetate works through acetyl similar to P. Overexpression of Pta also greatly inhibited temperature and cell density-induced activation of RpoS and OspC, suggesting that these environmental cues affect the Rrp2-RpoN-RpoS pathway by influencing acetyl similar to P. Finally, overexpression of Pta partially reduced infectivity of B. burgdorferi in mice. Taken together, these findings suggest that acetyl similar to P is one of the key activating molecule for the activation of the Rrp2-RpoN-RpoS pathway and support the emerging concept that acetyl similar to P can serve as a global signal in bacterial pathogenesis.
C1 [Xu, Haijun] Zhejiang Univ, Inst Insect Sci, Hangzhou 310003, Zhejiang, Peoples R China.
[Xu, Haijun; He, Ming; Yang, X. Frank] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN USA.
[Caimano, Melissa J.; Radolf, Justin D.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA.
[Lin, Tao; Radolf, Justin D.] Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, Farmington, CT USA.
[Norris, Steven J.] Univ Texas Houston, Sch Med, Dept Pathol & Lab Med, Houston, TX 77030 USA.
[Gheradini, Frank] NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA.
[Wolfe, Alan J.] Loyola Univ Chicago, Stritch Sch Med, Dept Microbiol & Immunol, Maywood, IL USA.
RP Xu, HJ (reprint author), Zhejiang Univ, Inst Insect Sci, Hangzhou 310003, Zhejiang, Peoples R China.
EM xfyang@iupui.edu
RI Yang, X. Frank/F-3266-2010;
OI Norris, Steven/0000-0002-2501-8034; Xu, Hai-Jun/0000-0002-7314-377X
FU NIH [R03 AR054942, R01 AI083640, AI-29735, GM066130]; National Research
Fund; American Heart Association; Lilly Endowment, Inc.
FX Funding for this work was partially provided by NIH grants R03 AR054942,
R01 AI083640 (to X.F.Y.), AI-29735 (to J.D.R. and M.J.C.), GM066130 (to
A.J.W.), a National Research Fund for Tick-Borne Diseases grant (to
M.J.C.), an American Heart Association Scientist Development Grant (to
X.F.Y.), and Indiana INGEN and METACyt grants of Indiana University,
funded by the Lilly Endowment, Inc. (to X.F.Y.). The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 68
TC 50
Z9 52
U1 3
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD SEP
PY 2010
VL 6
IS 9
AR e1001104
DI 10.1371/journal.ppat.1001104
PG 13
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 656WY
UT WOS:000282373000026
PM 20862323
ER
PT J
AU Brell, JM
AF Brell, Joanna M.
TI Prolonged QTc interval in Cancer Therapeutic Drug Development: Defining
Arrhythmic Risk in Malignancy'
SO PROGRESS IN CARDIOVASCULAR DISEASES
LA English
DT Review
ID TORSADES-DE-POINTES; PROARRHYTHMIC RISK; ANTICANCER AGENTS; ONCOLOGY;
CHALLENGES; RELEVANCE; TRIALS; LONG
AB Anticancer therapy drug development is an arduous task, taking 10 to 15 years to complete, requiring approximately I billion dollars, and rarely leads to Food and Drug Administration approval Methods to predict unacceptable drug-induced toxicity, such as a prolonged QTc interval/risk of torsade de pointes, should be highly informative to quickly and accurately determine if further resources should be allocated in the continued development of an agent Expert consensus has established guidelines to ascertain the ability of a new drug to prolong the QTc interval Although QTc measurement is the best way to assess arrhythmic risk, it is imprecise for a variety of reasons In addition, oncology patients have multiple risk factors for QTc prolongation at baseline Competing interests involved in assessing arrhythmic risk of a new oncology agent include inability to precisely follow published guidelines for QTc assessment, patients' concomitant medical problems interfering with drug assessment and therefore clinical trial enrollment, patient safety concerns, general public safety concerns regarding toxicity assessment, need for discovery of more curative drug therapies, and individual patient perception of therapeutic risk vs benefit Oncology patients are concerned about access to experimental agents, as well as early abandonment of a potentially beneficial agent because of a low estimated risk of toxicity, even if the event is catastrophic We review the issues involved in evaluating the QTc interval prolonging risk in new anticancer agents (Prog Cardiovasc Dis 2010,53: 164-172) (C) 2010 Elsevier Inc All rights reserved
C1 NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
RP Brell, JM (reprint author), NCI, Canc Prevent Div, NIH, 6130 Execut Blvd,EPN 2017, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [Z99 CA999999]
NR 31
TC 20
Z9 20
U1 0
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0033-0620
J9 PROG CARDIOVASC DIS
JI Prog. Cardiovasc. Dis.
PD SEP-OCT
PY 2010
VL 53
IS 2
BP 164
EP 172
DI 10.1016/j.pcad.2010.05.005
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 645TC
UT WOS:000281488100012
PM 20728704
ER
PT J
AU Shah, NG
Tulapurkar, ME
Singh, IS
Shelhamer, JH
Cowan, MJ
Hasday, JD
AF Shah, Nirav G.
Tulapurkar, Mohan E.
Singh, Ishwar S.
Shelhamer, James H.
Cowan, Mark J.
Hasday, Jeffrey D.
TI Prostaglandin E2 potentiates heat shock-induced heat shock protein 72
expression in A549 cells
SO PROSTAGLANDINS & OTHER LIPID MEDIATORS
LA English
DT Article
DE Heat shock; HSP-72; Prostaglandin E2; Arachidonic acid
ID CYTOSOLIC PHOSPHOLIPASE A(2); TRANSCRIPTION FACTOR-I;
GENE-TRANSCRIPTION; DNA-BINDING; ARACHIDONIC-ACID; ACTIVATION; FACTOR-1;
STRESS; HSP70; PHOSPHORYLATION
AB The heat shock (HS) response is an important cytoprotective response comprising the expression of heat shock proteins (HSPs) and orchestrated by the heat/stress-induced transcription factor, heat shock factor-1 (HSF-1) Previous studies suggest that the activation threshold and magnitude of the HS response may be modified by treatment with arachidonic acid (AA) We analyzed the effect of exogenous AA and its metabolites, PGE(2), LTD(4), and 15-HETE on HSF-1-dependent gene expression in A549 human respiratory epithelial-like cells When added at 1 mu M, PGE(2) much more than LTD(4), but not 15-HETE Increased activity of a synthetic HSF-1-dependent reporter after HS exposure (42 degrees C for 2h), but had no effect in the absence of HS. Exposing A549 cells to HS stimulated the release of PGE(2) and treatment with the cyclooxygenase ibuprofen. reduced HS-induced HSF-1-dependent transcription PGE(2) Increased HS-induced HSP72 mRNA and protein expression but EMSA and Western blot analysis failed to show an effect on HSF-1 DNA binding activity or post-translational modification. In summary, we showed that HS stimulates the generation of PGE(2), which augments the generation of HSPs The clinical consequences of this pathway have yet to be determined (C) 2010 Elsevier Inc All rights reserved
C1 [Shah, Nirav G.; Tulapurkar, Mohan E.; Singh, Ishwar S.; Cowan, Mark J.; Hasday, Jeffrey D.] Univ Maryland, Sch Med, Dept Med, Div Pulm & Crit Care,Hlth Sci Fac 2, Baltimore, MD 21201 USA.
[Singh, Ishwar S.; Hasday, Jeffrey D.] Univ Maryland, Sch Med, Mucosal Biol Res Ctr, Baltimore, MD 21201 USA.
[Singh, Ishwar S.; Cowan, Mark J.; Hasday, Jeffrey D.] Res Serv Baltimore VA Med Ctr, Baltimore, MD 21201 USA.
[Shelhamer, James H.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
RP Hasday, JD (reprint author), Univ Maryland, Sch Med, Dept Med, Div Pulm & Crit Care,Hlth Sci Fac 2, Rm S347,20 Penn St, Baltimore, MD 21201 USA.
RI tulapurkar, mohan/F-1926-2015
OI tulapurkar, mohan/0000-0002-2476-5417
FU NIH [GM069431, GM066855, HL69057, HL085256]; VA
FX This work was supported by NIH grants GM069431 (ISS) and GM066855,
HL69057 and HL085256 (JDH), and by VA Merit Review grants (JDH and ISS).
NR 50
TC 6
Z9 6
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1098-8823
J9 PROSTAG OTH LIPID M
JI Prostaglandins Other Lipid Mediat.
PD SEP
PY 2010
VL 93
IS 1-2
BP 1
EP 7
DI 10.1016/j.prostaglandins.2010.03.006
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 649DO
UT WOS:000281748000001
PM 20382255
ER
PT J
AU Moulaei, T
Stuchlik, O
Reed, M
Yuan, WR
Pohl, J
Lu, WY
Haugh-Krumpe, L
O'Keefe, BR
Wlodawer, A
AF Moulaei, Tinoush
Stuchlik, Olga
Reed, Matthew
Yuan, Weirong
Pohl, Jan
Lu, Wuyuan
Haugh-Krumpe, Lauren
O'Keefe, Barry R.
Wlodawer, Alexander
TI Topology of the disulfide bonds in the antiviral lectin scytovirin
SO PROTEIN SCIENCE
LA English
DT Article
DE lectins; disulfides; disulfide interchange; protein domain; mass
spectrometry; synthetic protein
ID SOMATOMEDIN-B-DOMAIN; CYANOBACTERIUM SCYTONEMA-VARIUM; ANTI-HIV PROTEIN;
MASS-SPECTROMETRY; HUMAN VITRONECTIN; PEPTIDE; POTENT; DESULFURIZATION;
CHEMISTRY; RESIDUES
AB The antiviral lectin scytovirin (SVN) contains a total of five disulfide bonds in two structurally similar domains. Previous reports provided contradictory results on the disulfide pairing in each individual domain, and we have now re-examined the disulfide topology. N-terminal sequencing and mass spectrometry were used to analyze proteolytic fragments of native SVN obtained at acidic pH, yielding the assignment as Cys7-Cys55, Cys20-Cys32, Cys26-Cys38, Cys68-Cys80, and Cys74-Cys86. We also analyzed the N-terminal domain of SVN (SD1, residues 1-48) prepared by expression/oxidative folding of the recombinant protein and by chemical synthesis. The disulfide pairing in the chemically synthesized SD1 was forced into predetermined topologies: SD1A (Cys20-Cys26, Cys32-Cys38) or SD1 B (Cys20-Cys32, Cys26-Cys38). The topology of native SVN was found to be in agreement with the SD1B and the one determined for the recombinant SD1 domain. Although the two synthetic forms of SD1 were distinct when subjected to chromatography, their antiviral properties were indistinguishable, having low nM activity against HIV. Tryptic fragments, the "cystine clusters" [Cys20-Cys32/Cys26-Cys38; SD1] and [Cys68-Cys80/Cys74-C-86; SD2], were found to undergo rapid disulfide interchange at pH 8. This interchange resulted in accumulation of artifactual fragments in alkaline pH digests that are structurally unrelated to the original topology, providing a rational explanation for the differences between the topology reported herein and the one reported earlier (Bokesh et al., Biochemistry 2003;42:2578-2584). Our observations emphasize the fact that proteins such as SVN, with disulfide bonds in close proximity, require considerable precautions when being fragmented for the purpose of disulfide assignment.
C1 [Moulaei, Tinoush; Wlodawer, Alexander] NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA.
[Stuchlik, Olga; Reed, Matthew; Pohl, Jan] Ctr Dis Control & Prevent, Biotechnol Core Facil Branch, Div Sci Resources, Atlanta, GA 30333 USA.
[Yuan, Weirong; Lu, Wuyuan] Univ Maryland, Sch Med, Inst Human Virol, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA.
[Haugh-Krumpe, Lauren] NCI, SAIC Frederick Inc, Frederick, MD 21702 USA.
[O'Keefe, Barry R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Wlodawer, A (reprint author), NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA.
EM wlodawer@nih.gov
RI Lu, Wuyuan/B-2268-2010
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research; Office of the Director of the National Institutes of Health;
National Institute of Allergy and Infectious Diseases, National
Institutes of Health [5R01A1072732]
FX Contract sponsor: National Cancer Institute, National Institutes of
Health; Contract number: HHSN261200800001E; Grant sponsors: Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research, Intramural AIDS Targeted Antiviral Program of the
Office of the Director of the National Institutes of Health; National
Institute of Allergy and Infectious Diseases, National Institutes of
Health; Grant number: 5R01A1072732.
NR 31
TC 5
Z9 5
U1 1
U2 3
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0961-8368
J9 PROTEIN SCI
JI Protein Sci.
PD SEP
PY 2010
VL 19
IS 9
BP 1649
EP 1661
DI 10.1002/pro.445
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 646SL
UT WOS:000281563000005
PM 20572021
ER
PT J
AU Cohen, RA
AF Cohen, Robert A.
TI Notes on the Life and Work of Frieda Fromm-Reichmann
SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES
LA English
DT Reprint
AB IT IS now 25 years since Frieda Fromm-Reichmann died over 30 years since she published her only book, Principles of Intensive Psychotherapy. Most of those who now attend the presentations of the annual research award of the Academy or the annual lectures of the Washington School of Psychiatry, both of which are named in her honor, never saw her. It seem appropriate to ask whether she still speaks to us today, whether in any significant way she influenced the development of what is now common practice in our field.
C1 [Cohen, Robert A.] Chestnut Lodge, Rockville, MD 20850 USA.
[Cohen, Robert A.] NIMH, Div Clin & Behav Res, Bethesda, MD USA.
RP Cohen, RA (reprint author), Chestnut Lodge, Rockville, MD 20850 USA.
NR 5
TC 0
Z9 0
U1 0
U2 2
PU GUILFORD PUBLICATIONS INC
PI NEW YORK
PA 72 SPRING STREET, NEW YORK, NY 10012 USA
SN 0033-2747
J9 PSYCHIATRY
JI Psychiatry-Interpers. Biol. Process.
PD FAL
PY 2010
VL 73
IS 3
BP 209
EP 218
PG 10
WC Psychiatry
SC Psychiatry
GA 649OU
UT WOS:000281782600002
PM 20843211
ER
PT J
AU Sutin, AR
Terracciano, A
Deiana, B
Naitza, S
Ferrucci, L
Uda, M
Schlessinger, D
Costa, PT
AF Sutin, A. R.
Terracciano, A.
Deiana, B.
Naitza, S.
Ferrucci, L.
Uda, M.
Schlessinger, D.
Costa, P. T., Jr.
TI High Neuroticism and low Conscientiousness are associated with
interleukin-6
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE C-reactive protein; health; impulsivity; inflammation; interleukin-6;
personality
ID NEO-PI-R; ANTIINFLAMMATORY SIGNALING PATHWAYS; C-REACTIVE PROTEIN;
PERSONALITY-TRAITS; INFLAMMATORY MARKERS; PSYCHOSOCIAL FACTORS; CAREER
SUCCESS; 5-FACTOR MODEL; HEALTH-STATUS; LIFE-SPAN
AB Background. High Neuroticism and low Conscientiousness are frequently implicated in health-risk behaviors, such as smoking and overeating, as well as health outcomes, including mortality. Their associations with physiological markers of morbidity and mortality, such as inflammation, are less well documented. The present research examines the association between the five major dimensions of personality and interleukin-6 (IL-6), a pro-inflammatory cytokine often elevated in patients with chronic morbidity and frailty.
Method. A population-based sample (n-4923) from four towns in Sardinia, Italy, had their levels of IL-6 measured and completed a comprehensive personality questionnaire, the NEO-PI-R. Analyses controlled for factors known to have an effect on IL-6 : age; sex; smoking; weight; aspirin use; disease burden.
Results. High Neuroticism and low Conscientiousness were both associated with higher levels of IL-6. The findings remained significant after controlling for the relevant covariates. Similar results were found for C-reactive protein, a related marker of chronic inflammation. Further, smoking and weight partially mediated the association between impulsivity-related traits and higher IL-6 levels. Finally, logistic regressions revealed that participants either in the top 10% of the distribution of Neuroticism or the bottom 10% of conscientiousness had an approximately 40% greater risk of exceeding clinically relevant thresholds of IL-6.
Conclusions. Consistent with the literature on personality and self-reported health, individuals high on Neuroticism or low on Conscientiousness show elevated levels of this inflammatory cytokine. Identifying critical medical biomarkers associated with personality may help to elucidate the physiological mechanisms responsible for the observed connections between personality traits and physical health.
C1 [Sutin, A. R.] NIA, Lab Personal & Cognit, NIH, DHHS, Baltimore, MD 21224 USA.
[Deiana, B.; Naitza, S.; Uda, M.] CNR, Ist Neurogenet & Neurofarmacol, I-00185 Rome, Italy.
RP Sutin, AR (reprint author), NIA, Lab Personal & Cognit, NIH, DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM sutina@mail.nih.gov
RI terracciano, antonio/B-1884-2008; Naitza, Silvia/D-5620-2017;
OI Costa, Paul/0000-0003-4375-1712
FU NIH, National Institute on Aging
FX This research was supported entirely by the Intramural Research Program
of the NIH, National Institute on Aging.
NR 39
TC 73
Z9 74
U1 2
U2 31
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0033-2917
J9 PSYCHOL MED
JI Psychol. Med.
PD SEP
PY 2010
VL 40
IS 9
BP 1485
EP 1493
DI 10.1017/S0033291709992029
PG 9
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 644VD
UT WOS:000281408500008
PM 19995479
ER
PT J
AU Sutin, AR
Costa, PT
Wethington, E
Eaton, W
AF Sutin, Angelina R.
Costa, Paul T., Jr.
Wethington, Elaine
Eaton, William
TI Turning Points and Lessons Learned: Stressful Life Events and
Personality Trait Development Across Middle Adulthood
SO PSYCHOLOGY AND AGING
LA English
DT Article
DE five-factor model; personality; narrative; life events; turning points
ID SELF-DEFINING MEMORIES; EPIDEMIOLOGIC CATCHMENT-AREA; 5-FACTOR MODEL;
POSTTRAUMATIC GROWTH; TEMPORAL STABILITY; NARRATIVE IDENTITY; EMERGING
ADULTS; AGE-DIFFERENCES; MIDLIFE ADULTS; FOLLOW-UP
AB The present research examined stressful life events and personality development across middle adulthood. Participants (N = 533) related the most stressful event they had experienced within the last 10 years, indicated whether they considered the event to be a turning point and/or lesson learned, and twice completed a comprehensive measure of traits defined by the five-factor model of personality; the stressful event occurred between these two assessments. Descriptions were coded to classify events into broad content domains based on the nature of the event. Prospectively, individuals high in Neuroticism perceived the event as a turning point; extraverts learned a lesson from it. Longitudinally, perceiving the event as a negative turning point was associated with increases in Neuroticism, whereas learning a lesson from the event was associated with increases in Extraversion and Conscientiousness. Characteristics of the events themselves were primarily unrelated to trait change. Across middle adulthood, personality trait change may be more strongly related to how individuals understand the stressful events in their lives rather than simply the occurrence of such events.
C1 [Sutin, Angelina R.; Costa, Paul T., Jr.] NIA, Lab Personal & Cognit, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
[Wethington, Elaine] Cornell Univ, Dept Human Dev & Sociol, Ithaca, NY 14853 USA.
[Eaton, William] Johns Hopkins Univ, Dept Mental Hlth, Baltimore, MD 21218 USA.
RP Sutin, AR (reprint author), NIA, Lab Personal & Cognit, NIH, Dept Hlth & Human Serv, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM sutina@mail.nih.gov
OI Costa, Paul/0000-0003-4375-1712
FU Intramural NIH HHS; NIDA NIH HHS [DA026652]; NIMH NIH HHS [MH 47447, MH
50616, MH64543, R01 MH047447]
NR 58
TC 21
Z9 21
U1 4
U2 28
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0882-7974
J9 PSYCHOL AGING
JI Psychol. Aging
PD SEP
PY 2010
VL 25
IS 3
BP 524
EP 533
DI 10.1037/a0018751
PG 10
WC Gerontology; Psychology, Developmental
SC Geriatrics & Gerontology; Psychology
GA 651NR
UT WOS:000281934900003
PM 20853963
ER
PT J
AU Fox, MA
French, HT
LaPorte, JL
Blackler, AR
Murphy, DL
AF Fox, Meredith A.
French, Helen T.
LaPorte, Justin L.
Blackler, Adele R.
Murphy, Dennis L.
TI The serotonin 5-HT2A receptor agonist TCB-2: a behavioral and
neurophysiological analysis
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE TCB-2; DOI; MDL 11,939; 5-HT2A receptors; Serotonin transporter knockout
mice; Head twitch response; Feeding; Hypothermia; Corticosterone;
Anxiety
ID OBSESSIVE-COMPULSIVE DISORDER; TRANSPORTER KNOCKOUT MICE; HALLUCINOGENIC
PHENETHYLAMINE; FUNCTIONAL SELECTIVITY; HYPOTHERMIC RESPONSE;
ARACHIDONIC-ACID; RAT; LACKING; DOI; CORTICOSTERONE
AB There are few reports on the high-affinity 5-HT2A agonist (4-Bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine hydrobromide (TCB-2).
Here we provide the first behavioral and neurophysiological profile of TCB-2 in C57BL/6J mice, with direct comparisons to the 5-HT2A/2C agonist (+/-)-2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI), in addition to determinations of 5-HT2A mediation via pretreatment with the selective 5-HT2A antagonist MDL 11,939.
In a dose-dependent manner, TCB-2 induced head twitches, decreased food consumption in food-deprived mice, induced hypothermia, and increased corticosterone levels, with no effects on locomotor activity or anxiety-like behaviors in the open field. Similar effects were observed in side-by-side dose-response comparisons with DOI; although at the highest dose tested (5.0 mg/kg), TCB-2 induced significantly fewer head twitches, and a significantly enhanced hypothermic response, versus DOI. Pretreatment with MDL 11,939 blocked head twitches and temperature change following TCB-2 and DOI, confirming 5-HT2A mediation of these responses. Although MDL 11,939 pretreatment blocked DOI-induced suppression of feeding, MDL 11,939 had no effect on TCB-2-induced suppression of feeding. Previous studies show that 5-HT2A function is altered by changes in serotonin transporter (SERT) expression and function. In SERT knockout (-/-) mice, TCB-2-induced head twitches and hypothermia were greatly diminished compared to SERT wild-type (+/+) mice.
The current studies are important, as they are the first to assess the effects of TCB-2 in mice, and are among the first to report the behavioral and neurophysiological effects of this conformationally restricted phenethylamine analog compound, which has 65-fold greater effects on signaling via the phosphoinositide versus arachidonic acid pathways.
C1 [Fox, Meredith A.; French, Helen T.; LaPorte, Justin L.; Blackler, Adele R.; Murphy, Dennis L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA.
RP Fox, MA (reprint author), NIMH, Clin Sci Lab, NIH, 10 Ctr Dr,Bldg 10-3D41,MSC 1264, Bethesda, MD 20892 USA.
EM mfox@mail.nih.gov
FU NIMH
FX This research was supported by the NIMH Intramural Research program.
NR 44
TC 32
Z9 32
U1 3
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD SEP
PY 2010
VL 212
IS 1
BP 13
EP 23
DI 10.1007/s00213-009-1694-1
PG 11
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 638UQ
UT WOS:000280922900002
PM 19823806
ER
PT J
AU Choi, JK
Mandeville, JB
Chen, YI
Grundt, P
Sarkar, SK
Newman, AH
Jenkins, BG
AF Choi, Ji-Kyung
Mandeville, Joseph B.
Chen, Y. Iris
Grundt, Peter
Sarkar, Susanta K.
Newman, Amy H.
Jenkins, Bruce G.
TI Imaging brain regional and cortical laminar effects of selective D3
agonists and antagonists
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Cortical layers; Dopamine D3 receptor; Hippocampus; Hypothalamus;
Infralimbic cortex; Limbic circuitry; MRI; Nucleus accumbens; Subiculum
ID DOPAMINE D-3 RECEPTOR; ABUSE THERAPEUTIC AGENTS; COCAINE-SEEKING;
RAT-BRAIN; MRI; 7-OH-DPAT; PRIMATES; BINDING; CORTEX; LIGAND
AB Dopamine D3 receptors (D3R) may be important therapeutic targets for both drug abuse and dyskinesias in Parkinson's disease; however, little is known about their functional circuitry.
We wished to determine if D3R antagonists SB-277011 and PG-01037 and D3R-preferring agonist 7-OH-DPAT are D3R selective in vivo. We further wished to characterize the response to D3R drugs using whole brain imaging to identify novel D3R circuitry.
We investigated D3R circuitry in rats using pharmacologic MRI and challenge with selective D3R antagonists and agonist at various doses to examine regional changes in cerebral blood volume (CBV). We compared regional activation patterns with D2R/D3R agonists, as well as with prior studies of mRNA expression and autoradiography.
D3R antagonists induced positive CBV changes and D3R agonist negative CBV changes in brain regions including nucleus accumbens, infralimbic cortex, thalamus, interpeduncular region, hypothalamus, and hippocampus (strongest in subiculum). All D3R-preferring drugs showed markedly greater responses in nucleus accumbens than in caudate/putamen consistent with D3R selectivity and contrary to what was observed with D2R agonists. At high doses of D3R agonist, functional changes were differentiated across cortical laminae, with layer V-VI yielding positive CBV changes and layer IV yielding negative CBV changes. These results are not inconsistent with differential D1R and D3R innervation in these layers respectively showed previously using post-mortem techniques.
MRI provides a new tool for testing the in vivo selectivity of novel D3R dopaminergic ligands where radiolabels may not be available. Further, the functional D3R circuitry strongly involves hypothalamus and subiculum as well as the limbic striatum.
C1 [Choi, Ji-Kyung; Mandeville, Joseph B.; Chen, Y. Iris; Jenkins, Bruce G.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA.
[Choi, Ji-Kyung; Mandeville, Joseph B.; Chen, Y. Iris; Jenkins, Bruce G.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
[Grundt, Peter; Newman, Amy H.] NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD USA.
[Sarkar, Susanta K.] GlaxoSmithKline Inc, Med Dev, Oncol R&D, Collegeville, PA 19426 USA.
RP Jenkins, BG (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA.
EM bgj@nmr.mgh.harvard.edu
FU NIH/NIDA [DA16187-06]
FX This work was supported by NIH/NIDA DA16187-06.
NR 47
TC 17
Z9 17
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD SEP
PY 2010
VL 212
IS 1
BP 59
EP 72
DI 10.1007/s00213-010-1924-6
PG 14
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 638UQ
UT WOS:000280922900006
PM 20628733
ER
PT J
AU Cippitelli, A
Karlsson, C
Shaw, JL
Thorsell, A
Gehlert, DR
Heilig, M
AF Cippitelli, Andrea
Karlsson, Camilla
Shaw, Janice L.
Thorsell, Annika
Gehlert, Donald R.
Heilig, Markus
TI Suppression of alcohol self-administration and reinstatement of alcohol
seeking by melanin-concentrating hormone receptor 1 (MCH1-R) antagonism
in Wistar rats
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Footshock; Reinstatement; Alcohol; Seeking; Saccharin; MCH1-R
ID NUCLEUS-ACCUMBENS; COCAINE-SEEKING; DEFICIENT MICE; MESSENGER-RNA;
DOPAMINE; SYSTEM; BRAIN; BEHAVIOR; ETHANOL; REWARD
AB Melanin-concentrating hormone (MCH) is involved in regulation of appetitive behaviors as well as emotional reactivity and reward, behavioral domains relevant to alcohol addiction.
We evaluated the effects of the non-peptide MCH1 receptor antagonist, GW803430 [6-(4-chloro-phenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-3H-thieno[3,2-d]pyrimidin-4-one; 3-30 mg/kg, i.p.] on alcohol-related behaviors in Wistar rats.
Ex vivo binding experiments demonstrated that the GW803430 dose range used resulted in high central MCH1 receptor occupancy. Alcohol self-administration was dose-dependently and potently suppressed, by approximately 80% at the highest dose. Reinstatement of alcohol-seeking induced by alcohol-associated cues was essentially eliminated. In contrast, reinstatement induced by footshock stress was not significantly altered. Taste preference for a quinine/saccharin solution, locomotor activity, and alcohol elimination were unaffected.
Together, these observations support a specific involvement of the MCH system in mediating alcohol reward and cue-induced relapse to alcohol seeking. MCH1-R antagonism may constitute an attractive treatment target for alcohol use disorders.
C1 [Cippitelli, Andrea; Karlsson, Camilla; Thorsell, Annika; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
[Shaw, Janice L.; Gehlert, Donald R.] Div Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN USA.
RP Heilig, M (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, 10 Ctr Dr,1-5330, Bethesda, MD 20892 USA.
EM markus.heilig@mail.nih.gov
OI Heilig, Markus/0000-0003-2706-2482; Thorsell, Annika/0000-0003-3535-3845
NR 39
TC 21
Z9 21
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD SEP
PY 2010
VL 211
IS 4
BP 367
EP 375
DI 10.1007/s00213-010-1891-y
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 630AP
UT WOS:000280243700001
PM 20628734
ER
PT J
AU Wang, YF
Beydoun, MA
Caballero, B
Gary, TL
Lawrence, R
AF Wang, Youfa
Beydoun, May A.
Caballero, Benjamin
Gary, Tiffany L.
Lawrence, Robert
TI Trends and correlates in meat consumption patterns in the US adult
population
SO PUBLIC HEALTH NUTRITION
LA English
DT Article
DE Meat consumption; Food intake; Trend; Diet; NHANES; CSFII; United States
ID WEIGHT-LOSS; FOOD-INTAKE; SOCIOECONOMIC-STATUS; DIETARY-INTAKE;
ENERGY-INTAKE; QUALITY; HEALTH; ATKINS; WOMEN; RISK
AB Objective: Few studies have examined recent shifts in meat consumption (MC), differences among US population groups, and the influence of psychosocial-behavioural factors.
Design: Nationally representative data collected for US adults aged >= 18 years in the 1988-1994 and 1999-2004 National Health and Nutrition Examination Survey (NHANES) and the 1994-1996 Continuing Survey of Food Intakes by Individuals (CSFII) and Diet and Health Knowledge Survey (DHKS) were used.
Results: We found a U-shaped trend in MC, a decrease between 1988-1994 and 1994-1996, and an increase from 1994-1996 to 1999-2004. NHANES 1988-1994 and 1999-2004 indicate that MC did not change significantly, particularly for all meat, red meat, poultry and seafood. Between 1994-1996 and 1999-2004, average MC, including red meat, poultry, seafood and other meat products, increased in men. Women's total MC decreased, mainly due to decreased red meat and other meat products, except for increased seafood. Noticeable differences existed in the changes across population groups. Black men had the largest increase in consumption of total meat, poultry and seafood; Mexican American men had the smallest increase in poultry, seafood and other meat products. In 1999-2004, ethnic differences in MC became greater in women than among women in 1994-1996. Associations between MC and energy intake changed over time. Perceived benefit of dietary quality and food label use were associated with reduced red MC.
Conclusions: Noticeable differences exist in the shifts in MC across population groups and surveys. MC increased in men but decreased in women in recent years.
C1 [Wang, Youfa; Beydoun, May A.; Caballero, Benjamin] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Human Nutr, Dept Int Hlth, Baltimore, MD 21205 USA.
[Wang, Youfa; Gary, Tiffany L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Beydoun, May A.] NIA, NIH, IRP, Bethesda, MD 20892 USA.
[Lawrence, Robert] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Livable Future, Dept Environm Hlth Sci, Baltimore, MD 21205 USA.
RP Wang, YF (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Human Nutr, Dept Int Hlth, 615 N Wolfe St, Baltimore, MD 21205 USA.
EM ywang@jhsph.edu
FU Johns Hopkins Center for a Livable Future; US Department of Agriculture
[2044-05322]; NIDDK/NIH [R01DK81335-01A1]; NICHD/NIH [R03HD058077-01A1,
R03HD056073]; National Institute on Aging (NIA/NIH/IRP)
FX The study was supported in part by the Johns Hopkins Center for a
Livable Future, the US Department of Agriculture (2044-05322), the
NIDDK/NIH (R01DK81335-01A1), the NICHD/NIH (R03HD058077-01A1,
R03HD056073) and the Intramural Research Program of the National
Institute on Aging (NIA/NIH/IRP). Y.W. contributed to the
conceptualisation, statistical analysis, literature review,
interpretation of results and write-up of manuscript. M. A. B. helped
the data management and statistical analysis, interpretation of results,
literature review and write-up of the manuscript. B. C., T. L. G and R.
L. interpreted the results and revised the manuscript. The authors
declare that they have no conflict of interest.
NR 40
TC 22
Z9 24
U1 1
U2 12
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 1368-9800
J9 PUBLIC HEALTH NUTR
JI Public Health Nutr.
PD SEP
PY 2010
VL 13
IS 9
BP 1333
EP 1345
DI 10.1017/S1368980010000224
PG 13
WC Public, Environmental & Occupational Health; Nutrition & Dietetics
SC Public, Environmental & Occupational Health; Nutrition & Dietetics
GA 652RC
UT WOS:000282026600007
PM 20188005
ER
PT J
AU Schulte, JM
Kay, R
Hamilton, JJ
Mellinger, C
Yambor, P
Luce, C
Ginzl, D
Gill, J
Hopkins, RS
AF Schulte, Joann M.
Kay, Robyn
Hamilton, Janet J.
Mellinger, Cathy
Yambor, Phyllis
Luce, Christie
Ginzl, Dawn
Gill, Julia
Hopkins, Richard S.
TI Pertussis in Florida, 2000-2006: Trends in a Historically Low-Incidence
State
SO PUBLIC HEALTH REPORTS
LA English
DT Article
ID UNITED-STATES; ADULTS; VACCINE; ADOLESCENTS; MORBIDITY; RECOMMENDATIONS;
INFECTION; DISEASE; PCR
AB Objective. Florida, the fourth most populous state in the nation, has had historically low incidence rates of pertussis, the only vaccine-preventable disease with increasing numbers of reported cases. We compared the epidemiology and incidence rates of pertussis in Florida with other states and the United States.
Methods. We used Florida and federal surveillance data from 2000 through 2006.
Results. Reported incidence of pertussis in Florida, numbers of cases, and proportions of adolescents and adults all increased during the seven-year study period. Florida incidence rates increased from 0.44 to 1.28, but the state's incidence was always ranked 45th or lower among the states. Reported pertussis cases and those among adolescents and adults in Florida increased during the study period. Ten counties, containing 60% of Florida's population, reported two-thirds of the state's cases.
Conclusions. Pertussis reported from Florida mirrored national trends with increasing incidence, numbers of cases, and proportions of adolescent and adult cases. Despite the increases, Florida maintained its historic pattern of pertussis incidence rates that are consistently lower than national figures. Limited laboratory diagnostics and a focus on the pediatric population likely contributed to the lower rates of pertussis in Florida. More emphasis on surveillance of adolescent and adult cases is needed.
C1 [Schulte, Joann M.; Kay, Robyn; Hamilton, Janet J.; Mellinger, Cathy; Yambor, Phyllis; Luce, Christie; Ginzl, Dawn; Hopkins, Richard S.] Florida Dept Hlth, Bur Epidemiol, Tallahassee, FL USA.
[Schulte, Joann M.; Kay, Robyn; Hamilton, Janet J.; Mellinger, Cathy; Yambor, Phyllis; Luce, Christie; Ginzl, Dawn; Hopkins, Richard S.] Florida Dept Hlth, Bur Immunizat, Tallahassee, FL USA.
[Schulte, Joann M.; Gill, Julia] Ctr Dis Control & Prevent, Atlanta, GA USA.
RP Schulte, JM (reprint author), NIAID, NIH, DMID, STD Branch, 6610 Rockledge Dr,Rm 3106, Bethesda, MD 20817 USA.
EM schultej@niaid.nih.gov
NR 45
TC 1
Z9 1
U1 0
U2 0
PU ASSOC SCHOOLS PUBLIC HEALTH
PI WASHINGTON
PA 1101 15TH ST NW, STE 910, WASHINGTON, DC 20005 USA
SN 0033-3549
J9 PUBLIC HEALTH REP
JI Public Health Rep.
PD SEP-OCT
PY 2010
VL 125
IS 5
BP 728
EP 735
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 638MI
UT WOS:000280898600015
PM 20873289
ER
PT J
AU Bijwaard, H
Brenner, A
Dekkers, F
van Dilien, T
Land, CE
Boice, JD
AF Bijwaard, Harmen
Brenner, Alina
Dekkers, Fieke
van Dilien, Teun
Land, Charles E.
Boice, John D., Jr.
TI Breast Cancer Risk from Different Mammography Screening Practices
SO RADIATION RESEARCH
LA English
DT Article
ID LUNG-CANCER; 2-STAGE MODEL; STEM-CELLS; CARCINOGENESIS; RADIATION;
TUMOR; TUBERCULOSIS; POPULATIONS; SURVIVAL; COHORTS
AB Mammography screening is an accepted procedure for early detection of breast tumors among asymptomatic women. Since this procedure involves the use of X rays, it is itself potentially carcinogenic. Although there is general consensus about the benefit of screening for older women, screening practices differ between countries. In this paper radiation risks for these different practices are estimated using a new approach. We model breast cancer induction by ionizing radiation in a cohort of patients exposed to frequent X-ray examinations. The biologically based, mechanistic model provides a better foundation for the extrapolation of risks to different mammography screening practices than empirical models do. The model predicts that the excess relative risk (ERR) doubles when screening starts at age 40 instead of 50 and that a continuation of screening at ages 75 and higher carries little extra risk. The number of induced fatal breast cancers is estimated to be considerably lower than derived from epidemiological studies and from internationally accepted radiation protection risks. The present findings, if used in a risk-benefit analysis for mammography screening, would be more favorable to screening than estimates currently recommended for radiation protection. This has implications for the screening ages that are currently being reconsidered in several countries. (C) 2010 by Radiation Research Society
C1 [Bijwaard, Harmen; Dekkers, Fieke; van Dilien, Teun] RIVM Natl Inst Publ Hlth & Environm, Radiat Res Lab, NL-3721 MA Bilthoven, Netherlands.
[Brenner, Alina; Land, Charles E.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
[Boice, John D., Jr.] Int Epidemiol Inst, Rockville, MD USA.
[Boice, John D., Jr.] Vanderbilt Univ, Dept Med, Nashville, TN USA.
[Boice, John D., Jr.] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
RP Bijwaard, H (reprint author), RIVM Natl Inst Publ Hlth & Environm, Radiat Res Lab, Antonie van Leeuwenhoeklaan 9, NL-3721 MA Bilthoven, Netherlands.
EM Harmen.Bijwaard@rivm.nl
FU Dutch National Institute for Public Health and the Environment (RIVM)
FX This work was supported by the strategic research program of the Dutch
National Institute for Public Health and the Environment (RIVM) and
conducted as a part of the Modelling Ionising Radiation And Cancer for
Low-dose Effects (MIRACLE) project.
NR 38
TC 9
Z9 9
U1 0
U2 9
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
J9 RADIAT RES
JI Radiat. Res.
PD SEP
PY 2010
VL 174
IS 3
BP 367
EP 376
DI 10.1667/RR2067.1
PG 10
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA 647ZH
UT WOS:000281658900012
PM 20726723
ER
PT J
AU Little, MP
Wakeford, R
Lubin, JH
Kendall, GM
AF Little, M. P.
Wakeford, R.
Lubin, J. H.
Kendall, G. M.
TI The Statistical Power of Epidemiological Studies Analyzing the
Relationship between Exposure to Ionizing Radiation and Cancer, with
Special Reference to Childhood Leukemia and Natural Background Radiation
SO RADIATION RESEARCH
LA English
DT Article
ID GREAT-BRITAIN; NATIONAL-REGISTRY; DOMESTIC SOURCES; BOMB SURVIVORS;
RADON; MORTALITY; RISK; DOSIMETRY; CHILDREN; DISEASE
AB The etiology of childhood leukemia remains generally unknown, although risk models based on the Japanese A-bomb survivors imply that the dose accumulated from protracted exposure to low-level natural background ionizing radiation materially raises the risk of leukemia in children. In this paper a novel Monte Carlo score-test methodology is used to assess the statistical power of cohort, ecological and case-control study designs, using the linear low-dose part of the BEIRV model derived from the Japanese data. With 10 (or 20) years of follow-up of childhood leukemias in Great Britain, giving about 4600 (or 9200) cases, under an individual-based cohort design there is 67.9% (or 90.9%) chance of detecting an excess (at 5% significance level, one-sided test); little difference is made by extreme heterogeneity in risk. For an ecological design these figures reduce to 57.9% (or 83.2%). Case-control studies with five controls per case achieve much of the power of a cohort design, 61.1% (or 86.0%). However, participation bias may seriously affect studies that require individual consent, and area-based studies are subject to severe interpretational problems. For this reason register-based studies, in particular those that make use of predicted doses that avoid the need for interviews, have considerable advantages. We argue that previous studies have been underpowered (all have power <80%), and some are also subject to unquantifiable biases and confounding. Sufficiently large studies should be capable of detecting the predicted risk attributable to natural background radiation. (C) 2010 by Radiation Research Society
C1 [Little, M. P.] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, Sch Publ Hlth, Fac Med, London W2 1PG, England.
[Wakeford, R.] Univ Manchester, Dalton Nucl Inst, Manchester M60 1QD, Lancs, England.
[Lubin, J. H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Kendall, G. M.] Univ Oxford, Childhood Canc Res Grp, Oxford OX3 7LG, England.
RP Little, MP (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, Sch Publ Hlth, Fac Med, London W2 1PG, England.
EM mark.little@nih.gov
OI Wakeford, Richard/0000-0002-2934-0987; Little, Mark/0000-0003-0980-7567
FU European Commission [FP6-036465]; National Institutes of Health; U.S.
National Cancer Institute, Department of Health and Human Services
FX The authors are grateful to Tim Vincent for supplying cancer incidence
data and to the three referees for their detailed and helpful comments.
MPL was funded partially by the European Commission under contract
FP6-036465 (NOTE). JHL was supported by the Intramural Research Program
of the National Institutes of Health and the U.S. National Cancer
Institute, Department of Health and Human Services.
NR 47
TC 19
Z9 19
U1 1
U2 8
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
J9 RADIAT RES
JI Radiat. Res.
PD SEP
PY 2010
VL 174
IS 3
BP 387
EP 402
DI 10.1667/RR2110.1
PG 16
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA 647ZH
UT WOS:000281658900014
PM 20726729
ER
PT J
AU Dachman, AH
Obuchowski, NA
Hoffmeister, JW
Hinshaw, JL
Frew, MI
Winter, TC
Van Uitert, RL
Periaswamy, S
Summers, RM
Hillman, BJ
AF Dachman, Abraham H.
Obuchowski, Nancy A.
Hoffmeister, Jeffrey W.
Hinshaw, J. Louis
Frew, Michael I.
Winter, Thomas C.
Van Uitert, Robert L.
Periaswamy, Senthil
Summers, Ronald M.
Hillman, Bruce J.
TI Effect of Computer-aided Detection for CT Colonography in a Multireader,
Multicase Trial
SO RADIOLOGY
LA English
DT Article
ID ASSISTED READER SOFTWARE; TOMOGRAPHIC COLONOGRAPHY; POLYP DETECTION;
DETECTION CAD; VIRTUAL COLONOSCOPY; 2ND READER; PRIMARY 2D; PERFORMANCE;
PARADIGM; SENSITIVITY
AB Purpose: To assess the effect of using computer-aided detection (CAD) in second-read mode on readers' accuracy in interpreting computed tomographic (CT) colonographic images.
Materials and Methods: The contributing institutions performed the examinations under approval of their local institutional review board, with waiver of informed consent, for this HIPAA-compliant study. A cohort of 100 colonoscopy-proved cases was used: In 52 patients with findings positive for polyps, 74 polyps of 6 mm or larger were observed in 65 colonic segments; in 48 patients with findings negative for polyps, no polyps were found. Nineteen blinded readers interpreted each case at two different times, with and without the assistance of a commercial CAD system. The effect of CAD was assessed in segment-level and patient-level receiver operating characteristic (ROC) curve analyses.
Results: Thirteen (68%) of 19 readers demonstrated higher accuracy with CAD, as measured with the segment-level area under the ROC curve (AUC). The readers' average segment-level AUC with CAD (0.758) was significantly greater (P = .015) than the average AUC in the unassisted read (0.737). Readers' per-segment, per-patient, and per-polyp sensitivity for all polyps of 6 mm or larger was higher (P < .011,.007,.005, respectively) for readings with CAD compared with unassisted readings (0.517 versus 0.465, 0.521 versus 0.466, and 0.477 versus 0.422, respectively). Sensitivity for patients with at least one large polyp of 10 mm or larger was also higher (P < .047) with CAD than without (0.777 versus 0.743). Average reader sensitivity also improved with CAD by more than 0.08 for small adenomas. Use of CAD reduced specificity of readers by 0.025 (P = .05).
Conclusion: Use of CAD resulted in a significant improvement in overall reader performance. CAD improves reader sensitivity when measured per segment, per patient, and per polyp for small polyps and adenomas and also reduces specificity by a small amount. (C) RSNA, 2010
C1 [Dachman, Abraham H.] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA.
[Obuchowski, Nancy A.] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH USA.
[Hoffmeister, Jeffrey W.; Van Uitert, Robert L.; Periaswamy, Senthil] ICAD, Nashua, NH USA.
[Hinshaw, J. Louis] Univ Wisconsin Hosp & Clin, Dept Radiol, Madison, WI USA.
[Frew, Michael I.] Walter Reed Army Med Ctr, Dept Radiol, Washington, DC 20307 USA.
[Winter, Thomas C.] Univ Utah, Dept Radiol, Salt Lake City, UT 84132 USA.
[Summers, Ronald M.] Natl Inst Hlth Clin Ctr, Imaging Biomarkers & Computer Aided Diag Lab, Dept Radiol & Imaging Sci, Bethesda, MD USA.
[Hillman, Bruce J.] Univ Virginia Hlth Syst, Dept Radiol Res, Charlottesville, VA USA.
RP Dachman, AH (reprint author), Univ Chicago, Dept Radiol, MC2026,5841 S Maryland Ave, Chicago, IL 60637 USA.
EM ahdachma@uchicago.edu
FU National Institutes of Health Clinical Center
FX R.M.S. is an employee of and this research was supported by the National
Institutes of Health Clinical Center.
NR 39
TC 52
Z9 53
U1 0
U2 2
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD SEP
PY 2010
VL 256
IS 3
BP 827
EP 835
DI 10.1148/radiol.10091890
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 656LD
UT WOS:000282335300017
PM 20663975
ER
PT J
AU Hotchkiss, AK
Rider, CV
Furr, J
Howdeshell, KL
Blystone, CR
Wilson, VS
Gray, LE
AF Hotchkiss, A. K.
Rider, C. V.
Furr, J.
Howdeshell, K. L.
Blystone, C. R.
Wilson, V. S.
Gray, L. E., Jr.
TI In utero exposure to an AR antagonist plus an inhibitor of fetal
testosterone synthesis induces cumulative effects on F1 male rats
SO REPRODUCTIVE TOXICOLOGY
LA English
DT Article; Proceedings Paper
CT 38th Annual Conference of the European-Teratology-Society
CY SEP 05-08, 2010
CL Barcelona, SPAIN
SP European Teratol Soc
DE Cumulative risk assessment; Male rat sexual differentiation; Di-n-butyl
phthalate; Androgen receptor antagonist; Procymidone
ID ALTERS SEXUAL-DIFFERENTIATION; LEYDIG-CELL AGGREGATION; DI(N-BUTYL)
PHTHALATE; REPRODUCTIVE DEVELOPMENT; DIETHYLHEXYL PHTHALATE; TESTICULAR
DYSGENESIS; TESTIS DESCENT; WILD FISH; ANTIANDROGENS; MALFORMATIONS
AB Risk assessments are typically conducted on a chemical-by-chemical basis; however, many regulatory bodies are developing frameworks for assessing the cumulative risk of chemical mixtures of chemicals. The current investigation examined how chemicals that disrupt rat sex differentiation via two diverse mechanisms disrupt F1 male rat reproductive development, when administered together orally on days 14-18 of gestation. Experiment 1 used a mixture of 50 mg/kg-d procymidone and 500 mg/kg-d dibutyl phthalate (DBP), whereas experiment 2 used 150 mg/kg-d procymidone and 1125 mg/kg-d DBP (top dose), or 0, 4.17, 8.33, 16.7, 33.3, 50, 66.7, and 83.3% of the top dose. When we compared the dose and response addition predictions to the observed effects we found that dose addition models were more accurate than response addition models, indicating that compounds that act by different mechanisms of toxicity produce cumulative dose-additive effects. Published by Elsevier Inc.
C1 [Hotchkiss, A. K.; Rider, C. V.; Furr, J.; Howdeshell, K. L.; Blystone, C. R.; Wilson, V. S.; Gray, L. E., Jr.] US EPA, Reprod Toxicol Branch, TAD, NHEERL,ORD, Res Triangle Pk, NC 27711 USA.
[Rider, C. V.; Howdeshell, K. L.; Blystone, C. R.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
RP Gray, LE (reprint author), US EPA, Reprod Toxicol Branch, TAD, NHEERL,ORD, MD 72, Res Triangle Pk, NC 27711 USA.
EM gray.earl@epa.gov
OI Wilson, Vickie/0000-0003-1661-8481
FU NIEHS NIH HHS [HHS Y1-ES-8014-01, K99 ES016806, K99 ES016806-02]
NR 35
TC 13
Z9 13
U1 0
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0890-6238
J9 REPROD TOXICOL
JI Reprod. Toxicol.
PD SEP
PY 2010
VL 30
IS 2
SI SI
BP 261
EP 270
DI 10.1016/j.reprotox.2010.06.001
PG 10
WC Reproductive Biology; Toxicology
SC Reproductive Biology; Toxicology
GA 640JF
UT WOS:000281046800004
PM 20558277
ER
PT J
AU Kavsek, M
Bornstein, MH
AF Kavsek, Michael
Bornstein, Marc H.
TI Visual habituation and dishabituation in preterm infants: A review and
meta-analysis
SO RESEARCH IN DEVELOPMENTAL DISABILITIES
LA English
DT Review
DE Habituation; Dishabituation; Preterm development; Cognitive development;
Meta-analysis
ID LOW-BIRTH-WEIGHT; FULL-TERM INFANTS; ADOLESCENTS BORN PRETERM;
PAIRED-COMPARISON PARADIGM; WORKING-MEMORY DEFICITS; MEDIAL
TEMPORAL-LOBE; SCHOOL-AGED CHILDREN; COGNITIVE-DEVELOPMENT; RECOGNITION
MEMORY; NEURODEVELOPMENTAL OUTCOMES
AB We review comparative studies of infant habituation and dishabituation performance focusing on preterm infants. Habituation refers to cognitive encoding, and dishabituation refers to discrimination and memory. If habituation and dishabituation constitute basic information-processing skills, and preterm infants suffer cognitive disadvantages, then preterms should show diminished habituation and dishabituation performance. Our review provides evidence that preterm infants' habituation and dishabituation are impoverished relative to term infants. On the whole, effect sizes indicated that the differences between preterms and terms are of a medium magnitude. We also find that preterms' performance is moderated by risk factors, stimulus materials, procedural variables, and age. These factors need to be taken into account in the construction of tests in which habituation-dishabituation tasks are employed. Overall, the habituation-dishabituation paradigm presents a promising approach in the diagnosis of cognitive status and development in preterm infants. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Kavsek, Michael] Univ Bonn, Inst Psychol, Dept Dev & Educ Psychol, D-53111 Bonn, Germany.
[Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
RP Kavsek, M (reprint author), Univ Bonn, Inst Psychol, Dept Dev & Educ Psychol, Kaiser Karl Ring 9, D-53111 Bonn, Germany.
EM kavsek@uni-bonn.de; Marc_H_Bornstein@nih.gov
FU Intramural NIH HHS [Z01 HD001119-20]
NR 195
TC 13
Z9 13
U1 7
U2 21
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0891-4222
J9 RES DEV DISABIL
JI Res. Dev. Disabil.
PD SEP-OCT
PY 2010
VL 31
IS 5
BP 951
EP 975
DI 10.1016/j.ridd.2010.04.016
PG 25
WC Education, Special; Rehabilitation
SC Education & Educational Research; Rehabilitation
GA 611SK
UT WOS:000278842100002
PM 20488657
ER
PT J
AU Bishop, RJ
Ding, XY
Heller, CK
Illei, G
Caruso, RC
Cunningham, D
Pavletic, S
Chan, CC
AF Bishop, Rachel J.
Ding, Xiaoyan
Heller, Charles K., III
Illei, Gabor
Caruso, Rafael C.
Cunningham, Denise
Pavletic, Steven
Chan, Chi-Chao
TI RAPID VISION LOSS ASSOCIATED WITH FLUDARABINE ADMINISTRATION
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article
DE fludarabine; purine analog; ocular toxicity; ophthalmic pathology;
adoptive cell therapy; stem cell transplantation
ID NERVOUS-SYSTEM TOXICITY; PHASE-I; LEUKEMIA; PHOSPHATE; CYCLOPHOSPHAMIDE
AB Purpose: The purpose of this study was to report the clinical and pathologic findings of three cases of rapid vision loss associated with fludarabine toxicity.
Methods: A retrospective, single-center case series was conducted. Autopsies of the eyes from three cases were performed.
Results: A 23-year-old man (Case 1) with systemic lupus erythematosus developed rapid and severe vision loss, generalized neurologic decline, and eventual death after administration of fludarabine before stem cell transplantation. A 48-year-old woman (Case 2) and a 60-year-old man (Case 3), both with metastatic melanoma, had similar courses after receiving fludarabine as part of a preparatory regimen before adoptive cell therapy. Fundus examination showed punctuate yellow flecks in the macula after visual decline in two cases. In all three cases, serum antiretinal antibodies were negative before and after treatment; electrophysiological testing showed markedly decreased B-waves; and pathologic analysis showed loss of retinal bipolar and ganglion cells, gliosis within the retina and optic nerve, and optic nerve atrophy.
Conclusion: Fludarabine toxicity can result in severe vision loss attributable to damage to retinal bipolar and ganglion cells. Although effective treatments are not known, care should be taken to consider fludarabine toxicity in patients who present with vision loss; 1 month after treatment. RETINA 30: 1272-1277, 2010
C1 [Bishop, Rachel J.; Ding, Xiaoyan; Caruso, Rafael C.; Cunningham, Denise; Chan, Chi-Chao] NEI, NIH, Bethesda, MD 20892 USA.
[Illei, Gabor] NCI, NIH, Bethesda, MD 20892 USA.
[Illei, Gabor] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
[Illei, Gabor] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Ding, Xiaoyan] Sun Yet Sen Univ, Ophthalm Ctr, Guangzhou, Guangdong, Peoples R China.
RP Bishop, RJ (reprint author), 10 Ctr Dr,Bldg 10,Room 10C432A, Bethesda, MD 20892 USA.
EM bishopra@nei.nih.gov
FU National Eye Institute
FX Supported by the National Eye Institute Intramural Research programs.
NR 9
TC 3
Z9 3
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0275-004X
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD SEP
PY 2010
VL 30
IS 8
BP 1272
EP 1277
DI 10.1097/IAE.0b013e3181d20589
PG 6
WC Ophthalmology
SC Ophthalmology
GA 647JF
UT WOS:000281614100019
PM 20224467
ER
PT J
AU Nieratschker, V
Frank, J
Muhleisen, TW
Strohmaier, J
Wendland, JR
Schumacher, J
Treutlein, J
Breuer, R
Abou Jamra, R
Mattheisen, M
Herms, S
Schmal, C
Maier, W
Nothen, MM
Cichon, S
Rietschel, M
Schulze, TG
AF Nieratschker, Vanessa
Frank, Josef
Muehleisen, Thomas W.
Strohmaier, Jana
Wendland, Jens R.
Schumacher, Johannes
Treutlein, Jens
Breuer, Rene
Abou Jamra, Rami
Mattheisen, Manuel
Herms, Stefan
Schmael, Christine
Maier, Wolfgang
Noethen, Markus M.
Cichon, Sven
Rietschel, Marcella
Schulze, Thomas G.
TI The catechol-O-methyl transferase (COMT) gene and its potential
association with schizophrenia: Findings from a large German
case-control and family-based sample
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Schizophrenia; COMT; Catechol-O-Methyltransferase; Polymorphism;
Cognitive function
ID METHYLTRANSFERASE GENE; FUNCTIONAL POLYMORPHISM; BIPOLAR DISORDER; HUMAN
BRAIN; METAANALYSIS; HAPLOTYPE; GENOME; SUSCEPTIBILITY; PSYCHIATRY;
EXPRESSION
AB The aim of the present study was to investigate possible associations between schizophrenia and 13 SNP markers in COMT. No association was observed in 631 cases, 207 nuclear families, and 776 controls. A cognitive performance phenotype (Trail Marking Test) was available for a subgroup of the patients. No association was found between the 13 markers and this phenotype. Four clinically-defined subgroups (early age at onset, negative symptoms, family history of schizophrenia, and life-time major depressive episode) were also investigated. Associations were observed for 3 of these subgroups, although none withstood correction for multiple testing. COMT does not appear to be a risk factor for schizophrenia in this population. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Nieratschker, Vanessa; Frank, Josef; Strohmaier, Jana; Treutlein, Jens; Breuer, Rene; Schmael, Christine; Rietschel, Marcella; Schulze, Thomas G.] Cent Inst Mental Hlth, Dept Genet Epidemiol, D-68159 Mannheim, Germany.
[Muehleisen, Thomas W.; Schumacher, Johannes; Mattheisen, Manuel; Herms, Stefan; Noethen, Markus M.; Cichon, Sven] Univ Bonn, Life & Brain Ctr, Dept Genom, D-53127 Bonn, Germany.
[Muehleisen, Thomas W.; Abou Jamra, Rami; Mattheisen, Manuel; Herms, Stefan; Noethen, Markus M.; Cichon, Sven] Univ Bonn, Biomed Ctr, Inst Human Genet, D-53127 Bonn, Germany.
[Wendland, Jens R.; Schumacher, Johannes] NIMH, Unit Genet Basis Mood & Anxiety Disorders, NIH, Bethesda, MD 20892 USA.
[Abou Jamra, Rami] Univ Erlangen Nurnberg, Inst Human Genet, D-91054 Erlangen, Germany.
[Mattheisen, Manuel] Univ Bonn, IMBIE, D-53127 Bonn, Germany.
[Maier, Wolfgang] Univ Bonn, Dept Psychiat & Psychotherapy, D-53127 Bonn, Germany.
[Cichon, Sven] Res Ctr Juelich, Inst Neurosci & Med INM 1, D-52428 Julich, Germany.
[Schulze, Thomas G.] Univ Gottingen, Dept Psychiat & Psychotherapy, D-37075 Gottingen, Germany.
RP Schulze, TG (reprint author), Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-68159 Mannheim, Germany.
EM vanessa.nieratschker@zi.mannheim.de; josef.frank@zi-mannheim.de;
thomas.muhleisen@uni-bonn.de; jana.strohmaier@zi-mannheim.de;
wendlandj@mail.nih.gov; johannes.schumacher@uni-bonn.de;
jens.treutlein@zi-mannheim.de; rene.breuer@zi-mannheim.de;
rami.aboujamra@uni-bonn.de; manuel.mattheisen@uni-bonn.de;
stefan.herms@uni-bonn.de; c.schmael@gmx.de;
wolfgang.maier@ukb.uni-bonn.de; markus.noethen@uni-bonn.de;
sven.cichon@uni-bonn.de; marcella.rietschel@zi-mannheim.de;
thomas.schulze@zi-mannheim.de
RI Wendland, Jens/A-1809-2012; Schulze, Thomas/H-2157-2013; Cichon,
Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Abou Jamra,
Rami/I-4805-2015; Mattheisen, Manuel/B-4949-2012; Schumacher,
Johannes/F-4970-2015; Herms, Stefan/J-1949-2014;
OI Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Abou
Jamra, Rami/0000-0002-1542-1399; Mattheisen, Manuel/0000-0002-8442-493X;
Schumacher, Johannes/0000-0001-9217-6457; Herms,
Stefan/0000-0002-2786-8200; Nothen, Markus/0000-0002-8770-2464
FU NARSAD; German Federal Ministry of Education and Research (BMBF);
National Institute of Mental Health (NIMH); Alfreid-Krupp-von Bohlen und
Halbach-Foundation
FX Funding for this study was provided by NARSAD (Young Investigator Awards
2002 and 2007 to TGS), the German Federal Ministry of Education and
Research (BMBF) in the context of the German National Genome Research
Network (NGFN-2 and NGFN-plus) to MR, SC and MMN, the National Institute
of Mental Health (NIMH), and the Alfreid-Krupp-von Bohlen und
Halbach-Foundation (to MMN).
NR 34
TC 14
Z9 14
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD SEP
PY 2010
VL 122
IS 1-3
BP 24
EP 30
DI 10.1016/j.schres.2010.06.018
PG 7
WC Psychiatry
SC Psychiatry
GA 709AH
UT WOS:000286406900002
PM 20643532
ER
PT J
AU Lau, ST
Li, X
Zhou, QF
Shung, KK
Ryu, J
Park, DS
AF Lau, S. T.
Li, X.
Zhou, Q. F.
Shung, K. K.
Ryu, J.
Park, D-S.
TI Aerosol-deposited KNN-LSO lead-free piezoelectric thick film for high
frequency transducer applications
SO SENSORS AND ACTUATORS A-PHYSICAL
LA English
DT Article
DE Thick film technology; Lead-free ceramics; Ultrasonic transducer
ID ULTRASONIC TRANSDUCERS; PARTICLES
AB In this report, we fabricated and characterized a high frequency transducer with lead-free piezoelectric thick film, 0.948(K0.5Na0.5)NbO3-0.052LiSbO(3), formed on a platinized silicon substrate by aerosol-deposition. X-ray diffraction analysis and scanning electron microscopy revealed that the film had well-crystallized perovskite structure and was dense and crack-free microstructure. The film showed the dielectric constant of 766 at 1 kHz and the remnant polarization of 13.2 mu C/cm(2). The film was used to fabricate a high frequency needle transducer with an aperture size of similar to 200 mu m. The center frequency of the transducer was 197 MHz and the -6 dB bandwidth was 50% which was comparable to the PZT-based transducers. A 6-mu m tungsten wire phantom was imaged to assess the -6 dB axial and lateral resolution of the transducer, which were found to be 12 and 66 mu m, respectively. (c) 2010 Elsevier B.V. All rights reserved.
C1 [Lau, S. T.; Li, X.; Zhou, Q. F.; Shung, K. K.] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA.
[Lau, S. T.; Li, X.; Zhou, Q. F.; Shung, K. K.] Univ So Calif, NIH Transducer Resource Ctr, Los Angeles, CA 90089 USA.
[Ryu, J.; Park, D-S.] Korea Inst Mat Sci, Funct Ceram Res Grp, Chang Won 641831, Gyeongnam, South Korea.
RP Lau, ST (reprint author), Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA.
EM sienlau@usc.edu
RI Lau, Sien-Ting/B-6091-2013
FU NIH [P41-EB2182]; Ministry of Knowledge Economy, Republic of Korea
FX This work was financially supported by NIH Grant P41-EB2182. The authors
from KIMS acknowledge the funding through Component-Material Development
Programme, Ministry of Knowledge Economy, Republic of Korea.
NR 20
TC 8
Z9 8
U1 1
U2 16
PU ELSEVIER SCIENCE SA
PI LAUSANNE
PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND
SN 0924-4247
J9 SENSOR ACTUAT A-PHYS
JI Sens. Actuator A-Phys.
PD SEP
PY 2010
VL 163
IS 1
BP 226
EP 230
DI 10.1016/j.sna.2010.08.020
PG 5
WC Engineering, Electrical & Electronic; Instruments & Instrumentation
SC Engineering; Instruments & Instrumentation
GA 673NU
UT WOS:000283671000032
ER
PT J
AU Landesman, B
Church, JM
Pope, BM
AF Landesman, Betty
Church, Jill M.
Pope, Barbara M.
TI Informing Innovation: Tracking Student Interest in Emerging Library
Technologies at Ohio University
SO SERIALS REVIEW
LA English
DT Book Review
C1 [Landesman, Betty] NIH, NIH Lib, Bethesda, MD 20892 USA.
[Church, Jill M.] Youville Coll, Montante Family Lib, Buffalo, NY 14201 USA.
[Pope, Barbara M.] Pittsburg State Univ, Axe Lib, Pittsburg, KS 66762 USA.
RP Landesman, B (reprint author), NIH, NIH Lib, Bldg 10, Bethesda, MD 20892 USA.
EM landesb@mail.nih.gov; churchj@dyc.edu; bpope@pittstate.edu
NR 1
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0098-7913
J9 SERIALS REV
JI Ser. Rev.
PD SEP
PY 2010
VL 36
IS 3
BP 199
EP 200
DI 10.1016/j.serrev.2010.05.006
PG 2
WC Information Science & Library Science
SC Information Science & Library Science
GA 663DM
UT WOS:000282863200007
ER
PT J
AU Ma, MC
Ding, SL
Lundqvist, A
San, H
Fang, F
Konoplyannikov, M
Berry, C
Beltran, LE
Chen, GB
Kovacic, JC
Boehm, M
AF Ma, Mingchao
Ding, Shunli
Lundqvist, Andreas
San, Hong
Fang, Fang
Konoplyannikov, Mikhail
Berry, Colin
Beltran, Leilani E.
Chen, Guibin
Kovacic, Jason C.
Boehm, Manfred
TI Major Histocompatibility Complex-I Expression on Embryonic Stem
Cell-Derived Vascular Progenitor Cells Is Critical for Syngeneic
Transplant Survival
SO STEM CELLS
LA English
DT Article
DE Embryonic stem cell; MHC-I; Immunosuppression; Progenitor cells;
Transplantation; NK cells
ID BONE-MARROW; DIFFERENTIATION; INDUCTION; MICE; VIVO; MESODERM; ICAM-1;
BLOOD; GAMMA
AB Donor-recipient cell interactions are essential for functional engraftment after nonautologous cell transplantation. During this process, transplant engraftment is characterized and defined by interactions between transplanted cells with local and recruited inflammatory cells. The outcome of these interactions determines donor cell fate. Here, we provide evidence that lineage-committed embryonic stem cell (ESC)-derived vascular progenitor cells are the target of major histocompatibility complex (MHC) class I-dependent, natural killer (NK) cell-mediated elimination in vitro and in vivo. Treatment with interferon c was found to significantly upregulate MHC class I expression on ESC-derived vascular progenitor cells, rendering them less susceptible to syngeneic NK cell-mediated killing in vitro and enhancing their survival and differentiation potential in vivo. Furthermore, in vivo ablation of NK cells led to enhanced progenitor cell survival after transplantation into a syngeneic murine ischemic hindlimb model, providing additional evidence that NK cells mediate ESC-derived progenitor cell transplant rejection. These data highlight the importance of recipient immune-donor cell interactions, and indicate a functional role for MHC-I antigen expression during successful ESC-derived syngeneic transplant engraftment. STEM CELLS 2010; 28: 1465-1475
C1 [Boehm, Manfred] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
[Lundqvist, Andreas] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
[San, Hong] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA.
[Fang, Fang] Cent S Univ, Xiang Ya Hosp, Dept Cardiol, Changsha, Hunan, Peoples R China.
[Berry, Colin] Univ Glasgow, Coll Med Vet & Life Sci, Glasgow, Lanark, Scotland.
RP Boehm, M (reprint author), NHLBI, Translat Med Branch, NIH, 9,000 Rockville Pike, Bethesda, MD 20892 USA.
EM boehmm@nhlbi.nih.gov
OI Lundqvist, Andreas/0000-0002-9709-2970
FU National Heart, Lung, and Blood Institute; Faculty of Medicine,
University of Glasgow
FX We thank Dr. Gordon Keller for kindly providing Brachyury-GFP ESCs and
Dr. Eve Mezey for providing template mouse genomic DNA. We also thank
the staff of the Laboratory of Animal Medicine and Surgery and Ms. Robin
Schwartzbeck for their assistance with the mice surgery. We acknowledge
the professional skills and advice of Drs. Christian A. Combs and
Daniela Malide (Light Microscopy Core Facility, National Heart, Lung and
Blood Institute) and Dr. J. Philip McCoy (Flow Cytometry Core Facility,
National Heart, Lung and Blood Institute). This research was supported
by the Intramural Research Program of the National Heart, Lung, and
Blood Institute. C. B. is supported by the Faculty of Medicine,
University of Glasgow.
NR 31
TC 13
Z9 14
U1 1
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1066-5099
J9 STEM CELLS
JI Stem Cells
PD SEP
PY 2010
VL 28
IS 9
BP 1465
EP 1475
DI 10.1002/stem.475
PG 11
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 657YG
UT WOS:000282454700003
PM 20629173
ER
PT J
AU Mazzetto-Betti, KC
Leoni, RF
Pontes-Neto, OM
Santos, AC
Leite, JP
Silva, AC
de Araujo, DB
AF Mazzetto-Betti, Kelley C.
Leoni, Renata F.
Pontes-Neto, Octavio M.
Santos, Antonio C.
Leite, Joao P.
Silva, Afonso C.
de Araujo, Draulio B.
TI The Stability of the Blood Oxygenation Level-Dependent Functional MRI
Response to Motor Tasks Is Altered in Patients With Chronic Ischemic
Stroke
SO STROKE
LA English
DT Article
DE BOLD signal instability; cortical plasticity; patients with stroke;
primary motor cortex; supplementary motor cortex
ID BOLD FMRI SIGNAL; DISEASE; CORTEX; BRAIN; PERFORMANCE; ACTIVATION;
ENTROPY; ADULTS
AB Background and Purpose-Functional MRI is a powerful tool to investigate recovery of brain function in patients with stroke. An inherent assumption in functional MRI data analysis is that the blood oxygenation level-dependent (BOLD) signal is stable over the course of the examination. In this study, we evaluated the validity of such assumption in patients with chronic stroke.
Methods-Fifteen patients performed a simple motor task with repeated epochs using the paretic and the unaffected hand in separate runs. The corresponding BOLD signal time courses were extracted from the primary and supplementary motor areas of both hemispheres. Statistical maps were obtained by the conventional General Linear Model and by a parametric General Linear Model.
Results-Stable BOLD amplitude was observed when the task was executed with the unaffected hand. Conversely, the BOLD signal amplitude in both primary and supplementary motor areas was progressively attenuated in every patient when the task was executed with the paretic hand. The conventional General Linear Model analysis failed to detect brain activation during movement of the paretic hand. However, the proposed parametric General Linear Model corrected the misdetection problem and showed robust activation in both primary and supplementary motor areas.
Conclusions-The use of data analysis tools that are built on the premise of a stable BOLD signal may lead to misdetection of functional regions and underestimation of brain activity in patients with stroke. The present data urge the use of caution when relying on the BOLD response as a marker of brain reorganization in patients with stroke. (Stroke. 2010; 41:1921-1926.)
C1 [de Araujo, Draulio B.] Univ Fed Rio Grande do Norte, Coordenacao CDI, HUOL, BR-59012300 Natal, RN, Brazil.
[Mazzetto-Betti, Kelley C.; Pontes-Neto, Octavio M.; Santos, Antonio C.; Leite, Joao P.; de Araujo, Draulio B.] Univ Sao Paulo, FMRP, Dept Neurosci & Behav Sci, BR-14049 Ribeirao Preto, Brazil.
[Leoni, Renata F.; de Araujo, Draulio B.] Univ Sao Paulo, Dept Math & Phys, FFCLRP, BR-14049 Ribeirao Preto, Brazil.
[Leoni, Renata F.; Santos, Antonio C.] Natl Inst Neurol Disorders & Stroke, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, Bethesda, MD USA.
[de Araujo, Draulio B.] Edmond & Lily Safra Int Inst Neurosci Natal, Natal, RN, Brazil.
RP de Araujo, DB (reprint author), Univ Fed Rio Grande do Norte, Coordenacao CDI, HUOL, Av Nilo Pecanha 620, BR-59012300 Natal, RN, Brazil.
EM draulio@ufrnet.br
RI Silva, Afonso/A-7129-2009; Leite, Joao/B-9070-2012; Santos,
Antonio/F-5419-2012; Pontes-Neto, Octavio/G-4294-2012; Araujo,
Draulio/I-6038-2012;
OI Leite, Joao/0000-0003-0558-3519; Pontes-Neto,
Octavio/0000-0003-0317-843X; Araujo, Draulio/0000-0002-6934-2485; Leoni,
Renata/0000-0002-4568-0746
FU Brazilian Financial Agencies FAPESP [05/03225-7]; CNPq; CAPES
[PROCAD-NF: 23/2010]; FINEP; National Institutes of Health, National
Institute of Neurological Disorders and Stroke
FX We thank the Brazilian Financial Agencies FAPESP (05/03225-7), CNPq,
CAPES, and FINEP for financial support.; This research was supported in
part by the Brazilian financial agencies CAPES (PROCAD-NF: 23/2010);
FAPESP (05/03225-7), CNPq and FINEP and by the Intramural Research
Program of the National Institutes of Health, National Institute of
Neurological Disorders and Stroke (Alan P. Koretsky, Scientific
Director).
NR 25
TC 13
Z9 13
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD SEP
PY 2010
VL 41
IS 9
BP 1921
EP 1926
DI 10.1161/STROKEAHA.110.590471
PG 6
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 645YV
UT WOS:000281503000013
PM 20705926
ER
PT J
AU Chiocco, MJ
Zhu, XG
Walther, D
Pletnikova, O
Troncoso, JC
Uhl, GR
Liu, QR
AF Chiocco, Matthew J.
Zhu, Xuguang
Walther, Donna
Pletnikova, Olga
Troncoso, Juan C.
Uhl, George R.
Liu, Qing-Rong
TI Fine Mapping of Calcineurin (PPP3CA) Gene Reveals Novel Alternative
Splicing Patterns, Association of 5 ' UTR Trinucleotide Repeat With
Addiction Vulnerability, and Differential Isoform Expression in
Alzheimer's Disease
SO SUBSTANCE USE & MISUSE
LA English
DT Article
DE phosphatase; SNP association; gene regulation; alternative splicing
ID LONG-TERM POTENTIATION; HAPLOTYPE RECONSTRUCTION; PHOSPHATASE 2B;
PROTEIN; MEMORY; AMPHETAMINE; INHIBITION; VALIDATION; ACTIVATION;
SUBUNIT
AB Fine mapping of calcineurin (PPP3CA) gene identified single nucleotide polymorphisms (SNPs) and simple sequence repeat polymorphisms that are associated with addiction vulnerability. A trinucleotide repeat marker, located in the 5'untranslated region (5'UTR) of the PPP3CA mRNA, exhibited significantly different genotype and allele frequencies between abusers and controls in the NIDA African-American sample. The polymorphism showed allelic-specific expression in mRNA extracted from postmortem brain specimens. Novel alternatively spliced isoforms of PPP3CA were identified and their expressions were found altered in brain regions of postmortem Alzheimer's disease patients. These data underscore the importance of calcineurin gene in the molecular mechanism of addiction and Alzheimer's diseases.
C1 [Liu, Qing-Rong] NIDA, Behav Neurosci Res Branch, NIH, IRP,DHHS, Baltimore, MD 21224 USA.
[Chiocco, Matthew J.; Zhu, Xuguang; Walther, Donna; Uhl, George R.] NIDA, Mol Neurobiol Branch, NIH, IRP,DHHS, Baltimore, MD 21224 USA.
[Pletnikova, Olga; Troncoso, Juan C.] Johns Hopkins Univ, Sch Med, Dept Pathol, Div Neuropathol, Baltimore, MD 21205 USA.
RP Liu, QR (reprint author), NIDA, Behav Neurosci Res Branch, NIH, IRP,DHHS, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM qliu@intra.nida.nih.gov
RI Liu, Qing-Rong/A-3059-2012
OI Liu, Qing-Rong/0000-0001-8477-6452
FU NIH IRP (NIDA)
FX We thank Judith Hess, Feely Carillo, and Brenda Campbell for assistance
with collection of the NIDA clinical samples studied here and cite
financial support from NIH IRP (NIDA). We also thank Dr. Florence
Theberge and Dr. Maria Flavia Barbano for the abstract translations to
French and Spanish, respectively.
NR 25
TC 8
Z9 9
U1 0
U2 3
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1082-6084
J9 SUBST USE MISUSE
JI Subst. Use Misuse
PD SEP
PY 2010
VL 45
IS 11
BP 1809
EP 1826
DI 10.3109/10826084.2010.482449
PG 18
WC Substance Abuse; Psychiatry; Psychology
SC Substance Abuse; Psychiatry; Psychology
GA 633RO
UT WOS:000280522400007
PM 20590401
ER
PT J
AU Skinbjerg, M
Seneca, N
Liow, JS
Hong, JS
Weinshenker, D
Pike, VW
Halldin, C
Sibley, DR
Innis, RB
AF Skinbjerg, Mette
Seneca, Nicholas
Liow, Jeih-San
Hong, Jinsoo
Weinshenker, David
Pike, Victor W.
Halldin, Christer
Sibley, David R.
Innis, Robert B.
TI Dopamine beta-Hydroxylase-Deficient Mice Have Normal Densities of D-2
Dopamine Receptors in the High-Affinity State Based on In Vivo PET
Imaging and In Vitro Radioligand Binding
SO SYNAPSE
LA English
DT Article
DE [C-11]MNPA; D-2 dopamine receptor; high-affinity state; dopamine
beta-hydroxylase; PET
ID AMPHETAMINE-SENSITIZED ANIMALS; POSITRON-EMISSION-TOMOGRAPHY; ENDOGENOUS
DOPAMINE; EX-VIVO; NOREPINEPHRINE; OCCUPANCY; BRAIN
AB In vitro, D-2 dopamine receptors (DAR) can exist in low- and high-affinity states for agonists and increases of D-2 receptors in high-affinity state have been proposed to underlie DA receptor supersensitivity in vivo. Deletion of the gene for dopamine p-hydroxylase (DBH) causes mice to become hypersensitive to the effects of psychostimulants, and in vitro radioligand binding results suggest an increased percentage of D-2 receptors in a high-affinity state. To determine whether DBH knockout mice display an increase of high-affinity state D-2 receptors in vivo, we scanned DBH knockout and control mice with the agonist PET radioligand [C-11]MNPA, which is thought to bind preferentially to the high-affinity state of the D-2 receptor. In addition, we performed in vitro binding experiments on striatal homogenates with [H-3]methylspiperone to measure B-max values and the percentages of high- and low-affinity states of the D-2 receptor. We found that the in vivo striatal binding of [C-11]MNPA was similar in DBH knockout mice and heterozygous controls and the in vitro B-max values and percentages of D-2 receptors in the high-affinity state, were not significantly different between these two groups. In summary, our results suggest that DBH knockout mice have normal levels of D-2 receptors in the high-affinity state and that additional mechanisms contribute to their behavioral sensitivity to psychostimulants. Synapse 64:699-703, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Skinbjerg, Mette; Seneca, Nicholas; Liow, Jeih-San; Hong, Jinsoo; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
[Skinbjerg, Mette; Halldin, Christer] Karolinska Inst, Psychiat Sect, Dept Clin Neurosci, Stockholm, Sweden.
[Skinbjerg, Mette; Sibley, David R.] NINDS, Mol Neuropharmacol Sect, Bethesda, MD 20892 USA.
[Weinshenker, David] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA.
RP Innis, RB (reprint author), NIMH, Mol Imaging Branch, 31 Ctr Dr, Bethesda, MD 20892 USA.
EM robert.innis@nih.gov
FU NIMH [Z01-MH-002795-07]; NINDS [NS002263-33]
FX Contract grant sponsor: Intramural Program of NIMH; Contract grant
number: Z01-MH-002795-07; Contract grant sponsor: Intramural Program of
NINDS; Contract grant number: NS002263-33
NR 17
TC 14
Z9 14
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0887-4476
J9 SYNAPSE
JI Synapse
PD SEP
PY 2010
VL 64
IS 9
BP 699
EP 703
DI 10.1002/syn.20781
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 633IR
UT WOS:000280495800004
PM 20336622
ER
PT J
AU Shomron, N
Hamasaki-Katagiri, N
Hunt, R
Hershko, K
Pommier, E
Geetha, S
Blaisdell, A
Marple, A
Roma, I
Newell, J
Allen, C
Friedman, S
Kimchi-Sarfaty, C
AF Shomron, Noam
Hamasaki-Katagiri, Nobuko
Hunt, Ryan
Hershko, Klilah
Pommier, Elie
Geetha, S.
Blaisdell, Adam
Marple, Andrew
Roma, Isabella
Newell, Jordan
Allen, Courtni
Friedman, Scott
Kimchi-Sarfaty, Chava
TI A splice variant of ADAMTS13 is expressed in human hepatic stellate
cells and cancerous tissues
SO THROMBOSIS AND HAEMOSTASIS
LA English
DT Article
DE ADAMTS13; alternative splicing; intron retention; TTP; CUB domain
ID THROMBOTIC THROMBOCYTOPENIC PURPURA; VON-WILLEBRAND-FACTOR;
FACTOR-CLEAVING PROTEASE; MESSENGER-RNA; METALLOPROTEASE; ASSOCIATION;
MUTATION; COMPLEX
AB Although ADAMTS13, the von Willebrand factor (VWF)-cleaving protease, is expressed in a range of tissues, the physiological significance of tissue-specific ADAMTS13 alternative splicing isoforms have yet to be clarified. Screening a panel of human tissues and cell lines revealed a spliced ADAMTS13 transcript in hepatic stellate cells and a hepatoma cell line that retains the 25(th) intron.A nonsense codon within the intron truncates the protease, which gains 64 novel amino acids in lieu of both CUB domains. This isoform, while retaining VWF-cleaving capability, accumulates intracellularly and its biological inaccessibility may prevent its participation in regulating haemostasis and other physiologic functions.
C1 [Shomron, Noam] Tel Aviv Univ, Sackler Fac Med, Dept Cell & Dev Biol, IL-69978 Tel Aviv, Israel.
[Hamasaki-Katagiri, Nobuko; Hunt, Ryan; Hershko, Klilah; Pommier, Elie; Geetha, S.; Blaisdell, Adam; Newell, Jordan; Allen, Courtni; Kimchi-Sarfaty, Chava] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
[Marple, Andrew; Roma, Isabella] Natl Canc Inst, Cell Biol Lab, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD USA.
[Friedman, Scott] Mt Sinai Sch Med, Div Liver Dis, New York, NY USA.
RP Kimchi-Sarfaty, C (reprint author), 29 Lincoln Dr, Bethesda, MD 20982 USA.
EM Chava.kimchi-sarfaty@fda.hhs.gov
FU Intramural NIH HHS [Z01 BC005598-18]
NR 18
TC 6
Z9 6
U1 0
U2 3
PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN
PI STUTTGART
PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY
SN 0340-6245
J9 THROMB HAEMOSTASIS
JI Thromb. Haemost.
PD SEP
PY 2010
VL 104
IS 3
BP 531
EP 535
DI 10.1160/TH09-12-0860
PG 5
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 651ZV
UT WOS:000281969900014
PM 20664912
ER
PT J
AU O'Kane, P
Shelkovoy, E
McConnell, RJ
Shpak, V
Parker, L
Brenner, A
Zablotska, L
Tronko, M
Hatch, M
AF O'Kane, Patrick
Shelkovoy, Evgeniy
McConnell, Robert J.
Shpak, Victor
Parker, Laurence
Brenner, Alina
Zablotska, Lydia
Tronko, Mykola
Hatch, Maureen
TI Frequency of Undetected Thyroid Nodules in a Large I-131-Exposed
Population Repeatedly Screened by Ultrasonography: Results from the
Ukrainian-American Cohort Study of Thyroid Cancer and Other Thyroid
Diseases Following the Chornobyl Accident
SO THYROID
LA English
DT Article
ID NATURAL-HISTORY; ULTRASOUND; CARCINOMA; CHILDHOOD; RADIATION; CHILDREN;
RISK
AB Background: Imperfect detection on screening tests can lead to erroneous conclusions about the natural history of thyroid nodules following radiation exposure. Our objective was to assess in a repeatedly screened I-131-exposed population the frequency with which a thyroid nodule could be retrospectively identified on ultrasonography studies preceding the one on which it was initially detected.
Methods: A cohort of over 13,000 young people exposed to fallout from Chornobyl underwent ultrasonography screening at 2-year intervals from 1998 to 2007. The study group consisted of screening examinations on which a thyroid nodule was detected following one or more prior negative examinations. In the study group there were 48 cancers and 92 benign nodules. For each of these 140 index studies a comparison set was created containing all available prior studies plus (to test for bias) negative studies from control subjects. While viewing the index study, three independent reviewers scored the comparison studies for the presence and size of a preexisting nodule. Detection rates were compared for true priors versus controls, for cancer versus benign, and for histologic subtypes of papillary carcinoma.
Results: A preexisting nodule was identified by at least one reviewer in 24.0% of the true prior versus 8.3% of the controls and by all three reviewers in 11% versus 1% (Fisher's exact test, p < 0.0001). There was no significant difference in detection rates between cancers and benign nodules (22.4% vs. 24.7%, p = 0.411). There was no correlation between time from prior to index study and change in nodule size for either malignant or benign nodules (r = 0.01, NS). There were no differences in detection rates or size among papillary cancer subtypes. Reviewers could not distinguish between true priors and controls.
Conclusions: These findings, showing significant rates of undetected benign and malignant nodules and no evidence for rapid growth, suggest that conclusions drawn from screening studies about the frequency of late-developing, rapidly growing thyroid nodules following radiation exposure should be interpreted with caution.
C1 [O'Kane, Patrick; Parker, Laurence] Thomas Jefferson Univ Hosp, Dept Radiol, Philadelphia, PA 19107 USA.
[Shelkovoy, Evgeniy; Shpak, Victor; Tronko, Mykola] Inst Endocrinol & Metab, Kiev, Ukraine.
[McConnell, Robert J.] Columbia Univ, Coll Phys & Surg, Dept Med, Thyroid Ctr, New York, NY USA.
[Zablotska, Lydia] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
[Brenner, Alina; Hatch, Maureen] NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Bethesda, MD 20892 USA.
[Zablotska, Lydia] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
RP O'Kane, P (reprint author), Thomas Jefferson Univ Hosp, Dept Radiol, 796 Main Bldg,10th & Walnut St, Philadelphia, PA 19107 USA.
EM patrick.okane@jefferson.edu
FU U.S. National Cancer Institute, NIH, DHHS; Department of Energy; U.S.
Nuclear Regulatory Commission
FX This research was supported by the Intramural Research Program of the
U.S. National Cancer Institute, NIH, DHHS. The Department of Energy and
the U.S. Nuclear Regulatory Commission have also contributed funds. The
study team is grateful to the Louise Hamilton Kyiv Data Management
Center of the University of Illinois at Chicago, supported in part by
the U.S. NIH Fogarty International Center, and its head Oleksandr
Zvinchuk, for database management.
NR 23
TC 2
Z9 2
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
J9 THYROID
JI Thyroid
PD SEP
PY 2010
VL 20
IS 9
BP 959
EP 964
DI 10.1089/thy.2010.0032
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 648BW
UT WOS:000281666400005
PM 20615138
ER
PT J
AU Wolff, EF
Hughes, M
Merino, MJ
Reynolds, JC
Davis, JL
Cochran, CS
Celi, FS
AF Wolff, Erin F.
Hughes, Marybeth
Merino, Maria J.
Reynolds, James C.
Davis, Jeremy L.
Cochran, Craig S.
Celi, Francesco S.
TI Expression of Benign and Malignant Thyroid Tissue in Ovarian Teratomas
and the Importance of Multimodal Management as Illustrated by a
BRAF-Positive Follicular Variant of Papillary Thyroid Cancer
SO THYROID
LA English
DT Article
ID OF-THE-LITERATURE; PSEUDO-MEIGS-SYNDROME; MATURE CYSTIC TERATOMA;
LOW-IODINE DIET; STRUMA-OVARII; I-131 THERAPY; PERITONEAL STRUMOSIS;
CARCINOMA; PRESERVATION; FERTILITY
AB Background: The most common type of ovarian germ cell tumor is the teratoma. Thyroid tissue, both benign and malignant, may be a component of an ovarian teratoma. Here we review this topic and illustrate major features by presenting multimodal management of a patient with BRAF-positive disseminated follicular thyroid cancer arising in an ovarian teratoma.
Summary: Malignant thyroid tissue is often difficult to distinguish from benign thyroid tissue arising in ovarian teratomas. Preoperatively, an elevated thyroglobulin (Tg) level, laboratory or clinical evidence of hyperthyroidism, or ultrasonography appearance of "struma pearl" should prompt referral to oncologist for surgical management of a possibly malignant ovarian teratoma. Postoperatively, tumor tissue should be referred to pathologists experienced with differentiating benign from malignant struma ovarii. Once diagnosed, treatment of this rare condition should be handled by a team of specialists with combined treatment modalities. We cared for woman with disseminated thyroid cancer arising in an ovarian teratoma whose history illustrates the complexity of managing ovarian teratomas with malignant thyroid tissue. At age 33 she had an intraoperative rupture of an ovarian cyst, thought to be struma ovarii. During her next pregnancy, pelvic masses were noted; biopsies revealed well-differentiated papillary thyroid carcinoma, follicular variant. She was euthyroid, but had elevated serum Tg levels. Surgical staging demonstrated widely metastatic intraabdominal dissemination. A thyroidectomy revealed no malignancy. A post-(131)I treatment scan revealed diffuse uptake throughout the abdomen. She then developed abdominal pain and, on computed tomography, was found to have multiple intraabdominal foci of disease. Serum Tg was 264 ng/mL while on L-thyroxine for hypothyroidism and to obtain thyrotropin suppression. A 18 fluorodeoxyglucose positron emission tomography scan showed no pathological uptake. The tumor was found to be BRAF mutation positive (K601E). She underwent extensive secondary debulking and a second course of (131)I with lithium pretreatment. Posttreatment scan revealed diffuse abdominal uptake. Six months posttherapy, the patient is asymptomatic with a serum Tg of 18.1 ng/mL.
Conclusions: Aggressive multimodal management appears to be the most promising approach for malignant thyroid tissue arising in ovarian teratomas.
C1 [Celi, Francesco S.] Natl Inst Diabet Digest & Kidney Dis, Clin Endocrinol Branch, NIH, CRC, Bethesda, MD 20892 USA.
[Wolff, Erin F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA.
[Hughes, Marybeth; Merino, Maria J.; Davis, Jeremy L.] NCI, Bethesda, MD 20892 USA.
[Reynolds, James C.] Ctr Clin, Bethesda, MD USA.
RP Celi, FS (reprint author), Natl Inst Diabet Digest & Kidney Dis, Clin Endocrinol Branch, NIH, CRC, Bldg 10,Room 6-3950,10 Ctr Dr,MSC 1613, Bethesda, MD 20892 USA.
EM francescoc@niddk.nih.gov
FU NIDDK [Z01-DK047057-02]
FX This work was supported by the Intramural Research Program of the NIDDK,
project number Z01-DK047057-02. The authors gratefully acknowledge the
comments and suggestions of Dr. E. Kebebew (NCI-NIH).
NR 38
TC 10
Z9 10
U1 1
U2 5
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
J9 THYROID
JI Thyroid
PD SEP
PY 2010
VL 20
IS 9
BP 981
EP 987
DI 10.1089/thy.2009.0458
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 648BW
UT WOS:000281666400008
PM 20718682
ER
PT J
AU Jensen-Taubman, S
Wang, XY
Linnoila, RI
AF Jensen-Taubman, Sandra
Wang, Xiao-Yang
Linnoila, R. Ilona
TI Achaete-Scute Homologue-1 Tapers Neuroendocrine Cell Differentiation in
Lungs after Exposure to Naphthalene
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE achaete-scute homologue-1; bronchiolization of the alveoli; lung repair;
neuroendocrine; transgenic mouse
ID CLARA CELL; NEUROEPITHELIAL BODIES; TERMINAL BRONCHIOLES; PULMONARY
EPITHELIUM; AIRWAY INJURY; 10-KD PROTEIN; MESSENGER-RNA; CANCER; MICE;
PROLIFERATION
AB The basic helix-loop-helix transcription factor achaete-scute homologue-1 (ASH1) plays a critical role in regulating the neuroendocrine (NE) phenotype in normal and neoplastic lung. Transgenic (TG) mice that constitutively express human ASH1 (hASH1) under control of the Clara cell 10-kDa protein (CC10) promoter in non-NE airway lining cells display progressive epithelial hyperplasia and bronchiolar metaplasia or bronchiolization of the alveoli (BOA). However, little is known about the involvement of hASH1 in regeneration of the conducting airway. In this study, we investigated the impact of hASH1 on airway cell injury and repair in the TG mice following an intraperitoneal injection of naphthalene, which specifically ablates bronchiolar Clara cells and induces pulmonary NE cell hyperplasia. We discovered an overall attenuation of NE maturation coupled with increased proliferation in TG mice during post-naphthalene repair. In addition, BOA lesions revealed enhanced epithelial cell proliferation while preserving Clara cell markers CC10 and the principal naphthalene-metabolizing enzyme cytochrome P4502F2. These data suggest that ASH1 may play an important role in maintaining a progenitor phenotype that promotes renewal of both NE and epithelial cells. Moreover, ASH1 may propagate a stem cell microenvironment in BOA where epithelium becomes resistant to naphthalene toxicity.
C1 [Linnoila, R. Ilona] NCI, Expt Pathol Sect, Cell & Canc Biol Branch, CCR,NIH, Bethesda, MD 20892 USA.
RP Linnoila, RI (reprint author), NCI, Expt Pathol Sect, Cell & Canc Biol Branch, CCR,NIH, 37 Convent Dr,Bldg 37,Room 1056B, Bethesda, MD 20892 USA.
EM linnoila@mail.nih.gov
FU National Institutes of Health, National Cancer Institute
FX Intramural Research Program of the National Institutes of Health,
National Cancer Institute.
NR 38
TC 7
Z9 7
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD SEP
PY 2010
VL 117
IS 1
BP 238
EP 248
DI 10.1093/toxsci/kfq177
PG 11
WC Toxicology
SC Toxicology
GA 642FC
UT WOS:000281188400026
PM 20554700
ER
PT J
AU Tang, S
Zhao, J
Viswanath, R
Nyambi, PN
Vermeulen, M
Redd, AD
Dastyar, A
Wang, X
Gaddam, D
Hewlett, IK
AF Tang, S.
Zhao, J.
Viswanath, R.
Nyambi, P. N.
Vermeulen, M.
Redd, A. D.
Dastyar, A.
Wang, X.
Gaddam, D.
Hewlett, I. K.
TI Absence of Detectable Xenotropic Murine Leukemia Virus-Related Virus in
Plasma or Peripheral Blood Mononuclear Cells of Human Immunodeficiency
Virus Type One (HIV-1) Infected Individuals in Cameroon, South Africa,
and Uganda
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting 2010
CY OCT 09-12, 2010
CL Baltimore, MD
SP AABB
C1 [Tang, S.; Zhao, J.; Viswanath, R.; Dastyar, A.; Wang, X.; Gaddam, D.; Hewlett, I. K.] US FDA, LMV DETTD OBRR CBER, Bethesda, MD 20014 USA.
[Nyambi, P. N.] NYU, Sch Med, Dept Pathol, New York, NY USA.
[Vermeulen, M.] S African Natl Blood Serv, ZA-1715 Weltevreden Pk, South Africa.
[Redd, A. D.] NIAID, Div Intramural Res, Bethesda, MD 20892 USA.
EM shixing.tang@fda.hhs.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2010
VL 50
SU 2
BP 5A
EP 6A
PG 2
WC Hematology
SC Hematology
GA 649JM
UT WOS:000281764900011
ER
PT J
AU Leitman, SF
Vitale, S
Kim, J
Byrne, PJ
Conry-Cantilena, C
Clayton, JA
AF Leitman, S. F.
Vitale, S.
Kim, J.
Byrne, P. J.
Conry-Cantilena, C.
Clayton, J. A.
TI Risk of Posterior Subcapsular Cataracts in Granulocyte and Platelet
Apheresis Donors
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting 2010
CY OCT 09-12, 2010
CL Baltimore, MD
SP AABB
C1 [Leitman, S. F.; Byrne, P. J.; Conry-Cantilena, C.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
[Vitale, S.; Clayton, J. A.] NEI, NIH, Bethesda, MD 20892 USA.
[Kim, J.] Emmes Corp, Rockville, MD USA.
EM sleitman@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2010
VL 50
SU 2
BP 14A
EP 14A
PG 1
WC Hematology
SC Hematology
GA 649JM
UT WOS:000281764900029
ER
PT J
AU Leitman, SF
Yau, Y
Matthews, CL
Hopkins, JA
Min, K
AF Leitman, S. F.
Yau, Y.
Matthews, C. L.
Hopkins, J. A.
Min, K.
TI Optimization of Unstimulated Mononuclear Cell Collections Using the
Amicus Continuous-Flow Apheresis Device
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting 2010
CY OCT 09-12, 2010
CL Baltimore, MD
SP AABB
C1 [Leitman, S. F.; Yau, Y.; Matthews, C. L.; Hopkins, J. A.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
[Min, K.] Fenwal Inc, Lake Zurich, IL USA.
EM sleitman@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2010
VL 50
SU 2
BP 15A
EP 15A
PG 1
WC Hematology
SC Hematology
GA 649JM
UT WOS:000281764900031
ER
PT J
AU Hendrickson, JE
Patel, S
Smith, NH
Cadwell, CM
Ozato, K
Morse, HC
Yoshimi, R
Zimring, JC
AF Hendrickson, J. E.
Patel, S.
Smith, N. H.
Cadwell, C. M.
Ozato, K.
Morse, H. C.
Yoshimi, R.
Zimring, J. C.
TI Decreased TRIM 21 Is Not an Independent Variable in Frequency or
Magnitude of ABC Alloimmunization in a Murine Model
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting 2010
CY OCT 09-12, 2010
CL Baltimore, MD
SP AABB
C1 [Hendrickson, J. E.; Patel, S.; Smith, N. H.; Cadwell, C. M.; Zimring, J. C.] Emory Univ, Atlanta, GA 30322 USA.
[Morse, H. C.] NIAID, NIH, Rockville, MD USA.
[Ozato, K.] NICHD, NIH, Bethesda, MD USA.
EM jeanne.hendrickson@choa.org
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2010
VL 50
SU 2
BP 16A
EP 16A
PG 1
WC Hematology
SC Hematology
GA 649JM
UT WOS:000281764900034
ER
PT J
AU von Zabern, I
Wagner, FF
Flegel, WA
AF von Zabern, I.
Wagner, F. F.
Flegel, W. A.
TI The Rhesus Immunization Registry: a 10 Year Record of D Positive
Individuals with Anti-D
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting 2010
CY OCT 09-12, 2010
CL Baltimore, MD
SP AABB
C1 [von Zabern, I.] Inst Clin Transfus Med & Immunogenet Ulm, Ulm, Germany.
[Wagner, F. F.] NSTOB, German Red Cross DRK Blood Donor Serv, Springe, Germany.
[Flegel, W. A.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
EM ingeborg.von-zabern@uni-ulm.de
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2010
VL 50
SU 2
BP 17A
EP 18A
PG 2
WC Hematology
SC Hematology
GA 649JM
UT WOS:000281764900038
ER
PT J
AU Cable, RG
Steele, WR
Wright, DJ
Glynn, SA
Kiss, JE
Mast, AE
Murphy, EL
Carey, PM
Gottschall, JL
Simon, TL
AF Cable, R. G.
Steele, W. R.
Wright, D. J.
Glynn, S. A.
Kiss, J. E.
Mast, A. E.
Murphy, E. L.
Carey, P. M.
Gottschall, J. L.
Simon, T. L.
TI Predicting Hemoglobin Deferral in Blood Donors: A Multi-Center,
Prospective Study
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting 2010
CY OCT 09-12, 2010
CL Baltimore, MD
SP AABB
C1 [Cable, R. G.] Amer Red Cross, Blood Serv, New England Reg, Dedham, MA USA.
[Steele, W. R.; Wright, D. J.] Westat Corp, Rockville, MD USA.
[Glynn, S. A.] NHLBI, Div Blood Dis & Resources, Bethesda, MD 20892 USA.
[Kiss, J. E.] Life Source Blood Serv, Inst Transfus Med, Pittsburgh, PA USA.
[Mast, A. E.; Gottschall, J. L.] Blood Ctr SE Wisconsin Inc, Milwaukee, WI 53233 USA.
[Murphy, E. L.] Blood Ctr Pacific, Blood Syst Res Inst, San Francisco, CA USA.
[Carey, P. M.] Univ Cincinnati, Acad Hlth Ctr, Hoxworth Blood Ctr, Cincinnati, OH USA.
[Simon, T. L.] CSL Plasma, Boca Raton, FL USA.
EM cabler@usa.redcross.org
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2010
VL 50
SU 2
BP 44A
EP 45A
PG 2
WC Hematology
SC Hematology
GA 649JM
UT WOS:000281764900103
ER
PT J
AU Booth, GS
Nghiem, KL
Lozier, JN
Johnson, SE
Klein, HG
Flegel, WA
AF Booth, G. S.
Nghiem, K. L.
Lozier, J. N.
Johnson, S. E.
Klein, H. G.
Flegel, W. A.
TI Spray Dried Plasma: Human Plasma Can Be Stored at Room Temperature: A
Pilot Study
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting 2010
CY OCT 09-12, 2010
CL Baltimore, MD
SP AABB
C1 [Nghiem, K. L.; Lozier, J. N.] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
[Johnson, S. E.] Velico Med, Beverly, MA USA.
EM boothgs@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2010
VL 50
SU 2
BP 62A
EP 62A
PG 1
WC Hematology
SC Hematology
GA 649JM
UT WOS:000281764900144
ER
PT J
AU Norris, PJ
Operskalski, EA
Schechterly, C
Lebedeva, M
Alter, HJ
Busch, MP
AF Norris, P. J.
Operskalski, E. A.
Schechterly, C.
Lebedeva, M.
Alter, H. J.
Busch, M. P.
TI HLA Alloimmunization After Transfusion Is Frequently Detected Using a
Sensitive Antibody Detection System
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting 2010
CY OCT 09-12, 2010
CL Baltimore, MD
SP AABB
C1 [Norris, P. J.; Lebedeva, M.; Busch, M. P.] Blood Syst Res Inst, San Francisco, CA USA.
[Norris, P. J.; Busch, M. P.] Univ Calif San Francisco, Media Lab, San Francisco, CA 94143 USA.
[Operskalski, E. A.] Univ So Calif, Los Angeles, CA USA.
[Schechterly, C.; Alter, H. J.] NIH, Bethesda, MD 20892 USA.
EM pnorris@bloodsystems.org
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2010
VL 50
SU 2
BP 121A
EP 121A
PG 1
WC Hematology
SC Hematology
GA 649JM
UT WOS:000281764900301
ER
PT J
AU Sanchez, R
Montalvo, L
Wen, L
Lee, T
Schechterly, C
Colvin, C
Alter, HJ
Luban, N
Busch, MP
AF Sanchez, R.
Montalvo, L.
Wen, L.
Lee, T.
Schechterly, C.
Colvin, C.
Alter, H. J.
Luban, N.
Busch, M. P.
TI Absence of Transfusion-Associated Microchimerism in Medical and Surgical
Adult and Pediatric Blood Recipients
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting 2010
CY OCT 09-12, 2010
CL Baltimore, MD
SP AABB
C1 [Sanchez, R.; Montalvo, L.; Wen, L.; Lee, T.; Busch, M. P.] Blood Syst Res Inst, San Francisco, CA USA.
[Schechterly, C.; Alter, H. J.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Colvin, C.; Luban, N.] Childrens Natl Med Ctr, Lab Med, Washington, DC 20010 USA.
EM rsanchezrosen@bloodsystems.org
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2010
VL 50
SU 2
BP 128A
EP 129A
PG 2
WC Hematology
SC Hematology
GA 649JM
UT WOS:000281764900319
ER
PT J
AU Ravenell, KR
Schmid, P
Byrne, KM
Stroka-Lee, AH
Sheldon, SL
Flegel, WA
AF Ravenell, K. R.
Schmid, P.
Byrne, K. M.
Stroka-Lee, A. H.
Sheldon, S. L.
Flegel, W. A.
TI DARC Gene Sequences in 52 African-American Blood Donors
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting 2010
CY OCT 09-12, 2010
CL Baltimore, MD
SP AABB
C1 [Ravenell, K. R.; Schmid, P.; Byrne, K. M.; Stroka-Lee, A. H.; Sheldon, S. L.; Flegel, W. A.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
EM ravenellkr@mail.nih.gov
RI Schmid, Pirmin/A-1457-2009
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2010
VL 50
SU 2
BP 140A
EP 140A
PG 1
WC Hematology
SC Hematology
GA 649JM
UT WOS:000281764900350
ER
PT J
AU Borge, PD
Stroka-Lee, AH
Schmid, P
Hsieh, MM
Tisdale, JF
Klein, HG
Flegel, WA
AF Borge, P. D.
Stroka-Lee, A. H.
Schmid, P.
Hsieh, M. M.
Tisdale, J. F.
Klein, H. G.
Flegel, W. A.
TI Delayed Red Blood Cell Chimerism in an HSC Transplant for Sickle Cell
Disease Associated with a Non-ABO Alloantibody
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting 2010
CY OCT 09-12, 2010
CL Baltimore, MD
SP AABB
C1 [Borge, P. D.; Stroka-Lee, A. H.; Schmid, P.; Klein, H. G.; Flegel, W. A.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
[Hsieh, M. M.; Tisdale, J. F.] NIDDK, Mol & Clin Hematol Branch, NHLBI, NIH, Bethesda, MD USA.
EM borgepd@mail.nih.gov
RI Schmid, Pirmin/A-1457-2009
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2010
VL 50
SU 2
BP 155A
EP 155A
PG 1
WC Hematology
SC Hematology
GA 649JM
UT WOS:000281764900392
ER
PT J
AU Halverson, GR
Stroka-Lee, AH
AF Halverson, G. R.
Stroka-Lee, A. H.
TI Converting Neutral Buffered Gel Cards to Murine IgG Gel Cards for Use in
the ID-Micro Typing System (TM)
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting 2010
CY OCT 09-12, 2010
CL Baltimore, MD
SP AABB
C1 [Halverson, G. R.] New York Blood Ctr, New York, NY 10021 USA.
[Stroka-Lee, A. H.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
EM ghalverson@nybloodcenter.org
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2010
VL 50
SU 2
BP 167A
EP 167A
PG 1
WC Hematology
SC Hematology
GA 649JM
UT WOS:000281764900425
ER
PT J
AU Stroka-Lee, AH
Halverson, GR
AF Stroka-Lee, A. H.
Halverson, G. R.
TI Collecting GPI-Negative RBCs from Patients with Paroxysmal Nocturnal
Hemoglobinuria for Use in Serological Investigations
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting 2010
CY OCT 09-12, 2010
CL Baltimore, MD
SP AABB
C1 [Stroka-Lee, A. H.] NIH, Dept Transfus Med, Bethesda, MA USA.
[Halverson, G. R.] New York Blood Ctr, New York, NY 10021 USA.
EM leestrokaa@cc.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2010
VL 50
SU 2
BP 167A
EP 168A
PG 2
WC Hematology
SC Hematology
GA 649JM
UT WOS:000281764900427
ER
PT J
AU Booth, GS
Mejia, R
Hsieh, MM
Klein, HG
Klion, A
Flegel, WA
AF Booth, G. S.
Mejia, R.
Hsieh, M. M.
Klein, H. G.
Klion, A.
Flegel, W. A.
TI Plasmodium Falciparium Transmission by a Cryopreserved Stem Cell Product
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting 2010
CY OCT 09-12, 2010
CL Baltimore, MD
SP AABB
C1 [Booth, G. S.; Klein, H. G.; Flegel, W. A.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
[Hsieh, M. M.] NHLBI, NIH, Bethesda, MD 20892 USA.
EM boothgs@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2010
VL 50
SU 2
BP 199A
EP 199A
PG 1
WC Hematology
SC Hematology
GA 649JM
UT WOS:000281764900510
ER
PT J
AU Struble, E
Duan, H
Zhong, L
Harman, C
Virata-Theimer, M
Yu, MW
Feinstone, S
Alter, HJ
Zhang, P
AF Struble, E.
Duan, H.
Zhong, L.
Harman, C.
Virata-Theimer, M.
Yu, M. W.
Feinstone, S.
Alter, H. J.
Zhang, P.
TI Presence of Neutralizing Antibodies in the Plasma of Chronic Hepatitis C
Patients
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting 2010
CY OCT 09-12, 2010
CL Baltimore, MD
SP AABB
C1 [Struble, E.; Zhong, L.; Harman, C.; Virata-Theimer, M.; Yu, M. W.; Zhang, P.] US FDA, OBRR, DH, CBER, Bethesda, MD 20014 USA.
[Duan, H.; Feinstone, S.] US FDA, OVRR, CBER, Bethesda, MD 20014 USA.
[Alter, H. J.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
EM evi.struble@fda.hhs.gov
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2010
VL 50
SU 2
BP 204A
EP 204A
PG 1
WC Hematology
SC Hematology
GA 649JM
UT WOS:000281764900523
ER
PT J
AU Chancey, C
Stroka-Lee, AH
Rios, M
AF Chancey, C.
Stroka-Lee, A. H.
Rios, M.
TI Investigation of Potential Ligands for West Nile Virus on Human RBC
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting 2010
CY OCT 09-12, 2010
CL Baltimore, MD
SP AABB
C1 [Chancey, C.; Rios, M.] US FDA, DETTD, CBER, Bethesda, MD 20014 USA.
[Stroka-Lee, A. H.] NIH, DTM, Bethesda, MD 20892 USA.
EM caren.chancey@fda.hhs.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2010
VL 50
SU 2
BP 209A
EP 209A
PG 1
WC Hematology
SC Hematology
GA 649JM
UT WOS:000281764900536
ER
PT J
AU Mikovits, JA
Hagen, K
Sadowski, C
Ruscetti, FW
Liu, W
Lin, L
AF Mikovits, J. A.
Hagen, K.
Sadowski, C.
Ruscetti, F. W.
Liu, W.
Lin, L.
TI Inactivation of XMRV by the Intercept Blood System (TM) in Platelet
Concentrates
SO TRANSFUSION
LA English
DT Meeting Abstract
CT AABB Annual Meeting 2010
CY OCT 09-12, 2010
CL Baltimore, MD
SP AABB
C1 [Mikovits, J. A.; Hagen, K.] Whittemore Peterson Inst, Reno, NV USA.
[Sadowski, C.; Ruscetti, F. W.] NCI, Frederick, MD 21701 USA.
[Liu, W.; Lin, L.] Cerus Corp, Concord, CA USA.
EM wliu@cerus.com
NR 0
TC 1
Z9 1
U1 0
U2 3
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2010
VL 50
SU 2
BP 211A
EP 212A
PG 2
WC Hematology
SC Hematology
GA 649JM
UT WOS:000281764900543
ER
PT J
AU Woods, I
Tawab-Amiri, A
Byrne, K
Sabatino, M
Stroncek, DF
AF Woods, Iyonna
Tawab-Amiri, Abdul
Byrne, Karen
Sabatino, Marianna
Stroncek, David F.
TI Pilot analysis of cytokines levels in stored
granulocyte-colony-stimulating factor-mobilized peripheral blood stem
cell concentrates
SO TRANSFUSION
LA English
DT Article
ID TRANSFORMING-GROWTH-FACTOR; TRANSFUSION REACTIONS; TGF-BETA;
ACCUMULATION; PLATELETS; PLASMA; GENERATION; REMOVAL; FEBRILE; STORAGE
AB BACKGROUND:
The transfusion of peripheral blood stem cell (PBSC) concentrates is sometimes associated with febrile transfusion reactions. PBSC concentrates contain large numbers of white blood cells, and during storage the levels of soluble cytokines that could cause transfusion reactions may increase.
STUDY DESIGN AND METHODS:
Aliquots of granulocyte-colony-stimulating factor (CSF)-mobilized PBSC concentrates from nine healthy subjects were stored in bags at 2 to 8 degrees C for 48 hours. The levels of 19 growth factors and biologic response modifiers were measured in the plasma of PBSC concentrates at 0, 24, and 48 hours of storage using a nested enzyme-linked immunosorbent assay. The same 19 factor levels were also measured in blood plasma from six healthy subjects.
RESULTS:
There were no significant differences in the PBSC and plasma levels of soluble interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha, which can cause febrile reactions. The levels of TGF-beta 1, matrix metalloproteinase-8, CCL5/(reduced on activation normal T expressed and secreted), and platelet (PLT)-derived growth factor-AB were significantly greater in PBSCs than in plasma and the level of CCL2/MCP-1 was significantly less in PBSCs. Duration of PBSC storage had no effect on the levels of these five factors. There was a trend for reduced levels of IL-1 beta, IL-2, IL-7, IL-8, IL-12p70, IL-15, interferon-gamma, CD40L, and granulocyte-macrophage-CSF and increased levels of TNF-alpha and IL-10 levels in PBSC concentrates, but the differences were not significant.
CONCLUSIONS:
There was no increase in stored PBSC concentrates of cytokines that have been associated with febrile transfusion reactions; however, the levels of other factors that were likely released by PLTs and granulocytes during the collection process were elevated.
C1 [Woods, Iyonna; Tawab-Amiri, Abdul; Byrne, Karen; Sabatino, Marianna; Stroncek, David F.] NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA.
RP Stroncek, DF (reprint author), NIH, Ctr Clin, Dept Transfus Med, Bldg 10,Room 1C711, Bethesda, MD 20892 USA.
EM dstroncek@cc.nih.gov
FU Intramural NIH HHS [ZIA CL002120-02]
NR 24
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD SEP
PY 2010
VL 50
IS 9
BP 2011
EP 2015
DI 10.1111/j.1537-2995.2010.02695.x
PG 5
WC Hematology
SC Hematology
GA 646OZ
UT WOS:000281553200022
PM 20492614
ER
PT J
AU Noh, SJ
Lee, YT
Byrnes, C
Miller, JL
AF Noh, S. -J.
Lee, Y. T.
Byrnes, C.
Miller, J. L.
TI A transcriptome-based examination of blood group expression
SO TRANSFUSION CLINIQUE ET BIOLOGIQUE
LA English
DT Article
DE Transcriptome; Blood group; Erythropoiesis; RNA
ID GENE-EXPRESSION; CELLS; DIFFERENTIATION; ERYTHROPOIESIS; IDENTIFICATION;
PROLIFERATION; ANTIGENS; ELEMENTS; MARROW; ARRAYS
AB Over the last two decades, red cell biologists witnessed a vast expansion of genetic-based information pertaining to blood group antigens and their carrier molecules Genetic progress has led to a better comprehension of the associated antigens To assist with studies concerning the integrated regulation and function of blood groups. transcript levels for each of the 36 associated genes were studied Profiles using mRNA from directly sampled reticulocytes and cultured primary erythroblasts are summarized in this report Transcriptome profiles suggest a highly regulated pattern of blood group gene expression during erythroid differentiation and ontogeny Approximately one-third of the blood group carrier genes are transcribed in an erythroid-specific fashion Low-level and indistinct expression was noted for most of the carbohydrate-associated genes Methods are now being developed to further explore and manipulate expression of the blood group genes at all stages of human erythropoiesis (C) 2010 Elsevier Masson SAS All rights reserved
C1 [Noh, S. -J.; Lee, Y. T.; Byrnes, C.; Miller, J. L.] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
RP Miller, JL (reprint author), NIDDK, Mol Med Branch, NIH, 31 Ctr Dr,Bldg 10,Room 9N311, Bethesda, MD 20892 USA.
FU NIH, NIDDK
FX The Intramural Research Program of the NIH, NIDDK supported this
research
NR 24
TC 2
Z9 2
U1 0
U2 2
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 1246-7820
J9 TRANSFUS CLIN BIOL
JI Transfu. Clin. Biol.
PD SEP
PY 2010
VL 17
IS 3
BP 120
EP 125
DI 10.1016/j.tracli.2010.06.010
PG 6
WC Hematology; Immunology
SC Hematology; Immunology
GA 646LY
UT WOS:000281543300006
PM 20685146
ER
PT J
AU Roukos, V
Misteli, T
Schmidt, CK
AF Roukos, Vassilis
Misteli, Tom
Schmidt, Christine K.
TI Descriptive no more: the dawn of high-throughput microscopy
SO TRENDS IN CELL BIOLOGY
LA English
DT Article
ID FUNCTIONAL GENOMIC SCREEN; RNA INTERFERENCE; GENETIC SCREEN; PROTEINS;
CELLS; INFECTION
AB The next revolution in microscopy is upon us: it is High-Throughput Imaging (HTI). In HTI large numbers of images from many samples are acquired and analyzed. This has become possible due to a confluence of dramatic progress in microscope engineering, enabling efficient image collection, and the availability of high computing power for data analysis. Combining HTI with genome-wide RNA interference (RNAi)-based gene knockdown technology offers a powerful approach for unbiased discovery of cellular mechanisms.
C1 [Roukos, Vassilis; Misteli, Tom; Schmidt, Christine K.] NCI, NIH, Bethesda, MD 20892 USA.
RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM mistelit@mail.nih.gov
RI Roukos, Vassilis/K-6248-2012;
OI Schmidt, Christine/0000-0002-8363-7933
FU Intramural NIH HHS [ZIA BC010309-11]
NR 25
TC 3
Z9 3
U1 0
U2 1
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0962-8924
J9 TRENDS CELL BIOL
JI Trends Cell Biol.
PD SEP
PY 2010
VL 20
IS 9
BP 503
EP 506
DI 10.1016/j.tcb.2010.06.008
PG 4
WC Cell Biology
SC Cell Biology
GA 653RY
UT WOS:000282115600001
PM 20667736
ER
PT J
AU Romero, R
AF Romero, Roberto
TI Excellence, innovation and impact factor of Ultrasound in Obstetrics &
Gynecology
SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY
LA English
DT Editorial Material
ID PRETERM BIRTH; FETAL HEART; CERVICAL LENGTH; PREGNANCY; JOURNALS; RISK;
DISCOVERY; BRAIN; INDEX; VIEWS
C1 [Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Romero, Roberto] Wayne State Univ, Sch Med, Hutzel Womens Hosp, Ctr Mol Med & Genet,Detroit Med Ctr, Detroit, MI USA.
[Romero, Roberto] Michigan State Univ, E Lansing, MI 48824 USA.
RP Romero, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
NR 42
TC 0
Z9 0
U1 0
U2 4
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0960-7692
J9 ULTRASOUND OBST GYN
JI Ultrasound Obstet. Gynecol.
PD SEP
PY 2010
VL 36
IS 3
BP 263
EP 265
DI 10.1002/uog.7763
PG 3
WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine &
Medical Imaging
SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine &
Medical Imaging
GA 654DY
UT WOS:000282149900001
PM 20812305
ER
PT J
AU Mai, PL
Friedlander, M
Tucker, K
Phillips, KA
Hogg, D
Jewett, MAS
Lohynska, R
Daugaard, G
Richard, S
Bonaiti-Pellie, C
Heidenreich, A
Albers, P
Bodrogi, I
Geczi, L
Olah, E
Daly, PA
Guilford, P
Fossa, SD
Heimdal, K
Liubchenko, L
Tjulandin, SA
Stoll, H
Weber, W
Easton, DF
Dudakia, D
Huddart, R
Stratton, MR
Einhorn, L
Korde, L
Nathanson, KL
Bishop, T
Rapley, EA
Greene, MH
AF Mai, Phuong L.
Friedlander, Michael
Tucker, Kathy
Phillips, Kelly-Anne
Hogg, David
Jewett, Michael A. S.
Lohynska, Radka
Daugaard, Gedske
Richard, Stephane
Bonaiti-Pellie, Catherine
Heidenreich, Axel
Albers, Peter
Bodrogi, Istvan
Geczi, Lajos
Olah, Edith
Daly, Peter A.
Guilford, Parry
Fossa, Sophie D.
Heimdal, Ketil
Liubchenko, Ludmila
Tjulandin, Sergei A.
Stoll, Hans
Weber, Walter
Easton, Douglas F.
Dudakia, Darshna
Huddart, Robert
Stratton, Michael R.
Einhorn, Lawrence
Korde, Larissa
Nathanson, Katherine L.
Bishop, Timothy
Rapley, Elizabeth A.
Greene, Mark H.
TI The International Testicular Cancer Linkage Consortium: A
clinicopathologic descriptive analysis of 461 familial malignant
testicular germ cell tumor kindred
SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
LA English
DT Article
DE Testicular neoplasms; Familial; Epidemiology; Clinicopathologic
characteristics
ID OF-THE-LITERATURE; SUSCEPTIBILITY GENES; RISK-FACTORS; EXPERIENCE;
ANTICIPATION; EPIDEMIOLOGY; POPULATION; TESTIS; FATHER
AB Objectives: Familial aggregation of testicular germ cell tumor (TGCT) has been reported, but it is unclear if familial TGCT represents a unique entity with distinct clinicopathologic characteristics. Here we describe a collection of familial TGCT cases from an international consortium, in an effort to elucidate any clinical characteristics that are specific to this population.
Materials and methods: Families with >= 2 cases of TGCT enrolled at 18 of the sites participating in the International Testicular Cancer Linkage Consortium were included. We analyzed clinicopathologic characteristics of 985 cases from 461 families.
Results: A majority (88.5%) of families had only 2 cases of TGCT. Men with seminoma (50% of cases) had an older mean age at diagnosis than nonseminoma cases (P = 0.001). Among individuals with a history of cryptorchidism. TGCT was more likely to occur in the ipsilateral testis (kappa = 0.65). Cousin pairs appeared to represent a unique group, with younger age at diagnosis and a higher prevalence of cryptorchidism than other families.
Conclusions: Clinicopathologic characteristics in these familial TGCT cases were similar to those generally described for nonfamilial eases. However, we observed a unique presentation of familial TGCT among cousin pairs. Additional studies are needed to further explore this observation. Published by Elsevier Inc.
C1 [Mai, Phuong L.; Korde, Larissa; Greene, Mark H.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Friedlander, Michael; Tucker, Kathy] Univ New S Wales, Dept Med Oncol, Div Med, Sydney, NSW, Australia.
[Friedlander, Michael; Tucker, Kathy] Prince Wales Hosp Randwick, Sydney, NSW, Australia.
[Phillips, Kelly-Anne] Peter MacCallum Canc Ctr, Dept Haematol & Med Oncol, Melbourne, Australia.
[Hogg, David; Jewett, Michael A. S.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
[Hogg, David; Jewett, Michael A. S.] Univ Toronto, Toronto, ON, Canada.
[Lohynska, Radka] Univ Hosp, Dept Radiotherapy & Oncol, Prague, Czech Republic.
[Daugaard, Gedske] Rigshosp, Dept Oncol, DK-2100 Copenhagen, Denmark.
[Richard, Stephane] Fac Med Paris Sud, Genet Oncol EPHE CNRS FRE 2939, Paris, France.
[Richard, Stephane] CHU, Serv Urol, Le Kremlin Bicetre, France.
[Richard, Stephane] Inst Gustave Roussy, Villejuif, France.
[Bonaiti-Pellie, Catherine] INSERM, U535, F-94817 Villejuif, France.
[Bonaiti-Pellie, Catherine] Univ Paris Sud, Villejuif, France.
[Heidenreich, Axel] Univ Cologne, Dept Urol, Div Oncol Urol, Cologne, Germany.
[Albers, Peter] Klinikum Kassel GmbH, Dept Urol, Kassel, Germany.
[Bodrogi, Istvan; Geczi, Lajos; Olah, Edith] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary.
[Geczi, Lajos; Olah, Edith] Natl Inst Oncol, Dept Chemotherapy, Budapest, Hungary.
[Daly, Peter A.] St James Hosp, Dept Med Oncol, Dublin, Ireland.
[Guilford, Parry] Univ Otago, Canc Genet Lab, Dunedin, New Zealand.
[Fossa, Sophie D.; Heimdal, Ketil] Radiumhosp, Rikshosp, Dept Clin Canc Res, Oslo, Norway.
[Liubchenko, Ludmila; Tjulandin, Sergei A.] NN Blokhin Russian Canc Res Ctr, Lab Clin Genet, Inst Clin Oncol, Moscow, Russia.
[Stoll, Hans; Weber, Walter] Univ Basel Hosp, CH-4031 Basel, Switzerland.
[Easton, Douglas F.] CRC Genet Epidemiol Unit, Cambridge, England.
[Fossa, Sophie D.; Heimdal, Ketil] Radiumhosp, Rikshosp, Dept Med Genet, Oslo, Norway.
[Dudakia, Darshna; Stratton, Michael R.; Rapley, Elizabeth A.] Inst Canc Res, Sect Canc Genet, Sutton, Surrey, England.
[Huddart, Robert] Inst Canc Res, Acad Radiotherapy Unit, Sutton, Surrey, England.
[Einhorn, Lawrence] Indiana Univ, Dept Med, Sch Med, Indianapolis, IN 46204 USA.
[Nathanson, Katherine L.] Univ Penn, Sch Med, Div Med Genet, Dept Med, Philadelphia, PA 19104 USA.
[Bishop, Timothy] Imperial Canc Res Fund Genet Epidemiol Lab, Leeds, W Yorkshire, England.
RP Mai, PL (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
EM maip@mail.nih.gov
RI friedlander, michael/G-3490-2013;
OI friedlander, michael/0000-0002-6488-0604; Daugaard,
Gedske/0000-0002-9618-9180; Nathanson, Katherine/0000-0002-6740-0901;
Phillips, Kelly-Anne/0000-0002-0475-1771; Bishop,
Tim/0000-0002-8752-8785; Heimdal, Ketil/0000-0002-8911-3508
FU National Cancer Institute, National Institutes of Health; Westat, Inc.
[N02-CP-11019, N02-CP-65504]; [R01 CA114478]
FX This research was funded in part by the Intramural Research Program of
the National Cancer Institute, National Institutes of Health, and
supported by contracts N02-CP-11019 and N02-CP-65504 with Westat, Inc.
Other funding includes grant R01 CA114478 (K.L.N.).
NR 34
TC 16
Z9 17
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1078-1439
J9 UROL ONCOL-SEMIN ORI
JI Urol. Oncol.-Semin. Orig. Investig.
PD SEP-OCT
PY 2010
VL 28
IS 5
BP 492
EP 499
DI 10.1016/j.urolonc.2008.10.004
PG 8
WC Oncology; Urology & Nephrology
SC Oncology; Urology & Nephrology
GA 659BT
UT WOS:000282542700007
PM 19162511
ER
PT J
AU Lane, BR
Fergany, AF
Linehan, WM
Bratslavsky, G
AF Lane, Brian R.
Fergany, Amr F.
Linehan, W. Marston
Bratslavsky, Gennady
TI Should Preservable Parenchyma, and Not Tumor Size, Be the Main
Determinant of the Feasibility of Partial Nephrectomy?
SO UROLOGY
LA English
DT Editorial Material
ID RENAL-CELL CARCINOMA; NEPHRON-SPARING SURGERY; RADICAL NEPHRECTOMY;
KIDNEY; SURVIVAL; CM.
C1 [Bratslavsky, Gennady] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
Spectrum Hlth Hosp Syst, Div Urol, Grand Rapids, MI USA.
Michigan State Univ, Dept Surg, Grand Rapids, MI USA.
Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USA.
RP Bratslavsky, G (reprint author), NCI, Urol Oncol Branch, NIH, 10 Ctr Dr MSC 1107,Bldg 10,CRC,Room 2W-5942, Bethesda, MD 20892 USA.
EM bratslag@mail.nih.gov
NR 22
TC 10
Z9 11
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0090-4295
J9 UROLOGY
JI Urology
PD SEP
PY 2010
VL 76
IS 3
BP 608
EP 609
DI 10.1016/j.urology.2010.04.041
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 649AD
UT WOS:000281736300027
PM 20832610
ER
PT J
AU Williamson, MM
Torres-Velez, FJ
AF Williamson, M. M.
Torres-Velez, F. J.
TI Henipavirus: A Review of Laboratory Animal Pathology
SO VETERINARY PATHOLOGY
LA English
DT Article
DE animal efficacy rule; Hendra virus; laboratory animal models; Nipah
virus
ID NIPAH-VIRUS-INFECTION; EQUINE MORBILLIVIRUS INFECTION; BATS
PTEROPUS-POLIOCEPHALUS; HENDRA VIRUS; HAMSTER MODEL; FLYING-FOXES;
ENCEPHALITIS OUTBREAK; FATAL ENCEPHALITIS; SUBUNIT VACCINE; PIG-FARMERS
AB The genus Henipavirus contains two members-Hendra virus (HeV) and Nipah virus (NiV)-and each can cause fatal disease in humans and animals. HeV and Niv are currently classified as biosafety level 4, and NiV is classified as a category C priority pathogen. The aim of this article is to discuss the pathology of laboratory animal models of henipavirus infection and to assess their suitability as animal models for the development and testing of human therapeutics and vaccines. There has been considerable progress in the development of animal models for henipavirus disease. Suitable animal models include the golden hamster, ferrets, cats, and pigs, which develop disease resembling that observed in humans. Guinea pigs are a less reliable model for henipavirus disease, but they do develop henipavirus-induced encephalitis. Because human efficacy studies with henipaviruses are not permitted, animal studies are critical for the development of antiviral therapeutics and vaccines. Current research indicates that passive immunotherapy using monoclonal antibodies is protective of ferrets against NiV infection and that passive immunotherapy using NiV antibodies protects hamsters from HeV. Recombinant vaccines have been used to protect cats and pigs against NiV infection. Ribavirin and 6-aza-uridine were able to delay but not prevent NiV-induced mortality in hamsters. Further research is needed to develop a model and therapy for late-onset henipavirus encephalitis.
C1 [Williamson, M. M.] Gribbles Vet Pathol, Clayton, Vic 3168, Australia.
[Torres-Velez, F. J.] NIAID, Infect Dis Pathogenesis Sect, Comparat Med Branch, NIH, Bethesda, MD 20892 USA.
RP Williamson, MM (reprint author), Gribbles Vet Pathol, 1868 Dandenong Rd, Clayton, Vic 3168, Australia.
EM mark.williamson@gribbles.com.au
NR 89
TC 23
Z9 23
U1 2
U2 10
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0300-9858
J9 VET PATHOL
JI Vet. Pathol.
PD SEP
PY 2010
VL 47
IS 5
BP 871
EP 880
DI 10.1177/0300985810378648
PG 10
WC Pathology; Veterinary Sciences
SC Pathology; Veterinary Sciences
GA 675BN
UT WOS:000283798900010
PM 20682803
ER
PT J
AU Zerfas, PM
Brinster, LR
Starost, MF
Burkholder, TH
Raffeld, M
Eckhaus, MA
AF Zerfas, P. M.
Brinster, L. R.
Starost, M. F.
Burkholder, T. H.
Raffeld, M.
Eckhaus, M. A.
TI Amelanotic Melanoma in a New Zealand White Rabbit (Oryctolagus
cuniculus)
SO VETERINARY PATHOLOGY
LA English
DT Article
DE amelanotic melanoma; immunohistochemistry; rabbit; skin; transmission
electron microscopy
ID MALIGNANT-MELANOMA; IMMUNOHISTOCHEMISTRY; MELANOSOMES
AB A 3.5-year-old intact male double-transgenic New Zealand white rabbit (Oryctolagus cuniculus), apoA-I and LCAT (apolipoprotein and lecithin:cholesterol acyltransferase), was presented with a discrete, raised facial mass (0.5 x 1.0 x 1.0 cm). The mass was surgically excised, with reoccurrence to the same site 88 days later. A second surgical excision was performed, and the rabbit died 3 weeks later from respiratory distress. At necropsy, multiple varying-sized masses were observed in the ventral mandibular region and throughout the lungs, pleura, and diaphragm. On histopathology, the masses were composed of moderately anisocytotic and anisokaryotic polygonal to spindloid cells with moderate finely granular, lightly eosinophilic cytoplasm, having round to oval nuclei with one to several nucleoli and finely stippled chromatin. Mitotic figures were frequent. Lymphatic and venous invasion were noted with neoplastic cells metastasized to the submandibular lymph nodes, lungs, liver, and adventitial surface of the aorta. Fontana-Masson stain was negative for melanin, thereby necessitating immunohistochemistry and transmission electron microscopy. Positive staining with MART-1 (a melanocyte protein marker) combined with transmission electron microscopy revealing type II melanosomes confirmed the diagnosis of an amelanotic melanoma.
C1 [Zerfas, P. M.; Brinster, L. R.; Starost, M. F.; Burkholder, T. H.; Eckhaus, M. A.] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA.
[Raffeld, M.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Zerfas, PM (reprint author), 9000 Rockville Pike,Bldg 28A,Room 106,MSC 5230, Bethesda, MD 20892 USA.
EM zerfasp@ors.od.nih.gov
FU National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institutes of Health. Excellent technical support was provided
by Jorge Chavez and Erik Lasker. Thanks to Rick Dreyfuss for
photography.
NR 27
TC 3
Z9 3
U1 0
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0300-9858
J9 VET PATHOL
JI Vet. Pathol.
PD SEP
PY 2010
VL 47
IS 5
BP 977
EP 981
DI 10.1177/0300985810369898
PG 5
WC Pathology; Veterinary Sciences
SC Pathology; Veterinary Sciences
GA 675BN
UT WOS:000283798900023
PM 20460451
ER
PT J
AU Kumar, S
Dias, FM
Nayak, B
Collins, PL
Samal, SK
AF Kumar, Sachin
Dias, Flavia Militino
Nayak, Baibaswata
Collins, Peter L.
Samal, Siba K.
TI Experimental avian paramyxovirus serotype-3 infection in chickens and
turkeys
SO VETERINARY RESEARCH
LA English
DT Article
DE avian paramyxovirus; pathogenicity
ID NEWCASTLE-DISEASE VIRUS; COMPLETE GENOME SEQUENCE;
HEMAGGLUTININ-NEURAMINIDASE PROTEIN; COMPLETE NUCLEOTIDE-SEQUENCE;
MONOCLONAL-ANTIBODIES; GREAT-BRITAIN; PATHOGENICITY; VIRULENCE; POULTRY;
TYPE-3
AB Avian paramyxoviruses (APMV) are divided into nine serotypes. Newcastle disease virus (APMV-1) is the most extensively characterized, while relatively little information is available for the other APMV serotypes. In the present study, we examined the pathogenicity of two divergent strains of APMV-3, Netherlands and Wisconsin, in (i) 9-day-old embryonated chicken eggs, (ii) 1-day-old specific pathogen free (SPF) chicks and turkeys, and (iii) 2-week-old SPF chickens and turkeys. The mean death time in 9-day-old embryonated chicken eggs was 112 h for APMV-3 strain Netherlands and > 168 h for strain Wisconsin. The intracerebral pathogenicity index in 1-day-old chicks for strain Netherlands was 0.39 and for strain Wisconsin was zero. Thus, both strains are lentogenic. Both the strains replicated well in brain tissue when inoculated intracerebrally in 1-day-old SPF chicks, but without causing death. Mild respiratory disease signs were observed in 1-day-old chickens and turkeys when inoculated through oculonasal route with either strain. There were no overt signs of illness in 2-weeks-old chickens and turkeys by either strain, although all the birds seroconverted after infection. The viruses were isolated predominantly from brain, lungs, spleens, trachea, pancreas and kidney. Immunohistochemistry studies also showed the presence of large amount of viral antigens in both epithelial and sub-epithelial lining of respiratory and alimentary tracts. Our result suggests systemic spread of APMV-3 even though the viral fusion glycoprotein does not contain the canonical furin proteases cleavage site. Furthermore, there was little or no disease despite systemic viral spread and abundant viral replication in all the tissues tested.
C1 [Kumar, Sachin; Dias, Flavia Militino; Nayak, Baibaswata; Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
[Collins, Peter L.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Samal, SK (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
EM ssamal@umd.edu
RI Nayak, Baibaswata/L-6156-2016
FU NIAID [N01A060009]; NIAID, NIH
FX We thank Daniel Rockemann and all our laboratory members for their
excellent technical assistance and help. This research was supported by
NIAID contract No. N01A060009 (85% support) and NIAID, NIH Intramural
Research Program (15% support). The views expressed herein do not
necessarily reflect the official policies of the Department of Health
and Human Services; nor does mention of trade names, commercial
practices, or organizations imply endorsement by the U.S. Government.
NR 42
TC 6
Z9 7
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 0928-4249
J9 VET RES
JI Vet. Res.
PD SEP-OCT
PY 2010
VL 41
IS 5
AR 72
DI 10.1051/vetres/2010042
PG 14
WC Veterinary Sciences
SC Veterinary Sciences
GA 678GY
UT WOS:000284063300015
PM 20663473
ER
PT J
AU Mikovits, JA
Lombardi, VC
Pfost, MA
Hagen, KS
Ruscetti, FW
AF Mikovits, Judy A.
Lombardi, Vincent C.
Pfost, Max A.
Hagen, Kathryn S.
Ruscetti, Francis W.
TI Detection of an infectious retrovirus, XMRV, in blood cells of patients
with chronic fatigue syndrome
SO VIRULENCE
LA English
DT Article
DE biological amplification; molecular amplification; XMRV; myalgic
encephalomyelitis/chronic fatigue; syndrome
AB In October 2009, we reported the first direct isolation of infectious xenotropic murine leukemia virus-related virus (XMRV). In that study, we used a combination of biological amplification and molecular enhancement techniques to detect XMRV in more than 75% of 101 patients with chronic fatigue syndrome (CFS). Since our report, controversy arose after the publication of several studies that failed to detect XMRV infection in their CFS patient populations. In this addenda, we further detail the multiple detection methods we used in order to observe XMRV infection in our CFS cohort. Our results indicate that PCR from DNA of unstimulated peripheral blood mononuclear cells is the least sensitive method for detection of XMRV in subjects' blood. We advocate the use of more than one type of assay in order to determine the frequency of XMRV infection in patient cohorts in future studies of the relevance of XMRV to human disease.
C1 [Mikovits, Judy A.; Lombardi, Vincent C.; Pfost, Max A.; Hagen, Kathryn S.] Whittemore Peterson Inst, Reno, NV USA.
[Ruscetti, Francis W.] NCI, Lab Expt Immunol, Canc & Inflammat Program, Frederick, MD 21701 USA.
RP Mikovits, JA (reprint author), Whittemore Peterson Inst, Reno, NV USA.
EM judym@wpinstitute.org
NR 10
TC 22
Z9 23
U1 2
U2 11
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 2150-5594
J9 VIRULENCE
JI Virulence
PD SEP-OCT
PY 2010
VL 1
IS 5
BP 386
EP 390
DI 10.4161/viru.1.5.12486
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 789MY
UT WOS:000292520800006
PM 21178474
ER
PT J
AU Subbiah, M
Nayak, S
Collins, PL
Samal, SK
AF Subbiah, Madhuri
Nayak, Shreeraj
Collins, Peter L.
Samal, Siba K.
TI Complete genome sequences of avian paramyxovirus serotype 2 (APMV-2)
strains Bangor, England and Kenya: Evidence for the existence of
subgroups within serotype 2
SO VIRUS RESEARCH
LA English
DT Article
DE Avian paramyxovirus serotype 2; Strain Yucaipa; Strain Bangor; Strain
England; Strain Kenya; Complete genome sequences; Subgroup of serotype 2
ID NEWCASTLE-DISEASE VIRUS; YUCAIPA-LIKE; WILD BIRDS; RNA-SYNTHESIS;
V-PROTEIN; ISRAEL; IDENTIFICATION; POULTRY; REVEALS; FINCH
AB The complete consensus genome sequences of avian paramyxovirus (APMV) serotype 2 strains Bangor, England and Kenya were determined and compared with those of APMV-2 prototype strain Yucaipa and other paramyxoviruses. The genome lengths of APMV-2 strains Bangor, England and Kenya are 15,024, 14,904, 14,916 nucleotides (nt), respectively, compared to 14,904 nt for Yucaipa. Each genome consists of six non-overlapping genes in the order of 3' N-P/V/W-M-F-HN-L5', with a 55-nt leader at the 3' end. The length of the trailer at the 5' end of strain Bangor was 173 nt, compared to 154 nt for strains England. Kenya, and Yucaipa. In general, sequence comparison of APMV-2 strains England and Kenya with strain Yucaipa have 94.5 and 88% nt and 96 and 92% aggregate amino acid (aa) identity, respectively. In contrast, strain Bangor has a much lower percent nt identity (70.4, 69.4, and 70.8%) and aa identity (75.3, 76.2, and 76.3%) with strains Yucaipa, England, and Kenya, respectively. Furthermore, strain Bangor has a single basic aa residue ((101)TLPSAR down arrow F(108)) at the fusion protein cleavage site compared to the dibasic aa ((93)DKPASR down arrow F(100)) found in those of other three strains. Reciprocal cross-hemagglutination inhibition (HI) and cross-neutralization assays using post-infection chicken sera indicated that strain Bangor is antigenically related to the other APMV-2 strains, but with a 4- to 8-fold difference in homologous versus heterologous HI titer. These differences in antigenic relatedness suggest that these four APMV-2 strains represent a single serotype with two antigenic subgroups, and this is strongly supported by the dimorphism in nt and aa sequence identity. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Subbiah, Madhuri; Nayak, Shreeraj; Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
[Collins, Peter L.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
RP Samal, SK (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, 8075 Greenmead Dr, College Pk, MD 20742 USA.
EM ssamal@umd.edu
FU NIAID [N01A060009]; NIAID, NIH
FX We thank all our laboratory members for their excellent technical
assistance. This research was supported by NIAID contract no. N01A060009
(85% support) and NIAID, NIH Intramural Research Program (15% support).
The views expressed herein do not necessarily reflect the official
policies of the Department of Health and Human Services; nor does
mention of trade names, commercial practices, or organizations imply
endorsement by the U.S. Government.
NR 50
TC 13
Z9 13
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1702
J9 VIRUS RES
JI Virus Res.
PD SEP
PY 2010
VL 152
IS 1-2
BP 85
EP 95
DI 10.1016/j.virusres.2010.06.009
PG 11
WC Virology
SC Virology
GA 644FX
UT WOS:000281360300011
PM 20600395
ER
PT J
AU Ptak, K
Farrell, D
Panaro, NJ
Grodzinski, P
Barker, AD
AF Ptak, Krzysztof
Farrell, Dorothy
Panaro, Nicholas J.
Grodzinski, Piotr
Barker, Anna D.
TI The NCI Alliance for Nanotechnology in Cancer: achievement and path
forward
SO WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY
LA English
DT Review
ID POSITRON-EMISSION-TOMOGRAPHY; LIVING MICE; MOUSE MODEL; NANOPARTICLES;
ANGIOGENESIS; DELIVERY; TUMORS; NANOCRYSTALS; PARTICLES; RESPONSES
AB Nanotechnology is a 'disruptive technology', which can lead to a generation of new diagnostic and therapeutic products, resulting in dramatically improved cancer outcomes. The National Cancer Institute (NCI) of National Institutes of Health explores innovative approaches to multidisciplinary research allowing for a convergence of molecular biology, oncology, physics, chemistry, and engineering and leading to the development of clinically worthy technological approaches. These initiatives include programmatic efforts to enable nanotechnology as a driver of advances in clinical oncology and cancer research, known collectively as the NCI Alliance for Nanotechnology in Cancer (ANC). Over the last 5 years, ANC has demonstrated that multidisciplinary approach catalyzes scientific developments and advances clinical translation in cancer nanotechnology. The research conducted by ANC members has improved diagnostic assays and imaging agents, leading to the development of point-of-care diagnostics, identification and validation of numerous biomarkers for novel diagnostic assays, and the development of multifunctional agents for imaging and therapy. Numerous nanotechnology-based technologies developed by ANC researchers are entering clinical trials. NCI has re-issued ANC program for next 5 years signaling that it continues to have high expectations for cancer nanotechnology's impact on clinical practice. The goals of the next phase will be to broaden access to cancer nanotechnology research through greater clinical translation and outreach to the patient and clinical communities and to support development of entirely new models of cancer care. (C) 2010 John Wiley & Sons, Inc. WIREs Nanomed Nanobiotechnol 2010 2 450-460
C1 [Ptak, Krzysztof; Farrell, Dorothy; Grodzinski, Piotr; Barker, Anna D.] NCI, Off Canc Nanotechnol Res, Ctr Strateg Sci Initiat, NIH, Bethesda, MD 20892 USA.
[Panaro, Nicholas J.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 20892 USA.
[Barker, Anna D.] NCI, Off Director, NIH, Bethesda, MD 20892 USA.
RP Grodzinski, P (reprint author), NCI, Off Canc Nanotechnol Res, Ctr Strateg Sci Initiat, NIH, 31 Ctr Dr, Bethesda, MD 20892 USA.
EM grodzinp@mail.nih.gov
FU NCI, NIH [HHSN261200800001E]
FX This project has been funded in whole or in part with federal funds from
the NCI, NIH, 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
U.S. Government.
NR 43
TC 10
Z9 10
U1 0
U2 5
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1939-5116
J9 WIRES NANOMED NANOBI
JI Wiley Interdiscip. Rev.-Nanomed. Nanobiotechnol.
PD SEP-OCT
PY 2010
VL 2
IS 5
BP 450
EP 460
DI 10.1002/wnan.98
PG 11
WC Nanoscience & Nanotechnology; Medicine, Research & Experimental
SC Science & Technology - Other Topics; Research & Experimental Medicine
GA 645KU
UT WOS:000281456300002
PM 20552623
ER
PT J
AU Abdelmohsen, K
Gorospe, M
AF Abdelmohsen, Kotb
Gorospe, Myriam
TI Posttranscriptional regulation of cancer traits by HuR
SO WILEY INTERDISCIPLINARY REVIEWS-RNA
LA English
DT Review
AB Cancer-related gene expression programs are strongly influenced by posttran-scriptional mechanisms. The RNA-binding protein HuR is highly abundant in many cancers. Numerous HuR-regulated mRNAs encode proteins implicated in carcinogenesis. Here, we review the collections of HuR target mRNAs that encode proteins responsible for implementing five major cancer traits. By interacting with specific mRNA subsets, HuR enhances the levels of proteins that (1) promote cell proliferation, (2) increase cell survival, (3) elevate local angiogenesis, (4) help the cancer cell evade immune recognition, and (5) facilitate cancer cell invasion and metastasis. We propose that HuR exerts a tumorigenic function by enabling these cancer phenotypes. We discuss evidence that links HuR to several specific cancers and suggests its potential usefulness in cancer diagnosis, prognosis, and therapy. (C) 2010 John Wiley & Sons, Ltd. WIREs RNA 2010 1 214-229
C1 [Abdelmohsen, Kotb; Gorospe, Myriam] NIA, LCMB, IRP, NIH, Baltimore, MD 21224 USA.
RP Gorospe, M (reprint author), NIA, LCMB, IRP, NIH, Baltimore, MD 21224 USA.
EM myriam-gorospe@nih.gov
OI abdelmohsen, Kotb/0000-0001-6240-5810
FU Intramural NIH HHS [Z01 AG000511-10, Z01 AG000393-01]
NR 174
TC 140
Z9 144
U1 3
U2 14
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1757-7004
J9 WIRES RNA
JI Wiley Interdiscip. Rev.-RNA
PD SEP-OCT
PY 2010
VL 1
IS 2
BP 214
EP 229
DI 10.1002/wrna.4
PG 16
WC Cell Biology
SC Cell Biology
GA V22HV
UT WOS:000208267200003
PM 21935886
ER
PT J
AU Park, SR
Lee, KD
Kim, UK
Gil, YG
Oh, KS
Park, BS
Kim, GC
AF Park, Sang Rye
Lee, Kyoung Duk
Kim, Uk Kyu
Gil, Young Gi
Oh, Kyu Seon
Park, Bong Soo
Kim, Gyoo Cheon
TI Pseudomonas aeruginosa Exotoxin A Reduces Chemoresistance of Oral
Squamous Carcinoma Cell via Inhibition of Heat Shock Proteins 70 (HSP70)
SO YONSEI MEDICAL JOURNAL
LA English
DT Article
DE Pseudomonas aeruginosa exotoxin A; chemoresistance; oral squamous cell
carcinoma cells; heat shock protein 70; apoptosis
ID BREAST-CANCER CELLS; DOWN-REGULATION; SURFACE EXPRESSION;
MELANOMA-CELLS; COLEYS TOXIN; APOPTOSIS; HEAT-SHOCK-PROTEIN-70;
INDUCTION; THERAPY; DEATH
AB Purpose: Oral squamous carcinoma (OSCC) cells exhibit resistance to chemotherapeutic agent-mediated apoptosis in the late stage of malignancy. Increased levels of heat shock proteins 70 (HSP70) in cancer cells are known to confer resistance to apoptosis. Since recent advances in the understanding of bacterial toxins have produced new strategies for the treatment of cancers, we investigated the effect of Pseudomonas aeruginosa exotoxin A (PEA) on HSP70 expression and induction of apoptosis in chemoresistant OSCC cell line (YD-9). Materials and Methods: The apoptotic effect of PEA on chemoresistant YD-9 cells was confirmed by MTT, Hoechst and TUNEL stains, DNA electrophoresis, and Western blot analysis. Results: While YD-9 cells showed high resistance to chemotherapeutic agents such as etoposide and 5-fluorouraci (5-FU), HSP70 antisense oligonucelotides sensitized chemoresistant YD-9 cells to etoposide and 5-FU. On the other hand, PEA significantly decreased the viability of YD-9 cells by deteriorating the HSP70-relating protecting system through inhibition of HSP70 expression and inducing apoptosis in YD-9 cells. Apoptotic manifestations were evidenced by changes in nuclear morphology, generation of DNA fragmentation, and activation of caspases. While p53, p21, and E2F-1 were upregulated, cdk2 and cyclin B were downregulated by PEA treatment, suggesting that PEA caused cell cycle arrest at the G2/M checkpoint. Conclusion: Therefore, these results indicate that PEA reduced the chemoresistance through inhibition of HSP70 expression and also induced apoptosis in chemoresistant YD-9 cells.
C1 [Park, Sang Rye; Lee, Kyoung Duk; Park, Bong Soo; Kim, Gyoo Cheon] Pusan Natl Univ, Res Inst Oral Biotechnol, Sch Dent, Dept Oral Anat, Yangsan 626870, South Korea.
[Kim, Uk Kyu] Pusan Natl Univ, Res Inst Oral Biotechnol, Sch Dent, Dept Oral & Maxillofacial Surg, Yangsan 626870, South Korea.
[Gil, Young Gi] Kosin Univ, Coll Med, Dept Anat, Pusan, South Korea.
[Oh, Kyu Seon] NCI, Basic Res Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Kim, GC (reprint author), Pusan Natl Univ, Res Inst Oral Biotechnol, Sch Dent, Dept Oral Anat, Yangsan 626870, South Korea.
EM ki91000m@pusan.ac.kr
FU the Korean Government (MOEHRD) [KRF-2008-331-E00342]
FX This work was supported by a Korea Research Foundation grant funded by
the Korean Government (MOEHRD, Basic Research Promotion Fund)
(KRF-2008-331-E00342).
NR 45
TC 4
Z9 5
U1 0
U2 0
PU YONSEI UNIV COLLEGE MEDICINE
PI SEOUL
PA IN-HONG CHOI, MD, PH D, 250 SEONGSAN-RO, SEODAEMUN-GU, SEOUL 120-752,
SOUTH KOREA
SN 0513-5796
J9 YONSEI MED J
JI Yonsei Med. J.
PD SEP 1
PY 2010
VL 51
IS 5
BP 708
EP 716
DI 10.3349/ymj.2010.51.5.708
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 633RL
UT WOS:000280522000013
PM 20635445
ER
PT J
AU Friedman, JS
Chang, B
Krauth, DS
Lopez, I
Waseem, NH
Hurd, RE
Feathers, KL
Branham, KE
Shaw, M
Thomas, GE
Brooks, MJ
Liu, CQ
Bakeri, HA
Campos, MM
Maubaret, C
Webster, AR
Rodriguez, IR
Thompson, DA
Bhattacharya, SS
Koenekoop, RK
Heckenlively, JR
Swaroop, A
AF Friedman, James S.
Chang, Bo
Krauth, Daniel S.
Lopez, Irma
Waseem, Naushin H.
Hurd, Ron E.
Feathers, Kecia L.
Branham, Kari E.
Shaw, Manessa
Thomas, George E.
Brooks, Matthew J.
Liu, Chunqiao
Bakeri, Hirva A.
Campos, Maria M.
Maubaret, Cecilia
Webster, Andrew R.
Rodriguez, Ignacio R.
Thompson, Debra A.
Bhattacharya, Shomi S.
Koenekoop, Robert K.
Heckenlively, John R.
Swaroop, Anand
TI Loss of lysophosphatidylcholine acyltransferase 1 leads to photoreceptor
degeneration in rd11 mice
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE gene discovery; lipid enzyme; phospholipid remodeling; retinal
degeneration; visual dysfunction
ID LEBER CONGENITAL AMAUROSIS; RETINAL DEGENERATION; RETINITIS-PIGMENTOSA;
DOCOSAHEXAENOIC ACID; MACULAR DEGENERATION; BETA-SUBUNIT;
CGMP-PHOSPHODIESTERASE; SPATIAL-DISTRIBUTION; DISK MEMBRANES; VISUAL
CYCLE
AB Retinal degenerative diseases, such as retinitis pigmentosa and Leber congenital amaurosis, are a leading cause of untreatable blindness with substantive impact on the quality of life of affected individuals and their families. Mouse mutants with retinal dystrophies have provided a valuable resource to discover human disease genes and helped uncover pathways critical for photoreceptor function. Here we show that the rd11 mouse mutant and its allelic strain, B6-JR2845, exhibit rapid photoreceptor dysfunction, followed by degeneration of both rods and cones. Using linkage analysis, we mapped the rd11 locus to mouse chromosome 13. We then identified a one-nucleotide insertion (c.420-421insG) in exon 3 of the Lpcat1 gene. Subsequent screening of this gene in the B6-JR2845 strain revealed a seven-nucleotide deletion (c.14-20delGCCGCGG) in exon 1. Both sequence changes are predicted to result in a frame-shift, leading to premature truncation of the lysophosphatidylcholine acyltransferase-1 (LPCAT1) protein. LPCAT1 (also called AYTL2) is a phospholipid biosynthesis/remodeling enzyme that facilitates the conversion of palmitoyl-lysophosphatidylcholine to dipalmitoyl-phosphatidylcholine (DPPC). The analysis of retinal lipids from rd11 and B6-JR2845 mice showed substantially reduced DPPC levels compared with C57BL/6J control mice, suggesting a causal link to photoreceptor dysfunction. A follow-up screening of LPCAT1 in retinitis pigmentosa and Leber congenital amaurosis patients did not reveal any obvious disease-causing mutations. Previously, LPCAT1 has been suggested to be critical for the production of lung surfactant phospholipids and biosynthesis of platelet-activating factor in noninflammatory remodeling pathway. Our studies add another dimension to an essential role for LPCAT1 in retinal photoreceptor homeostasis.
C1 [Friedman, James S.; Krauth, Daniel S.; Brooks, Matthew J.; Liu, Chunqiao; Bakeri, Hirva A.; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
[Rodriguez, Ignacio R.] NEI, Mech Retinal Dis Sect, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Chang, Bo; Hurd, Ron E.] Jackson Lab, Bar Harbor, ME 04609 USA.
[Lopez, Irma; Koenekoop, Robert K.] McGill Univ, Ctr Hlth, Montreal Childrens Hosp, McGill Ocular Genet Lab, Montreal, PQ H3H 1P3, Canada.
[Waseem, Naushin H.; Maubaret, Cecilia; Webster, Andrew R.; Bhattacharya, Shomi S.] UCL, Inst Ophthalmol, Dept Genet, London EC1V 9EL, England.
[Feathers, Kecia L.; Branham, Kari E.; Shaw, Manessa; Thomas, George E.; Thompson, Debra A.; Heckenlively, John R.; Swaroop, Anand] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA.
RP Swaroop, A (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
EM swaroopa@nei.nih.gov
RI Waseem, Naushin/C-9573-2013; Liu, Chunqiao/O-3391-2013;
OI Liu, Chunqiao/0000-0002-0299-7401; Swaroop, Anand/0000-0002-1975-1141
FU National Eye Institute, National Institutes of Health [EY019943];
Foundation Fighting Blindness; Research to Prevent Blindness; Canadian
Institutes of Health Research; Foundation Fighting Blindness-Canada;
Fonds de la Recherche en Sante Quebec; Reseau de Vision; Foundation for
Retinal Research; Fight for Sight
FX We thank Jessica Chang, Mohammad Othman, and Renee Pigeon for assistance
and the National Eye Institute Biological Imaging Core for equipment
usage. Funding for this research was provided by the National Eye
Institute Intramural program, National Institutes of Health Grant
EY019943, Foundation Fighting Blindness, Research to Prevent Blindness,
Canadian Institutes of Health Research, Foundation Fighting
Blindness-Canada, Fonds de la Recherche en Sante Quebec, Reseau de
Vision, and Foundation for Retinal Research. G. E. T. was a recipient of
a Fight for Sight Summer Student Fellowship.
NR 60
TC 23
Z9 25
U1 0
U2 3
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 AUG 31
PY 2010
VL 107
IS 35
BP 15523
EP 15528
DI 10.1073/pnas.1002897107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 645NT
UT WOS:000281468500043
PM 20713727
ER
PT J
AU Kao, WT
Wang, YH
Kleinman, JE
Lipska, BK
Hyde, TM
Weinberger, DR
Law, AJ
AF Kao, Wee-Tin
Wang, Yanhong
Kleinman, Joel E.
Lipska, Barbara K.
Hyde, Thomas M.
Weinberger, Daniel R.
Law, Amanda J.
TI Common genetic variation in Neuregulin 3 (NRG3) influences risk for
schizophrenia and impacts NRG3 expression in human brain
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE clinical genetics; development; ErbB4; neuregulin; NRG1
ID SUSCEPTIBILITY; ERBB4; ISOFORM; DISEASE; SCAN; IDENTIFICATION; VARIANTS;
FAMILIES; LINKAGE
AB Structural and polymorphic variations in Neuregulin 3 (NRG3), 10q22-23 are associated with a broad spectrum of neurodevelopmental disorders including developmental delay, cognitive impairment, autism, and schizophrenia. NRG3 is a member of the neuregulin family of EGF proteins and a ligand for the ErbB4 receptor tyrosine kinase that plays pleotropic roles in neurodevelopment. Several genes in the NRG-ErbB signaling pathway including NRG1 and ErbB4 have been implicated in genetic predisposition to schizophrenia. Previous fine mapping of the 10q22-23 locus in schizophrenia identified genome-wide significant association between delusion severity and polymorphisms in intron 1 of NRG3 (rs10883866, rs10748842, and rs6584400). The biological mechanisms remain unknown. We identified significant association of these SNPs with increased risk for schizophrenia in 350 families with an affected offspring and confirmed association to patient delusion and positive symptom severity. Molecular cloning and cDNA sequencing in human brain revealed that NRG3 undergoes complex splicing, giving rise to multiple structurally distinct isoforms. RNA expression profiling of these isoforms in the prefrontal cortex of 400 individuals revealed that NRG3 expression is developmentally regulated and pathologically increased in schizophrenia. Moreover, we show that rs10748842 lies within a DNA ultraconserved element and homedomain and strongly predicts brain expression of NRG3 isoforms that contain a unique developmentally regulated 5' exon (P = 1.097E(-12) to 1.445E(-15)). Our observations strengthen the evidence that NRG3 is a schizophrenia susceptibility gene, provide quantitative insight into NRG3 transcription traits in the human brain, and reveal a probable mechanistic basis for disease association.
C1 [Kao, Wee-Tin; Wang, Yanhong; Kleinman, Joel E.; Lipska, Barbara K.; Hyde, Thomas M.; Weinberger, Daniel R.; Law, Amanda J.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
[Kao, Wee-Tin] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20814 USA.
RP Law, AJ (reprint author), NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
EM lawa@mail.nih.gov
RI Law, Amanda/G-6372-2012; Lipska, Barbara/E-4569-2017;
OI Law, Amanda/0000-0002-2574-1564
FU National Institute of Mental Health, National Institutes of Health,
Bethesda, MD; Medical Research Council United Kingdom
FX We thank Qiang Chen and John Meyers for help with data analysis and
Richard Straub and Radhakrishna Vakkalanka for genotyping assistance.
This research was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health,
Bethesda, MD, and by a Medical Research Council United Kingdom Career
Development Award held by A.J.L. at the University of Oxford, United
Kingdom.
NR 32
TC 57
Z9 60
U1 0
U2 8
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 31
PY 2010
VL 107
IS 35
BP 15619
EP 15624
DI 10.1073/pnas.1005410107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 645NT
UT WOS:000281468500059
PM 20713722
ER
PT J
AU Okun, E
Griffioen, K
Barak, B
Roberts, NJ
Castro, K
Pita, MA
Cheng, AW
Mughal, MR
Wan, RQ
Ashery, U
Mattson, MP
AF Okun, Eitan
Griffioen, Kathleen
Barak, Boaz
Roberts, Nicholas J.
Castro, Kamilah
Pita, Mario A.
Cheng, Aiwu
Mughal, Mohamed R.
Wan, Ruiqian
Ashery, Uri
Mattson, Mark P.
TI Toll-like receptor 3 inhibits memory retention and constrains adult
hippocampal neurogenesis
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE anxiety; cognition; GluR1; CREB
ID ELEMENT-BINDING PROTEIN; LONG-TERM POTENTIATION; ANTIDEPRESSANT
ACTIVITY; NEGATIVE REGULATOR; MICE; BEHAVIOR; REQUIREMENT; BRAIN; MOUSE;
GLUR1
AB Toll-like receptors (TLRs) are innate immune receptors that have recently emerged as regulators of neuronal survival and developmental neuroplasticity. Adult TLR3-deficient mice exhibited enhanced hippocampus-dependent working memory in the Morris water maze, novel object recognition, and contextual fear-conditioning tasks. In contrast, TLR3-deficient mice demonstrated impaired amygdala-related behavior and anxiety in the cued fear-conditioning, open field, and elevated plus maze tasks. Further, TLR3-deficient mice exhibited increased hippocampal CA1 and dentate gyrus volumes, increased hippocampal neurogenesis, and elevated levels of the AMPA receptor subunit GluR1 in the CA1 region of the hippocampus. In addition, levels of activated forms of the kinase ERK and the transcription factor CREB were elevated in the hippocampus of TLR3-deficient mice, suggesting that constitutive TLR3 signaling negatively regulates pathways known to play important roles in hippocampal plasticity. Direct activation of TLR3 by intracerebroventricular infusion of a TLR3 ligand impaired working memory, but not reference memory. Our findings reveal previously undescribed roles for TLR3 as a suppressor of hippocampal cellular plasticity and memory retention.
C1 [Okun, Eitan; Griffioen, Kathleen; Roberts, Nicholas J.; Castro, Kamilah; Pita, Mario A.; Cheng, Aiwu; Mughal, Mohamed R.; Wan, Ruiqian; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Barak, Boaz; Ashery, Uri] Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiol, IL-69978 Tel Aviv, Israel.
RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM mattsonm@grc.nia.nih.gov
RI Mattson, Mark/F-6038-2012; okun, eitan/K-1314-2016;
OI okun, eitan/0000-0001-8474-1487; Castro, Kamilah/0000-0002-0176-0998
FU National Institute on Aging of the National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute on Aging of the National Institutes of Health.
NR 34
TC 78
Z9 80
U1 0
U2 8
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD AUG 31
PY 2010
VL 107
IS 35
BP 15625
EP 15630
DI 10.1073/pnas.1005807107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 645NT
UT WOS:000281468500060
PM 20713712
ER
PT J
AU Tang, YY
Lu, QL
Geng, XJ
Stein, EA
Yang, YH
Posner, MI
AF Tang, Yi-Yuan
Lu, Qilin
Geng, Xiujuan
Stein, Elliot A.
Yang, Yihong
Posner, Michael I.
TI Short-term meditation induces white matter changes in the anterior
cingulate
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE anterior cingulate cortex; anterior corona radiata; integrative
body-mind training; relaxation training; self-regulation
ID SELF-REGULATION; WORKING-MEMORY; NERVOUS-SYSTEM; CORTEX; TRACT;
ARCHITECTURE; ADDICTION; MECHANISM; INTEGRITY; CONFLICT
AB The anterior cingulate cortex (ACC) is part of a network implicated in the development of self-regulation and whose connectivity changes dramatically in development. In previous studies we showed that 3 h of mental training, based on traditional Chinese medicine (integrative body-mind training, IBMT), increases ACC activity and improves self-regulation. However, it is not known whether changes in white matter connectivity can result from small amounts of mental training. We here report that 11 h of IBMT increases fractional anisotropy (FA), an index indicating the integrity and efficiency of white matter in the corona radiata, an important white-matter tract connecting the ACC to other structures. Thus IBMT could provide a means for improving self-regulation and perhaps reducing or preventing various mental disorders.
C1 [Tang, Yi-Yuan; Lu, Qilin] Dalian Univ Technol, Inst Neuroinformat, Dalian 116024, Peoples R China.
[Tang, Yi-Yuan; Lu, Qilin] Dalian Univ Technol, Lab Body & Mind, Dalian 116024, Peoples R China.
[Tang, Yi-Yuan; Posner, Michael I.] Univ Oregon, Dept Psychol, Eugene, OR 97403 USA.
[Geng, Xiujuan; Stein, Elliot A.; Yang, Yihong] Natl Inst Drug Abuse, Neuroimaging Res Branch, Intramural Res Program, Baltimore, MD 21224 USA.
RP Tang, YY (reprint author), Dalian Univ Technol, Inst Neuroinformat, Dalian 116024, Peoples R China.
EM yiyuan@uoregon.edu; mposner@uoregon.edu
RI Geng, Xiujuan/I-3852-2012
FU James S. Bower Foundation; John Templeton Foundation; National Natural
Science Foundation of China [60971096, R21DA030066]; National Institute
on Drug Abuse-Intramural Research Program
FX Comments on this manuscript from Mary Rothbart (University of Oregon)
are gratefully acknowledged. This study was supported by the James S.
Bower and John Templeton Foundations, National Natural Science
Foundation of China Grants 60971096 and R21DA030066, and the National
Institute on Drug Abuse-Intramural Research Program.
NR 37
TC 157
Z9 161
U1 10
U2 57
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 AUG 31
PY 2010
VL 107
IS 35
BP 15649
EP 15652
DI 10.1073/pnas.1011043107
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 645NT
UT WOS:000281468500064
PM 20713717
ER
PT J
AU Gunaratne, R
Braucht, DWW
Rinschen, MM
Chou, CL
Hoffert, JD
Pisitkun, T
Knepper, MA
AF Gunaratne, Ruwan
Braucht, Drew W. W.
Rinschen, Markus M.
Chou, Chung-Lin
Hoffert, Jason D.
Pisitkun, Trairak
Knepper, Mark A.
TI Quantitative phosphoproteomic analysis reveals
cAMP/vasopressin-dependent signaling pathways in native renal thick
ascending limb cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE protein phosphatase; glucose transporters; mass spectrometry; ion
transporters; protein kinase
ID PROTEIN-KINASE; COLLECTING DUCT; MASS-SPECTROMETRY; GENE-EXPRESSION;
HENLES LOOP; RAT-KIDNEY; PHOSPHORYLATION; HYPERTONICITY; ACTIVATION;
TRANSPORT
AB Quantitative mass spectrometry was used to identify hormone-dependent signaling pathways in renal medullary thick ascending limb (mTAL) cells via phosphoproteomic analysis. Active transport of NaCl across the mTAL epithelium is accelerated by hormones that increase cAMP levels (vasopressin, glucagon, parathyroid hormone, and calcitonin). mTAL suspensions from rat kidneys were exposed (15 min) to a mixture of these four hormones. Tryptic phosphopeptides (immobilized metal affinity chromatography-enriched) were identified and quantified by mass spectrometry (LTQ-Orbitrap) using label-free methodology. We quantified a total of 654 phosphopeptides, of which 414 were quantified in three experimental pairs (hormone vs. vehicle). Of these phosphopeptides, 82% were statistically unchanged in abundance in response to the hormone mixture. In contrast, 48 phosphopeptides were significantly increased, whereas 28 were significantly decreased. The population of up-regulated phosphopeptides was highly enriched in basophilic kinase substrate motifs (AGC or calmodulin-sensitive kinase families), whereas the down-regulated sites were dominated by "proline-directed" motifs (cyclin-dependent or MAP kinase families). Bioinformatic classification uncovered overrepresentation of transmembrane transporters, protein phosphatase regulators, and cytoskeletal binding proteins among the regulated proteins. Immunoblotting with phospho-specific antibodies confirmed cAMP/vasopressin-dependent phosphorylation at Thr96, Ser126, and Ser874 of the Na(+):K(+):2Cl(-) cotransporter NKCC2, at Ser552 of the Na(+):H(+) exchanger NHE3, and at Ser552 of beta-catenin. Vasopressin also increased phosphorylation of NKCC2 at both Ser126 (more than fivefold) and Ser874 (more than threefold) in rats in vivo. Both sites were phosphorylated by purified protein kinase A during in vitro assays. These results support the view that, although protein kinase A plays a central role in mTAL signaling, additional kinases, including those that target proline-directed motifs, may be involved.
C1 [Gunaratne, Ruwan; Braucht, Drew W. W.; Rinschen, Markus M.; Chou, Chung-Lin; Hoffert, Jason D.; Pisitkun, Trairak; Knepper, Mark A.] NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Knepper, MA (reprint author), NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20892 USA.
EM knepperm@nhlbi.nih.gov
OI Pisitkun, Trairak/0000-0001-6677-2271
FU Division of Intramural Research, National Heart, Lung and Blood
Institute [ZO1-HL001285]; Braun Foundation (Melsungen, Germany);
Biomedical Sciences Exchange Program (Hannover, Germany)
FX We thank Luke Xie, Ming-Jiun Yu, and Jae Song for assistance and advice.
Mass spectrometry was conducted in the National Heart, Lung and Blood
Institute Proteomics Core Facility (director, Marjan Gucek). Confocal
fluorescence imaging was performed in the National Heart, Lung and Blood
Institute Light Microscopy Core Facility (director, Christian Combs).
This work was funded by the operating budget of Division of Intramural
Research, National Heart, Lung and Blood Institute Project ZO1-HL001285
(to M. A. K.). M. M. R. was supported by the Braun Foundation
(Melsungen, Germany) and the Biomedical Sciences Exchange Program
(Hannover, Germany).
NR 31
TC 53
Z9 54
U1 0
U2 1
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 AUG 31
PY 2010
VL 107
IS 35
BP 15653
EP 15658
DI 10.1073/pnas.1007424107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 645NT
UT WOS:000281468500065
PM 20713729
ER
PT J
AU Xie, J
Lee, S
Chen, XY
AF Xie, Jin
Lee, Seulki
Chen, Xiaoyuan
TI Nanoparticle-based theranostic agents
SO ADVANCED DRUG DELIVERY REVIEWS
LA English
DT Review
DE Theranostics; Drug delivery; Gene delivery; Nanomedicine; Molecular
imaging; Iron oxide nanoparticles; Quantum dots; Gold nanoparticles;
Carbon nanotubes; Silica nanoparticles
ID WALLED CARBON NANOTUBES; SEMICONDUCTOR QUANTUM DOTS; IRON-OXIDE
NANOPARTICLES; RESONANCE ENERGY-TRANSFER; NONCOVALENT
SIDEWALL-FUNCTIONALIZATION; MONODISPERSE MAGNETIC NANOPARTICLES;
MESOPOROUS SILICA NANOPARTICLES; RESPONSIVE CONTROLLED-RELEASE;
DIIMIDE-ACTIVATED AMIDATION; DRUG-DELIVERY
AB Theranostic nanomedicine is emerging as a promising therapeutic paradigm. It takes advantage of the high capacity of nanoplatforms to ferry cargo and loads onto them both imaging and therapeutic functions. The resulting nanosystems, capable of diagnosis, drug delivery and monitoring of therapeutic response, are expected to play a significant role in the dawning era of personalized medicine, and much research effort has been devoted toward that goal. A convenience in constructing such function-integrated agents is that many nanoplatforms are already, themselves, imaging agents. Their well-developed surface chemistry makes it easy to load them with pharmaceutics and promote them to be theranostic nanosystems. Iron oxide nanoparticles, quantum dots, carbon nanotubes, gold nanoparticles and silica nanoparticles, have been previously well investigated in the imaging setting and are candidate nanoplatforms for building up nanoparticle-based theranostics. In the current article, we will outline the progress along this line, organized by the category of the core materials. We will focus on construction strategies and will discuss the challenges and opportunities associated with this emerging technology. Published by Elsevier B.V.
C1 [Xie, Jin; Lee, Seulki; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, 31 Ctr Dr,Suite 1C14, Bethesda, MD 20892 USA.
RI Xie, Jin/E-8193-2010
FU NIBIB, NIH; NIH/NIST
FX This work was supported by the Intramural Research Program, NIBIB, NIH.
S.L. is partially funded by the NIH/NIST NRC fellowship. We acknowledge
Dr. Henry S. Eden for proof-reading this manuscript.
NR 183
TC 457
Z9 461
U1 73
U2 457
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0169-409X
EI 1872-8294
J9 ADV DRUG DELIVER REV
JI Adv. Drug Deliv. Rev.
PD AUG 30
PY 2010
VL 62
IS 11
BP 1064
EP 1079
DI 10.1016/j.addr.2010.07.009
PG 16
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 693LI
UT WOS:000285225200006
PM 20691229
ER
PT J
AU Zhang, YH
Wang, XM
Ennis, M
AF Zhang, Yi-Hong
Wang, Xiao-Min
Ennis, Matthew
TI Effects of neonatal inflammation on descending modulation from the
rostroventromedial medulla
SO BRAIN RESEARCH BULLETIN
LA English
DT Article
DE Development; Pain; Nociception; Hypoalgesia; Hyperalgesia
ID RAT DORSAL-HORN; ADULT RATS; PERIPHERAL INFLAMMATION; GENE-EXPRESSION;
PAIN; PLASTICITY; INSULT; NOCICEPTION; CIRCUITRY; HYPERSENSITIVITY
AB Cutaneous tissue inflammation during the first postnatal week is known to alter long-term development of spinal cord nociceptive circuitry and to alter behavioral responses to noxious stimuli in adult animals. The impact of neonatal inflammation on descending projections arising from supraspinal sites that modulate spinal nociceptive processing is unknown. In the present study, we investigated if altered behavioral responses to pain in adult animals after neonatal inflammation are associated with changes in descending modulation of nocifensive responses elicited from the rostroventromedial medulla (RVM) in lightly anesthetized rats. Compared to handled control animals, hindpaw injection of 0.25% carrageenan (CG) at postnatal day 3 produced adult basal hypoalgesia and increased hyperalgesia 24 h after reinflammation with Complete Freund's Adjuvant (CFA) in awake animals. These effects were specific to the neonatally treated hindpaw, partially replicating previous findings, but were absent in lightly anesthetized animals. However, focal electrical stimulation of the RVM in lightly anesthetized CG treated animals produced significantly greater descending inhibition of nocifensive responses to noxious thermal stimuli applied to the hindpaws and the tail. These effects were partially replicated by intra-RVM microinjection of AMPA. No differences in the efficacy of RVM stimulation between CG and control animals were observed 24 h after reinflammation with CFA. These findings indicate that neonatal tissue injury and inflammation produces lasting alterations in descending modulatory systems that modify nociceptive processing. Taken together with previous studies, these results indicate that changes in pain sensitivity following neonatal tissue injury involve long-term alterations in spinal and supraspinal circuitry. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Zhang, Yi-Hong; Ennis, Matthew] Univ Tennessee, Hlth Sci Ctr, Dept Anat & Neurobiol, Inst Neurosci, Memphis, TN 38163 USA.
[Wang, Xiao-Min] NINR, NIH, Bethesda, MD 20892 USA.
RP Zhang, YH (reprint author), Univ Tennessee, Hlth Sci Ctr, Dept Anat & Neurobiol, Inst Neurosci, 855 Monroe Ave,Suite 515, Memphis, TN 38163 USA.
EM yzhang32@uthsc.edu
FU PHS [NS41384]; University of Tennessee Health Science Center
Neuroscience Institute
FX We thank Ms. Dongxia Jiang for histological assistance. This work was
supported by PHS grant NS41384 and the University of Tennessee Health
Science Center Neuroscience Institute.
NR 29
TC 15
Z9 16
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0361-9230
J9 BRAIN RES BULL
JI Brain Res. Bull.
PD AUG 30
PY 2010
VL 83
IS 1-2
BP 16
EP 22
DI 10.1016/j.brainresbull.2010.07.007
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 652IB
UT WOS:000281996000003
PM 20638459
ER
PT J
AU Lai, AY
Fatemi, M
Dhasarathy, A
Malone, C
Sobol, SE
Geigerman, C
Jaye, DL
Mav, D
Shah, R
Li, LP
Wade, PA
AF Lai, Anne Y.
Fatemi, Mehrnaz
Dhasarathy, Archana
Malone, Christine
Sobol, Steve E.
Geigerman, Cissy
Jaye, David L.
Mav, Deepak
Shah, Ruchir
Li, Leping
Wade, Paul A.
TI DNA methylation prevents CTCF-mediated silencing of the oncogene BCL6 in
B cell lymphomas
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID ENHANCER-BLOCKING ACTIVITY; GENE-EXPRESSION; HUMAN GENOME;
TRANSCRIPTIONAL REPRESSOR; MAMMALIAN DEVELOPMENT; DOWN-REGULATION;
UP-REGULATION; X-CHROMOSOME; PROTEIN CTCF; CANCER-CELLS
AB Aberrant DNA methylation commonly occurs in cancer cells where it has been implicated in the epigenetic silencing of tumor suppressor genes. Additional roles for DNA methylation, such as transcriptional activation, have been predicted but have yet to be clearly demonstrated. The BCL6 oncogene is implicated in the pathogenesis of germinal center-derived B cell lymphomas. We demonstrate that the intragenic CpG islands within the first intron of the human BCL6 locus were hypermethylated in lymphoma cells that expressed high amounts of BCL6 messenger RNA (mRNA). Inhibition of DNA methyltransferases decreased BCL6 mRNA abundance, suggesting a role for these methylated CpGs in positively regulating BCL6 transcription. The enhancer-blocking transcription factor CTCF bound to this intronic region in a methylation-sensitive manner. Depletion of CTCF by short hairpin RNA in neoplastic plasma cells that do not express BCL6 resulted in up-regulation of BCL6 transcription. These data indicate that BCL6 expression is maintained during lymphomagenesis in part through DNA methylation that prevents CTCF-mediated silencing.
C1 [Lai, Anne Y.; Fatemi, Mehrnaz; Dhasarathy, Archana; Malone, Christine; Wade, Paul A.] Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
[Li, Leping] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA.
[Sobol, Steve E.] Emory Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Atlanta, GA 30322 USA.
[Geigerman, Cissy; Jaye, David L.] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
[Mav, Deepak; Shah, Ruchir] SRA Int Inc, Res Triangle Pk, NC 27709 USA.
RP Wade, PA (reprint author), Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
EM wadep2@niehs.nih.gov
FU National Institute of Environmental Health Sciences, National Institutes
of Health [Z01ES101965, Z01ES101765]; National Institutes of Health
[DK60647]; National Institute of Environmental Health Sciences, National
Institutes of Health, Department of Health and Human Services
[HHSN291200555547C, GS-00F-003L]
FX This work was supported by the Intramural Research Program of the
National Institute of Environmental Health Sciences, National Institutes
of Health (Project number Z01ES101965 to P. A. Wade, Project number
Z01ES101765 to L. Li) and by grants from the National Institutes of
Health (DK60647 to D.L. Jaye). D. Mav and R. Shah were supported in
whole or in part with Federal funds from the National Institute of
Environmental Health Sciences, National Institutes of Health, Department
of Health and Human Services, under Delivery Order Number
HHSN291200555547C, GSA Contract Number GS-00F-003L.
NR 83
TC 35
Z9 36
U1 0
U2 2
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD AUG 30
PY 2010
VL 207
IS 9
BP 1939
EP 1950
DI 10.1084/jem.20100204
PG 12
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 660NQ
UT WOS:000282650700013
PM 20733034
ER
PT J
AU Sundling, C
Forsell, MNE
O'Dell, S
Feng, Y
Chakrabarti, B
Rao, SS
Lore, K
Mascola, JR
Wyatt, RT
Douagi, I
Hedestam, GBK
AF Sundling, Christopher
Forsell, Mattias N. E.
O'Dell, Sijy
Feng, Yu
Chakrabarti, Bimal
Rao, Srinivas S.
Lore, Karin
Mascola, John R.
Wyatt, Richard T.
Douagi, Iyadh
Hedestam, Gunilla B. Karlsson
TI Soluble HIV-1 Env trimers in adjuvant elicit potent and diverse
functional B cell responses in primates
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID TYPE-1 ENVELOPE GLYCOPROTEINS; SIMIAN/HUMAN IMMUNODEFICIENCY VIRUS;
HUMAN MONOCLONAL-ANTIBODY; MUCOSAL SHIV CHALLENGE; NEUTRALIZING
ANTIBODIES; RECOMBINANT GLYCOPROTEIN-120; SEXUAL TRANSMISSION; PARTICLE
VACCINE; RHESUS MACAQUES; INFLUENZA-VIRUS
AB Broadly neutralizing antibodies (bNAbs) against the HIV-1 envelope glycoproteins (Envs) have proven difficult to elicit by immunization. Therefore, to identify effective Env neutralization targets, efforts are underway to define the specificities of bNAbs in chronically infected individuals. For a prophylactic vaccine, it is equally important to define the immunogenic properties of the heavily glycosylated Env in healthy primates devoid of confounding HIV-induced pathogenic factors. We used rhesus macaques to investigate the magnitude and kinetics of B cell responses stimulated by Env trimers in adjuvant. Robust Env-specific memory B cell responses and high titers of circulating antibodies developed after trimer inoculation. Subsequent immunizations resulted in significant expansion of Env-specific IgG-producing plasma cell populations and circulating Abs that displayed increasing avidity and neutralization capacity. The neutralizing activity elicited with the regimen used was, in most aspects, superior to that elicited by a regimen based on monomeric Env immunization in humans. Despite the potency and breadth of the trimer-elicited response, protection against heterologous rectal simian-HIV (SHIV) challenge was modest, illustrating the challenge of eliciting sufficient titers of cross-reactive protective NAbs in mucosal sites. These data provide important information for the design and evaluation of vaccines aimed at stimulating protective HIV-1 immune responses in humans.
C1 [Sundling, Christopher; Forsell, Mattias N. E.; Douagi, Iyadh; Hedestam, Gunilla B. Karlsson] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, SE-17177 Stockholm, Sweden.
[Lore, Karin] Karolinska Inst, Ctr Infect Dis, SE-17177 Stockholm, Sweden.
[O'Dell, Sijy; Feng, Yu; Chakrabarti, Bimal; Rao, Srinivas S.; Mascola, John R.; Wyatt, Richard T.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Hedestam, Gunilla B. Karlsson] Swedish Inst Infect Dis Control, SE-17182 Solna, Sweden.
RP Hedestam, GBK (reprint author), Karolinska Inst, Dept Microbiol Tumor & Cell Biol, SE-17177 Stockholm, Sweden.
EM Gunilla.Karlsson.Hedestam@ki.se
RI Feng, Yu/A-3396-2012;
OI Sundling, Christopher/0000-0002-6138-690X
FU Swedish Research Council, Sida/Swedish Agency for Research Cooperation;
International AIDS Vaccine Initiative; Bill and Melinda Gates
Foundation; Vaccine Research Center, National Institute of Allergy and
Infectious Diseases, National Institutes of Health; Karolinska
Institutet
FX This study was supported by grants from the Swedish Research Council,
Sida/Swedish Agency for Research Cooperation, the International AIDS
Vaccine Initiative, the Bill and Melinda Gates Foundation, the
intramural program of the Vaccine Research Center, National Institute of
Allergy and Infectious Diseases, National Institutes of Health
intramural research program, and a Karolinska Institutet Doctoral grant
from Karolinska Institutet.
NR 73
TC 67
Z9 67
U1 0
U2 9
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD AUG 30
PY 2010
VL 207
IS 9
BP 2003
EP 2017
DI 10.1084/jem.20100025
PG 15
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 660NQ
UT WOS:000282650700018
PM 20679401
ER
PT J
AU Lauer, MS
AF Lauer, Michael S.
TI The historical and moral imperatives of comparative effectiveness
research
SO STATISTICS IN MEDICINE
LA English
DT Editorial Material
ID MYOCARDIAL-INFARCTION; TRIAL; CANCER; MORTALITY; PROGRAM
C1 NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
RP Lauer, MS (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 8128, Bethesda, MD 20892 USA.
EM lauerm@nhlbi.nih.gov
RI Lauer, Michael/L-9656-2013
OI Lauer, Michael/0000-0002-9217-8177
NR 19
TC 5
Z9 5
U1 0
U2 1
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD AUG 30
PY 2010
VL 29
IS 19
BP 1982
EP 1984
DI 10.1002/sim.3927
PG 3
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 642EB
UT WOS:000281185500003
PM 20683887
ER
PT J
AU Wang, XH
Baldwin, S
Wainer, H
Bradlow, ET
Reeve, BB
Smith, AW
Bellizzi, KM
Baumgartner, KB
AF Wang, Xiaohui
Baldwin, Su
Wainer, Howard
Bradlow, Eric T.
Reeve, Bryce B.
Smith, Ashley W.
Bellizzi, Keith M.
Baumgartner, Kathy B.
TI Using Testlet Response Theory to analyze data from a survey of attitude
change among breast cancer survivors
SO STATISTICS IN MEDICINE
LA English
DT Article
DE testlet; Bayesian; MCMC; local independence; breast cancer survey
ID QUALITY-OF-LIFE; POSTTRAUMATIC GROWTH INVENTORY; LONG-TERM; MODELS;
IMPACT; WOMEN; FIT
AB In this paper we examine alternative measurement models for fitting data from health surveys. We show why a testlet-based latent trait model that includes covariate information, embedded within a fully Bayesian framework, can allow multiple simultaneous inferences and aid interpretation. We illustrate our approach with a survey of breast cancer survivors that reveals how the attitudes of those patients change after diagnosis toward a focus on appreciating the here-and-now, and away from consideration of longer-term goals. Using the covariate information, we also show the extent to which individual-level variables such as race, age and Tamoxifen treatment are related to a patient's change in attitude.
The major contribution of this research is to demonstrate the use of a hierarchical Bayesian IRT model with covariates in this application area; hence a novel case study, and one that is certainly closely aligned with but distinct from the educational testing applications that have made IRT the dominant test scoring model. Copyright (C) 2010 John Wiley & Sons, Ltd.
C1 [Wang, Xiaohui] Univ Virginia, Dept Stat, Charlottesville, VA 22903 USA.
[Baldwin, Su; Wainer, Howard] Natl Board Med Examiners, Philadelphia, PA USA.
[Wainer, Howard; Bradlow, Eric T.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA.
[Reeve, Bryce B.; Smith, Ashley W.] NCI, Bethesda, MA USA.
[Bellizzi, Keith M.] Univ Connecticut, Storrs, CT USA.
[Baumgartner, Kathy B.] Univ Louisville, Louisville, KY 40292 USA.
RP Wang, XH (reprint author), Univ Virginia, Dept Stat, Charlottesville, VA 22903 USA.
EM xw5a@virginia.edu
FU National Board of Medical Examiners, the Wharton Interactive Media
Initiative; National Science Foundation [DMS0631639]; National Security
Agent [GG11184]
FX This work was supported by the National Board of Medical Examiners, the
Wharton Interactive Media Initiative. The research of Xiaohui Wang was
partially supported by the National Science Foundation grant DMS0631639
and the National Security Agent grant GG11184. We are delighted to take
this opportunity to express our gratitude. The data were supplied by the
National Cancer Institute.
NR 46
TC 3
Z9 3
U1 2
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD AUG 30
PY 2010
VL 29
IS 19
BP 2028
EP 2044
DI 10.1002/sim.3945
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 642EB
UT WOS:000281185500010
PM 20683894
ER
PT J
AU Li, M
Romero, R
Fu, WJJ
Cui, YH
AF Li, Ming
Romero, Roberto
Fu, Wenjiang J.
Cui, Yuehua
TI Mapping Haplotype-haplotype Interactions with Adaptive LASSO
SO BMC GENETICS
LA English
DT Article
ID HUMAN-DISEASES; GENE INTERACTIONS; KAPPA-B; EXPRESSION; EPISTASIS;
REGRESSION; SUSCEPTIBILITY; ASSOCIATION; PROGRESSION; METABOLISM
AB Background: The genetic etiology of complex diseases in human has been commonly viewed as a complex process involving both genetic and environmental factors functioning in a complicated manner. Quite often the interactions among genetic variants play major roles in determining the susceptibility of an individual to a particular disease. Statistical methods for modeling interactions underlying complex diseases between single genetic variants (e.g. single nucleotide polymorphisms or SNPs) have been extensively studied. Recently, haplotype-based analysis has gained its popularity among genetic association studies. When multiple sequence or haplotype interactions are involved in determining an individual's susceptibility to a disease, it presents daunting challenges in statistical modeling and testing of the interaction effects, largely due to the complicated higher order epistatic complexity.
Results: In this article, we propose a new strategy in modeling haplotype-haplotype interactions under the penalized logistic regression framework with adaptive L(1)-penalty. We consider interactions of sequence variants between haplotype blocks. The adaptive L(1)-penalty allows simultaneous effect estimation and variable selection in a single model. We propose a new parameter estimation method which estimates and selects parameters by the modified Gauss-Seidel method nested within the EM algorithm. Simulation studies show that it has low false positive rate and reasonable power in detecting haplotype interactions. The method is applied to test haplotype interactions involved in mother and offspring genome in a small for gestational age (SGA) neonates data set, and significant interactions between different genomes are detected.
Conclusions: As demonstrated by the simulation studies and real data analysis, the approach developed provides an efficient tool for the modeling and testing of haplotype interactions. The implementation of the method in R codes can be freely downloaded from http://www.stt.msu.edu/similar to cui/software.html.
C1 [Li, Ming; Fu, Wenjiang J.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA.
[Cui, Yuehua] Michigan State Univ, Dept Stat & Probabil, E Lansing, MI 48824 USA.
[Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI 48201 USA.
RP Fu, WJJ (reprint author), Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA.
EM fuw@epi.msu.edu; cui@stt.msu.edu
FU NSF [DMS-0707031]; Perinatology Research Branch; Division of Intramural
Research; Eunice Kennedy Shriver National Institute of Child Health and
Human Development; NIH; DHHS
FX The authors wish to thank the two anonymous referees for their helpful
comments that improved the manuscript, and thank Dr. Kelian Sun for
helping data processing. This work was supported in part by NSF grant
DMS-0707031 and by the Perinatology Research Branch, Division of
Intramural Research, Eunice Kennedy Shriver National Institute of Child
Health and Human Development, NIH, DHHS.
NR 44
TC 11
Z9 11
U1 0
U2 4
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 AUG 27
PY 2010
VL 11
AR 79
DI 10.1186/1471-2156-11-79
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 662BR
UT WOS:000282782200001
PM 20799953
ER
PT J
AU Go, AS
Parikh, CR
Ikizler, TA
Coca, S
Siew, ED
Chinchilli, VM
Hsu, CY
Garg, AX
Zappitelli, M
Liu, KD
Reeves, WB
Ghahramani, N
Devarajan, P
Faulkner, GB
Tan, TC
Kimmel, PL
Eggers, P
Stokes, JB
AF Go, Alan S.
Parikh, Chirag R.
Ikizler, T. Alp
Coca, Steven
Siew, Edward D.
Chinchilli, Vernon M.
Hsu, Chi-yuan
Garg, Amit X.
Zappitelli, Michael
Liu, Kathleen D.
Reeves, W. Brian
Ghahramani, Nasrollah
Devarajan, Prasad
Faulkner, Georgia Brown
Tan, Thida C.
Kimmel, Paul L.
Eggers, Paul
Stokes, John B.
CA ASSESS-AKI Study Investigators
TI The assessment, serial evaluation, and subsequent sequelae of acute
kidney injury (ASSESS-AKI) study: design and methods
SO BMC NEPHROLOGY
LA English
DT Article
ID ACUTE-RENAL-FAILURE; ACUTE MYOCARDIAL-INFARCTION; CRITICALLY-ILL
PATIENTS; NATIONAL-DEATH-INDEX; LONG-TERM RISK; CARDIAC-SURGERY;
CARDIOTHORACIC SURGERY; METHODOLOGICAL ISSUES; REQUIRING DIALYSIS;
HEART-FAILURE
AB Background: The incidence of acute kidney injury (AKI) has been increasing over time and is associated with a high risk of short-term death. Previous studies on hospital-acquired AKI have important methodological limitations, especially their retrospective study designs and limited ability to control for potential confounding factors.
Methods: The Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) Study was established to examine how a hospitalized episode of AKI independently affects the risk of chronic kidney disease development and progression, cardiovascular events, death, and other important patient-centered outcomes. This prospective study will enroll a cohort of 1100 adult participants with a broad range of AKI and matched hospitalized participants without AKI at three Clinical Research Centers, as well as 100 children undergoing cardiac surgery at three Clinical Research Centers. Participants will be followed for up to four years, and will undergo serial evaluation during the index hospitalization, at three months post-hospitalization, and at annual clinic visits, with telephone interviews occurring during the intervening six-month intervals. Biospecimens will be collected at each visit, along with information on lifestyle behaviors, quality of life and functional status, cognitive function, receipt of therapies, interim renal and cardiovascular events, electrocardiography and urinalysis.
Conclusions: ASSESS-AKI will characterize the short-term and long-term natural history of AKI, evaluate the incremental utility of novel blood and urine biomarkers to refine the diagnosis and prognosis of AKI, and identify a subset of high-risk patients who could be targeted for future clinical trials to improve outcomes after AKI.
C1 [Go, Alan S.; Tan, Thida C.] Kaiser Permanente No Calif, Oakland, CA 94612 USA.
[Go, Alan S.; Hsu, Chi-yuan; Liu, Kathleen D.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Parikh, Chirag R.; Coca, Steven] Yale Univ, New Haven, CT USA.
[Ikizler, T. Alp; Siew, Edward D.] Vanderbilt Univ, Nashville, TN USA.
[Chinchilli, Vernon M.; Reeves, W. Brian; Ghahramani, Nasrollah; Faulkner, Georgia Brown] Penn State Univ, Hershey, PA USA.
[Garg, Amit X.] London Hlth Sci Ctr, London, ON, Canada.
[Zappitelli, Michael] Montreal Childrens Hosp, Montreal, PQ H3H 1P3, Canada.
[Devarajan, Prasad] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
[Kimmel, Paul L.; Eggers, Paul] NIDDKD, Bethesda, MD 20892 USA.
[Stokes, John B.] Univ Iowa, Iowa City, IA USA.
RP Go, AS (reprint author), Kaiser Permanente No Calif, Oakland, CA 94612 USA.
EM alan.s.go@kp.org
RI Ghahramani, Nasrollah/B-1139-2009
FU National Institute of Digestive, Diabetes and Kidney Diseases of the
National Institutes of Health, U.S. Department of Health and Human
Services [U01-DK082223, U01-DK082185, U01DK082192, U01DK082183]
FX Supported by research grants U01-DK082223, U01-DK082185, U01DK082192 and
U01DK082183 from the National Institute of Digestive, Diabetes and
Kidney Diseases of the National Institutes of Health, U.S. Department of
Health and Human Services.
NR 62
TC 62
Z9 62
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2369
J9 BMC NEPHROL
JI BMC Nephrol.
PD AUG 27
PY 2010
VL 11
AR 22
DI 10.1186/1471-2369-11-22
PG 13
WC Urology & Nephrology
SC Urology & Nephrology
GA 669JK
UT WOS:000283343500001
PM 20799966
ER
PT J
AU Zhou, F
Roy, B
von Arnim, AG
AF Zhou, Fujun
Roy, Bijoyita
von Arnim, Albrecht G.
TI Translation reinitiation and development are compromised in similar ways
by mutations in translation initiation factor eIF3h and the ribosomal
protein RPL24
SO BMC PLANT BIOLOGY
LA English
DT Article
ID OPEN READING FRAME; ARABIDOPSIS GENE MONOPTEROS; MESSENGER-RNA; VASCULAR
DEVELOPMENT; PATTERN-FORMATION; AUXIN TRANSPORT; DWARF PHENOTYPE; ACL5
MUTANT; H-SUBUNIT; EXPRESSION
AB Background: Within the scanning model of translation initiation, reinitiation is a non-canonical mechanism that operates on mRNAs harboring upstream open reading frames. The h subunit of eukaryotic initiation factor 3 (eIF3) boosts translation reinitiation on the uORF-containing mRNA coding for the Arabidopsis bZip transcription factor, AtbZip11, among others. The RPL24B protein of the large ribosomal subunit, which is encoded by SHORT VALVE1, likewise fosters translation of uORF-containing mRNAs, for example mRNAs for auxin response transcription factors (ARFs).
Results: Here we tested the hypothesis that RPL24B and eIF3h affect translation reinitiation in a similar fashion. First, like eif3h mutants, rpl24b mutants under-translate the AtbZip11 mRNA, and the detailed spectrum of translational defects in rpl24b is remarkably similar to that of eif3h. Second, eif3h mutants display defects in auxin mediated organogenesis and gene expression, similar to rpl24b. Like AtbZip11, the uORF-containing ARF mRNAs are indeed undertranslated in eif3h mutant seedlings.
Conclusion: We conclude that, similar to eIF3h, RPL24B bolsters the reinitiation competence of uORF-translating ribosomes. Coordination between eIF3 and the large ribosomal subunit helps to fine-tune translation of uORF-containing mRNAs and, in turn, to orchestrate plant development.
C1 [Roy, Bijoyita; von Arnim, Albrecht G.] Univ Tennessee, Dept Biochem Cellular & Mol Biol, Knoxville, TN 37996 USA.
[Zhou, Fujun] Univ Tennessee, Genome Sci & Technol Program, Knoxville, TN 37996 USA.
[Zhou, Fujun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA.
RP von Arnim, AG (reprint author), Univ Tennessee, Dept Biochem Cellular & Mol Biol, Knoxville, TN 37996 USA.
EM vonarnim@utk.edu
FU DOE [DE-FG02-96ER20223]; BARD [IS3901-06C]
FX We are grateful for transgenic lines contributed by Klaus Palme and
Thomas Guilfoyle, and for numerous cDNAs clones as well as the
rpl24b/stv1-1 mutant distributed by the Arabidopsis stock center. We
appreciate access to microscopes granted by Mariano Labrador, Andreas
Nebenfuhr and John Dunlap of the Biology Microscopy Core Facility and
discussions with John Golz, Andreas Nebenfuhr, and Elena Shpak. This
work was supported by a grant from the DOE Energy Biosciences Program
(DE-FG02-96ER20223) and by BARD grant IS3901-06C.
NR 53
TC 27
Z9 28
U1 2
U2 12
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2229
J9 BMC PLANT BIOL
JI BMC Plant Biol.
PD AUG 27
PY 2010
VL 10
AR 193
DI 10.1186/1471-2229-10-193
PG 11
WC Plant Sciences
SC Plant Sciences
GA 650IJ
UT WOS:000281842200002
PM 20799971
ER
PT J
AU Darmoise, A
Teneberg, S
Bouzonville, L
Brady, RO
Beck, M
Kaufmann, SHE
Winau, F
AF Darmoise, Alexandre
Teneberg, Susann
Bouzonville, Lauriane
Brady, Roscoe O.
Beck, Michael
Kaufmann, Stefan H. E.
Winau, Florian
TI Lysosomal alpha-Galactosidase Controls the Generation of Self Lipid
Antigens for Natural Killer T Cells
SO IMMUNITY
LA English
DT Article
ID INVARIANT NKT CELLS; ENZYME REPLACEMENT; IMMUNE-RESPONSE; CD1D
TETRAMERS; ACTIVATION; RECOGNITION; MICE; MATURATION; RECEPTORS;
MOLECULES
AB Natural Killer T (NKT) cells are lipid-reactive, CD1 drestricted T lymphocytes important in infection, cancer, and autoimmunity. In addition to foreign antigens, NKT cells react with endogenous self lipids. However, in the face of stimulating self antigen, it remains unclear how overstimulation of NKT cells is avoided. We hypothesized that constantly degraded endogenous antigen only accumulates upon inhibition of alpha-galactosidase A (alpha-Gal-A) in lysosomes. Here, we show that alpha-Gal-A deficiency caused vigorous activation of NKT cells. Moreover, microbes induced inhibition of alpha-Gal-A activity in antigen-presenting cells. This temporary enzyme block depended on Toll-like receptor (TLR) signaling and ultimately triggered lysosomal lipid accumulation. Thus, we present TLR-dependent negative regulation of alpha-Gal-A as a mechanistic link between pathogen recognition and self lipid antigen induction for NKT cells.
C1 [Darmoise, Alexandre; Bouzonville, Lauriane; Winau, Florian] Harvard Univ, Sch Med, Dept Pathol,Immune Dis Inst, Childrens Hosp,Program Cellular & Mol Med, Boston, MA 02115 USA.
[Teneberg, Susann] Univ Gothenburg, Dept Med Biochem & Cell Biol, Inst Biomed, S-40530 Gothenburg, Sweden.
[Brady, Roscoe O.] NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Beck, Michael] Johannes Gutenberg Univ Mainz, Childrens Hosp, D-55131 Mainz, Germany.
[Darmoise, Alexandre; Kaufmann, Stefan H. E.; Winau, Florian] Max Planck Inst Infect Biol, Dept Immunol, D-10117 Berlin, Germany.
RP Winau, F (reprint author), Harvard Univ, Sch Med, Dept Pathol,Immune Dis Inst, Childrens Hosp,Program Cellular & Mol Med, Boston, MA 02115 USA.
EM winau@idi.harvard.edu
RI Kaufmann, Stefan HE/I-5454-2014
OI Kaufmann, Stefan HE/0000-0001-9866-8268
FU European Union Marie Curie Actions [MEST-CT-2005-020311]; German Science
Foundation [SFB 421]
FX We thank S. Weber for expert technical assistance. We are grateful to
Dr. S. Porcelli for sharing mAb K253 with us. We thank Dr. A. d'Azzo for
providing us with beta-Gal-deficient mice. We thank the NIH Tetramer
Facility for CD1d-tetramers. This work was supported in part by the
European Union Marie Curie Actions (MEST-CT-2005-020311 to A.D.) and the
German Science Foundation (SFB 421 to S.H.E.K. and F.W.).
NR 46
TC 64
Z9 64
U1 0
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD AUG 27
PY 2010
VL 33
IS 2
BP 216
EP 228
DI 10.1016/j.immuni.2010.08.003
PG 13
WC Immunology
SC Immunology
GA 647XU
UT WOS:000281654900011
PM 20727792
ER
PT J
AU Deenick, EK
Chan, AN
Ma, CS
Gatto, D
Schwartzberg, PL
Brink, R
Tangye, SG
AF Deenick, Elissa K.
Chan, Anna
Ma, Cindy S.
Gatto, Dominique
Schwartzberg, Pamela L.
Brink, Robert
Tangye, Stuart G.
TI Follicular Helper T Cell Differentiation Requires Continuous Antigen
Presentation that Is Independent of Unique B Cell Signaling
SO IMMUNITY
LA English
DT Article
ID LINKED LYMPHOPROLIFERATIVE DISEASE; HUMORAL IMMUNE-RESPONSES; INDUCIBLE
COSTIMULATOR LIGAND; GERMINAL CENTER RESPONSES; CXC CHEMOKINE
RECEPTOR-5; MICE DEFICIENT; CD40 LIGAND; IMMUNOGLOBULIN PRODUCTION;
DENDRITIC CELLS; EXPRESSION
AB Effective humoral immunity depends on the support of B cell responses by T follicular helper (Tfh) cells. Although it has been proposed that Tfh cell differentiation requires T-B interactions, the relative contribution of specific populations of Ag-presenting cells remains unknown. We employed three independent strategies that compromised interactions between CD4(+) T cells and activated B cells in vivo. Whereas the expansion of CD4(+) T cells was relatively unaffected, Tfh cell differentiation was completely blocked in all scenarios. Surprisingly, augmenting antigen presentation by non-B cells rescued Tfh cell differentiation, as determined by surface phenotype, gene expression, and germinal center localization. We conclude that although Ag presentation by responding B cells is typically required for the generation of Tfh cells, this does not result from the provision of a unique B cell-derived signal, but rather because responding B cells rapidly become the primary source of antigen.
C1 [Deenick, Elissa K.; Chan, Anna; Ma, Cindy S.; Gatto, Dominique; Brink, Robert; Tangye, Stuart G.] St Vincents Hosp, Garvan Inst Med Res, Program Immunol, Darlinghurst, NSW 2010, Australia.
[Deenick, Elissa K.; Ma, Cindy S.; Gatto, Dominique; Brink, Robert; Tangye, Stuart G.] Univ New S Wales, St Vincents Clin Sch, Kensington, NSW 2033, Australia.
[Schwartzberg, Pamela L.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Deenick, EK (reprint author), St Vincents Hosp, Garvan Inst Med Res, Program Immunol, Darlinghurst, NSW 2010, Australia.
EM e.deenick@garvan.org.au; s.tangye@garvan.org.au
RI Brink, Robert/B-7910-2010; Ma, Cindy/B-2340-2012; Tangye,
Stuart/H-4023-2014;
OI Brink, Robert/0000-0002-9586-3655; Deenick, Elissa/0000-0002-9271-0004
FU Australian NHMRC
FX We thank the Garvan Flow Facility for cell sorting, T. Chan for the
HEL4x, D. Fulcher, B. Gaspar, and S. Riminton for patient
samples, L. Corcoran for the BcI-6 antibody, and T. Phan for critically
reviewing this manuscript. This work was funded by grants and
fellowships awarded by the Australian NHMRC to E.K.D., C.S.M., D.G.,
R.B., and S.G.T.
NR 59
TC 152
Z9 157
U1 0
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD AUG 27
PY 2010
VL 33
IS 2
BP 241
EP 253
DI 10.1016/j.immuni.2010.07.015
PG 13
WC Immunology
SC Immunology
GA 647XU
UT WOS:000281654900013
PM 20691615
ER
PT J
AU Eriksen, J
Bjorn-Yoshimoto, WE
Jorgensen, TN
Newman, AH
Gether, U
AF Eriksen, Jacob
Bjorn-Yoshimoto, Walden Emil
Jorgensen, Trine Nygaard
Newman, Amy Hauck
Gether, Ulrik
TI Postendocytic Sorting of Constitutively Internalized Dopamine
Transporter in Cell Lines and Dopaminergic Neurons
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; MONOAMINE TRANSPORTERS; STRIATAL
SYNAPTOSOMES; MEMBRANE TRAFFICKING; RECYCLING PATHWAY; UBIQUITINATION;
ENDOCYTOSIS; IDENTIFICATION; GLUTAMATE; MECHANISM
AB The dopamine transporter (DAT) mediates reuptake of released dopamine and is the target for psychostimulants, such as cocaine and amphetamine. DAT undergoes marked constitutive endocytosis, but little is known about the fate and sorting of the endocytosed transporter. To study DAT sorting in cells lines, we fused the one-transmembrane segment protein Tac to DAT, thereby generating a transporter (TacDAT) with an extracellular antibody epitope suited for trafficking studies. TacDAT was functional and endocytosed constitutively in HEK293 cells. According to an ELISA-based assay, TacDAT intracellular accumulation was increased by the lysosomal protease inhibitor leupeptin and by monensin, an inhibitor of lysosomal degradation and recycling. Monensin also reduced TacDAT surface expression consistent with partial recycling. In both HEK293 cells and in the dopaminergic cell line 1Rb3An27, constitutively internalized TacDAT displayed primary co-localization with the late endosomal marker Rab7, less co-localization with the "short loop" recycling marker Rab4, and little co-localization with the marker of "long loop" recycling endosomes, Rab11. Removal by mutation of N-terminal ubiquitination sites did not affect this sorting pattern. The sorting pattern was distinct from a bona fide recycling membrane protein, the beta 2-adrenergic receptor, that co-localized primarily with Rab11 and Rab4. Constitutively internalized wild type DAT probed with the fluorescently tagged cocaine analogue JHC 1-64, exhibited the same co-localization pattern as TacDAT in 1Rb3An27 cells and in cultured midbrain dopaminergic neurons. We conclude that DAT is constitutively internalized and sorted in a ubiquitination-independent manner to late endosomes/lysosomes and in part to a Rab4 positive short loop recycling pathway.
C1 [Eriksen, Jacob; Bjorn-Yoshimoto, Walden Emil; Jorgensen, Trine Nygaard; Gether, Ulrik] Panum Inst, Dept Neurosci & Pharmacol, Mol Neuropharmacol Grp, DK-2200 Copenhagen N, Denmark.
[Eriksen, Jacob; Bjorn-Yoshimoto, Walden Emil; Jorgensen, Trine Nygaard; Gether, Ulrik] Panum Inst, Dept Neurosci & Pharmacol, Ctr Pharmacogen, DK-2200 Copenhagen, Denmark.
[Newman, Amy Hauck] Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, Baltimore, MD 21224 USA.
RP Gether, U (reprint author), Panum Inst, Dept Neurosci & Pharmacol, Mol Neuropharmacol Grp, 18-6 Blegdamsvej 3, DK-2200 Copenhagen N, Denmark.
EM gether@sund.ku.dk
OI Eriksen, Jacob/0000-0003-0726-9769; Bjorn-Yoshimoto, Walden
Emil/0000-0003-1019-9239; Gether, Ulrik/0000-0002-0020-3807
FU National Institutes of Health [P01 DA 12408]; National Institute on Drug
Abuse; Lundbeck Foundation; Danish Medical Research Councils; Fabrikant
Vilhelm Pedersen og Hustrus Mindelegat
FX This work was supported, in whole or in part, by National Institutes of
Health Grant P01 DA 12408 (to U. G.) and by the National Institute on
Drug Abuse Intramural Research Program (to A. H. N.). This work was also
supported by the Lundbeck Foundation (to U. G.), the Danish Medical
Research Councils (to U. G.), and "Fabrikant Vilhelm Pedersen og Hustrus
Mindelegat" (to U. G.).
NR 61
TC 29
Z9 29
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 27
PY 2010
VL 285
IS 35
BP 27289
EP 27301
DI 10.1074/jbc.M110.131003
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 641ZQ
UT WOS:000281172700059
PM 20551317
ER
PT J
AU Navarro, G
Ferre, S
Cordomi, A
Moreno, E
Mallol, J
Casado, V
Cortes, A
Hoffmann, H
Ortiz, J
Canela, EI
Lluis, C
Pardo, L
Franco, R
Woods, AS
AF Navarro, Gemma
Ferre, Sergi
Cordomi, Arnau
Moreno, Estefania
Mallol, Josefa
Casado, Vicent
Cortes, Antoni
Hoffmann, Hanne
Ortiz, Jordi
Canela, Enric I.
Lluis, Carme
Pardo, Leonardo
Franco, Rafael
Woods, Amina S.
TI Interactions between Intracellular Domains as Key Determinants of the
Quaternary Structure and Function of Receptor Heteromers
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PROTEIN-COUPLED-RECEPTOR; CRYSTAL-STRUCTURE; ADENOSINE A(2A); KNOCKOUT
MICE; RHODOPSIN; OLIGOMERS; DIMERS; FRET; DOPAMINE-D-2; ACTIVATION
AB G protein-coupled receptor (GPCR) heteromers are macromolecular complexes with unique functional properties different from those of its individual protomers. Little is known about what determines the quaternary structure of GPCR heteromers resulting in their unique functional properties. In this study, using resonance energy transfer techniques in experiments with mutated receptors, we provide for the first time clear evidence for a key role of intracellular domains in the determination of the quaternary structure of GPCR heteromers between adenosine A(2A), cannabinoid CB(1), and dopamine D(2) receptors. In these interactions, arginine-rich epitopes form salt bridges with phosphorylated serine or threonine residues from CK1/2 consensus sites. Each receptor (A(2A), CB(1), and D(2)) was found to include two evolutionarily conserved intracellular domains to establish selective electrostatic interactions with intracellular domains of the other two receptors, indicating that these particular electrostatic interactions constitute a general mechanism for receptor heteromerization. Mutation experiments indicated that the interactions of the intracellular domains of the CB(1) receptor with A(2A) and D(2) receptors are fundamental for the correct formation of the quaternary structure needed for the function (MAPK signaling) of the A(2A)-CB(1)-D(2) receptor heteromers. Analysis of MAPK signaling in striatal slices of CB(1) receptor KO mice and wild-type littermates supported the existence of A(1)-CB(1)-D(2) receptor heteromer in the brain. These findings allowed us to propose the first molecular model of the quaternary structure of a receptor heteromultimer.
C1 [Ferre, Sergi; Woods, Amina S.] Natl Inst Drug Abuse, Intramural Res Program, Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
[Navarro, Gemma; Moreno, Estefania; Mallol, Josefa; Casado, Vicent; Cortes, Antoni; Canela, Enric I.; Lluis, Carme; Franco, Rafael] Univ Barcelona, Ctr Invest Biomed Red Sobre Enfermedades Neurodeg, Dept Biochem & Mol Biol, Fac Biol, E-08028 Barcelona, Spain.
[Cordomi, Arnau; Pardo, Leonardo] Univ Autonoma Barcelona, Lab Med Computac, Unitat Bioestadist, Bellaterra 08193, Spain.
[Hoffmann, Hanne; Ortiz, Jordi] Univ Autonoma Barcelona, Inst Neurosci, Bellaterra 08193, Spain.
[Hoffmann, Hanne; Ortiz, Jordi] Univ Autonoma Barcelona, Dept Biochem & Mol Biol, Facultat Medicina, Bellaterra 08193, Spain.
[Franco, Rafael] Univ Navarra, Ctr Invest Med Aplicada, Pamplona 31008, Spain.
RP Woods, AS (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Dept Hlth & Human Serv, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM awoods@intra.nida.nih.gov
RI Ortiz, Jordi/E-9018-2011; Cordomi, Arnau/A-1686-2009; Canela, Enric
I./M-8726-2013; Ferre, Sergi/K-6115-2014; Franco, Rafael/C-3694-2015;
Casado, Vicent/K-1660-2014;
OI Ortiz, Jordi/0000-0002-9748-2290; Casado, Vicent/0000-0002-1764-3825;
Cordomi, Arnau/0000-0002-3848-2928; Canela, Enric
I./0000-0003-4992-7440; Ferre, Sergi/0000-0002-1747-1779; Franco,
Rafael/0000-0003-2549-4919; Pardo, Leonardo/0000-0003-1778-7420; Moreno,
Estefania/0000-0002-2491-5753
FU National Institutes of Health; Spanish Ministerio de Ciencia y
Tecnologia [SAF2008-00146, SAF2006-05481, SAF2008-03229-E/]; Fundacio La
Marato de TV3 [RD07/0067/0008, 060110]
FX This work was supported, in whole or in part, by a National Institutes
of Health grant from intramural funds to NIDA. This work was also
supported by Spanish Ministerio de Ciencia y Tecnologia Grants
SAF2008-00146, SAF2006-05481, and SAF2008-03229-E/ for ERA-NET
Coordination of Research Activities and Instituto de Salud Carlos III
(RD07/0067/0008) Grant 060110 from Fundacio La Marato de TV3.
NR 34
TC 53
Z9 53
U1 0
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 27
PY 2010
VL 285
IS 35
BP 27346
EP 27359
DI 10.1074/jbc.M110.115634
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 641ZQ
UT WOS:000281172700064
PM 20562103
ER
PT J
AU Qian, SB
Zhang, XQ
Sun, J
Bennink, JR
Yewdell, JW
Patterson, C
AF Qian, Shu-Bing
Zhang, Xingqian
Sun, Jun
Bennink, Jack R.
Yewdell, Jonathan W.
Patterson, Cam
TI mTORC1 Links Protein Quality and Quantity Control by Sensing Chaperone
Availability
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HEAT-SHOCK FACTOR; MOLECULAR CHAPERONES; TRANSLATIONAL CONTROL;
SIGNALING PATHWAY; HYDROGEN-PEROXIDE; LIFE-SPAN; BINDING PARTNER;
STRESS; TOR; RAPAMYCIN
AB Balanced protein synthesis and degradation are crucial for proper cellular function. Protein synthesis is tightly coupled to energy status and nutrient levels by the mammalian target of rapamycin complex 1 (mTORC1). Quality of newly synthesized polypeptides is maintained by the molecular chaperone and ubiquitin-proteasome systems. Little is known about how cells integrate information about the quantity and quality of translational products simultaneously. We demonstrate that cells distinguish moderate reductions in protein quality from severe protein misfolding using molecular chaperones to differentially regulate mTORC1 signaling. Moderate reduction of chaperone availability enhances mTORC1 signaling, whereas stress-induced complete depletion of chaperoning capacity suppresses mTORC1 signaling. Molecular chaperones regulate mTORC1 assembly in coordination with nutrient availability. This mechanism enables mTORC1 to rapidly detect and respond to environmental cues while also sensing intracellular protein misfolding. The tight linkage between protein quality and quantity control provides a plausible mechanism coupling protein misfolding with metabolic dyshomeostasis.
C1 [Qian, Shu-Bing; Zhang, Xingqian; Sun, Jun] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
[Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Patterson, Cam] Univ N Carolina, McAllister Heart Inst, Chapel Hill, NC 27599 USA.
RP Qian, SB (reprint author), Cornell Univ, Div Nutr Sci, 301 Biotech, Ithaca, NY 14853 USA.
EM sq38@cornell.edu; cpatters@med.unc.edu
RI yewdell, jyewdell@nih.gov/A-1702-2012
FU National Institutes of Health through NIAID; National Institutes of
Health [GM61728, AG024282, DK056350]; Cornell Startup Research Funds;
Ellison Medical Foundation
FX This work was supported, in whole or in part, by the Intramural Research
Program of the National Institutes of Health through NIAID (to J. R. B.
and J. W. Y.) and National Institutes of Health Grants GM61728,
AG024282, and DK056350 (to C. P.). This work was also supported by
Cornell Startup Research Funds and the Ellison Medical Foundation (to S.
B. Q.).
NR 49
TC 21
Z9 21
U1 0
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 27
PY 2010
VL 285
IS 35
BP 27385
EP 27395
DI 10.1074/jbc.M110.120295
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 641ZQ
UT WOS:000281172700067
PM 20605781
ER
PT J
AU Jourd'heuil, D
Lancaster, JR
Fukuto, J
Roberts, DD
Miranda, KM
Mayer, B
Grisham, MB
Wink, DA
AF Jourd'heuil, David
Lancaster, Jack R., Jr.
Fukuto, Jon
Roberts, David D.
Miranda, Katrina M.
Mayer, Bernd
Grisham, Mathew B.
Wink, David A.
TI The Bell-shaped Curve for Peroxynitrite-mediated Oxidation and Nitration
of NO/O-2(center dot-) Is Alive and Well
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Letter
ID NITRIC-OXIDE; SUPEROXIDE
C1 [Jourd'heuil, David] Albany Med Coll, Ctr Cardiovasc Sci, Albany, NY 12208 USA.
[Lancaster, Jack R., Jr.] Univ Alabama, Ctr Free Radical Biol, Birmingham, AL USA.
[Lancaster, Jack R., Jr.] Univ Alabama, Dept Anesthesiol Physiol & Biophys, Birmingham, AL USA.
[Lancaster, Jack R., Jr.] Univ Alabama, Dept Environm Hlth Sci, Birmingham, AL USA.
[Fukuto, Jon] Sonoma State Univ, Dept Chem, Sonoma, CA USA.
[Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Miranda, Katrina M.] Univ Arizona, Dept Chem, Tucson, AZ 85721 USA.
[Mayer, Bernd] Graz Univ, Dept Pharmacol & Toxicol, A-8010 Graz, Austria.
[Grisham, Mathew B.] Louisiana State Univ, Dept Mol & Cellular Physiol, Hlth Sci Ctr, Shreveport, LA 71105 USA.
[Wink, David A.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA.
RP Jourd'heuil, D (reprint author), Albany Med Coll, Ctr Cardiovasc Sci, Albany, NY 12208 USA.
EM jourdhd@mail.amc.edu
RI Roberts, David/A-9699-2008; Mayer, Bernd/B-9391-2008; Miranda,
Katrina/B-7823-2009;
OI Roberts, David/0000-0002-2481-2981; Mayer, Bernd/0000-0002-2921-3494
NR 4
TC 4
Z9 4
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 27
PY 2010
VL 285
IS 35
BP LE15
EP LE15
DI 10.1074/jbc.L110.110080
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 641ZQ
UT WOS:000281172700081
PM 20729216
ER
PT J
AU Satoh, T
Li, M
Nguyen, JT
Kiso, Y
Gustchina, A
Wlodawer, A
AF Satoh, Tadashi
Li, Mi
Nguyen, Jeffrey-Tri
Kiso, Yoshiaki
Gustchina, Alla
Wlodawer, Alexander
TI Crystal Structures of Inhibitor Complexes of Human T-Cell Leukemia Virus
(HTLV-1) Protease
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE retrovirus; protease; leukemia; inhibitors; drug design
ID DRUG DESIGN; MOLECULAR REPLACEMENT; HIV-1 PROTEASE; TYPE-1;
LEUKEMIA/LYMPHOMA; PROTEINASES
AB Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus associated with several serious diseases, such as adult T-cell leukemia and tropical spastic paraparesis/myelopathy. For a number of years, the protease (PR) encoded by HTLV-1 has been a target for designing antiviral drugs, but that effort was hampered by limited available structural information. We report a high-resolution crystal structure of HTLV-1 PR complexed with a statine-containing inhibitor, a significant improvement over the previously available moderate-resolution structure. We also report crystal structures of the complexes of HTLV-1 PR with five different inhibitors that are more compact and more potent. A detailed study of structure activity relationships was performed to interpret in detail the influence of the polar and hydrophobic interactions between the inhibitors and the protease. Published by Elsevier Ltd.
C1 [Satoh, Tadashi; Li, Mi; Gustchina, Alla; Wlodawer, Alexander] NCI, Prot Struct Sect, Macromol Crystallog Lab, Ft Detrick, MD 21702 USA.
[Li, Mi] SAIC Frederick, Basic Res Program, Frederick, MD USA.
[Nguyen, Jeffrey-Tri; Kiso, Yoshiaki] Kyoto Pharmaceut Univ, Ctr Frontier Res Med Sci, Dept Med Chem, Yamashina Ku, Kyoto 6078412, Japan.
RP Wlodawer, A (reprint author), NCI, Prot Struct Sect, Macromol Crystallog Lab, Ft Detrick, MD 21702 USA.
EM wlodawer@nih.gov
FU U.S. Department of Energy, Office of Science, Office of Basic Energy
Sciences [W-31-109-Eng-38]; NIH, National Cancer Institute, Center for
Cancer Research; National Cancer Institute, NIH [HHSN261200800001E];
Ministry of Education, Culture, Sports, Science and Technology (MEXT),
Japan
FX We are grateful for Dr. T. Kimura and Dr. K. Hidaka, Kyoto
Pharmaceutical University, for their advice and assistance. We
acknowledge the use of beamline 22-ID of the Southeast Regional
Collaborative Access Team (SER-CAT) located at the APS, Argonne National
Laboratory. Use of the APS was supported by the U.S. Department of
Energy, Office of Science, Office of Basic Energy Sciences, under
Contract No. W-31-109-Eng-38. This project was funded in part by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research, in part with federal funds from the National
Cancer Institute, NIH, under contract HHSN261200800001E, and in part by
the Frontier Research Program from the Ministry of Education, Culture,
Sports, Science and Technology (MEXT), Japan. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. government.
NR 33
TC 10
Z9 10
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
J9 J MOL BIOL
JI J. Mol. Biol.
PD AUG 27
PY 2010
VL 401
IS 4
BP 626
EP 641
DI 10.1016/j.jmb.2010.06.052
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 642ZW
UT WOS:000281262400007
PM 20600105
ER
PT J
AU Pugach, P
Krarup, A
Gettie, A
Kuroda, M
Blanchard, J
Piatak, M
Lifson, JD
Trkola, A
Robbiani, M
AF Pugach, Pavel
Krarup, Anders
Gettie, Agegnehu
Kuroda, Marcelo
Blanchard, James
Piatak, Michael, Jr.
Lifson, Jeffrey D.
Trkola, Alexandra
Robbiani, Melissa
TI In Vivo Binding and Retention of CD4-Specific DARPin 57.2 in Macaques
SO PLOS ONE
LA English
DT Article
ID ANKYRIN REPEAT PROTEINS; ANTI-CD4 MONOCLONAL-ANTIBODY; ANTIRETROVIRAL
ACTIVITY; VIRUS; LYMPHOCYTES; SELECTION; EFFICACY; TNX-355; TYPE-1
AB Background: The recently described Designed Ankyrin Repeat Protein (DARPin) technology can produce highly selective ligands to a variety of biological targets at a low production cost.
Methodology/Principal Findings: To investigate the in vivo use of DARPins for future application to novel anti-HIV strategies, we identified potent CD4-specific DARPins that recognize rhesus CD4 and followed the fate of intravenously injected CD4-specific DARPin 57.2 in rhesus macaques. The human CD4-specific DARPin 57.2 bound macaque CD4(+) cells and exhibited potent inhibitory activity against SIV infection in vitro. DARPin 57.2 or the control E3_5 DARPin was injected into rhesus macaques and the fate of cell-free and cell-bound CD4-specific DARPin was evaluated. DARPin-bound CD4(+) cells were detected in the peripheral blood as early as 30 minutes after the injection, decreasing within 6 hours and being almost undetectable within 24 hours. The amount of DARPin bound was dependent on the amount of DARPin injected. CD4-specific DARPin was also detected on CD4(+) cells in the lymph nodes within 30 minutes, which persisted with similar kinetics to blood. More extensive analysis using blood revealed that DARPin 57.2 bound to all CD4(+) cell types (T cells, monocytes, dendritic cells) in vivo and in vitro with the amount of binding directly proportional to the amount of CD4 on the cell surface. Cell-free DARPins were also detected in the plasma, but were rapidly cleared from circulation.
Conclusions/Significance: We demonstrated that the CD4-specific DARPin can rapidly and selectively bind its target cells in vivo, warranting further studies on possible clinical use of the DARPin technology.
C1 [Pugach, Pavel; Robbiani, Melissa] Populat Council, Ctr Biomed Res, New York, NY 10021 USA.
[Gettie, Agegnehu] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10021 USA.
[Krarup, Anders; Trkola, Alexandra] Univ Zurich Hosp, Div Infect Dis, CH-8091 Zurich, Switzerland.
[Kuroda, Marcelo; Blanchard, James] Tulane Univ, Hlth Sci Ctr, Tulane Natl Primate Res Ctr, Covington, LA USA.
[Piatak, Michael, Jr.; Lifson, Jeffrey D.] SAIC Frederick Inc, AIDS & Canc Virus Program, Natl Canc Inst, Frederick, MD USA.
RP Pugach, P (reprint author), Populat Council, Ctr Biomed Res, 1230 York Ave, New York, NY 10021 USA.
EM mrobbiani@popcouncil.org
RI Infektiologie, USZ/A-6921-2011; Trkola, Alexandra/K-2115-2012
OI Trkola, Alexandra/0000-0003-1013-876X
FU Campbell Foundation; National Institutes of Health (NIH) [AI040877,
AI084133]; National Cancer Institute, NIH [HHSN261200800001E]
FX This work was supported by the Campbell Foundation, by National
Institutes of Health (NIH) grants AI040877 and AI084133 and in part with
federal funds from the National Cancer Institute, NIH, under contract
HHSN261200800001E. PP is an F.M. Kirby Foundation fellow. MR is a 2002
and AT is a 2006 Elizabeth Glaser Scientist. The funders had no role in
study design, data collection and analysis, decision to publish, or the
preparation of the manuscript.
NR 25
TC 5
Z9 5
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 27
PY 2010
VL 5
IS 8
AR e12455
DI 10.1371/journal.pone.0012455
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 643MT
UT WOS:000281301500021
PM 20805996
ER
PT J
AU Baur, JA
Chen, D
Chini, EN
Chua, K
Cohen, HY
De Cabo, R
Deng, CX
Dimmeler, S
Gius, D
Guarente, LP
Helfand, SL
Imai, SI
Itoh, H
Kadowaki, T
Koya, D
Leeuwenburgh, C
Mcburney, M
Nabeshima, YI
Neri, C
Oberdoerffer, P
Pestell, RG
Rogina, B
Sadoshima, J
Sartorelli, V
Serrano, M
Sinclair, DA
Steegborn, C
Tatar, M
Tissenbaum, HA
Tong, QA
Tsubota, K
Vaquero, A
Verdin, E
AF Baur, Joseph A.
Chen, Danica
Chini, Eduardo N.
Chua, Katrin
Cohen, Haim Y.
De Cabo, Rafael
Deng, Chuxia
Dimmeler, Stefanie
Gius, David
Guarente, Leonard P.
Helfand, Stephen L.
Imai, Shin-Ichiro
Itoh, Hiroshi
Kadowaki, Takashi
Koya, Daisuke
Leeuwenburgh, Christiaan
Mcburney, Michael
Nabeshima, Yo-Ichi
Neri, Christian
Oberdoerffer, Philipp
Pestell, Richard G.
Rogina, Blanka
Sadoshima, Junichi
Sartorelli, Vittorio
Serrano, Manuel
Sinclair, David A.
Steegborn, Clemens
Tatar, Marc
Tissenbaum, Heidi A.
Tong, Qiang
Tsubota, Kazuo
Vaquero, Alejandro
Verdin, Eric
TI Dietary Restriction: Standing Up for Sirtuins
SO SCIENCE
LA English
DT Letter
ID CALORIC RESTRICTION; LIFE-SPAN; DROSOPHILA; DISEASE; SIRT1
C1 [Guarente, Leonard P.] MIT, Dept Biol, Cambridge, MA 02139 USA.
[Baur, Joseph A.] Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA.
[Chen, Danica] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA.
[Chini, Eduardo N.] St Marys Hosp, Mayo Clin, Rochester, MN 55905 USA.
[Chua, Katrin] Stanford Univ, Dept Med, Palo Alto, CA 94305 USA.
[Cohen, Haim Y.] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel.
[De Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA.
[Deng, Chuxia] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
[Dimmeler, Stefanie] Goethe Univ Frankfurt, Dept Internal Med 3, D-60325 Frankfurt, Germany.
[Gius, David] Vanderbilt Univ, Med Ctr, Dept Radiat Oncol & Pediat, Nashville, TN 37232 USA.
[Helfand, Stephen L.] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA.
[Imai, Shin-Ichiro] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA.
[Itoh, Hiroshi] Keio Univ, Sch Med, Div Endocrinol Metab & Nephrol, Tokyo, Japan.
[Kadowaki, Takashi] Univ Tokyo, Dept Diabet & Metab Dis, Tokyo 1608582, Japan.
[Koya, Daisuke] Kanazawa Med Univ, Uchinada, Ishikawa 9200293, Japan.
[Leeuwenburgh, Christiaan] Univ Florida, Dept Aging & Geriatr, Gainesville, FL 32611 USA.
[Mcburney, Michael] Ottawa Hlth Res Inst, Dept Med & Biochem, Ottawa, ON K1H 8L6, Canada.
[Nabeshima, Yo-Ichi] Inst Biomed Res & Innovat Fdn Biomed Res & Innova, Chuo Ku, Kobe, Hyogo 6500047, Japan.
[Neri, Christian] INSERM, U894, Lab Neuronal Cell Biol & Pathol, F-75014 Paris, France.
[Oberdoerffer, Philipp] NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA.
[Pestell, Richard G.] Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Canc Biol & Med Oncol, Philadelphia, PA 19107 USA.
[Rogina, Blanka] Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, Farmington, CT 06030 USA.
[Sadoshima, Junichi] Univ Med & Dent New Jersey, Cardiovasc Res Inst, Newark, NJ 07103 USA.
[Sartorelli, Vittorio] NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA.
[Serrano, Manuel] Spanish Natl Canc Res Ctr CNIO, Madrid, Spain.
[Sinclair, David A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Steegborn, Clemens] Univ Bayreuth, Dept Biochem, D-95440 Bayreuth, Germany.
[Tatar, Marc] Brown Univ, Dept Ecol & Evolut Biol, Providence, RI 02912 USA.
[Tissenbaum, Heidi A.] Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA.
[Tong, Qiang] Baylor Coll Med, Houston, TX 77030 USA.
[Tsubota, Kazuo] Keio Univ, Sch Med, Dept Ophthalmol, Tokyo, Japan.
[Vaquero, Alejandro] ICREA, PEBC, Barcelona 08907, Spain.
[Vaquero, Alejandro] IDIBELL, Barcelona 08907, Spain.
[Verdin, Eric] Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94158 USA.
RP Guarente, LP (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM leng@mit.edu; marc_tatar@brown.edu
RI Baur, Joseph/D-8163-2011; Neri, Christian/F-6729-2013; Vaquero,
Alejandro/I-9845-2014; Koya, Daisuke /J-3257-2014; Serrano,
Manuel/H-2634-2015; de Cabo, Rafael/J-5230-2016; deng,
chuxia/N-6713-2016;
OI , rafael/0000-0003-2830-5693; Vaquero, Alejandro/0000-0002-8735-4156;
Serrano, Manuel/0000-0001-7177-9312; de Cabo,
Rafael/0000-0002-3354-2442; Baur, Joseph/0000-0001-8262-6549; Rogina,
Blanka/0000-0003-1195-905X; Verdin, Eric/0000-0003-3703-3183; Sinclair,
David/0000-0002-9936-436X
FU Intramural NIH HHS [Z99 DK999999]; NHLBI NIH HHS [R01 HL067724, R01
HL091469, R01 HL102738]; NIA NIH HHS [R01 AG023039, P01 AG027916, R00
AG031182, R01 AG019719, R01 AG023088, R01 AG023088-08, R01 AG024360, R01
AG028730, R01 AG028730-05, R37 AG024360]
NR 9
TC 38
Z9 38
U1 2
U2 25
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD AUG 27
PY 2010
VL 329
IS 5995
BP 1012
EP 1013
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 642WZ
UT WOS:000281253500011
PM 20798296
ER
PT J
AU Wei, CJ
Boyington, JC
McTamney, PM
Kong, WP
Pearce, MB
Xu, L
Andersen, H
Rao, S
Tumpey, TM
Yang, ZY
Nabel, GJ
AF Wei, Chih-Jen
Boyington, Jeffrey C.
McTamney, Patrick M.
Kong, Wing-Pui
Pearce, Melissa B.
Xu, Ling
Andersen, Hanne
Rao, Srinivas
Tumpey, Terrence M.
Yang, Zhi-Yong
Nabel, Gary J.
TI Induction of Broadly Neutralizing H1N1 Influenza Antibodies by
Vaccination
SO SCIENCE
LA English
DT Article
ID RECOMBINANT ADENOVIRAL VECTORS; VIRUS; IMMUNIZATION; IMMUNOGENICITY;
IMMUNITY; EPITOPE; HIV-1
AB The rapid dissemination of the 2009 pandemic influenza virus underscores the need for universal influenza vaccines that elicit protective immunity to diverse viral strains. Here, we show that vaccination with plasmid DNA encoding H1N1 influenza hemagglutinin (HA) and boosting with seasonal vaccine or replication-defective adenovirus 5 vector encoding HA stimulated the production of broadly neutralizing influenza antibodies. This prime/boost combination increased the neutralization of diverse H1N1 strains dating from 1934 to 2007 as compared to either component alone and conferred protection against divergent H1N1 viruses in mice and ferrets. These antibodies were directed to the conserved stem region of HA and were also elicited in nonhuman primates. Cross-neutralization of H1N1 subtypes elicited by this approach provides a basis for the development of a universal influenza vaccine for humans.
C1 [Wei, Chih-Jen; Boyington, Jeffrey C.; McTamney, Patrick M.; Kong, Wing-Pui; Xu, Ling; Rao, Srinivas; Yang, Zhi-Yong; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Pearce, Melissa B.; Tumpey, Terrence M.] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Influenza Div, Atlanta, GA 30333 USA.
[Andersen, Hanne] BIOQUAL, Rockville, MD 20850 USA.
RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM gnabel@nih.gov
FU Vaccine Research Center, NIAID, NIH
FX We thank A. Ault, J.-P. Todd, A. Zajac, and C. Chiedi for help with the
animal studies; K. Dai, W. Shi, and S. Y. Ko for technical support; M.
Lewis (BIOQUAL), B. Sanders (BIOQUAL), and members of the Nabel lab for
helpful discussions; A. Tislerics and B. Hartman for manuscript
preparation; and Y. Okuno for providing the C179 mAb. NIH has filed a
patent application (U.S. patent E-341-2008l; international patent WO
2010/036958 A2) on this work (authors: C-J.W., Z-y.Y, and G.J.N.),
related to gene-and protein-based approaches to influenza vaccination.
This research was supported by the Intramural Research Program of the
Vaccine Research Center, NIAID, NIH. The findings and conclusions in
this report are those of the authors and do not necessarily reflect the
views of the funding agency.
NR 18
TC 216
Z9 221
U1 6
U2 34
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD AUG 27
PY 2010
VL 329
IS 5995
BP 1060
EP 1064
DI 10.1126/science.1192517
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 642WZ
UT WOS:000281253500036
PM 20647428
ER
PT J
AU Young, BP
Shin, JJH
Orij, R
Chao, JT
Li, SC
Guan, XL
Khong, A
Jan, E
Wenk, MR
Prinz, WA
Smits, GJ
Loewen, CJR
AF Young, Barry P.
Shin, John J. H.
Orij, Rick
Chao, Jesse T.
Li, Shu Chen
Guan, Xue Li
Khong, Anthony
Jan, Eric
Wenk, Markus R.
Prinz, William A.
Smits, Gertien J.
Loewen, Christopher J. R.
TI Phosphatidic Acid Is a pH Biosensor That Links Membrane Biogenesis to
Metabolism
SO SCIENCE
LA English
DT Article
ID SACCHAROMYCES-CEREVISIAE; TRANSCRIPTION FACTOR; H+-ATPASE; YEAST;
PROTEIN; LOCALIZATION; HOMEOSTASIS; VACUOLAR
AB Recognition of lipids by proteins is important for their targeting and activation in many signaling pathways, but the mechanisms that regulate such interactions are largely unknown. Here, we found that binding of proteins to the ubiquitous signaling lipid phosphatidic acid (PA) depended on intracellular pH and the protonation state of its phosphate headgroup. In yeast, a rapid decrease in intracellular pH in response to glucose starvation regulated binding of PA to a transcription factor, Opi1, that coordinately repressed phospholipid metabolic genes. This enabled coupling of membrane biogenesis to nutrient availability.
C1 [Young, Barry P.; Shin, John J. H.; Chao, Jesse T.; Li, Shu Chen; Loewen, Christopher J. R.] Univ British Columbia, Dept Cellular & Physiol Sci, Vancouver, BC V6T 1Z3, Canada.
[Orij, Rick; Smits, Gertien J.] Univ Amsterdam, Dept Mol Biol & Microbial Food Safety, NL-1018 WV Amsterdam, Netherlands.
[Guan, Xue Li] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 119077, Singapore.
[Guan, Xue Li; Wenk, Markus R.] Univ Geneva, Dept Biochem, CH-1211 Geneva, Switzerland.
[Khong, Anthony; Jan, Eric] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada.
[Wenk, Markus R.] Natl Univ Singapore, Dept Biol Sci, Singapore 119077, Singapore.
[Wenk, Markus R.] Univ Basel, Swiss Trop & Publ Hlth Inst, Basel, Switzerland.
[Prinz, William A.] NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA.
[Loewen, Christopher J. R.] Univ British Columbia, Brain Res Ctr, Vancouver, BC V6T 1Z3, Canada.
RP Loewen, CJR (reprint author), Univ British Columbia, Dept Cellular & Physiol Sci, Vancouver, BC V6T 1Z3, Canada.
EM christopher.loewen@ubc.ca
RI Wenk, Markus/D-1441-2014; Guan, Xue Li/D-2935-2014; Smits,
Gertien/I-4327-2014
OI Smits, Gertien/0000-0002-8439-7791
FU National Sciences and Engineering Council of Canada (NSERC); Canadian
Institute of Health Research (CIHR); Michael Smith Foundation for Health
Research (MSFHR); Canada Foundation for Innovation; British Columbia
Knowledge Development Fund; National Institute of Diabetes and Digestive
and Kidney Diseases; Singapore National Research Foundation [2007-04];
Biomedical Research Council of Singapore [R-183-000-211-305]; National
Medical Research Council [R-183-000-224-213]; SystemsX.ch RTD project
LipidX
FX We are grateful to T. Levine for insight and critical reading of the
manuscript; C. Boone for access to SGA technologies; M. Davies and L.
Conibear for a preliminary inositol screen; and J. Church for
discussions. This research was supported by grants from the National
Sciences and Engineering Council of Canada (NSERC), the Canadian
Institute of Health Research (CIHR), the Michael Smith Foundation for
Health Research (MSFHR), the Canada Foundation for Innovation, and the
British Columbia Knowledge Development Fund (C.J.R.L. and E.J.); the
Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases (W.A.P.); and the Singapore National
Research Foundation under CRP Award 2007-04, the Biomedical Research
Council of Singapore (R-183-000-211-305), the National Medical Research
Council (R-183-000-224-213), and the SystemsX.ch RTD project LipidX
(M.R.W.). J.J.H.S. is the recipient of a NSERC Alexander Graham Bell
Canada Graduate Scholarship. C.J.R.L. is a CIHR New Investigator, a
MSFHR Scholar, and a Tula Foundation Investigator.
NR 20
TC 111
Z9 113
U1 4
U2 43
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD AUG 27
PY 2010
VL 329
IS 5995
BP 1085
EP 1088
DI 10.1126/science.1191026
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 642WZ
UT WOS:000281253500043
PM 20798321
ER
PT J
AU De Ravin, SS
Cowen, EW
Zarember, KA
Whiting-Theobald, NL
Kuhns, DB
Sandler, NG
Douek, DC
Pittaluga, S
Poliani, PL
Lee, YN
Notarangelo, LD
Wang, L
Alt, FW
Kang, EM
Milner, JD
Niemela, JE
Fontana-Penn, M
Sinal, SH
Malech, HL
AF De Ravin, Suk See
Cowen, Edward W.
Zarember, Kol A.
Whiting-Theobald, Narda L.
Kuhns, Douglas B.
Sandler, Netanya G.
Douek, Daniel C.
Pittaluga, Stefania
Poliani, Pietro L.
Lee, Yu Nee
Notarangelo, Luigi D.
Wang, Lei
Alt, Frederick W.
Kang, Elizabeth M.
Milner, Joshua D.
Niemela, Julie E.
Fontana-Penn, Mary
Sinal, Sara H.
Malech, Harry L.
TI Hypomorphic Rag mutations can cause destructive midline granulomatous
disease
SO BLOOD
LA English
DT Article
ID SEVERE COMBINED IMMUNODEFICIENCY; COMMON VARIABLE IMMUNODEFICIENCY;
T-CELL DEVELOPMENT; OMENN-SYNDROME; V(D)J RECOMBINATION;
AUTOINFLAMMATORY DISEASE; EPITHELIAL-CELLS; CMV INFECTION; B-CELL; AIRE
AB Destructive midline granulomatous disease characterized by necrotizing granulomas of the head and neck is most commonly caused by Wegener granulomatosis, natural killer/T-cell lymphomas, cocaine abuse, or infections. An adolescent patient with myasthenia gravis treated with thymectomy subsequently developed extensive granulomatous destruction of midface structures, palate, nasal septum, airways, and epiglottis. His lymphocyte numbers, total immunoglobulin G level, and T-cell receptor (TCR) repertoire appeared normal. Sequencing of Recombination activating gene-1 (Rag1) showed compound heterozygous Rag1 mutations; a novel deletion with no recombinase activity and a missense mutation resulting in 50% Rag activity. His thymus was dysplastic and, although not depleted of T cells, showed a notable absence of autoimmune regulator (AIRE) and Foxp3(+) regulatory T cells. This distinct Rag-deficient phenotype characterized by immune dysregulation with granulomatous hyperinflammation and autoimmunity, with relatively normal T and B lymphocyte numbers and a diverse TCR repertoire expands the spectrum of presentation in Rag deficiency. This study was registered at www.clinicaltrials.gov as #NCT00128973. (Blood. 2010; 116(8): 1263-1271)
C1 [De Ravin, Suk See; Zarember, Kol A.; Whiting-Theobald, Narda L.; Kang, Elizabeth M.; Milner, Joshua D.; Malech, Harry L.] NIAID, Lab Host Defenses, NIH, Bethesda, MD 20892 USA.
[Cowen, Edward W.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
[Kuhns, Douglas B.] SAIC Frederick Inc, Clin Serv Program, Frederick, MD USA.
[Sandler, Netanya G.; Douek, Daniel C.] NCI, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Poliani, Pietro L.] Univ Brescia, Dept Pathol, Brescia, Italy.
[Lee, Yu Nee; Notarangelo, Luigi D.; Wang, Lei; Alt, Frederick W.] Harvard Univ, Sch Med, Div Immunol, Childrens Hosp Boston, Boston, MA USA.
[Niemela, Julie E.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Fontana-Penn, Mary; Sinal, Sara H.] Wake Forest Univ, Dept Pediat, Sch Med, Winston Salem, NC 27109 USA.
RP De Ravin, SS (reprint author), NIAID, Lab Host Defenses, NIH, CRC 5W Rm 5-3816,10 Ctr Dr, Bethesda, MD 20892 USA.
EM sderavin@niaid.nih.gov
RI Poliani, Pietro Luigi/E-8145-2010; Notarangelo, Luigi/F-9718-2016;
OI Poliani, Pietro Luigi/0000-0002-5662-8978; Notarangelo,
Luigi/0000-0002-8335-0262; Malech, Harry/0000-0001-5874-5775; Utay,
Netanya/0000-0002-6407-8670; Niemela, Julie/0000-0003-4197-3792
FU NIAID Division of Intramural Research [N01-CO-12400]; Clinical Center of
the NIH; National Cancer Institute, National Institutes of Health
[N01-CO-12400]
FX This work was supported by the NIAID Division of Intramural Research and
the Clinical Center of the NIH. It was also funded in part by the
National Cancer Institute, National Institutes of Health (contract
N01-CO-12400).
NR 51
TC 51
Z9 51
U1 0
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 26
PY 2010
VL 116
IS 8
BP 1263
EP 1271
DI 10.1182/blood-2010-02-267583
PG 9
WC Hematology
SC Hematology
GA 644DY
UT WOS:000281354300014
PM 20489056
ER
PT J
AU Yedjou, C
Tchounwou, P
Jenkins, J
McMurray, R
AF Yedjou, Clement
Tchounwou, Paul
Jenkins, John
McMurray, Robert
TI Basic Mechanisms of Arsenic Trioxide (ATO)-Induced Apoptosis in Human
Leukemia (HL-60) Cells
SO JOURNAL OF HEMATOLOGY & ONCOLOGY
LA English
DT Article
ID ACUTE PROMYELOCYTIC LEUKEMIA; FLOW-CYTOMETRIC DETECTION; CASPASE 3
ACTIVATION; IN-VITRO; OXIDATIVE STRESS; DOWN-REGULATION; CYCLE ARREST;
PHOSPHATIDYLSERINE EXPRESSION; GROWTH-INHIBITION; INDUCE APOPTOSIS
AB Background: Acute promyelocytic leukemia (APL) is a blood cancer that affects people of all ages and strikes about 1,500 patients in the United States each year. The standard treatment of APL has been based on the combined administration of all-trans retinoic acid and chemotherapy including anthracyclins and cytarabine. However, 10-20% of patients relapse, with their disease becoming resistant to conventional treatment. Recently the Food and Drug Administration has approved the use of arsenic trioxide (ATO) or Trisenox for the treatment of APL, based on clinical studies showing a complete remission, especially in relapsed patients. In a recently published study we demonstrated that ATO pharmacology as an anti-cancer drug is associated with its cytotoxic and genotoxic effects in human leukemia cells.
Methods: In the present study, we further investigated the apoptotic mechanisms of ATO toxicity using the HL-60 cell line as a test model. Apoptosis was measured by flow cytometry analysis of phosphatidylserine externalization (Annexin V assay) and caspase 3 activity, and by DNA laddering assay.
Results: Flow cytometry data showed a strong dose-response relationship between ATO exposure and Annexin-V positive HL-60 cells. Similarly, a statistically significant and dose-dependent increase (p < 0.05) was recorded with regard to caspase 3 activity in HL60 cells undergoing late apoptosis. These results were confirmed by data of DNA laddering assay showing a clear evidence of nucleosomal DNA fragmentation in ATO-treated cells.
Conclusion: Taken together, our research demonstrated that ATO represents an apoptosis-inducing agent and its apoptotic mechanisms involve phosphatidylserine externalization, caspase 3 activation and nucleosomal DNA fragmentation.
C1 [Yedjou, Clement; Tchounwou, Paul] Jackson State Univ, Cell & Toxicogenom Res Lab, NIH RCMI Ctr Environm Hlth, Coll Sci Engn & Technol, Jackson, MS USA.
[Jenkins, John; McMurray, Robert] Univ Mississippi, Med Ctr, Dept Med, Div Rheumatol & Immunol, Jackson, MS 39216 USA.
RP Tchounwou, P (reprint author), Jackson State Univ, Cell & Toxicogenom Res Lab, NIH RCMI Ctr Environm Hlth, Coll Sci Engn & Technol, 1400 Lynch St,Box 18540, Jackson, MS USA.
EM paul.b.tchounwou@jsums.edu
FU National Institutes of Health through the RCMI-Center for Environmental
Health at Jackson State University [5G12RR013459-12]
FX The research described in this publication was made possible by a grant
from the National Institutes of Health (Grant No. 5G12RR013459-12),
through the RCMI-Center for Environmental Health at Jackson State
University. An oral presentation on this manuscript was presented at the
7th International Drug Discovery Science and Technology Conference at
Shanghai, China in October 22-26, 2009.
NR 47
TC 27
Z9 29
U1 0
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-8722
J9 J HEMATOL ONCOL
JI J. Hematol. Oncol.
PD AUG 26
PY 2010
VL 3
AR 28
DI 10.1186/1756-8722-3-28
PG 9
WC Oncology; Hematology
SC Oncology; Hematology
GA 656OW
UT WOS:000282347100001
PM 20796291
ER
PT J
AU Zhang, P
Cyriac, G
Kopajtic, T
Zhao, YF
Javitch, JA
Katz, JL
Newman, AH
AF Zhang, Peng
Cyriac, George
Kopajtic, Theresa
Zhao, Yongfang
Javitch, Jonathan A.
Katz, Jonathan L.
Newman, Amy Hauck
TI Structure-Activity Relationships for a Novel Series of Citalopram
(1-(3-(Dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran
-5-carbonitrile) Analogues at Monoamine Transporters
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID DEPENDENT NEUROTRANSMITTER TRANSPORTERS; ANTIDEPRESSANT BINDING-SITE;
HUMAN SEROTONIN TRANSPORTER; LEUCINE TRANSPORTER; BACTERIAL HOMOLOG;
ESCITALOPRAM; LEUT; DOPAMINE; REUPTAKE; RECOGNITION
AB (+/-)-Citalopram (1, 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile), and its eutomer, escitalopram (S-(+)-1) are selective serotonin reuptake inhibitors (SSRIs) that are used clinically to treat anxiety and depression. To further explore structure-activity relationships at the serotonin transporter (SERT), a series of (+/-)-4- and 5-substituted citalopram analogues were designed, synthesized, and evaluated for binding at the SERT, dopamine transporter (DAT) and norepinephrine transporter (NET) in native rodent tissue. Many of these analogues showed high SERT binding affinities (K(i) = 1-40 nM) and selectivities over both NET and DAT. Selected enantiomeric pairs of analogues were synthesized and both retained enantioselectivity as with S- and wherein S > R at the SERT. In addition, the enantiomeric pairs of 1 and 5 were tested for binding at the homologous bacterial leucine transporter (LeuT), wherein low affinities and the absence of enantioselectivity suggested distinctive binding sites for these compounds at SERT as compared to LeuT. These novel ligands will provide molecular tools to elucidate drug-protein interactions at the SERT and to relate those to behavioral actions in vivo.
C1 [Zhang, Peng; Cyriac, George; Newman, Amy Hauck] NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Kopajtic, Theresa; Katz, Jonathan L.] NIDA, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Zhao, Yongfang; Javitch, Jonathan A.] Columbia Univ Coll Phys & Surg, Ctr Mol Recognit, New York, NY 10032 USA.
[Zhao, Yongfang; Javitch, Jonathan A.] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
[Zhao, Yongfang; Javitch, Jonathan A.] Columbia Univ Coll Phys & Surg, Dept Pharmacol, New York, NY 10032 USA.
RP Newman, AH (reprint author), NIDA, Med Chem Sect, Intramural Res Program, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM anewman@intra.nida.nih.gov
RI Zhao, Yongfang/B-5437-2010;
OI Katz, Jonathan/0000-0002-1068-1159
FU Intramural NIH HHS [Z99 DA999999, ZIA DA000389-14]; NIDA NIH HHS
[DA022413, DA17293, K05 DA022413, R01 DA017293]
NR 40
TC 24
Z9 25
U1 0
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD AUG 26
PY 2010
VL 53
IS 16
BP 6112
EP 6121
DI 10.1021/jm1005034
PG 10
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 639GX
UT WOS:000280962700019
PM 20672825
ER
PT J
AU Subotnik, JE
Vura-Weis, J
Sodt, AJ
Ratner, MA
AF Subotnik, Joseph E.
Vura-Weis, Josh
Sodt, Alex J.
Ratner, Mark A.
TI Predicting Accurate Electronic Excitation Transfer Rates via Marcus
Theory with Boys or Edmiston-Ruedenberg Localized Diabatization
SO JOURNAL OF PHYSICAL CHEMISTRY A
LA English
DT Article
ID COUPLING MATRIX-ELEMENTS; TRIPLET ENERGY-TRANSFER; MOLECULAR-ORBITALS;
MULLIKEN-HUSH; AB-INITIO; CHEMISTRY; SYSTEMS; HOLE; APPROXIMATION;
DIFFERENCE
AB We model the triplet triplet energy-transfer experiments from the Closs group [Closs, G. L., et al J. Am. Chem. Soc. 1988, 110, 2652] using a combination of Marcus theory and either Boys or Edmiston-Ruedenberg localized diabatization, and we show that relative and absolute rates of electronic excitation transfer may be computed successfully. For the case where both the donor and acceptor occupy equatorial positions on a rigid cyclohexane bridge, we find beta(calc) = 2 8 per C C bond, compared with the experimental value beta(exp) = 2.6. This work highlights the power of using localized diabatization methods as a tool for modeling nonequilibrium processes
C1 [Subotnik, Joseph E.; Vura-Weis, Josh; Ratner, Mark A.] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA.
[Sodt, Alex J.] NIH, NHLBI, Lab Computat Biol, Bethesda, MD 20892 USA.
RP Subotnik, JE (reprint author), Univ Penn, Dept Chem, Philadelphia, PA 19104 USA.
FU ANSER Center, an Energy Frontier Research Center; US Department of
Energy, Office of Science, Office of Basic Energy Sciences
[DE-SC0001059]
FX We thank Abraham Nitzan, Yihan Shao, Todd Martinez, Gemma Solomon, David
Chandler, Seogjoo Jang, Robert J. Cave, and Mat shall Newton for very
illuminating conversations. M A.R thanks the chemistry division of both
the NSF and the ONR for financial support This work was supported in
part by the ANSER Center, an Energy Frontier Research Center funded by
the US Department of Energy, Office of Science, Office of Basic Energy
Sciences, under Award Number DE-SC0001059
NR 41
TC 50
Z9 50
U1 1
U2 33
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1089-5639
J9 J PHYS CHEM A
JI J. Phys. Chem. A
PD AUG 26
PY 2010
VL 114
IS 33
BP 8665
EP 8675
DI 10.1021/jp101235a
PG 11
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 639GW
UT WOS:000280962400018
PM 20446743
ER
PT J
AU Schmidt, MW
Ivanic, J
Ruedenberg, K
AF Schmidt, Michael W.
Ivanic, Joseph
Ruedenberg, Klaus
TI Electronic Structure Analysis of the Ground-State Potential Energy Curve
of Be-2
SO JOURNAL OF PHYSICAL CHEMISTRY A
LA English
DT Article
ID DIRECT CONFIGURATION-INTERACTION; DOUGLAS-KROLL TRANSFORMATION;
MOLECULAR WAVE-FUNCTIONS; CONSISTENT-FIELD METHOD; MULTIPLE ACTIVE
SPACES; BERYLLIUM DIMER; BENCHMARK CALCULATIONS; VARIABLE OCCUPATIONS;
PERTURBATION-THEORY; BINDING-ENERGY
AB The recently measured ground-state potential energy curve of the diatomic beryllium molecule is reproduced to within an accuracy of 20 cm(-1) by a full valence configuration interaction calculation based on augmented correlation-consistent double-, triple-, and quadruple-zeta basis sets, followed by a two-tier extrapolation to the complete basis set limit and complemented by a configuration interaction estimate of the core and core-valence correlations The origin of binding in Be-2 as well as the unusual shape of its potential energy curve is elucidated by an in-depth analysis of the contributions of the various components of this wave function to the bonding process. Beyond the bonding region, the 6/8 London dispersion interaction is recovered.
C1 [Schmidt, Michael W.; Ruedenberg, Klaus] Iowa State Univ, Dept Chem, Ames, IA 50011 USA.
[Schmidt, Michael W.; Ruedenberg, Klaus] Iowa State Univ, Ames Lab, US DOE, Ames, IA 50011 USA.
[Ivanic, Joseph] NCI Frederick, SAIC Frederick Inc, Informat Syst Program, Adv Biomed Comp Ctr, Frederick, MD 21702 USA.
RP Schmidt, MW (reprint author), Iowa State Univ, Dept Chem, Ames, IA 50011 USA.
FU DOE; NSF
FX The authors are grateful to David Feller for arranging access to the
various new Correlation Consistent basis sets for Be, in advance of
their publication.28 They thank Laimutis Bytautas for
stimulating discussions and help in the literature search The present
work was supported by the DOE Chemical Physics program (M.W S, K R), the
NSF Petascale Applications grant (M.W.S.), and the NSF
Cyberinfrastructure grant (M W S) J . I. thanks Jack Collins for
valuable discussions and the staff and administration of the Advanced
Biomedical Computing Center for their help and support. MW S (35 years)
and J.I. (15 years) wish to thank K R. for his long-standing willingness
to share with them his deep insights into quantum
NR 59
TC 33
Z9 33
U1 1
U2 14
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1089-5639
J9 J PHYS CHEM A
JI J. Phys. Chem. A
PD AUG 26
PY 2010
VL 114
IS 33
BP 8687
EP 8696
DI 10.1021/jp101506t
PG 10
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 639GW
UT WOS:000280962400021
PM 20507164
ER
PT J
AU Fodeke, AA
Minton, AP
AF Fodeke, Adedayo A.
Minton, Allen P.
TI Quantitative Characterization of Polymer-Polymer, Protein-Protein, and
Polymer-Protein Interaction via Tracer Sedimentation Equilibrium
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID HARD PARTICLE MODEL; SELF-ASSOCIATING PROTEINS; STATIC LIGHT-SCATTERING;
BOVINE SERUM-ALBUMIN; CONFORMATION; EXCLUSION; MIXTURES; BEHAVIOR; SIZE
AB Quantitative analysis of the composition dependence of the concentration gradient of each species of macromolecule within a solution mixture at sedimentation equilibrium permits the quantitative characterization of self- and heterointeractions between sedimenting solutes. Sedimentation equilibrium experiments were conducted on solutions containing a trace concentration of FITC-labeled BSA in varying concentrations of Ficoll 70 and on solutions containing a trace concentration of FITC-labeled Ficoll 70 in varying concentrations of BSA. The equilibrium gradient of each solute component in each mixture was measured independently. Analysis of the resulting gradients resulted in evaluation of the dependence of the activity coefficient of Ficoll upon the concentrations of Ficoll and BSA at concentrations of up to 100 g/L and the dependence of the activity coefficient of BSA upon the concentrations of Ficoll and BSA at concentrations of up to 100 g/L. The activity coefficients of both species increase significantly with increasing Ficoll and BSA concentration and do not vary with temperature, to within the precision of measurement, over the temperature range of 5-37 degrees C, indicating that the dominant interaction between Ficoll molecules and between BSA and Ficoll molecules is repulsive and probably due to steric volume exclusion. The measured dependences may be accounted for quantitatively by a simple model in which BSA and Ficoll 70 are represented by equivalent rigid particles.
C1 [Fodeke, Adedayo A.; Minton, Allen P.] NIDDKD, Sect Phys Biochem, Lab Biochem & Genet, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Fodeke, Adedayo A.] Obafemi Awolowo Univ, Dept Chem, Ife, Nigeria.
RP Minton, AP (reprint author), NIDDKD, Sect Phys Biochem, Lab Biochem & Genet, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM minton@helix.nih.gov
OI Minton, Allen/0000-0001-8459-1247
FU Division of Intramural Research, National Institute of Diabetes and
Digestive and Kidney Diseases
FX The authors thank Cristina Fernandez (NIH) for assistance with
chromatographic characterization, and Peter McPhie (NIH) for critical
review of a draft of this report. This research was supported by the
Division of Intramural Research, National Institute of Diabetes and
Digestive and Kidney Diseases.
NR 22
TC 19
Z9 19
U1 0
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-6106
J9 J PHYS CHEM B
JI J. Phys. Chem. B
PD AUG 26
PY 2010
VL 114
IS 33
BP 10876
EP 10880
DI 10.1021/jp104342f
PG 5
WC Chemistry, Physical
SC Chemistry
GA 639GU
UT WOS:000280962100022
PM 20677765
ER
PT J
AU Mariappan, M
Li, XZ
Stefanovic, S
Sharma, A
Mateja, A
Keenan, RJ
Hegde, RS
AF Mariappan, Malaiyalam
Li, Xingzhe
Stefanovic, Sandra
Sharma, Ajay
Mateja, Agnieszka
Keenan, Robert J.
Hegde, Ramanujan S.
TI A ribosome-associating factor chaperones tail-anchored membrane proteins
SO NATURE
LA English
DT Article
ID ENDOPLASMIC-RETICULUM; ER MEMBRANE; INSERTION; GET3; COMPLEX;
RECOGNITION; BINDING; IDENTIFICATION; TRANSLATION; TERMINATION
AB Hundreds of proteins are inserted post-translationally into the endoplasmic reticulum (ER) membrane by a single carboxyterminal transmembrane domain (TMD)(1). During targeting through the cytosol, the hydrophobic TMD of these tail-anchored (TA) proteins requires constant chaperoning to prevent aggregation or inappropriate interactions. A central component of this targeting system is TRC40, a conserved cytosolic factor that recognizes the TMD of TA proteins and delivers them to the ER for insertion(2-4). The mechanism that permits TRC40 to find and capture its TA protein cargos effectively in a highly crowded cytosol is unknown. Here we identify a conserved three-protein complex composed of Bat3, TRC35 and Ubl4A that facilitates TA protein capture by TRC40. This Bat3 complex is recruited to ribosomes synthesizing membrane proteins, interacts with the TMDs of newly released TA proteins, and transfers them to TRC40 for targeting. Depletion of the Bat3 complex allows non-TRC40 factors to compete for TA proteins, explaining their mislocalization in the analogous yeast deletion strains(5-7). Thus, the Bat3 complex acts as a TMD-selective chaperone that effectively channels TA proteins to the TRC40 insertion pathway.
C1 [Mariappan, Malaiyalam; Li, Xingzhe; Stefanovic, Sandra; Sharma, Ajay; Hegde, Ramanujan S.] NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
[Li, Xingzhe] Peking Univ, Sch Basic Med Sci, Beijing 100191, Peoples R China.
[Mateja, Agnieszka; Keenan, Robert J.] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA.
RP Hegde, RS (reprint author), NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
EM hegder@mail.nih.gov
RI mariappan, malaiyalam/K-9024-2012;
OI Hegde, Ramanujan/0000-0001-8338-852X
FU National Institutes of Health; Edward Mallinckrodt Jr Foundation
FX We thank S. Appathurai and M. Downing for technical assistance, Hegde
lab members for advice, and J. Weissman and W. Clemons for useful
discussions and sharing results before publication. This work was
supported by the Intramural Research Program of the National Institutes
of Health (R.S.H.) and Edward Mallinckrodt Jr Foundation (R.J.K.).
NR 30
TC 115
Z9 120
U1 4
U2 23
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 AUG 26
PY 2010
VL 466
IS 7310
BP 1120
EP U138
DI 10.1038/nature09296
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 642IK
UT WOS:000281203600043
PM 20676083
ER
PT J
AU Watnick, T
Germino, GG
AF Watnick, Terry
Germino, Gregory G.
TI mTOR Inhibitors in Polycystic Kidney Disease
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID PATHWAY; PKD1
C1 [Watnick, Terry] Johns Hopkins Sch Med, Div Nephrol, Dept Med, Baltimore, MD 21218 USA.
[Germino, Gregory G.] NIDDKD, NIH, Bethesda, MD 20892 USA.
RP Watnick, T (reprint author), Johns Hopkins Sch Med, Div Nephrol, Dept Med, Baltimore, MD 21218 USA.
OI Germino, Gregory/0000-0002-3609-5588
NR 11
TC 36
Z9 37
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
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD AUG 26
PY 2010
VL 363
IS 9
BP 879
EP 881
DI 10.1056/NEJMe1006925
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 642HG
UT WOS:000281196600013
PM 20581393
ER
PT J
AU Behnke, MS
Wootton, JC
Lehmann, MM
Radke, JB
Lucas, O
Nawas, J
Sibley, LD
White, MW
AF Behnke, Michael S.
Wootton, John C.
Lehmann, Margaret M.
Radke, Josh B.
Lucas, Olivier
Nawas, Julie
Sibley, L. David
White, Michael W.
TI Coordinated Progression through Two Subtranscriptomes Underlies the
Tachyzoite Cycle of Toxoplasma gondii
SO PLOS ONE
LA English
DT Article
ID PARASITE PLASMODIUM-FALCIPARUM; CELL-NUCLEAR-ANTIGENS; GENE-EXPRESSION
DATA; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTION FACTORS; BRADYZOITE
DIFFERENTIATION; COMPARATIVE GENOMICS; PROMOTER ELEMENTS; MALARIA
PARASITES; REGULATED GENES
AB Background: Apicomplexan parasites replicate by varied and unusual processes where the typically eukaryotic expansion of cellular components and chromosome cycle are coordinated with the biosynthesis of parasite-specific structures essential for transmission.
Methodology/Principal Findings: Here we describe the global cell cycle transcriptome of the tachyzoite stage of Toxoplasma gondii. In dividing tachyzoites, more than a third of the mRNAs exhibit significant cyclical profiles whose timing correlates with biosynthetic events that unfold during daughter parasite formation. These 2,833 mRNAs have a bimodal organization with peak expression occurring in one of two transcriptional waves that are bounded by the transition into S phase and cell cycle exit following cytokinesis. The G1-subtranscriptome is enriched for genes required for basal biosynthetic and metabolic functions, similar to most eukaryotes, while the S/M-subtranscriptome is characterized by the uniquely apicomplexan requirements of parasite maturation, development of specialized organelles, and egress of infectious daughter cells. Two dozen AP2 transcription factors form a series through the tachyzoite cycle with successive sharp peaks of protein expression in the same timeframes as their mRNA patterns, indicating that the mechanisms responsible for the timing of protein delivery might be mediated by AP2 domains with different promoter recognition specificities.
Conclusion/Significance: Underlying each of the major events in apicomplexan cell cycles, and many more subordinate actions, are dynamic changes in parasite gene expression. The mechanisms responsible for cyclical gene expression timing are likely crucial to the efficiency of parasite replication and may provide new avenues for interfering with parasite growth.
C1 [Behnke, Michael S.; Lehmann, Margaret M.; Radke, Josh B.; White, Michael W.] Montana State Univ, Dept Vet Mol Biol, Bozeman, MT 59717 USA.
[Radke, Josh B.; Lucas, Olivier; White, Michael W.] Univ S Florida, Dept Mol Med, Tampa, FL USA.
[Radke, Josh B.; Lucas, Olivier; White, Michael W.] Univ S Florida, Dept Global Hlth, Tampa, FL USA.
[Wootton, John C.] Natl Lib Med, Computat Biol Branch, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD USA.
[Behnke, Michael S.; Nawas, Julie; Sibley, L. David] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
RP Behnke, MS (reprint author), Montana State Univ, Dept Vet Mol Biol, Bozeman, MT 59717 USA.
EM mwhite.usf@gmail.com
RI White, Michael/A-4978-2012; Behnke, Michael/R-8839-2016
OI Behnke, Michael/0000-0002-4668-8109
FU National Institutes of Health [AI 48390, AI077662, AI072739, AI034036];
NCBI, National Library of Medicine, National Institutes of Health
FX This work was supported in part by grants from the National Institutes
of Health to MWW (AI 48390, AI077662, and AI072739) and LDS (AI034036).
JCW is supported by the Intramural program of NCBI, National Library of
Medicine, National Institutes of Health. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 87
TC 90
Z9 90
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 26
PY 2010
VL 5
IS 8
AR e12354
DI 10.1371/journal.pone.0012354
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 643JL
UT WOS:000281292100008
PM 20865045
ER
PT J
AU Mills, JL
Carter, TC
AF Mills, James L.
Carter, Tonia C.
TI Acyclovir Exposure and Birth Defects An Important Advance, But More Are
Needed
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID PREGNANCY OUTCOMES
C1 [Mills, James L.; Carter, Tonia C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA.
RP Mills, JL (reprint author), NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd,Room 7B03, Bethesda, MD 20892 USA.
EM jamesmills@nih.gov
FU Intramural NIH HHS [Z99 HD999999]
NR 9
TC 2
Z9 2
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD AUG 25
PY 2010
VL 304
IS 8
BP 905
EP 906
DI 10.1001/jama.2010.1214
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 644OY
UT WOS:000281389900032
PM 20736478
ER
PT J
AU Gunsolly, C
Nicholson, JD
Listwak, SJ
Ledee, D
Zelenka, P
Verthelyi, D
Chapoval, S
Keegan, A
Tonelli, LH
AF Gunsolly, Chad
Nicholson, James D.
Listwak, Samuel J.
Ledee, Dolena
Zelenka, Peggy
Verthelyi, Daniela
Chapoval, Svetlana
Keegan, Achsah
Tonelli, Leonardo H.
TI Expression and regulation in the brain of the chemokine CCL27 gene locus
SO JOURNAL OF NEUROIMMUNOLOGY
LA English
DT Article
DE CTACK; PESKY; Alternative splicing; In situ hybridization; Neuroimmune;
RT-PCR
ID CENTRAL-NERVOUS-SYSTEM; SKIN-ASSOCIATED CHEMOKINE; ALLERGIC RHINITIS;
MESSENGER-RNA; CUTTING EDGE; CC-CHEMOKINE; MOUSE MODEL; T-CELLS;
RECEPTOR; INFLAMMATION
AB The chemokine CCL27 has chemoattractant properties for memory T cells and has been implicated in skin allergic reactions. The present study reports the expression in the brain of two CCL27 splice variants localized in the cerebral cortex and limbic regions. CCL27-like immunoreactivity was identified mainly in neurons. Variant 1 was found elevated in the olfactory bulbs during allergic inflammation induced by intranasal challenge with allergen. This was accompanied by the presence of T cells in the olfactory bulbs. Intranasal administration of neutralizing antibodies against CCL27 reduced the presence of T cells in the olfactory bulbs suggesting a function in T cell activity in the brain. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Gunsolly, Chad; Nicholson, James D.; Tonelli, Leonardo H.] Univ Maryland, Sch Med, Dept Psychiat, Lab Behav Neuroimmunol,Mood & Anxiety Program, Baltimore, MD 21201 USA.
[Listwak, Samuel J.] NIMH, NIH, Bethesda, MD 20892 USA.
[Ledee, Dolena; Zelenka, Peggy] NEI, Cell Differentiat Sect, NIH, Bethesda, MD 20892 USA.
[Verthelyi, Daniela] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Review, Bethesda, MD 20014 USA.
[Chapoval, Svetlana; Keegan, Achsah] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA.
[Chapoval, Svetlana; Keegan, Achsah] Univ Maryland, Sch Med, Program Oncol, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
RP Tonelli, LH (reprint author), 685 W Baltimore St,MSTF Bldg,Room 934 C, Baltimore, MD 21201 USA.
EM Ltonelli@psych.umaryland.edu
FU NIH; Department of Psychiatry, University of Maryland School of Medicine
FX The authors wish to thank Dr. Esther M. Sternberg from the National
Institute of Mental Health for her logistic support and Dr. Steven
Bernstein from the University of Maryland for his help with antibodies
used in this study. This study was supported by an Intramural Award from
the Integrative Neural Immune Program, NIH, to PZ and LHT and by
research seed funding from the Department of Psychiatry, University of
Maryland School of Medicine.
NR 45
TC 4
Z9 4
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-5728
J9 J NEUROIMMUNOL
JI J. Neuroimmunol.
PD AUG 25
PY 2010
VL 225
IS 1-2
BP 82
EP 90
DI 10.1016/j.jneuroim.2010.04.019
PG 9
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 651LA
UT WOS:000281928000011
PM 20605223
ER
PT J
AU Lelli, A
Kazmierczak, P
Kawashima, Y
Muller, U
Holt, JR
AF Lelli, Andrea
Kazmierczak, Piotr
Kawashima, Yoshiyuki
Mueller, Ulrich
Holt, Jeffrey R.
TI Development and Regeneration of Sensory Transduction in Auditory Hair
Cells Requires Functional Interaction Between Cadherin-23 and
Protocadherin-15
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID TIP-LINK INTEGRITY; SYNDROME TYPE 1F; INNER-EAR; MUTANT ALLELES; MOUSE
COCHLEA; WALTZER MICE; CROSS-LINKS; MYOSIN-XVA; STEREOCILIA; ADAPTATION
AB Tip links are extracellular filaments that connect pairs of hair cell stereocilia and convey tension to mechanosensitive channels. Recent evidence suggests that tip links are formed by calcium-dependent interactions between the N-terminal domains of cadherin-23 (CDH23) and protocadherin-15 (PCDH15). Mutations in either CDH23 or PCDH15 cause deafness in mice and humans, indicating the molecules are required for normal inner ear function. However, there is little physiological evidence to support a direct role for CDH23 and PCDH15 in hair cell mechanotransduction. To investigate the contributions of CDH23 and PCDH15 to mechanotransduction and tip-link formation, we examined outer hair cells of mouse cochleas during development and after chemical disruption of tip links. We found that tip links and mechanotransduction with all the qualitative properties of mature transduction recovered within 24 h after disruption. To probe tip-link formation, we measured transduction currents after extracellular application of recombinant CDH23 and PCDH15 fragments, which included putative interaction domains (EC1). Both fragments inhibited development and regeneration of transduction but did not disrupt transduction in mature cells. PCDH15 fragments that carried a mutation in EC1 that causes deafness in humans did not inhibit transduction development or regeneration. Immunolocalization revealed wild-type fragments bound near the tips of hair cell stereocilia. Scanning electron micrographs revealed that hair bundles exposed to fragments had a reduced number of linkages aligned along the morphological axis of sensitivity of the bundle. Together, the data provide direct evidence implicating CDH23 and PCDH15 proteins in the formation of tip links during development and regeneration of mechanotransduction.
C1 [Lelli, Andrea; Holt, Jeffrey R.] Univ Virginia, Sch Med, Dept Neurosci, Charlottesville, VA 22908 USA.
[Holt, Jeffrey R.] Univ Virginia, Sch Med, Dept Otolaryngol, Charlottesville, VA 22908 USA.
[Kazmierczak, Piotr; Mueller, Ulrich] Scripps Res Inst, Dorris Neurosci Ctr, Dept Cell Biol, La Jolla, CA 92037 USA.
[Kawashima, Yoshiyuki] Natl Inst Deafness & Other Commun Disorders, Sect Gene Struct & Funct, NIH, Rockville, MD 20850 USA.
RP Holt, JR (reprint author), Univ Virginia, Sch Med, Dept Neurosci, MR4,Room 5126,Box 801392, Charlottesville, VA 22908 USA.
EM jeffholt@virginia.edu
FU National Institutes of Health (NIH)/National Institute on Deafness and
Other Communication Disorders [DC05439, DC05965, DC07704]; NIH
[Z01-DC-000060]
FX This work was supported by National Institutes of Health (NIH)/National
Institute on Deafness and Other Communication Disorders Grants DC05439
(J.R.H.), DC05965, and DC07704 (U.M.), and NIH intramural research fund
Z01-DC-000060 (Y.K.). We thank members of the Holt/Geleoc and Corwin
laboratories for helpful discussions and Journal of Neuroscience
reviewers for their constructive comments.
NR 45
TC 27
Z9 29
U1 0
U2 6
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 AUG 25
PY 2010
VL 30
IS 34
BP 11259
EP 11269
DI 10.1523/JNEUROSCI.1949-10.2010
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 643BQ
UT WOS:000281268200002
PM 20739546
ER
PT J
AU Giannone, RJ
McDonald, HW
Hurst, GB
Shen, RF
Wang, YS
Liu, Y
AF Giannone, Richard J.
McDonald, Hayes W.
Hurst, Gregory B.
Shen, Rong-Fong
Wang, Yisong
Liu, Yie
TI The Protein Network Surrounding the Human Telomere Repeat Binding
Factors TRF1, TRF2, and POT1
SO PLOS ONE
LA English
DT Article
ID DNA-DAMAGE RESPONSE; DOUBLE-STRAND BREAKS; MAMMALIAN TELOMERES;
HOMOLOGOUS RECOMBINATION; DYSFUNCTIONAL TELOMERES; INDUCED
PHOSPHORYLATION; IMPORTIN-ALPHA; HUMAN-CELLS; HUMAN RAP1; COMPLEX
AB Telomere integrity (including telomere length and capping) is critical in overall genomic stability. Telomere repeat binding factors and their associated proteins play vital roles in telomere length regulation and end protection. In this study, we explore the protein network surrounding telomere repeat binding factors, TRF1, TRF2, and POT1 using dual-tag affinity purification in combination with multidimensional protein identification technology liquid chromatography - tandem mass spectrometry (MudPIT LC-MS/MS). After control subtraction and data filtering, we found that TRF2 and POT1 co-purified all six members of the telomere protein complex, while TRF1 identified five of six components at frequencies that lend evidence towards the currently accepted telomere architecture. Many of the known TRF1 or TRF2 interacting proteins were also identified. Moreover, putative associating partners identified for each of the three core components fell into functional categories such as DNA damage repair, ubiquitination, chromosome cohesion, chromatin modification/remodeling, DNA replication, cell cycle and transcription regulation, nucleotide metabolism, RNA processing, and nuclear transport. These putative protein-protein associations may participate in different biological processes at telomeres or, intriguingly, outside telomeres.
C1 [Giannone, Richard J.; Wang, Yisong] Oak Ridge Natl Lab, Biosci Div, Oak Ridge, TN 37831 USA.
[Giannone, Richard J.; Hurst, Gregory B.] Oak Ridge Natl Lab, Div Chem Sci, Oak Ridge, TN USA.
[McDonald, Hayes W.] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Shen, Rong-Fong; Liu, Yie] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Wang, Yisong] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Giannone, RJ (reprint author), Oak Ridge Natl Lab, Biosci Div, Oak Ridge, TN 37831 USA.
EM yisong.wang@nih.gov; liuyie@mail.nih.gov
OI Hurst, Gregory/0000-0002-7650-8009
FU National Institute on Aging, National Institutes of Health; Oak Ridge
National Laboratory; Office of Biological and Environmental Research,
U.S. Department of Energy [DE-AC05-00OR22725]
FX This study was supported by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health. Y.W. and
R.J.G. acknowledge the support of the Laboratory Directed Research and
Development Program (LDRD), Oak Ridge National Laboratory, and the
Office of Biological and Environmental Research, U.S. Department of
Energy (DE-AC05-00OR22725). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 75
TC 21
Z9 23
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 25
PY 2010
VL 5
IS 8
AR e12407
DI 10.1371/journal.pone.0012407
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 642RO
UT WOS:000281234700028
PM 20811636
ER
PT J
AU Wuchty, S
Siwo, G
Ferdig, MT
AF Wuchty, Stefan
Siwo, Geoffrey
Ferdig, Michael T.
TI Viral Organization of Human Proteins
SO PLOS ONE
LA English
DT Article
ID INTERACTION DATABASE; INTERACTION MAP; PHOSPHORYLATION NETWORKS;
SACCHAROMYCES-CEREVISIAE; INTERACTOME; COMPLEXES; IDENTIFICATION;
INFECTION; LANDSCAPE; RESOURCE
AB Although maps of intracellular interactions are increasingly well characterized, little is known about large-scale maps of host-pathogen protein interactions. The investigation of host-pathogen interactions can reveal features of pathogenesis and provide a foundation for the development of drugs and disease prevention strategies. A compilation of experimentally verified interactions between HIV-1 and human proteins and a set of HIV-dependency factors (HDF) allowed insights into the topology and intricate interplay between viral and host proteins on a large scale. We found that targeted and HDF proteins appear predominantly in rich-clubs, groups of human proteins that are strongly intertwined among each other. These assemblies of proteins may serve as an infection gateway, allowing the virus to take control of the human host by reaching protein pathways and diversified cellular functions in a pronounced and focused way. Particular transcription factors and protein kinases facilitate indirect interactions between HDFs and viral proteins. Discerning the entanglement of directly targeted and indirectly interacting proteins may uncover molecular and functional sites that can provide novel perspectives on the progression of HIV infection and highlight new avenues to fight this virus.
C1 [Wuchty, Stefan] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
[Siwo, Geoffrey; Ferdig, Michael T.] Univ Notre Dame, Dept Biol, Eck Inst Global Hlth, Notre Dame, IN 46556 USA.
RP Wuchty, S (reprint author), NIH, Natl Ctr Biotechnol Informat, Bldg 10, Bethesda, MD 20892 USA.
EM wuchtys@ncbi.nlm.nih.gov
RI Ferdig, Michael/C-6627-2016
FU NCBI/NLM/NIH; NIH [AI071121]
FX SW was supported by NCBI/NLM/NIH. MTF and GS are supported by NIH grant
AI071121. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 31
TC 15
Z9 15
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 25
PY 2010
VL 5
IS 8
AR e11796
DI 10.1371/journal.pone.0011796
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 642RO
UT WOS:000281234700001
PM 20827298
ER
PT J
AU Fox, MP
Sanne, IM
Conradie, F
Zeinecker, J
Orrell, C
Ive, P
Rassool, M
Dehlinger, M
van der Horst, C
McIntyre, J
Wood, R
AF Fox, Matthew P.
Sanne, Ian M.
Conradie, Francesca
Zeinecker, Jennifer
Orrell, Catherine
Ive, Prudence
Rassool, Mohammed
Dehlinger, Marjorie
van der Horst, Charles
McIntyre, James
Wood, Robin
TI Initiating patients on antiretroviral therapy at CD4 cell counts above
200 cells/mu l is associated with improved treatment outcomes in South
Africa
SO AIDS
LA English
DT Article
DE CD4 cell count; highly active antiretroviral therapy; HIV; mortality;
Sub-Saharan Africa; tuberculosis; virologic failure
ID HIV-INFECTED PATIENTS; HIV-1-INFECTED PATIENTS; BASE-LINE; MORTALITY;
ADULTS; DETERMINANTS; SETTINGS; PROGRAMS; SEARCH; COHORT
AB Objectives: To compare treatment outcomes by starting CD4 cell counts using data from the Comprehensive International Program of Research on AIDS-South Africa trial.
Design: An observational cohort study.
Methods: Patients presenting to primary care clinics with CD4 cell counts below 350 cells/mu l were randomized to either doctor or nurse-managed HIV care and followed for at least 2 years after antiretroviral therapy (ART) initiation. Clinical and laboratory outcomes were compared by baseline CD4 cell counts.
Results: Eight hundred and twelve patients were followed for a median of 27.5 months and 36% initiated ART with a CD4 cell count above 200 cells/mu l. Although 10% of patients failed virologically, the risk was nearly double among those with a CD4 cell count of 200 cells/mu l or less vs. above 200 cells/mu l (12.2 vs. 6.8%). Twenty-one deaths occurred, with a five-fold increased risk for the low CD4 cell count group (3.7 vs. 0.7%). After adjustment, those with a CD4 cell count of 200 cells/mu l had twice the risk of death/virologic failure [hazard ratio 1.9; 95% confidence interval (CI), 1.1-3.3] and twice the risk of incident tuberculosis (hazard ratio 1.90; 95% CI, 0.89-4.04) as those above 200 cells/mu l. Those with either a CD4 cell count of 200 cells/mu l or less (hazard ratio 2.1; 95% CI, 1.2-3.8) or a WHO IV condition (hazard ratio 2.9; 95% CI, 0.93-8.8) alone had a two-to-three-fold increased risk of death/virologic failure vs. those with neither, but those with both conditions had a four-fold increased risk (hazard ratio 3.9; 95% CI, 1.9-8.1). We observed some decreased loss to follow-up among those initiating ART at less than 200 cells/mu l (hazard ratio 0.79; 95% CI, 0.50-1.25).
Conclusion: Patients initiating ART with higher CD4 cell counts had reduced mortality, tuberculosis and less virologic failure than those initiated at lower CD4 cell counts. Our data support increasing CD4 cell count eligibility criteria for ART initiation. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Fox, Matthew P.] Boston Univ, Crosstown Ctr, Ctr Global Hlth & Dev, Boston, MA 02118 USA.
[Fox, Matthew P.] Hlth Econ & Epidemiol Res Off, Johannesburg, South Africa.
[Fox, Matthew P.; Sanne, Ian M.; Conradie, Francesca; Ive, Prudence; Rassool, Mohammed] Univ Witwatersrand, Fac Hlth Sci, Johannesburg, South Africa.
[Fox, Matthew P.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA.
[Zeinecker, Jennifer; Orrell, Catherine; Wood, Robin] Univ Cape Town, ZA-7925 Cape Town, South Africa.
[Dehlinger, Marjorie] NIAID, NIH, Bethesda, MD 20892 USA.
[van der Horst, Charles] Univ N Carolina, Chapel Hill, NC USA.
[McIntyre, James] ANOVA Hlth Inst, Johannesburg, South Africa.
RP Fox, MP (reprint author), Boston Univ, Crosstown Ctr, Ctr Global Hlth & Dev, 3rd Floor,801 Massachusetts Ave, Boston, MA 02118 USA.
EM mfox@bu.edu
FU US National Institute of Allergy and Infectious Diseases (NIAID) through
the CIPRA network [U19 AI53217]; NIAID [K01AI083097, P30-AI50410];
Fogarty International Center [5U2RTW007373-03]; United States Agency for
International Development (USAID) with Right to Care (RTC)
[674-A-00-08-00007-00]
FX Support for this study was provided by the US National Institute of
Allergy and Infectious Diseases (NIAID) through the CIPRA network, grant
#U19 AI53217. The project described was also supported by K01AI083097
and P30-AI50410 from the NIAID and 5U2RTW007373-03 from the Fogarty
International Center and was also provided by the United States Agency
for International Development (USAID) under the terms of agreement
674-A-00-08-00007-00 with Right to Care (RTC). The content of this
publication does not necessarily reflect the views or policies of NIAID,
the Fogarty Center, USAID or RTC nor does mention of trade names,
commercial projects or organizations imply endorsement by the US
Government. The content is solely the responsibility of the authors and
does not necessarily represent the official views of the NIAID, the
Fogarty Center, the National Institutes of Health, USAID or other
parties.
NR 30
TC 32
Z9 33
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD AUG 24
PY 2010
VL 24
IS 13
BP 2041
EP 2050
DI 10.1097/QAD.0b013e32833c703e
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 634BY
UT WOS:000280555200008
PM 20613459
ER
PT J
AU Wimalasena, DS
Janowiak, BE
Lovell, S
Miyagi, M
Sun, JJ
Zhou, HY
Hajduch, J
Pooput, C
Kirk, KL
Battaile, KP
Bann, JG
AF Wimalasena, D. Shyamali
Janowiak, Blythe E.
Lovell, Scott
Miyagi, Masaru
Sun, Jianjun
Zhou, Haiying
Hajduch, Jan
Pooput, Chaya
Kirk, Kenneth L.
Battaile, Kevin P.
Bann, James G.
TI Evidence That Histidine Protonation of Receptor-Bound Anthrax Protective
Antigen Is a Trigger for Pore Formation
SO BIOCHEMISTRY
LA English
DT Article
ID TOXIN RECEPTOR; PROTEIN TRANSLOCATION; CRYSTAL-STRUCTURE;
BINDING-ENERGY; RESIDUES; LETHAL; CHANNEL; INTERNALIZATION;
IDENTIFICATION; MUTATIONS
AB The protective antigen (PA) component or the anthrax toxin forms pores within the low pH environment of host endosomes through mechanisms that are poorly understood. It has been proposed that pore formation is dependent on histidine protonation. In previous work, we biosynthetically incorporated 2-fluorohistidine (2-FHis), an isosteric analogue of histidine with a significantly reduced pK(a) (similar to 1), into PA and showed that the pH-dependent conversion from the soluble prepore to a pore was unchanged. However, we also observed that 2-FHisPA was nonfunctional in the ability to mediate cytotoxicity of CHO-K1 cells by LF(N)-DTA and was defective in translocation through planar lipid bilayers. Here, we show that the defect in cytotoxicity is due to both a defect in translocation and, when bound to the host cellular receptor, an inability to undergo low pH-induced pore formation. Combining X-ray crystallography with hydrogen deuterium (H-D) exchange mass spectrometry, our studies lead to a model in which hydrogen bonds to the histidine ring are strengthened by receptor binding. The combination of both fluorination and receptor binding is sufficient to block low pH-induced pore formation.
C1 [Wimalasena, D. Shyamali; Zhou, Haiying; Bann, James G.] Wichita State Univ, Dept Chem, Wichita, KS 67260 USA.
[Janowiak, Blythe E.; Sun, Jianjun] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
[Lovell, Scott] Univ Kansas, Del Shankel Struct Biol Ctr, Lawrence, KS 66047 USA.
[Miyagi, Masaru] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Dept Pharmacol, Case Ctr Prote & Bioinformat, Cleveland, OH 44106 USA.
[Hajduch, Jan; Pooput, Chaya; Kirk, Kenneth L.] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Battaile, Kevin P.] Argonne Natl Lab, Adv Photon Source, IMCA CAT, Argonne, IL 60439 USA.
RP Bann, JG (reprint author), Wichita State Univ, Dept Chem, Wichita, KS 67260 USA.
EM Jim.Bann@wichita.edu
RI Zhou, Haiying/N-4092-2014;
OI Battaile, Kevin/0000-0003-0833-3259
FU NIH [5P20 RR17708, R01 AI022021, IF32 AI077280]; Cleveland Foundation;
NIDDK, NIH; University of Chicago; U.S. Department of Energy, Office of
Science, Office of Basic Energy Sciences [W-31-109-Eng-38]
FX This work supported by NIH 5P20 RR17708 (J.G.B. and S.L.), NIH R01
AI022021 to R. John Collier (financial support to B.E.J. and J.S.), NIH
IF32 AI077280 (B.E.J.), Cleveland Foundation (M.M.), and intramural
research funds from the NIDDK, NIH (K.L.K.). Use of the IMCA-CAT
beamline 17-BM at the Advanced Photon Source was supported by the
companies of the Industrial Macromolecular Crystallography Association
through a contract with the Center for Advanced Radiation Sources at the
University of Chicago. Use of the Advanced Photon Source was supported
by the U.S. Department of Energy, Office of Science, Office of Basic
Energy Sciences, under Contract W-31-109-Eng-38.
NR 54
TC 16
Z9 16
U1 1
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD AUG 24
PY 2010
VL 49
IS 33
BP 6973
EP 6983
DI 10.1021/bi100647z
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 637YS
UT WOS:000280855200001
PM 20672855
ER
PT J
AU Kotova, S
Vijayasarathy, C
Dimitriadis, EK
Ikonomou, L
Jaffe, H
Sieving, PA
AF Kotova, Svetlana
Vijayasarathy, Camasamudram
Dimitriadis, Emilios K.
Ikonomou, Laertis
Jaffe, Howard
Sieving, Paul A.
TI Retinoschisin (RS1) Interacts with Negatively Charged Lipid Bilayers in
the Presence of Ca2+: An Atomic Force Microscopy Study
SO BIOCHEMISTRY
LA English
DT Article
ID X-LINKED RETINOSCHISIS; MEMBRANE DOMAINS; BIPOLAR CELLS; MOUSE MODEL;
BINDING; PROTEIN; GENE; EXPRESSION; PHOTORECEPTOR; KNOCKOUT
AB Retinoschisin (RS1) is a retina-specific secreted protein encoding a conserved discoidin domain sequence. As an adhesion molecule, RS1 preserves the retinal cell architecture and promotes visual signal transduction. In young males, loss-of-function mutations in the X-linked retinoschisis gene (RS1) cause X-linked retinoschisis, a form of progressive blindness. Neither the structure of RS1 nor the nature of its anchoring and organization on the plasma membranes is fully understood. The discoidin C2 domains of coagulation factors V and VIII are known to interact with extracellular phosphatidylserine (PS). In this study we have used atomic force microscopy (AFM) to study the interactions of murine retinoschisin (Rs1) with supported anionic lipid bilayers in the presence of Ca2+. The bilayers consisting of a single lipid, PS, and mixtures of lipids with or without PS were used. Consistent with previous X-ray diffraction studies, ANA imaging showed two distinct domains in pure PS bilayers when Ca2+ was present. Upon Rs1 adsorption, these PS and PS-containing mixed bilayers underwent fast and extensive reorganization. Protein localization was ascertained by immunolabeling. AFM imaging showed the Rs1 antibody bound exclusively to the calcium-rich ordered phase of the bilayers pointing lathe sequestration of Rs1 within those domains. This was further supported by the increased mechanical strength of these domains after Rs1 binding. Besides, changes in bilayer thickness suggested that Rs1 was partially embedded into the bilayer. These findings support a model whereby the Rs1 protein binds to PS in the retinal cell plasma membranes in a calcium-dependent manner.
C1 [Kotova, Svetlana; Dimitriadis, Emilios K.] Natl Inst Biomed Imaging & Bioengn, LBPS, NIH, Bethesda, MD 20892 USA.
[Vijayasarathy, Camasamudram] Natl Inst Deafness & Other Commun Disorders, STRRMD, NIH, Bethesda, MD 20892 USA.
[Ikonomou, Laertis] NIDDKD, CEB RHAS, NIH, Bethesda, MD 20892 USA.
[Jaffe, Howard] NINDS, NIH, Bethesda, MD 20892 USA.
[Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA.
RP Dimitriadis, EK (reprint author), Natl Inst Biomed Imaging & Bioengn, LBPS, NIH, Bethesda, MD 20892 USA.
EM dimitria@helix.nih.gov; paulsieving@nei.nih.gov
RI Ikonomou, Laertis/D-4579-2009
OI Ikonomou, Laertis/0000-0003-0993-6713
FU National Eye Institute; National Institute of Biomedical Imaging and
Bioengineering; National Institute on Deafness and Other Communication
Disorders, at the National Institutes of Health
FX This work was supported by the Intramural Programs of the National Eye
Institute, National Institute of Biomedical Imaging and Bioengineering,
and the National Institute on Deafness and Other Communication
Disorders, at the National Institutes of Health.
NR 33
TC 9
Z9 9
U1 2
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD AUG 24
PY 2010
VL 49
IS 33
BP 7023
EP 7032
DI 10.1021/bi1007029
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 637YS
UT WOS:000280855200006
PM 20677810
ER
PT J
AU Wright, JM
Hoffman, CS
Savitz, DA
AF Wright, J. Michael
Hoffman, Caroline S.
Savitz, David A.
TI The relationship between water intake and foetal growth and preterm
delivery in a prospective cohort study
SO BMC PREGNANCY AND CHILDBIRTH
LA English
DT Article
ID DISINFECTION BY-PRODUCTS; DRINKING-WATER; BIRTH-WEIGHT;
SPONTANEOUS-ABORTION; GESTATIONAL-AGE; EARLY-PREGNANCY; UNITED-STATES;
EXPOSURE; POPULATION; DURATION
AB Background: Interpretation of previous associations between water intake and adverse birth outcomes is challenging given that amount and type of water consumed can be non-specific markers of exposure or underlying behavioural characteristics. We examined the relationship between water intake measures and adverse birth outcomes in participants from three study sites in the United States.
Methods: Using a prospective cohort study, we examined daily intake of bottled, cold tap, total tap, and total water in relation to birth weight and risk of small-for-gestational-age (SGA) among term births and risk of preterm delivery.
Results: Based on water consumption data collected between 20-24 weeks of gestation, the adjusted mean birth weight was 27 (95% confidence interval [CI]: -34, 87), 39 (95% CI: -22, 99), and 50 (95% CI: -11, 110) grams higher for the upper three total water intake quartiles (> 51-78, > 78-114, and > 114 ounces/day) compared to the lowest quartile (<= 51 ounces/day). Adjusted birth weight results were similar for bottled water, cold tap water, and total tap water intake. An exposure-response gradient was not detected for either preterm delivery or SGA with increasing total water intake and total tap water intake, but adjusted relative risks for all three upper quartiles were below 1.0 (range: 0.6-0.9) for SGA.
Conclusion: These data suggest that high water intake may be associated with higher mean birth weight following adjustment for confounding.
C1 [Wright, J. Michael] US EPA, Natl Ctr Environm Assessment, Cincinnati, OH 45268 USA.
[Hoffman, Caroline S.] Natl Inst Environm Hlth Sci, Div Extramural Res & Training, Res Triangle Pk, NC USA.
[Savitz, David A.] Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY USA.
RP Wright, JM (reprint author), US EPA, Natl Ctr Environm Assessment, Cincinnati, OH 45268 USA.
EM wright.michael@epa.gov
FU AWWA Research Foundation [2579, CR825625-01, CR827268-01, CR828216-01];
US Environmental Protection Agency (USEPA) [CR825625-01, CR827268-01,
CR828216-01]; Center for Environmental Health and Susceptibility (CEHS)
at the University of North Carolina at Chapel Hill [P30E510126]; US EPA
[RD-83184301-0]; National Institute of Environmental Health Sciences
[5-T32-ES07018]; NHEERL-DESE [EPA CT8229471, CR83323601]
FX Supported jointly by the AWWA Research Foundation (AwwaRF: Project 2579)
and the US Environmental Protection Agency (USEPA) under Cooperative
Agreement nos. CR825625-01, CR827268-01, and CR828216-01, the Center for
Environmental Health and Susceptibility (CEHS) at the University of
North Carolina at Chapel Hill (P30E510126), US EPA STAR award
RD-83184301-0, the Biostatistics for Research in Environmental Health
training award of the National Institute of Environmental Health
Sciences (5-T32-ES07018), and the NHEERL-DESE cooperative training grant
in Environmental Sciences Research (EPA CT8229471 and CR83323601).
NR 22
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 1471-2393
J9 BMC PREGNANCY CHILDB
JI BMC Pregnancy Childbirth
PD AUG 24
PY 2010
VL 10
AR 48
DI 10.1186/1471-2393-10-48
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 840MB
UT WOS:000296443500001
PM 20735835
ER
PT J
AU Lee, KM
Chapman, RS
Shen, M
Lubin, JH
Silverman, DT
He, X
Hosgood, HD
Chen, BE
Rajaraman, P
Caporaso, NE
Fraumeni, JF
Blair, A
Lan, Q
AF Lee, K-M
Chapman, R. S.
Shen, M.
Lubin, J. H.
Silverman, D. T.
He, X.
Hosgood, H. D., III
Chen, B. E.
Rajaraman, P.
Caporaso, N. E.
Fraumeni, J. F., Jr.
Blair, A.
Lan, Q.
TI Differential effects of smoking on lung cancer mortality before and
after household stove improvement in Xuanwei, China
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE smoky coal; smoking; lung cancer; mortality; Xuanwei cohort;
time-dependent variable
ID COMBUSTION EMISSIONS; GUATEMALAN WOMEN; AIR-POLLUTION; INDOOR COAL;
RISK; WEI; EXPOSURE; INTERVENTION; RATS
AB BACKGROUND: In Xuanwei County, Yunnan Province, China, lung cancer mortality rates in both males and females are among the highest in China.
METHODS: We evaluated differential effects of smoking on lung cancer mortality before and after household stove improvement with chimney to reduce exposure to smoky coal emissions in the unique cohort in Xuanwei, China. Effects of independent variables on lung cancer mortality were measured as hazard ratios and 95% confidence intervals using a multivariable Cox regression model that included separate time-dependent variables for smoking duration (years) before and after stove improvement.
RESULTS AND CONCLUSION: We found that the effect of smoking on lung cancer risk becomes considerably stronger after chimney installation and consequent reduction of indoor coal smoke exposure. British Journal of Cancer (2010) 103, 727-729. doi:10.1038/sj.bjc.6605791 www.bjcancer.com Published online 20 July 2010 (C) 2010 Cancer Research UK
C1 [Lee, K-M; Shen, M.; Lubin, J. H.; Silverman, D. T.; Hosgood, H. D., III; Rajaraman, P.; Caporaso, N. E.; Fraumeni, J. F., Jr.; Blair, A.; Lan, Q.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Chapman, R. S.] Chulalongkorn Univ, Coll Publ Hlth Sci, Bangkok, Thailand.
[He, X.] Chinese Acad Prevent Med, Inst Environm Hlth & Engn, Beijing, Peoples R China.
[Hosgood, H. D., III] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
[Chen, B. E.] Queens Univ, Dept Epidemiol & Community Hlth, Kingston, ON, Canada.
RP Lee, KM (reprint author), Seoul Natl Univ, Coll Med, Clin Res Inst, Dept Prevent Med, Seoul, South Korea.
EM kmlee92@snu.ac.kr
FU Chinese Academy of Preventive Medicine, Beijing, China; Yunnan Province
Antiepidemic Station, Kunming, China; US Environmental Protection Agency
[5D2290NFFX]; NIH, Division of Cancer Epidemiology and Genetics,
National Cancer Institute
FX This study were supported by the Chinese Academy of Preventive Medicine,
Beijing, China; Yunnan Province Antiepidemic Station, Kunming, China; US
Environmental Protection Agency (contract No 5D2290NFFX); and Intramural
Research Programme of the NIH, Division of Cancer Epidemiology and
Genetics, National Cancer Institute.
NR 15
TC 14
Z9 15
U1 1
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD AUG 24
PY 2010
VL 103
IS 5
BP 727
EP 729
DI 10.1038/sj.bjc.6605791
PG 3
WC Oncology
SC Oncology
GA 643IB
UT WOS:000281287700018
PM 20648014
ER
PT J
AU Gudmundsson, LS
Scher, AI
Aspelund, T
Eliasson, JH
Johannsson, M
Thorgeirsson, G
Launer, L
Gudnason, V
AF Gudmundsson, Larus S.
Scher, Ann I.
Aspelund, Thor
Eliasson, Jon H.
Johannsson, Magnus
Thorgeirsson, Gudmundur
Launer, Lenore
Gudnason, Vilmundur
TI Migraine with aura and risk of cardiovascular and all cause mortality in
men and women: prospective cohort study
SO BRITISH MEDICAL JOURNAL
LA English
DT Article
ID ENDOTHELIAL PROGENITOR CELLS; MYOCARDIAL-INFARCTION; BLOOD-PRESSURE;
DISEASE; STROKE; REYKJAVIK; HEADACHE; PROJECT; PREVALENCE; RESIDUALS
AB Objective To estimate whether migraine in mid-life is associated with mortality from cardiovascular disease, other causes, and all causes.
Design Population based cohort study.
Setting Reykjavik, Iceland.
Participants 18 725 men and women, born 1907-35 and living in Reykjavik and adjacent communities.
Main outcome measures Mortality from cardiovascular disease, non-cardiovascular disease, and all causes. Questionnaires and clinical measures were obtained in mid-life (mean age 53, range 33-81) in the Reykjavik Study (1967-91). Headache was classified as migraine without aura, migraine with aura, or non-migraine headache. Median follow-up was 25.9 years (0.1-40. 2 years), with 470 990 person years and 10 358 deaths: 4323 from cardiovascular disease and 6035 from other causes. We used Cox regression to estimate risk of death in those with migraine compared with others, after adjusting for baseline risk factors.
Results People with migraine with aura were at increased risk of all cause mortality (adjusted (for sex and multivariables) hazard ratio 1.21, 95% confidence interval 1.12 to 1.30) and mortality from cardiovascular disease (1.27, 1.13 to 1.43) compared with people with no headache, while those with migraine without aura and non-migraine headache were not. Further examination of mortality from cardiovascular disease shows that people with migraine with aura were at increased risk of mortality from coronary heart disease (1.28, 1.11 to 1.49) and stroke (1.40, 1.10 to 1.78). Women with migraine with aura were also at increased risk of mortality from non-cardiovascular disease (1.19, 1.06 to 1.35).
Conclusions Migraine with aura is an independent risk factor for cardiovascular and all cause mortality in men and women. The risk of mortality from coronary heart disease and stroke mortality is modestly increased in people with migraine, particularly those with aura.
C1 [Gudmundsson, Larus S.; Johannsson, Magnus] Univ Iceland, Dept Pharmacol & Toxicol, IS-107 Reykjavik, Iceland.
[Scher, Ann I.] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD USA.
[Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, IS-201 Kopavogur, Iceland.
[Aspelund, Thor; Thorgeirsson, Gudmundur; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Eliasson, Jon H.] Reykjalundur Rehabil Ctr, Mosfellsbaer, Iceland.
[Thorgeirsson, Gudmundur] Landspitali Univ Hosp, Reykjavik, Iceland.
[Launer, Lenore] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RP Gudmundsson, LS (reprint author), Univ Iceland, Dept Pharmacol & Toxicol, Hagi Hofsvallagata 53, IS-107 Reykjavik, Iceland.
EM lsg@hi.is; v.gudnason@hjarta.is
RI Aspelund, Thor/F-4826-2011; Aspelund, Thor/C-5983-2008; Gudnason,
Vilmundur/K-6885-2015
OI Aspelund, Thor/0000-0002-7998-5433; Gudnason,
Vilmundur/0000-0001-5696-0084
FU University of Iceland; Pharmaceutical Society of Iceland; National
Headache Foundation; American Headache Society
FX This study was funded by the University of Iceland Research Fund. The
current study was conducted without any influence from the University of
Iceland Research Fund.; All authors have completed the Unified Competing
Interest form at www.icmje.org/coi_disclosure.pdf (available on request
from the corresponding author) and declare that no company has supported
the submitted work; LSG has received a travel grant from the
Pharmaceutical Society of Iceland Science Fund, AIS has served on
advisory boards for Endo Pharmaceuticals and OrthoMcNeil Neurologics,
has received an honorarium and a travel grant from the National Headache
Foundation and a travel grant from the American Headache Society; no
other relationships or activities that could appear to have influenced
the submitted work.
NR 42
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U1 1
U2 7
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0959-535X
J9 BRIT MED J
JI Br. Med. J.
PD AUG 24
PY 2010
VL 341
AR c3966
DI 10.1136/bmj.c3966
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 645IG
UT WOS:000281445900003
PM 20736269
ER
PT J
AU Miller, MA
Ulisney, K
Baldwin, JT
AF Miller, Marissa A.
Ulisney, Karen
Baldwin, J. Timothy
TI INTERMACS (Interagency Registry for Mechanically Assisted Circulatory
Support): A New Paradigm for Translating Registry Data Into Clinical
Practice
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT News Item
DE Centers for Medicare and Medicaid Services; Food and Drug
Administration; National Heart, Lung, and Blood Institute; heart
failure; mechanical circulatory support; randomized clinical trial;
registry; transplant; ventricular assist device
ID ADVANCED HEART-FAILURE; INTERVAL-ANALYSIS; BLOOD INSTITUTE; NATIONAL
HEART; DEVICE; THERAPY; LUNG
C1 [Miller, Marissa A.] NHLBI, Adv Technol & Surg Branch, Div Cardiovasc Sci DCVS, Bethesda, MD 20892 USA.
RP Miller, MA (reprint author), NHLBI, Adv Technol & Surg Branch, Div Cardiovasc Sci DCVS, 6701 Rockledge Dr,Room 8214,MSC 7940, Bethesda, MD 20892 USA.
EM millerma2@nhlbi.nih.gov
NR 17
TC 13
Z9 13
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD AUG 24
PY 2010
VL 56
IS 9
BP 738
EP 740
DI 10.1016/j.jacc.2010.05.021
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 639UI
UT WOS:000280999600010
PM 20723804
ER
PT J
AU Paaijmans, KP
Blanford, S
Bell, AS
Blanford, JI
Read, AF
Thomas, MB
AF Paaijmans, Krijn P.
Blanford, Simon
Bell, Andrew S.
Blanford, Justine I.
Read, Andrew F.
Thomas, Matthew B.
TI Influence of climate on malaria transmission depends on daily
temperature variation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE Anopheles mosquitoes; climate change; diurnal temperature variability;
ectotherms; Plasmodium malaria
ID EAST-AFRICAN HIGHLANDS; INFECTIOUS-DISEASES; GLOBAL CLIMATE; PLASMODIUM;
RISK; ANOPHELES; VECTOR; TERRESTRIAL; RESURGENCE; IMPACTS
AB Malaria transmission is strongly influenced by environmental temperature, but the biological drivers remain poorly quantified. Most studies analyzing malaria-temperature relations, including those investigating malaria risk and the possible impacts of climate change, are based solely on mean temperatures and extrapolate from functions determined under unrealistic laboratory conditions. Here, we present empirical evidence to show that, in addition to mean temperatures, daily fluctuations in temperature affect parasite infection, the rate of parasite development, and the essential elements of mosquito biology that combine to determine malaria transmission intensity. In general, we find that, compared with rates at equivalent constant mean temperatures, temperature fluctuation around low mean temperatures acts to speed up rate processes, whereas fluctuation around high mean temperatures acts to slow processes down. At the extremes (conditions representative of the fringes of malaria transmission, where range expansions or contractions will occur), fluctuation makes transmission possible at lower mean temperatures than currently predicted and can potentially block transmission at higher mean temperatures. If we are to optimize control efforts and develop appropriate adaptation or mitigation strategies for future climates, we need to incorporate into predictive models the effects of daily temperature variation and how that variation is altered by climate change.
C1 [Paaijmans, Krijn P.; Blanford, Simon; Read, Andrew F.; Thomas, Matthew B.] Penn State Univ, Dept Entomol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Blanford, Simon; Bell, Andrew S.; Read, Andrew F.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Blanford, Justine I.] Penn State Univ, Dept Geog, University Pk, PA 16802 USA.
[Blanford, Justine I.] Penn State Univ, GeoVISTA Ctr, University Pk, PA 16802 USA.
[Read, Andrew F.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Thomas, MB (reprint author), Penn State Univ, Dept Entomol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
EM mbt13@psu.edu
FU Netherlands Organisation for Scientific Research
FX We thank B. Chan, K. Glunt, S. Huijben, and D. Kroczynski for their
assistance during experiments. This study benefited from discussions in
working groups of the Research and Policy for Infectious Disease
Dynamics (RAPIDD) program of the Science and Technology Directorate,
Department of Homeland Security, and the Fogarty International Center,
National Institutes of Health, and was supported by a Netherlands
Organisation for Scientific Research grant to K. P. P., a grant with the
Pennsylvania Department of Health using Tobacco Settlement Funds, and a
National Science Foundation EID program grant (EF-0914384).
NR 37
TC 157
Z9 165
U1 13
U2 116
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 AUG 24
PY 2010
VL 107
IS 34
BP 15135
EP 15139
DI 10.1073/pnas.1006422107
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 643PT
UT WOS:000281311500037
PM 20696913
ER
PT J
AU Adams, KM
Kaczmarek, P
Keay, SK
Barchi, JJ
AF Adams, Kristie M.
Kaczmarek, Piotr
Keay, Susan K.
Barchi, Joseph J., Jr.
TI NMR spectroscopic studies of APF: A small glycopeptide possessing potent
antiproliferative activity
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 NCI, Biol Chem Lab, Frederick, MD 21701 USA.
Univ Maryland, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21201 USA.
Vet Affairs Maryland Hlth Care Syst, Res Serv, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 107-CARB
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164700767
ER
PT J
AU Austin, C
AF Austin, Christopher
TI New ecology of collaborative pharmaceutical research
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Austin, Christopher] NIH, NIH Chem Genom Ctr, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 9-BMGT
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164700757
ER
PT J
AU Austin, CP
AF Austin, Christopher P.
TI Chemical genomics: How do we combat disease
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Austin, Christopher P.] NIH Chem Genom Ctr, Dept Chem, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 6-SCHB
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164707221
ER
PT J
AU Barchi, JJ
Brinas, R
Sundgren, A
Sahoo, P
Houghten, A
Morey, S
Sanford, M
Young, H
AF Barchi, Joseph John, Jr.
Brinas, Ray
Sundgren, Andreas
Sahoo, Padmini
Houghten, Amy
Morey, Susan
Sanford, Michael
Young, Howard
TI New glycopeptide-based nanoparticle constructions for anticancer therapy
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 NCI, Frederick, MD 21701 USA.
SUNY Buffalo, Biotech & Clin Lab Sci, Buffalo, NY 14260 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 26-CARB
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164700808
ER
PT J
AU Belanger, JM
Raviv, Y
Viard, M
Bess, JW
Blumenthal, R
AF Belanger, Julie M.
Raviv, Yossef
Viard, Mathias
Bess, Julian W., Jr.
Blumenthal, Robert
TI Insights and applications of using various aryl-azido compounds for the
inactivation of human immunodeficiency virus (HIV-1): Towards the
generation of a novel inactivated vaccine strategy
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA.
NCI, Basic Res Program, SAIC, Frederick, MD 21701 USA.
NCI, AIDS & Canc Virus Program, SAIC, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 74-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164705326
ER
PT J
AU Belanger, JM
Raviv, Y
Viard, M
Bess, JW
Blumenthal, R
AF Belanger, Julie M.
Raviv, Yossef
Viard, Mathias
Bess, Julian W., Jr.
Blumenthal, Robert
TI Insights and applications of using various aryl-azido compounds for the
inactivation of human immunodeficiency virus (HIV-1): Towards the
generation of a novel inactivated vaccine strategy
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA.
NCI, Basic Res Program, SAIC, Frederick, MD 21701 USA.
NCI, AIDS & Canc Virus Program, SAIC, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 8-AEI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164700064
ER
PT J
AU Birnbaum, LS
AF Birnbaum, Linda S.
TI NIEHS Director's Perspective: Opportunities and Challenges
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Birnbaum, Linda S.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 141-TOXI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164707264
ER
PT J
AU Biswas, D
DeRosa, F
Kibbe, M
Citro, ML
Keefer, LK
Hrabie, JA
AF Biswas, Debanjan
DeRosa, Frank
Kibbe, Melina
Citro, Michael L.
Keefer, Larry K.
Hrabie, Joseph A.
TI Fundamental amidine diazeniumdiolate chemistry: Applications in the
bio-medical realm
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 Natl Canc Inst Frederick, Comparat Carcinogenesis Lab, Frederick, MD USA.
Northwestern Univ, Div Vasc Surg, Chicago, IL 60611 USA.
Natl Canc Inst Frederick, Basic Sci Program, SAIC Frederick, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 659-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164705255
ER
PT J
AU Brinas, RP
Sundgren, A
Maetani, M
Abbudayyeh, O
Young, HA
Sanford, M
Barchi, JJ
AF Brinas, Raymond P.
Sundgren, Andreas
Maetani, Micah
Abbudayyeh, Omar
Young, Howard A.
Sanford, Michael
Barchi, Joseph J.
TI Development of a novel cancer vaccine based on multivalent presentation
of tumor-associated carbohydrate antigens on gold nanoparticle scaffolds
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 NCI, Biol Chem Lab, NIH, Frederick, MD 21701 USA.
NCI, Lab Expt Biol, NIH, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 109-CARB
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164700769
ER
PT J
AU Brooks, BR
AF Brooks, Bernard R.
TI Examining methods for general multi-scale modeling using CHARMM
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 98-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164702486
ER
PT J
AU Campbell, C
Zhang, YL
Ludek, O
Farnsworth, D
Gildersleeve, J
AF Campbell, Christopher
Zhang, Yalong
Ludek, Olaf
Farnsworth, David
Gildersleeve, Jeffrey
TI High-throughput glycoarray for monitoring immune responses to a cancer
vaccine
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Campbell, Christopher; Zhang, Yalong; Ludek, Olaf; Farnsworth, David; Gildersleeve, Jeffrey] NCI, Biol Chem Lab, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 106-CARB
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164700766
ER
PT J
AU Carta, D
McGuigan, C
Vanpouille, C
Margolis, L
Balzarini, J
AF Carta, Davide
McGuigan, Christopher
Vanpouille, Christophe
Margolis, Leonid
Balzarini, Jan
TI Synthesis and evaluation of novel phosphoramidates of acyclic
nucleosides in the bypass of the first phosphorylation step mediated by
the thymidine kinase
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 Cardiff Univ, Welsh Sch Pharm, Cardiff, S Glam, Wales.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
Katholieke Univ Leuven, Rega Inst Med Res, Louvain, Belgium.
RI McGuigan, Chris/P-1580-2014
OI McGuigan, Chris/0000-0001-8409-710X
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 132-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704035
ER
PT J
AU Chatterjee, K
Lin-Gibson, S
Parekh, SH
Moore, NM
Cicerone, MT
Young, MF
Simon, CG
AF Chatterjee, Kaushik
Lin-Gibson, Sheng
Parekh, Sapun H.
Moore, Nicole M.
Cicerone, Marcus T.
Young, Marian F.
Simon, Carl G., Jr.
TI Effect of 3D hydogel scaffold modulus and topology on human bone marrow
stromal cell fate
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 NIST, Div Polymers, Gaithersburg, MD 20899 USA.
Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 359-POLY
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164706843
ER
PT J
AU Cheng, KJ
Kimura, T
Gawrisch, K
Jacobson, AE
Rice, KC
AF Cheng, Kejun
Kimura, Tomohiro
Gawrisch, Klaus
Jacobson, Arthur E.
Rice, Kenner C.
TI Synthesis of deuterated enantiomer of CP55,940, d(6)-(-)-CP55,940
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 NIDA, Chem Biol Res Branch, Bethesda, MD 20892 USA.
NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 649-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164705245
ER
PT J
AU Cheruku, P
Keffer, JL
Bewley, CA
AF Cheruku, Pradeep
Keffer, Jessica L.
Bewley, Carole A.
TI Motualevic acid analogs: Synthesis, antimicrobial activity, and
structure-activity relationship (SAR) studies
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Cheruku, Pradeep; Keffer, Jessica L.; Bewley, Carole A.] NIDDK, Dept Bioorgan Chem, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 144-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704048
ER
PT J
AU Chun, JH
Pike, VW
AF Chun, Joong-Hyun
Pike, Victor W.
TI Synthesis of functionally diverse iodonium salts via in-situ generated
[hydroxy(tosyloxy)iodo]arenes as precursors to F-18-labeling agents
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Chun, Joong-Hyun; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 1001-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704579
ER
PT J
AU Clements, GV
Boshoff, HI
Dowd, CS
AF Clements, Gail V.
Boshoff, Helena I.
Dowd, Cynthia S.
TI Design and synthesis of Mycobacterial proteasome inhibitors
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 George Washington Univ, Dept Chem, Washington, DC 20052 USA.
NIAID, TB Res Sect, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 470-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704373
ER
PT J
AU Costanzi, S
Vilar, S
Ferino, G
Phatak, SS
Berk, B
Cavasotto, CN
AF Costanzi, Stefano
Vilar, Santiago
Ferino, Giulio
Phatak, Sharangdhar S.
Berk, Barkin
Cavasotto, Claudio N.
TI Assessment and optimization of docking-based virtual screening for GPCR
ligands: Not only crystal structures but also homology models
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 Natl Inst Diabet & Digest & Kidney Dis, Lab Biol Modeling, NIH, Bethesda, MD USA.
Univ Texas Hlth Sci Ctr Houston, Sch Hlth Informat Sci, Houston, TX USA.
RI berk, barkin/P-2088-2014
NR 0
TC 0
Z9 0
U1 0
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 287-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164702296
ER
PT J
AU Deck, JA
Martin, SF
AF Deck, Jason A.
Martin, Stephen F.
TI Enantioselective synthesis of (+)-isolysergol via ring closing
metathesis
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 NIH, Drug Design & Synth Sect, Rockville, MD USA.
Univ Texas Austin, Dept Chem, Austin, TX 78712 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 505-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164705117
ER
PT J
AU Decker, AM
Blough, BE
Partilla, JS
Landavazo, A
Rothman, RB
AF Decker, Ann M.
Blough, Bruce E.
Partilla, John S.
Landavazo, Antonio
Rothman, Richard B.
TI Monoamine releasers as potential treatments for stimulant addictions
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 Res Triangle Inst Int, Dept Organ & Med Chem, Res Triangle Pk, NC USA.
NIH, Dept Hlth & Human Serv, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 352-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704255
ER
PT J
AU Deflorian, F
Szabo, A
Jacobson, KA
AF Deflorian, Francesca
Szabo, Angela
Jacobson, Kenneth A.
TI Structure-based Virtual Screening for the discovery of potential P2Y14
receptor ligands
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Deflorian, Francesca; Szabo, Angela; Jacobson, Kenneth A.] NIDDK, NIH, Bethesda, MD USA.
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 204-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704107
ER
PT J
AU Dogo-Isonagie, CI
Lam, SN
Bewley, CA
AF Dogo-Isonagie, Cajetan I.
Lam, Son N.
Bewley, Carole A.
TI Targeting Gp120's binding sites
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Dogo-Isonagie, Cajetan I.; Lam, Son N.; Bewley, Carole A.] NIDDKD, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 941-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164705516
ER
PT J
AU Egli, M
Eoff, RL
Marquez, VE
Guengerich, FP
AF Egli, Martin
Eoff, Robert L.
Marquez, Victor E.
Guengerich, F. Peter
TI Selective modulation of DNA polymerase activity by fixed-conformation
nucleoside analogs
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA.
Vanderbilt Univ, Ctr Mol Toxicol, Nashville, TN USA.
NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 76-CARB
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164700855
ER
PT J
AU Elking, DM
Perera, L
Duke, R
Pedersen, LG
AF Elking, Dennis M.
Perera, Lalith
Duke, Robert
Pedersen, Lee G.
TI Modeling molecular charge density with Gaussian multipoles
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 Univ N Carolina, Dept Chem, Chapel Hill, NC USA.
NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA.
RI perera, Lalith/B-6879-2012; Pedersen, Lee/E-3405-2013
OI perera, Lalith/0000-0003-0823-1631; Pedersen, Lee/0000-0003-1262-9861
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 34-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164702341
ER
PT J
AU Gangjee, A
Lin, L
Mooberry, SL
Hamel, E
AF Gangjee, Aleem
Lin, Lu
Mooberry, Susan L.
Hamel, Ernest
TI Discovery of substituted pyrrolo[2,3-d] pyrimidines as water soluble
antitubulin antitumor agents
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 Duquesne Univ, Div Med Chem, Grad Sch Pharmaceut Sci, Pittsburgh, PA 15219 USA.
Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA.
Natl Canc Inst Frederick, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 53-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704418
ER
PT J
AU Grodzinski, P
Farrell, D
Ptak, K
Panaro, N
AF Grodzinski, Piotr
Farrell, Dorothy
Ptak, Krzysztof
Panaro, Nicholas
TI Nanotechnology-based cancer therapeutics: View from the NCI Alliance for
Nanotechnology in Cancer
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 NCI, Off Canc Nanotechnol, Ctr Strateg Sci Initiat, NIH, Bethesda, MD 20892 USA.
SAIC Frederick Inc, Nanotechnol Characterizat Lab, Adv Technol Program, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 87-PMSE
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164706598
ER
PT J
AU Guha, R
AF Guha, Rajarshi
TI What makes a good structure activity landscape? Network metrics and
structure representations as a way of exploring activity landscapes
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Guha, Rajarshi] NIH Chem Genom Ctr, Dept Informat, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 62-CINF
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164701556
ER
PT J
AU Guha, R
AF Guha, Rajarshi
TI Data drive life sciences: The Pyramids meet the Tower of Babel
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Guha, Rajarshi] NIH, Dept Informat, Chem Genom Ctr, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 16-CINF
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164701509
ER
PT J
AU Hanover, JA
AF Hanover, John A.
TI Targeting O-GlcNAc cycling: Impact on the epigenetics of diabesity and
immunity
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Hanover, John A.] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 14-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704043
ER
PT J
AU Holland, RJ
Saavedra, JE
Keefer, LK
Maciag, AE
Chakrapani, H
AF Holland, Ryan J.
Saavedra, Joseph E.
Keefer, Larry K.
Maciag, Anna E.
Chakrapani, Harinath
TI Effect of O-2-arylated diazeniumdiolates on cellular glutathione status
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 Natl Canc Inst Frederick, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD USA.
Natl Canc Inst Frederick, Basic Res Program, SAIC Frederick, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 28-TOXI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164707276
ER
PT J
AU Horkay, F
AF Horkay, Ferenc
TI Ionic effects and self-assembly in the solution of the biopolymer
aggrecan
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Horkay, Ferenc] NICHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 257-POLY
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164706749
ER
PT J
AU Horkay, F
Horkayne-Szakaly, I
Dimitriadis, EK
Silva, C
Basser, PJ
AF Horkay, Ferenc
Horkayne-Szakaly, Iren
Dimitriadis, Emilios K.
Silva, Candida
Basser, Peter J.
TI Depth dependent swelling and mechanical behavior of cartilage
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 NIH, Sect Tissue Biophys & Biomimet, Bethesda, MD 20892 USA.
NIBIB, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA.
RI Basser, Peter/H-5477-2011
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 481-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704383
ER
PT J
AU Hummer, G
Rasaiah, JC
Yin, H
Feng, GG
AF Hummer, Gerhard
Rasaiah, Jayendran C.
Yin, Hao
Feng, Guogang
TI Molecular dynamics studies of water-protein interactions
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 NIH, Chem Phys Lab, Bethesda, MD 20892 USA.
Univ Maine, Dept Chem, Orono, ME 04469 USA.
RI Hummer, Gerhard/A-2546-2013
OI Hummer, Gerhard/0000-0001-7768-746X
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 217-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164702231
ER
PT J
AU Hurley, JH
AF Hurley, James H.
TI Membrane trafficking complexes of the ESCRT pathway
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Hurley, James H.] NIDDK, Dept Struct Biol & Cell Signaling Sect HNK6CB, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 15-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704053
ER
PT J
AU Jackson, ER
Kehn-Hall, K
Kashanchi, F
Boshoff, HI
Dowd, CS
AF Jackson, Emily R.
Kehn-Hall, Kylene
Kashanchi, Fatah
Boshoff, Helena I.
Dowd, Cynthia S.
TI Small molecules to target Mycobacterium tuberculosis
1-Deoxy-D-xylulose-5-phosphate reducto-isomerase (MtbDxr)
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 George Washington Univ, Dept Chem, Washington, DC 20052 USA.
George Mason Univ, Dept Mol & Microbiol, Manassas, VA USA.
NIAID, Dept TB Res Sect, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 141-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704045
ER
PT J
AU Jacobson, KA
AF Jacobson, Kenneth A.
TI New frontiers for selective agonists and antagonists of adenosine and
P2Y receptors
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Jacobson, Kenneth A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 17-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704074
ER
PT J
AU Jose, GS
Kehn-Hall, K
Kashanchi, F
Boshoff, HI
Dowd, CS
AF Jose, Geraldine San
Kehn-Hall, Kylene
Kashanchi, Fatah
Boshoff, Helena I.
Dowd, Cynthia S.
TI Synthesis of small molecule inhibitors of Mtb Dxr from Mycobacterium
tuberculosis
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 George Washington Univ, Dept Chem, Washington, DC 20052 USA.
George Mason Univ, Dept Mol & Microbiol, Manassas, VA USA.
NIAID, Dept TB Res Sect, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 374-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704276
ER
PT J
AU Jun, JH
Dexheimer, TS
Weidlich, IE
Nicklaus, MC
Pommier, Y
Malhotra, SV
AF Jun, Jung Ho
Dexheimer, Thomas S.
Weidlich, Iwona E.
Nicklaus, Marc C.
Pommier, Yves
Malhotra, Sanjay V.
TI Sulfamide based inhibitors of tyrosyl-DNA phosphodiesterase 1 (Tdp1)
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 NCI, Lab Synthet Chem SAIC, Frederick, MD 21701 USA.
NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH,DHHS, Frederick, MD 21701 USA.
NCI, Biol Chem Lab, Ctr Canc Res, NIH,DHHS, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 666-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164705261
ER
PT J
AU Keefer, L
AF Keefer, Larry
TI Nitric oxide-based drug development
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Keefer, Larry] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 140-TOXI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164707263
ER
PT J
AU Kim, SW
Hooker, JM
Alexoff, D
Otto, N
Win, K
Volkow, N
Fowler, JS
AF Kim, Sung Won
Hooker, Jacob M.
Alexoff, David
Otto, Nicola
Win, Khaing
Volkow, Nora
Fowler, Joanna S.
TI Synthesis and positron emission tomography studies of three C-11 labeled
carboxylic acid drugs, [C-11]butyric acid, [C-11]valporic acid,
[C-11]4-phenylbutyric acid
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 NIAAA, Lab Neuroimaging, Upton, NY USA.
Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 114-NUCL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704477
ER
PT J
AU Kiselev, E
Dexhemier, T
Pommier, Y
Cushman, M
AF Kiselev, Evgeny
Dexhemier, Thomas
Pommier, Yves
Cushman, Mark
TI Design, synthesis and evaluation of dibenzo[c,h][1,6]naphthyridines as
Top1 inhibitors and potential anticancer agents
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA.
Purdue Univ, Purdue Ctr Canc Res, W Lafayette, IN 47907 USA.
NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 62-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704427
ER
PT J
AU Kosturko, GW
Bulut, G
Rodriguez, V
Glasgow, E
Hong, SH
Khanna, C
Brown, M
Paige, M
Uren, A
AF Kosturko, George W.
Bulut, Gulay
Rodriguez, Veronica
Glasgow, Eric
Hong, Sung-Hyeok
Khanna, Chand
Brown, Milton
Paige, Mikell
Ueren, Aykut
TI Design and synthesis of ezrin inhibitors for metastatic osteosarcoma
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20007 USA.
NCI, Dept Pediat Oncol, NIH, Bethesda, MD 20892 USA.
Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Dept Drug Discovery, Washington, DC 20007 USA.
RI BULUT, GULAY/J-3180-2012
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 63-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704428
ER
PT J
AU Kumar, V
Talisman, IJ
Malhotra, SV
AF Kumar, Vineet
Talisman, Ian Jamie
Malhotra, Sanjay V.
TI Dual role of ionic liquids as phase transfer catalysts and solvents for
O-glycosidation reactions
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Kumar, Vineet; Talisman, Ian Jamie; Malhotra, Sanjay V.] NCI, Lab Synthet Chem, SAIC Frederick Inc, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 994-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164705565
ER
PT J
AU Kumar, V
Talisman, IJ
Malhotra, SV
AF Kumar, Vineet
Talisman, Ian Jamie
Malhotra, Sanjay V.
TI Application of in situ silver-imidazolylidene complexes in ionic liquid
mediated glycosidation reactions
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Kumar, Vineet; Talisman, Ian Jamie; Malhotra, Sanjay V.] NCI, Lab Synthet Chem, SAIC Frederick Inc, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 993-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164705564
ER
PT J
AU Larkin, JD
Fossey, JS
James, TD
Brooks, BR
Bock, CW
AF Larkin, Joseph D.
Fossey, John S.
James, Tony D.
Brooks, Bernard R.
Bock, Charles W.
TI Computational investigation of the Nitrogen-Boron interaction in o-(N,
N-dialkylaminomethyl)arylboronate systems
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 NHLBI, NIH, Bethesda, MD 20892 USA.
Univ Birmingham, Sch Chem, Birmingham B15 2TT, W Midlands, England.
Univ Bath, Dept Chem, Bath BA2 7AY, Avon, England.
Philadelphia Univ, Sch Sci & Hlth, Dept Chem & Biochem, Philadelphia, PA USA.
Fox Chase Canc Ctr, Inst Canc Res, Philadelphia, PA 19111 USA.
RI James, Tony/B-5125-2009; Fossey, John/C-3172-2009
OI James, Tony/0000-0002-4095-2191; Fossey, John/0000-0002-2626-5117
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 300-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164702309
ER
PT J
AU Liu, F
Chen, X
Allali-Hassani, A
Quinn, AM
Wigle, TJ
Barsyte, D
Yost, JM
Wasney, GA
Dong, AP
Kozieradzki, I
Senisterra, G
Chau, I
Siarheyeva, A
Van Deusen, A
Kireev, DB
Jadhav, A
Herold, M
Frye, SV
Arrowsmith, CH
Janzen, WP
Brown, PJ
Simeonov, A
Vedadi, M
Jin, J
AF Liu, Feng
Chen, Xin
Allali-Hassani, Abdellah
Quinn, Amy M.
Wigle, Timothy J.
Barsyte, Dalia
Yost, Julianne M.
Wasney, Gregory A.
Dong, Aiping
Kozieradzki, Ivona
Senisterra, Guillermo
Chau, Irene
Siarheyeva, Alena
Van Deusen, Amy
Kireev, Dmitri B.
Jadhav, Ajit
Herold, Martin
Frye, Stephen V.
Arrowsmith, Cheryl H.
Janzen, William P.
Brown, Peter J.
Simeonov, Anton
Vedadi, Masoud
Jin, Jian
TI Discovery of chemical probes for protein lysine methyltransferase G9a
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 Univ N Carolina, Ctr Integrated Chem Biol & Drug Discovery, Chapel Hill, NC USA.
Univ Toronto, Struct Genom Consortium, Toronto, ON, Canada.
NHGRI, NIH Chem Genom Ctr, Bethesda, MD 20892 USA.
RI Kireev, Dmitri/B-7225-2012
OI Kireev, Dmitri/0000-0001-8479-8555
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 316-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704218
ER
PT J
AU Liu, J
Nussinov, R
AF Liu, Jin
Nussinov, Ruth
TI Conformational control of ubiquitination in the cullin-RING E3 ligase
machinery: A molecular dynamics study
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Liu, Jin; Nussinov, Ruth] NCI, Ctr Canc Res, SAIC Frederick Inc, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 612-PHYS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164706224
ER
PT J
AU Lucas, HR
George, SD
Lee, JC
AF Lucas, Heather R.
George, Serena Debeer
Lee, Jennifer C.
TI Insights into copper coordination and copper-dioxygen reactivity of
a-synuclein
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY USA.
RI DeBeer, Serena/G-6718-2012
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 172-PHYS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164705712
ER
PT J
AU Malhotra, R
Patel, V
Gutkind, JS
Rusling, JF
AF Malhotra, Ruchika
Patel, Vyomesh
Gutkind, J. Silvio
Rusling, James F.
TI Measurement of four cancer biomarker proteins in oral cancer using
nanoparticle-based immunoelectrochemical arrays
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 Univ Connecticut, Dept Chem, Storrs, CT USA.
Univ Connecticut, Inst Mat Sci, Storrs, CT USA.
Univ Connecticut, Dept Cell Biol, Ctr Hlth, Storrs, CT USA.
Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
RI Gutkind, J. Silvio/A-1053-2009
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 291-ANYL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164700440
ER
PT J
AU Memarzadeh, F
AF Memarzadeh, Farhad
TI Beyond ANSI/ASHRAE 110: Factoring turbulent intensity into the chemical
fume hood test protocol
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Memarzadeh, Farhad] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 5-CHAS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164701131
ER
PT J
AU Milne, GW
AF Milne, George W.
TI Fifteen years of JCICS
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Milne, George W.] NCI, NIH, Williamsburg, VA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 38-CINF
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164701530
ER
PT J
AU Mittal, J
Hummer, G
AF Mittal, Jeetain
Hummer, Gerhard
TI Effects of molecular-scale density fluctuations and surface roughness on
hydrophobic hydration
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 Lehigh Univ, Dept Chem Engn, Bethlehem, PA 18015 USA.
NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RI Hummer, Gerhard/A-2546-2013
OI Hummer, Gerhard/0000-0001-7768-746X
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 43-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164702425
ER
PT J
AU Nandurdikar, RS
Hong, SY
Oladeinde, OA
Maciag, AE
Saavedra, JE
Keefer, LK
AF Nandurdikar, Rahul S.
Hong, Sam Y.
Oladeinde, Oyebola A.
Maciag, Anna E.
Saavedra, Joseph E.
Keefer, Larry K.
TI Synthetic strategies for developing multivalent nitric oxide donors
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA.
SAIC Frederick, Basic Sci Program, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 83-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704445
ER
PT J
AU Pepe, A
Kim, YS
Trepel, JB
Malhotra, SV
AF Pepe, Antonella
Kim, Yeong Sang
Trepel, Jane B.
Malhotra, Sanjay V.
TI Fused bicyclic ring systems with nitrogen bridgehead: Synthesis and
biological evaluation
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 NCI, Lab Synthet Chem SAIC, Frederick, MD 21701 USA.
NCI, Med Oncol Branch, Ctr Canc Res, NIH,DHHS, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 665-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164705260
ER
PT J
AU Peprah, K
Eyunni, SVK
Etukala, JR
Setola, V
Roth, BL
Abblodeppey, SY
AF Peprah, Kwakye
Eyunni, Suresh V. K.
Etukala, Jagan R.
Setola, Vincent
Roth, Bryan L.
Abblodeppey, Seth Y.
TI Design, synthesis, and pharmacological evaluation of multireceptor
modulating agents as potential atypical antipsychotics
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 Florida A&M Univ, Coll Pharm, Dept Basic Pharmaceut Sci, Tallahassee, FL 32307 USA.
Univ N Carolina, Dept Pharmacol Med Chem & Psychiat, Chapel Hill, NC USA.
Univ N Carolina, NIMH PDSP, Chapel Hill, NC USA.
RI Roth, Bryan/F-3928-2010
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 81-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704443
ER
PT J
AU Pickard, FC
Miller, BT
Woodcock, HL
Schaefer, HF
Brooks, BR
AF Pickard, Frank C.
Miller, Benjamin T.
Woodcock, Henry L.
Schaefer, Henry F.
Brooks, Bernard R.
TI Multi-scale modeling of coarse grained protein interactions: A CHARMMing
implementation
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 NHLBI, NIH, Bethesda, MD 20892 USA.
Univ Georgia, Ctr Computat Quantum Chem, Athens, GA 30602 USA.
Univ S Florida, Dept Chem, Tampa, FL 33620 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 283-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164702292
ER
PT J
AU Rasaiah, JC
Feng, GG
Hummer, G
AF Rasaiah, Jayendran C.
Feng, Guogang
Hummer, Gerhard
TI Chemical potential from particle removal and insertion: Upper and lower
bounds and accurate estimates from computer simulations
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 Univ Maine, Dept Chem, Orono, ME 04469 USA.
NIDDK, Chem Phys Lab, NIH, Orono, ME USA.
RI Hummer, Gerhard/A-2546-2013
OI Hummer, Gerhard/0000-0001-7768-746X
NR 0
TC 0
Z9 0
U1 1
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 22-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164702233
ER
PT J
AU Rice, KC
AF Rice, Kenner C.
TI Medicinal chemistry in opioid research: Looking back
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Rice, Kenner C.] NIDA, NIH, Rockville, MD 20852 USA.
[Rice, Kenner C.] NIAAA, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 13-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704032
ER
PT J
AU Rosenthal, AS
Tanega, C
Shen, M
Mott, BT
Auld, DS
Inglese, J
Austin, CP
Maloney, DJ
Thomas, CJ
AF Rosenthal, Andrew S.
Tanega, Cordelle
Shen, Min
Mott, Bryan T.
Auld, Douglas S.
Inglese, James
Austin, Christopher P.
Maloney, David J.
Thomas, Craig J.
TI Design and synthesis of substituted 6-arylquinazolin-4-amines as potent
and selective inhibitors of members of the CLK and DYRK kinase families
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Rosenthal, Andrew S.; Tanega, Cordelle; Shen, Min; Mott, Bryan T.; Auld, Douglas S.; Inglese, James; Austin, Christopher P.; Maloney, David J.; Thomas, Craig J.] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 174-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704077
ER
PT J
AU Schneider, J
Sinthuvanich, C
AF Schneider, Joel
Sinthuvanich, Chomdao
TI Designing peptide hydrogels for cellular encapsulation and delivery:
Progress towards engineered cartilage
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Schneider, Joel; Sinthuvanich, Chomdao] NCI, Biol Chem Lab, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 358-POLY
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164706842
ER
PT J
AU Sitzmann, M
Ihlenfeldt, WD
Nicklaus, MC
AF Sitzmann, Markus
Ihlenfeldt, Wolf-Dietrich
Nicklaus, Marc C.
TI Tautomerism in large databases
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 NCI, Biol Chem Lab, Ctr Canc Res, NIH,DHHS, Frederick, MD 21701 USA.
Xemistry GmbH, Konigstein, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 14-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164702159
ER
PT J
AU Talisman, IJ
Kumar, V
Malhotra, SV
AF Talisman, Ian Jamie
Kumar, Vineet
Malhotra, Sanjay V.
TI Discovery of silver-N-heterocylic carbenes as novel promoters for
O-glycosidation reactions
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Talisman, Ian Jamie; Kumar, Vineet; Malhotra, Sanjay V.] SAIC Frederick Inc, Lab Synthet Chem, Natl Canc Inst Frederick, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 310-ORGN
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704843
ER
PT J
AU Thatikonda, SK
Zhou, SY
Joshi, BV
Balasubramanian, R
Yang, TH
Liang, BT
Jacobson, KA
AF Thatikonda, Santhosh Kumar
Zhou, Si-Yuan
Joshi, Bhalchandra V.
Balasubramanian, Ramachandran
Yang, Tiehong
Liang, Bruce T.
Jacobson, Kenneth A.
TI Structure-activity relationship of (N)-methanocarba phosphonate analogs
of 5 phi-AMP as cardioprotective agents acting through a cardiac P2X
receptor
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 NIDDKD, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA.
Univ Connecticut, Ctr Hlth, Pat & Jim Calhoun Cardiol Ctr, Farmington, CT USA.
Nektar Therapeut, Huntsville, AL USA.
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 221-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704124
ER
PT J
AU Tosh, DK
Yoo, LS
Chinn, M
Gao, ZG
Jacobson, KA
AF Tosh, Dilip K.
Yoo, Leena S.
Chinn, Moshe
Gao, Zhan-Guo
Jacobson, Kenneth A.
TI Strategy for conjugation of "clickable" agonists of the A(3) adenosine
receptor to polyamidoamine (PAMAM) dendrimers
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Tosh, Dilip K.; Yoo, Leena S.; Chinn, Moshe; Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDKD, Lab Biorgan Chem, NIH, Bethesda, MD 20892 USA.
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 220-MEDI
PG 2
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704123
ER
PT J
AU Tullius, TD
Parker, SCJ
Margulies, EH
AF Tullius, Thomas D.
Parker, Stephen C. J.
Margulies, Elliott H.
TI Evolutionary constraint on DNA structure in the human genome
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 Boston Univ, Dept Chem, Boston, MA 02215 USA.
Boston Univ, Program Bioinformat, Boston, MA 02215 USA.
NHGRI, Genome Informat Sect, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 378-INOR
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164703475
ER
PT J
AU Wang, YQ
Zimmt, M
Gnepp, D
Gildersleeve, J
AF Wang, Yaqi
Zimmt, Matthew
Gnepp, Douglas
Gildersleeve, Jeffrey
TI Lectin-conjugated fluorescent silica nanoparticles for quantitative
histopathology evaluations of tissue biopsies
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 Brown Univ, Dept Chem, Providence, RI 02912 USA.
NCI, Biol Chem Lab, Frederick, MD 21701 USA.
Rhode Isl Hosp, Dept Pathol, Providence, RI 02902 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 371-COLL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164701841
ER
PT J
AU Watson, RP
Kramer-Marek, G
Capala, J
AF Watson, Russell P.
Kramer-Marek, Gabriela
Capala, Jacek
TI Instrumental neutron activation analysis of gold in mouse tissues
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 Natl Inst Stand & Technol, Div Analyt Chem, Gaithersburg, MD USA.
NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 160-ANYL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164700315
ER
PT J
AU Wei, LY
Malhotra, SV
AF Wei, Linyi
Malhotra, Sanjay V.
TI Design and synthesis of novel heterocyclic scaffolds as protein kinase
inhibitor
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Wei, Linyi; Malhotra, Sanjay V.] NCI, Lab Synthet Chem SAIC, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 185-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704087
ER
PT J
AU Wess, J
AF Wess, Juergen
TI G Protein-coupled receptor signaling pathways in pancreatic beta-cells
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Wess, Juergen] NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 16-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704064
ER
PT J
AU Wink, D
Switzer, C
Flores-Santana, W
Glynn, S
Ridnour, L
Cheng, R
AF Wink, David
Switzer, Christopher
Flores-Santana, Wilmarie
Glynn, Sharon
Ridnour, Lisa
Cheng, Robert
TI Chemical biology of NO in mechanisms of inflammation
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Wink, David; Switzer, Christopher; Flores-Santana, Wilmarie; Glynn, Sharon; Ridnour, Lisa; Cheng, Robert] NCI, NIH, Bethesda, MD 20892 USA.
RI Glynn, Sharon/D-7136-2013
OI Glynn, Sharon/0000-0003-1459-2580
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 129-TOXI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164707252
ER
PT J
AU Woods, AS
Lewis, EK
Post, J
Delvolve, A
Egan, TF
Schultz, JA
AF Woods, Amina S.
Lewis, Ernest K.
Post, Jeremy
Delvolve, Alice
Egan, Thomas F.
Schultz, J. Albert
TI Use of sub-monolayer nanoparticulate matrices for lipid imaging by
matrix implanted laser desorption/ionization (MILDI) ion mobility MS
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 NIH Baltimore MD, NIDA IRP, Cellular Neurobiol, Baltimore, MD USA.
Ionwerks Inc, Res & Dev, Houston, TX USA.
NR 0
TC 0
Z9 0
U1 2
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 664-PHYS
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164706271
ER
PT J
AU Yang, H
Morgan, D
Cai, C
Dai, W
Pike, RD
Trenkle, WC
Sweigart, DA
AF Yang, Huan
Morgan, Daniel
Cai, Chen
Dai, Wei
Pike, Robert D.
Trenkle, William C.
Sweigart, Dwight A.
TI Synthesis of ruthenium quinone methide complexes
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 Brown Univ, Dept Chem, Providence, RI 02912 USA.
Coll William & Mary, Dept Chem, Williamsburg, VA 23185 USA.
NIDDK, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 791-INOR
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164703857
ER
PT J
AU Yost, JM
Liu, F
Chen, X
Allali-Hassani, A
Quinn, AM
Wigle, TJ
Barsyte, D
Wasney, GA
Dong, AP
Kozieradzki, I
Senisterra, G
Chau, I
Siarheyeva, A
Van Deusen, A
Kireev, DB
Jadhav, A
Herold, JM
Frye, SV
Arrowsmith, CH
Janzen, WP
Brown, PJ
Simeonov, A
Vedadi, M
Jin, J
AF Yost, Julianne M.
Liu, Feng
Chen, Xin
Allali-Hassani, Abdellah
Quinn, Amy M.
Wigle, Tim J.
Barsyte, Dalia
Wasney, Gregory A.
Dong, Aiping
Kozieradzki, Ivona
Senisterra, Guillermo
Chau, Irene
Siarheyeva, Alena
Van Deusen, Amy
Kireev, Dmitri B.
Jadhav, Ajit
Herold, J. Martin
Frye, Stephen V.
Arrowsmith, Cheryl H.
Janzen, William P.
Brown, Peter J.
Simeonov, Anton
Vedadi, Masoud
Jin, Jian
TI Development of small molecule protein lysine methyltransferase G9a
inhibitors
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 Univ N Carolina, Ctr Integrated Chem Biol & Drug Discovery, Div Med Chem & Nat Prod, Eshelman Sch Pharm, Chapel Hill, NC USA.
Univ Toronto, Struct Genom Consortium, Toronto, ON, Canada.
NHGRI, NIH Genom Ctr, NIH, Bethesda, MD 20892 USA.
RI Kireev, Dmitri/B-7225-2012
OI Kireev, Dmitri/0000-0001-8479-8555
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 100-MEDI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164704003
ER
PT J
AU Zhang, YL
Campbell, C
Li, Q
Gildersleeve, J
AF Zhang, Yalong
Campbell, Christopher
Li, Qian
Gildersleeve, Jeffrey
TI Multidimensional glycan arrays for enhanced lectin and antibody
profiling
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Zhang, Yalong; Campbell, Christopher; Li, Qian; Gildersleeve, Jeffrey] NCI, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 64-CARB
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164700847
ER
PT J
AU Zhang, YL
Li, Q
Rodriguez, LG
Campbell, C
Farnsworth, D
Gildersleeve, JC
AF Zhang, Yalong
Li, Qian
Rodriguez, Luis G.
Campbell, Christopher
Farnsworth, David
Gildersleeve, Jeffrey C.
TI New format carbohydrate microarray: Its application for identification
of multivalent inhibitors
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 NCI, Frederick, MD 21701 USA.
SAIC Frederick Inc, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 46-AEI
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164700035
ER
PT J
AU Zhao, Z
AF Zhao, Zhong
TI Identify the lysine acetylation targets of GCN5 by chemical proteomics
with click chemistry
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
C1 [Zhao, Zhong] NIDDK, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD AUG 22
PY 2010
VL 240
MA 229-BIOL
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA V20UK
UT WOS:000208164700625
ER
PT J
AU Pepin, KM
Volkov, I
Banavar, JR
Wilke, CO
Grenfell, BT
AF Pepin, K. M.
Volkov, I.
Banavar, J. R.
Wilke, C. O.
Grenfell, B. T.
TI Phenotypic differences in viral immune escape explained by linking
within-host dynamics to host-population immunity
SO JOURNAL OF THEORETICAL BIOLOGY
LA English
DT Article
DE Cross-immunity; Within-host dynamics; Original antigenic sin; Adaptive
immunity; Competition
ID CYTOTOXIC T-LYMPHOCYTES; A VIRUS-INFECTION; INFLUENZA-A; BENEFICIAL
MUTATIONS; CLONAL INTERFERENCE; CELL MEMORY; EVOLUTION; NUCLEOPROTEIN;
PATHOGENS; VIRULENCE
AB Viruses that do not cause life-long immunity persist by evolving rapidly in response to prevailing host immunity. The immune-escape mutants emerge frequently, displacing or co-circulating with native strains even though mutations conferring immune evasion are often detrimental to viral replication. The epidemiological dynamics of immune-escape in acute-infection viruses with high transmissibility have been interpreted mainly through immunity dynamics at the host population level, despite the fact that immune-escape evolution involves dynamical processes that feedback across the within- and between-host scales. To address this gap, we use a nested model of within- and between-host infection dynamics to examine how the interaction of viral replication rate and cross-immunity imprint host population immunity, which in turn determines viral immune escape. Our explicit consideration of direct and immune-mediated competitive interactions between strains within-hosts revealed three insights pertaining to risk and control of viral immune-escape: (1) replication rate and immune-stimulation deficiencies (i.e., original antigenic sin) act synergistically to increase immune escape, (2) immune-escape mutants with replication deficiencies relative to their wildtype progenitor are most successful under moderate cross-immunity and frequent re-infections, and (3) the immunity profile along short host-transmission chains (local host-network structure) is a key determinant of immune escape. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Pepin, K. M.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Pepin, K. M.; Volkov, I.; Banavar, J. R.] Penn State Univ, Dept Phys, University Pk, PA 16802 USA.
[Wilke, C. O.] Univ Texas Austin, Ctr Computat Biol & Bioinformat, Inst Cell & Mol Biol, Austin, TX 78712 USA.
[Wilke, C. O.] Univ Texas Austin, Sect Integrat Biol, Austin, TX 78712 USA.
[Grenfell, B. T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Grenfell, B. T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Pepin, KM (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
EM kmp29@psu.edu; igor.volkov@gmail.com; jayanth@phys.psu.edu;
cwilke@mail.utexas.edu; grenfell@princeton.edu
RI Wilke, Claus/B-4643-2008
OI Wilke, Claus/0000-0002-7470-9261
FU NSF [EF-0742373]; NIH [R01 GM083983-01]; Science & Technology
Directorate, Department of Homeland Security; Fogarty International
Center, National Institutes of Health
FX This research was supported by NSF Grant EF-0742373. KP and BG were also
supported by NIH Grant R01 GM083983-01. BG was also supported by the
RAPIDD program of the Science & Technology Directorate, Department of
Homeland Security, and the Fogarty International Center, National
Institutes of Health. We are grateful for the constructive criticism
from three anonymous reviewers that helped to improve the manuscript.
NR 39
TC 11
Z9 11
U1 0
U2 19
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-5193
J9 J THEOR BIOL
JI J. Theor. Biol.
PD AUG 21
PY 2010
VL 265
IS 4
BP 501
EP 510
DI 10.1016/j.jtbi.2010.05.036
PG 10
WC Biology; Mathematical & Computational Biology
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology
GA 632RL
UT WOS:000280445300002
PM 20570681
ER
PT J
AU Nelson, EAS
Glass, RI
AF Nelson, E. Anthony S.
Glass, Roger I.
TI Rotavirus: realising the potential of a promising vaccine
SO LANCET
LA English
DT Editorial Material
ID EFFICACY; GASTROENTERITIS; DIARRHEA; INFANTS; SAFETY
C1 [Nelson, E. Anthony S.] Chinese Univ Hong Kong, Dept Paediat, Hong Kong, Hong Kong, Peoples R China.
[Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Nelson, EAS (reprint author), Chinese Univ Hong Kong, Dept Paediat, Hong Kong, Hong Kong, Peoples R China.
EM tony-nelson@cuhk.edu.hk
OI Nelson, Edmund Anthony Severn/0000-0002-2521-3403
NR 19
TC 23
Z9 23
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD AUG 21
PY 2010
VL 376
IS 9741
BP 568
EP 570
DI 10.1016/S0140-6736(10)60896-3
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 643PB
UT WOS:000281309100005
PM 20692032
ER
PT J
AU Wang, XY
Penalva, LOF
Yuan, HY
Linnoila, RI
Lu, JC
Okano, H
Glazer, RI
AF Wang, Xiao-Yang
Penalva, Luiz O. F.
Yuan, Hongyan
Linnoila, R. Ilona
Lu, Jiachun
Okano, Hideyuki
Glazer, Robert I.
TI Musashi1 regulates breast tumor cell proliferation and is a prognostic
indicator of poor survival
SO MOLECULAR CANCER
LA English
DT Article
ID RNA-BINDING PROTEIN; CANCER STEM-CELLS; ENHANCED SELF-RENEWAL;
STEM/PROGENITOR CELLS; GENE-EXPRESSION; EPITHELIAL-CELLS; POPULATION;
CD133(+); ACTIVATION; INDUCTION
AB Background: Musashi1 (Msi1) is a conserved RNA-binding protein that regulates the Notch and Wnt pathways, and serves as a stem cell marker in the breast and other tissues. It is unknown how Msi1 relates to other breast cancer markers, whether it denotes tumor initiating cells (TICs), and how it affects gene expression and tumor cell survival in breast cancer cells.
Results: Msi1 expression was analyzed in 20 breast cancer cell lines and in 140 primary breast tumors by western blotting and immunohistochemistry, respectively. Lentivirus RNA interference was used to reduce Msi1 expression in breast cancer cell lines MCF-7 and T47D grown as spheroid cultures and to assess stem cell gene expression and the growth of these cell lines as xenografts. In normal human breast tissue, Msi1 was expressed in 10.6% of myoepithelum and 1.2% of ductal epithelium in the terminal ductal lobular unit (TDLU), whereas, less than 0.05% of ductal epithelium and myoepithelium in large ducts outside the TDLU expressed Msi1. Msi1 was expressed in 55% of the breast cancer cell lines and correlated with ErbB2 expression in 50% of the cell lines. Msi1 was expressed in 68% of primary tumors and in 100% of lymph node metastases, and correlated with 5 year survival. Msi1 was enriched in CD133(+) MCF-7 and T47D cells and in spheroid cultures of these cells, and Msi1 'knockdown' (KD) with a lentivirus-expressed shRNA decreased the number and size of spheroid colonies. Msi1 KD reduced Notch1, c-Myc, ErbB2 and pERK1/2 expression, and increased p21(CIP1) expression, which is consistent with known Msi1 target mRNAs. Msi1 KD also reduced the expression of the somatic and embryonic stem cell markers, CD133, Bmi1, Sox2, Nanog and Oct4. Xenografts of MCF-7 and T47D Msi1 KD cells resulted in a marked reduction of tumor growth, reduced Msi1 and Notch1 expression and increased p21(CIP1) expression.
Conclusion: Msi1 is a negative prognostic indicator of breast cancer patient survival, and is indicative of tumor cells with stem cell-like characteristics. Msi1 KD reduces tumor cell survival and tumor xenograft growth, suggesting that it may represent a novel target for drug discovery.
C1 [Wang, Xiao-Yang; Yuan, Hongyan; Glazer, Robert I.] Georgetown Univ, Dept Oncol, Washington, DC 20007 USA.
[Wang, Xiao-Yang; Yuan, Hongyan; Glazer, Robert I.] Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
[Wang, Xiao-Yang; Linnoila, R. Ilona] NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Penalva, Luiz O. F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cell & Struct Biol, San Antonio, TX 78229 USA.
[Lu, Jiachun] Guangzhou Med Coll, State Key Lab Resp Dis, Dept Epidemiol, Guangzhou, Guangdong, Peoples R China.
[Okano, Hideyuki] Keio Univ, Sch Med, Dept Physiol, Tokyo 160, Japan.
RP Wang, XY (reprint author), Georgetown Univ, Dept Oncol, Washington, DC 20007 USA.
EM wangxiao@mail.nih.gov; glazerr@georgetown.edu
RI Hidokano, Hideyuki/J-5973-2013
FU National Cancer Institute, National Institutes of Health [R01 CA11482];
Charlotte Geyer Foundation; NIH; Cancer Therapy and Research Center;
American Cancer Society [PDID 124139]; San Antonio Area Foundation
[PGID122760]; National Natural Scientific Foundation of China [30671813,
30872178]
FX This study was supported by Grant R01 CA11482 (RIG) from the National
Cancer Institute, National Institutes of Health, The Charlotte Geyer
Foundation (RIG), the Intramural Research Program of the NIH (XYW, RIL),
Cancer Therapy and Research Center (LP), American Cancer Society Grant
PDID 124139 (LP), the San Antonio Area Foundation Grant PGID122760 (LP)
and the National Natural Scientific Foundation of China grants 30671813
and 30872178 (JL). We thank Dr. Karen Creswell and Idalia Cruz for their
assistance with the flow cytometry and xenograft studies, respectively.
NR 50
TC 57
Z9 62
U1 1
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-4598
J9 MOL CANCER
JI Mol. Cancer
PD AUG 21
PY 2010
VL 9
AR 221
DI 10.1186/1476-4598-9-221
PG 12
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 658AP
UT WOS:000282461200001
PM 20727204
ER
PT J
AU Moon, HR
Siddiqui, MA
Sun, G
Filippov, IV
Landsman, NA
Lee, YC
Adams, KM
Barchi, JJ
Deschamps, JR
Nicklaus, MC
Kelley, JA
Marquez, VE
AF Moon, Hyung Ryong
Siddiqui, Maqbool A.
Sun, Guangyu
Filippov, Igor V.
Landsman, Nicholas A.
Lee, Yi-Chien
Adams, Kristie M.
Barchi, Joseph J., Jr.
Deschamps, Jeffrey R.
Nicklaus, Marc C.
Kelley, James A.
Marquez, Victor E.
TI Using conformationally locked nucleosides to calibrate the anomeric
effect: implications for glycosyl bond stability
SO TETRAHEDRON
LA English
DT Article
ID PSEUDOROTATIONAL EQUILIBRIUM; PENTOFURANOSE MOIETY; ALCOHOLS; H-1-NMR;
SYSTEM
AB Steric and electronic parameters, such as the anomeric effect (AE) and gauche effect play significant roles in steering the North <-> South equilibrium of nucleosides in solution.
Two isomeric oxa-bicyclo[3.1.0]hexane nucleosides that are conformationally locked in either the North or the South conformation of the pseudorotational cycle were designed to study the consequences of having the AE operational or not, independent of other parameters. The rigidity of the system allowed the orientation of the orbitals involved to be set in 'fixed' relationships, either antiperiplanar where the AE is permanently 'on', or gauche where the AE is impaired. The consequences of these two alternatives were subjected to high-level calculations and measured experimentally by X-ray crystallography, hydrolytic stability of the glycosyl bond, and pK(a) values. Published by Elsevier Ltd.
C1 [Moon, Hyung Ryong; Siddiqui, Maqbool A.; Sun, Guangyu; Landsman, Nicholas A.; Lee, Yi-Chien; Adams, Kristie M.; Barchi, Joseph J., Jr.; Nicklaus, Marc C.; Kelley, James A.; Marquez, Victor E.] NCI, Biol Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21701 USA.
[Filippov, Igor V.] SAIC Frederick Inc, Frederick, MD 21702 USA.
[Deschamps, Jeffrey R.] USN, Res Lab, Washington, DC 20375 USA.
RP Marquez, VE (reprint author), NCI, Biol Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21701 USA.
EM marquezv@mail.nih.gov
RI Nicklaus, Marc/N-4183-2014; Barchi Jr., Joseph/N-3784-2014;
OI Deschamps, Jeffrey/0000-0001-5845-0010; Nicklaus,
Marc/0000-0002-4775-7030
FU NIH, National Cancer Institute, Center for Cancer Research; National
Cancer Institute, National Institutes of Health [N01-00-12400]
FX The authors wish to express their gratitude to Professor Christopher J.
Cramer from the Department of Chemical Physics and Scientific
Computation at the University of Minnesota for his advice. This research
was supported by the Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research. The project was also
funded in part with federal funds from the National Cancer Institute,
National Institutes of Health, under contract N01-00-12400.
NR 22
TC 2
Z9 2
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0040-4020
J9 TETRAHEDRON
JI Tetrahedron
PD AUG 21
PY 2010
VL 66
IS 34
BP 6707
EP 6717
DI 10.1016/j.tet.2010.06.044
PG 11
WC Chemistry, Organic
SC Chemistry
GA 639EL
UT WOS:000280953500002
PM 21052524
ER
PT J
AU Stahl, A
Sapieha, P
Connor, KM
SanGiovanni, JP
Chen, J
Aderman, CM
Willett, KL
Krah, NM
Dennison, RJ
Seaward, MR
Guerin, KI
Hua, J
Smith, LEH
AF Stahl, Andreas
Sapieha, Przemyslaw
Connor, Kip M.
SanGiovanni, John Paul
Chen, Jing
Aderman, Christopher M.
Willett, Keirnan L.
Krah, Nathan M.
Dennison, Roberta J.
Seaward, Molly R.
Guerin, Karen I.
Hua, Jing
Smith, Lois E. H.
TI PPAR gamma Mediates a Direct Antiangiogenic Effect of omega 3-PUFAs in
Proliferative Retinopathy
SO CIRCULATION RESEARCH
LA English
DT Article
DE omega 3 PUFA; PPAR; retinopathy; neovascularization; oxygen-induced
retinopathy
ID OXYGEN-INDUCED RETINOPATHY; RETINAL NEOVASCULARIZATION; ACTIVATED
RECEPTORS; FATTY-ACIDS; ANGIOGENESIS; EXPRESSION; MODEL;
THIAZOLIDINEDIONES; ROSIGLITAZONE; INFLAMMATION
AB Rationale: Omega3 long-chain polyunsaturated fatty acids (omega 3-PUFAs) are powerful modulators of angiogenesis. However, little is known about the mechanisms governing omega 3-PUFA-dependent attenuation of angiogenesis.
Objective: This study aims to identify a major mechanism by which omega 3-PUFAs attenuate retinal neovascularization.
Methods and Results: Administering omega 3-PUFAs exclusively during the neovascular stage of the mouse model of oxygen-induced retinopathy induces a direct neovascularization reduction of more than 40% without altering vasoobliteration or the regrowth of normal vessels. Cotreatment with an inhibitor of peroxisome proliferator-activated receptor (PPAR)gamma almost completely abrogates this effect. Inhibition of PPAR gamma also reverses the omega 3-PUFA-induced reduction of retinal tumor necrosis factor-alpha, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial selectin, and angiopoietin 2 but not vascular endothelial growth factor.
Conclusions: These results identify a direct, PPAR gamma -mediated effect of omega 3-PUFAs on retinal neovascularization formation and retinal angiogenic activation that is independent of vascular endothelial growth factor. (Circ Res. 2010; 107: 495-500.)
C1 [Stahl, Andreas; Sapieha, Przemyslaw; Connor, Kip M.; Chen, Jing; Aderman, Christopher M.; Willett, Keirnan L.; Krah, Nathan M.; Dennison, Roberta J.; Seaward, Molly R.; Guerin, Karen I.; Hua, Jing; Smith, Lois E. H.] Harvard Univ, Childrens Hosp Boston, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA.
[Stahl, Andreas] Univ Eye Hosp, Freiburg, Germany.
[SanGiovanni, John Paul] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA.
RP Smith, LEH (reprint author), Harvard Univ, Childrens Hosp Boston, Sch Med, Dept Ophthalmol, 300 Longwood Ave, Boston, MA 02115 USA.
EM lois.smith@childrens.harvard.edu
FU Deutsche Forschungsgemeinschaft; Canadian Institutes of Health Research;
Charles A. King Trust Award; William Randolph Hearst Award; March of
Dimes Foundation; Simeon Burt Wolbach Research Fellowship; Juvenile
Diabetes Research Foundation International; Knights Templar Eye
Foundation; CHB Manton Center for Orphan Disease; NIH [EY017017,
EY017017-S1]; V. Kann Rasmussen Foundation; RoFAR; CHB Mental
Retardation and Developmental Disabilities Research Center; RPB Senior
Investigator Award; Alcon Research Institute Award; MacTel Foundation
FX This work was supported by the Deutsche Forschungsgemeinschaft (to
A.S.); Canadian Institutes of Health Research and Charles A. King Trust
Award (to P.S.); William Randolph Hearst Award, March of Dimes
Foundation, and a Simeon Burt Wolbach Research Fellowship (to K.M.C.);
Juvenile Diabetes Research Foundation International, Knights Templar Eye
Foundation, and CHB Manton Center for Orphan Disease (to J.C.); NIH
grants EY017017 and EY017017-S1, V. Kann Rasmussen Foundation, RoFAR,
CHB Mental Retardation and Developmental Disabilities Research Center,
an RPB Senior Investigator Award, Alcon Research Institute Award, and
the MacTel Foundation (to L.E.H.S.).
NR 18
TC 42
Z9 44
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD AUG 20
PY 2010
VL 107
IS 4
BP 495
EP 500
DI 10.1161/CIRCRESAHA.110.221317
PG 6
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 641VH
UT WOS:000281157800009
PM 20634487
ER
PT J
AU Takemura, T
Lee, K
Yuen, W
Mulky, A
Martin, TD
Ambrose, Z
Bieniasz, PD
Hatziioannou, T
KewalRamani, VN
AF Takemura, Taichiro
Lee, Kyeongeun
Yuen, Wendy
Mulky, Alok
Martin, Thomas D.
Ambrose, Zandrea
Bieniasz, Paul D.
Hatziioannou, Theodora
KewalRamani, Vineet N.
TI HIV-1 Restriction by a Cyclophilin-related Factor in Human Cells
SO EUROPEAN JOURNAL OF MEDICAL RESEARCH
LA English
DT Meeting Abstract
C1 [Bieniasz, Paul D.; Hatziioannou, Theodora] Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA.
[Takemura, Taichiro] Natl Inst Infect Dis, AIDS Res Ctr, Tokyo, Japan.
[Takemura, Taichiro; Lee, Kyeongeun; Yuen, Wendy; Mulky, Alok; Martin, Thomas D.; Ambrose, Zandrea; KewalRamani, Vineet N.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
EM taichiro@nih.go.jp
NR 0
TC 0
Z9 0
U1 0
U2 0
PU I HOLZAPFEL VERLAG GMBH
PI MUNICH
PA HARTHAUSER STR 105, 81545 MUNICH, GERMANY
SN 0949-2321
J9 EUR J MED RES
JI Eur. J. Med. Res.
PD AUG 20
PY 2010
VL 15
IS 8
BP 324
EP 324
PG 1
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 648MS
UT WOS:000281698800005
ER
PT J
AU Iwatani, Y
Chan, DSB
Liu, L
Yoshii, H
Shibata, J
Levin, JG
Gronenborn, AM
Sugiura, W
AF Iwatani, Yasumasa
Chan, Denise S. B.
Liu, Lin
Yoshii, Hiroaki
Shibata, Junko
Levin, Judith G.
Gronenborn, Angela M.
Sugiura, Wataru
TI Structure-guided mutagenesis of APOBEC3G reveals four lysine residues
critical for HIV-1 Vif-mediated ubiquitination/degradation near the
C-terminal end
SO EUROPEAN JOURNAL OF MEDICAL RESEARCH
LA English
DT Meeting Abstract
C1 [Iwatani, Yasumasa; Yoshii, Hiroaki; Shibata, Junko; Sugiura, Wataru] Natl Hosp Org, Nagoya Med Ctr, Clin Res Ctr, Nagoya, Aichi, Japan.
[Iwatani, Yasumasa; Sugiura, Wataru] Nagoya Univ, Grad Sch Med, Nagoya, Aichi 4648601, Japan.
[Chan, Denise S. B.; Liu, Lin; Gronenborn, Angela M.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Levin, Judith G.] NICHD, NIH, Bethesda, MD USA.
EM iwataniy@nnh.hosp.go.jp
NR 0
TC 0
Z9 0
U1 0
U2 2
PU I HOLZAPFEL VERLAG GMBH
PI MUNICH
PA HARTHAUSER STR 105, 81545 MUNICH, GERMANY
SN 0949-2321
J9 EUR J MED RES
JI Eur. J. Med. Res.
PD AUG 20
PY 2010
VL 15
IS 8
BP 325
EP 326
PG 2
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 648MS
UT WOS:000281698800010
ER
PT J
AU Kashiwaya, Y
Pawlosky, R
Markis, W
King, MT
Bergman, C
Srivastava, S
Murray, A
Clarke, K
Veech, RL
AF Kashiwaya, Yoshihiro
Pawlosky, Robert
Markis, William
King, M. Todd
Bergman, Christian
Srivastava, Shireesh
Murray, Andrew
Clarke, Kieran
Veech, Richard L.
TI A Ketone Ester Diet Increases Brain Malonyl-CoA and Uncoupling Proteins
4 and 5 while Decreasing Food Intake in the Normal Wistar Rat
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID D-BETA-HYDROXYBUTYRATE; KETOGENIC DIET; IN-VIVO; ENERGY HOMEOSTASIS;
HEALTHY-MEN; METABOLISM; BODIES; INSULIN; EXPRESSION; GLUTAMATE
AB Three groups of male Wistar rats were pair fed NIH-31 diets for 14 days to which were added 30% of calories as corn starch, palm oil, or R-3-hydroxybutyrate-R-1,3-butanediol monoester (3HB-BD ester). On the 14th day, animal brains were removed by freeze-blowing, and brain metabolites measured. Animals fed the ketone ester diet had elevated mean blood ketone bodies of 3.5 mM and lowered plasma glucose, insulin, and leptin. Despite the decreased plasma leptin, feeding the ketone ester diet ad lib decreased voluntary food intake 2-fold for 6 days while brain malonyl-CoA was increased by about 25% in ketone-fed group but not in the palm oil fed group. Unlike the acute effects of ketone body metabolism in the perfused working heart, there was no increased reduction in brain free mitochondrial [NAD(+)]/[NADH] ratio nor in the free energy of ATP hydrolysis, which was compatible with the observed 1.5-fold increase in brain uncoupling proteins 4 and 5. Feeding ketone ester or palm oil supplemented diets decreased brain L-glutamate by 15-20% and GABA by about 34% supporting the view that fatty acids as well as ketone bodies can be metabolized by the brain.
C1 [Veech, Richard L.] NIAAA, Lab Metab Control, NIH, DHHS, Rockville, MD 20852 USA.
[Murray, Andrew] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3EG, England.
[Clarke, Kieran] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3PT, England.
RP Veech, RL (reprint author), NIAAA, Lab Metab Control, NIH, DHHS, 5625 Fishers Lane,Rm 2S28, Rockville, MD 20852 USA.
EM rveech@mail.nih.gov
RI Murray, Andrew/B-3130-2010; Bergman, Christian/D-8680-2012
OI Murray, Andrew/0000-0002-0929-9315;
FU Defense Advanced Research Projects Administration, United States Dept.
of Defense
FX This work was supported in part by the Defense Advanced Research
Projects Administration, United States Dept. of Defense.
NR 58
TC 28
Z9 29
U1 0
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 20
PY 2010
VL 285
IS 34
BP 25950
EP 25956
DI 10.1074/jbc.M110.138198
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 638UB
UT WOS:000280921000009
PM 20529850
ER
PT J
AU Kang, SA
Lee, ES
Yoon, HY
Randazzo, PA
Lee, ST
AF Kang, Shin-Ae
Lee, Eun-Saem
Yoon, Hye-Young
Randazzo, Paul A.
Lee, Seung-Taek
TI PTK6 Inhibits Down-regulation of EGF Receptor through Phosphorylation of
ARAP1
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID EPIDERMAL-GROWTH-FACTOR; BREAST-TUMOR KINASE; NONRECEPTOR TYROSINE
KINASE; MAMMARY EPITHELIAL-CELLS; INDEPENDENT ENDOCYTOSIS;
GASTROINTESTINAL-TRACT; STAT3 ACTIVATION; PLASMA-MEMBRANE; FAMILY
KINASES; ARF GAPS
AB PTK6 (also known as Brk) is a non-receptor-tyrosine kinase containing SH3, SH2, and catalytic domains, that is expressed in more than 60% of breast carcinomas but not in normal mammary tissues. To analyze PTK6-interacting proteins, we have expressed Flag-tagged PTK6 in HEK293 cells and performed co-immunoprecipitation assays with Flag antibody-conjugated agarose. A 164-kDa protein in the precipitated fraction was identified as ARAP1 (also known as centaurin delta-2) by MALDI-TOF mass analysis. ARAP1 associated with PTK6 in an EGF/EGF receptor (EGFR)-dependent manner. In addition, the SH2 domain of PTK6, particularly the Arg(105) residue that contacts the phosphate group of the tyrosine residue, was essential for the association. Moreover, PTK6 phosphorylated residue Tyr(231) in the N-terminal domain of ARAP1. Expression of ARAP1, but not of the Y231F mutant, inhibited the down-regulation of EGFR in HEK293 cells expressing PTK6. Silencing of endogenous PTK6 expression in breast carcinoma cells decreased EGFR levels. These results demonstrate that PTK6 enhances EGFR signaling by inhibition of EGFR down-regulation through phosphorylation of ARAP1 in breast cancer cells.
C1 [Kang, Shin-Ae; Lee, Eun-Saem; Lee, Seung-Taek] Yonsei Univ, Dept Biochem, Coll Life Sci & Biotechnol, Seoul 120749, South Korea.
[Yoon, Hye-Young; Randazzo, Paul A.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Lee, ST (reprint author), Yonsei Univ, Dept Biochem, Coll Life Sci & Biotechnol, Seoul 120749, South Korea.
EM stlee@yonsei.ac.kr
OI Lee, Seung-Taek/0000-0001-7300-9784
FU Seoul Research and Business Development [10527]; Korea Science and
Engineering Foundation; Brain Korea 21 trainee program
FX This work was supported by the Seoul Research and Business Development
Grant 10527, the project for Studies on Ubiquitome Functions from the
Korea Science and Engineering Foundation, and the Brain Korea 21 trainee
program.
NR 49
TC 17
Z9 17
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 20
PY 2010
VL 285
IS 34
BP 26013
EP 26021
DI 10.1074/jbc.M109.088971
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 638UB
UT WOS:000280921000016
PM 20554524
ER
PT J
AU de Castro, RO
Zhang, J
Jamur, MC
Oliver, C
Siraganian, RP
AF de Castro, Rodrigo O.
Zhang, Juan
Jamur, Maria C.
Oliver, Constance
Siraganian, Reuben P.
TI Tyrosines in the Carboxyl Terminus Regulate Syk Kinase Activity and
Function
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID FC-EPSILON-RI; AFFINITY IGE RECEPTOR; CELL ANTIGEN RECEPTOR;
PHOSPHOTYROSINE-BINDING DOMAIN; BASOPHILIC LEUKEMIA-CELLS; ACTIVATION
LOOP TYROSINES; PROTEIN-COUPLED RECEPTOR; MAST-CELLS;
SIGNAL-TRANSDUCTION; IMMUNOGLOBULIN-E
AB The Syk tyrosine kinase family plays an essential role in immunoreceptor tyrosine-based activation motif (ITAM) signaling. The binding of Syk to tyrosine-phosphorylated ITAM subunits of immunoreceptors, such as Fc epsilon RI on mast cells, results in a conformational change, with an increase of enzymatic activity of Syk. This conformational change exposes the COOH-terminal tail of Syk, which has three conserved Tyr residues (Tyr-623, Tyr-624, and Tyr-625 of rat Syk). To understand the role of these residues in signaling, wild-type and mutant Syk with these three Tyr mutated to Phe was expressed in Syk-deficient mast cells. There was decreased Fc epsilon RI-induced degranulation, nuclear factor for T cell activation and NF kappa B activation with the mutated Syk together with reduced phosphorylation of MAP kinases p38 and p42/44 ERK. In non-stimulated cells, the mutated Syk was more tyrosine phosphorylated predominantly as a result of autophosphorylation. In vitro, there was reduced binding of mutated Syk to phosphorylated ITAM due to this increased phosphorylation. This mutated Syk from non-stimulated cells had significantly reduced kinase activity toward an exogenous substrate, whereas its autophosphorylation capacity was not affected. However, the kinase activity and the autophosphorylation capacity of this mutated Syk were dramatically decreased when the protein was dephosphorylated before the in vitro kinase reaction. Furthermore, mutation of these tyrosines in the COOH-terminal region of Syk transforms it to an enzyme, similar to its homolog ZAP-70, which depends on other tyrosine kinases for optimal activation. In testing Syk mutated singly at each one of the tyrosines, Tyr-624 but especially Tyr-625 had the major role in these reactions. Therefore, these results indicate that these tyrosines in the tail region play a critical role in regulating the kinase activity and function of Syk.
C1 [Siraganian, Reuben P.] Natl Inst Dent & Craniofacial Res, Receptors & Signal Transduct Sect, NIH, Bethesda, MD 20892 USA.
[de Castro, Rodrigo O.; Jamur, Maria C.; Oliver, Constance] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Cell & Mol Biol & Pathogen Bioagents, BR-14049900 Sao Paulo, Brazil.
RP Siraganian, RP (reprint author), Natl Inst Dent & Craniofacial Res, Receptors & Signal Transduct Sect, NIH, Bldg 49,Rm 1A16,NIDCR, Bethesda, MD 20892 USA.
EM rs53x@nih.gov
RI Jamur, Maria Celia/L-5520-2016
OI Jamur, Maria Celia/0000-0001-7065-8543
FU NIDCR, National Institutes of Health
FX This work was supported, in whole or in part, by the National Institutes
of Health Intramural Research Program, NIDCR.
NR 65
TC 14
Z9 14
U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 20
PY 2010
VL 285
IS 34
BP 26674
EP 26684
DI 10.1074/jbc.M110.134262
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 638UB
UT WOS:000280921000082
PM 20554527
ER
PT J
AU Korn, EL
Freidlin, B
AF Korn, Edward L.
Freidlin, Boris
TI Causal Inference for Definitive Clinical End Points in a Randomized
Clinical Trial With Intervening Nonrandomized Treatments
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID RENAL-CELL CARCINOMA; PHASE-III TRIAL; CANCER; EFFICACY
C1 [Korn, Edward L.; Freidlin, Boris] NCI, Bethesda, MD 20892 USA.
RP Korn, EL (reprint author), NCI, Bethesda, MD 20892 USA.
NR 11
TC 6
Z9 6
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD AUG 20
PY 2010
VL 28
IS 24
BP 3800
EP 3802
DI 10.1200/JCO.2010.30.0442
PG 4
WC Oncology
SC Oncology
GA 641ME
UT WOS:000281129700002
PM 20660828
ER
PT J
AU Park, JK
Hodges, T
Arko, L
Shen, M
Dello Iacono, D
McNabb, A
Bailey, NO
Kreisl, TN
Iwamoto, FM
Sul, J
Auh, S
Park, GE
Fine, HA
Black, PM
AF Park, John K.
Hodges, Tiffany
Arko, Leopold
Shen, Michael
Dello Iacono, Donna
McNabb, Adrian
Bailey, Nancy Olsen
Kreisl, Teri Nguyen
Iwamoto, Fabio M.
Sul, Joohee
Auh, Sungyoung
Park, Grace E.
Fine, Howard A.
Black, Peter McL.
TI Scale to Predict Survival After Surgery for Recurrent Glioblastoma
Multiforme
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID MALIGNANT GLIOMAS; REOPERATION; CLASSIFICATION; RADIOTHERAPY; SYSTEM;
ADULTS
AB Purpose
Despite initial treatment with surgical resection, radiotherapy, and chemotherapy, glioblastoma multiforme (GBM) virtually always recurs. Surgery is sometimes recommended to treat recurrence. In this study, we sought to devise a preoperative scale that predicts survival after surgery for recurrent glioblastoma multiforme.
Patients and Methods
The preoperative clinical and radiographic data of 34 patients who underwent re-operation of recurrent GBM tumors were analyzed using Kaplan-Meier survival analysis and Cox proportional hazards regression modeling. The factors associated with decreased postoperative survival (P =.05) were used to devise a prognostic scale which was validated with a separate cohort of 109 patients.
Results
The factors associated with poor postoperative survival were: tumor involvement of prespecified eloquent/ critical brain regions (P =021), Karnofsky performance status (KPS)= 80 (P =030), and tumor volume 50 cm3 (P =048). An additive scale (range, 0 to 3 points) comprised of these three variables distinguishes patients with good (0 points), intermediate (1 to 2 points), and poor (3 points) postoperative survival (median survival, 10.8, 4.5, and 1.0 months, respectively; P=.001). The scale identified three statistically distinct groups within the validation cohort as well (median survival, 9.2, 6.3, and 1.9 months, respectively; P = 001).
Conclusion
We devised and validated a preoperative scale that identifies patients likely to have poor, intermediate, and good relative outcomes after surgical resection of a recurrent GBM tumor. Application of this simple scale may be useful in counseling patients regarding their treatment options and in designing clinical trials.
C1 NINDS, Surg & Mol Neurooncol Unit, Neurooncol Branch, NCI, Bethesda, MD USA.
NIAMSD, NIH, Bethesda, MD 20892 USA.
Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Park, JK (reprint author), 35 Convent Dr,MSC 3706,Rm 2B-1002, Bethesda, MD 20892 USA.
EM parkjk@ninds.nih.gov
OI Arko, Leopold/0000-0003-1052-5671
FU Intramural NIH HHS
NR 16
TC 111
Z9 114
U1 1
U2 7
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD AUG 20
PY 2010
VL 28
IS 24
BP 3838
EP 3843
DI 10.1200/JCO.2010.30.0582
PG 6
WC Oncology
SC Oncology
GA 641ME
UT WOS:000281129700008
PM 20644085
ER
PT J
AU Kantoff, PW
Blumenstein, BA
Gulley, JL
Godfrey, WR
AF Kantoff, Philip W.
Blumenstein, Brent A.
Gulley, James L.
Godfrey, Wayne R.
TI Poxviral-Based Prostate-Specific Antigen Vaccine in Prostate Cancer
Reply
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
ID SURVIVAL
C1 [Kantoff, Philip W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Blumenstein, Brent A.] Trial Architecture Consulting, Washington, DC USA.
[Gulley, James L.] NCI, Bethesda, MD 20892 USA.
[Godfrey, Wayne R.] BN ImmunoTherapeut, Mountain View, CA USA.
RP Kantoff, PW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 3
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
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD AUG 20
PY 2010
VL 28
IS 24
BP E417
EP E417
DI 10.1200/JCO.2010.29.3472
PG 1
WC Oncology
SC Oncology
GA 641ME
UT WOS:000281129700020
ER
PT J
AU Cardone, A
Hassan, SA
Albers, RW
Sriram, RD
Pant, HC
AF Cardone, A.
Hassan, S. A.
Albers, R. W.
Sriram, R. D.
Pant, H. C.
TI Structural and Dynamic Determinants of Ligand Binding and Regulation of
Cyclin-Dependent Kinase 5 by Pathological Activator p25 and Inhibitory
Peptide CIP
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE cdk5; CIP; kinase; regulation; dynamics
ID MOLECULAR-DYNAMICS; TRYPSIN-INHIBITOR; CDK5 ACTIVATOR; PROTEIN; P35;
HYPERPHOSPHORYLATION; FLUCTUATIONS; DOMAINS; MOTIONS; DISEASE
AB The crystal structure of the cdk5/p25 complex has provided information on possible molecular mechanisms of the ligand binding, specificity, and regulation of the kinase. Comparative molecular dynamics simulations are reported here for physiological conditions. This study provides new insight on the mechanisms that modulate such processes, which may be exploited to control pathological activation by p25. The structural changes observed in the kinase are stabilized by a network of interactions involving highly conserved residues within the cyclin-dependent kinase (cdk) family. Collective motions of the proteins (cdk5, p25, and CIP) and their complexes are identified by principal component analysis, revealing two conformational states of the activation loop upon p25 complexation, which are absent in the uncomplexed kinase and not apparent from the crystal. Simulations of the uncomplexed inhibitor CIP show structural rearrangements and increased flexibility of the interfacial loop containing the critical residue E240, which becomes fully hydrated and available for interactions with one of several positively charged residues in the kinase. These changes provide a rationale for the observed high affinity and enhanced inhibitory action of CIP when compared to either p25 or the physiological activators of cdk5. Published by Elsevier Ltd.
C1 [Hassan, S. A.] NIH, Ctr Mol Modeling, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Cardone, A.; Sriram, R. D.] NIST, Informat Technol Lab, Gaithersburg, MD 20899 USA.
[Cardone, A.] Univ Maryland, Dept Mech Engn, College Pk, MD 20742 USA.
[Albers, R. W.] Natl Inst Neurol Disorders & Stroke, Enzyme Chem Sect, Neurochem Lab, NIH, Bethesda, MD 20892 USA.
[Pant, H. C.] Natl Inst Neurol Disorders & Stroke, Neuronal Cytoskeletal Prot Regulat Sect, Neurochem Lab, NIH, Bethesda, MD 20892 USA.
RP Hassan, SA (reprint author), NIH, Ctr Mol Modeling, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
EM mago@helix.nih.gov
FU National Institutes of Health through the Center for Information
Technology; National Institute of Neurological Disorders and Stroke;
Internal National Institute of Standards and Technology
FX This study utilized the high-performance computer capabilities of the
Biowulf PC/Linux cluster at the National Institutes of Health. This work
was supported by the National Institutes of Health Intramural Research
Program through the Center for Information Technology and the National
Institute of Neurological Disorders and Stroke, and by the Internal
National Institute of Standards and Technology Research Fund.
NR 39
TC 11
Z9 11
U1 0
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD AUG 20
PY 2010
VL 401
IS 3
BP 478
EP 492
DI 10.1016/j.jmb.2010.06.040
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 641ZB
UT WOS:000281171000012
PM 20599546
ER
PT J
AU Fischer, W
Ganusov, VV
Giorgi, EE
Hraber, PT
Keele, BF
Leitner, T
Han, CS
Gleasner, CD
Green, L
Lo, CC
Nag, A
Wallstrom, TC
Wang, SY
McMichael, AJ
Haynes, BF
Hahn, BH
Perelson, AS
Borrow, P
Shaw, GM
Bhattacharya, T
Korber, BT
AF Fischer, Will
Ganusov, Vitaly V.
Giorgi, Elena E.
Hraber, Peter T.
Keele, Brandon F.
Leitner, Thomas
Han, Cliff S.
Gleasner, Cheryl D.
Green, Lance
Lo, Chien-Chi
Nag, Ambarish
Wallstrom, Timothy C.
Wang, Shuyi
McMichael, Andrew J.
Haynes, Barton F.
Hahn, Beatrice H.
Perelson, Alan S.
Borrow, Persephone
Shaw, George M.
Bhattacharya, Tanmoy
Korber, Bette T.
TI Transmission of Single HIV-1 Genomes and Dynamics of Early Immune Escape
Revealed by Ultra-Deep Sequencing
SO PLOS ONE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; IN-VIVO; RHESUS-MONKEYS; INFECTION;
EVOLUTION; RESPONSES; VARIANTS; VACCINES; MUTATIONS; PHENOTYPE
AB We used ultra-deep sequencing to obtain tens of thousands of HIV-1 sequences from regions targeted by CD8+ T lymphocytes from longitudinal samples from three acutely infected subjects, and modeled viral evolution during the critical first weeks of infection. Previous studies suggested that a single virus established productive infection, but these conclusions were tempered because of limited sampling; now, we have greatly increased our confidence in this observation through modeling the observed earliest sample diversity based on vastly more extensive sampling. Conventional sequencing of HIV-1 from acute/early infection has shown different patterns of escape at different epitopes; we investigated the earliest escapes in exquisite detail. Over 3-6 weeks, ultradeep sequencing revealed that the virus explored an extraordinary array of potential escape routes in the process of evading the earliest CD8 T-lymphocyte responses - using 454 sequencing, we identified over 50 variant forms of each targeted epitope during early immune escape, while only 2-7 variants were detected in the same samples via conventional sequencing. In contrast to the diversity seen within epitopes, non-epitope regions, including the Envelope V3 region, which was sequenced as a control in each subject, displayed very low levels of variation. In early infection, in the regions sequenced, the consensus forms did not have a fitness advantage large enough to trigger reversion to consensus amino acids in the absence of immune pressure. In one subject, a genetic bottleneck was observed, with extensive diversity at the second time point narrowing to two dominant escape forms by the third time point, all within two months of infection. Traces of immune escape were observed in the earliest samples, suggesting that immune pressure is present and effective earlier than previously reported; quantifying the loss rate of the founder virus suggests a direct role for CD8 T-lymphocyte responses in viral containment after peak viremia. Dramatic shifts in the frequencies of epitope variants during the first weeks of infection revealed a complex interplay between viral fitness and immune escape.
C1 [Fischer, Will; Ganusov, Vitaly V.; Giorgi, Elena E.; Hraber, Peter T.; Leitner, Thomas; Han, Cliff S.; Gleasner, Cheryl D.; Green, Lance; Lo, Chien-Chi; Nag, Ambarish; Wallstrom, Timothy C.; Perelson, Alan S.; Bhattacharya, Tanmoy; Korber, Bette T.] Los Alamos Natl Lab, Los Alamos, NM USA.
[Ganusov, Vitaly V.] Univ Tennessee, Dept Microbiol, Knoxville, TN 37996 USA.
[Giorgi, Elena E.] Univ Massachusetts, Dept Math & Stat, Amherst, MA 01003 USA.
[Keele, Brandon F.] NCI, SAIC Frederick, Frederick, MD 21701 USA.
[Wang, Shuyi; Hahn, Beatrice H.; Shaw, George M.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[McMichael, Andrew J.] Univ Oxford, Weatherall Inst Mol Med, Oxford, England.
[Haynes, Barton F.] Duke Univ, Med Ctr, Durham, NC USA.
[Borrow, Persephone] Univ Oxford, Jenner Inst, Compton, England.
[Bhattacharya, Tanmoy; Korber, Bette T.] Santa Fe Inst, Santa Fe, NM 87501 USA.
RP Fischer, W (reprint author), Los Alamos Natl Lab, Los Alamos, NM USA.
EM btk@lanl.gov
RI Fischer, Will/B-1323-2013; Bhattacharya, Tanmoy/J-8956-2013;
OI Fischer, Will/0000-0003-4579-4062; Bhattacharya,
Tanmoy/0000-0002-1060-652X; Ganusov, Vitaly/0000-0001-6572-1691;
Wallstrom, Timothy/0000-0002-9295-2441; Korber,
Bette/0000-0002-2026-5757; Hraber, Peter/0000-0002-2920-4897
FU Los Alamos National Laboratory; National Institutes of Health (NIH)
[AI-0678501]; Bill and Melinda Gates Foundation [37874]
FX Funding for this work was supplied by a Los Alamos National Laboratory
Directed Research grant, National Institutes of Health (NIH) grant
AI-0678501 (CHAVI), and the Bill and Melinda Gates Foundation (#37874).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 45
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Z9 146
U1 1
U2 28
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 20
PY 2010
VL 5
IS 8
AR e12303
DI 10.1371/journal.pone.0012303
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 640TW
UT WOS:000281077000010
PM 20808830
ER
PT J
AU Li, KY
Singh, A
Crooks, DR
Dai, XM
Cong, ZZ
Pan, LA
Ha, D
Rouault, TA
AF Li, Kuanyu
Singh, Anamika
Crooks, Daniel R.
Dai, Xiaoman
Cong, Zhuangzhuang
Pan, Liang
Ha, Dung
Rouault, Tracey A.
TI Expression of Human Frataxin Is Regulated by Transcription Factors SRF
and TFAP2
SO PLOS ONE
LA English
DT Article
ID TRIPLET REPEAT EXPANSION; FRIEDREICH-ATAXIA; MITOCHONDRIAL IRON;
EPIGENETIC CHANGES; YEAST FRATAXIN; INTRON 1; ELEMENTS; GENE; PROTEIN;
DEFICIENCY
AB Background: Friedreich ataxia is an autosomal recessive neurodegenerative disease caused by reduced expression levels of the frataxin gene (FXN) due to expansion of triplet nucleotide GAA repeats in the first intron of FXN. Augmentation of frataxin expression levels in affected Friedreich ataxia patient tissues might substantially slow disease progression.
Methodology/Principal Findings: We utilized bioinformatic tools in conjunction with chromatin immunoprecipitation and electrophoretic mobility shift assays to identify transcription factors that influence transcription of the FXN gene. We found that the transcription factors SRF and TFAP2 bind directly to FXN promoter sequences. SRF and TFAP2 binding sequences in the FXN promoter enhanced transcription from luciferase constructs, while mutagenesis of the predicted SRF or TFAP2 binding sites significantly decreased FXN promoter activity. Further analysis demonstrated that robust SRF- and TFAP2-mediated transcriptional activity was dependent on a regulatory element, located immediately downstream of the first FXN exon. Finally, over-expression of either SRF or TFAP2 significantly increased frataxin mRNA and protein levels in HEK293 cells, and frataxin mRNA levels were also elevated in SH-SY5Y cells and in Friedreich ataxia patient lymphoblasts transfected with SRF or TFAP2.
Conclusions/Significance: We identified two transcription factors, SRF and TFAP2, as well as an intronic element encompassing EGR3-like sequence, that work together to regulate expression of the FXN gene. By providing new mechanistic insights into the molecular factors influencing frataxin expression, our results should aid in the discovery of new therapeutic targets for the treatment of Friedreich ataxia.
C1 [Li, Kuanyu; Dai, Xiaoman; Cong, Zhuangzhuang; Pan, Liang] Nanjing Univ, Sch Med, Jiangsu Key Lab Mol Med, Nanjing 210008, Peoples R China.
[Singh, Anamika; Crooks, Daniel R.; Ha, Dung; Rouault, Tracey A.] NICHHD, Program Mol Med, Bethesda, MD 20892 USA.
[Crooks, Daniel R.] Georgetown Univ, Med Ctr, Dept Biochem Mol & Cellular Biol, Washington, DC 20007 USA.
RP Li, KY (reprint author), Nanjing Univ, Sch Med, Jiangsu Key Lab Mol Med, Nanjing 210008, Peoples R China.
EM likuanyu@nju.edu.cn; trou@helix.nih.gov
FU NICHD, National Institutes of Health; Friedreich Ataxia Research
Alliance (FARA)
FX This work was supported by the intramural program of the NICHD, National
Institutes of Health, and in part by a research grant from Friedreich
Ataxia Research Alliance (FARA): http://www.curefa.org/. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 37
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Z9 13
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 20
PY 2010
VL 5
IS 8
AR e12286
DI 10.1371/journal.pone.0012286
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 640TW
UT WOS:000281077000005
PM 20808827
ER
PT J
AU Daniel, JA
Santos, MA
Wang, ZB
Zang, CZ
Schwab, KR
Jankovic, M
Filsuf, D
Chen, HT
Gazumyan, A
Yamane, A
Cho, YW
Sun, HW
Ge, K
Peng, WQ
Nussenzweig, MC
Casellas, R
Dressler, GR
Zhao, KJ
Nussenzweig, A
AF Daniel, Jeremy A.
Santos, Margarida Almeida
Wang, Zhibin
Zang, Chongzhi
Schwab, Kristopher R.
Jankovic, Mila
Filsuf, Darius
Chen, Hua-Tang
Gazumyan, Anna
Yamane, Arito
Cho, Young-Wook
Sun, Hong-Wei
Ge, Kai
Peng, Weiqun
Nussenzweig, Michel C.
Casellas, Rafael
Dressler, Gregory R.
Zhao, Keji
Nussenzweig, Andre
TI PTIP Promotes Chromatin Changes Critical for Immunoglobulin Class Switch
Recombination
SO SCIENCE
LA English
DT Article
ID LYSINE-4 METHYLTRANSFERASE COMPLEX; CYTIDINE DEAMINASE AID;
RNA-POLYMERASE-II; BRCT-DOMAIN; HISTONE MODIFICATIONS; CHROMOSOME
BREAKS; PROTEIN PTIP; DNA-DAMAGE; TRANSCRIPTION; METHYLATION
AB Programmed genetic rearrangements in lymphocytes require transcription at antigen receptor genes to promote accessibility for initiating double-strand break (DSB) formation critical for DNA recombination and repair. Here, we showed that activated B cells deficient in the PTIP component of the MLL3 (mixed-lineage leukemia 3)-MLL4 complex display impaired trimethylation of histone 3 at lysine 4 (H3K4me3) and transcription initiation of downstream switch regions at the immunoglobulin heavy-chain (Igh) locus, leading to defective immunoglobulin class switching. We also showed that PTIP accumulation at DSBs contributes to class switch recombination (CSR) and genome stability independently of Igh switch transcription. These results demonstrate that PTIP promotes specific chromatin changes that control the accessibility of the Igh locus to CSR and suggest a nonredundant role for the MLL3-MLL4 complex in altering antibody effector function.
C1 [Daniel, Jeremy A.; Santos, Margarida Almeida; Filsuf, Darius; Chen, Hua-Tang; Nussenzweig, Andre] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Wang, Zhibin; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Zang, Chongzhi; Peng, Weiqun] George Washington Univ, Dept Phys, Washington, DC 20052 USA.
[Schwab, Kristopher R.; Dressler, Gregory R.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Jankovic, Mila; Gazumyan, Anna; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
[Jankovic, Mila; Gazumyan, Anna; Nussenzweig, Michel C.] Howard Hughes Med Inst, New York, NY 10065 USA.
[Yamane, Arito; Casellas, Rafael] NIAMSD NIAMS, Bethesda, MD 20892 USA.
[Cho, Young-Wook; Ge, Kai] NIDDKD, Nucl Receptor Biol Sect, CEB, NIH, Bethesda, MD 20892 USA.
[Sun, Hong-Wei] NIAMS, Biodata Min & Discovery Sect, NIH, Bethesda, MD 20892 USA.
RP Nussenzweig, A (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM andre_nussenzweig@nih.gov
RI Cho, Young-Wook /F-8269-2011; Zang, Chongzhi/D-1445-2011; Yamane,
Arito/A-2959-2013; Daniel, Jeremy/S-4729-2016;
OI Daniel, Jeremy/0000-0002-1981-5571; Ge, Kai/0000-0002-7442-5138
FU NIH, National Cancer Institute, and Center for Cancer Research; National
Heart, Lung, and Blood Institute; NIH
FX We thank G. Gutierrez-Cruz, V. Sartorelli, M. Kruhlak, K. Cui, and Q.
Tang for technical assistance. This work was supported by funding from
the Intramural Research Program of the NIH, National Cancer Institute,
and Center for Cancer Research to A.N.; the Division of Intramural
Research at the National Heart, Lung, and Blood Institute to K.Z.; and
an NIH Director's Challenge Award on "Epigenomic regulation of mammalian
development and differentiation" to A.N., K.Z., and R.C. M.C.N. is a
Howard Hughes Medical Institute investigator. The authors declare no
competing financial interests and apologize for not being able to cite
all primary references due to space limitations. All sequence data have
been deposited in the Gene Expression Omnibus database (accession number
GSE20852) at http://ncbi.nlm.nih.gov/geo/.
NR 39
TC 68
Z9 70
U1 1
U2 11
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD AUG 20
PY 2010
VL 329
IS 5994
BP 917
EP 923
DI 10.1126/science.1187942
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 640WN
UT WOS:000281084800027
PM 20671152
ER
PT J
AU Leshchenko, VV
Kuo, PY
Shaknovich, R
Yang, DT
Gellen, T
Petrich, A
Yu, YT
Remache, Y
Weniger, MA
Rafiq, S
Suh, KS
Goy, A
Wilson, W
Verma, A
Braunschweig, I
Muthusamy, N
Kahl, BS
Byrd, JC
Wiestner, A
Melnick, A
Parekh, S
AF Leshchenko, Violetta V.
Kuo, Pei-Yu
Shaknovich, Rita
Yang, David T.
Gellen, Tobias
Petrich, Adam
Yu, Yiting
Remache, Yvonne
Weniger, Marc A.
Rafiq, Sarwish
Suh, K. Stephen
Goy, Andre
Wilson, Wyndham
Verma, Amit
Braunschweig, Ira
Muthusamy, Natarajan
Kahl, Brad S.
Byrd, John C.
Wiestner, Adrian
Melnick, Ari
Parekh, Samir
TI Genomewide DNA methylation analysis reveals novel targets for drug
development in mantle cell lymphoma
SO BLOOD
LA English
DT Article
ID CANDIDATE TUMOR-SUPPRESSOR; CYTOSINE METHYLATION; FOLLICULAR LYMPHOMA;
ABERRANT EXPRESSION; ANTI-CD37 ANTIBODY; MASS-SPECTROMETRY; CDK
INHIBITORS; BREAST-CANCER; B-CELLS; GENES
AB Mantle cell lymphoma (MCL) is a mostly incurable malignancy arising from naive B cells (NBCs) in the mantle zone of lymph nodes. We analyzed genomewide methylation in MCL patients with the HELP (Hpali tiny fragment Enrichment by Ligation-mediated PCR) assay and found significant aberrancy in promoter methylation patterns compared with normal NBCs. Using biologic and statistical criteria, we further identified 4 hypermethylated genes CDKN2B, MLF-1, PCDH8, and HOXD8 and 4 hypomethylated genes CD37, HDAC1, NOTCH1, and CDK5 when aberrant methylation was associated with inverse changes in mRNA levels. Immunohistochemical analysis of an independent cohort of MCL patient samples confirmed CD37 surface expression in 93% of patients, validating its selection as a target for MCL therapy. Treatment of MCL cell lines with a small modular immunopharmaceutical (CD37-SMIP) resulted in significant loss of viability in cell lines with intense surface CD37 expression. Treatment of MCL cell lines with the DNA methyltransferase inhibitor decitabine resulted in reversal of aberrant hypermethylation and synergized with the histone deacetylase inhibitor suberoylanilide hydroxamic acid in induction of the hypermethylated genes and anti-MCL cytotoxicity. Our data show prominent and aberrant promoter methylation in MCL and suggest that differentially methylated genes can be targeted for therapeutic benefit in MCL. (Blood. 2010; 116(7): 1025-1034)
C1 [Leshchenko, Violetta V.; Kuo, Pei-Yu; Gellen, Tobias; Petrich, Adam; Yu, Yiting; Verma, Amit; Braunschweig, Ira; Parekh, Samir] Yeshiva Univ, Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10461 USA.
[Shaknovich, Rita; Melnick, Ari] Weill Cornell Med Coll, Dept Med, New York, NY USA.
[Yang, David T.] Univ Wisconsin, Pathol & Lab Med, Madison, WI 53706 USA.
[Remache, Yvonne; Suh, K. Stephen; Goy, Andre] Hackensack Univ, Med Ctr, Hackensack, NJ USA.
[Weniger, Marc A.; Wilson, Wyndham; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Rafiq, Sarwish; Muthusamy, Natarajan; Byrd, John C.] Ohio State Univ, Div Hematol Oncol, Columbus, OH 43210 USA.
[Kahl, Brad S.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53706 USA.
RP Parekh, S (reprint author), Yeshiva Univ, Albert Einstein Coll Med, Albert Einstein Canc Ctr, 1300 Morris Pk Ave,Chanin 302-D2, Bronx, NY 10461 USA.
EM samir.parekh@einstein.yu.edu
OI Rafiq, Sarwish/0000-0002-9295-3065; Rafiq, Sajjad/0000-0003-4873-4540
FU Chemotherapy Foundation; Paul Calabresi Career Development Award [K12
CA132783-01]; National Cancer Institute [R01 CA104348, R01 HL082946, P01
CA95426, P01 CA813534]; Samuel Waxman Research Foundation; Gabrielle
Angel Foundation; Leukemia & Lymphoma Society; Hershaft Family
Foundation; Warren Brown Foundation
FX This work was supported by a grant from the Chemotherapy Foundation and
by a Paul Calabresi Career Development Award (K12 CA132783-01; S. P.);
by the National Cancer Institute (R01 CA104348 to A. M.; R01 HL082946 to
A. V.; P01 CA95426 and P01 CA813534 to J.C.B. and N.M.); by the
Chemotherapy Foundation and the Samuel Waxman Research Foundation (A.
M.); by the Gabrielle Angel Foundation, the Leukemia & Lymphoma Society,
and the Hershaft Family Foundation (A. V.); and by the D. Warren Brown
Foundation and the Leukemia & Lymphoma Society (J.C.B. and N.M.). A. M.
is a Leukemia & Lymphoma Scholar and Burroughs-Wellcome Clinical
Translational Scientist.
NR 51
TC 63
Z9 65
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 19
PY 2010
VL 116
IS 7
BP 1025
EP 1034
DI 10.1182/blood-2009-12-257485
PG 10
WC Hematology
SC Hematology
GA 641IE
UT WOS:000281117500005
PM 20427703
ER
PT J
AU Landgren, O
Rajkumar, SV
Pfeiffer, RM
Kyle, RA
Katzmann, JA
Dispenzieri, A
Cai, QY
Goldin, LR
Caporaso, NE
Fraumeni, JF
Blot, WJ
Signorello, LB
AF Landgren, Ola
Rajkumar, S. Vincent
Pfeiffer, Ruth M.
Kyle, Robert A.
Katzmann, Jerry A.
Dispenzieri, Angela
Cai, Qiuyin
Goldin, Lynn R.
Caporaso, Neil E.
Fraumeni, Joseph F.
Blot, William J.
Signorello, Lisa B.
TI Obesity is associated with an increased risk of monoclonal gammopathy of
undetermined significance among black and white women
SO BLOOD
LA English
DT Article
ID MULTIPLE-MYELOMA; SIGNIFICANCE MGUS; UNITED-STATES; PREVALENCE;
MORTALITY; PATTERNS; MEN; MACROGLOBULINEMIA; AMERICAN; CANCER
AB Obesity and black race have been associated with excess risk of multiple myeloma. The association of obesity with monoclonal gammopathy of undetermined significance (MGUS) is unknown. Further, it is not known whether the increased risk of multiple myeloma and MGUS in blacks is related to socioeconomic status, genetic susceptibility, or both. We screened 1000 black and 996 white women (range, 40-79 years) of similar socioeconomic status for MGUS; the aim of the study was to assess MGUS risk in relation to obesity and race. A total of 39 (3.9%) blacks and 21 (2.1%) whites had MGUS. On multivariate analysis, obesity (odds ratio [ OR] = 1.8; P = .04), black race (OR = 1.8; P = .04), and increasing age (> 55 vs < 43 years; OR = 2.5; P = .03) were independently associated with an excess risk of MGUS. Our findings support the hypothesis that obesity is etiologically linked to myelomagenesis. The 2-fold excess of MGUS among blacks compared with whites of similar socioeconomic status supports a role for susceptibility genes in MGUS. (Blood. 2010;116(7):1056-1059)
C1 [Landgren, Ola] NCI, NIH, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA.
[Landgren, Ola; Pfeiffer, Ruth M.; Goldin, Lynn R.; Caporaso, Neil E.; Fraumeni, Joseph F.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Rajkumar, S. Vincent; Kyle, Robert A.; Katzmann, Jerry A.; Dispenzieri, Angela] Mayo Clin, Coll Med, Div Hematol & Internal Med, Rochester, MN USA.
[Cai, Qiuyin; Blot, William J.; Signorello, Lisa B.] Vanderbilt Univ, Sch Med, Div Epidemiol, Nashville, TN 37212 USA.
[Cai, Qiuyin; Blot, William J.; Signorello, Lisa B.] Vanderbilt Univ, Dept Med, Vanderbilt Epidemiol Ctr, Nashville, TN USA.
[Cai, Qiuyin; Blot, William J.; Signorello, Lisa B.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Blot, William J.; Signorello, Lisa B.] Int Epidemiol Inst, Rockville, MD USA.
RP Landgren, O (reprint author), NCI, NIH, Ctr Canc Res, Med Oncol Branch, 9000 Rockville Pike,Bldg 10,Rm 13N240, Bethesda, MD 20892 USA.
EM landgreo@mail.nih.gov
RI Pfeiffer, Ruth /F-4748-2011;
OI Rajkumar, S. Vincent/0000-0002-5862-1833; Dispenzieri,
Angela/0000-0001-8780-9512
FU National Cancer Institute, National Institutes of Health; National
Cancer Institute providing basic support for the Southern Community
Cohort Study [R01 CA092447]; Susan G. Komen for the Cure
[OP05-0927-DR1]; National Cancer Institute [CA 62242, CA 107-476-03];
Vanderbilt-Ingram Cancer Center [P30 CA68485]
FX This work was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health, the National
Cancer Institute providing basic support for the Southern Community
Cohort Study (grant R01 CA092447), Susan G. Komen for the Cure (grant
OP05-0927-DR1) providing for additional information on the study
participants, the National Cancer Institute (grants CA 62242 and CA
107-476-03) and the facilities and resources of the Divisions of
Hematology, Biostatistics, Clinical Biochemistry and Immunology, and
Epidemiology at the Mayo Clinic. All electrophoresis and immunofixation
analyses were conducted by Ms Clark at the Mayo Clinic. Serum sample
preparation was conducted at the Survey and Biospecimen Shared Resource,
which is supported in part by the Vanderbilt-Ingram Cancer Center (P30
CA68485).
NR 27
TC 42
Z9 42
U1 2
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 19
PY 2010
VL 116
IS 7
BP 1056
EP 1059
DI 10.1182/blood-2010-01-262394
PG 4
WC Hematology
SC Hematology
GA 641IE
UT WOS:000281117500009
PM 20421448
ER
PT J
AU Li, HJ
Ji, M
Klarmann, KD
Keller, JR
AF Li, Huajie
Ji, Ming
Klarmann, Kimberly D.
Keller, Jonathan R.
TI Repression of Id2 expression by Gfi-1 is required for B-cell and myeloid
development
SO BLOOD
LA English
DT Article
ID LOOP-HELIX PROTEINS; HEMATOPOIETIC STEM-CELLS; ZINC-FINGER PROTEIN;
TRANSCRIPTIONAL REPRESSOR; DNA-BINDING; ERYTHROID DEVELOPMENT; HUMAN
NEUTROPENIA; ADULT MICE; IN-VIVO; PROGENITORS
AB The development of mature blood cells from hematopoietic stem cells requires coordinated activities of transcriptional networks. Transcriptional repressor growth factor independence 1 (Gfi-1) is required for the development of B cells, T cells, neutrophils, and for the maintenance of hematopoietic stem cell function. However, the mechanisms by which Gfi-1 regulates hematopoiesis and how Gfi-1 integrates into transcriptional networks remain unclear. Here, we provide evidence that Id2 is a transcriptional target of Gfi-1, and repression of Id2 by Gfi-1 is required for B-cell and myeloid development. Gfi-1 binds to 3 conserved regions in the Id2 promoter and represses Id2 promoter activity in transient reporter assays. Increased Id2 expression was observed in multipotent progenitors, myeloid progenitors, T-cell progenitors, and B-cell progenitors in Gfi-1(-/-) mice. Knockdown of Id2 expression or heterozygosity at the Id2 locus partially rescues the B-cell and myeloid development but not the T-cell development in Gfi-1(-/-) mice. These studies demonstrate a role of Id2 in mediating Gfi-1 functions in B-cell and myeloid development and provide a direct link between Gfi-1 and the B-cell transcriptional network by its ability to repress Id2 expression. (Blood. 2010;116(7):1060-1069)
C1 [Li, Huajie; Ji, Ming; Klarmann, Kimberly D.; Keller, Jonathan R.] NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res, Frederick, MD 21702 USA.
RP Keller, JR (reprint author), NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res, Bldg 560,Rm 12-03, Frederick, MD 21702 USA.
EM kellerjo@mail.nih.gov
RI Ji, Ming/C-2795-2011
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; National Institutes of Health, National Cancer
Institute, Center for Cancer Research
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract HHSN261200800001E. This research was supported, in part, by the
Intramural Research Program of National Institutes of Health, National
Cancer Institute, Center for Cancer Research.
NR 51
TC 27
Z9 29
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 19
PY 2010
VL 116
IS 7
BP 1060
EP 1069
DI 10.1182/blood-2009-11-255075
PG 10
WC Hematology
SC Hematology
GA 641IE
UT WOS:000281117500010
PM 20453161
ER
PT J
AU Ratajczak, P
Janin, A
de Latour, RP
Leboeuf, C
Desveaux, A
Keyvanfar, K
Robin, M
Clave, E
Douay, C
Quinquenel, A
Pichereau, C
Bertheau, P
Mary, JY
Socie, G
AF Ratajczak, Philippe
Janin, Anne
de Latour, Regis Peffault
Leboeuf, Christophe
Desveaux, Allison
Keyvanfar, Keyvan
Robin, Marie
Clave, Emmanuel
Douay, Corine
Quinquenel, Anne
Pichereau, Claire
Bertheau, Philippe
Mary, Jean Yves
Socie, Gerard
TI Th17/Treg ratio in human graft-versus-host disease
SO BLOOD
LA English
DT Article
ID REGULATORY T-CELLS; TH17 CELLS; SJOGRENS-SYNDROME; T(H)17 CELLS;
DIFFERENTIATION; EXPRESSION; ABSENCE; IL-17; GVHD
AB Th17 cells have never been explored in human graft-versus-host disease (GVHD). We studied the correlation between the presence of Th17 cells with histologic and clinical parameters. We first analyzed a cohort of 40 patients with GVHD of the gastrointestinal tract. Tumor necrosis factor (TNF), TNF receptors, and Fas expression, and apoptotic cells, CD4(+)IL-17(+) cells (Th17), and CD4(+)Foxp3(+) cells (Treg) were quantified. A Th17/Treg ratio less than 1 correlated both with the clinical diagnosis (P < .001) and more than 2 pathologic grades (P < .001). A Th17/Treg ratio less than 1 also correlated with the intensity of apoptosis of epithelial cells (P = .03), Fas expression in the cellular infiltrate (P = .003), TNF, and TNF receptor expression (P < .001). We then assessed Th17/Treg ratio in 2 other independent cohorts; a second cohort of 30 patients and confirmed that Th17/Treg ratio less than 1 correlated with the pathologic grade of GI GVHD. Finally, 15 patients with skin GVHD and 11 patients with skin rash but without pathologic GVHD were studied. Results in this third cohort of patients with skin disease confirmed those found in patients with GI GVHD. These analyses in 96 patients suggest that Th17/Treg ratio could be a sensitive and specific pathologic in situ biomarker of GVHD. (Blood. 2010;116(7):1165-1171)
C1 [Socie, Gerard] Hop St Louis, INSERM, U728, Serv Hematol Greffe, F-75010 Paris, France.
[Ratajczak, Philippe; Janin, Anne; de Latour, Regis Peffault; Leboeuf, Christophe; Desveaux, Allison; Clave, Emmanuel; Douay, Corine; Bertheau, Philippe; Mary, Jean Yves; Socie, Gerard] Univ Paris 07, Paris, France.
[Janin, Anne; Bertheau, Philippe] Hop St Louis, AP HP, Serv Pathol, Paris, France.
[de Latour, Regis Peffault; Robin, Marie; Quinquenel, Anne; Pichereau, Claire; Socie, Gerard] Hop St Louis, Serv Hematol Greffe, AP HP, F-75010 Paris, France.
[de Latour, Regis Peffault; Keyvanfar, Keyvan] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Mary, Jean Yves] Hop St Louis, AP HP, Lab Immunol & Histocompatibilite, F-75010 Paris, France.
[Clave, Emmanuel; Douay, Corine] INSERM, U940, Paris, France.
[Mary, Jean Yves] INSERM, U717, Paris, France.
RP Socie, G (reprint author), Hop St Louis, INSERM, U728, Serv Hematol Greffe, 1 Av Vellefaux, F-75010 Paris, France.
EM gerard.socie@sls.aphp.fr
RI Leboeuf, christophe/H-4583-2012; Ratajczak, Philippe/H-5398-2012;
OI Leboeuf, christophe/0000-0002-6537-0550; Clave,
Emmanuel/0000-0001-8217-5039
FU European Commission Stem-Diagnositics [LSHB-CT-2007-037703]; Institut
National du Cancer and Canceropole Ile de France; Conseil regional Ile
de France; Agence de Biomedecine; Aplastic Anemia and Myelodysplastic
Syndrome International Foundation
FX This work was supported by the European Commission Stem-Diagnositics
(contract no. LSHB-CT-2007-037703), Institut National du Cancer and
Canceropole Ile de France, Conseil regional Ile de France, and Agence de
Biomedecine. R.P.d.L. received a bursary award from the Aplastic Anemia
and Myelodysplastic Syndrome International Foundation.
NR 27
TC 60
Z9 66
U1 0
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 19
PY 2010
VL 116
IS 7
BP 1165
EP 1171
DI 10.1182/blood-2009-12-255810
PG 7
WC Hematology
SC Hematology
GA 641IE
UT WOS:000281117500022
PM 20484086
ER
PT J
AU Fuchs, A
Lin, TY
Beasley, DW
Stover, CM
Schwaeble, WJ
Pierson, TC
Diamond, MS
AF Fuchs, Anja
Lin, Tsai-Yu
Beasley, David W.
Stover, Cordula M.
Schwaeble, Wilhelm J.
Pierson, Theodore C.
Diamond, Michael S.
TI Direct Complement Restriction of Flavivirus Infection Requires Glycan
Recognition by Mannose-Binding Lectin
SO CELL HOST & MICROBE
LA English
DT Article
ID WEST-NILE-VIRUS; ANTIBODY-MEDIATED NEUTRALIZATION; DC-SIGN;
DENGUE-VIRUS; MONOCLONAL-ANTIBODIES; LINKED GLYCANS; CELLS; ACTIVATION;
PATHWAY; MOUSE
AB An intact complement system is crucial for limiting West Nile virus (WNV) dissemination. Herein, we define how complement directly restricts flavivirus infection in an antibody-independent fashion. Mannose-binding lectin (MBL) recognized N-linked glycans on the structural proteins of WNV and Dengue virus (DENV), resulting in neutralization through a C3- and C4-dependent mechanism that utilized both the canonical and bypass lectin activation pathways. For WNV, neutralization occurred with virus produced in insect cells, whereas for DENV, neutralization of insect and mammalian cell-derived virus was observed. Mechanism of action studies suggested that the MBL-dependent neutralization occurred, in part, by blocking viral fusion. Experiments in mice showed an MBL-dependent accelerated intravascular clearance of DENV or a WNV mutant with two N-linked glycans on its E protein, but not with wild-type WNV. Our studies show that MBL recognizes terminal mannose-containing carbohydrates on flaviviruses, resulting in neutralization and efficient clearance in vivo.
C1 [Fuchs, Anja; Diamond, Michael S.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
[Diamond, Michael S.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA.
[Diamond, Michael S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Diamond, Michael S.] Washington Univ, Sch Med, Midwest Reg Ctr Excellence Biodef & Emerging Infe, St Louis, MO 63110 USA.
[Lin, Tsai-Yu; Pierson, Theodore C.] NIH, Viral Pathogenesis Sect, Viral Dis Lab, Bethesda, MD 20892 USA.
[Beasley, David W.] Univ Texas Med Branch, Dept Microbiol & Immunol, Inst Human Infect & Immun, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA.
[Beasley, David W.] Univ Texas Med Branch, Sealy Ctr Vaccine Dev, Galveston, TX 77555 USA.
[Stover, Cordula M.; Schwaeble, Wilhelm J.] Univ Leicester, Dept Infect Immun & Inflammat, Leicester LE1 9HN, Leics, England.
RP Diamond, MS (reprint author), Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
RI Lin, Tsai-Yu/B-8873-2016;
OI Lin, Tsai-Yu/0000-0002-8076-1584; Stover, Cordula/0000-0002-0125-4868
FU National Institutes of Allergy and Infectious Diseases (NIAID); National
Institutes of Health (NIH) [R01 AI073755]; Midwest Regional Center of
Excellence for Biodefense and Emerging Infectious Diseases Research [U54
AI057160]
FX We thank J Atkinson for critical comments on the manuscript We also
thank X Wu for the C3-/- x C4-/- mice and C
Tedford (Omeros, Inc) for shipment of the MASP-2-
/ mice This work was supported by the Intramural Research
Program of the National Institutes of Allergy and Infectious Diseases
(NIAID) and grants from the National Institutes of Health (NIH) (R01
AI073755 and the Midwest Regional Center of Excellence for Biodefense
and Emerging Infectious Diseases Research [U54 AI057160])
NR 50
TC 30
Z9 32
U1 0
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD AUG 19
PY 2010
VL 8
IS 2
BP 186
EP 195
DI 10.1016/j.chom.2010.07.007
PG 10
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 641YR
UT WOS:000281169600008
PM 20709295
ER
PT J
AU Sul, B
Iwasa, KH
AF Sul, Bora
Iwasa, Kuni H.
TI Gating of Two Mechanoelectrical Transducer Channels Associated with a
Single Tip Link
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID SACCULAR HAIR CELL; NEGATIVE STIFFNESS; FAST ADAPTATION; BUNDLE;
LOCALIZATION; STEREOCILIA; SENSITIVITY; MECHANISMS; EPITHELIA; EAR
AB Although gating of mechanoelectrical transducer (MET) channels has been successfully described by assuming that one channel is associated with a tip link in the hair bundle, recent reports indicate that a single tip link is associated with more than one channel. To address the consistency of the model with the observations, gating of MET channels is described here by assuming that each tip link is associated with two identical MET channels, which are connected either in series or in parallel. We found that series connection does not lead to a single minimum of stiffness with respect to hair bundle displacement unless the minimum is above a certain positive value. Thus, negative stiffness must appear in pairs in the displacement axis. In contrast, parallel connection of the two channels predicts gating compliance similar to that predicted by the one-channel-per-tip-link model of channel gating, within the physiological range of parameters. Parallel connection of MET channels is, therefore, a reasonable assumption to explain most experimental observations. However, the compatibility with series connection cannot be ruled out for experimental data on turtle hair cells.
C1 [Sul, Bora; Iwasa, Kuni H.] Natl Inst Deafness & Other Commun Disorders, Biophys Sect, Lab Cellular Biol, NIH, Rockville, MD USA.
[Sul, Bora] Univ Maryland, Dept Phys, College Pk, MD 20742 USA.
RP Sul, B (reprint author), Natl Inst Deafness & Other Commun Disorders, Biophys Sect, Lab Cellular Biol, NIH, Rockville, MD USA.
EM sulb@nidcd.nih.gov
OI Iwasa, Kuni/0000-0002-9397-7704
FU National Institute on Deafness and Other Communication Disorders,
National Institutes of Health, Bethesda, Maryland
FX This work was supported by the intramural program of the National
Institute on Deafness and Other Communication Disorders, National
Institutes of Health, Bethesda, Maryland.
NR 23
TC 2
Z9 2
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD AUG 18
PY 2010
VL 99
IS 4
BP 1027
EP 1033
DI 10.1016/j.bpj.2010.05.029
PG 7
WC Biophysics
SC Biophysics
GA 641CW
UT WOS:000281103200005
PM 20712985
ER
PT J
AU Roos, WH
Gibbons, MM
Arkhipov, A
Uetrecht, C
Watts, NR
Wingfield, PT
Steven, AC
Heck, AJR
Schulten, K
Klug, WS
Wuite, GJL
AF Roos, W. H.
Gibbons, M. M.
Arkhipov, A.
Uetrecht, C.
Watts, N. R.
Wingfield, P. T.
Steven, A. C.
Heck, A. J. R.
Schulten, K.
Klug, W. S.
Wuite, G. J. L.
TI Squeezing Protein Shells: How Continuum Elastic Models, Molecular
Dynamics Simulations, and Experiments Coalesce at the Nanoscale
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID B-VIRUS CAPSIDS; VIRAL CAPSIDS; MECHANICAL-PROPERTIES; MOSAIC-VIRUS;
IN-VITRO; STABILITY; NANOINDENTATION; DEFORMATION
AB The current rapid growth in the use of nanosized particles is fueled in part by our increased understanding of their physical properties and ability to manipulate them, which is essential for achieving optimal functionality. Here we report detailed quantitative measurements of the mechanical response of nanosized protein shells (viral capsids) to large-scale physical deformations and compare them with theoretical descriptions from continuum elastic modeling and molecular dynamics (MD). Specifically, we used nanoindentation by atomic force microscopy to investigate the complex elastic behavior of Hepatitis B virus capsids. These capsids are hollow, similar to 30 nm in diameter, and conform to icosahedral (5-3-2) symmetry. First we show that their indentation behavior, which is symmetry-axis-dependent, cannot be reproduced by a simple model based on Foppl-von Karman thin-shell elasticity with the fivefold vertices acting as prestressed disclinations. However, we can properly describe the measured nonlinear elastic and orientation-dependent force response with a three-dimensional, topographically detailed, finite-element model. Next, we show that coarse-grained MD simulations also yield good agreement with our nanoindentation measurements, even without any fitting of force-field parameters in the MD model. This study demonstrates that the material properties of viral nanoparticles can be correctly described by both modeling approaches. At the same time, we show that even for large deformations, it suffices to approximate the mechanical behavior of nanosized viral shells with a continuum approach, and ignore specific molecular interactions. This experimental validation of continuum elastic theory provides an example of a situation in which rules of macroscopic physics can apply to nanoscale molecular assemblies.
C1 [Roos, W. H.; Wuite, G. J. L.] Vrije Univ Amsterdam, Ctr Laser, Amsterdam, Netherlands.
[Gibbons, M. M.] Univ Calif Los Angeles, Dept Mech & Aerosp Engn, Los Angeles, CA USA.
[Arkhipov, A.; Schulten, K.] Univ Illinois, Dept Phys, Urbana, IL 61801 USA.
[Arkhipov, A.; Schulten, K.] Univ Illinois, Beckman Inst, Urbana, IL USA.
[Uetrecht, C.; Heck, A. J. R.] Univ Utrecht, Biomol Mass Spectrometry & Prote Grp, Utrecht Inst Pharmaceut Sci, Utrecht, Netherlands.
[Uetrecht, C.; Heck, A. J. R.] Univ Utrecht, Bijvoet Ctr, NL-3508 TB Utrecht, Netherlands.
[Uetrecht, C.; Heck, A. J. R.] Netherlands Prote Ctr, Utrecht, Netherlands.
[Watts, N. R.; Wingfield, P. T.; Steven, A. C.] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Wuite, GJL (reprint author), Vrije Univ Amsterdam, Ctr Laser, Amsterdam, Netherlands.
EM gwuite@nat.vu.nl
RI Uetrecht, Charlotte/D-1883-2010; Schulten, Klaus/D-5561-2009; Heck,
Albert/D-7098-2011; Roos, Wouter/L-8346-2014
OI Uetrecht, Charlotte/0000-0002-1991-7922; Heck,
Albert/0000-0002-2405-4404; Roos, Wouter/0000-0002-5104-0139
FU Stichting voor de Technische Wetenschappen; Netherlands Organisation for
Scientific Research; National Science Foundation [CMMI-0748034,
DMS-0349195, PHY0822613, MCA93S028]; National Institutes of Health
[K25AI058672, 5T32AI060567-05, P41-RR005969]; National Institute of
Arthritis and Musculoskeletal and Skin Diseases; U.S. Department of
Education; L. S. Edelheit fellowship
FX This work was supported by a NanoSci-E+ grant administered by Stichting
voor de Technische Wetenschappen (G.J.L.W.), the Netherlands
Organisation for Scientific Research through a CW-ECHO grant (G.J.L.W.),
a Rubicon grant (W.H.R.), a CAREER Award from the National Science
Foundation (CMMI-0748034 to W.S.K.), grants DMS-0349195 (M.M.G.) and
PHY0822613 (K.S.), supercomputer time (MCA93S028), National Institutes
of Health grants K25AI058672 and 5T32AI060567-05 (M.M.G.) and
P41-RR005969 (K.S.), and the intramural research program of the National
Institute of Arthritis and Musculoskeletal and Skin Diseases (N.R.W.,
P.T.W., and A.C.S.). M.M.G. was supported by a Graduate Assistance in
Areas of National Need fellowship from the U.S. Department of Education,
and A.A. was supported by an L. S. Edelheit fellowship.
NR 36
TC 44
Z9 44
U1 2
U2 35
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD AUG 18
PY 2010
VL 99
IS 4
BP 1175
EP 1181
DI 10.1016/j.bpj.2010.05.033
PG 7
WC Biophysics
SC Biophysics
GA 641CW
UT WOS:000281103200021
PM 20713001
ER
PT J
AU Haspel, G
O'Donovan, MJ
Hart, AC
AF Haspel, Gal
O'Donovan, Michael J.
Hart, Anne C.
TI Motoneurons Dedicated to Either Forward or Backward Locomotion in the
Nematode Caenorhabditis elegans
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID C-ELEGANS; NEURONAL-ACTIVITY; NEURAL MECHANISMS; NERVOUS-SYSTEM;
MOTOR-NEURONS; IN-VIVO; BEHAVIOR; ASCARIS; MUSCLE; INDICATORS
AB Multifunctional motoneurons and muscles, which are active during forward and backward locomotion are ubiquitous in animal models. However, studies in the nematode Caenorhabditis elegans suggest that some locomotor motoneurons are necessary only for forward locomotion (dorsal B-motoneurons, DB), while others (dorsal A-motoneurons, DA) are necessary only for backward locomotion. We tested this hypothesis directly by recording the activity of these motoneurons during semirestrained locomotion. For this purpose, we used epifluorescence imaging of the genetically encoded calcium sensor cameleon, expressed in specific motoneurons, while monitoring locomotor behavior through the microscope condenser using a second camera. We found that ventral and dorsal B-motoneurons (DB and VB) were coactive during forward locomotion while ventral A-motoneurons (VA) were only active during backward locomotion. The signals we recorded correlated with the direction of locomotion but not with the faster undulatory cycles. To our knowledge, these are the first recordings of motoneuron activity in C. elegans and the only direction-dedicated motoneurons described to date.
C1 [Haspel, Gal; Hart, Anne C.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA.
[Haspel, Gal; O'Donovan, Michael J.] NINDS, Neural Control Lab, Sect Dev Neurobiol, NIH, Bethesda, MD 20892 USA.
RP Hart, AC (reprint author), Brown Univ, Dept Neurosci, 60 Olive St,SFH458 Mailbox GL-N, Providence, RI 02912 USA.
EM Anne_Hart@brown.edu
RI o'donovan, michael/A-2357-2015;
OI o'donovan, michael/0000-0003-2487-7547; Haspel, Gal/0000-0001-6701-697X
FU National Institutes of Health (NIH); National Institute of General
Medical Sciences; National Institute of Neurological Disorders and
Stroke (NINDS); The International Human Frontier Science Program
Organization; NIH NINDS; NIH National Center for Research Resources
FX This work was supported by funding from National Institutes of Health
(NIH) National Institute of General Medical Sciences and National
Institute of Neurological Disorders and Stroke (NINDS) (A.C.H.). G.H.
was supported by The International Human Frontier Science Program
Organization. The work was supported in part by the intramural program
of the NIH NINDS. We thank S. Lockery and S. Faumont (University of
Oregon) for their help and comments. YC2.60 and YC3.60 plasmids were a
generous gift from A. Miyawaki (RIKEN, Japan). Some nematode strains
used in this work were provided by the Caenorhabditis Genetics Center,
which is funded by the NIH National Center for Research Resources.
NR 39
TC 26
Z9 26
U1 0
U2 2
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 AUG 18
PY 2010
VL 30
IS 33
BP 11151
EP 11156
DI 10.1523/JNEUROSCI.2244-10.2010
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 642HK
UT WOS:000281197900021
PM 20720122
ER
PT J
AU Daw, MI
Pelkey, KA
Chittajallu, R
McBain, CJ
AF Daw, Michael I.
Pelkey, Kenneth A.
Chittajallu, Ramesh
McBain, Chris J.
TI Presynaptic Kainate Receptor Activation Preserves Asynchronous GABA
Release Despite the Reduction in Synchronous Release from Hippocampal
Cholecystokinin Interneurons
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID MOSSY FIBER SYNAPSES; RAT HIPPOCAMPUS; EXPRESSING CHOLECYSTOKININ;
PERISOMATIC INHIBITION; SYNAPTIC-TRANSMISSION; GABAERGIC INHIBITION;
CELLS; CA1; PARVALBUMIN; MECHANISMS
AB Inhibitory synaptic transmission in the hippocampus in mediated by a wide variety of different interneuron classes which are assumed to play different roles in network activity. Activation of presynaptic kainate receptors (KARs) has been shown to reduce inhibitory transmission but the interneuron class(es) at which they act is only recently beginning to emerge. Using paired recordings we show that KAR activation causes a decrease in presynaptic release from cholecystokinin (CCK)- but not parvalbumin-containing interneurons and that this decrease is observed when pyramidal cells, but not interneurons, are the postsynaptic target. We also show that although the synchronous release component is reduced, the barrage of asynchronous GABA release from CCK interneurons during sustained firing is unaffected by KAR activation. This indicates that presynaptic KARs preserve and act in concert with asynchronous release to switch CCK interneurons from a phasic inhibition mode to produce prolonged inhibition during periods of intense activity.
C1 [Daw, Michael I.; Pelkey, Kenneth A.; McBain, Chris J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurosci, Bethesda, MD 20892 USA.
[Chittajallu, Ramesh] NINDS, Dev Synapt Plast Sect, NIH, Bethesda, MD 20892 USA.
RP Daw, MI (reprint author), Univ Edinburgh, Ctr Integrat Physiol, Edinburgh EH8 9XD, Midlothian, Scotland.
EM michael.daw@ed.ac.uk
OI Daw, Michael/0000-0002-8374-5977
FU National Institute of Child Health and Human Development
FX This research was supported by the Intramural Research Program of the
National Institute of Child Health and Human Development to C.J.M.
Thanks to Josh Huang for the generous gift of the B13 PV-GFP mouse line
and Gabor Szabo for the gift of the GAD-65 GFP line. We thank Christine
Torborg for comments on the manuscript. We also thank Brian Jeffries for
expert technical assistance.
NR 35
TC 19
Z9 19
U1 0
U2 3
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 AUG 18
PY 2010
VL 30
IS 33
BP 11202
EP 11209
DI 10.1523/JNEUROSCI.6334-09.2010
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 642HK
UT WOS:000281197900027
PM 20720128
ER
PT J
AU Braithwaite, EK
Kedar, PS
Stumpo, DJ
Bertocci, B
Freedman, JH
Samson, LD
Wilson, SH
AF Braithwaite, Elena K.
Kedar, Padmini S.
Stumpo, Deborah J.
Bertocci, Barbara
Freedman, Jonathan H.
Samson, Leona D.
Wilson, Samuel H.
TI DNA Polymerases beta and lambda Mediate Overlapping and Independent
Roles in Base Excision Repair in Mouse Embryonic Fibroblasts
SO PLOS ONE
LA English
DT Article
ID CELL NUCLEAR ANTIGEN; DAMAGE; IOTA; HYPERMUTATION; GLYCOSYLASE;
DEFICIENT; BYPASS; SITES
AB Base excision repair (BER) is a DNA repair pathway designed to correct small base lesions in genomic DNA. While DNA polymerase beta (pol beta) is known to be the main polymerase in the BER pathway, various studies have implicated other DNA polymerases in back-up roles. One such polymerase, DNA polymerase lambda (pol lambda), was shown to be important in BER of oxidative DNA damage. To further explore roles of the X-family DNA polymerases lambda and beta in BER, we prepared a mouse embryonic fibroblast cell line with deletions in the genes for both pol beta and pol lambda. Neutral red viability assays demonstrated that pol lambda and pol beta double null cells were hypersensitive to alkylating and oxidizing DNA damaging agents. In vitro BER assays revealed a modest contribution of pol lambda to single-nucleotide BER of base lesions. Additionally, using co-immunoprecipitation experiments with purified enzymes and whole cell extracts, we found that both pol lambda and pol beta interact with the upstream DNA glycosylases for repair of alkylated and oxidized DNA bases. Such interactions could be important in coordinating roles of these polymerases during BER.
C1 [Braithwaite, Elena K.; Kedar, Padmini S.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Braithwaite, Elena K.; Freedman, Jonathan H.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
[Stumpo, Deborah J.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
[Bertocci, Barbara] INSERM, Fac Med Paris Descartes, U783, Paris, France.
[Samson, Leona D.] MIT, Biol Engn Dept, Cambridge, MA 02139 USA.
RP Braithwaite, EK (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM wilson5@niehs.nih.gov
FU National Institutes of Health (NIH) [ES050158, ES050159, CA055042,
HHSN273200700046U]
FX This work was supported by National Institutes of Health (NIH) grants
ES050158 and ES050159 from the Intramural Research Program and by NIH
grant CA055042 (to L.S.). P.K.'s contribution was supported in whole
with funds from NIH, under delivery order HHSN273200700046U to
Constella/SRA, LLC. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 24
TC 29
Z9 29
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 18
PY 2010
VL 5
IS 8
AR e12229
DI 10.1371/journal.pone.0012229
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 639XY
UT WOS:000281011600011
PM 20805875
ER
PT J
AU Jacox, E
Gotea, V
Ovcharenko, I
Elnitski, L
AF Jacox, Edwin
Gotea, Valer
Ovcharenko, Ivan
Elnitski, Laura
TI Tissue-Specific and Ubiquitous Expression Patterns from Alternative
Promoters of Human Genes
SO PLOS ONE
LA English
DT Article
ID TRANSPOSABLE ELEMENTS; MAMMALIAN GENOMES; P1 PROMOTER; DNA;
IDENTIFICATION; LIVER; RNA; CONSERVATION; EVOLUTION; SELECTION
AB Background: Transcriptome diversity provides the key to cellular identity. One important contribution to expression diversity is the use of alternative promoters, which creates mRNA isoforms by expanding the choice of transcription initiation sites of a gene. The proximity of the basal promoter to the transcription initiation site enables prediction of a promoter's location based on the gene annotations. We show that annotation of alternative promoters regulating expression of transcripts with distinct first exons enables a novel methodology to quantify expression levels and tissue specificity of mRNA isoforms.
Principal Findings: The use of distinct alternative first exons in 3,296 genes was examined using exon-microarray data from 11 human tissues. Comparing two transcripts from each gene we found that the activity of alternative promoters (i.e., P1 and P2) was not correlated through tissue specificity or level of expression. Furthermore neither P1 nor P2 conferred any bias for tissue-specific or ubiquitous expression. Genes associated with specific diseases produced transcripts whose limited expression patterns were consistent with the tissue affected in disease. Notably, genes that were historically designated as tissue-specific or housekeeping had alternative isoforms that showed differential expression. Furthermore, only a small number of alternative promoters showed expression exclusive to a single tissue indicating that "tissue preference" provides a better description of promoter activity than tissue specificity. When compared to gene expression data in public databases, as few as 22% of the genes had detailed information for more than one isoform, whereas the remainder collapsed the expression patterns from individual transcripts into one profile.
Conclusions: We describe a computational pipeline that uses microarray data to assess the level of expression and breadth of tissue profiles for transcripts with distinct first exons regulated by alternative promoters. We conclude that alternative promoters provide individualized regulation that is confirmed through expression levels, tissue preference and chromatin modifications. Although the selective use of alternative promoters often goes uncharacterized in gene expression analyses, transcripts produced in this manner make unique contributions to the cell that requires further exploration.
C1 [Jacox, Edwin; Gotea, Valer; Elnitski, Laura] NHGRI, NIH, Rockville, MD USA.
[Gotea, Valer; Ovcharenko, Ivan] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
RP Jacox, E (reprint author), NHGRI, NIH, Rockville, MD USA.
EM Elnitski@mail.nih.gov
OI Gotea, Valer/0000-0001-7857-3309
FU National Human Genome Research Institute, National Institutes of Health;
National Center for Biotechnology Information, National Institutes of
Health
FX LE is supported by the Intramural Research Program of the National Human
Genome Research Institute, National Institutes of Health. IO is
supported by the Intramural Research Program of the National Center for
Biotechnology Information, National Institutes of Health. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 48
TC 17
Z9 17
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 18
PY 2010
VL 5
IS 8
AR e12274
DI 10.1371/journal.pone.0012274
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 639XY
UT WOS:000281011600032
PM 20806066
ER
PT J
AU Sengupta, A
Lichti, UF
Carlson, BA
Ryscavage, AO
Gladyshev, VN
Yuspa, SH
Hatfield, DL
AF Sengupta, Aniruddha
Lichti, Ulrike F.
Carlson, Bradley A.
Ryscavage, Andrew O.
Gladyshev, Vadim N.
Yuspa, Stuart H.
Hatfield, Dolph L.
TI Selenoproteins Are Essential for Proper Keratinocyte Function and Skin
Development
SO PLOS ONE
LA English
DT Article
ID VITAMIN-E; IN-VITRO; SELENIUM DEFICIENCY; STRATUM-CORNEUM; TRANSGENIC
MICE; HAIR FOLLICLE; BETA-CAROTENE; GENE TRSP; ANTIOXIDANTS; EXPRESSION
AB Dietary selenium is known to protect skin against UV-induced damage and cancer and its topical application improves skin surface parameters in humans, while selenium deficiency compromises protective antioxidant enzymes in skin. Furthermore, skin and hair abnormalities in humans and rodents may be caused by selenium deficiency, which are overcome by dietary selenium supplementation. Most important biological functions of selenium are attributed to selenoproteins, proteins containing selenium in the form of the amino acid, selenocysteine (Sec). Sec insertion into proteins depends on Sec tRNA; thus, knocking out the Sec tRNA gene (Trsp) ablates selenoprotein expression. We generated mice with targeted removal of selenoproteins in keratin 14 (K14) expressing cells and their differentiated descendents. The knockout progeny had a runt phenotype, developed skin abnormalities and experienced premature death. Lack of selenoproteins in epidermal cells led to the development of hyperplastic epidermis and aberrant hair follicle morphogenesis, accompanied by progressive alopecia after birth. Further analyses revealed that selenoproteins are essential antioxidants in skin and unveiled their role in keratinocyte growth and viability. This study links severe selenoprotein deficiency to abnormalities in skin and hair and provides genetic evidence for the role of these proteins in keratinocyte function and cutaneous development.
C1 [Sengupta, Aniruddha; Carlson, Bradley A.; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, NIH, Bethesda, MD 20892 USA.
[Lichti, Ulrike F.; Ryscavage, Andrew O.; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
[Gladyshev, Vadim N.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA USA.
RP Sengupta, A (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
EM yuspas@dc37a.nci.nih.gov; hatfield@mail.nih.gov
RI Gladyshev, Vadim/A-9894-2013
FU National Institutes of Health, National Cancer Institute; Center for
Cancer Research; NIH
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, and Center for
Cancer Research, and in addition, NIH grants awarded to VNG. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 41
TC 24
Z9 24
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 18
PY 2010
VL 5
IS 8
AR e12249
DI 10.1371/journal.pone.0012249
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 639XY
UT WOS:000281011600021
PM 20805887
ER
PT J
AU Sobocinski, GP
Toy, K
Bobrowski, WF
Shaw, S
Anderson, AO
Kaldjian, EP
AF Sobocinski, Gregg P.
Toy, Katherine
Bobrowski, Walter F.
Shaw, Stephen
Anderson, Arthur O.
Kaldjian, Eric P.
TI Ultrastructural localization of extracellular matrix proteins of the
lymph node cortex: evidence supporting the reticular network as a
pathway for lymphocyte migration
SO BMC IMMUNOLOGY
LA English
DT Article
ID HIGH ENDOTHELIAL VENULES; DENDRITIC CELLS; T-LYMPHOCYTES; FIBRONECTIN;
ADHESION; ANTIGEN; FIBERS; RAT; ORGANIZATION; INFORMATION
AB Background: The lymph node (LN) is a crossroads of blood and lymphatic vessels allowing circulating lymphocytes to efficiently recognize foreign molecules displayed on antigen presenting cells. Increasing evidence indicates that after crossing high endothelial venules, lymphocytes migrate within the node along the reticular network (RN), a scaffold of fibers enwrapped by fibroblastic reticular cells (FRC). Light microscopy has shown that the RN contains specific extracellular matrix (ECM) proteins, which are putative molecular "footholds" for migration, and are known ligands for lymphocyte integrin adhesion receptors.
Results: To investigate whether ECM proteins of the RN are present on the outer surface of the FRC and are thus accessible to migrating lymphocytes, ultrastructural immunohistochemical staining of cynomolgus monkey LN was performed using antibodies to human ECM proteins that were successfully employed at the light microscopic level. The fibrillar collagens I and III were observed primarily within the reticular network fibers themselves. In contrast, the matrix proteins laminin, fibronectin, collagen IV, and tenascin were observed within the reticular fibers and also on the outer membrane surface of the FRC.
Conclusions: These findings suggest a molecular basis for how the RN functions as a pathway for lymphocyte migration within the lymph node.
C1 [Kaldjian, Eric P.] Hearing Hlth Sci, Ann Arbor, MI USA.
[Sobocinski, Gregg P.] Univ Michigan, MCDB Dept, Ann Arbor, MI 48109 USA.
[Toy, Katherine] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Bobrowski, Walter F.] Pfizer Global R&D, Groton, CT USA.
[Shaw, Stephen] NCI, Bethesda, MD 20892 USA.
[Anderson, Arthur O.] USAMRIID, Frederick, MD USA.
RP Kaldjian, EP (reprint author), Hearing Hlth Sci, Ann Arbor, MI USA.
EM eric.kaldjian@umich.edu
NR 31
TC 11
Z9 11
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 AUG 17
PY 2010
VL 11
AR 42
DI 10.1186/1471-2172-11-42
PG 11
WC Immunology
SC Immunology
GA 666PK
UT WOS:000283128000001
PM 20716349
ER
PT J
AU Shin, R
Ikemoto, S
AF Shin, Rick
Ikemoto, Satoshi
TI Administration of the GABA(A) receptor antagonist picrotoxin into rat
supramammillary nucleus induces c-Fos in reward-related brain
structures. Supramammillary picrotoxin and c-Fos expression
SO BMC NEUROSCIENCE
LA English
DT Article
ID VENTRAL TEGMENTAL AREA; CONDITIONED PLACE PREFERENCE; MEDIAL PREOPTIC
AREA; SELF-STIMULATION; DOPAMINERGIC MECHANISMS; PRIMARY REINFORCEMENT;
FRONTAL-CORTEX; RAPHE NUCLEI; MORPHINE; PROJECTIONS
AB Background: Picrotoxin blocks GABA(A) receptors, whose activation typically inhibits neuronal firing activity. We recently found that rats learn to selectively self-administer picrotoxin or bicuculline, another GABA(A) receptor antagonist, into the supramammillary nucleus (SuM), a posterior hypothalamic structure localized anterior to the ventral tegmental area. Other drugs such as nicotine or the excitatory amino acid AMPA are also self-administered into the SuM. The SuM appears to be functionally linked with the mesolimbic dopamine system and is closely connected with other brain structures that are implicated in motivational processes, including the prefrontal cortex, septal area, preoptic area, lateral hypothalamic area and dorsal raphe nucleus. Here, we hypothesized that these brain structures are activated by picrotoxin injections into the SuM.
Results: Picrotoxin administration into the SuM markedly facilitated locomotion and rearing. Further, it increased c-Fos expression in this region, suggesting blockade of tonic inhibition and thus the disinhibition of local neurons. This manipulation also increased c-Fos expression in structures including the ventral tegmental area, medial shell of the nucleus accumbens, medial prefrontal cortex, septal area, preoptic area, lateral hypothalamic area and dorsal raphe nucleus.
Conclusions: Picrotoxin administration into the SuM appears to disinhibit local neurons and recruits activation of brain structures associated with motivational processes, including the mesolimbic dopamine system, prefrontal cortex, septal area, preoptic area, lateral hypothalamic area and dorsal raphe nucleus. These regions may be involved in mediating positive motivational effects triggered by intra-SuM picrotoxin.
C1 [Shin, Rick; Ikemoto, Satoshi] NIDA, Behav Neurosci Branch, NIH, US Dept HHS, Baltimore, MD 21224 USA.
RP Ikemoto, S (reprint author), NIDA, Behav Neurosci Branch, NIH, US Dept HHS, Baltimore, MD 21224 USA.
EM Satoshi.Ikemoto@nih.gov
OI Ikemoto, Satoshi/0000-0002-0732-7386
FU National Institute on Drug Abuse, National Institutes of Health
[Z01-DA000439]
FX This research was supported by the Intramural Research Program of
National Institute on Drug Abuse, National Institutes of Health
(Z01-DA000439).
NR 36
TC 5
Z9 5
U1 1
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2202
J9 BMC NEUROSCI
JI BMC Neurosci.
PD AUG 17
PY 2010
VL 11
AR 101
DI 10.1186/1471-2202-11-101
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 650AC
UT WOS:000281817400002
PM 20716371
ER
PT J
AU Lu, CH
Han, HD
Mangala, LS
Ali-Fehmi, R
Newton, CS
Ozbun, L
Armaiz-Pena, GN
Hu, W
Stone, RL
Munkarah, A
Ravoori, MK
Shahzad, MMK
Lee, JW
Mora, E
Langley, RR
Carroll, AR
Matsuo, K
Spannuth, WA
Schmandt, R
Jennings, NB
Goodman, BW
Jaffe, RB
Nick, AM
Kim, HS
Guven, EO
Chen, YH
Li, LY
Hsu, MC
Coleman, RL
Calin, GA
Denkbas, EB
Lim, JY
Lee, JS
Kundra, V
Birrer, MJ
Hung, MC
Lopez-Berestein, G
Sood, AK
AF Lu, Chunhua
Han, Hee Dong
Mangala, Lingegowda S.
Ali-Fehmi, Rouba
Newton, Christopher S.
Ozbun, Laurent
Armaiz-Pena, Guillermo N.
Hu, Wei
Stone, Rebecca L.
Munkarah, Adnan
Ravoori, Murali K.
Shahzad, Mian M. K.
Lee, Jeong-Won
Mora, Edna
Langley, Robert R.
Carroll, Amy R.
Matsuo, Koji
Spannuth, Whitney A.
Schmandt, Rosemarie
Jennings, Nicholas B.
Goodman, Blake W.
Jaffe, Robert B.
Nick, Alpa M.
Kim, Hye Sun
Guven, Eylem Ozturk
Chen, Ya-Huey
Li, Long-Yuan
Hsu, Ming-Chuan
Coleman, Robert L.
Calin, George A.
Denkbas, Emir B.
Lim, Jae Yun
Lee, Ju-Seog
Kundra, Vikas
Birrer, Michael J.
Hung, Mien-Chie
Lopez-Berestein, Gabriel
Sood, Anil K.
TI Regulation of Tumor Angiogenesis by EZH2
SO CANCER CELL
LA English
DT Article
ID NEGATIVE FEEDBACK REGULATOR; INTERFERING RNA DELIVERY; OVARIAN-CANCER;
GROWTH-FACTOR; IN-VIVO; ANTIVASCULAR THERAPY; CHROMATIN-STRUCTURE;
ENDOTHELIAL-CELLS; BREAST-CANCER; EXPRESSION
AB Although VEGF-targeted therapies are showing promise, new angiogenesis targets are needed to make additional gains. Here, we show that increased Zeste homolog 2 (EZH2) expression in either tumor cells or in tumor vasculature is predictive of poor clinical outcome. The increase in endothelial EZH2 is a direct result of VEGF stimulation by a paracrine circuit that promotes angiogenesis by methylating and silencing vasohibin1 (vash1). Ezh2 silencing in the tumor-associated endothelial cells inhibited angiogenesis mediated by reactivation of VASH1, and reduced ovarian cancer growth, which is further enhanced in combination with ezh2 silencing in tumor cells. Collectively, these data support the potential for targeting ezh2 as an important therapeutic approach.
C1 [Lu, Chunhua; Han, Hee Dong; Mangala, Lingegowda S.; Armaiz-Pena, Guillermo N.; Hu, Wei; Stone, Rebecca L.; Shahzad, Mian M. K.; Lee, Jeong-Won; Mora, Edna; Carroll, Amy R.; Matsuo, Koji; Spannuth, Whitney A.; Schmandt, Rosemarie; Jennings, Nicholas B.; Goodman, Blake W.; Nick, Alpa M.; Kim, Hye Sun; Coleman, Robert L.; Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA.
[Ravoori, Murali K.; Kundra, Vikas] Univ Texas MD Anderson Canc Ctr, Dept Expt Diagnost Imaging, Houston, TX 77030 USA.
[Langley, Robert R.; Lopez-Berestein, Gabriel; Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA.
[Hsu, Ming-Chuan; Hung, Mien-Chie] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA.
[Coleman, Robert L.; Calin, George A.; Lopez-Berestein, Gabriel; Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Ctr RNA & Noncoding RNA, Houston, TX 77030 USA.
[Calin, George A.; Lopez-Berestein, Gabriel] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA.
[Lim, Jae Yun; Lee, Ju-Seog] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
[Ali-Fehmi, Rouba] Wayne State Univ, Sch Med, Karmanos Canc Inst, Dept Pathol, Detroit, MI 48201 USA.
[Newton, Christopher S.; Ozbun, Laurent] NCI, Dept Cell & Canc Biol, Bethesda, MD 20892 USA.
[Munkarah, Adnan] Henry Ford Hlth Syst, Womens Hlth Serv, Detroit, MI 48202 USA.
[Shahzad, Mian M. K.] Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA.
[Lee, Jeong-Won] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Obstet & Gynecol, Seoul 135710, South Korea.
[Mora, Edna] Univ Puerto Rico, Dept Surg, San Juan, PR 00935 USA.
[Jaffe, Robert B.] Univ Calif San Francisco, Ctr Reprod Sci, San Francisco, CA 94143 USA.
[Kim, Hye Sun] Kwandong Univ Coll Med, Cheil Gen Hosp, Dept Pathol, Seoul 100380, South Korea.
[Kim, Hye Sun] Kwandong Univ Coll Med, Womens Healthcare Ctr, Seoul 100380, South Korea.
[Guven, Eylem Ozturk] Hacettepe Univ, Nanotechnol & Nanomed Div, TR-06532 Ankara, Turkey.
[Chen, Ya-Huey; Li, Long-Yuan; Hung, Mien-Chie] China Med Univ & Hosp, Ctr Mol Med, Taichung 40447, Taiwan.
[Chen, Ya-Huey; Li, Long-Yuan; Hung, Mien-Chie] China Med Univ & Hosp, Grad Inst Canc Biol, Taichung 40447, Taiwan.
[Li, Long-Yuan] Asia Univ, Dept Biotechnol, Taichung 41354, Taiwan.
[Birrer, Michael J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr,Dept Med, Boston, MA 02114 USA.
RP Sood, AK (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, 1515 Holcombe Blvd,Unit 950, Houston, TX 77030 USA.
RI lee, jw/O-6237-2014;
OI Armaiz-Pena, Guillermo N/0000-0002-9081-5339
FU NIH [CA 110793, 109298, P50 CA083639, P50 CA098258, CA128797,
RC2GM092599]; Ovarian Cancer Research Fund, Inc; DOD [OC073399,
W81XWH-10-1-0158, BC085265]; Zarrow Foundation; Marcus Foundation; Kim
Medlin Fund; NCI-DHHS-NIH [T32 CA101642]; GCF/OCRF Ann Schreiber Ovarian
Cancer Research; Meyer and Ida Gordon Foundation; NIH/NICHD [HD050128];
GCF-Molly Cade Ovarian Cancer Research; NSC [97-3111-B-039];
[NSC-96-3111-B]
FX The authors thank Donna Reynolds, and Fang Wang for their technical
expertise and helpful discussion We also thank Dr Vickie Williams for
reviewing the manuscript Portions of this work were supported by the NIH
(CA 110793, 109298, P50 CA083639, P50 CA098258, CA128797, RC2GM092599).
the Ovarian Cancer Research Fund, Inc (Program Project Development
Grant), the DOD (OC073399, W81XWH-10-1-0158, BC085265). NSC-96-3111-B,
the Zarrow Foundation, the Marcus Foundation, the Kim Medlin Fund, and
the Betty Anne Asche Murray Distinguished Professorship W A S A M N,A R
C, and R S are supported by NCI-DHHS-NIH T32 Training Grant (T32
CA101642) K M is supported by the GCF/OCRF Ann Schreiber Ovarian Cancer
Research grant and an award from the Meyer and Ida Gordon Foundation 2 M
M K S is supported by the NIH/NICHD WRHR Grant (HD050128) and the
GCF-Molly Cade Ovarian Cancer Research Grant M C H and L Y L are
supported by the NSC 97-3111-B-039
NR 51
TC 163
Z9 178
U1 5
U2 39
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
J9 CANCER CELL
JI Cancer Cell
PD AUG 17
PY 2010
VL 18
IS 2
BP 185
EP 197
DI 10.1016/j.ccr.2010.06.016
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 640LF
UT WOS:000281052000011
PM 20708159
ER
PT J
AU Jefferson, AL
Himali, JJ
Beiser, AS
Au, R
Massaro, JM
Seshadri, S
Gona, P
Salton, CJ
DeCarli, C
O'Donnell, CJ
Benjamin, EJ
Wolf, PA
Manning, WJ
AF Jefferson, Angela L.
Himali, Jayandra J.
Beiser, Alexa S.
Au, Rhoda
Massaro, Joseph M.
Seshadri, Sudha
Gona, Philimon
Salton, Carol J.
DeCarli, Charles
O'Donnell, Christopher J.
Benjamin, Emelia J.
Wolf, Philip A.
Manning, Warren J.
TI Cardiac Index Is Associated With Brain Aging The Framingham Heart Study
SO CIRCULATION
LA English
DT Article
DE brain; cardiac output; epidemiology; imaging; neuropsychology; atrophy
ID CARDIOVASCULAR MAGNETIC-RESONANCE; CHRONIC CEREBRAL HYPOPERFUSION;
WHITE-MATTER LESIONS; STROKE RISK PROFILE; ALZHEIMERS-DISEASE;
BLOOD-FLOW; COGNITIVE IMPAIRMENT; OFFSPRING COHORT; APOLIPOPROTEIN-E;
FAILURE
AB Background-Cardiac dysfunction is associated with neuroanatomic and neuropsychological changes in aging adults with prevalent cardiovascular disease, theoretically because systemic hypoperfusion disrupts cerebral perfusion, contributing to subclinical brain injury. We hypothesized that cardiac function, as measured by cardiac index, would be associated with preclinical brain magnetic resonance imaging (MRI) and neuropsychological markers of ischemia and Alzheimer disease in the community.
Methods and Results-Brain MRI, cardiac MRI, neuropsychological, and laboratory data were collected on 1504 Framingham Offspring Cohort participants free of clinical stroke, transient ischemic attack, or dementia (age, 61 +/- 9 years; 54% women). Neuropsychological and brain MRI variables were related to cardiac MRI-assessed cardiac index (cardiac output/body surface area). In multivariable-adjusted models, cardiac index was positively related to total brain volume (P=0.03) and information processing speed (P=0.02) and inversely related to lateral ventricular volume (P=0.048). When participants with clinically prevalent cardiovascular disease were excluded, the relation between cardiac index and total brain volume remained (P=0.02). Post hoc comparisons revealed that participants in the bottom cardiac index tertile (values <2.54) and middle cardiac index tertile (values between 2.54 and 2.92) had significantly lower brain volumes (P=0.04) than participants in the top cardiac index tertile (values >2.92).
Conclusions-Although observational data cannot establish causality, our findings are consistent with the hypothesis that decreasing cardiac function, even at normal cardiac index levels, is associated with accelerated brain aging. (Circulation. 2010;122:690-697.)
C1 [Jefferson, Angela L.; Seshadri, Sudha] Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02118 USA.
[Jefferson, Angela L.; Himali, Jayandra J.; Beiser, Alexa S.; Au, Rhoda; Seshadri, Sudha; Wolf, Philip A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Jefferson, Angela L.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Jefferson, Angela L.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Himali, Jayandra J.; Beiser, Alexa S.; Massaro, Joseph M.; Gona, Philimon] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Himali, Jayandra J.; Beiser, Alexa S.; Au, Rhoda; Massaro, Joseph M.; Seshadri, Sudha; Gona, Philimon; O'Donnell, Christopher J.; Benjamin, Emelia J.; Wolf, Philip A.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Salton, Carol J.; Manning, Warren J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiovasc,Dept Med, Boston, MA 02215 USA.
[Manning, Warren J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, Boston, MA 02215 USA.
[DeCarli, Charles] Univ Calif Davis, Ctr Neurosci & Imaging, Dementia & Aging Lab, Dept Neurol, Davis, CA 95616 USA.
[O'Donnell, Christopher J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol,Dept Med, Boston, MA 02215 USA.
RP Jefferson, AL (reprint author), Boston Univ, Sch Med, Alzheimers Dis Ctr, 72 E Concord St,B 7800, Boston, MA 02118 USA.
EM angelaj@bu.edu
RI DeCarli, Charles/B-5541-2009;
OI Massaro, Joseph/0000-0002-2682-4812; Seshadri,
Sudha/0000-0001-6135-2622; Au, Rhoda/0000-0001-7742-4491; Benjamin,
Emelia/0000-0003-4076-2336; Beiser, Alexa/0000-0001-8551-7778;
/0000-0003-1391-9481
FU National Heart Lung Blood Institute [HC25195]; Paul B. Beeson Career
Development Award [AG027480, AG030962]; Alzheimer's Association
[IIRG-08-88733]; Boston University Alzheimer's Disease Core Center
[P30-AG013846]; University of California at Davis Alzheimer's Disease
Core Center [AG033193, AG031287, AG021028, AG010129, HL070279];
[AG08122]; [NS017950]; [AG033040]; [AG16495]; [AG028321];
[HL076784]
FX This research was supported by the National Heart Lung Blood Institute's
Framingham Heart Study HC25195; AG027480, AG030962, Paul B. Beeson
Career Development Award in Aging Program, and Alzheimer's Association
IIRG-08-88733 to Dr Jefferson; P30-AG013846 (Boston University
Alzheimer's Disease Core Center); AG08122, NS017950, AG033040, and
AG16495 to Dr Wolf; AG028321 and HL076784 to Dr Benjamin; AG033193 and
AG031287 to Dr Seshadri; AG021028 to Dr DeCarli; AG010129 (University of
California at Davis Alzheimer's Disease Core Center); and HL070279 to Dr
Manning.
NR 48
TC 80
Z9 83
U1 0
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD AUG 17
PY 2010
VL 122
IS 7
BP 690
EP 697
DI 10.1161/CIRCULATIONAHA.109.905091
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 639FS
UT WOS:000280958300004
PM 20679552
ER
PT J
AU Maes, C
Kobayashi, T
Selig, MK
Torrekens, S
Roth, SI
Mackem, S
Carmeliet, G
Kronenberg, HM
AF Maes, Christa
Kobayashi, Tatsuya
Selig, Martin K.
Torrekens, Sophie
Roth, Sanford I.
Mackem, Susan
Carmeliet, Geert
Kronenberg, Henry M.
TI Osteoblast Precursors, but Not Mature Osteoblasts, Move into Developing
and Fractured Bones along with Invading Blood Vessels
SO DEVELOPMENTAL CELL
LA English
DT Article
ID SITE-SPECIFIC RECOMBINATION; CARTILAGE DEVELOPMENT; SKELETAL
DEVELOPMENT; DIFFERENTIATION; CELLS; CHONDROCYTES; GROWTH; MICE;
EXPRESSION; HEDGEHOG
AB During endochondral bone development, the first osteoblasts differentiate in the perichondrium surrounding avascular cartilaginous rudiments; the source of trabecular osteoblasts inside the later bone is, however, unknown. Here, we generated tamoxifen-inducible transgenic mice bred to Rosa26R-LacZ reporter mice to follow the fates of stage-selective subsets of osteoblast lineage cells. Pulse-chase studies showed that osterix-expressing osteoblast precursors, labeled in the perichondrium prior to vascular invasion of the cartilage, give rise to trabecular osteoblasts, osteocytes, and stromal cells inside the developing bone. Throughout the translocation, some precursors were found to intimately associate with invading blood vessels, in pericyte-like fashion. A similar coinvasion occurs during endochondral healing of bone fractures. In contrast, perichondrial mature osteoblasts did not exhibit perivascular localization and remained in the outer cortex of developing bones. These findings reveal the specific involvement of immature osteoblast precursors in the coupled vascular and osteogenic transformation essential to endochondral bone development and repair.
C1 [Maes, Christa; Kobayashi, Tatsuya; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[Maes, Christa; Kobayashi, Tatsuya; Selig, Martin K.; Roth, Sanford I.; Kronenberg, Henry M.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Maes, Christa; Torrekens, Sophie; Carmeliet, Geert] Katholieke Univ Leuven, Dept Expt Med & Endocrinol, B-3000 Louvain, Belgium.
[Selig, Martin K.; Roth, Sanford I.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Mackem, Susan] NCI, Canc & Dev Biol Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA.
RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
EM hkronenberg@partners.org
FU NIH [DK056246]; FWO [G.0569.07, G.0500.08]
FX We thank Abhishek Cole, Jennifer Paruch, Greg Nachtrab, and Ingrid
Stock-mans for assistance with mouse breeding and genotyping. The
Histology Core at the Endocrine Unit of Massachusetts General Hospital,
Riet Van Looveren, and Karen Moermans (Legendo, K.U. Leuven) are
acknowledged for excellent help with histology. For expert advice on
ISH, FAGS analysis, confocal microscopy, and image analysis, we thank
Przemko Tylzanowski (Rheumatology, K.U. Leuven), Aernout Luttun (CMVB,
K.U. Leuven), Sebastian Munck (CME and VIB, K.U. Leuven), Nick Van
Gastel, Maarten Depypere, and An Vanden Bosch (Legendo, K.U. Leuven). We
thank Andy McMahon (Harvard) for generously providing the Osx-Cre:GFP
mouse. We are also grateful to Joy Wu, Ernestina Schipani, and the
members of the Endocrine Unit for helpful discussions. This work was
supported by NIH grant DK056246 to H.M.K., FWO grants G.0569.07 and
G.0500.08 to G.C., and a postdoctoral fellowship of the Fund for
Scientific Research Flanders (FWO) to C.M. All authors declare no
conflicts of interest.
NR 28
TC 278
Z9 284
U1 1
U2 22
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1534-5807
J9 DEV CELL
JI Dev. Cell
PD AUG 17
PY 2010
VL 19
IS 2
BP 329
EP 344
DI 10.1016/j.devcel.2010.07.010
PG 16
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 640YK
UT WOS:000281090000017
PM 20708594
ER
PT J
AU Lu, XF
Ma, LL
Ruan, LF
Kong, Y
Mou, HW
Zhang, ZJ
Wang, ZJ
Wang, JM
Le, YY
AF Lu, Xiaofeng
Ma, Lili
Ruan, Lingfei
Kong, Yan
Mou, Haiwei
Zhang, Zhijie
Wang, Zhijun
Wang, Ji Ming
Le, Yingying
TI Resveratrol differentially modulates inflammatory responses of microglia
and astrocytes
SO JOURNAL OF NEUROINFLAMMATION
LA English
DT Article
ID NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; NITRIC-OXIDE SYNTHASE; PROSTAGLANDIN
E-2 PRODUCTION; ACTIVATED PROTEIN-KINASE; CENTRAL-NERVOUS-SYSTEM;
ALZHEIMERS-DISEASE; MOLECULAR TARGETS; GENE-EXPRESSION; GLIAL-CELLS
AB Background: Inflammatory responses in the CNS mediated by activated glial cells play an important role in host-defense but are also involved in the development of neurodegenerative diseases. Resveratrol is a natural polyphenolic compound that has cardioprotective, anticancer and anti-inflammatory properties. We investigated the capacity of resveratrol to protect microglia and astrocyte from inflammatory insults and explored mechanisms underlying different inhibitory effects of resveratrol on microglia and astrocytes.
Methods: A murine microglia cell line (N9), primary microglia, or astrocytes were stimulated by LPS with or without different concentrations of resveratrol. The expression and release of proinflammatory cytokines (TNF-alpha, IL-1 beta, IL-6, MCP-1) and iNOS/NO by the cells were measured by PCR/real-time PCR and ELISA, respectively. The phosphorylation of the MAP kinase superfamily was analyzed by western blotting, and activation of NF-kappa B and AP-1 was measured by luciferase reporter assay and/or electrophoretic mobility shift assay.
Results: We found that LPS stimulated the expression of TNF-alpha, IL-1 beta, IL-6, MCP-1 and iNOS in murine microglia and astrocytes in which MAP kinases, NF-kappa B and AP-1 were differentially involved. Resveratrol inhibited LPS-induced expression and release of TNF-alpha, IL-6, MCP-1, and iNOS/NO in both cell types with more potency in microglia, and inhibited LPS-induced expression of IL-1 beta in microglia but not astrocytes. Resveratrol had no effect on LPS-stimulated phosphorylation of ERK1/2 and p38 in microglia and astrocytes, but slightly inhibited LPS-stimulated phosphorylation of JNK in astrocytes. Resveratrol inhibited LPS-induced NF-kappa B activation in both cell types, but inhibited AP-1 activation only in microglia.
Conclusion: These results suggest that murine microglia and astrocytes produce proinflammatory cytokines and NO in response to LPS in a similar pattern with some differences in signaling molecules involved, and further suggest that resveratrol exerts anti-inflammatory effects in microglia and astrocytes by inhibiting different proinflammatory cytokines and key signaling molecules.
C1 [Lu, Xiaofeng; Ma, Lili; Ruan, Lingfei; Kong, Yan; Mou, Haiwei; Zhang, Zhijie; Le, Yingying] Chinese Acad Sci, Key Lab Nutr & Metab, Inst Nutr Sci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.
[Ruan, Lingfei; Kong, Yan; Mou, Haiwei; Le, Yingying] Chinese Acad Sci, Grad Sch, Shanghai 200031, Peoples R China.
[Wang, Ji Ming] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
[Wang, Zhijun] Chinese Acad Sci, Shanghai Synchrotron Radiat Facil, Shanghai Inst Appl Phys, Shanghai 201204, Peoples R China.
RP Le, YY (reprint author), Chinese Acad Sci, Key Lab Nutr & Metab, Inst Nutr Sci, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.
EM yyle@sibs.ac.cn
FU National Basic Research Program of China (973 program) [2010CB529701];
National Natural Science Foundation of China [30970917]; Chinese Academy
of Sciences [KSCX2-YW-N-034]; Science & Technology Commission of
Shanghai Municipality [07DJ14005, 09ZR1436700]
FX This study was supported by grants from the National Basic Research
Program of China (973 program) (2010CB529701), the National Natural
Science Foundation of China (30970917), the Knowledge Innovation Project
of the Chinese Academy of Sciences (KSCX2-YW-N-034), and the Science &
Technology Commission of Shanghai Municipality (07DJ14005, 09ZR1436700).
NR 47
TC 85
Z9 85
U1 1
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-2094
J9 J NEUROINFLAMM
JI J. Neuroinflamm.
PD AUG 17
PY 2010
VL 7
AR 46
DI 10.1186/1742-2094-7-46
PG 14
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 657BE
UT WOS:000282385200001
PM 20712904
ER
PT J
AU Wang, AB
Ma, XF
Conti, MA
Liu, CY
Kawamoto, S
Adelstein, RS
AF Wang, Aibing
Ma, Xuefei
Conti, Mary Anne
Liu, Chengyu
Kawamoto, Sachiyo
Adelstein, Robert S.
TI Nonmuscle myosin II isoform and domain specificity during early mouse
development
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cell migration; genetic substitution; placenta development; visceral
endoderm formation; chimeric myosin II
ID MIGRATING CELLS; ADHESION; DEFECTS; MICE; CYTOKINESIS; ACTIVATION;
ABLATION; RESCUE; BRAIN
AB Nonmuscle myosins (NMs) II-A and II-B are essential for embryonic mouse development, but their specific roles are not completely defined. Here we examine the isoforms and their domain specifically in vivo and in vitro by studying mice and cells in which nonmuscle myosin heavy chain (NMHC) II-A is genetically replaced by NMHC II-B or chimeric NMHC IIs that exchange the rod and head domains of NM II-A and II-B. In contrast with the failure of visceral endoderm formation resulting in embryonic day (E)6.5 lethality of A(-)/A(-) mice, replacement with NM II-B or chimeric NM IIs restores a normal visceral endoderm. This finding is consistent with NM II's role in cell adhesion and also confirms an essential, isoform-independent requirement for NM II in visceral endoderm function. The knock-in mice die between E9.5 and 12.5 because of defects in placenta formation associated with abnormal angiogenesis and cell migration, revealing a unique function for NM II-A in placenta development. In vitro results further support a requirement for NM II-A in directed cell migration and focal adhesion formation. These findings demonstrate an isoform-specific role for NM II-A during these processes, making replacement by another isoform, or chimeric NM II isoforms, less successful. The failure of these substitutions is not only related to the different kinetic properties of NM II-A and II-B, but also to their subcellular localization determined by the C-terminal domain. These results highlight the functions of the N-terminal motor and C-terminal rod domains of NM II and their different roles in cell-cell and cell-matrix adhesion.
C1 [Wang, Aibing; Ma, Xuefei; Conti, Mary Anne; Kawamoto, Sachiyo; Adelstein, Robert S.] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA.
[Liu, Chengyu] NHLBI, Transgen Mouse Core Facil, NIH, Bethesda, MD 20892 USA.
RP Adelstein, RS (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA.
EM adelster@nhlbi.nih.gov
OI Adelstein, Robert/0000-0002-8683-2144
FU National Heart, Lung, and Blood Institute, National Institutes of Health
FX We thank Dr. Christian A. Combs and Daniela Malide (Light Microscopy
Core Facility, National Heart, Lung, and Blood Institute) for
professional skills and advice regarding microscopy-related experiments
performed in this study. This work was funded by the intramural program
of National Heart, Lung, and Blood Institute, National Institutes of
Health.
NR 28
TC 27
Z9 29
U1 0
U2 1
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 AUG 17
PY 2010
VL 107
IS 33
BP 14645
EP 14650
DI 10.1073/pnas.1004023107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 643IA
UT WOS:000281287600025
PM 20679233
ER
PT J
AU Yedavalli, VSRK
Jeang, KT
AF Yedavalli, Venkat S. R. K.
Jeang, Kuan-Teh
TI Trimethylguanosine capping selectively promotes expression of
Rev-dependent HIV-1 RNAs
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE required for chromosome region maintenance; RNA export; peroxisome
proliferator-activated receptor-interacting protein with
methyltransferase
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CAP GUANINE-N2 METHYLTRANSFERASE;
MESSENGER-RNA; NUCLEAR EXPORT; TELOMERASE RNA; CONSERVED
METHYLTRANSFERASE; CAENORHABDITIS-ELEGANS; CONDITIONAL MUTANTS;
LOCALIZATION SIGNAL; 5'-TERMINAL CAP
AB 5'-mRNA capping is an early modification that affects pre-mRNA synthesis/splicing, RNA cytoplasmic transport, and mRNA translation and turnover. In eukaryotes, a 7-methylguanosine (m7G) cap is added to newly transcribed RNA polymerase II (RNAPII) transcripts. A subset of RNAP II-transcribed cellular RNAs, including small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), and telomerase RNA, is further hypermethylated at the exocyclic N2 of the guanosine to create a trimethylguanosine (TMG)-capped RNA. Some of these TMG-capped RNAs are transported within the nucleus and from the nucleus to the cytoplasm by the CRM-1 (required for chromosome region maintenance) protein. CRM-1 is also used to export Rev/RRE-dependent unspliced/partially spliced HIV-1 RNAs. Here we report that like snRNAs and snoRNAs, some Rev/RRE-dependent HIV-1 RNAs are TMG-capped. The methyltransferase responsible for TMG modification of HIV-1 RNAs is the human PIMT (peroxisome proliferator-activated receptor-interacting protein with methyltransferase) protein. TMG capping of unspliced/partially spliced HIV-1 RNAs represents a new regulatory mechanism for selective expression.
C1 [Yedavalli, Venkat S. R. K.; Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kjeang@niaid.nih.gov
RI Jeang, Kuan-Teh/A-2424-2008
FU National Institute of Allergy and Infectious Diseases; National
Institutes of Health; Office of the Director, National Institutes of
Health
FX This work was supported in part by intramural funding from the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, and by the Intramural AIDS Targeted Program from the Office of
the Director, National Institutes of Health.
NR 66
TC 29
Z9 29
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 AUG 17
PY 2010
VL 107
IS 33
BP 14787
EP 14792
DI 10.1073/pnas.1009490107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 643IA
UT WOS:000281287600049
PM 20679221
ER
PT J
AU Grice, EA
Snitkin, ES
Yockey, LJ
Bermudez, DM
Liechty, KW
Segre, JA
AF Grice, Elizabeth A.
Snitkin, Evan S.
Yockey, Laura J.
Bermudez, Dustin M.
Liechty, Kenneth W.
Segre, Julia A.
CA NISC Comparative Sequencing
TI Longitudinal shift in diabetic wound microbiota correlates with
prolonged skin defense response
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE wound healing; microbiome; innate immunity; diabetes; gene expression
ID DB/DB MICE; IN-VITRO; GENE; INFLAMMATION; DIVERSITY; ULCERS; FOOT;
MACROPHAGES; BACTERIA; PROJECT
AB Diabetics frequently suffer from chronic, nonhealing wounds. Although bacterial colonization and/or infection are generally acknowledged to negatively impact wound healing, the precise relationship between the microbial community and impaired wound healing remains unclear. Because the host cutaneous defense response is proposed to play a key role in modulating microbial colonization, we longitudinally examined the diabetic wound microbiome in tandem with host tissue gene expression. By sequencing 16S ribosomal RNA genes, we show that a longitudinal selective shift in wound microbiota coincides with impaired healing in diabetic mice (Lepr(db/db); db/db). We demonstrate a parallel shift in longitudinal gene expression that occurs in a cluster of genes related to the immune response. Further, we establish a correlation between relative abundance of Staphylococcus spp. and the expression of cutaneous defense response genes. Our data demonstrate that integrating two types of global datasets lends a better under standing to the dynamics governing host-microbe interactions.
C1 [Liechty, Kenneth W.] Univ Mississippi, Med Ctr, Dept Surg, Jackson, MS 39216 USA.
[Grice, Elizabeth A.; Snitkin, Evan S.; Yockey, Laura J.; Segre, Julia A.] NHLBI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA.
[NISC Comparative Sequencing] NHLBI, NIH, Intramural Sequencing Ctr, Bethesda, MD 20892 USA.
[Bermudez, Dustin M.] Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA.
RP Liechty, KW (reprint author), Univ Mississippi, Med Ctr, Dept Surg, Jackson, MS 39216 USA.
EM kliechty@surgery.umsmed.edu; jsegre@nhgri.nih.gov
OI Grice, Elizabeth/0000-0003-3939-2200
FU National Human Genome Research Institute Microarray Core; National Human
Genome Research Institute; National Institute of Diabetes and Digestive
and Kidney Diseases [1R56DK080672-01A1, 1P2DK083085-02]; National
Institute of General Medical Sciences Pharmacology Research Associate
FX We thank S. Conlan for bioinformatics support; A. Young, R. Blakesley,
M. Park, C. Sison, R. Legaspi, and the staff at NIH Intramural
Sequencing Center for sequencing support; A. Elkahloun and the National
Human Genome Research Institute Microarray Core for microarray services
and support; B. Herdrich for assistance with pilot experiments; L. Zhang
for providing technical assistance; S. Hoogenstraten-Miller and the
National Human Genome Research Institute Animal Facility for veterinary
support; M. Turner, H. Kong, and S. Rafail for critical advice and
reading of the manuscript; and members of the J.A.S. and K. W. L.
laboratories for their underlying contributions. This work was funded by
the National Human Genome Research Institute Intramural Research Program
(J.A.S.) and National Institute of Diabetes and Digestive and Kidney
Diseases Grants 1R56DK080672-01A1 (to K. W. L.) and 1P2DK083085-02 (to
K. W. L.). E. A. G. is funded by a National Institute of General Medical
Sciences Pharmacology Research Associate Training fellowship.
NR 33
TC 71
Z9 73
U1 2
U2 20
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 AUG 17
PY 2010
VL 107
IS 33
BP 14799
EP 14804
DI 10.1073/pnas.1004204107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 643IA
UT WOS:000281287600051
PM 20668241
ER
PT J
AU Li, QA
Rodriguez, LG
Farnsworth, DF
Gildersleeve, JC
AF Li, Qian
Rodriguez, Luis G.
Farnsworth, David F.
Gildersleeve, Jeffrey C.
TI Effects of Hapten Density on the Induced Antibody Repertoire
SO CHEMBIOCHEM
LA English
DT Article
DE antibodies; carbohydrates; glycoconjugates; ligand density; vaccines
ID EPITOPE DENSITY; TN-ANTIGEN; CARBOHYDRATE MICROARRAYS; VACCINE
DEVELOPMENT; SYNTHETIC VACCINE; SERUM ANTIBODIES; CANCER ANTIGEN;
GLYCOPEPTIDE; SPECIFICITY; INDUCTION
AB Small peptides and oligosaccharides are important antigens for the development of vaccines and the production of monoclonal antibodies Because of their small size, peptides and oligosaccharides are non-immunogenic on their own and typically must be conjugated to a larger carrier protein to elicit an immune response. Selection of a suitable carrier protein, conjugation method, and hapten density are critical for generating an optimal immune response We used a glycan array to compare the repertoire of antibodies induced after immunizing with either low or high-density conjugates of the tumor-associated Tn antigen. At high hapten density, a broader range of antibodies was induced, and reactivity to the clustered Tn antigen was observed. In contrast, antibodies induced by the low-density conjugate had narrower reactivity and did not bind the clustered Tn antigen.
C1 [Li, Qian; Farnsworth, David F.; Gildersleeve, Jeffrey C.] NCI, Biol Chem Lab, NIH, Frederick, MD 21702 USA.
[Rodriguez, Luis G.] NCI, Opt Microscopy & Anal Lab, SAIC Frederick Inc, Adv Technol Program, Frederick, MD 21702 USA.
RP Gildersleeve, JC (reprint author), NCI, Biol Chem Lab, NIH, Bldg 376, Frederick, MD 21702 USA.
RI Gildersleeve, Jeffrey/N-3392-2014
FU NIH, National Cancer Institute, Center for Cancer Research
FX We thank Jack Simpson (Protein Chemistry Laboratory, SAIC/NCI-Frederick)
for MALDI-MS analysis of HSA and BSA conjugates. We thank ProSci, Inc.
for vaccinations, care, and handling of the rabbits. This research was
supported by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research.
NR 50
TC 14
Z9 14
U1 0
U2 9
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 1439-4227
J9 CHEMBIOCHEM
JI ChemBioChem
PD AUG 16
PY 2010
VL 11
IS 12
BP 1686
EP 1691
DI 10.1002/cbic.201000235
PG 6
WC Biochemistry & Molecular Biology; Chemistry, Medicinal
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 646KI
UT WOS:000281538500010
PM 20602400
ER
PT J
AU Wang, B
Navath, RS
Menjoge, AR
Balakrishnan, B
Bellair, R
Dai, H
Romero, R
Kannan, S
Kannan, RM
AF Wang, Bing
Navath, Raghavendra S.
Menjoge, Anupa R.
Balakrishnan, Bindu
Bellair, Robert
Dai, Hui
Romero, Roberto
Kannan, Sujatha
Kannan, Rangaramanujam M.
TI Inhibition of bacterial growth and intramniotic infection in a guinea
pig model of chorioamnionitis using PAMAM dendrimers
SO INTERNATIONAL JOURNAL OF PHARMACEUTICS
LA English
DT Article
DE PAMAM dendrimer; Antimicrobial activity; Gram negative bacteria;
Cytotoxicity; Cell membrane
ID GRAM-NEGATIVE BACTERIA; POLY(PROPYLENE IMINE) DENDRIMERS;
POLY(AMIDOAMINE) DENDRIMERS; ANTIMICROBIAL ACTIVITY; POLY(ETHYLENE
GLYCOL); MEMBRANE-PERMEABILITY; POLYCATIONIC POLYMERS; ESCHERICHIA-COLI;
DRUG-DELIVERY; PRETERM BIRTH
AB Dendrimers have emerged as topical microbicides to treat vaginal infections. This study explores the in vitro, in vivo antimicrobial activity of PAMAM dendrimers, and the associated mechanism. Interestingly, topical cervical application of 500 mu g of generation-4 neutral dendrimer (G(4)-PAMAM-OH) showed potential to treat the Escherichia coli induced ascending uterine infection in guinea pig model of chorioamnionitis. Amniotic fluid collected from different gestational sacs of infected guinea pigs posttreatment showed absence of E. coli growth in the cultures plated with it. The cytokine level [tumor necrosis factor (TNF alpha) and interleukin (IL-6 and lL-1 beta)] in placenta of the G(4)-PAMAM-OH treated animals were comparable to those in healthy animals while these were notably high in infected animals. Since, antibacterial activity of amine-terminated PAMAM dendrimers is known, the activity of hydroxyl and carboxylic acid terminated PAMAM dendrimers was compared with it. Though the G(4)-PAMAM-NH2 shows superior antibacterial activity, it was found to be cytotoxic to human cervical epithelial cell line above 10 mu g/mL, while the G(4)-PAMAM-OH was non-cytotoxic up to 1 mg/mL concentration. Cell integrity, outer (OM) and inner (IM) membrane permeabilization assays showed that G(4)-PAMAM-OH dendrimer efficiently changed the OM permeability, while G(4)-PAMAM-NH2 and G(3.5)-PAMAM-COOH damaged both OM and IM causing the bacterial lysis. The possible antibacterial mechanism are G(4)-PAMAM-NH2 acts as polycation binding to the polyanionic lipopolysaccharide in E. coli, the G(4)-PAMAM-OH forms hydrogen bonds with the hydrophilic O-antigens in E. coli membrane and the G(3.5)-PAMAM-COOH acts as a polyanion, chelating the divalent ions in outer cell membrane of E. coli. This is the first study which shows that G(4)-PAMAM-OH dendrimer acts as an antibacterial agent. (C) 2010 Elsevier B.V. All rights reserved.
C1 [Wang, Bing; Balakrishnan, Bindu; Dai, Hui; Kannan, Sujatha] Wayne State Univ, Childrens Hosp Michigan, Dept Pediat Crit Care Med, Detroit, MI 48201 USA.
[Navath, Raghavendra S.; Menjoge, Anupa R.; Bellair, Robert; Kannan, Rangaramanujam M.] Wayne State Univ, Dept Chem Engn & Mat Sci, Detroit, MI 48202 USA.
[Wang, Bing; Navath, Raghavendra S.; Menjoge, Anupa R.; Dai, Hui; Romero, Roberto; Kannan, Sujatha; Kannan, Rangaramanujam M.] NICHD, Perinatol Res Branch, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH,DHHS, Detroit, MI 48201 USA.
RP Kannan, S (reprint author), Wayne State Univ, Childrens Hosp Michigan, Dept Pediat Crit Care Med, Detroit, MI 48201 USA.
EM skannan@med.wayne.edu; rkannan.wsu@gmail.edu
FU National Institute of Child Health and Human Development, NIH, DHHS;
NICHD [K08]
FX This study was supported by the Intramural Research Program of the
National Institute of Child Health and Human Development, NIH, DHHS, and
the Pediatric Critical Care Scientist Development Program NICHD-K08.
NR 51
TC 62
Z9 63
U1 2
U2 35
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-5173
EI 1873-3476
J9 INT J PHARMACEUT
JI Int. J. Pharm.
PD AUG 16
PY 2010
VL 395
IS 1-2
BP 298
EP 308
DI 10.1016/j.ijpharm.2010.05.030
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 629PP
UT WOS:000280212500039
PM 20580797
ER
PT J
AU Ascierto, PA
Napolitano, M
Celentano, E
Simeone, E
Gentilcore, G
Daponte, A
Capone, M
Caraco, C
Calemma, R
Beneduce, G
Cerrone, M
De Rosa, V
Palmieri, G
Castello, G
Kirkwood, JM
Marincola, FM
Mozzillo, N
AF Ascierto, Paolo A.
Napolitano, Maria
Celentano, Egidio
Simeone, Ester
Gentilcore, Giusy
Daponte, Antonio
Capone, Mariaelena
Caraco, Corrado
Calemma, Rosa
Beneduce, Gerardo
Cerrone, Margherita
De Rosa, Vincenzo
Palmieri, Giuseppe
Castello, Giuseppe
Kirkwood, John M.
Marincola, Francesco M.
Mozzillo, Nicola
TI Regulatory T cell frequency in patients with melanoma with different
disease stage and course, and modulating effects of high-dose
interferon-alpha 2b treatment
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
ID HIGH-RISK MELANOMA; IMMUNOLOGICAL SELF-TOLERANCE;
COOPERATIVE-ONCOLOGY-GROUP; ADJUVANT THERAPY; METASTATIC MELANOMA;
LYMPH-NODES; TRIAL; ALPHA; FOXP3; IFN-ALPHA-2B
AB Background: High-dose interferon-alpha 2b (IFN-alpha 2b) is the only approved systemic therapy in the United States for the adjuvant treatment of melanoma. The study objective was to explore the immunomodulatory mechanism of action for IFN-alpha 2b by measuring serum regulatory T cell (Treg), serum transforming growth factor-beta (TGF-beta), interleukin (IL)-10, and autoantibody levels in patients with melanoma treated with the induction phase of the high-dose IFN-alpha 2b regimen.
Methods: Patients with melanoma received IFN-alpha 2b administered intravenously (20 MU/m(2) each day from day 1 to day 5 for 4 consecutive weeks). Serum Treg levels were measured as whole lymphocytes in CD4(+) cells using flow cytometry while TGF-beta, IL-10, and autoantibody levels were measured using enzyme-linked immunosorbent assays.
Results: Twenty-two patients with melanoma received IFN-alpha 2b treatment and were evaluated for Treg levels. Before treatment, Treg levels were significantly higher in patients with melanoma when compared with data from 20 healthy subjects (P = 0.001; Mann-Whitney test). Although a trend for reduction of Treg levels following IFN-alpha 2b treatment was observed (average decrease 0.29% per week), statistical significance was not achieved. Subgroup analyses indicated higher baseline Treg levels for stage III versus IV disease (P = 0.082), early recurrence versus no recurrence (P = 0.017), deceased versus surviving patients (P = 0.021), and preoperative neoadjuvant versus postoperative adjuvant treatment groups (not significant). No significant effects were observed on the levels of TGF-beta, IL-10, and autoantibodies in patients with melanoma treated with IFN-alpha 2b.
Conclusions: Patients with melanoma in this study showed increased basal levels of Treg that may be relevant to their disease and its progression. Treg levels shifted in patients with melanoma treated with IFN-alpha 2b, although no firm conclusions regarding the role of Tregs as a marker of treatment response or outcome can be made at present.
C1 [Ascierto, Paolo A.; Napolitano, Maria; Celentano, Egidio; Simeone, Ester; Gentilcore, Giusy; Daponte, Antonio; Capone, Mariaelena; Caraco, Corrado; Calemma, Rosa; Beneduce, Gerardo; Cerrone, Margherita; De Rosa, Vincenzo; Castello, Giuseppe; Mozzillo, Nicola] Natl Tumor Inst, Unit Med Oncol & Innovat Therapy, Naples, Italy.
[Ascierto, Paolo A.; Napolitano, Maria; Celentano, Egidio; Simeone, Ester; Gentilcore, Giusy; Daponte, Antonio; Capone, Mariaelena; Caraco, Corrado; Calemma, Rosa; Beneduce, Gerardo; Cerrone, Margherita; De Rosa, Vincenzo; Castello, Giuseppe; Mozzillo, Nicola] Natl Tumor Inst, Melanoma Cooperat Grp, Naples, Italy.
[Palmieri, Giuseppe] Inst Biomol Chem CNR, Sassari, Italy.
[Kirkwood, John M.] Univ Pittsburgh, Dept Med, Div Hematol Oncol, Inst Canc, Pittsburgh, PA USA.
[Marincola, Francesco M.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Ascierto, PA (reprint author), Natl Tumor Inst, Unit Med Oncol & Innovat Therapy, Naples, Italy.
EM paolo.ascierto@gmail.com
RI napolitano, maria/K-1615-2016
OI Castello, Giuseppe/0000-0002-0924-6248; napolitano,
maria/0000-0002-8996-3297
FU Italian Ministry of Health; Associazione UMANA Onlus; Merck and Co. Inc;
BMS; Pfizer; Lilly; Intrexon
FX This work was supported by the Italian Ministry of Health "Ricerca
Oncologica - Programma Integrato Oncologia" and Associazione UMANA
Onlus. The author wishes to thank Ilenia Visconti for data management.
Editorial support for this manuscript was provided by Stephen Gregson,
PhD, Evidence Scientific Solutions, Horsham, UK, and supported by Merck
and Co. Inc (formerly Schering Corporation).; PAA participated in an
advisory board for Bristol-Myers Squibb and has received honoraria from
Schering-Plough and Genta. JMK receives research funding to the
University of Pittsburgh from BMS, Pfizer, Lilly, and Intrexon, and is
on the Speaker Bureau of Schering-Plough. The other authors have no
competing interests to declare.
NR 31
TC 26
Z9 27
U1 2
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD AUG 16
PY 2010
VL 8
AR 76
DI 10.1186/1479-5876-8-76
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 657WR
UT WOS:000282450200001
PM 20712892
ER
PT J
AU Luo, Y
Good, CH
Diaz-Ruiz, O
Zhang, YJ
Hoffman, AF
Shan, LF
Kuang, SY
Malik, N
Chefer, VI
Tomac, AC
Lupica, CR
Backman, CM
AF Luo, Yu
Good, Cameron H.
Diaz-Ruiz, Oscar
Zhang, YaJun
Hoffman, Alexander F.
Shan, Lufei
Kuang, Serena Y.
Malik, Nasir
Chefer, Vladimir I.
Tomac, Andreas C.
Lupica, Carl R.
Backman, Cristina M.
TI NMDA Receptors on Non-Dopaminergic Neurons in the VTA Support Cocaine
Sensitization
SO PLOS ONE
LA English
DT Article
ID VENTRAL TEGMENTAL AREA; INDUCED NEUROBEHAVIORAL PLASTICITY; D-ASPARTATE
RECEPTOR; DOPAMINE NEURONS; NUCLEUS-ACCUMBENS; SYNAPTIC PLASTICITY;
ENVIRONMENTAL CONTEXT; PREFRONTAL CORTEX; GLUTAMATE; POTENTIATION
AB Background: The initiation of behavioral sensitization to cocaine and other psychomotor stimulants is thought to reflect N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic plasticity in the mesolimbic dopamine (DA) circuitry. The importance of drug induced NMDAR mediated adaptations in ventral tegmental area (VTA) DA neurons, and its association with drug seeking behaviors, has recently been evaluated in Cre-loxp mice lacking functional NMDARs in DA neurons expressing Cre recombinase under the control of the endogenous dopamine transporter gene (NR1(DATCre) mice).
Methodology and Principal Findings: Using an additional NR1(DATCre) mouse transgenic model, we demonstrate that while the selective inactivation of NMDARs in DA neurons eliminates the induction of molecular changes leading to synaptic strengthening, behavioral measures such as cocaine induced locomotor sensitization and conditioned place preference remain intact in NR1(DATCre) mice. Since VTA DA neurons projecting to the prefrontal cortex and amygdala express little or no detectable levels of the dopamine transporter, it has been speculated that NMDA receptors in DA neurons projecting to these brain areas may have been spared in NR1(DATCre) mice. Here we demonstrate that the NMDA receptor gene is ablated in the majority of VTA DA neurons, including those exhibiting undetectable DAT expression levels in our NR1(DATCre) transgenic model, and that application of an NMDAR antagonist within the VTA of NR1(DATCre) animals still blocks sensitization to cocaine.
Conclusions/Significance: These results eliminate the possibility of NMDAR mediated neuroplasticity in the different DA neuronal subpopulations in our NR1(DATCre) mouse model and therefore suggest that NMDARs on non-DA neurons within the VTA must play a major role in cocaine-related addictive behavior.
C1 [Luo, Yu; Good, Cameron H.; Diaz-Ruiz, Oscar; Zhang, YaJun; Hoffman, Alexander F.; Shan, Lufei; Kuang, Serena Y.; Malik, Nasir; Tomac, Andreas C.; Lupica, Carl R.; Backman, Cristina M.] Natl Inst Drug Abuse, Cellular Neurobiol Res Branch, NIH, Baltimore, MD USA.
[Chefer, Vladimir I.] Natl Inst Drug Abuse, Behav Neurosci Branch, NIH, Baltimore, MD USA.
RP Luo, Y (reprint author), Natl Inst Drug Abuse, Cellular Neurobiol Res Branch, NIH, Baltimore, MD USA.
EM cbackman@mail.nih.gov
RI Diaz-Ruiz, Oscar/F-3162-2010; backman, cristina/C-1276-2013; Hoffman,
Alexander/H-3035-2012
OI Hoffman, Alexander/0000-0002-2676-0628
FU National Institute on Drug Abuse, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute on Drug Abuse, National Institutes of Health. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 36
TC 25
Z9 26
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 16
PY 2010
VL 5
IS 8
AR e12141
DI 10.1371/journal.pone.0012141
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 639IH
UT WOS:000280968000003
PM 20808436
ER
PT J
AU Salvadore, G
Viale, CI
Luckenbaugh, DA
Zanatto, VC
Portela, LV
Souza, DO
Zarate, CA
Machado-Vieira, R
AF Salvadore, Giacomo
Viale, Carlos I.
Luckenbaugh, David A.
Zanatto, Vanessa C.
Portela, Luiz V.
Souza, Diogo O.
Zarate, Carlos A., Jr.
Machado-Vieira, Rodrigo
TI Increased uric acid levels in drug-naive subjects with bipolar disorder
during a first manic episode
SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
LA English
DT Review
DE Bipolar disorder; Depression; Gout; Mania; Purines; Uric acid
ID DOUBLE-BLIND; ALLOPURINOL; LITHIUM; EFFICACY; ILLNESS; MODEL
AB Recent evidence suggests that purinergic system dysfunction may play a role in the pathophysiology and therapeutics of bipolar disorder (BPD). Uric acid is a key nitrogenous end product of purine metabolism. In addition to being a potential marker of treatment response, high levels of uric acid may represent a state marker during mania. In this study, we assessed the presence of purinergic dysfunction in 20 treatment-naive first episode patients with BPD who were experiencing a manic episode. Patients were matched with 24 healthy controls. We found that acutely manic patients had significantly higher levels of plasma uric acid (4.85 +/- 1.60 mg/dL) compared to healthy controls (2.96 +/- 0.63 mg/dL, p<0.001; F=28.1). No association between uric acid levels with severity of manic symptoms was observed. These results support the role of purinergic system dysfunction in BPD early in the course of illness, and suggest that this phenomenon is not the result of chronicity or medication exposure. Overall, our findings suggest a novel mechanism in the pathophysiology of BPD. Published by Elsevier Inc.
C1 [Salvadore, Giacomo; Luckenbaugh, David A.; Zarate, Carlos A., Jr.; Machado-Vieira, Rodrigo] NIMH, Expt Therapeut Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
[Viale, Carlos I.; Zanatto, Vanessa C.; Portela, Luiz V.; Souza, Diogo O.] Univ Fed Rio Grande do Sul, Dept Biochem, BR-90035003 Porto Alegre, RS, Brazil.
[Machado-Vieira, Rodrigo] Univ Sao Paulo, Inst & Dept Psychiat, BR-05508 Sao Paulo, SP, Brazil.
RP Machado-Vieira, R (reprint author), NIMH, Expt Therapeut Mood & Anxiety Disorders Program, NIH, 10 Ctr Dr,CRC Unit 7 SE,Room 7-3445, Bethesda, MD 20892 USA.
EM machadovieirar@mail.nih.gov
RI Souza, Diogo/J-8894-2014; MACHADO-VIEIRA, RODRIGO/D-8293-2012
OI Souza, Diogo/0000-0002-4322-0404; MACHADO-VIEIRA,
RODRIGO/0000-0002-4830-1190
FU National Institute of Mental Health, National Institutes of Health,
Department of Health & Human Services (IRP-NIMH-NIH-DHHS); NARSAD
FX The authors gratefully acknowledge the support of the Intramural
Research Program of the National Institute of Mental Health, the
National Institutes of Health, and the Department of Health & Human
Services (IRP-NIMH-NIH-DHHS) and NARSAD (CAZ). Dr. Machado-Vieira would
also like to thank the Stanley Medical Research Institute (SMRI). Ioline
Henter provided outstanding editorial assistance.
NR 16
TC 27
Z9 28
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-5846
J9 PROG NEURO-PSYCHOPH
JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry
PD AUG 16
PY 2010
VL 34
IS 6
BP 819
EP 821
DI 10.1016/j.pnpbp.2010.02.027
PG 3
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 642EX
UT WOS:000281187800001
PM 20206224
ER
PT J
AU Al-Mallah, MH
Nasir, K
Katz, R
Takasu, J
Lima, JA
Bluemke, DA
Hundley, G
Blumenthal, RS
Budoff, MJ
AF Al-Mallah, Mouaz H.
Nasir, Khurram
Katz, Ronit
Takasu, Junichiro
Lima, Joao A.
Bluemke, David A.
Hundley, Gregory
Blumenthal, Roger S.
Budoff, Matthew J.
TI Thoracic Aortic Distensibility and Thoracic Aortic Calcium (from the
Multi-Ethnic Study of Atherosclerosis [MESA])
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID CORONARY-ARTERY-DISEASE; ELECTRON-BEAM CT; CARDIOVASCULAR RISK-FACTORS;
COMPUTED-TOMOGRAPHY; INDEPENDENT PREDICTOR; SCANNER TYPE; CALCIFICATION;
STIFFNESS; REPRODUCIBILITY; QUANTIFICATION
AB Decreased arterial distensibility is an early manifestation of adverse structural and functional changes within the vessel wall. Its correlation with thoracic aortic calcium (TAC), a marker of atherosclerosis, has not been well demonstrated. We tested the hypothesis that decreasing aortic compliance and increasing arterial stiffness would be independently associated with increased TAC. We included 3,540 subjects (61 +/- 10 years, 46% men) from the Multi-ethnic Study of Atherosclerosis who had undergone an aortic distensibility (AD) assessment using magnetic resonance imaging. TAC was calculated using a modified Agatston algorithm on noncontrast cardiac computed tomographic scans. Multivariate regression models were calculated for the presence of TAC. Overall, 861 subjects (24%) had detectable TAC. Lower AD was observed among those with versus without TAC (2.02 +/- 1.34 vs 1.28 +/- 0.74, p <0.0001). The prevalence of TAC increased significantly across decreasing quartiles of AD (7%, 17%, 31%, and 42%, p <0.0001). Using multivariate analysis, TAC was independently associated with AD after adjusting for age, gender, ethnicity, and other covariates. In conclusion, our analysis has demonstrated that increased arterial stiffness is associated with increased TAC, independent of ethnicity and other atherosclerotic risk factors. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010; 106:575-580)
C1 [Al-Mallah, Mouaz H.] Wayne State Univ, Henry Ford Hosp, Div Cardiol, Detroit, MI 48202 USA.
[Nasir, Khurram] Boston Univ, Med Ctr, Dept Internal Med, Boston, MA USA.
[Katz, Ronit] Univ Washington, Dept Biostat, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA.
[Takasu, Junichiro; Budoff, Matthew J.] Harbor Univ Calif, Med Ctr, Div Cardiol, Los Angeles Biomed Res Inst, Torrance, CA USA.
[Lima, Joao A.; Blumenthal, Roger S.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA.
[Bluemke, David A.] Natl Inst Hlth, Dept Radiol & Imaging Sci, Bethesda, MD USA.
[Hundley, Gregory] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Cardiol Sect, Winston Salem, NC 27103 USA.
RP Al-Mallah, MH (reprint author), Wayne State Univ, Henry Ford Hosp, Div Cardiol, Detroit, MI 48202 USA.
EM mouaz74@gmail.com
OI Bluemke, David/0000-0002-8323-8086; Al-Mallah, Mouaz/0000-0003-2348-0484
FU National Heart, Lung, and Blood Institute (Bethesda, Maryland) [R01
HL071739, N01-HC-95159, N01-HC-95165, N01-HC-95169]
FX This research was supported by R01 HL071739 and contracts N01-HC-95159
through N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and
Blood Institute (Bethesda, Maryland).
NR 23
TC 21
Z9 21
U1 0
U2 1
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD AUG 15
PY 2010
VL 106
IS 4
BP 575
EP 580
DI 10.1016/j.amjcard.2010.03.074
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 642AH
UT WOS:000281174500020
PM 20691319
ER
PT J
AU Epplein, M
Shu, XO
Xiang, YB
Chow, WH
Yang, G
Li, HL
Ji, BT
Cai, H
Gao, YT
Zheng, W
AF Epplein, Meira
Shu, Xiao-Ou
Xiang, Yong-Bing
Chow, Wong-Ho
Yang, Gong
Li, Hong-Lan
Ji, Bu-Tian
Cai, Hui
Gao, Yu-Tang
Zheng, Wei
TI Fruit and Vegetable Consumption and Risk of Distal Gastric Cancer in the
Shanghai Women's and Men's Health Studies
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE diet; fruit; micronutrients; stomach neoplasms; vegetables
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; HELICOBACTER-PYLORI INFECTION;
PREDIAGNOSTIC LEVELS; PROSPECTIVE COHORT; CIGARETTE-SMOKING; TOCOPHEROL
LEVELS; DIETARY PATTERNS; NUTRITION; JAPANESE; RETINOL
AB Results from case-control and cohort studies of the association between fruit and vegetable consumption and gastric cancer risk have been inconsistent. Cases for the current study consisted of incident distal gastric cancers identified between 1996 and 2007 among members of the Shanghai Women's Health Study (n = 206) and the Shanghai Men's Health Study (n = 132). Intakes of fruits, vegetables, and select micronutrients were assessed on the basis of validated food frequency questionnaires. Multivariate-adjusted hazards ratios and 95% confidence intervals were calculated by Cox proportional hazards regression. For women, no associations were found between gastric cancer risk and the highest intake of fruits (hazard ratio (HR) = 1.02, 95% confidence interval (CI): 0.68, 1.54; P(trend) = 0.87) or vegetables (HR = 0.89, 95% CI: 0.60, 1.31; P(trend) = 0.32). For men, increased fruit intake was associated with decreased risk of distal gastric cancer (for the highest quartile of intake, HR = 0.50, 95% CI: 0.29, 0.84; P(trend) = 0.004), but no association was seen with increased intake of vegetables (HR = 1.00, 95% CI: 0.59, 1.68; P(trend) = 0.87). The inverse association with fruit intake for men was more evident among ever smokers (P(trend) = 0.001) than never smokers (P(trend) = 0.67). No associations between dietary intakes of select antioxidant micronutrients were seen for men or women. Fruit intake is inversely associated with distal gastric cancer risk among men in Shanghai, China.
C1 [Epplein, Meira; Shu, Xiao-Ou; Yang, Gong; Cai, Hui; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med, Nashville, TN 37203 USA.
[Xiang, Yong-Bing; Li, Hong-Lan; Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Chow, Wong-Ho; Ji, Bu-Tian] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Epplein, M (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, 2525 W End Ave,6th Floor, Nashville, TN 37203 USA.
EM meira.epplein@vanderbilt.edu
OI Epplein, Meira/0000-0001-5646-6430
FU National Cancer Institute [R37 CA70867-12, R01 CA82729-09]
FX Supported by National Cancer Institute grants R37 CA70867-12 and R01
CA82729-09.
NR 37
TC 24
Z9 26
U1 1
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 15
PY 2010
VL 172
IS 4
BP 397
EP 406
DI 10.1093/aje/kwq144
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 638NX
UT WOS:000280902700007
PM 20647333
ER
PT J
AU Schisterman, EF
Gaskins, AJ
Mumford, SL
Browne, RW
Yeung, E
Trevisan, M
Hediger, M
Zhang, CL
Perkins, NJ
Hovey, K
Wactawski-Wende, J
AF Schisterman, Enrique F.
Gaskins, Audrey J.
Mumford, Sunni L.
Browne, Richard W.
Yeung, Edwina
Trevisan, Maurizio
Hediger, Mary
Zhang, Cuilin
Perkins, Neil J.
Hovey, Kathleen
Wactawski-Wende, Jean
CA BioCycle Study Grp
TI Influence of Endogenous Reproductive Hormones on F-2-Isoprostane Levels
in Premenopausal Women
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE hormones; menstrual cycle; oxidative stress; women
ID LOW-DENSITY-LIPOPROTEIN; BREAST-CANCER RISK; OXIDATIVE STRESS;
LIPID-PEROXIDATION; MENSTRUAL-CYCLE; ESTROGENS; PLASMA; SERUM;
ANTIOXIDANTS; BIOMARKERS
AB Endogenous reproductive hormones and oxidative stress have been independently linked to risk of chronic disease but mostly in postmenopausal women. The interplay between endogenous reproductive hormones and oxidative stress among premenopausal women, however, has yet to be clearly elucidated. The objective of this study was to investigate the association between endogenous reproductive hormones and F-2-isoprostanes in the BioCycle Study. Women aged 18-44 years from western New York State were followed prospectively for up to 2 menstrual cycles (n = 259) during 2005-2007. Estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, sex hormone-binding globulin, F-2-isoprostanes, and thiobarbituric acid-reactive substances were measured up to 8 times per cycle at clinic visits timed by using fertility monitors. F-2-Isoprostane levels had an independent positive association with estradiol (beta = 0.02, 95% confidence interval: 0.01, 0.03) and inverse associations with sex hormone-binding globulin and follicle-stimulating hormone (beta = -0.04, 95% confidence interval: -0.07, -0.003; beta = -0.02, 95% confidence interval: -0.03, -0.002, respectively) after adjustment for age, race, age at menarche, gamma-tocopherol, beta-carotene, total cholesterol, and homocysteine by inverse probability weighting. Thiobarbituric acid-reactive substances, a less specific marker of oxidative stress, had similar associations. If F-2-isoprostanes are specific markers of oxidative stress, these results call into question the commonly held hypothesis that endogenous estradiol reduces oxidative stress.
C1 [Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA.
[Browne, Richard W.] SUNY Buffalo, Dept Biotech Lab Sci, Buffalo, NY 14260 USA.
[Browne, Richard W.] SUNY Buffalo, Dept Clin Lab Sci, Buffalo, NY 14260 USA.
[Trevisan, Maurizio] Hlth Sci Syst Nevada Syst Higher Educ, Las Vegas, NV USA.
[Hovey, Kathleen; Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,7B03M, Rockville, MD 20852 USA.
EM schistee@mail.nih.gov
RI Yeung, Edwina/F-5992-2015;
OI Yeung, Edwina/0000-0002-3851-2613; Schisterman,
Enrique/0000-0003-3757-641X
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), National Institutes of Health
FX The BioCycle Study and its researchers were supported in part or full by
the Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD), National
Institutes of Health.
NR 40
TC 27
Z9 27
U1 3
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 15
PY 2010
VL 172
IS 4
BP 430
EP 439
DI 10.1093/aje/kwq131
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 638NX
UT WOS:000280902700010
PM 20679069
ER
PT J
AU Terasaki, Y
Yahiro, K
Pacheco-Rodriguez, G
Steagall, WK
Stylianou, MP
Evans, JF
Walker, AM
Moss, J
AF Terasaki, Yasuhiro
Yahiro, Kinnosuke
Pacheco-Rodriguez, Gustavo
Steagall, Wendy K.
Stylianou, Mario P.
Evans, Jilly F.
Walker, Ameae M.
Moss, Joel
TI Effects of Prolactin on TSC2-Null Rat Cells and in Pulmonary
Lymphangioleiomyomatosis
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE proliferation; pneumothorax; pulmonary function tests; tuberous
sclerosis complex
ID TUBEROUS SCLEROSIS COMPLEX; BREAST-CANCER; S179D PROLACTIN; KINASE
ACTIVATION; PROSTATE-CANCER; RECEPTOR; EXPRESSION; GROWTH;
PROLIFERATION; GENE
AB Rationale: Lymphangioleiomyomatosis, a cystic lung disease of women, is characterized by proliferation of smooth muscle-like lymphangioleiomyomatosis cells, which possess mutations in the tuberous sclerosis complex genes, TSC1/TSC2. Growth factors involved in lymphangioleiomyomatosis cell proliferation are unknown. Prolactin, an important reproductive hormone in women, is known to promote cell proliferation and survival in other tissues.
Objectives: To determine the role of prolactin in signaling and proliferation in lymphangioleiomyomatosis.
Methods: Prolactin levels in the sera of patients with lymphangioleiomyomatosis were correlated with clinical status. Components of prolactin signal transduction pathways were assessed in lymphangioleiomyomatosis lesions from human lung explants by real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Prolactin effects on proliferation and signaling were quantified in tuberin-deficient and tuberin-expressing rat cells in vitro.
Measurements and Main Results: Higher prolactin levels in the sera of patients with lymphangioleiomyomatosis were associated with a faster rate of decline in FEV(1) and an increased history of pneumothorax (P < 0 01). Higher levels of prolactin and prolactin receptor mRNA and immunoreactivity were found in lymphangioleiomyomatosis lesions when compared with vascular smooth muscle cells in the same region of tissue. This was accompanied by evidence of activation of signal transducer and activator of transcription-1 (STAT1), STAT3, p44/42, and p38 mitogen-activated protein kinase. Tsc2(-/-) Eker rat embryonic fibroblasts expressed more prolactin receptor than did Tsc2(+/+) cells, and responded to prolactin with increased proliferation and activation of the same signaling pathways seen in vivo.
Conclusions: Prolactin may be an important growth factor in the pathogenesis of lymphangioleiomyomatosis.
C1 [Terasaki, Yasuhiro; Yahiro, Kinnosuke; Pacheco-Rodriguez, Gustavo; Steagall, Wendy K.; Moss, Joel] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
[Stylianou, Mario P.] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
[Evans, Jilly F.] Amira Pharmaceut, San Diego, CA USA.
[Walker, Ameae M.] Univ Calif Riverside, Div Biomed Sci, Riverside, CA 92521 USA.
RP Moss, J (reprint author), NHLBI, Translat Med Branch, NIH, Bldg 10 Room 6D05,9000 Rockville Pike, Bethesda, MD 20892 USA.
FU NHLBI, NIH
FX Supported in part by the Intramural Research Program (NHLBI, NIH)
NR 42
TC 4
Z9 4
U1 2
U2 3
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD AUG 15
PY 2010
VL 182
IS 4
BP 531
EP 539
DI 10.1164/rccm.200911-1737OC
PG 9
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 640LI
UT WOS:000281052300013
PM 20413627
ER
PT J
AU Kecskes, M
Kumar, TS
Yoo, L
Gao, ZG
Jacobson, KA
AF Kecskes, Miklos
Kumar, T. Santhosh
Yoo, Lena
Gao, Zhan-Guo
Jacobson, Kenneth A.
TI Novel Alexa Fluor-488 labeled antagonist of the A(2A) adenosine
receptor: Application to a fluorescence polarization-based receptor
binding assay
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Purines; Fluorescence polarization; G protein-coupled receptor;
High-throughput screening; A(2A) adenosine receptor
ID LIGANDS; PHARMACOLOGY; DERIVATIVES; SELECTIVITY; ANALOGS; RAT
AB Fluorescence polarization (FP) assay has many advantages over the traditional radioreceptor binding studies. We developed an A(2A) adenosine receptor (AR) FP assay using a newly synthesized fluorescent antagonist of the A(2A)AR (MRS5346), a pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine derivative conjugated to the fluorescent dye Alexa Fluor-488. MRS5346 displayed a K-i; value of 111 +/- 16 nM in radioligand binding using ([H-3]CGS21680 and membranes prepared from HEK293 cells stably expressing the human A(2A)AR. In a cyclic AMP functional assay, MRS5346 was shown to be an A(2A)AR antagonist. MRS5346 did not show any effect on A(1) and A(3) ARs in binding or the A(2B)AR in a cyclic AMP assay at 10 mu M. Its suitability as a fluorescent tracer was indicated in an initial observation of an FP signal following A(2A)AR binding. The FP signal was optimal with 20 nM MRS5346 and 150 mu g protein/mL HEK293 membranes. The association and dissociation kinetic parameters were readily determined using this FP assay. The K-d value of MRS5346 calculated from kinetic parameters was 16.5 +/- 4.7 nM. In FP competition binding experiments using MRS5346 as a tracer, K-i values of known AR agonists and antagonists consistently agreed with K-i values from radioligand binding. Thus, this FP assay, which eliminates using radioisotopes, appears to be appropriate for both routine receptor binding and high-throughput screening with respect to speed of analysis, displaceable signal and precision. The approach used in the present study could be generally applicable to other GPCRs. Published by Elsevier Inc.
C1 [Kecskes, Miklos; Kumar, T. Santhosh; Yoo, Lena; Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Jacobson, KA (reprint author), NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU NIH, National Institute of Diabetes and Digestive and Kidney Diseases
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Diabetes and Digestive and Kidney Diseases.
Special thanks to Csaba Vizier, Ph.D. (BRC-HAS).
NR 30
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U1 0
U2 13
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
EI 1873-2968
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD AUG 15
PY 2010
VL 80
IS 4
BP 506
EP 511
DI 10.1016/j.bcp.2010.04.027
PG 6
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 624GB
UT WOS:000279803800010
PM 20438717
ER
PT J
AU Kahn, AB
Zeeberg, BR
Ryan, MC
Jamison, DC
Rockoff, DM
Pommier, Y
Weinstein, JN
AF Kahn, Ari B.
Zeeberg, Barry R.
Ryan, Michael C.
Jamison, D. Curtis
Rockoff, David M.
Pommier, Yves
Weinstein, John N.
TI Ontogenomic study of the relationship between number of gene splice
variants and GO categorization
SO BIOINFORMATICS
LA English
DT Article
ID HUMAN-DISEASE; DIVERSITY; ISOFORMS; EXPRESSION; ONTOLOGY; ACTIVATION;
MECHANISMS; EVOLUTION; BIOLOGY; TOOL
AB Motivation: Splice variation plays important roles in evolution and cancer. Different splice variants of a gene may be characteristic of particular cellular processes, subcellular locations or organs. Although several genomic projects have identified splice variants, there have been no large-scale computational studies of the relationship between number of splice variants and biological function. The Gene Ontology (GO) and tools for leveraging GO, such as GoMiner, now make such a study feasible.
Results: We partitioned genes into two groups: those with numbers of splice variants <= b and > b (b=1,...,10). Then we used GoMiner to determine whether any GO categories are enriched in genes with particular numbers of splice variants. Since there was no a priori 'appropriate' partition boundary, we studied those 'robust' categories whose enrichment did not depend on the selection of a particular partition boundary. Furthermore, because the distribution of splice variant number was a snapshot taken at a particular point in time, we confirmed that those observations were stable across successive builds of GenBank. A small number of categories were found for genes in the lower partitions. A larger number of categories were found for genes in the higher partitions. Those categories were largely associated with cell death and signal transduction. Apoptotic genes tended to have a large repertoire of splice variants, and genes with splice variants exhibited a distinctive 'apoptotic island' in clustered image maps (CIMs).
C1 [Kahn, Ari B.; Ryan, Michael C.; Jamison, D. Curtis] George Mason Univ, Dept Bioinformat, Fairfax, VA 22030 USA.
[Kahn, Ari B.; Zeeberg, Barry R.; Ryan, Michael C.; Pommier, Yves; Weinstein, John N.] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA.
[Ryan, Michael C.] Tiger Team Consulting, Fairfax, VA USA.
[Jamison, D. Curtis] Cincinnati Childrens Hosp, Dept Biomed Informat, Cincinnati, OH USA.
[Rockoff, David M.] Iowa State Univ, Dept Stat, Ames, IA USA.
[Weinstein, John N.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
RP Kahn, AB (reprint author), George Mason Univ, Dept Bioinformat, Fairfax, VA 22030 USA.
EM barry@discover.nci.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research.
NR 41
TC 1
Z9 1
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD AUG 15
PY 2010
VL 26
IS 16
BP 1945
EP 1949
DI 10.1093/bioinformatics/btq335
PG 5
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 636BS
UT WOS:000280703500004
PM 20616384
ER
PT J
AU Bale, TL
Baram, TZ
Brown, AS
Goldstein, JM
Insel, TR
McCarthy, MM
Nemeroff, CB
Reyes, TM
Simerly, RB
Susser, ES
Nestler, EJ
AF Bale, Tracy L.
Baram, Tallie Z.
Brown, Alan S.
Goldstein, Jill M.
Insel, Thomas R.
McCarthy, Margaret M.
Nemeroff, Charles B.
Reyes, Teresa M.
Simerly, Richard B.
Susser, Ezra S.
Nestler, Eric J.
TI Early Life Programming and Neurodevelopmental Disorders
SO BIOLOGICAL PSYCHIATRY
LA English
DT Review
ID CORTICOTROPIN-RELEASING-FACTOR; STRUCTURAL BRAIN ABNORMALITIES; MAJOR
AFFECTIVE-DISORDER; PRENATAL EXPOSURE; SEX-DIFFERENCES; ADULT
SCHIZOPHRENIA; CHILDHOOD ABUSE; EPIGENETIC REGULATION; HPA AXIS; STRESS
AB For more than a century, clinical investigators have focused on early life as a source of adult psychopathology. Early theories about psychic conflict and toxic parenting have been replaced by more recent formulations of complex interactions of genes and environment. Although the hypothesized mechanisms have evolved, a central notion remains: early life is a period of unique sensitivity during which experience confers enduring effects. The mechanisms for these effects remain almost as much a mystery today as they were a century ago. Recent studies suggest that maternal diet can program offspring growth and metabolic pathways, altering lifelong susceptibility to diabetes and obesity. If maternal psychosocial experience has similar programming effects on the developing offspring, one might expect a comparable contribution to neurodevelopmental disorders, including affective disorders, schizophrenia, autism, and eating disorders. Due to their early onset, prevalence, and chronicity, some of these disorders, such as depression and schizophrenia, are among the highest causes of disability worldwide according to the World Health Organization 2002 report. Consideration of the early life programming and transcriptional regulation in adult exposures supports a critical need to understand epigenetic mechanisms as a critical determinant in disease predisposition. Incorporating the latest insight gained from clinical and epidemiological studies with potential epigenetic mechanisms from basic research, the following review summarizes findings from a workshop on Early Life Programming and Neurodevelopmental Disorders held at the University of Pennsylvania in 2009.
C1 [Bale, Tracy L.] Univ Penn, Dept Anim Biol, Philadelphia, PA 19104 USA.
[Reyes, Teresa M.] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA.
[Baram, Tallie Z.] Univ Calif Irvine, Dept Pediat, Irvine, CA 92717 USA.
[Baram, Tallie Z.] Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92717 USA.
[Brown, Alan S.; Susser, Ezra S.] Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, New York, NY USA.
[Goldstein, Jill M.] Brigham & Womens Hosp, Connors Ctr Womens Hlth & Gender Biol, Boston, MA 02115 USA.
[Goldstein, Jill M.] Harvard Univ, Sch Med, Boston, MA USA.
[Insel, Thomas R.] NIMH, Bethesda, MD 20892 USA.
[McCarthy, Margaret M.] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA.
[Nemeroff, Charles B.] Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA.
[Simerly, Richard B.] Univ So Calif, Saban Res Inst, Los Angeles, CA USA.
[Nestler, Eric J.] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA.
RP Bale, TL (reprint author), Univ Penn, Dept Anim Biol, 201E Vet 6046,3800 Spruce St, Philadelphia, PA 19104 USA.
EM tbale@vet.upenn.edu
RI Baram, Tallie/J-6447-2014
FU National Institutes of Health [MH086157]; AstraZeneca; Wilmington;
Delaware; AstraZeneca anti consults for PsychoGenics; Merck; Danone
FX The Early Life Programming and Neurodevelopmental Disorders Conference
was funded by Grants from National Institutes of Health MH086157 and
AstraZeneca, Wilmington, Delaware.; Drs. Mike Baram, Jill Goldstein,
Thomas Insel, Margaret McCarthy, Teresa Reyes, and Ezra Susser report no
biomedical financial interests or potential conflicts of interest. Dr.
Nestler receives research grants from AstraZeneca anti consults for
PsychoGenics and Merck. Dr. Nemeroff has served on the Board of
Directors of Novadel Pharma and Mt Cook Pharma and on the Scientific
Advisory Board of PharmaNeuroboost, Cenerx, and AstraZeneca. He holds
stock stock options, or equity in Novadel Pharma, Cenerx, Reevax, and
PharmaNeuroboost. He holds two US patents, one on transdermal delivery
of lithium and one on ex vivo measurement of monoamine transporter
occupancy during antidepressant treatment. Dr. Simerly reports receipt
of consulting fees from Danone and has received a speaker honorarium
from Amylin Pharmaceuticals. Dr. Tracy Bale has received grant funding
from AstraZeneca. Dr. Brown has received honorarium from Merck for
speaker training and is expected to receive further honoraria for future
speaking engagements from this company.
NR 80
TC 271
Z9 274
U1 14
U2 92
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD AUG 15
PY 2010
VL 68
IS 4
BP 314
EP 319
DI 10.1016/j.biopsych.2010.05.028
PG 6
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 638MU
UT WOS:000280899800002
PM 20674602
ER
PT J
AU Nwe, K
Bernardo, M
Regino, CAS
Williams, M
Brechbiel, MW
AF Nwe, K.
Bernardo, M.
Regino, C. A. S.
Williams, M.
Brechbiel, M. W.
TI Comparison of MRI properties between derivatized DTPA and DOTA
gadolinium-dendrimer conjugates
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE 2-(p-Isothiocyanato benzyl)-6-methyl-diethylenetriaminepentaacetic acid
(1B4M-DTPA); Polyamidoamine (PAMAM) generation; 4 dendrimer (G4D);
2-(4-Isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-N,N '; N '',N
'''-tetraacetic acid gadolinium complex; (p-SCN-C-DOTA[Gd])
ID MAGNETIC-RESONANCE; CONTRAST AGENTS; DRUG-DELIVERY; WATER EXCHANGE;
GD-DOTA; RENAL-FAILURE; COMPLEXES; RELAXATION; RELAXIVITY; NMR
AB In this report we directly compare the in vivo and in vitro MRI properties of gadolinium-dendrimer conjugates of derivatized acyclic diethylenetriamine-N,N ',N ',N '',N ''-pentaacetic acid (1B4M-DTPA) and macrocyclic 1,4,7,10-tetraazacyclododecane-N, N ', N '', N '''-tetraacetic acid (C-DOTA). The metal-ligand chelates were pre-formed in alcohol prior to conjugation to the generation 4 PAMAM dendrimer (G4D), and the dendrimer-based agents were purified by Sephadex (R) G-25 column. The analysis and SE-HPLC data indicated chelate to dendrimer ratios of 30:1 and 28:1, respectively. Molar relaxivity measured at pH 7.4, 22 degrees C, and 3T are comparable (29.5 vs 26.9 mM (1) s (1)), and both conjugates are equally viable as MRI contrast agents based on the images obtained. The macrocyclic agent however exhibits a faster rate of clearance in vivo (t(1/2) = 16 vs 29 min). Our conclusion is that the macrocyclic-based agent is the more suitable agent for in vivo use for these reasons combined with kinetic inertness associated with the Gd(III) DOTA complex stability properties. Published by Elsevier Ltd.
C1 [Brechbiel, M. W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Regino, C. A. S.; Williams, M.] NCI, Mol Imaging Program, Bethesda, MD 20892 USA.
[Bernardo, M.] NCI, Res Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bldg 10,Room B3B69,10 Ctr Dr, Bethesda, MD 20892 USA.
EM martinwb@mail.nih.gov
FU National Institute of Health, National Cancer Institute, Center for
Cancer Research; United States Department of Health and Human Services
FX This research was supported by the Intramural Research Program of the
National Institute of Health, National Cancer Institute, Center for
Cancer Research and the United States Department of Health and Human
Services.
NR 46
TC 27
Z9 29
U1 3
U2 30
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD AUG 15
PY 2010
VL 18
IS 16
BP 5925
EP 5931
DI 10.1016/j.bmc.2010.06.086
PG 7
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 635OD
UT WOS:000280664100015
PM 20663676
ER
PT J
AU Balboni, G
Marzola, E
Sasaki, Y
Ambo, A
Marczak, ED
Lazarus, LH
Salvadori, S
AF Balboni, Gianfranco
Marzola, Erika
Sasaki, Yusuke
Ambo, Akihiro
Marczak, Ewa D.
Lazarus, Lawrence H.
Salvadori, Severo
TI Role of 2 ',6 '-dimethyl-L-tyrosine (Dmt) in some opioid lead compounds
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Dmt-Tic pharmacophore; Opioid peptides; Opioid receptors; delta-Opioid
agonists; UFP-512; delta-Opioid antagonists
ID MU AGONIST/DELTA ANTAGONIST; TIC PHARMACOPHORE; ASYMMETRIC-SYNTHESIS;
RECEPTOR LIGANDS; SELECTIVITY; AFFINITY; BENZIMIDAZOLE; ENDOMORPHIN-2;
ALKYLATION; CONVENIENT
AB Here we evaluated how the interchange of the amino acids 2',6'-dimethyl-L-tyrosine (Dmt), 2',6'-difluoro-L- tyrosine (Dft), and tyrosine in position 1 can affect the pharmacological characterization of some reference opioid peptides and pseudopeptides. Generally, Dft and Tyr provide analogues with a similar pharmacological profile, despite different pK(a) values. Dmt/Tyr(Dft) replacement gives activity changes depending on the reference opioid in which the modification was made. Whereas, H-Dmt-Tic-Asp*-Bid is a potent and selective delta agonist (MVD, IC50 = 0.12 nM); H-Dft-Tic-Asp*-Bid and H-Tyr-Tic-Asp*-Bid are potent and selective delta antagonists (pA(2) = 8.95 and 8.85, respectively). When these amino acids are employed in the synthesis of deltorphin B and its Dmt(1) and Dft(1) analogues, the three compounds maintain a very similar delta agonism (MVD, IC50 0.32-0.53 nM) with a decrease in selectivity relative to the Dmt(1) analogue. In the less selective H-Dmt-Tic-Gly*-Bid the replacement of Dmt with Dft and Tyr retains the delta agonism but with a decrease in potency. Antagonists containing the Dmt-Tic pharmacophore do not support the exchange of Dmt with Dft or Tyr. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Balboni, Gianfranco] Univ Cagliari, Dept Toxicol, I-09124 Cagliari, Italy.
[Marzola, Erika; Salvadori, Severo] Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy.
[Marzola, Erika; Salvadori, Severo] Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy.
[Sasaki, Yusuke; Ambo, Akihiro] Tohoku Pharmaceut Univ, Dept Pharmacol, Aoba Ku, Sendai, Miyagi 9818558, Japan.
[Marczak, Ewa D.; Lazarus, Lawrence H.] Natl Inst Environm Hlth Sci, Med Chem Grp, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA.
RP Balboni, G (reprint author), Univ Cagliari, Dept Toxicol, I-09124 Cagliari, Italy.
EM gbalboni@unica.it; sal@unife.it
OI Marzola, Erika/0000-0002-1428-1363; SALVADORI,
Severo/0000-0002-8224-2358
FU University of Cagliari; University of Ferrara; NIH; NIEHS
FX This work was supported in part by the University of Cagliari (to G.B.),
the University of Ferrara (S.S.), and in part by the Intramural Research
Program of the NIH and NIEHS (to L.H.L.).
NR 36
TC 5
Z9 5
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
EI 1464-3391
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD AUG 15
PY 2010
VL 18
IS 16
BP 6024
EP 6030
DI 10.1016/j.bmc.2010.06.073
PG 7
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 635OD
UT WOS:000280664100027
PM 20637637
ER
PT J
AU Yang, MH
Sun, S
Bruck, HA
Kostov, Y
Rasooly, A
AF Yang, Minghui
Sun, Steven
Bruck, Hugh Alan
Kostov, Yordan
Rasooly, Avraham
TI Electrical percolation-based biosensor for real-time direct detection of
staphylococcal enterotoxin B (SEB)
SO BIOSENSORS & BIOELECTRONICS
LA English
DT Article
DE Biosensor; Semiconductor; Carbon nanotubes; Electrical percolation;
Antibody; Point of care; Personalized medicine
ID CARBON NANOTUBES; ATOPIC-DERMATITIS; RHEUMATOID-ARTHRITIS; FOOD;
SUPERANTIGENS; FUNCTIONALIZATION; PREVALENCE; CHILDREN; TOXINS; ELISA
AB Electrical percolation-based biosensing is a new technology. This is the first report of an electrical percolation-based biosensor for real-time detection. The label-free biosensor is based on electrical percolation through a single-walled carbon nanotubes (SWNTs)-antibody complex that forms a network functioning as a "Biological Semiconductor (BSC). The conductivity of a BSC is directly related to the number of contacts facilitated by the antibody-antigen "connectors" within the SWNT network. BSCs are fabricated by immobilizing a pre-functionalized SWNTs-antibody complex directly on a poly(methyl methacrylate) (PMMA) and polycarbonate (PC) surface. Each BSC is connected via silver electrodes to a computerized ohmmeter, thereby enabling a continuous electronic measurement of molecular interactions (e.g. antibody-antigen binding) via the change in resistance. Using anti-staphylococcal enterotoxin B (SEB) IgG to functionalize the BSC, we demonstrate that the biosensor was able to detect SEB at concentrations as low as 5 ng/mL at a signal to baseline (S/B) ratio of 2. Such measurements were performed on the chip in wet conditions.
The actuation of the chip by SEB is immediate, permitting real-time signal measurements. In addition to this "direct" label-free detection mode, a secondary antibody can be used to "label" the target molecule bound to the BSC in a manner analogous to an immunological sandwich "indirect" detection-type assay. Although a secondary antibody is not needed for direct detection, the indirect mode of detection may be useful as an additional measurement to verify or amplify signals from direct detection in clinical, food safety and other critical assays. The BSC was used to measure SEB both in buffer and in milk, a complex matrix, demonstrating the potential of electrical percolation-based biosensors for real-time label-free multi-analyte detection in clinical and complex samples. Assembly of BSCs is simple enough that multiple sensors can be fabricated on the same chip, thereby creating "Biological Central Processing Units (BCPUs)" capable of parallel processing and sorting out information on multiple analytes simultaneously which may be used for complex analysis and for point of care diagnostics. Published by Elsevier B.V.
C1 [Yang, Minghui; Sun, Steven; Kostov, Yordan] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA.
[Bruck, Hugh Alan] Univ Maryland, College Pk, MD 20742 USA.
[Sun, Steven; Rasooly, Avraham] US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA.
[Rasooly, Avraham] NCI, Bethesda, MD 20892 USA.
[Yang, Minghui] Univ Jinan, Sch Chem & Chem Engn, Jinan 250022, Peoples R China.
RP Rasooly, A (reprint author), NCI, NIH, 6130 Execut Blvd,EPN,Room 6035A, Rockville, MD 20852 USA.
EM rasoolya@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 40
TC 14
Z9 16
U1 0
U2 19
PU ELSEVIER ADVANCED TECHNOLOGY
PI OXFORD
PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON,
OXFORD OX5 1GB, OXON, ENGLAND
SN 0956-5663
J9 BIOSENS BIOELECTRON
JI Biosens. Bioelectron.
PD AUG 15
PY 2010
VL 25
IS 12
BP 2573
EP 2578
DI 10.1016/j.bios.2010.04.019
PG 6
WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical;
Electrochemistry; Nanoscience & Nanotechnology
SC Biophysics; Biotechnology & Applied Microbiology; Chemistry;
Electrochemistry; Science & Technology - Other Topics
GA 620YI
UT WOS:000279538700004
PM 20447819
ER
PT J
AU Yasui, H
Matsumoto, S
Devasahayam, N
Munasinghe, JP
Choudhuri, R
Saito, K
Subramanian, S
Mitchell, JB
Krishna, MC
AF Yasui, Hironobu
Matsumoto, Shingo
Devasahayam, Nallathamby
Munasinghe, Jeeva P.
Choudhuri, Rajani
Saito, Keita
Subramanian, Sankaran
Mitchell, James B.
Krishna, Murali C.
TI Low-Field Magnetic Resonance Imaging to Visualize Chronic and Cycling
Hypoxia in Tumor-Bearing Mice
SO CANCER RESEARCH
LA English
DT Article
ID ELECTRON-PARAMAGNETIC-RESONANCE; X-RAY-IRRADIATION; IN-VIVO; TRANSIENT
HYPOXIA; MURINE TUMORS; OXYGEN; CELL; ANGIOGENESIS; CANCER; EPR
AB Tumors exhibit fluctuations in blood flow that influence oxygen concentrations and therapeutic resistance. To assist therapeutic planning and improve prognosis, noninvasive dynamic imaging of spatial and temporal variations in oxygen partial pressure (pO(2)) would be useful. Here, we illustrate the use of pulsed electron paramagnetic resonance imaging (EPRI) as a novel imaging method to directly monitor fluctuations in oxygen concentrations in mouse models. A common resonator platform for both EPRI and magnetic resonance imaging (MRI) provided pO(2) maps with anatomic guidance and microvessel density. Oxygen images acquired every 3 minutes for a total of 30 minutes in two different tumor types revealed that fluctuation patterns in pO(2) are dependent on tumor size and tumor type. The magnitude of fluctuations in pO(2) in SCCVII tumors ranged between 2- to 18-fold, whereas the fluctuations in HT29 xenografts were of lower magnitude. Alternating breathing cycles with air or carbogen (95% O(2) plus 5% CO(2)) distinguished higher and lower sensitivity regions, which responded to carbogen, corresponding to cycling hypoxia and chronic hypoxia, respectively. Immunohistochemical analysis suggests that the fluctuation in pO(2) correlated with pericyte density rather than vascular density in the tumor. This EPRI technique, combined with MRI, may offer a powerful clinical tool to noninvasively detect variable oxygenation in tumors. Cancer Res; 70(16); 6427-36. (C)2010 AACR.
C1 [Yasui, Hironobu; Matsumoto, Shingo; Devasahayam, Nallathamby; Choudhuri, Rajani; Saito, Keita; Subramanian, Sankaran; Mitchell, James B.; Krishna, Murali C.] NCI, Ctr Canc Res, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA.
[Munasinghe, Jeeva P.] Natl Inst Neurol Disorder & Stroke, NIH, Bethesda, MD USA.
RP Yasui, H (reprint author), NCI, Ctr Canc Res, Radiat Biol Branch, NIH, Bldg 10,Room B3B69,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM murali@helix.nih.gov
RI Yasui, Hironobu/E-3794-2010
FU Center for Cancer Research, NCI, NIH
FX Intramural Research Program, Center for Cancer Research, NCI, NIH.
NR 50
TC 58
Z9 58
U1 1
U2 11
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD AUG 15
PY 2010
VL 70
IS 16
BP 6427
EP 6436
DI 10.1158/0008-5472.CAN-10-1350
PG 10
WC Oncology
SC Oncology
GA 638IK
UT WOS:000280887000005
PM 20647318
ER
PT J
AU Cao, LA
Yu, YK
Bilke, S
Walker, RL
Mayeenuddin, LH
Azorsa, DO
Yang, F
Pineda, M
Helman, LJ
Meltzer, PS
AF Cao, Liang
Yu, Yunkai
Bilke, Sven
Walker, Robert L.
Mayeenuddin, Linnia H.
Azorsa, David O.
Yang, Fan
Pineda, Marbin
Helman, Lee J.
Meltzer, Paul S.
TI Genome-Wide Identification of PAX3-FKHR Binding Sites in
Rhabdomyosarcoma Reveals Candidate Target Genes Important for
Development and Cancer
SO CANCER RESEARCH
LA English
DT Article
ID MUSCLE PROGENITOR CELLS; ALVEOLAR RHABDOMYOSARCOMAS; ACTIVATING
MUTATIONS; TRANSCRIPTION FACTOR; ALK KINASE; PAX GENES; NEUROBLASTOMA;
EXPRESSION; RECEPTOR; MYOD
AB The PAX3-FKHR fusion protein is present in a majority of alveolar rhabdomyosarcomas associated with increased aggressiveness and poor prognosis. To better understand the molecular pathogenesis of PAX3-FKHR, we carried out the first, unbiased genome-wide identification of PAX3-FKHR binding sites and associated target genes in alveolar rhabdomyosarcoma. The data shows that PAX3-FKHR binds to the same sites as PAX3 at both MYF5 and MYOD enhancers. The genome-wide analysis reveals that the PAX3-FKHR sites are (a) mostly distal to transcription start sites, (b) conserved, (c) enriched for PAX3 motifs, and (d) strongly associated with genes overexpressed in PAX3-FKHR-positive rhabdomyosarcoma cells and tumors. There is little evidence in our data set for PAX3-FKHR binding at the promoter sequences. The genome-wide analysis further illustrates a strong association between PAX3 and E-box motifs in these binding sites, suggestive of a common coregulation for many target genes. We also provide the first direct evidence that FGFR4 and IGF1R are the targets for PAX3-FKHR. The map of PAX3-FKHR binding sites provides a framework for understanding the pathogenic roles of PAX3-FKHR, as well as its molecular targets to allow a systematic evaluation of agents against this aggressive rhabdomyosarcoma. Cancer Res; 70(16); 6497-508. (C)2010 AACR.
C1 [Cao, Liang; Yu, Yunkai; Bilke, Sven; Walker, Robert L.; Mayeenuddin, Linnia H.; Yang, Fan; Pineda, Marbin; Meltzer, Paul S.] NCI, Ctr Canc Res, Genet Branch, Bethesda, MD 20892 USA.
[Helman, Lee J.] NCI, Ctr Canc Res, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Azorsa, David O.] NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA.
[Yu, Yunkai; Mayeenuddin, Linnia H.] Sci Applicat Int Corp, Lab Prote & Analyt Technol, Frederick, MD USA.
[Yu, Yunkai; Mayeenuddin, Linnia H.] NCI, Frederick, MD 21701 USA.
RP Cao, LA (reprint author), NCI, Ctr Canc Res, Genet Branch, Bethesda, MD 20892 USA.
EM caoli@mail.nih.gov
FU NIH, National Cancer Institute; NIH [N01-CO-12400]
FX The Intramural Research Program of the NIH, National Cancer Institute,
and in part with federal funds from the NIH, under contract
N01-CO-12400. The contents of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government.
NR 50
TC 93
Z9 95
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD AUG 15
PY 2010
VL 70
IS 16
BP 6497
EP 6508
DI 10.1158/0008-5472.CAN-10-0582
PG 12
WC Oncology
SC Oncology
GA 638IK
UT WOS:000280887000012
PM 20663909
ER
PT J
AU Moore, LE
Boffetta, P
Karami, S
Brennan, P
Stewart, PS
Hung, R
Zaridze, D
Matveev, V
Janout, V
Kollarova, H
Bencko, V
Navratilova, M
Szeszenia-Dabrowska, N
Mates, D
Gromiec, J
Holcatova, I
Merino, M
Chanock, S
Chow, WH
Rothman, N
AF Moore, Lee E.
Boffetta, Paolo
Karami, Sara
Brennan, Paul
Stewart, Patricia S.
Hung, Rayjean
Zaridze, David
Matveev, Vsevolod
Janout, Vladimir
Kollarova, Helena
Bencko, Vladimir
Navratilova, Marie
Szeszenia-Dabrowska, Neonila
Mates, Dana
Gromiec, Jan
Holcatova, Ivana
Merino, Maria
Chanock, Stephen
Chow, Wong-Ho
Rothman, Nathaniel
TI Occupational Trichloroethylene Exposure and Renal Carcinoma Risk:
Evidence of Genetic Susceptibility by Reductive Metabolism Gene Variants
SO CANCER RESEARCH
LA English
DT Article
ID CELL CANCER-RISK; KIDNEY CANCER; HYDROCARBON EXPOSURES; POLYMORPHISMS;
SMOKING; WORKERS; HISTORY; GERMANY; EUROPE; GSTT1
AB Trichloroethylene (TCE) is a suspected renal carcinogen. TCE-associated renal genotoxicity occurs predominantly through glutathione S-transferase (GST) conjugation and bioactivation by renal cysteine beta-lyase (CCBL1). We conducted a case-control study in Central Europe (1,097 cases and 1,476 controls) specifically designed to assess risk associated with occupational exposure to TCE through analysis of detailed job histories. All jobs were coded for organic/chlorinated solvent and TCE exposure (ever/never) as well as the frequency and intensity of exposure based on detailed occupational questionnaires, specialized questionnaires, and expert assessments. Increased risk was observed among subjects ever TCE exposed [odds ratio (OR) = 1.63; 95% confidence interval (95% CI), 1.04-2.54]. Exposure-response trends were observed among subjects above and below the median exposure [average intensity (OR = 1.38; 95% CI, 0.81-2.35; OR = 2.34; 95% CI, 1.05-5.21; P(trend) = 0.02)]. A significant association was found among TCE-exposed subjects with at least one intact GSTT1 allele (active genotype; OR = 1.88; 95% CI, 1.06-3.33) but not among subjects with two deleted alleles (null genotype; OR = 0.93; 95% CI, 0.35-2.44; P(interaction) = 0.18). Similar associations for all exposure metrics including average intensity were observed among GSTT1-active subjects (OR = 1.56; 95% CI, 0.79-3.10; OR = 2.77; 95% CI, 1.01-7.58; P(trend) = 0.02) but not among GSTT1 nulls (OR = 0.81; 95% CI, 0.24-2.72; OR = 1.16; 95% CI, 0.27-5.04; P(trend) = 1.00; P(interaction) = 0.34). Further evidence of heterogeneity was seen among TCE-exposed subjects with >= 1 minor allele of several CCBL1-tagging single nucleotide polymorphisms: rs2293968, rs2280841, rs2259043, and rs941960. These findings provide the strongest evidence to date that TCE exposure is associated with increased renal cancer risk, particularly among individuals carrying polymorphisms in genes that are important in the reductive metabolism of this chemical, and provides biological plausibility of the association in humans. Cancer Res; 70(16); 6527-36. (C)2010 AACR.
C1 [Moore, Lee E.; Karami, Sara; Stewart, Patricia S.; Chanock, Stephen; Chow, Wong-Ho; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20852 USA.
[Chanock, Stephen] NCI, Core Genotyping Facil, Dept Hlth & Human Serv, Adv Technol Ctr,NIH, Bethesda, MD 20852 USA.
[Merino, Maria] NCI, Dept Pathol, Clin Canc Res Ctr, NIH, Bethesda, MD 20892 USA.
[Boffetta, Paolo; Brennan, Paul] IARC, Lyon, France.
[Stewart, Patricia S.] LLC, Stewart Exposure Assessments, Arlington, VA USA.
[Hung, Rayjean] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Zaridze, David; Matveev, Vsevolod] Russian Acad Med Sci, Canc Res Ctr, Inst Carcinogenesis, Moscow, Russia.
[Janout, Vladimir; Kollarova, Helena] Palacky Univ, Dept Prevent Med, Fac Med, CR-77147 Olomouc, Czech Republic.
[Bencko, Vladimir; Holcatova, Ivana] Charles Univ Prague, Inst Hyg & Epidemiol, Fac Med 1, Prague, Czech Republic.
[Navratilova, Marie] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic.
[Szeszenia-Dabrowska, Neonila] Nofer Inst Occupat Med, Dept Epidemiol, Lodz, Poland.
[Gromiec, Jan] Nofer Inst Occupat Med, Dept Chem Hazards, Lodz, Poland.
[Mates, Dana] Inst Publ Hlth, Bucharest, Romania.
RP Moore, LE (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, 6120 Execut Blvd,EPS Room 8102, Bethesda, MD 20852 USA.
EM moorele@mail.nih.gov
RI Gromiec, Jan/G-4938-2010; Hung, Rayjean/A-7439-2013; Zaridze,
David/K-5605-2013; Janout, Vladimir/M-5133-2014; Szeszenia-Dabrowska,
Neonila/F-7190-2010;
OI mates, dana/0000-0002-6219-9807
FU NIH, NCI, Division of Cancer Epidemiology and Genetics (Bethesda, MD)
FX Intramural Research Program of the NIH, NCI, Division of Cancer
Epidemiology and Genetics (Bethesda, MD).
NR 43
TC 45
Z9 47
U1 1
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD AUG 15
PY 2010
VL 70
IS 16
BP 6527
EP 6536
DI 10.1158/0008-5472.CAN-09-4167
PG 10
WC Oncology
SC Oncology
GA 638IK
UT WOS:000280887000015
PM 20663906
ER
PT J
AU Xu, JM
Timares, L
Heilpern, C
Weng, ZP
Li, CZ
Xu, H
Pressey, JG
Elmets, CA
Kopelovich, L
Athar, M
AF Xu, Jianmin
Timares, Laura
Heilpern, Clay
Weng, Zhiping
Li, Changzhao
Xu, Hui
Pressey, Joseph G.
Elmets, Craig A.
Kopelovich, Levy
Athar, Mohammad
TI Targeting Wild-Type and Mutant p53 with Small Molecule CP-31398 Blocks
the Growth of Rhabdomyosarcoma by Inducing Reactive Oxygen
Species-Dependent Apoptosis
SO CANCER RESEARCH
LA English
DT Article
ID CELL-LINES; CANCER-CELLS; PROGNOSTIC-FACTORS; INHIBITS GROWTH; IN-VITRO;
TUMORS; CHILDHOOD; PATHWAY; DRUG; GENE
AB Rhabdomyosarcoma (RMS) is a common soft-tissue sarcoma of childhood in need of more effective therapeutic options. The expression of p53 in RMS is heterogeneous such that some tumors are wild-type whereas others are p53 mutant. The small molecule CP-31398 modulates both the wild-type and the mutant p53 proteins. Here, we show that CP-31398 blocks the growth of RMS cells that have either wild-type or mutant p53 status. In wild-type A204 cells, CP-31398 increased the expression of p53 and its downstream transcriptional targets, p21 and mdm2; enhanced the expression of apoptosis-related proteins; and reduced proliferation biomarkers. Flow profiling of CP-31398-treated cells indicated an enhancement in sub-G(0) and G(1) populations. CP-31398 inhibited proliferation in a manner associated with co-induction of SOX9 and p21. Apoptosis induced by CP-31398 occurred with translocation of p53 to mitochondria, leading to altered mitochondrial membrane potential, cytochrome c release, and reactive oxygen species release. In vivo, CP-31398 decreased the growth of tumor xenografts composed of wild-type or mutant p53 tumor cells, increasing tumor-free host survival. Our findings indicate that the ability of CP-31398 to modulate wild-type and mutant p53 results in the inhibition of RMS growth and invasiveness. Cancer Res; 70(16); 6566-76. (C)2010 AACR.
C1 [Xu, Jianmin; Timares, Laura; Heilpern, Clay; Weng, Zhiping; Li, Changzhao; Xu, Hui; Elmets, Craig A.; Athar, Mohammad] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA.
[Pressey, Joseph G.] Univ Alabama, Div Hematol Oncol, Dept Pediat, Birmingham, AL 35294 USA.
[Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Athar, M (reprint author), Univ Alabama, Dept Dermatol, Volker Hall,Room 509,1670 Univ Blvd, Birmingham, AL 35294 USA.
EM mathar@uab.edu
RI Xu, Hui/A-8167-2009; Li, Changzhao/P-7766-2015
FU NIH [R01 ES015323, NO1-CN-43300, P30 AR050948]
FX NIH grants R01 ES015323, NO1-CN-43300, and P30 AR050948.
NR 42
TC 23
Z9 24
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD AUG 15
PY 2010
VL 70
IS 16
BP 6566
EP 6576
DI 10.1158/0008-5472.CAN-10-0942
PG 11
WC Oncology
SC Oncology
GA 638IK
UT WOS:000280887000019
PM 20682800
ER
PT J
AU Aggarwal, M
Brosh, RM
AF Aggarwal, Monika
Brosh, Robert M., Jr.
TI Genetic mutants illuminate the roles of RecQ helicases in
recombinational repair or response to replicational stress
SO CELL CYCLE
LA English
DT Editorial Material
DE Werner syndrome; Bloom's syndrome; helicase; DNA repair; recombination;
replication; yeast genetics; Exonuclease 1; RecQ
ID DNA-REPAIR; EXO1
C1 [Aggarwal, Monika; Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
EM broshr@mail.nih.gov
FU Intramural NIH HHS
NR 12
TC 2
Z9 2
U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD AUG 15
PY 2010
VL 9
IS 16
BP 3139
EP 3141
DI 10.4161/cc.9.16.12953
PG 3
WC Cell Biology
SC Cell Biology
GA 639EZ
UT WOS:000280955700005
PM 20703073
ER
PT J
AU Wright, JJ
AF Wright, John J.
TI Combination Therapy of Bortezomib with Novel Targeted Agents: An
Emerging Treatment Strategy
SO CLINICAL CANCER RESEARCH
LA English
DT Review
ID PROTEASOME INHIBITOR BORTEZOMIB; MULTIPLE-MYELOMA CELLS; HISTONE
DEACETYLASE INHIBITORS; LYMPHOCYTIC-LEUKEMIA CELLS; MIMETIC GX15-070
OBATOCLAX; UNFOLDED PROTEIN RESPONSE; CANCER-THERAPY; LUNG-CANCER;
FLAVOPIRIDOL INTERACT; MONOCLONAL-ANTIBODY
AB Clinical trials evaluating combinations of targeted agents with bortezomib, the first-in-class proteasome inhibitor, have been initiated, with the objective of enhancing its single agent activity in hematologic malignancies (myeloma, mantle cell lymphoma), as well as expanding its efficacy in solid tumors. In most cases, preclinical studies have provided a supportive rationale for designing these doublet combination studies. Novel, small molecule-targeted agents being investigated with bortezomib in clinical trials include protein deacetylase inhibitors, kinase inhibitors, farnesyltransferase inhibitors, heat-shock protein 90 inhibitors, pan-Bcl-2 family inhibitors, and other classes of targeted inhibitors. Preliminary clinical data, available from a number of ongoing trials, suggest that most of these combinations are well tolerated and some have promising clinical efficacy that will require subsequent confirmation. Translational studies, conducted as part of the trials, may provide important insights into the putative mechanism of action delineated by preclinical studies of the combinations. The emergence of novel proteasome inhibitors may also expand the opportunities for optimizing these combination therapies. There is potential for an increasingly broad clinical trials program to investigate this therapeutic approach in a range of tumor types, as well as to consider additional agents in sequence or in combination. Clin Cancer Res; 16(16); 4094-104. (C) 2010 AACR.
C1 NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Wright, JJ (reprint author), NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, 6130 Execut Blvd,EPN 7122, Bethesda, MD 20892 USA.
EM WrightJ@ctep.nci.nih.gov
FU Millennium Pharmaceuticals, Inc.
FX The author would like to acknowledge the support of Millennium
Pharmaceuticals, Inc. and assistance of Sarah Maloney and Jane Saunders
of FireKite
NR 100
TC 67
Z9 69
U1 1
U2 10
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD AUG 15
PY 2010
VL 16
IS 16
BP 4094
EP 4104
DI 10.1158/1078-0432.CCR-09-2882
PG 11
WC Oncology
SC Oncology
GA 637PJ
UT WOS:000280830300006
PM 20682705
ER
PT J
AU Terzuoli, E
Donnini, S
Giachetti, A
Iniguez, MA
Fresno, M
Melillo, G
Ziche, M
AF Terzuoli, Erika
Donnini, Sandra
Giachetti, Antonio
Iniguez, Miguel A.
Fresno, Manuel
Melillo, Giovanni
Ziche, Marina
TI Inhibition of Hypoxia Inducible Factor-1 alpha by
Dihydroxyphenylethanol, a Product from Olive Oil, Blocks Microsomal
Prostaglandin-E Synthase-1/Vascular Endothelial Growth Factor Expression
and Reduces Tumor Angiogenesis
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID COLON-CANCER CELLS; E SYNTHASE; PROMOTES; CYCLOOXYGENASE-2; THERAPY;
PROTEIN; ERK1/2; GENE; INOS; E-2
AB Purpose: 2-(3,4-dihydroxyphenil)-ethanol (DPE), a polyphenol present in olive oil, has been found to attenuate the growth of colon cancer cells, an effect presumably related to its anti-inflammatory activity.
Experimental Design: To further explore the effects of DPE on angiogenesis and tumor growth we investigated the in vivo efficacy of DPE in a HT-29 xenograft model and in vitro activities in colon cancer cells exposed to interleukin-1 beta (IL-1 beta) and prostaglandin E-2 (PGE-2).
Results: DPE (10 mg/kg/day for 14 days) inhibited tumor growth, reducing vessel lumina and blood perfusion to tumor, and diminished expression of hypoxia inducible factor-1 alpha (HIF-1 alpha), vascular endothelial growth factor (VEGF), and microsomal prostaglandin-E synthase-1 (mPGEs-1). In vitro, DPE (100 mu mol/L) neither affected cell proliferation nor induced apoptosis in HT-29 and WiDr cells. DPE prevented the IL-1 beta-mediated increase of mPGEs-1 expression and PGE-2 generation, as it did the silencing of HIF-1a. Moreover, DPE blocked mPGEs-1-dependent expression of VEGF and inhibited endothelial sprouting induced by tumor cells in a coculture system. PGE-2 triggers a feed-forward loop involving HIF-1a, which impinges on mPGEs-1 and VEGF expression, events prevented by DPE via extracellular signal-related kinase 1/2. The reduction of PGE-2 and VEGF levels, caused by DPE, was invariably associated with a marked decrease in HIF-1a expression and activity, independent of proteasome activity, indicating that the DPE effects on tumor growth and angiogenesis are dependent on the inhibition of HIF-1a translation.
Conclusions: We show that the in vivo DPE antitumor effect is associated with anti-inflammatory and antiangiogenic activities resulting from the downregulation of the HIF-1 alpha/mPGEs-1/VEGF axis. Clin Cancer Res; 16(16); 4207-16. (C) 2010 AACR.
C1 [Terzuoli, Erika; Donnini, Sandra; Giachetti, Antonio; Ziche, Marina] Univ Siena, Dept Mol Biol, I-53100 Siena, Italy.
[Iniguez, Miguel A.; Fresno, Manuel] Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, Madrid, Spain.
[Melillo, Giovanni] NCI, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Ziche, M (reprint author), Univ Siena, Dept Mol Biol, Via A Moro 2, I-53100 Siena, Italy.
EM melillog@mail.nih.gov; ziche@unisi.it
RI Iniguez Pena, Miguel Angel/J-8518-2012;
OI Iniguez Pena, Miguel Angel/0000-0001-8262-6119; Fresno Escudero,
Manuel/0000-0002-9223-5477
FU Istituto Toscano Tumori (ITT); Progetto Ordinario-Ministero della
Salute; National Cancer Institute, NIH [N01-CO-12400]; DCTD, of the
National Cancer Institute, NIH
FX Istituto Toscano Tumori (ITT) (M. Ziche and S. Donnini), and Progetto
Ordinario-Ministero della Salute (2006). This project has been funded in
whole or in part with federal funds from the National Cancer Institute,
NIH, under Contract No. N01-CO-12400. The content of this publication
does not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U. S. Government.
This research was supported by the Developmental Therapeutics Program,
DCTD, of the National Cancer Institute, NIH.
NR 26
TC 29
Z9 30
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD AUG 15
PY 2010
VL 16
IS 16
BP 4207
EP 4216
DI 10.1158/1078-0432.CCR-10-0156
PG 10
WC Oncology
SC Oncology
GA 637PJ
UT WOS:000280830300017
PM 20682710
ER
PT J
AU Sun, XL
Niu, G
Yan, YJ
Yang, M
Chen, K
Ma, Y
Chan, N
Shen, BZ
Chen, XY
AF Sun, Xilin
Niu, Gang
Yan, Yongjun
Yang, Min
Chen, Kai
Ma, Ying
Chan, Nicholas
Shen, Baozhong
Chen, Xiaoyuan
TI Phage Display-Derived Peptides for Osteosarcoma Imaging
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID THERAPIES; CANCER
AB Purpose: Osteosarcoma represents the most common malignant primary bone tumor in childhood; however, the survival rate has remained unchanged for the past 20 years. To improve existing diagnosis and treatment methods and broaden the spectrum of imaging agents that can be used for early detection and assessment of tumor response to therapy, we performed a phage display-based screening for peptide sequences that bind specifically to osteosarcoma cells.
Experimental Design: From the Ph. D.-12 phage display peptide library composed of 2.7 x 109 different displayed peptides, one peptide was enriched after four rounds of in vitro selection in 143B osteosarcoma tumor cells with 293T human embryonic kidney cells as a control. Both the peptide and the phage clone displaying the peptide were conjugated with fluorescent dyes for in vitro cell and ex vivo tumor tissue stainings. The peptide was further labeled with (18)F for positron emission tomography imaging studies. Cell uptake and efflux and ex vivo biodistribution were also done with (18)F-labeled osteosarcoma specific peptide.
Results: ASGALSPSRLDT was the dominant sequence isolated from biopanning and named as OSP-1. OSP-1 shares a significant homology with heparinase II/III family protein, which binds and reacts with heparan sulfate proteoglycans. The fluorescence staining showed that FITC-OSP-1-phage or Cy5.5-OSP-1 had high binding with a panel of osteosarcoma cell lines, much less binding with UM-SCC1 human head and neck squamous cell carcinoma cells, and almost no binding with 293T cells, whereas the scrambled peptide OSP-S had virtually no binding to all the cell lines. (18)F-OSP-1 had significantly higher accumulation in 143B tumor cells both in vitro and in vivo than (18)F-OSP-S. (18)F-OSP-1 also had higher uptake in 143B tumors than in UM-SCC-1 tumors.
Conclusions: Our data suggest that OSP-1 peptide is osteosarcoma specific, and the binding site of OSP-1 might be related to heparan sulfate proteoglycans. Appropriately labeled OSP-1 peptide has the potential to serve as a novel probe for osteosarcoma imaging. Clin Cancer Res; 16(16); 4268-77. (C) 2010 AACR.
C1 [Sun, Xilin; Niu, Gang; Yan, Yongjun; Yang, Min; Chen, Kai; Ma, Ying; Chan, Nicholas; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
[Niu, Gang] NIH, Imaging Sci Training Program, Ctr Clin, Bethesda, MD 20892 USA.
[Sun, Xilin; Shen, Baozhong] Harbin Med Coll, Affiliated Hosp 4, Dept Med Imaging & Nucl Med, Harbin 150001, Peoples R China.
[Yang, Min] Jiangsu Inst Nucl Med, Key Lab Nucl Med, Wuxi, Peoples R China.
RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, 31 Ctr Dr,Suite 1C14, Bethesda, MD 20892 USA.
EM shenbzh@vip.sina.com; shawn.chen@nih.gov
FU National Institute of Biomedical Imaging and Bioengineering, NIH
FX Intramural Research Program of the National Institute of Biomedical
Imaging and Bioengineering, NIH.
NR 18
TC 20
Z9 21
U1 3
U2 15
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD AUG 15
PY 2010
VL 16
IS 16
BP 4268
EP 4277
DI 10.1158/1078-0432.CCR-10-0968
PG 10
WC Oncology
SC Oncology
GA 637PJ
UT WOS:000280830300023
PM 20570932
ER
PT J
AU Choi, SJ
Song, IS
Feng, JQ
Gao, T
Haruyama, N
Gautam, P
Robey, PG
Hart, TC
AF Choi, S. J.
Song, I. S.
Feng, J. Q.
Gao, T.
Haruyama, N.
Gautam, P.
Robey, P. G.
Hart, Thomas C.
TI Mutant DLX 3 disrupts odontoblast polarization and dentin formation
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE DLX3; Transgenic mouse; Dentin mineralization; Taurodontism TDO
odontoblast polarization; apoptosis TBC1D19
ID ENDOPLASMIC-RETICULUM STRESS; TRICHODENTOOSSEOUS SYNDROME; TOOTH
DEVELOPMENT; HOMEODOMAIN PROTEINS; TRANSGENIC MICE; GROWTH-FACTORS;
PRIMARY CILIA; EXPRESSION; DIFFERENTIATION; MUTATION
AB Tricho-dento-osseous (TDO) syndrome is an autosomal dominant disorder characterized by abnormalities in the thickness and density of bones and teeth. A 4-bp deletion mutation in the Distal-Less 3 (DIX3) gene is etiologic for most cases of TOO. To investigate the in vivo role of mutant DLX3 (MT-DLX3) on dentin development, we generated transgenic (TG) mice expressing MT-DLX3 driven by a mouse 2.3 CollA1 promoter. Dentin defects were radiographically evident in all teeth and the size of the nonmineralized pulp was enlarged in TG mice, consistent with clinical characteristics in patients with TDO. High-resolution radiography, microcomputed tomography, and SEM revealed a reduced zone of mineralized dentin with anomalies in the number and organization of dentinal tubules in MT-DLX3 TG mice. Histological and immunohistochemical studies demonstrated that the decreased dentin was accompanied by altered odontoblast cytology that included disruption of odontoblast polarization and reduced numbers of odontoblasts. TUNEL assays indicated enhanced odontoblast apoptosis. Expression levels of the apoptotic marker caspase-3 were increased in odontoblasts in TG mice as well as in odontoblastic-like MDPC-23 cells transfected with MT-DLX3 cDNA. Expression of Runx2, Wnt 10A, and TBC1D19 colocalized with DLX3 expression in odontoblasts, and MT-DLX3 significantly reduced expression of all three genes. TBC1D19 functions in cell polarity and decreased TBC1D19 expression may contribute to the observed disruption of odontoblast polarity and apoptosis. These data indicate that MT-DLX3 acts to disrupt odontoblast cytodifferentiation leading to odontoblast apoptosis, and aberrations of dentin tubule formation and dentin matrix production, resulting in decreased dentin and taurodontism.
In summary, this TG model demonstrates that MT-DLX3 has differential effects on matrix production and mineralization in dentin and bone and provides a novel tool for the investigation of odontoblast biology. Published by Elsevier Inc.
C1 [Choi, S. J.; Gautam, P.; Robey, P. G.; Hart, Thomas C.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
[Song, I. S.] Univ Ulsan, Sch Med, Dept Rheumatol, Asan Inst Life Sci,Lab Natl Investment Project, Seoul, South Korea.
[Feng, J. Q.; Gao, T.] Texas A&M Hlth Sci Ctr, Baylor Coll Dent, Dallas, TX USA.
[Haruyama, N.] Tokyo Med & Dent Univ, Grad Sch, Dept Maxillofacial Orthognath, Tokyo, Japan.
RP Hart, TC (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bldg 30,RM 524,30 Convent Dr, Bethesda, MD 20892 USA.
EM thart@mail.nih.gov
RI Haruyama, Naoto/D-1993-2011; Robey, Pamela/H-1429-2011
OI Haruyama, Naoto/0000-0001-6225-5816; Robey, Pamela/0000-0002-5316-5576
FU NIDCR, National Institutes of Health, Bethesda, MD, USA
FX We thank Dr. Larry Fisher for DSPP, Bgn, and Dcn antibodies and
acknowledge support from the Intramural Program of the NIDCR, National
Institutes of Health, Bethesda, MD 20892, USA.
NR 46
TC 24
Z9 24
U1 1
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD AUG 15
PY 2010
VL 344
IS 2
BP 682
EP 692
DI 10.1016/j.ydbio.2010.05.499
PG 11
WC Developmental Biology
SC Developmental Biology
GA 637AR
UT WOS:000280787100014
PM 20510228
ER
PT J
AU Lin, L
McCroskery, S
Ross, JM
Chak, Y
Neuhuber, B
Daniels, MP
AF Lin, Lin
McCroskery, Seumas
Ross, Jaime M.
Chak, Yvonne
Neuhuber, Birgit
Daniels, Mathew P.
TI Induction of filopodia-like protrusions by transmembrane agrin: Role of
agrin glycosaminoglycan chains and Rho-family GTPases
SO EXPERIMENTAL CELL RESEARCH
LA English
DT Article
DE Agrin; Filopodia; Glycosaminoglycan; Rho-family GTPases
ID HEPARAN-SULFATE PROTEOGLYCAN; ACETYLCHOLINE-RECEPTOR CLUSTERS;
CELL-ADHESION; NEURONAL DEVELOPMENT; DENDRITIC FILOPODIA; RECOMBINANT
AGRIN; LIPID RAFTS; PROTEIN; SYNAPSE; EXPRESSION
AB Filopodia sense the extracellular environment and direct movement in many cell types, including neurons. Recent reports suggest that the transmembrane form of the widely expressed proteoglycan agrin (TM-agrin) regulates formation and stability of neuronal filopodia. In order to elucidate the mechanism by which TM-agrin regulates filopodia, we investigated the role of agrin's glycosaminoglycan (GAG) chains in the induction of filopodia formation by TM-agrin overexpression in hippocampal neurons, and in the induction of filopodia-like processes in COS7 cells. Deletion of the GAG chains of TM-agrin sharply reduced formation of filopodia-like branched retraction fibers (BRFs) in COS7 cells, with deletion of the heparan sulfate GAG chains being most effective, and eliminated filopodia induction in hippocampal neurons. GAG chain deletion also reduced the activation of Cdc42 and Rac1 resulting from TM-agrin over-expression. Moreover, dominant-negative Cdc42 and Rac1 inhibited BRF formation. Lastly, over-expression of TM-agrin increased the adhesiveness of COS7 cells and this increase was reduced by deletion of the GAG chains. Our results suggest that TM-agrin regulates actin-based protrusions in large part through interaction of its GAG chains with extracellular or transmembrane proteins, leading to the activation of Cdc42 and Rac1. Published by Elsevier Inc.
C1 [Lin, Lin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Neurophysiol & Biophys Unit, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD USA.
[Lin, Lin; McCroskery, Seumas; Ross, Jaime M.; Chak, Yvonne; Neuhuber, Birgit; Daniels, Mathew P.] Natl Heart Lung & Blood Inst, Cell Biol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA.
[McCroskery, Seumas] ERMA New Zealand, New Organisms Grp, Wellington, New Zealand.
[Ross, Jaime M.] Natl Inst Drug Abuse, Karolinska Inst Grad Partnerships Program, NIH, Baltimore, MD USA.
[Chak, Yvonne] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA.
[Neuhuber, Birgit] Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19104 USA.
[Daniels, Mathew P.] Natl Heart Lung & Blood Inst, Electron Microscopy Core Facil, NIH, Bethesda, MD USA.
RP Lin, L (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Neurophysiol & Biophys Unit, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD USA.
EM LinL@mail.nih.gov
RI Ross, Jaime/A-6893-2012
FU Intramural NIH HHS [ZIC HL005906-02]
NR 57
TC 14
Z9 16
U1 0
U2 1
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4827
J9 EXP CELL RES
JI Exp. Cell Res.
PD AUG 15
PY 2010
VL 316
IS 14
BP 2260
EP 2277
DI 10.1016/j.yexcr.2010.05.006
PG 18
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 627DC
UT WOS:000280018300005
PM 20471381
ER
PT J
AU Zhao, H
Kim, G
Liu, CY
Levine, RL
AF Zhao, Hang
Kim, Geumsoo
Liu, Chengyu
Levine, Rodney L.
TI Transgenic mice overexpressing methionine sulfoxide reductase A:
Characterization of embryonic fibroblasts
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Methionine sulfoxide reductase A; Mouse embryonic fibroblast; Oxidative
stress; Reactive oxygen species; Thioredoxin; Thioredoxin reductase;
Free radicals
ID INDUCED CELL-DEATH; OXIDATIVE STRESS; ESCHERICHIA-COLI; A MSRA;
ANTIOXIDANT DEFENSE; PROTEIN DAMAGE; LIFE-SPAN; PEPTIDE; MITOCHONDRIAL;
CYTOTOXICITY
AB Methionine residues in protein can be oxidized by reactive oxygen species to generate methionine sulfoxide. Aerobic organisms have methionine sulfoxide reductases capable of reducing methionine sulfoxide back to methionine. Methionine sulfoxide reductase A acts on the S-epimer of methionine sulfoxide, and it is known that altering its cellular level by genetic ablation or overexpression has notable effects on resistance to oxidative stress and on life span in species from microorganisms to animals. In mammals, the enzyme is present in both the cytosol and the mitochondria, and this study was undertaken to assess the contribution of each subcellular compartment's reductase activity to resistance against oxidative stresses. Nontransgenic mouse embryonic fibroblasts lack methionine sulfoxide reductase A activity, providing a convenient cell type to determine the effects of expression of the enzyme in each compartment. We created transgenic mice with methionine sulfoxide reductase A targeted to the cytosol, mitochondria, or both and studied embryonic fibroblasts derived from each line. Unexpectedly, none of the transgenic cells gained resistance to a variety of oxidative stresses even though the expressed enzymes were catalytically active when assayed in vitro. Noting that activity in vivo requires thioredoxin and thioredoxin reductase, we determined the levels of these proteins in the fibroblasts and found that they were very low in both the nontransgenic and the transgenic cells. We conclude that overexpression of methionine sulfoxide reductase A did not confer resistance to oxidative stress because the cells lacked other proteins required to constitute a functional methionine sulfoxide reduction system. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Zhao, Hang; Kim, Geumsoo; Levine, Rodney L.] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA.
[Liu, Chengyu] NHLBI, Transgen Mouse Core Facil, NIH, Bethesda, MD 20892 USA.
RP Levine, RL (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3, Bethesda, MD 20892 USA.
EM rlevine@nih.gov
RI Zhao, Hang/A-2558-2012; Levine, Rodney/D-9885-2011
FU National Heart, Lung, and Blood Institute
FX We thank Angelique Biancotto and J. Philip McCoy of the Flow Cytometry
Core Facility of the National Heart, Lung, and Blood Institute for their
assistance with the flow cytometry. This research was supported by the
Intramural Research Program of the National Heart, Lung, and Blood
Institute.
NR 45
TC 11
Z9 11
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD AUG 15
PY 2010
VL 49
IS 4
BP 641
EP 648
DI 10.1016/j.freeradbiomed.2010.05.017
PG 8
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 630TA
UT WOS:000280295800016
PM 20510353
ER
PT J
AU Samuni, Y
Cook, JA
Choudhuri, R
DeGraff, W
Sowers, AL
Krishna, MC
Mitchell, JB
AF Samuni, Yuval
Cook, John A.
Choudhuri, Rajani
DeGraff, William
Sowers, Anastasia L.
Krishna, Murali C.
Mitchell, James B.
TI Inhibition of adipogenesis by Tempol in 3T3-L1 cells
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Adipogenesis; Tempol; Oxidative stress; Obesity; Nitroxide; Free
radicals
ID ADIPOCYTE DIFFERENTIATION; GENE-EXPRESSION; PPAR-GAMMA; OXIDATIVE
STRESS; WEIGHT-LOSS; CLONAL EXPANSION; BINDING-PROTEINS; GROWTH-FACTORS;
IN-VIVO; OBESITY
AB Obesity is highly associated with an increased risk of serious health conditions including hypertension, cardiovascular disease, diabetes, and cancer. Changes in redox status with increased oxidative stress have been linked with obesity. Previous studies have shown that administration of the antioxidant Tempol in the food of mice prevents obesity, causing significant weight loss without toxicity. To gain a better understanding of the molecular mechanism(s) underlying this effect, the influence of Tempol on the differentiation of mouse 3T3-L1 preadipocytes was studied. Tempol inhibited differentiation of 3T3-L1 cells, resulting in a reduction in cellular lipid storage, down-regulation of protein levels of key adipogenesis transcription factors (PPAR gamma and PPAR alpha), down-regulation of prolyl hydroxylase, and up-regulation of HIF-1 alpha. Mice on a Tempol diet demonstrated reduced systemic levels of IGF-1, in qualitative agreement with in vitro observations in 3T3-L1 cells, which also showed lower IGF-1 levels as a result of Tempol treatment. These results show that treatment of 3T3-L1 cells with Tempol inhibits the expression of key adipogenesis factors, adipose differentiation, and lipid storage and may underlie, at least in part, some of the in vivo effects of Tempol on body weight. Published by Elsevier Inc.
C1 [Samuni, Yuval; Cook, John A.; Choudhuri, Rajani; DeGraff, William; Sowers, Anastasia L.; Krishna, Murali C.; Mitchell, James B.] NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Mitchell, JB (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM jbm@helix.nih.gov
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX This research was supported by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health.
NR 47
TC 14
Z9 14
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD AUG 15
PY 2010
VL 49
IS 4
BP 667
EP 673
DI 10.1016/j.freeradbiomed.2010.05.028
PG 7
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 630TA
UT WOS:000280295800019
PM 20561604
ER
PT J
AU Corneveaux, JJ
Myers, AJ
Allen, AN
Pruzin, JJ
Ramirez, M
Engel, A
Nalls, MA
Chen, KW
Lee, W
Chewning, K
Villa, SE
Meechoovet, HB
Gerber, JD
Frost, D
Benson, HL
O'Reilly, S
Chibnik, LB
Shulman, JM
Singleton, AB
Craig, DW
Van Keuren-Jensen, KR
Dunckley, T
Bennett, DA
De Jager, PL
Heward, C
Hardy, J
Reiman, EM
Huentelman, MJ
AF Corneveaux, Jason J.
Myers, Amanda J.
Allen, April N.
Pruzin, Jeremy J.
Ramirez, Manuel
Engel, Anzhelika
Nalls, Michael A.
Chen, Kewei
Lee, Wendy
Chewning, Kendria
Villa, Stephen E.
Meechoovet, Hunsar B.
Gerber, Jill D.
Frost, Danielle
Benson, Hollie L.
O'Reilly, Sean
Chibnik, Lori B.
Shulman, Joshua M.
Singleton, Andrew B.
Craig, David W.
Van Keuren-Jensen, Kendall R.
Dunckley, Travis
Bennett, David A.
De Jager, Philip L.
Heward, Christopher
Hardy, John
Reiman, Eric M.
Huentelman, Matthew J.
TI Association of CR1, CLU and PICALM with Alzheimer's disease in a cohort
of clinically characterized and neuropathologically verified individuals
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID APOLIPOPROTEIN-E GENOTYPES; WHOLE-GENOME ASSOCIATION; COMMUNITY
POPULATION; IDENTIFIES VARIANTS; WIDE ASSOCIATION; OLDER PERSONS; TYPE-4
ALLELE; ONSET; RISK; GENE
AB In this study, we assess 34 of the most replicated genetic associations for Alzheimer's disease (AD) using data generated on Affymetrix SNP 6.0 arrays and imputed at over 5.7 million markers from a unique cohort of over 1600 neuropathologically defined AD cases and controls (1019 cases and 591 controls). Testing the top genes from the AlzGene meta-analysis, we confirm the well-known association with APOE single nucleotide polymorphisms (SNPs), the CLU, PICALM and CR1 SNPs recently implicated in unusually large data sets, and previously implicated CST3 and ACE SNPs. In the cases of CLU, PICALM and CR1, as well as in APOE, the odds ratios we find are slightly larger than those previously reported in clinical samples, consistent with what we believe to be more accurate classification of disease in the clinically characterized and neuropathologically confirmed AD cases and controls.
C1 [Corneveaux, Jason J.; Allen, April N.; Pruzin, Jeremy J.; Chewning, Kendria; Villa, Stephen E.; Meechoovet, Hunsar B.; Gerber, Jill D.; Frost, Danielle; Benson, Hollie L.; O'Reilly, Sean; Craig, David W.; Van Keuren-Jensen, Kendall R.; Dunckley, Travis; Reiman, Eric M.; Huentelman, Matthew J.] Translat Genom Res Inst TGen, Neurogenom Div, Phoenix, AZ 85004 USA.
[Corneveaux, Jason J.; Allen, April N.; Pruzin, Jeremy J.; Chen, Kewei; Lee, Wendy; Chewning, Kendria; Villa, Stephen E.; Meechoovet, Hunsar B.; Gerber, Jill D.; Frost, Danielle; Benson, Hollie L.; O'Reilly, Sean; Craig, David W.; Van Keuren-Jensen, Kendall R.; Dunckley, Travis; Reiman, Eric M.; Huentelman, Matthew J.] Arizona Alzheimers Consortium, Phoenix, AZ 85006 USA.
[Myers, Amanda J.; Ramirez, Manuel; Engel, Anzhelika] Univ Miami, Miller Sch Med, Lab Funct Neurogenom, Miami, FL 33136 USA.
[Myers, Amanda J.; Ramirez, Manuel; Engel, Anzhelika] Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Div Neurosci, Miami, FL 33136 USA.
[Myers, Amanda J.; Ramirez, Manuel; Engel, Anzhelika] Univ Miami, Miller Sch Med, Dept Human Genet & Genom, Miami, FL 33136 USA.
[Myers, Amanda J.] Johnnie B Byrd Sr Alzheimers Ctr & Res Inst, Tampa, FL 33613 USA.
[Nalls, Michael A.; Singleton, Andrew B.] NIA, Mol Genet Sect, Neurogenet Lab, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
[Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
[Chibnik, Lori B.; Shulman, Joshua M.; De Jager, Philip L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol,Program Translat NeuroPsychiat Genom, Boston, MA 02115 USA.
[Heward, Christopher] Kronos Sci, Phoenix, AZ 85016 USA.
[Hardy, John] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
[Hardy, John] UCL Inst Neurol, Reta Lila Res Labs, London WC1N 3BG, England.
[Chen, Kewei; Lee, Wendy; Reiman, Eric M.] Banner Alzheimers Inst, Phoenix, AZ 85006 USA.
RP Huentelman, MJ (reprint author), Translat Genom Res Inst TGen, Neurogenom Div, 445 N 5th St, Phoenix, AZ 85004 USA.
EM mhuentelman@tgen.org
RI Singleton, Andrew/C-3010-2009; Myers, Amanda/B-1796-2010; Hardy,
John/C-2451-2009; Chen, kewei/P-6304-2015
OI Myers, Amanda/0000-0002-3100-9396; Chen, kewei/0000-0001-8497-3069
FU Kronos Science; National Institute of Neurological Disorders and Stroke
[R01 NS059873]; National Institute on Aging [R01 AG031581, P30 AG19610,
AG034504, Z01 AG000950-06, P30AG10161, R01AG 15819, K01AG024079]; Banner
Alzheimer's Foundation; Johnnie B. Byrd Sr. Alzheimer's Disease
Institute; Medical Research Council; Intramural Research Program of the
National Institutes of Health; State of Arizona; National Institute on
Aging and National Alzheimer [U01 AG016976]
FX This work was supported by Kronos Science; The National Institute of
Neurological Disorders and Stroke (R01 NS059873 to M.J.H.); The National
Institute on Aging (R01 AG031581 to E.M.R.; P30 AG19610 to E.M.R.;
AG034504 to A.J.M.; Z01 AG000950-06, P30AG10161 and R01AG 15819 to D. A.
B.; and K01AG024079 to T.D.); The Banner Alzheimer's Foundation; The
Johnnie B. Byrd Sr. Alzheimer's Disease Institute; The Medical Research
Council (to J.H.); The Intramural Research Program of the National
Institutes of Health; and the State of Arizona. Biomaterials were
collected from several National Institute on Aging and National
Alzheimer's Coordinating Center (U01 AG016976) funded sites. Marcelle
Morrison-Bogorad, PhD, Tony Phelps, PhD and Walter Kukull, PhD are
thanked for helping to co-ordinate this collection. The directors,
pathologist and technicians involved include: National Institute on
Aging; Ruth Seemann, John Hopkins Alzheimer's Disease Research Center
(NIA grant no. AG05146); Juan C. Troncoso, MD, Dr Olga Pletnikova,
University of California, Los Angeles (NIA grant no. P50 AG16570); Harry
Vinters, MD, Justine Pomakian, The Kathleen Price Bryan Brain Bank, Duke
University Medical Center (NIA grant no. AG05128 and NIA P30 #AG028377,
NINDS grant no. NS39764, NIMH MH60451 also funded by Glaxo Smith Kline);
Christine Hulette, MD, Director, John F. Ervin, Stanford University;
Dikran Horoupian, MD, Ahmad Salehi, MD, PhD, New York Brain Bank, Taub
Institute, Columbia University (NYBB); Jean Paul Vonsattel, MD, Katerina
Mancevska, Massachusetts General Hospital; E. Tessa Hedley-Whyte, MD, Dr
M. P. Frosch, Karlotta Fitch (NIH grant P50 AG005134), University of
Michigan (NIH grant P50-AG08671); Dr Roger Albin, Lisa Bain, Eszter
Gombosi, University of Kentucky (NIH no. AG05144): William Markesbery,
MD, Sonya Anderson, Mayo Clinic, Jacksonville; Dennis W. Dickson, MD,
Natalie Thomas, University Southern California; Caroll A. Miller, MD,
Jenny Tang, M. S., Dimitri Diaz, Washington University, St Louis
Alzheimer's Disease Research Center (NIH no. P50AG05681): Dan McKeel,
MD, John C. Morris, MD, Eugene Johnson, Jr, PhD, Virginia Buckles, PhD,
Deborah Carter, University ofWashington, Seattle (NIH no. P50 AG05136);
Thomas Montine, MD, PhD, Aimee Schantz, MD, Ann C. McKee, Carol Kubilus
Sun Health Research Institute, Arizona (NIA no. P30 AG19610); Joseph
Rogers, PhD, Thomas G. Beach, MD, PhD, Lucia I. Sue Emory University;
Bruce H. Wainer, MD, PhD, Marla Gearing, PhD, University of Texas,
Southwestern Medical School; Charles L. White, III, MD, Roger Rosenberg,
Marilyn Howell, Joan Reisch, University of California, Davis; William
Ellis, MD, Mary Ann Jarvis, Rush University Medical Center, Rush
Alzheimer's Disease Center (NIH no. P30AG10161); David A. Bennett, MD,
Julie A. Schneider, MD, MS, Karen Skish, MS, PA (ASCP) MT, Wayne T
Longman, University of Miami/NPF Brain Endowment Bank; Deborah C. Mash,
MD, Margaret J. Basile, Mitsuko Tanaka Oregon Health & Science
University; Randy Wotljer, PhD, additional tissues include samples from
the following sites; Newcastle Brain Tissue Resource (funding via the UK
Medical Research Council, local NHS trusts and Newcastle University); C.
M.; Morris, PhD, Ian G McKeith (Tissue for this study was provided by
the Newcastle Brain Tissue Resource which is funded in part by a grant
from the UK Medical Research Council (G0400074), by the Newcastle NIHR
Biomedical Research Centre in Ageing and Age Related Diseases to the
Newcastle upon Tyne Hospitals NHS Foundation Trust and by a grant from
the Alzheimer's Society and Alzheimer'sResearch Trust as part of the
Brains for Dementia Research Project); the MRC London Brain Bank for
Neurodegenerative Diseases; Simon Lovestone, MD PhD, Safa Al-Sarraj, MD,
Claire Troakes, South West Dementia Brain Bank (funding via numerous
sources including the Higher Education Funding Council for England
(HEFCE), Alzheimer's Research Trust (ART), BRACE as well as North
Bristol NHS Trust Research and Innovation Department and DeNDRoN); Seth
Love, MD, Patrick Kehoe, PhD, Laura Palmer, The Netherlands Brain Bank
(funding via numerous sources including Stichting MS Research, Brain Net
Europe, Hersenstichting Nederland Breinbrekend Werk, International
Parkinson Fonds, Internationale Stiching Alzheimer Onderzoek); Inge
Huitinga, MD, Marleen Rademaker, Michiel Kooreman, Institut de
Neuropatologia, Servei Anatomia Patologica, Universitat de Barcelona;
Isidre Ferrer Abizanda, MD, PhD, Susana Casas Boluda.
NR 34
TC 117
Z9 119
U1 2
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD AUG 15
PY 2010
VL 19
IS 16
BP 3295
EP 3301
DI 10.1093/hmg/ddq221
PG 7
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 630NS
UT WOS:000280280800016
PM 20534741
ER
PT J
AU Wilkin, TJ
Su, ZH
Krambrink, A
Long, JM
Greaves, W
Gross, R
Hughes, MD
Flexner, C
Skolnik, PR
Coakley, E
Godfrey, C
Hirsch, M
Kuritzkes, DR
Gulick, RM
AF Wilkin, Timothy J.
Su, Zhaohui
Krambrink, Amy
Long, Jianmin
Greaves, Wayne
Gross, Robert
Hughes, Michael D.
Flexner, Charles
Skolnik, Paul R.
Coakley, Eoin
Godfrey, Catherine
Hirsch, Martin
Kuritzkes, Daniel R.
Gulick, Roy M.
TI Three-Year Safety and Efficacy of Vicriviroc, a CCR5 Antagonist, in
HIV-1-Infected Treatment-Experienced Patients
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE antiretroviral therapy; CCR5 antagonist; HIV-1; vicriviroc
ID PLACEBO-CONTROLLED TRIAL; HIV-1 INFECTION; DOUBLE-BLIND; SUSCEPTIBILITY
SCORES; TMC125 ETRAVIRINE; LARGE POPULATION; RESISTANT HIV-1; CORECEPTOR
USE; GROUP A5211; IN-VIVO
AB Background: Vicriviroc, an investigational CCR5 antagonist, demonstrated short-term safety and antiretroviral activity.
Methods: Phase 2, double-blind, randomized study of vicriviroc in treatment-experienced subjects with CCR5-using HIV-1. Vicriviroc (5, 10, or 15 mg) or placebo was added to a failing regimen with optimization of background antiretroviral medications at day 14. Subjects experiencing virologic failure and subjects completing 48 weeks were offered open-label vicriviroc.
Results: One hundred eighteen subjects were randomized. Virologic failure (<1 log(10) decline in HIV-1 RNA >= 16 weeks postrandomization) occurred by week 48 in 24 of 28 (86%), 12 of 30 (40%), 8 of 30 (27%), 10 of 30 (33%) of subjects randomized to placebo, 5, 10, and 15 mg, respectively. Overall, 113 subjects received vicriviroc at randomization or after virologic failure, and 52 (46%) achieved HIV-1 RNA <50 copies per milliliter within 24 weeks. Through 3 years, 49% of those achieving suppression did not experience confirmed viral rebound. Dual or mixed-tropic HIV-1 was detected in 33 (29%). Vicriviroc resistance (progressive decrease in maximal percentage inhibition on phenotypic testing) was detected in 6 subjects. Nine subjects discontinued vicriviroc due to adverse events.
Conclusions: Vicriviroc seems safe and demonstrates sustained virologic suppression through 3 years of follow-up. Further trials of vicriviroc will establish its clinical utility for the treatment of HIV-1 infection.
C1 [Wilkin, Timothy J.; Gulick, Roy M.] Weill Cornell Med Coll, Div Infect Dis, New York, NY USA.
[Su, Zhaohui; Krambrink, Amy; Hughes, Michael D.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Long, Jianmin; Greaves, Wayne] Schering Plough Res Inst, Kenilworth, NJ USA.
[Gross, Robert] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Gross, Robert] Univ Penn, Sch Med, Div Infect Dis, Philadelphia, PA 19104 USA.
[Flexner, Charles] Johns Hopkins Univ, Baltimore, MD USA.
[Skolnik, Paul R.] Boston Univ, Med Ctr, Ctr HIV AIDS Care & Res, Boston, MA USA.
[Coakley, Eoin] Monogram Biosci, San Francisco, CA USA.
[Godfrey, Catherine] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
[Hirsch, Martin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Kuritzkes, Daniel R.] Brigham & Womens Hosp, Sect Retroviral Therapeut, Boston, MA 02115 USA.
[Kuritzkes, Daniel R.] Harvard Univ, Sch Med, Boston, MA USA.
RP Wilkin, TJ (reprint author), 119 W 24th St Ground Floor, New York, NY 10011 USA.
EM tiw2001@med.cornell.edu
FU NCRR NIH HHS [M01 RR000046, M01 RR000052, M01 RR000096, M01 RR005280-08,
M01- RR025780, M01-RR00046, M01-RR00052, M01-RR00096, M01-RR024160,
RR024979, UL1 RR024160, UL1 RR024160-01, UL1 RR024979, UL1 RR024979-01,
UL1 RR024996, UL1 RR024996-01, UL1 RR025780, UL1 RR025780-01,
UL1-RR024996]; NIAID NIH HHS [U01 AI068636-01, AI- 69511, AI-25859,
AI-27661, AI-32782, AI-34853, AI-46370, AI-68634, AI-69418, AI-69419,
AI-69423, AI-69424, AI-69432, AI-69434, AI-69439, AI-69450, AI-69465,
AI-69467, AI-69471, AI-69472, AI-69474, AI-69494, AI-69495, AI-69501,
AI-69502, AI-69532, AI-69556, K23 AI055038, K23 AI055038-01,
K23-AI-55038, K24 AI051966, K24 AI051966-01A1, K24-AI-51966, P30
AI045008, P30 AI045008-05, P30 AI050410, P30 AI050410-04, P30-AI-45008,
P30-AI-50410, U01 AI025859, U01 AI025859-13, U01 AI027661, U01
AI027661-14, U01 AI032782, U01 AI032782-09, U01 AI034853, U01
AI034853-07, U01 AI046370, U01 AI046370-01, U01 AI068634, U01
AI068634-01, U01 AI068636, U01 AI069418, U01 AI069418-01, U01 AI069419,
U01 AI069419-01, U01 AI069423, U01 AI069423-01, U01 AI069424, U01
AI069424-01, U01 AI069432, U01 AI069432-01, U01 AI069434, U01
AI069434-01, U01 AI069439, U01 AI069439-01, U01 AI069450, U01
AI069450-01, U01 AI069465, U01 AI069465-01, U01 AI069467, U01
AI069467-01, U01 AI069471, U01 AI069471-01, U01 AI069472, U01
AI069472-01, U01 AI069474, U01 AI069474-01, U01 AI069494, U01
AI069494-01, U01 AI069495, U01 AI069495-01, U01 AI069501, U01
AI069501-01, U01 AI069502, U01 AI069502-01, U01 AI069511-01, U01
AI069532, U01 AI069532-01, U01 AI069556, U01 AI069556-01, U01-AI-68636,
UM1 AI068634, UM1 AI069418, UM1 AI069419, UM1 AI069423, UM1 AI069424,
UM1 AI069432, UM1 AI069434, UM1 AI069439, UM1 AI069450, UM1 AI069465,
UM1 AI069467, UM1 AI069471, UM1 AI069472, UM1 AI069474, UM1 AI069494,
UM1 AI069495, UM1 AI069501, UM1 AI069502, UM1 AI069532, UM1 AI069556]
NR 26
TC 15
Z9 17
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD AUG 15
PY 2010
VL 54
IS 5
BP 470
EP 476
DI 10.1097/QAI.0b013e3181e2cba0
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 628UU
UT WOS:000280149000004
PM 20672447
ER
PT J
AU Redd, AD
Eaton, KP
Kong, XR
Laeyendecker, O
Lutalo, T
Wawer, MJ
Gray, RH
Serwadda, D
Quinn, TC
AF Redd, Andrew D.
Eaton, Kevin P.
Kong, Xiangrong
Laeyendecker, Oliver
Lutalo, Tom
Wawer, Maria J.
Gray, Ronald H.
Serwadda, David
Quinn, Thomas C.
CA Rakai Hlth Sciences Program
TI C-Reactive Protein Levels Increase During HIV-1 Disease Progression in
Rakai, Uganda, Despite the Absence of Microbial Translocation
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE Africa; HIV disease progression; immune activation; microbial
translocation
ID IMMUNE ACTIVATION; AFRICAN; AIDS
AB Introduction: Microbial translocation has been implicated as a contributing factor to the heightened immune activation observed during HIV-1 disease progression. When examined in a longitudinal study of HIV-1 seroconverters in Rakai, Uganda, microbial translocation was not associated with HIV-1 disease progression. However, the role of general immune activation in HIV disease progression in this population was not fully examined.
Methods: Longitudinal serum samples of HIV-1 seroconverters in three HIV-1 disease progression groups [long-term nonprogressors (LTNP), standard progressors (SP), and rapid progressors (RP)] from Rakai, Uganda, were tested for levels of C-reactive protein (CRP), a marker for immune activation.
Results: CRP levels significantly increased in the SP group (P < 0.0001) but not in the RP group or the LTNP group. CRP levels during the first year post-HIV seroconversion in the RP group were significantly higher than those observed in the LTNP group (P < 0.05). For the entire population, CRP levels negatively correlated with lipopolysaccharide levels (P < 0.05) and were not associated with endotoxin antibody levels.
Conclusions: This study suggests that in this population, increased immune activation is significantly associated with HIV-1 disease progression but not microbial translocation.
C1 [Eaton, Kevin P.; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Redd, Andrew D.; Laeyendecker, Oliver; Quinn, Thomas C.] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Kong, Xiangrong; Wawer, Maria J.; Gray, Ronald H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, Baltimore, MD 21205 USA.
[Lutalo, Tom; Serwadda, David] Rakai Hlth Sci Program, Kalisizo, Uganda.
[Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda.
RP Quinn, TC (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, John Rangos Sr Bldg,Room 530,855 N Wolfe St, Baltimore, MD 21205 USA.
EM tquinn@jhmi.edu
RI Laeyendecker, Oliver/B-9331-2009;
OI Laeyendecker, Oliver/0000-0002-6429-4760
FU Division of Intramural Research, NIAID, NIH [R01 A134826, R01 A134265];
NICHD [5P30HD06826]; World Bank STI Project, Uganda; Henry M. Jackson
Foundation; Fogarty Foundation [5D43TW00010]; Bill and Melinda Gates
Institute for Population and Reproductive Health at JHU
FX Supported in part by funding from the Division of Intramural Research,
NIAID, NIH; NIAID (grants R01 A134826 and R01 A134265); NICHD (grant
5P30HD06826); the World Bank STI Project, Uganda; the Henry M. Jackson
Foundation; the Fogarty Foundation (grant 5D43TW00010); and the Bill and
Melinda Gates Institute for Population and Reproductive Health at JHU.
NR 12
TC 20
Z9 23
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD AUG 15
PY 2010
VL 54
IS 5
BP 556
EP 559
DI 10.1097/QAI.0b013e3181e0cdea
PG 4
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 628UU
UT WOS:000280149000017
PM 20463585
ER
PT J
AU Rogers, VE
Lewin, DS
Winnie, GB
Geiger-Brown, J
AF Rogers, Valerie E.
Lewin, Daniel S.
Winnie, Glenna B.
Geiger-Brown, Jeanne
TI Polysomnographic Characteristics of a Referred Sample of Children with
Sickle Cell Disease
SO JOURNAL OF CLINICAL SLEEP MEDICINE
LA English
DT Article
DE Adenoidectomy; tonsillectomy; child; adolescent; sickle cell disease;
sleep apnea, obstructive; periodic limb movement disorder;
polysomnography
ID OBSTRUCTIVE SLEEP-APNEA; PERIODIC LIMB MOVEMENTS; PULSE OXIMETRY;
OXYHEMOGLOBIN DESATURATION; PULMONARY-HYPERTENSION; ANEMIA; ADOLESCENTS;
HYPOXEMIA; SEVERITY; ADENOIDECTOMY
AB Study Objectives: To describe polysomnographic parameters and their clinical correlates in a referred sample of children with sickle cell disease (SOD).
Methods: This was a retrospective medical record review of 55 consecutive children aged 2-18 years with SOD (hemoglobin [Hb] SS and Hb SC genotypes) undergoing polysomnography for evaluation of sleep disordered breathing. Polysomnography values were compared between SOD genotypes, 4 age groups, and adenotonsillectomy status using descriptive and nonparametric statistics.
Results: Obstructive sleep apnea (OSA) was diagnosed in 38/55 (69%) children. Polysomnographic parameters differed significantly between Hb SS and Hb SC genotypes only on arterial oxyhemoglobin saturation (SpO(2); 95.2 +/- 3.8 vs. 98.0 +/- 0.8, respectively, p < 0.01) and percent of sleep time below SpO(2) 90% (T(90); 8.0 +/- 22.0 vs. 0.01 +/- 0.02, respectively, p < 0.05). Increasing age was associated with decreasing SpO(2) (rho = -0.282, p < 0.05), obstructive apnea-hypopnea index (OAHI; rho = -0.364, p < 0.01), total arousal index (rho = -0.272, p < 0.05) and respiratory arousal index (rho = -0.349, p < 0.01). Periodic limb movements in sleep (PLM) averaged 4.7 +/- 8.8/h, with a PLM index > 5/h in 5/17 children without OSA. Post- adenotonsillectomy, 8/10 children had OSA, but compared to untreated OSA-positive children they had a lower mean OAHI (4.4 +/- 5.5 vs. 8.9 +/- 12.5) and a lower T(90) (1.6 +/- 4.2 vs. 9.2 +/- 24.9).
Conclusions: Both OSA and PLMs were common in children with SOD. Children with Hb SS experienced more severe nocturnal oxygen desaturation than did those with Hb SC. Post-adenotonsillectomy, most children had OSA, although they experienced fewer obstructive respiratory events and less severe nocturnal oxygen desaturation than did untreated OSA-positive children.
C1 [Rogers, Valerie E.] Univ Penn, Sch Med, Div Biobehav Hlth Sci, Ctr Sleep & Resp Neurobiol, Philadelphia, PA 19104 USA.
[Lewin, Daniel S.] NHLBI, Div Lung Dis, Bethesda, MD 20892 USA.
[Winnie, Glenna B.] Pediat Lung Ctr, Pediat Sleep Ctr, Purcellville, VA USA.
[Geiger-Brown, Jeanne] Univ Maryland, Sch Nursing, Dept Family & Community Hlth, Work & Hlth Res Ctr, Baltimore, MD 21201 USA.
RP Rogers, VE (reprint author), 307D Claire M Fagin Hall,418 Curie Blvd, Philadelphia, PA 19104 USA.
EM vrog@nursing.upenn.edu
FU Children's National Medical Center
FX The authors thank several members of the medical staff at the Children's
National Medical Center, including Lori Luchtman-Jones, M.D., pediatric
hematologist-oncologist and Maria Pena, M.D., pediatric otolaryngologist
for their support of this study, and in particular Folasade Ogunlesi,
M.D., pediatric pulmonologist, whose interest in sleep in children with
sickle cell disease inspired this research.
NR 39
TC 17
Z9 17
U1 0
U2 1
PU AMER ACAD SLEEP MEDICINE
PI WESTCHESTER
PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA
SN 1550-9389
J9 J CLIN SLEEP MED
JI J. Clin. Sleep Med.
PD AUG 15
PY 2010
VL 6
IS 4
BP 374
EP 381
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 638BB
UT WOS:000280863500011
PM 20726287
ER
PT J
AU Cichocki, F
Lenvik, T
Sharma, N
Yun, G
Anderson, SK
Miller, JS
AF Cichocki, Frank
Lenvik, Todd
Sharma, Neeraj
Yun, Gong
Anderson, Stephen K.
Miller, Jeffrey S.
TI Cutting Edge: KIR Antisense Transcripts Are Processed into a 28-Base
PIWI-Like RNA in Human NK Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NATURAL-KILLER-CELLS; RECEPTOR EXPRESSION; DNA METHYLATION;
IDENTIFICATION; PROMOTERS; GENES
AB Killer Ig-like receptors (KIRs) are expressed in a variegated, clonally restricted fashion on NK cells and are important determinants of NK cell function. Although silencing of individual KIR genes is strongly correlated with the presence of CpG dinucleotide methylation within the promoter, the mechanism responsible for silencing has not been identified. Our results show that antisense transcripts mediate KIR transcriptional silencing through a novel PIWI-like 28-base small RNA. Although PIWI RNA-mediated silencing of transposable elements within germ cells have been described, this is the first report that identifies a PIWI-like RNA in an immune somatic cell lineage and identifies a mechanism that may be broadly used in orchestrating immune development. The Journal of Immunology, 2010, 185: 2009-2012.
C1 [Cichocki, Frank; Lenvik, Todd; Yun, Gong; Miller, Jeffrey S.] Univ Minnesota, Div Hematol Oncol & Transplantat, Ctr Canc, Minneapolis, MN 55455 USA.
[Sharma, Neeraj; Anderson, Stephen K.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Anderson, Stephen K.] NCI, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Miller, JS (reprint author), Univ Minnesota, Div Hematol Oncol & Transplantat, Ctr Canc, MMC 806,Harvard St & E River Rd, Minneapolis, MN 55455 USA.
EM mille011@umn.edu
RI Anderson, Stephen/B-1727-2012
OI Anderson, Stephen/0000-0002-7856-4266
FU National Institutes of Health [P01-CA-111412, R01-HL-55417]; National
Cancer Institute, National Institutes of Health [HHSN261200800001E];
National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX This work was supported in part by National Institutes of Health Grant
P01-CA-111412 (to J.S.M. and S. K. A.) and R01-HL-55417 (to J.S.M.).
This work was also funded in part by federal funds from the National
Cancer Institute, National Institutes of Health, under Contract
HHSN261200800001E (to S. K. A.) and supported in part by the Intramural
Research Program of the National Institutes of Health, National Cancer
Institute, Center for Cancer Research (to S. K. A.).
NR 13
TC 33
Z9 34
U1 0
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD AUG 15
PY 2010
VL 185
IS 4
BP 2009
EP 2012
DI 10.4049/jimmunol.1000855
PG 4
WC Immunology
SC Immunology
GA 635NH
UT WOS:000280661900006
PM 20631304
ER
PT J
AU Perrot, I
Deauvieau, F
Massacrier, C
Hughes, N
Garrone, P
Durand, I
Demaria, O
Viaud, N
Gauthier, L
Blery, M
Bonnefoy-Berard, N
Morel, Y
Tschopp, J
Alexopoulou, L
Trinchieri, G
Paturel, C
Caux, C
AF Perrot, Ivan
Deauvieau, Florence
Massacrier, Catherine
Hughes, Nicola
Garrone, Pierre
Durand, Isabelle
Demaria, Olivier
Viaud, Nicolas
Gauthier, Laurent
Blery, Mathieu
Bonnefoy-Berard, Nathalie
Morel, Yannis
Tschopp, Jurg
Alexopoulou, Lena
Trinchieri, Giorgio
Paturel, Carine
Caux, Christophe
TI TLR3 and Rig-Like Receptor on Myeloid Dendritic Cells and Rig-Like
Receptor on Human NK Cells Are Both Mandatory for Production of
IFN-gamma in Response to Double-Stranded RNA
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NATURAL-KILLER-CELLS; TOLL-LIKE RECEPTOR-3; CROSS-TALK; BACTERIAL
PEPTIDOGLYCAN; INNATE RESISTANCE; ADAPTIVE IMMUNITY; ACTIVATION;
CYTOTOXICITY; RECOGNITION; PATHWAY
AB Cross-talk between NK cells and dendritic cells (DCs) is critical for the potent therapeutic response to dsRNA, but the receptors involved remained controversial. We show in this paper that two dsRNAs, polyadenylic-polyuridylic acid and polyinosinic-polycytidylic acid [poly(I: C)], similarly engaged human TLR3, whereas only poly(I:C) triggered human RIG-I and MDA5. Both dsRNA enhanced NK cell activation within PBMCs but only poly(I:C) induced IFN-gamma. Although myeloid DCs (mDCs) were required for NK cell activation, induction of cytolytic potential and IFN-gamma production did not require contact with mDCs but was dependent on type I IFN and IL-12, respectively. Poly(I:C) but not polyadenylic-polyuridylic acid synergized with mDC-derived IL-12 for IFN-gamma production by acting directly on NK cells. Finally, the requirement of both TLR3 and Rig-like receptor (RLR) on mDCs and RLRs but not TLR3 on NK cells for IFN-gamma production was demonstrated using TLR3- and Cardif-deficient mice and human RIG-I-specific activator. Thus, we report the requirement of cotriggering TLR3 and RLR on mDCs and RLRs on NK cells for a pathogen product to induce potent innate cell activation. The Journal of Immunology, 2010, 185: 2080-2088.
C1 [Deauvieau, Florence; Durand, Isabelle; Caux, Christophe] Ctr Leon Berard, Inst Natl Sante, Equipe Cyto Kines & Canc, Rech Med Unite 590, F-69373 Lyon, France.
[Demaria, Olivier; Alexopoulou, Lena] Ctr Immunol Marseille Luminy, Marseille, France.
[Demaria, Olivier; Alexopoulou, Lena] Innate Pharma, Marseille, France.
[Bonnefoy-Berard, Nathalie] Inst Natl Sante, Rech Med Unite 851, Lyon, France.
[Tschopp, Jurg] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland.
[Paturel, Carine] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Deauvieau, Florence; Durand, Isabelle; Caux, Christophe] Epixis, Lyon, France.
RP Caux, C (reprint author), Ctr Leon Berard, Inst Natl Sante, Equipe Cyto Kines & Canc, Rech Med Unite 590, 28 Rue Laennec, F-69373 Lyon, France.
EM cauxc@lyon.fnclcc.fr
RI Caux, Christophe/G-2851-2013; Alexopoulou, Lena/A-5041-2017; morel,
yves/C-4757-2017
OI Alexopoulou, Lena/0000-0003-4619-697X;
FU Intramural NIH HHS [Z99 CA999999]
NR 45
TC 50
Z9 51
U1 0
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD AUG 15
PY 2010
VL 185
IS 4
BP 2080
EP 2088
DI 10.4049/jimmunol.1000532
PG 9
WC Immunology
SC Immunology
GA 635NH
UT WOS:000280661900014
PM 20639488
ER
PT J
AU Cummins, NW
Jiang, W
McGinty, J
Bren, GD
Bosch, RJ
Landay, A
Deeks, SG
Martin, JN
Douek, D
Lederman, MM
Brenchley, J
Badley, AD
AF Cummins, Nathan W.
Jiang, Wei
McGinty, John
Bren, Gary D.
Bosch, Ronald J.
Landay, Alan
Deeks, Steven G.
Martin, Jeffrey N.
Douek, Daniel
Lederman, Michael M.
Brenchley, Jason
Badley, Andrew D.
TI Intracellular Casp8p41 Content Is Inversely Associated with CD4 T Cell
Count
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID HIV-INFECTION; IN-VIVO; PROGRESSION; APOPTOSIS; DISEASE; PROCASPASE-8;
ACTIVATION; DEATH
AB Casp8p41 is a protein fragment generated by cleavage of procaspase 8 by human immunodeficiency virus (HIV) protease. We measured Casp8p41 content in memory CD4 T cells and analyzed the association of Casp8p41 content with CD4 T cell count, cross-sectionally and longitudinally. Casp8p41 content was inversely correlated with CD4 T cell count, and change in Casp8p41 content was associated with absolute CD4 T cell count with change over time. Casp8p41 change was a better predictor of CD4 T cell count change than activated CD8 T cell percentage or viral load and was comparable to bacterial 16s DNA levels. This suggests that Casp8p41 is a relevant mediator of CD4 T cell death during HIV infection.
C1 [Cummins, Nathan W.; Bren, Gary D.; Badley, Andrew D.] Mayo Clin, Div Infect Dis, Rochester, MN 55905 USA.
[Cummins, Nathan W.; Badley, Andrew D.] Mayo Clin, Program Translat Immunovirol & Biodef, Rochester, MN 55905 USA.
[McGinty, John; Brenchley, Jason] NIAID, Immunopathogenesis Unit, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Douek, Daniel] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Jiang, Wei; Lederman, Michael M.] Case Western Reserve Univ, Div Infect Dis, Cleveland, OH 44106 USA.
[Bosch, Ronald J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Landay, Alan] Rush Univ, Med Ctr, Dept Immunol Microbiol, Chicago, IL USA.
[Deeks, Steven G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
RP Badley, AD (reprint author), Mayo Clin, Div Infect Dis, 200 1st St SW, Rochester, MN 55905 USA.
EM badley.andrew@mayo.edu
RI badley, andrew/O-9022-2014;
OI Badley, Andrew/0000-0001-7796-7680
FU National Institutes of Health (NIH) [AI069994]; Center for AIDS Research
[P30 MH59037]; University of California, San Francisco (UCSF) [AI62261,
AI40384, AI068636, U01 AI068634, P30 A127763, AI 69501, UL1 RR024131,
P30 AI27763]; Ruth L. Kirschstein National Research Service Award
[DK007013-32]; UCSF Clinical and Translational Research Institute
Clinical Research Center [UL1 RR024131]
FX Work on this paper was supported by the National Institutes of Health
(NIH), the Center for AIDS Research, and the University of California,
San Francisco (UCSF) (grants AI62261, AI40384, AI068636, U01 AI068634,
P30 A127763, AI 69501, UL1 RR024131, P30 AI27763, and UL1 RR024131). Dr
Nathan Cummins is supported by a Ruth L. Kirschstein National Research
Service Award (award DK007013-32). This research was supported by the
NIH (grant AI069994), Center for AIDS Research (grant P30 MH59037), and
UCSF Clinical and Translational Research Institute Clinical Research
Center (grant UL1 RR024131).
NR 14
TC 7
Z9 7
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD AUG 15
PY 2010
VL 202
IS 3
BP 386
EP 391
DI 10.1086/653705
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 619QI
UT WOS:000279444300008
PM 20565257
ER
PT J
AU Chowell, G
Viboud, C
Simonsen, L
Miller, MA
Acuna-Soto, R
AF Chowell, Gerardo
Viboud, Cecile
Simonsen, Lone
Miller, Mark A.
Acuna-Soto, Rodolfo
TI Mortality Patterns Associated with the 1918 Influenza Pandemic in
Mexico: Evidence for a Spring Herald Wave and Lack of Preexisting
Immunity in Older Populations
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID H1N1 INFLUENZA; SPANISH FLU; TRANSMISSIBILITY; PNEUMONIA; IMPACT; CITY;
EPIDEMIC; NUMBERS
AB Background. Although the mortality burden of the devastating 1918 influenza pandemic has been carefully quantified in the United States, Japan, and European countries, little is known about the pandemic experience elsewhere. Here, we compiled extensive archival records to quantify the pandemic mortality patterns in 2 Mexican cities, Mexico City and Toluca.
Methods. We applied seasonal excess mortality models to age-specific respiratory mortality rates for 1915-1920 and quantified the reproduction number from daily data.
Results. We identified 3 pandemic waves in Mexico City in spring 1918, autumn 1918, and winter 1920, which were characterized by unusual excess mortality among people 25-44 years old. Toluca experienced 2-fold higher excess mortality rates than Mexico City but did not experience a substantial third wave. All age groups, including that of people >= 65 years old, experienced excess mortality during 1918-1920. Reproduction number estimates were < 2.5, assuming a 3-d generation interval.
Conclusion. Mexico experienced a herald pandemic wave with elevated young adult mortality in spring 1918, similar to the United States and Europe. In contrast to the United States and Europe, there was no mortality sparing among Mexican seniors >= 65 years old, highlighting potential geographical differences in preexisting immunity to the 1918 virus. We discuss the relevance of our findings to the 2009 pandemic mortality patterns.
C1 [Chowell, Gerardo] Arizona State Univ, Sch Human Evolut & Social Change, Math Computat & Modeling Sci Ctr, Tempe, AZ 85287 USA.
[Chowell, Gerardo; Viboud, Cecile; Simonsen, Lone; Miller, Mark A.] NIH, Div Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Simonsen, Lone] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Global Hlth, Washington, DC USA.
[Acuna-Soto, Rodolfo] Univ Nacl Autonoma Mexico, Fac Med, Dept Microbiol & Parasitol, Mexico City 04510, DF, Mexico.
RP Chowell, G (reprint author), Arizona State Univ, Sch Human Evolut & Social Change, Math Computat & Modeling Sci Ctr, Univ Ave, Tempe, AZ 85287 USA.
EM gchowell@asu.edu
RI Chowell, Gerardo/F-5038-2012;
OI Chowell, Gerardo/0000-0003-2194-2251; Simonsen, Lone/0000-0003-1535-8526
FU Science and Technology Directorate, Department of Homeland Security;
Fogarty International Center, National Institutes of Health; Office of
Global Health Affairs' International Influenza Unit, Office of the
Secretary of the Department of Health and Human Services
FX RAPIDD program of the Science and Technology Directorate, Department of
Homeland Security (grant to L.S.); Fogarty International Center,
National Institutes of Health (grant to L.S.); Office of Global Health
Affairs' International Influenza Unit, Office of the Secretary of the
Department of Health and Human Services.
NR 48
TC 40
Z9 40
U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD AUG 15
PY 2010
VL 202
IS 4
BP 567
EP 575
DI 10.1086/654897
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 625HR
UT WOS:000279886600009
PM 20594109
ER
PT J
AU Gilbert, P
Wang, M
Wrin, T
Petropoulos, C
Gurwith, M
Sinangil, F
D'Souza, P
Rodriguez-Chavez, IR
DeCamp, A
Giganti, M
Berman, PW
Self, SG
Montefiori, DC
AF Gilbert, Peter
Wang, Maggie
Wrin, Terri
Petropoulos, Chris
Gurwith, Marc
Sinangil, Faruk
D'Souza, Patricia
Rodriguez-Chavez, Isaac R.
DeCamp, Allan
Giganti, Mike
Berman, Phillip W.
Self, Steve G.
Montefiori, David C.
TI Magnitude and Breadth of a Nonprotective Neutralizing Antibody Response
in an Efficacy Trial of a Candidate HIV-1 gp120 Vaccine
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; RECOMBINANT GLYCOPROTEIN-120 VACCINE;
AIDS VACCINE; ENV CLONES; MONOCLONAL-ANTIBODIES; INFECTION; THAILAND;
PHASE-3; BINDING; PANEL
AB Background. A candidate vaccine consisting of human immunodeficiency virus type 1 (HIV-1) subunit gp120 protein was found previously to be nonprotective in an efficacy trial (Vax004) despite strong antibody responses against the vaccine antigens. Here we assessed the magnitude and breadth of neutralizing antibody responses in Vax004.
Methods. Neutralizing antibodies were measured against highly sensitive (tier 1) and moderately sensitive (tier 2) strains of HIV-1 subtype B in 2 independent assays. Vaccine recipients were stratified by sex, race, and high versus low behavioral risk of HIV-1 acquisition.
Results. Most vaccine recipients mounted potent neutralizing antibody responses against HIV-1(MN) and other tier 1 viruses. Occasional weak neutralizing activity was detected against tier 2 viruses. The response against tier 1 and tier 2 viruses was significantly stronger in women than in men. Race and behavioral risk of HIV-1 acquisition had no significant effect on the response. Prior vaccination had little effect on the neutralizing antibody response that arose after infection.
Conclusions. Weak overall neutralizing antibody responses against tier 2 viruses is consistent with a lack of protection in this trial. The magnitude and breadth of neutralization reported here should be useful for identifying improved vaccines.
C1 [Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
[Gilbert, Peter; Wang, Maggie; DeCamp, Allan; Giganti, Mike; Self, Steve G.] Fred Hutchinson Canc Res Ctr, Vaccine Infect Dis Inst, Seattle, WA 98104 USA.
[Sinangil, Faruk] Global Solut Infect Dis, San Francisco, CA USA.
[Gurwith, Marc] PaxVax Inc, San Diego, CA USA.
[Berman, Phillip W.] Univ Calif Santa Cruz, Baskin Sch Engn, Santa Cruz, CA 95064 USA.
[D'Souza, Patricia; Rodriguez-Chavez, Isaac R.] NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA.
RP Montefiori, DC (reprint author), Duke Univ, Med Ctr, Dept Surg, Box 2926, Durham, NC 27710 USA.
EM monte@duke.edu
FU HIV Vaccine Trials Network; National Institutes of Health [AI46705]
FX Financial support: HIV Vaccine Trials Network and the National
Institutes of Health (grant AI46705).
NR 50
TC 68
Z9 68
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD AUG 15
PY 2010
VL 202
IS 4
BP 595
EP 605
DI 10.1086/654816
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 625HR
UT WOS:000279886600012
PM 20608874
ER
PT J
AU Sezgin, E
Jabs, DA
Hendrickson, SL
Van Natta, M
Zdanov, A
Lewis, RA
Smith, MW
Troyer, JL
O'Brien, SJ
AF Sezgin, Efe
Jabs, Douglas A.
Hendrickson, Sher L.
Van Natta, Mark
Zdanov, Alexander
Lewis, Richard Alan
Smith, Michael W.
Troyer, Jennifer L.
O'Brien, Stephen J.
CA Soca Res Grp
TI Effect of Host Genetics on the Development of Cytomegalovirus Retinitis
in Patients with AIDS
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-1
DISEASE PROGRESSION; INTERLEUKIN-10 RECEPTOR; CRYSTAL-STRUCTURE; IL10
HAPLOTYPES; IFN-GAMMA; T-CELLS; INFECTION; VARIANTS
AB Background. Cytomegalovirus (CMV) retinitis is a common opportunistic infection among patients with AIDS and still causes visual morbidity despite the wide spread usage of highly active antiretroviral therapy (HAART). The ubiquitous CMV pathogen contains a human interleukin-10 (IL-10) homolog in its genome and utilizes it to evade host immune reactions through an IL-10 receptor mediated immune-suppression pathway.
Methods. Effects of IL-10R1, IL-10 and previously described AIDS restriction gene variants are investigated on the development of CMV retinitis in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) cohort (N = 1284).
Results. In European Americans (n = 750), a haplotype carrying an amino acid changing variation in the cytoplasmic domain (S420L) of IL-10R1 can be protective (OR, 0.14; 95% CI, 0.02-0.94; P = .04) against, whereas another haplotype carrying an amino acid changing variation in the extracellular domain (I224V) of IL-10R1 can be more susceptible (OR, 6.21; 95% CI, 1.22-31.54; P = .03) to CMV retinitis. In African Americans (n = 534), potential effects of IL-10 variants are observed.
Conclusion. Host genetics may have a role in the occurrence of CMV retinitis in patients infected with HIV.
C1 [Sezgin, Efe; Troyer, Jennifer L.] NCI, Lab Genom Divers, SAIC Frederick, Frederick, MD 21702 USA.
[Zdanov, Alexander] NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA.
[Smith, Michael W.] NCI, Genet & Genom Grp, Adv Technol Program, Frederick, MD 21702 USA.
[Jabs, Douglas A.; Van Natta, Mark] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Ctr Clin Trials, Dept Epidemiol, Baltimore, MD USA.
[Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA.
[Jabs, Douglas A.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
[Lewis, Richard Alan] Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA.
[Lewis, Richard Alan] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Lewis, Richard Alan] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Lewis, Richard Alan] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
RP Sezgin, E (reprint author), NCI, Lab Genom Divers, SAIC Frederick, Frederick, MD 21702 USA.
EM sezginef@mail.nih.gov; stephen.obrien@nih.gov
RI Smith, Michael/B-5341-2012; Sezgin, Efe/B-8418-2012; Troyer,
Jennifer/B-8415-2012
OI Sezgin, Efe/0000-0002-8000-7485;
FU National Cancer Institute; National Institutes of Health
[HHSN261200800001E, U10-EY-08052, U10-EY-08057, U10-EY-08067]; National
Eye Institute
FX Financial support: This project has been funded in whole or in part with
federal funds from the National Cancer Institute, National Institutes of
Health (contract HHSN261200800001E) and with cooperative agreements from
the National Eye Institute, National Institutes of Health (grant
U10-EY-08052 to the Mount Sinai School of Medicine, New York, NY; grant
U10-EY-08057 to the Johns Hopkins Bloomberg School of Public Health,
Baltimore, MD; and grant U10-EY-08067 to the University of Wisconsin,
Madison).
NR 49
TC 7
Z9 8
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD AUG 15
PY 2010
VL 202
IS 4
BP 606
EP 613
DI 10.1086/654814
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 625HR
UT WOS:000279886600013
PM 20617924
ER
PT J
AU Munster, VJ
Schrauwen, EJA
de Wit, E
van den Brand, JMA
Bestebroer, TM
Herfst, S
Rimmelzwaan, GF
Osterhaus, ADME
Fouchier, RAM
AF Munster, Vincent J.
Schrauwen, Eefje J. A.
de Wit, Emmie
van den Brand, Judith M. A.
Bestebroer, Theo M.
Herfst, Sander
Rimmelzwaan, Guus F.
Osterhaus, Albert D. M. E.
Fouchier, Ron A. M.
TI Insertion of a Multibasic Cleavage Motif into the Hemagglutinin of a
Low-Pathogenic Avian Influenza H6N1 Virus Induces a Highly Pathogenic
Phenotype
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID A VIRUS; MOLECULAR-CHANGES; REVERSE GENETICS; JAPANESE-QUAIL; CHICKENS;
ADAPTATION; VIRULENCE; TRANSMISSION; CLEAVABILITY; REPLICATION
AB The highly pathogenic avian influenza (HPAI) virus phenotype is restricted to influenza A viruses of the H5 and H7 hemagglutinin (HA) subtypes. To obtain more information on the apparent subtype-specific nature of the HPAI virus phenotype, a low-pathogenic avian influenza (LPAI) H6N1 virus was generated, containing an HPAI H5 RRRKKR down arrow G multibasic cleavage site (MBCS) motif in HA (the downward arrow indicates the site of cleavage). This insertion converted the LPAI virus phenotype into an HPAI virus phenotype in vitro and in vivo. The H6N1 virus with an MBCS displayed in vitro characteristics similar to those of HPAI H5 viruses, such as cleavage of HA(0) (the HA protein of influenza A virus initially synthesized as a single polypeptide precursor) and virus replication in the absence of exogenous trypsin. Studies of chickens confirmed the HPAI phenotype of the H6N1 virus with an MBCS, with an intravenous pathogenicity index of 1.4 and systemic virus replication upon intranasal inoculation, the hallmarks of HPAI viruses. This study provides evidence that the subtype-specific nature of the emergence of HPAI viruses is not at the molecular, structural, or functional level, since the introduction of an MBCS resulted in a fully functional virus with an HPAI virus genotype and phenotype.
C1 [Munster, Vincent J.] NIAID, Virol Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Munster, VJ (reprint author), NIAID, Virol Lab, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM vincent.munster@nih.gov
RI Fouchier, Ron/A-1911-2014;
OI Fouchier, Ron/0000-0001-8095-2869; Osterhaus,
Albert/0000-0002-6074-1172; de Wit, Emmie/0000-0002-9763-7758; Munster,
Vincent/0000-0002-2288-3196
FU National Institute of Allergy and Infectious Diseases, NIH
[HHSN266200700010C]
FX This research was financed through the National Institute of Allergy and
Infectious Diseases, NIH contract HHSN266200700010C.
NR 46
TC 32
Z9 33
U1 2
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG 15
PY 2010
VL 84
IS 16
BP 7953
EP 7960
DI 10.1128/JVI.00449-10
PG 8
WC Virology
SC Virology
GA 626QZ
UT WOS:000279983200004
PM 20519405
ER
PT J
AU Pancera, M
McLellan, JS
Wu, XL
Zhu, JA
Changela, A
Schmidt, SD
Yang, YP
Zhou, TQ
Phogat, S
Mascola, JR
Kwong, PD
AF Pancera, Marie
McLellan, Jason S.
Wu, Xueling
Zhu, Jiang
Changela, Anita
Schmidt, Stephen D.
Yang, Yongping
Zhou, Tongqing
Phogat, Sanjay
Mascola, John R.
Kwong, Peter D.
TI Crystal Structure of PG16 and Chimeric Dissection with Somatically
Related PG9: Structure-Function Analysis of Two Quaternary-Specific
Antibodies That Effectively Neutralize HIV-1
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; COMPLEMENTARITY-DETERMINING REGION; HUMAN
MONOCLONAL-ANTIBODY; ELECTRON-DENSITY; PROTEIN MODELS; COMBINING SITE;
ENV CLONES; BROAD; ALGORITHM; SOFTWARE
AB HIV-1 resists neutralization by most antibodies. Two somatically related human antibodies, PG9 and PG16, however, each neutralize 70 to 80% of circulating HIV-1 isolates. Here we present the structure of the antigen-binding fragment of PG16 in monoclinic and orthorhombic lattices at 2.4 and 4.0 angstrom, respectively, and use a combination of structural analysis, paratope dissection, and neutralization assessment to determine the functional relevance of three unusual PG9/PG16 features: N-linked glycosylation, extensive affinity maturation, and a heavy chain-third complementarity-determining region (CDR H3) that is one of the longest observed in human antibodies. Glycosylation extended off the side of the light chain variable domain and was not required for neutralization. The CDR H3 formed an axe-shaped subdomain, which comprised 42% of the CDR surface, with the axe head looming similar to 20 angstrom above the other combining loops. Comprehensive sets of chimeric swaps between PG9 and PG16 of light chain, heavy chain, and CDR H3 were employed to decipher structure-function relationships. Chimeric swaps generally complemented functionally, with differences in PG9/PG16 neutralization related primarily to residue differences in CDR H3. Meanwhile, chimeric reversions to genomic V genes showed isolate-dependent effects, with affinity maturation playing a significant role in augmenting neutralization breadth (P = 0.036) and potency (P < 0.0001). The structural and functional details of extraordinary CDR H3 and extensive affinity maturation provide insights into the neutralization mechanism of and the elicitation pathway for broadly neutralizing antibodies like PG9 and PG16.
C1 [Pancera, Marie; McLellan, Jason S.; Wu, Xueling; Zhu, Jiang; Changela, Anita; Schmidt, Stephen D.; Yang, Yongping; Zhou, Tongqing; Mascola, John R.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Phogat, Sanjay] Int AIDS Vaccine Initiat, AIDS Vaccine Design & Dev Lab, Brooklyn, NY USA.
RP Kwong, PD (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,Bldg 40,Room 4508, Bethesda, MD 20892 USA.
EM pdkwong@nih.gov
RI McLellan, Jason/A-6874-2010; Zhou, Tongqing/A-6880-2010; Schmidt,
Stephen/B-5398-2012
OI Zhou, Tongqing/0000-0002-3935-4637;
FU International AIDS Vaccine Initiative (IAVI); NIH; U.S. Department of
Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38]
FX Support for this work was provided by the International AIDS Vaccine
Initiative (IAVI) and by the Intramural Research Program of the NIH. Use
of sector 22 (Southeast Region Collaborative Access team) at the
Advanced Photon Source was supported by the U.S. Department of Energy,
Basic Energy Sciences, Office of Science, under contract number
W-31-109-Eng-38.
NR 65
TC 135
Z9 138
U1 0
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG 15
PY 2010
VL 84
IS 16
BP 8098
EP 8110
DI 10.1128/JVI.00966-10
PG 13
WC Virology
SC Virology
GA 626QZ
UT WOS:000279983200017
PM 20538861
ER
PT J
AU Americo, JL
Moss, B
Earl, PL
AF Americo, Jeffrey L.
Moss, Bernard
Earl, Patricia L.
TI Identification of Wild-Derived Inbred Mouse Strains Highly Susceptible
to Monkeypox Virus Infection for Use as Small Animal Models
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID VACCINIA VIRUS; PRAIRIE DOGS; CONGO BASIN; DISEASE; AFRICAN; MICE;
ORTHOPOXVIRUS; PATHOGENESIS; PROTECTION; PATHOLOGY
AB Infection with monkeypox virus (MPXV) causes disease manifestations in humans that are similar, although usually less severe, than those of smallpox. Since routine vaccination for smallpox ceased more than 30 years ago, there is concern that MPXV could be used for bioterrorism. Thus, there is a need to develop animal models to study MPXV infection. Accordingly, we screened 38 inbred mouse strains for susceptibility to MPXV. Three highly susceptible wild-derived inbred strains were identified, of which CAST/EiJ was further developed as a model. Using an intranasal route of infection with an isolate of the Congo Basin clade of MPXV, CAST/EiJ mice exhibited weight loss, morbidity, and death in a dose-dependent manner with a calculated 50% lethal dose (LD(50)) of 680 PFU, whereas there were no deaths of BALB/c mice at a 10,000-fold higher dose. CAST/EiJ mice exhibited greater MPXV sensitivity when infected via the intraperitoneal route, with an LD(50) of 14 PFU. Both routes resulted in MPXV replication in the lung, spleen, and liver. Intranasal infection with an isolate of the less-pathogenic West African clade yielded an LD(50) of 7,600 PFU. The immune competence of CAST/EiJ mice was established by immunization with vaccinia virus, which induced antigen-specific T-and B-lymphocyte responses and fully protected mice from lethal doses of MPXV. The new mouse model has the following advantages for studying pathogenesis of MPXV, as well as for evaluation of potential vaccines and therapeutics: relative sensitivity to MPXV through multiple routes, genetic homogeneity, available immunological reagents, and commercial production.
C1 [Americo, Jeffrey L.; Moss, Bernard; Earl, Patricia L.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Earl, PL (reprint author), NIAID, Viral Dis Lab, NIH, 33 N Dr,Bldg 33,Room 1E19, Bethesda, MD 20892 USA.
EM pearl@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This study was supported by the Intramural Research Program, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health.
NR 33
TC 27
Z9 29
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG 15
PY 2010
VL 84
IS 16
BP 8172
EP 8180
DI 10.1128/JVI.00621-10
PG 9
WC Virology
SC Virology
GA 626QZ
UT WOS:000279983200024
PM 20519404
ER
PT J
AU Sette, P
Jadwin, JA
Dussupt, V
Bello, NF
Bouamr, F
AF Sette, Paola
Jadwin, Joshua A.
Dussupt, Vincent
Bello, Nana F.
Bouamr, Fadila
TI The ESCRT-Associated Protein Alix Recruits the Ubiquitin Ligase Nedd4-1
To Facilitate HIV-1 Release through the LYPXnL L Domain Motif
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID VIRUS TYPE-1 GAG; INNATE ANTIVIRAL RESPONSE; LATE-BUDDING DOMAINS;
TSG101 UEV DOMAIN; C2 DOMAIN; PARTICLE RELEASE; SORTING PATHWAY;
ALIX/AIP1; ENDOSOME; NETWORK
AB The p6 region of HIV-1 Gag contains two late (L) domains, PTAP and LYPXnL, that bind Tsg101 and Alix, respectively. Interactions with these two cellular proteins recruit members of the host's fission machinery (ESCRT) to facilitate HIV-1 release. Other retroviruses gain access to the host ESCRT components by utilizing a PPXY-type L domain that interacts with cellular Nedd4-like ubiquitin ligases. Despite the absence of a PPXY motif in HIV-1 Gag, interaction with the ubiquitin ligase Nedd4-2 was recently shown to stimulate HIV-1 release. We show here that another Nedd4-like ubiquitin ligase, Nedd4-1, corrected release defects resulting from the disruption of PTAP (PTAP(-)), suggesting that HIV-1 Gag also recruits Nedd4-1 to facilitate virus release. Notably, Nedd4-1 remediation of HIV-1 PTAP(-) budding defects is independent of cellular Tsg101, implying that Nedd4-1's function in HIV-1 release does not involve ESCRT-I components and is therefore distinct from that of Nedd4-2. Consistent with this finding, deletion of the p6 region decreased Nedd4-1-Gag interaction, and disruption of the LYPXnL motif eliminated Nedd4-1-mediated restoration of HIV-1 PTAP(-). This result indicated that both Nedd4-1 interaction with Gag and function in virus release occur through the Alix-binding LYPXnL motif. Mutations of basic residues located in the NC domain of Gag that are critical for Alix's facilitation of HIV-1 release, also disrupted release mediated by Nedd4-1, further confirming a Nedd4-1-Alix functional interdependence. In fact we found that Nedd4-1 binds Alix in both immunoprecipitation and yeast-two-hybrid assays. In addition, Nedd4-1 requires its catalytic activity to promote virus release. Remarkably, RNAi knockdown of cellular Nedd4-1 eliminated Alix ubiquitination in the cell and impeded its ability to function in HIV-1 release. Together our data support a model in which Alix recruits Nedd4-1 to facilitate HIV-1 release mediated through the LYPXnL/Alix budding pathway via a mechanism that involves Alix ubiquitination.
C1 [Sette, Paola; Jadwin, Joshua A.; Dussupt, Vincent; Bello, Nana F.; Bouamr, Fadila] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
RP Bouamr, F (reprint author), NIAID, Mol Microbiol Lab, NIH, 4 Ctr Dr, Bethesda, MD 20892 USA.
EM bouamrf@mail.nih.gov
FU NIAID, NIH
FX This study was supported by the Intramural Research Program of the
NIAID, NIH.
NR 53
TC 35
Z9 35
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG 15
PY 2010
VL 84
IS 16
BP 8181
EP 8192
DI 10.1128/JVI.00634-10
PG 12
WC Virology
SC Virology
GA 626QZ
UT WOS:000279983200025
PM 20519395
ER
PT J
AU Yindom, LM
Leligdowicz, A
Martin, MP
Gao, XJ
Qi, Y
Zaman, SMA
van der Loeff, MS
van Tienen, C
Jaye, A
Aveika, A
Worwui, A
Diatta, M
Vincent, T
Whittle, HC
Rowland-Jones, SL
Walton, R
Carrington, M
AF Yindom, Louis-Marie
Leligdowicz, Aleksandra
Martin, Maureen P.
Gao, Xiaojiang
Qi, Ying
Zaman, Syed M. A.
van der Loeff, Maarten Schim
van Tienen, Carla
Jaye, Assan
Aveika, Akum
Worwui, Archibald
Diatta, Mathurin
Vincent, Tim
Whittle, Hilton C.
Rowland-Jones, Sarah L.
Walton, Robert
Carrington, Mary
TI Influence of HLA Class I and HLA-KIR Compound Genotypes on HIV-2
Infection and Markers of Disease Progression in a Manjako Community in
West Africa
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID MHC CLASS-I; GUINEA-BISSAU; OLDER WOMEN; RURAL AREA; AIDS; TRANSMISSION;
PREVALENCE; RETROVIRUS; DIVERSITY; POLYMORPHISMS
AB Overall, the time to AIDS after HIV-2 infection is longer than with HIV-1, and many individuals infected with HIV-2 virus remain healthy throughout their lives. Multiple HLA and KIR gene products have been implicated in the control of HIV-1, but the effect of variation at these loci on HIV-2 disease is unknown. We show here for the first time that HLA-B*1503 is associated significantly with poor prognosis after HIV-2 infection and that HLA-B*0801 is associated with susceptibility to infection. Interestingly, previous data indicate that HLA-B*1503 is associated with low viral loads in HIV-1 clade B infection but has no significant effect on viral load in clade C infection. In general, alleles strongly associated with HIV-1 disease showed no effect in HIV-2 disease. These data emphasize the unique nature of the effects of HLA and HLA/KIR combinations on HIV-2 immune responses relative to HIV-1, which could be related to their distinct clinical course.
C1 [Martin, Maureen P.; Gao, Xiaojiang; Qi, Ying; Carrington, Mary] NCI, Expt Immunol Lab, SAIC Frederick Inc, Ft Detrick, MD 21702 USA.
[Leligdowicz, Aleksandra; Rowland-Jones, Sarah L.] MRC, Human Immunol Unit, Oxford, England.
[Zaman, Syed M. A.] Hlth Protect Agcy, Ctr Infect, London NW9 5EQ, England.
[van der Loeff, Maarten Schim] GGD Amsterdam, NL-1000 CE Amsterdam, Netherlands.
[van der Loeff, Maarten Schim] Ctr Infect & Immun Amsterdam, NL-1000 CE Amsterdam, Netherlands.
[Walton, Robert] Barts & London Med Sch, Ctr Hlth Sci, London E1 2AT, England.
[Carrington, Mary] MGH, Ragon Inst, Boston, MA 02114 USA.
[Carrington, Mary] MIT, Boston, MA 02114 USA.
[Carrington, Mary] Harvard Univ, Boston, MA 02114 USA.
RP Carrington, M (reprint author), NCI, Expt Immunol Lab, SAIC Frederick Inc, Ft Detrick, MD 21702 USA.
EM carringm@mail.nih.gov
RI van Tienen, Carla/A-1119-2012;
OI Walton, Robert/0000-0001-7700-1907; Leligdowicz,
Aleksandra/0000-0001-6055-4644
FU European and Developing Countries Clinical Trials Partnership (EDCTP);
Medical Research Council (UK); Gambia; National Cancer Institute,
National Institutes of Health [HHSN261200800001E]; NIH; National Cancer
Institute, Center for Cancer Research
FX This study was funded by the European and Developing Countries Clinical
Trials Partnership (EDCTP) and by the Medical Research Council (UK) The
Gambia. This project was funded in part with federal funds from the
National Cancer Institute, National Institutes of Health, under contract
HHSN261200800001E. This research was supported in part by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research.
NR 45
TC 18
Z9 18
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD AUG 15
PY 2010
VL 84
IS 16
BP 8202
EP 8208
DI 10.1128/JVI.00116-10
PG 7
WC Virology
SC Virology
GA 626QZ
UT WOS:000279983200027
PM 20519398
ER
PT J
AU Zhang, Z
Hui, EF
Chapman, ER
Jackson, MB
AF Zhang, Zhen
Hui, Enfu
Chapman, Edwin R.
Jackson, Meyer B.
TI Regulation of Exocytosis and Fusion Pores by Synaptotagmin-Effector
Interactions
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID TRIGGER NEUROTRANSMITTER RELEASE; RECONSTITUTED MEMBRANE-FUSION;
DENSE-CORE VESICLES; PC12 CELLS; CA2+-TRIGGERED EXOCYTOSIS;
SYNAPTIC-TRANSMISSION; CALCIUM SENSOR; C(2)A DOMAIN; C2B DOMAIN; BINDING
AB Synaptotagmin (syt) serves as a Ca(2+) sensor in the release of neurotransmitters and hormones. This function depends on the ability of syt to interact with other molecules. Syt binds to phosphatidylserine (PS)-containing lipid bilayers as well as to soluble N-ethylmaleimide sensitive factor receptors (SNAREs) and promotes SNARE assembly. All these interactions are regulated by Ca(2+), but their specific roles in distinct kinetic steps of exocytosis are not well understood. To explore these questions we used amperometry recording from PC12 cells to investigate the kinetics of exocytosis. Syt isoforms and syt I mutants were overexpressed to perturb syt-PS and syt-SNARE interactions to varying degrees and evaluate the effects on fusion event frequency and the rates of fusion pore transitions. Syt I produced more rapid dilation of fusion pores than syt VII or syt IX, consistent with its role in synchronous synaptic release. Stronger syt-PS interactions were accompanied by a higher frequency of fusion events and more stable fusion pores. By contrast, syt-SNARE interactions and syt-induced SNARE assembly were uncorrelated with rates of exocytosis. This associates the syt-PS interaction with two distinct kinetic steps in Ca(2+) triggered exocytosis and supports a role for the syt-PS interaction in stabilizing open fusion pores.
C1 [Chapman, Edwin R.; Jackson, Meyer B.] Univ Wisconsin, Dept Psychol, Sch Med & Publ Hlth, Madison, WI 53706 USA.
[Zhang, Zhen] NINDS, Bethesda, MD 20892 USA.
[Hui, Enfu] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94158 USA.
[Chapman, Edwin R.] Univ Wisconsin, Sch Med & Publ Hlth, Howard Hughes Med Inst, Madison, WI 53706 USA.
RP Jackson, MB (reprint author), Univ Wisconsin, Dept Psychol, Sch Med & Publ Hlth, 1202 W Johnson St, Madison, WI 53706 USA.
EM MJackson@Physiology.Wisc.Edu
RI Zhang, Zhen/F-8561-2011; Hui, Enfu/C-2806-2012
FU National Institutes of Health [NS44057, MH61876]
FX This work was funded by National Institutes of Health grants NS44057 (to
M.B.J.) and MH61876 (to E.R.C.). E.R.C. is an investigator of the Howard
Hughes Medical Institute.
NR 40
TC 22
Z9 23
U1 0
U2 4
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD AUG 15
PY 2010
VL 21
IS 16
BP 2821
EP 2831
DI 10.1091/mbc.E10-04-0285
PG 11
WC Cell Biology
SC Cell Biology
GA 638EK
UT WOS:000280875200002
PM 20573977
ER
PT J
AU Vitek, JL
Lyons, KE
Bakay, R
Benabid, AL
Deuschl, G
Hallett, M
Kurlan, R
Pancrazio, JJ
Rezai, A
Walter, BL
Lang, AE
AF Vitek, Jerrold L.
Lyons, Kelly E.
Bakay, Roy
Benabid, Alim-Louis
Deuschl, Guenther
Hallett, Mark
Kurlan, Roger
Pancrazio, Joseph J.
Rezai, Ali
Walter, Benjamin L.
Lang, Anthony E.
TI Standard Guidelines for Publication of Deep Brain Stimulation Studies in
Parkinson's Disease (Guide4DBS-PD)
SO MOVEMENT DISORDERS
LA English
DT Article
DE deep brain stimulation; publication guidelines; movement disorders;
Parkinson's disease
ID TREATMENT-RESISTANT DEPRESSION; DYSKINESIA RATING-SCALE;
ACADEMY-OF-NEUROLOGY; SUBTHALAMIC NUCLEUS; CLINICAL-TRIALS; STEREOTACTIC
NEUROSURGERY; FUNCTIONAL NEUROSURGERY; PRACTICE PARAMETER; CLUSTER
HEADACHE; FOLLOW-UP
AB While the use of deep brain stimulation (DBS) for the treatment of neurological disorders has risen substantially over the last decade, it is often difficult to compare the results from different studies clue to the lack of consistent reporting of key study parameters. We present guidelines to standardize the reporting of clinical studies of DBS for Parkinson's disease (PD). These guidelines provide a minimal set of required data elements to facilitate the interpretation and comparison of results across published clinical studies. The guidelines, summarized in the format of a checklist, may also have utility in the planning of clinical studies of DBS for PD as well as other neurological and psychiatric disorders. (C) 2010 Movement Disorder Society
C1 [Vitek, Jerrold L.] Cleveland Clin Fdn, Neuromodulat Res Ctr, Cleveland, OH 44195 USA.
[Lyons, Kelly E.] Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS 66103 USA.
[Bakay, Roy] Rush Univ, Dept Neurosurg, Med Ctr, Chicago, IL 60612 USA.
[Benabid, Alim-Louis] Univ Grenoble, Dept Neurosurg, Grenoble, France.
[Deuschl, Guenther] Univ Kiel, Dept Neurol, D-2300 Kiel, Germany.
[Hallett, Mark] NINDS, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Kurlan, Roger] Overlook Hosp, Atlantic Neurosci Inst, Summit, NJ USA.
[Pancrazio, Joseph J.] NINDS, Div Extramural Res, NIH, Bethesda, MD 20892 USA.
[Rezai, Ali] Ohio State Univ, Dept Neurosurg, Columbus, OH 43210 USA.
[Walter, Benjamin L.] Univ Hosp Cleveland, Dept Neurol, Case Med Ctr, Cleveland, OH 44106 USA.
[Lang, Anthony E.] Univ Toronto, Toronto Western Hosp, Dept Neurol, Toronto, ON M5T 2S8, Canada.
RP Vitek, JL (reprint author), Cleveland Clin Fdn, Dept Neurol & Neurosci, Ctr Neurol Restorat, 9500 Euclid Ave, Cleveland, OH 44195 USA.
EM vitekj@ccf.org
RI Walter, Benjamin/A-6148-2012; Deuschl, Gunther/A-7986-2010; Pancrazio,
Joseph/M-3206-2015
OI Walter, Benjamin/0000-0002-8323-6873; Pancrazio,
Joseph/0000-0001-8276-3690
FU Intramural NIH HHS [ZIA NS003032-08]; NINDS NIH HHS [K23 NS055000,
K23-NS055000, R01 NS058945, U01 NS0500095]
NR 56
TC 11
Z9 14
U1 0
U2 4
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD AUG 15
PY 2010
VL 25
IS 11
BP 1530
EP 1537
DI 10.1002/mds.23151
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 644BW
UT WOS:000281346400002
PM 20544809
ER
PT J
AU Sanger, TD
Chen, DF
Fehlings, DL
Hallett, M
Lang, AE
Mink, JW
Singer, HS
Alter, K
Ben-Pazi, H
Butler, EE
Chen, R
Collins, A
Dayanidhi, S
Forssberg, H
Fowler, E
Gilbert, DL
Gorman, SL
Gormley, ME
Jinnah, HA
Kornblau, B
Krosschell, KJ
Lehman, RK
MacKinnon, C
Malanga, CJ
Mesterman, R
Michaels, MB
Pearson, TS
Rose, J
Russman, BS
Sternad, D
Swoboda, KJ
Valero-Cuevas, F
AF Sanger, Terence D.
Chen, Daofen
Fehlings, Darcy L.
Hallett, Mark
Lang, Anthony E.
Mink, Jonathan W.
Singer, Harvey S.
Alter, Katharine
Ben-Pazi, Hilla
Butler, Erin E.
Chen, Robert
Collins, Abigail
Dayanidhi, Sudarshan
Forssberg, Hans
Fowler, Eileen
Gilbert, Donald L.
Gorman, Sharon L.
Gormley, Mark E., Jr.
Jinnah, H. A.
Kornblau, Barbara
Krosschell, Kristin J.
Lehman, Rebecca K.
MacKinnon, Colum
Malanga, C. J.
Mesterman, Ronit
Michaels, Margaret Barry
Pearson, Toni S.
Rose, Jessica
Russman, Barry S.
Sternad, Dagmar
Swoboda, Kathy J.
Valero-Cuevas, Francisco
TI Definition and Classification of Hyperkinetic Movements in Childhood
SO MOVEMENT DISORDERS
LA English
DT Review
DE pediatric; dystonia; chorea; athetosis; hyperkinetic
ID AUTOIMMUNE NEUROPSYCHIATRIC DISORDERS; PROGRESSIVE MYOCLONUS EPILEPSIES;
FOCAL HAND DYSTONIA; BASAL GANGLIA; GENERALIZED DYSTONIA;
PARTIALIS-CONTINUA; TORSION DYSTONIA; ESSENTIAL TREMOR; PALATAL TREMOR;
TIC DISORDERS
AB Hyperkinetic movements are unwanted or excess movements that are frequently seen in children with neurologic disorders. They are an important clinical finding with significant implications for diagnosis and treatment. However, the lack of agreement on standard terminology and definitions interferes with clinical treatment and research. We describe definitions of dystonia, chorea, athetosis, myoclonus, tremor, tics, and stereotypies that arose from a consensus meeting in June 2008 of specialists from different clinical and basic science fields. Dystonia is a movement disorder in which involuntary sustained or intermittent muscle contractions cause twisting and repetitive movements, abnormal postures, or both. Chorea is an ongoing random-appearing sequence of one or more discrete involuntary movements or movement fragments. Athetosis is a slow, continuous, involuntary writhing movement that prevents maintenance of a stable posture. Myoclonus is a sequence of repeated, often nonrhythmic, brief shock-like jerks due to sudden involuntary contraction or relaxation of one or more muscles. Tremor is a rhythmic back-and-forth or oscillating involuntary movement about a joint axis. Tics are repeated, individually recognizable, intermittent movements or movement fragments that are almost always briefly suppressible and are usually associated with awareness of an urge to perform the movement. Stereotypies are repetitive, simple movements that can be voluntarily suppressed. We provide recommended techniques for clinical examination and suggestions for differentiating between the different types of hyperkinetic movements, noting that there may be overlap between conditions. These definitions and the diagnostic recommendations are intended to be reliable and useful for clinical practice, communication between clinicians and researchers, and for the design of quantitative tests that will guide and assess the outcome of future clinical trials. (C) 2010 Movement Disorder Society
C1 [Sanger, Terence D.; Valero-Cuevas, Francisco] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA.
[Sanger, Terence D.] Univ So Calif, Dept Biokinesiol, Los Angeles, CA 90089 USA.
[Sanger, Terence D.] Univ So Calif, Dept Neurol, Los Angeles, CA 90089 USA.
[Chen, Daofen] NINDS, Extramural Res Program, NIH, Bethesda, MD USA.
[Fehlings, Darcy L.] Univ Toronto, Div Dev Paediat, Toronto, ON, Canada.
[Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, Bethesda, MD USA.
[Lang, Anthony E.] Univ Toronto, Dept Med, Toronto, ON, Canada.
[Lang, Anthony E.] Toronto Western Hosp, Movement Disorders Ctr, Toronto, ON M5T 2S8, Canada.
[Mink, Jonathan W.; Lehman, Rebecca K.] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA.
[Singer, Harvey S.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Alter, Katharine] NIH, Funct & Appl Biomech Sect, Bethesda, MD 20892 USA.
[Ben-Pazi, Hilla] Shaare Zedek Med Ctr, Movement Disorders Clin, Neuropediat Unit, Jerusalem, Israel.
[Butler, Erin E.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
[Chen, Robert] Univ Toronto, Div Neurol, Dept Med, Toronto, ON, Canada.
[Collins, Abigail] Univ Colorado, Childrens Hosp, Aurora, CO USA.
[Dayanidhi, Sudarshan; Valero-Cuevas, Francisco] Univ So Calif, Div Biokinesiol & Phys Therapy, Los Angeles, CA 90089 USA.
[Forssberg, Hans] Karolinska Inst, Neuropediat Unit, Astrid Lindgren Childrens Hosp, Stockholm, Sweden.
[Fowler, Eileen] Univ Calif Los Angeles, Orthopaed Hosp, Ctr Cerebral Palsy, Tarjan Ctr, Los Angeles, CA USA.
[Gilbert, Donald L.] Cincinnati Childrens Hosp, Movement Disorder Clin, Med Ctr, Cincinnati, OH USA.
[Gilbert, Donald L.] Cincinnati Childrens Hosp, Tourette Syndrome Clin, Med Ctr, Cincinnati, OH USA.
[Gorman, Sharon L.] Samuel Merritt Univ, Dept Phys Therapy, Oakland, CA USA.
[Gormley, Mark E., Jr.] Gillette Childrens Specialty Healthcare, Pediat Rehabil Med, St Paul, MN USA.
[Jinnah, H. A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA.
[Jinnah, H. A.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA.
[Kornblau, Barbara] Univ Michigan, Sch Hlth Profess & Studies, Flint, MI 48503 USA.
[Krosschell, Kristin J.] Northwestern Univ Phys Therapy & Human Movement S, Chicago, IL USA.
[MacKinnon, Colum] Northwestern Univ, Dept Phys Therapy & Human Movement Sci, Feinberg Sch Med, Chicago, IL 60611 USA.
[Malanga, C. J.] Univ N Carolina, Dept Neurol, Chapel Hill, NC USA.
[Mesterman, Ronit] McMaster Univ, Hamilton, ON, Canada.
[Michaels, Margaret Barry] Slippery Rock Univ, Sch Phys Therapy, Slippery Rock, PA 16057 USA.
[Pearson, Toni S.] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA.
[Rose, Jessica] Stanford Univ, Med Ctr, Dept Orthoped Surg, Stanford, CA 94305 USA.
[Russman, Barry S.] Oregon Hlth & Sci Univ, Shriners Hosp Children, Portland, OR 97201 USA.
[Sternad, Dagmar] Northeastern Univ, Boston, MA 02115 USA.
[Swoboda, Kathy J.] Univ Utah, Sch Med, Pediat Motor Disorders Res Program, Salt Lake City, UT USA.
RP Sanger, TD (reprint author), Univ So Calif, Dept Biomed Engn, 1042 Downey Way,DRB 140, Los Angeles, CA 90089 USA.
EM terry@sangerlab.net
RI Chen, Robert/B-3899-2009; Sternad, Dagmar/D-8341-2013; Gilbert,
Donald/D-6443-2016;
OI Chen, Robert/0000-0002-8371-8629; Gilbert, Donald/0000-0002-9245-6878;
Butler, Erin/0000-0002-1659-2990; Forssberg, Hans/0000-0003-2069-6618;
Malanga, C.J./0000-0003-4808-3995
FU National Institute for Neurological Disorders and Stroke; National
Institute for Child Health and Development; Office of Rare Disorders;
Don and Linda Carter Foundation; Crowley Carter Foundation; Allergan
Inc.; Canadian Institutes of Health Research; Michael J. Fox Foundation
for Parkinson's Research; Dystonia Medical Research Foundation;
Medtronic Inc
FX We are grateful for the support of the National Institute for
Neurological Disorders and Stroke, the National Institute for Child
Health and Development, the Office of Rare Disorders, the Don and Linda
Carter Foundation, the Crowley Carter Foundation, and an unrestricted
educational grant from Allergan Inc.; Dr. Chen received research grants
from the Canadian Institutes of Health Research, Michael J. Fox
Foundation for Parkinson's Research, Dystonia Medical Research
Foundation and Medtronic Inc, honoraria from Allergan, Medtronic, Merz,
Novartis, Teva, and from expert testimony.
NR 66
TC 89
Z9 89
U1 7
U2 20
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD AUG 15
PY 2010
VL 25
IS 11
BP 1538
EP 1549
DI 10.1002/mds.23088
PG 12
WC Clinical Neurology
SC Neurosciences & Neurology
GA 644BW
UT WOS:000281346400003
PM 20589866
ER
PT J
AU Gardener, H
Gao, XA
Chen, HL
Schwarzschild, MA
Spiegelman, D
Ascherio, A
AF Gardener, Hannah
Gao, Xiang
Chen, Honglei
Schwarzschild, Michael A.
Spiegelman, Donna
Ascherio, Alberto
TI Prenatal and Early Life Factors and Risk of Parkinson's Disease
SO MOVEMENT DISORDERS
LA English
DT Article
DE birth weight; epidemiology; functional laterality; maternal exposure;
Parkinson's disease
ID HAND PREFERENCE; LEFT-HANDEDNESS; MATERNAL AGE; BIRTH-WEIGHT; DIGIT
RATIO; WOMEN; CHILDREN; PERFORMANCE; ORIGINS; DIETHYLSTILBESTROL
AB Few studies have investigated the relation between early life factors and risk of Parkinson's disease (PD), although a potential role of exposures during pregnancy and childhood has been hypothesized. The study population comprised participants in two prospective cohorts: the Nurses' Health Study (121,701 female nurses followed up from 1976-2002) and the Health Professionals Follow-up Study (51,529 male health professionals followed up from 1986-2002). PD risk was examined in relation to season of birth, birthweight, parental age at birth, preterm birth, multiple birth, ever having been breast-fed, and handedness. We identified 659 incident PD cases. No significant relation with PD was observed for birthweight, paternal age, preterm birth, multiple birth, and having been breast-fed. A modest nonsignificant association was suggested for season of birth (30% higher risk of PD associated with spring versus winter birth) and for older maternal age at birth (75% increased risk among those with mothers aged 30 years and older versus younger than 20 years). Left-handedness was associated with a 62% increased risk of PD in women but not in men. Further investigation of the relation between prenatal, perinatal, or neonatal factors and PD in other study populations is suggested. (C) 2010 Movement Disorder Society
C1 [Gardener, Hannah; Spiegelman, Donna; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Gao, Xiang; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Chen, Honglei] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA.
[Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA USA.
[Ascherio, Alberto] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
RP Gardener, H (reprint author), Univ Miami, Dept Neurol, Miller Sch Med, POB 016960 M-877, Miami, FL 33101 USA.
EM hgardener@med.miami.edu
OI Chen, Honglei/0000-0003-3446-7779
FU National Research Service [T32 MH17119]; NIH/NINDS; NIH; Department of
Defense; American Parkinson Disease Association; Parkinson's Disease
Foundation; Health Resources and Services Administration; NIH/NCI;
NIH/NIEHS; National Multiple Sclerosis Society
FX We thank Dr. Steve Buka and Dr. Janet Rich-Edwards for their help and
guidance in reviewing the results and manuscript. We also thank Alvin
Wing and Ellis O'Reilly for reviewing the statistical programs. This
work was supported by a National Research Service Award grant from the
Training Program in Psychiatric Epidemiology and Biostatistics (T32
MH17119).; Dr. Gardener: support from the NIH/NINDS. Dr. Gao: serves on
the Monitoring Committee of the Parkinson Study Group and support from
NIH/NINDS. Dr. Chen: support from the Intramural research program of the
NIH. Dr. Schwarzschild: support from the NIH/NINDS and the Department of
Defense and the American Parkinson Disease Association, Parkinson's
Disease Foundation, and the Michael J Fox Foundation. Dr. Spiegelman:
support from Health Resources and Services Administration, NIH/NCI, and
NIH/NIEHS. Dr. Ascherio: personal compensation for speaking activities
from Merck-Serono and research funding from the the Department of
Defense, Autism Speaks, the National Multiple Sclerosis Society, and the
Michael J. Fox Foundation.
NR 50
TC 13
Z9 14
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD AUG 15
PY 2010
VL 25
IS 11
BP 1560
EP 1567
DI 10.1002/mds.23339
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 644BW
UT WOS:000281346400005
PM 20740569
ER
PT J
AU Benninger, DH
Michel, J
Waldvogel, D
Candia, V
Poryazova, R
van Hedel, HJA
Bassetti, CL
AF Benninger, David H.
Michel, Jan
Waldvogel, Daniel
Candia, Victor
Poryazova, Rositsa
van Hedel, Hubertus J. A.
Bassetti, Claudio L.
TI REM Sleep Behavior Disorder is not Linked to Postural Instability and
Gait Dysfunction in Parkinson
SO MOVEMENT DISORDERS
LA English
DT Article
DE REM sleep behavior disorder; gait disorder; postural instability;
Parkinson's disease; pedunculopontine nucleus
ID DEEP BRAIN-STIMULATION; PEDUNCULOPONTINE NUCLEUS; BASAL GANGLIA;
DISEASE; REGION; PATHOPHYSIOLOGY; RESPONSES; PRIMATE
AB To evaluate a potential association of REM-sleep behavior disorder (RBD) with gait and postural impairment in Parkinson's disease (PD). Gait difficulties and postural impairment are frequent in PD and are a major cause of disability. Animal studies indicate a key role of the pedunculopontine nucleus (PPN) in gait, postural control, and REM sleep, and also in the pathophysiology of RBD. In humans, such an association has not been investigated. Twenty-six patients with mild-to-moderate PD (13 with polysomnography confirmed and 13 with excluded RBD), and 20 age-matched healthy controls were prospectively investigated. Gait assessment on a treadmill, and static and dynamic posturography were performed. PD patients with RBD do not differ from those without RBD in gait and postural control. Greater severity of PD or prevalence of gait and postural disturbances in the presence of RBD were not found. RBD was not associated with any particular motor phenotype. We found no association of RBD with gait disturbances and postural impairment. Human gait and postural control and RBD appear to depend upon different neuronal circuits. (C) 2010 Movement Disorder Society
C1 [Benninger, David H.] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Benninger, David H.; Waldvogel, Daniel; Poryazova, Rositsa; Bassetti, Claudio L.] Univ Zurich Hosp, Dept Neurol, CH-8091 Zurich, Switzerland.
[Michel, Jan; van Hedel, Hubertus J. A.] Balgrist Univ Hosp, Spinal Cord Injury Ctr, Zurich, Switzerland.
[Candia, Victor] Univ Zurich, Coll Helveticum, CH-8006 Zurich, Switzerland.
[Candia, Victor] Swiss Fed Inst Technol, Zurich, Switzerland.
RP Benninger, DH (reprint author), Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 5N240 MSC1428,Ctr Dr, Bethesda, MD 20892 USA.
EM benningerd@ninds.nih.gov
RI Benninger, David/A-8157-2015;
OI Benninger, David/0000-0002-1049-9533; van Hedel,
Hubertus/0000-0002-9577-5049
NR 39
TC 12
Z9 13
U1 0
U2 3
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD AUG 15
PY 2010
VL 25
IS 11
BP 1597
EP 1604
DI 10.1002/mds.23121
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 644BW
UT WOS:000281346400010
PM 20629146
ER
PT J
AU Jo, HJ
Saad, ZS
Simmons, WK
Milbury, LA
Cox, RW
AF Jo, Hang Joon
Saad, Ziad S.
Simmons, W. Kyle
Milbury, Lydia A.
Cox, Robert W.
TI Mapping sources of correlation in resting state FMRI, with artifact
detection and removal
SO NEUROIMAGE
LA English
DT Article
DE Resting state; Functional magnetic resonance imaging; Noise reduction;
Artifact correction; Human brain
ID FUNCTIONAL MRI; BOLD SIGNAL; GLOBAL SIGNAL; HUMAN BRAIN; CONNECTIVITY;
FLUCTUATIONS; NETWORK; NOISE; REGISTRATION; REGRESSION
AB Many components of resting-state (RS) FMRI show non-random structure that has little to do with neural connectivity but can covary over multiple brain structures. Some of these signals originate in physiology and others are hardware-related. One artifact discussed herein may be caused by defects in the receive coil array or the RF amplifiers powering it. During a scan, this artifact results in small image intensity shifts in parts of the brain imaged by the affected array components. These shifts introduce artifactual correlations in RS time series on the spatial scale of the coil's sensitivity profile, and can markedly bias RS connectivity results. We show that such a transient artifact can be substantially removed from RS time series by using locally formed regressors from white matter tissue. This is particularly important in arrays with larger numbers of coils, which may generate smaller artifact zones. In such a case, brain-wide average noise estimates would fail to capture the artifact. We also examine the anatomical structure of artifactual variance in RS FMRI time series, by identifying sources that contribute to these signals and where in the brain are they manifested. We consider current methods for reducing confounding sources (or noises) and their effects on connectivity maps, and offer an improved approach (ANATICOR) that can also reduce hardware artifacts. The methods described herein are currently available with AFNI, in addition to tools for rapid, interactive generation of seed-based correlation maps at single-subject and group levels. Published by Elsevier Inc.
C1 [Jo, Hang Joon; Saad, Ziad S.; Cox, Robert W.] NIMH, NIH, Bethesda, MD 20892 USA.
[Simmons, W. Kyle; Milbury, Lydia A.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
RP Saad, ZS (reprint author), NIMH, NIH, 10 Ctr DR Room 1D80, Bethesda, MD 20892 USA.
EM saadz@mail.nih.gov
RI JO, HANG JOON/D-1775-2011; Simmons, William/K-8925-2015
OI JO, HANG JOON/0000-0002-9180-3831; Simmons, William/0000-0002-0399-9003
FU NIMH; NIH
FX The authors appreciate Marta Bianciardi and Jongho Lee for useful
discussions about hardware-related and physiological noises, and Catie
E. Chang and Gary H. Glover for code and assistance with RETROICOR. We
especially wish to acknowledge the continuing encouragement and aid from
Alex Martin. This research was supported by the NIMH and NINDS
Intramural Research Programs of the NIH.
NR 32
TC 125
Z9 126
U1 0
U2 13
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD AUG 15
PY 2010
VL 52
IS 2
BP 571
EP 582
DI 10.1016/j.neuroimage.2010.04.246
PG 12
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 615TK
UT WOS:000279160200019
PM 20420926
ER
PT J
AU Clegg, LX
Hankey, BF
Tiwari, R
Feuer, EJ
Edwards, BK
AF Clegg, Limin X.
Hankey, Benjamin F.
Tiwari, Ram
Feuer, Eric J.
Edwards, Brenda K.
TI Comment on 'Estimating average annual per cent change in trend analysis'
Reply
SO STATISTICS IN MEDICINE
LA English
DT Letter
C1 [Clegg, Limin X.] US Dept Vet Affairs, Washington, DC 20001 USA.
[Tiwari, Ram] US FDA, Silver Spring, MD 20993 USA.
[Feuer, Eric J.; Edwards, Brenda K.] NCI, Bethesda, MD 20892 USA.
RP Clegg, LX (reprint author), US Dept Vet Affairs, 801 1 St NW,Room 1018, Washington, DC 20001 USA.
EM ram.tiwari@fda.hhs.gov; edwardsb@mail.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD AUG 15
PY 2010
VL 29
IS 18
BP 1961
EP 1961
DI 10.1002/sim.3983
PG 1
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 640XR
UT WOS:000281088000010
ER
PT J
AU Zanetti, E
Barozzi, P
Brown, EE
Bosco, R
Vallerini, D
Riva, G
Quadrelli, C
Potenza, L
Forghieri, F
Montagnani, G
D'Amico, R
Del Giovane, C
Duraes, C
Whitby, D
Machado, JC
Schulz, TF
Torelli, G
Luppi, M
AF Zanetti, Eleonora
Barozzi, Patrizia
Brown, Elizabeth E.
Bosco, Raffaella
Vallerini, Daniela
Riva, Giovanni
Quadrelli, Chiara
Potenza, Leonardo
Forghieri, Fabio
Montagnani, Giuliano
D'Amico, Roberto
Del Giovane, Cinzia
Duraes, Cecilia
Whitby, Denise
Machado, Jose C.
Schulz, Thomas F.
Torelli, Giuseppe
Luppi, Mario
TI Common Vascular Endothelial Growth Factor Variants and Risk for
Posttransplant Kaposi Sarcoma
SO TRANSPLANTATION
LA English
DT Letter
ID INFECTION
C1 [Zanetti, Eleonora; Barozzi, Patrizia; Bosco, Raffaella; Vallerini, Daniela; Riva, Giovanni; Quadrelli, Chiara; Potenza, Leonardo; Forghieri, Fabio; Montagnani, Giuliano; D'Amico, Roberto; Del Giovane, Cinzia; Torelli, Giuseppe; Luppi, Mario] Univ Modena & Reggio Emilia, Dept Oncol Hematol & Resp Dis, I-41100 Modena, Italy.
[Brown, Elizabeth E.] Univ Alabama, Dept Epidemiol, Birmingham, AL USA.
[Brown, Elizabeth E.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Brown, Elizabeth E.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA.
[Duraes, Cecilia; Machado, Jose C.] Univ Porto, IPATIMUP Inst Mol Pathol & Immunol, P-4100 Oporto, Portugal.
[Whitby, Denise] NCI, Viral Oncol Sect, AIDS & Canc Virus Program, SAIC Frederick, Frederick, MD 21701 USA.
[Machado, Jose C.] Univ Porto, Fac Med, P-4100 Oporto, Portugal.
[Schulz, Thomas F.] Hannover Med Sch, Dept Virol, D-3000 Hannover, Germany.
RP Luppi, M (reprint author), Univ Modena & Reggio Emilia, Dept Oncol Hematol & Resp Dis, Via Pozzo 71, I-41100 Modena, Italy.
EM mario.luppi@unimore.it
RI Machado, Jose Carlos/C-5907-2009; D'Amico, Roberto/I-8106-2014; Duraes,
Cecilia/I-2117-2013; Zanetti, Eleonora/J-6078-2016; Luppi,
Mario/J-3668-2016; Potenza, Leonardo/P-9579-2016; Barozzi,
Patrizia/Q-2638-2016
OI Machado, Jose Carlos/0000-0003-4741-8415; D'Amico,
Roberto/0000-0002-3211-6687; Duraes, Cecilia/0000-0001-9282-0708; Luppi,
Mario/0000-0002-0373-1154; Potenza, Leonardo/0000-0002-2738-6105;
Barozzi, Patrizia/0000-0002-8936-1114
NR 6
TC 2
Z9 2
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD AUG 15
PY 2010
VL 90
IS 3
BP 337
EP 338
DI 10.1097/TP.0b013e3181e4e4d9
PG 3
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 634KY
UT WOS:000280581200023
PM 20683431
ER
PT J
AU Berrigan, D
Forsyth, BH
Helba, C
Levin, K
Norberg, A
Willis, GB
AF Berrigan, David
Forsyth, Barbara H.
Helba, Cynthia
Levin, Kerry
Norberg, Alicia
Willis, Gordon B.
TI Cognitive testing of physical activity and acculturation questions in
recent and long-term Latino immigrants
SO BMC PUBLIC HEALTH
LA English
DT Article
ID HEALTH INTERVIEW SURVEY; DIVERSE POPULATIONS; LEISURE-TIME; QUALITATIVE
METHODS; MEXICAN-AMERICANS; UNITED-STATES; TOBACCO USE; HISPANICS;
CANCER; TRANSLATION
AB Background: We ascertained the degree to which language (English versus Spanish), and residence time in the US influence responses to survey questions concerning two topics: self-reported acculturation status, and recent physical activity (PA). This topic is likely to be of general interest because of growing numbers of immigrants in countries worldwide.
Methods: We carried out qualitative (cognitive) interviews of survey items on acculturation and physical activity on 27 Latino subjects from three groups: (a) In Spanish, of those of low residence time (less than five years living in the U. S.) (n = 9); (b) In Spanish, of those of high residence time (15 or more years in the U. S) (n = 9); and (c) in English, of those of high residence time (n = 9).
Results: There were very few language translation problems; general question design defects and socio-cultural challenges to survey responses were more common. Problems were found for both acculturation and PA questions, with distinct problem types for the two question areas. Residence time/language group was weakly associated with overall frequency of problems observed: low residence time/Spanish (86%), high residence time/ Spanish (67%), and English speaking groups (62%).
Conclusions: Standardized survey questions related to acculturation and physical activity present somewhat different cognitive challenges. For PA related questions, problems with such questions were similar regardless of subject residence time or language preference. For acculturation related questions, residence time/language or education level influenced responses to such questions. These observations should help in the interpretation of survey results for culturally diverse populations.
C1 [Berrigan, David; Willis, Gordon B.] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Forsyth, Barbara H.] Univ Maryland, Ctr Adv Study Language, College Pk, MD 20742 USA.
[Helba, Cynthia; Levin, Kerry; Norberg, Alicia] Westat Corp, Rockville, MD 20850 USA.
RP Berrigan, D (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, Execut Plaza N,MSC 7344, Bethesda, MD 20892 USA.
EM berrigad@mail.nih.gov
NR 58
TC 9
Z9 9
U1 3
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2458
J9 BMC PUBLIC HEALTH
JI BMC Public Health
PD AUG 13
PY 2010
VL 10
AR 481
DI 10.1186/1471-2458-10-481
PG 14
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 655GN
UT WOS:000282236900002
PM 20707902
ER
PT J
AU Louie, GH
Ward, MM
AF Louie, Grant H.
Ward, Michael M.
TI Association of measured physical performance and demographic and health
characteristics with self-reported physical function: implications for
the interpretation of self-reported limitations
SO HEALTH AND QUALITY OF LIFE OUTCOMES
LA English
DT Article
ID LOWER-EXTREMITY FUNCTION; OLDER PERSONS; DISABILITY; ADULTS; AGE;
SERVICES; INDEX; RISK; MEN; IMPAIRMENT
AB Background: Self-reported limitations in physical function often have only weak associations with measured performance on physical tests, suggesting that factors other than performance commonly influence self-reports. We tested if personal or health characteristics influenced self-reported limitations in three tasks, controlling for measured performance on these tasks.
Methods: We used cross-sectional data on adults aged >= 60 years (N = 5396) from the Third National Health and Nutrition Examination Survey to examine the association between the repeated chair rise test and self-reported difficulty rising from a chair. We then tested if personal characteristics, health indicators, body composition, and performance on unrelated tasks were associated with self-reported limitations in this task. We used the same approach to examine associations between personal and health characteristics and self-reported difficulty walking between rooms, controlling for timed 8-foot walk, and self-reported difficulty getting out of bed, controlling for repeated chair rise test results.
Results: In multivariate analyses, participants who performed worse on the repeated chair rise test were more likely to report difficulty with chair rise. However, older age, lower education level, lower serum albumin, comorbidities, knee pain, and being underweight were also significantly associated with self-reported limitations with chair rise. Results were similar for difficulty walking between rooms and getting out of bed.
Conclusions: Self-reports of limitations in physical function are influenced by personal and health characteristics that reflect frailty, and should not be interpreted solely as measured difficulty performing the task.
C1 [Louie, Grant H.; Ward, Michael M.] NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Louie, GH (reprint author), NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
EM grant.louie@nih.gov
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases at
the National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Arthritis and Musculoskeletal and Skin Diseases at
the National Institutes of Health.
NR 39
TC 12
Z9 14
U1 2
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1477-7525
J9 HEALTH QUAL LIFE OUT
JI Health Qual. Life Outcomes
PD AUG 13
PY 2010
VL 8
AR 84
DI 10.1186/1477-7525-8-84
PG 13
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 656BT
UT WOS:000282301500001
PM 20707890
ER
PT J
AU Mueller, GA
Gosavi, RA
Krahn, JM
Edwards, LL
Cuneo, MJ
Glesner, J
Pomes, A
Chapman, MD
London, RE
Pedersen, LC
AF Mueller, Geoffrey A.
Gosavi, Rajendrakumar A.
Krahn, Joseph M.
Edwards, Lori L.
Cuneo, Matthew J.
Glesner, Jill
Pomes, Anna
Chapman, Martin D.
London, Robert E.
Pedersen, Lars C.
TI Der p 5 Crystal Structure Provides Insight into the Group 5 Dust Mite
Allergens
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DNA-POLYMERASE-III; DERMATOPHAGOIDES-PTERONYSSINUS; BLOMIA-TROPICALIS;
X-RAY; CROSS-REACTIVITY; THETA-SUBUNIT; T-CELL; PROTEIN; RECOMBINANT;
SENSITIZATION
AB Group 5 allergens from house dust mites elicit strong IgE antibody binding in mite-allergic patients. The structure of Der p 5 was determined by x-ray crystallography to better understand the IgE epitopes, to investigate the biologic function in mites, and to compare with the conflicting published Blo t 5 structures, designated 2JMH and 2JRK in the Protein Data Bank. Der p 5 is a three-helical bundle similar to Blo t 5, but the interactions of the helices are more similar to 2JMH than 2JRK. The crystallo-graphic asymmetric unit contains three dimers of Der p 5 that are not exactly alike. Solution scattering techniques were used to assess the multimeric state of Der p 5 in vitro and showed that the predominant state was monomeric, similar to Blo t 5, but larger multimeric species are also present. In the crystal, the formation of the Der p 5 dimer creates a large hydrophobic cavity of similar to 3000 angstrom(3) that could be a ligand-binding site. Many allergens are known to bind hydrophobic ligands, which are thought to stimulate the innate immune system and have adjuvant-like effects on IgE-mediated inflammatory responses.
C1 [London, Robert E.; Pedersen, Lars C.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Edwards, Lori L.] NIEHS, Prot Express Core Facil, NIH, Res Triangle Pk, NC 27709 USA.
[Glesner, Jill; Pomes, Anna; Chapman, Martin D.] INDOOR Biotechnol Inc, Charlottesville, VA 22903 USA.
RP Mueller, GA (reprint author), 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM mueller3@niehs.nih.gov
OI Cuneo, Matthew/0000-0002-1475-6656; Pomes, Anna/0000-0002-8729-1829
FU NIAID [R01AI077653]; Intramural Research Program; NIEHS; National
Institutes of Health, NIEHS [HHSN273200700046U]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant R01AI077653 from NIAID (to A. P. and M. D. C.), by the
Intramural Research Program, and by NIEHS.; Supported by National
Institutes of Health, NIEHS, under Delivery Order HHSN273200700046U to
SRA International, Inc.
NR 44
TC 27
Z9 27
U1 0
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 13
PY 2010
VL 285
IS 33
BP 25394
EP 25401
DI 10.1074/jbc.M110.128306
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 635UN
UT WOS:000280682400032
PM 20534590
ER
PT J
AU Roger, JE
Nellissery, J
Kim, DS
Swaroop, A
AF Roger, Jerome E.
Nellissery, Jacob
Kim, Douglas S.
Swaroop, Anand
TI Sumoylation of bZIP Transcription Factor NRL Modulates Target Gene
Expression during Photoreceptor Differentiation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NUCLEAR RECEPTOR NR2E3; RETINAL CELL FATE; ROD PHOTORECEPTORS; MOUSE
RETINA; POSTTRANSLATIONAL MODIFICATIONS; HOMEOBOX GENE; SUBUNIT GENE;
IN-VIVO; CRX; PHOSPHORYLATION
AB Development of rod photoreceptors in the mammalian retina is critically dependent on the basic motif-leucine zipper transcription factor NRL (neural retina leucine zipper). In the absence of NRL, photoreceptor precursors in mouse retina produce only cones that primarily express S-opsin. Conversely, ectopic expression of NRL in post-mitotic precursors leads to a rod-only retina. To explore the role of signaling molecules in modulating NRL function, we identified putative sites of post-translational modification in the NRL protein by in silico analysis. Here, we demonstrate the sumoylation of NRL in vivo and in vitro, with two small ubiquitin-like modifier (SUMO) molecules attached to the Lys-20 residue. NRL-K20R and NRL-K20R/K24R sumoylation mutants show reduced transcriptional activation of Nr2e3 and rhodopsin promoters (two direct targets of NRL) in reporter assays when compared with wild-type NRL. Consistent with this, in vivo electroporation of the NRL-K20R/K24R mutant into newborn Nrl(-/-) mouse retina leads to reduced Nr2e3 activation and only a partial rescue of the Nrl(-/-) phenotype in contrast to the wild-type NRL that is able to convert cones to rod photoreceptors. Although PIAS3 (protein inhibitor of activated STAT3), an E3-SUMO ligase implicated in photoreceptor differentiation, can be immunoprecipitated with NRL, there appears to be redundancy in E3 ligases, and PIAS3 does not seem to be essential for NRL sumoylation. Our studies suggest an important role of sumoylation in fine-tuning the activity of NRL and thereby incorporating yet another layer of control in gene regulatory networks involved in photoreceptor development and homeostasis.
C1 [Roger, Jerome E.; Nellissery, Jacob; Kim, Douglas S.; Swaroop, Anand] NEI, N NRL, NIH, Bethesda, MD 20892 USA.
RP Swaroop, A (reprint author), NEI, N NRL, NIH, 6 Ctr Dr,MSC0610, Bethesda, MD 20892 USA.
EM swaroopa@nei.nih.gov
OI Roger, Jerome/0000-0002-5061-230X; Swaroop, Anand/0000-0002-1975-1141
FU National Institutes of Health through NEI
FX This work was supported, in whole or in part, by a National Institutes
of Health Grant through the NEI.
NR 63
TC 22
Z9 24
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 13
PY 2010
VL 285
IS 33
BP 25637
EP 25644
DI 10.1074/jbc.M110.142810
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 635UN
UT WOS:000280682400057
PM 20551322
ER
PT J
AU Zwolak, A
Fujiwara, I
Hammer, JA
Tjandra, N
AF Zwolak, Adam
Fujiwara, Ikuko
Hammer, John A., III
Tjandra, Nico
TI Structural Basis for Capping Protein Sequestration by Myotrophin (V-1)
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID FILAMENT BARBED END; 4-DIMENSIONAL NMR-SPECTROSCOPY; CHEMICAL-SHIFT
ASSIGNMENTS; NUCLEAR-MAGNETIC-RESONANCE; CAPPED ACTIN-FILAMENTS;
SECONDARY STRUCTURE; ARP2/3 COMPLEX; IN-VITRO; MYOSIN-I; BINDING
AB Capping protein (CP) is a ubiquitously expressed, heterodimeric 62-kDa protein that binds the barbed end of the actin filament with high affinity to block further filament elongation. Myotrophin (V-1) is a 13-kDa ankyrin repeat-containing protein that binds CP tightly, sequestering it in a totally inactive complex in vitro. Here, we elucidate the molecular interaction between CP and V-1 by NMR. Specifically, chemical shift mapping and intermolecular paramagnetic relaxation enhancement experiments reveal that the ankyrin loops of V-1, which are essential for V-1/CP interaction, bind the basic patch near the joint of the alpha tentacle of CP shown previously to drive most of the association of CP with and affinity for the barbed end. Consistently, site-directed mutagenesis of CP shows that V-1 and the strong electrostatic binding site for CP on the barbed end compete for this basic patch on CP. These results can explain how V-1 inactivates barbed end capping by CP and why V-1 is incapable of uncapping CP-capped actin filaments, the two signature biochemical activities of V-1.
C1 [Fujiwara, Ikuko; Hammer, John A., III] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
[Zwolak, Adam] NYU, Sch Med, Sackler Inst Biomed Sci, New York, NY 10016 USA.
RP Hammer, JA (reprint author), NHLBI, Cell Biol Lab, NIH, 50 South Dr,Bldg 50,Rm 2306, Bethesda, MD 20892 USA.
EM hammerj@nhlbi.nih.gov; tjandran@nhlbi.nih.gov
RI Fujiwara, Ikuko/H-5717-2016;
OI Fujiwara, Ikuko/0000-0002-9361-636X; Hammer, John/0000-0002-2496-5179
FU NHLBI
FX This work was supported, in whole or in part, by National Institutes of
Health grants from Intramural Research Program, NHLBI (to J. A. H. III
and N. T.).
NR 62
TC 13
Z9 14
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 13
PY 2010
VL 285
IS 33
BP 25767
EP 25781
DI 10.1074/jbc.M110.135848
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 635UN
UT WOS:000280682400069
PM 20538588
ER
PT J
AU Jeang, KT
AF Jeang, Kuan-Teh
TI Intelligence and ambition are distributed equally around the globe
SO RETROVIROLOGY
LA English
DT Editorial Material
AB The impact of freely accessible knowledge distribution platforms is briefly discussed.
C1 NIH, Bethesda, MD 20892 USA.
RP Jeang, KT (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM kj7e@nih.gov
RI Jeang, Kuan-Teh/A-2424-2008
FU Intramural NIH HHS
NR 7
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 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD AUG 13
PY 2010
VL 7
AR 67
DI 10.1186/1742-4690-7-67
PG 2
WC Virology
SC Virology
GA 659KG
UT WOS:000282564800001
PM 20707906
ER
PT J
AU Zhou, TQ
Georgiev, I
Wu, XL
Yang, ZY
Dai, KF
Finzi, A
Kwon, YD
Scheid, JF
Shi, W
Xu, L
Yang, YP
Zhu, JA
Nussenzweig, MC
Sodroski, J
Shapiro, L
Nabel, GJ
Mascola, JR
Kwong, PD
AF Zhou, Tongqing
Georgiev, Ivelin
Wu, Xueling
Yang, Zhi-Yong
Dai, Kaifan
Finzi, Andres
Kwon, Young Do
Scheid, Johannes F.
Shi, Wei
Xu, Ling
Yang, Yongping
Zhu, Jiang
Nussenzweig, Michel C.
Sodroski, Joseph
Shapiro, Lawrence
Nabel, Gary J.
Mascola, John R.
Kwong, Peter D.
TI Structural Basis for Broad and Potent Neutralization of HIV-1 by
Antibody VRC01
SO SCIENCE
LA English
DT Article
ID GP120 ENVELOPE GLYCOPROTEIN; RECEPTOR; SITE; EPITOPE; SURFACE;
INDIVIDUALS; ATTACHMENT; MATURATION; HYPOTHESIS; VACCINES
AB During HIV-1 infection, antibodies are generated against the region of the viral gp120 envelope glycoprotein that binds CD4, the primary receptor for HIV-1. Among these antibodies, VRC01 achieves broad neutralization of diverse viral strains. We determined the crystal structure of VRC01 in complex with a human immunodeficiency virus HIV-1 gp120 core. VRC01 partially mimics CD4 interaction with gp120. A shift from the CD4-defined orientation, however, focuses VRC01 onto the vulnerable site of initial CD4 attachment, allowing it to overcome the glycan and conformational masking that diminishes the neutralization potency of most CD4-binding-site antibodies. To achieve this recognition, VRC01 contacts gp120 mainly through immunoglobulin V-gene regions substantially altered from their genomic precursors. Partial receptor mimicry and extensive affinity maturation thus facilitate neutralization of HIV-1 by natural human antibodies.
C1 [Zhou, Tongqing; Georgiev, Ivelin; Wu, Xueling; Yang, Zhi-Yong; Dai, Kaifan; Kwon, Young Do; Shi, Wei; Xu, Ling; Yang, Yongping; Zhu, Jiang; Shapiro, Lawrence; Nabel, Gary J.; Mascola, John R.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Finzi, Andres; Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Pathol,Div AIDS, Boston, MA 02115 USA.
[Scheid, Johannes F.; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA.
[Scheid, Johannes F.; Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA.
[Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Shapiro, Lawrence] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
RP Kwong, PD (reprint author), NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
EM pdkwong@nih.gov
RI Kwon, Young Do/A-6957-2010; Zhou, Tongqing/A-6880-2010
OI Zhou, Tongqing/0000-0002-3935-4637
FU NIH; International AIDS Vaccine Initiative's Neutralizing Antibody
Consortium; U.S. Department of Energy, Basic Energy Sciences, Office of
Science [W-31-109-Eng-38]
FX T.Z., I.G., Z.Y., J.S., L.S., G.J.N., J.R.M., and P.D.K. designed the
research; T.Z., I.G., X.W., Z.Y., K.D.A.F., W.S., L.X., Y.Y., and J.Z.
performed the research; X.W., Y.K., J.F.S., M.C.N., and J.R.M.
contributed new reagents or reference data; T.Z., I.G., X.W., J.S.,
L.S., G.J.N., J.R.M., and P.D.K. analyzed the data; and T.Z., I.G.,
J.S., L.S., G.J.N., J.R.M., and P.D.K. wrote the paper, on which all
authors commented. We thank I.A. Wilson and members of the Structural
Biology Section and Structural Bioinformatics Core, Vaccine Research
Center, for discussions and comments on the manuscript; the staff of
sector 22 for assistance with data collection; and J. Stuckey for
assistance with figures. Support for this work was provided by the
Intramural Research Program of NIH and by grants from NIH and from the
International AIDS Vaccine Initiative's Neutralizing Antibody
Consortium. Use of sector 22 (Southeast Region Collaborative Access
team) at the Advanced Photon Source was supported by the U.S. Department
of Energy, Basic Energy Sciences, Office of Science, under contract
W-31-109-Eng-38. Coordinates and structure factors for the VRC01-gp120
complex have been deposited with the PDB under accession code 3NGB.
NR 38
TC 532
Z9 545
U1 11
U2 98
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD AUG 13
PY 2010
VL 329
IS 5993
BP 811
EP 817
DI 10.1126/science.1192819
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 637ID
UT WOS:000280809900043
PM 20616231
ER
PT J
AU Genovese, G
Friedman, DJ
Ross, MD
Lecordier, L
Uzureau, P
Freedman, BI
Bowden, DW
Langefeld, CD
Oleksyk, TK
Knob, ALU
Bernhardy, AJ
Hicks, PJ
Nelson, GW
Vanhollebeke, B
Winkler, CA
Kopp, JB
Pays, E
Pollak, MR
AF Genovese, Giulio
Friedman, David J.
Ross, Michael D.
Lecordier, Laurence
Uzureau, Pierrick
Freedman, Barry I.
Bowden, Donald W.
Langefeld, Carl D.
Oleksyk, Taras K.
Knob, Andrea L. Uscinski
Bernhardy, Andrea J.
Hicks, Pamela J.
Nelson, George W.
Vanhollebeke, Benoit
Winkler, Cheryl A.
Kopp, Jeffrey B.
Pays, Etienne
Pollak, Martin R.
TI Association of Trypanolytic ApoL1 Variants with Kidney Disease in
African Americans
SO SCIENCE
LA English
DT Article
ID STAGE RENAL-DISEASE; 9 GENE MYH9; POSITIVE SELECTION; NATURAL-SELECTION;
HUMAN SERUM; POLYMORPHISMS; RHODESIENSE; GENOME
AB African Americans have higher rates of kidney disease than European Americans. Here, we show that, in African Americans, focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (H-ESKD) are associated with two independent sequence variants in the APOL1 gene on chromosome 22 {FSGS odds ratio = 10.5 [95% confidence interval (CI) 6.0 to 18.4]; H-ESKD odds ratio = 7.3 (95% CI 5.6 to 9.5)}. The two APOL1 variants are common in African chromosomes but absent from European chromosomes, and both reside within haplotypes that harbor signatures of positive selection. ApoL1 (apolipoprotein L-1) is a serum factor that lyses trypanosomes. In vitro assays revealed that only the kidney disease-associated ApoL1 variants lysed Trypanosoma brucei rhodesiense. We speculate that evolution of a critical survival factor in Africa may have contributed to the high rates of renal disease in African Americans.
C1 [Genovese, Giulio; Friedman, David J.; Bernhardy, Andrea J.; Pollak, Martin R.] Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Boston, MA 02215 USA.
[Genovese, Giulio; Friedman, David J.; Bernhardy, Andrea J.; Pollak, Martin R.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
[Genovese, Giulio] Dartmouth Coll, Dept Math, Hanover, NH 03755 USA.
[Friedman, David J.] Beth Israel Deaconess Med Ctr, Dept Med, Vasc Biol Res Ctr, Boston, MA 02215 USA.
[Ross, Michael D.; Knob, Andrea L. Uscinski] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02215 USA.
[Lecordier, Laurence; Uzureau, Pierrick; Vanhollebeke, Benoit; Pays, Etienne] Univ Libre Bruxelles, Inst Biol & Med Mol, Mol Parasitol Lab, B-6041 Gosselies, Belgium.
[Freedman, Barry I.] Wake Forest Univ, Sch Med, Nephrol Sect, Dept Internal Med, Winston Salem, NC 27157 USA.
[Bowden, Donald W.; Hicks, Pamela J.] Wake Forest Univ, Sch Med, Dept Biochem, Winston Salem, NC 27157 USA.
[Bowden, Donald W.; Hicks, Pamela J.] Wake Forest Univ, Sch Med, Ctr Diabet Res, Winston Salem, NC 27157 USA.
[Bowden, Donald W.; Langefeld, Carl D.; Hicks, Pamela J.] Wake Forest Univ, Sch Med, Ctr Human Genom, Winston Salem, NC 27157 USA.
[Langefeld, Carl D.] Wake Forest Univ, Sch Med, Ctr Publ Hlth Genom, Dept Biostat Sci, Winston Salem, NC 27157 USA.
[Langefeld, Carl D.] Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27157 USA.
[Oleksyk, Taras K.] Univ Puerto Rico, Dept Biol, Mayaguez, PR 00681 USA.
[Nelson, George W.; Kopp, Jeffrey B.] NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA.
[Winkler, Cheryl A.] NCI, Lab Genom Divers, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Pollak, Martin R.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
RP Pollak, MR (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Boston, MA 02215 USA.
EM epays@ulb.ac.be; mpollak@bidmc.harvard.edu
RI Rinaldi2, Carlos/D-4479-2011; Taras, Oleksyk/J-8805-2013;
OI Taras, Oleksyk/0000-0002-8148-3918; Vanhollebeke,
Benoit/0000-0002-0353-365X; Kopp, Jeffrey/0000-0001-9052-186X
FU Walloon Region; Fonds National de la Recherche Scientifique; Belgian
Science Policy; NIH [R01 DK54931, K08-DK076868, R01 DK066358, R01
DK053591, R01 HL56266, R01 DK 070941, R01 DK 084149]; National Institute
of Diabetes, Digestive, and Kidney Disease [Z01 DK043308]; NCI, Center
for Cancer Research [ZIA BC 010022]; NephCure Foundation; NCI, NIH
[HHSN261200800001E]
FX We thank members of the Broad Institute Medical and Population Genetics
Program for helpful advice and review of the manuscript. We thank the
study participants for their participation and J. Robinson for the help
provided accessing the 1000 Genomes project data. We thank X. C. Zhou
[National Cancer Institute (NCI)] and E. Binns-Roemer (NCI), P.
Poelvoorde [Universite Libre de Bruxelles (ULB)], P. Tebabi (ULB) and A.
Pays (ULB) for excellent technical assistance. We thank the
investigators in the BWH and NIH FSGS genetic studies: W. Briggs, R.
Dart, S. Korbet, M. Mokrzycki, P. Kimmel, T. Ahuja, J. Berns, E. Simon,
M. Smith, H. Trachtman, M. Michel, J. R. Schelling, G. Appel, and A.
Katz. The work at the University of Brussels was supported by the
"CIBLES" program of the Walloon Region, the Fonds National de la
Recherche Scientifique, and the Interuniversity Attraction Poles program
of the Belgian Science Policy. This work was also supported by grants
from the NIH (R01 DK54931 to M.R.P; K08-DK076868 to D.J.F.; R01 DK066358
and R01 DK053591 to D. W. B.; and R01 HL56266, R01 DK 070941, and R01 DK
084149 to B.I.F.), the National Institute of Diabetes, Digestive, and
Kidney Disease Intramural research program (Z01 DK043308 to J.B.K.), the
Intramural Research Program of NCI, Center for Cancer Research (Project
ZIA BC 010022; C.A.W. and G.W.N.), and the NephCure Foundation (to
M.R.P). 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. The publisher or recipient
acknowledges right of the U.S. Government to retain a nonexclusive,
royalty-free license in and to any copyright covering the article. This
project has been funded in part with federal funds from the NCI, NIH,
under contract HHSN261200800001E. All participants gave informed consent
for genetic studies, and research was conducted under protocols approved
by the appropriate institutional review boards. J.B.K., G.W.N., C.A.W.,
and the NCI have a patent application pending for chromosome 22
polymorphisms and haplotypes for genetic screening and clinical
applications. M.R.P., G.G., the Brigham and Women's Hospital, and Beth
Israel Deaconess Medical Center have been added as coinventors to an
amendment to this application naming the specific ApoL1 SNPs described
in this manuscript. E.P., L.L., P.U., and ULB have applied for a patent
related to the use of plasma from ESKD patients to treat human sleeping
sickness by plasma transfer.
NR 23
TC 623
Z9 637
U1 5
U2 59
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD AUG 13
PY 2010
VL 329
IS 5993
BP 841
EP 845
DI 10.1126/science.1193032
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 637ID
UT WOS:000280809900051
PM 20647424
ER
PT J
AU Wu, XL
Yang, ZY
Li, YX
Hogerkorp, CM
Schief, WR
Seaman, MS
Zhou, TQ
Schmidt, SD
Wu, L
Xu, L
Longo, NS
McKee, K
O'Dell, S
Louder, MK
Wycuff, DL
Feng, Y
Nason, M
Doria-Rose, N
Connors, M
Kwong, PD
Roederer, M
Wyatt, RT
Nabel, GJ
Mascola, JR
AF Wu, Xueling
Yang, Zhi-Yong
Li, Yuxing
Hogerkorp, Carl-Magnus
Schief, William R.
Seaman, Michael S.
Zhou, Tongqing
Schmidt, Stephen D.
Wu, Lan
Xu, Ling
Longo, Nancy S.
McKee, Krisha
O'Dell, Sijy
Louder, Mark K.
Wycuff, Diane L.
Feng, Yu
Nason, Martha
Doria-Rose, Nicole
Connors, Mark
Kwong, Peter D.
Roederer, Mario
Wyatt, Richard T.
Nabel, Gary J.
Mascola, John R.
TI Rational Design of Envelope Identifies Broadly Neutralizing Human
Monoclonal Antibodies to HIV-1
SO SCIENCE
LA English
DT Article
ID TYPE-1 INFECTION; HIGH-AFFINITY; VIRUS; GP120; BREADTH; GLYCOPROTEIN;
INDIVIDUALS; PANEL; IMMUNOGENICITY; SPECIFICITIES
AB Cross-reactive neutralizing antibodies (NAbs) are found in the sera of many HIV-1-infected individuals, but the virologic basis of their neutralization remains poorly understood. We used knowledge of HIV-1 envelope structure to develop antigenically resurfaced glycoproteins specific for the structurally conserved site of initial CD4 receptor binding. These probes were used to identify sera with NAbs to the CD4-binding site (CD4bs) and to isolate individual B cells from such an HIV-1-infected donor. By expressing immunoglobulin genes from individual cells, we identified three monoclonal antibodies, including a pair of somatic variants that neutralized over 90% of circulating HIV-1 isolates. Exceptionally broad HIV-1 neutralization can be achieved with individual antibodies targeted to the functionally conserved CD4bs of glycoprotein 120, an important insight for future HIV-1 vaccine design.
C1 [Wu, Xueling; Yang, Zhi-Yong; Li, Yuxing; Hogerkorp, Carl-Magnus; Zhou, Tongqing; Schmidt, Stephen D.; Wu, Lan; Xu, Ling; Longo, Nancy S.; McKee, Krisha; O'Dell, Sijy; Louder, Mark K.; Wycuff, Diane L.; Feng, Yu; Kwong, Peter D.; Roederer, Mario; Wyatt, Richard T.; Nabel, Gary J.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Nason, Martha] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA.
[Doria-Rose, Nicole; Connors, Mark] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Schief, William R.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
[Seaman, Michael S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM gnabel@nih.gov; jmascola@nih.gov
RI Zhou, Tongqing/A-6880-2010; Schmidt, Stephen/B-5398-2012; Feng,
Yu/A-3396-2012
OI Zhou, Tongqing/0000-0002-3935-4637;
FU Vaccine Research Center; Division of Clinical Research; Laboratory of
Immunoregulation of National Institute of Allergy and Infectious
Diseases, NIH; Bill and Melinda Gates Foundation; International AIDS
Vaccine Initiative
FX This research was supported by the Intramural Research Program of the
Vaccine Research Center, the Division of Clinical Research and the
Laboratory of Immunoregulation of National Institute of Allergy and
Infectious Diseases, NIH. M.S.S. was supported in part by the Bill and
Melinda Gates Foundation's Collaboration for AIDS Vaccine Discovery,
Comprehensive Antibody-Vaccine Immune Monitoring Consortium, grant
number 38619. W.R.S. was supported by the Bill and Melinda Gates
Foundation Collaboration for AIDS Vaccine Discovery through a grant to
Seattle Biomedical Research Institute and by the International AIDS
Vaccine Initiative. Nucleotide sequences of VRC01, VRC02, and VRC03
variable regions are available under GenBank accession numbers GU980702
to GU980707. Patent applications have been filed by the NIH on mAbs
VRC01, VRC02, and VRC03 (listed investigators are X.W., Z.Y.Y., Y.L.,
C.M.H, W.R.S., T.Z., M.C., P.D.K., M.R., R.T.W., G.J.N., and J.R.M.) and
on the RSC3 probe (listed investigators are Z.Y.Y., W.R.S., T.Z., P.D.K.
and G.J.N.). We thank M. Nussenzweig and J. Scheid (Laboratory of
Molecular Immunology, Howard Hughes Medical Institute, Rockefeller
University, New York, NY) for sharing expertise and reagents for IgG
cloning and expression; B. Haynes (Duke University Medical Center,
Durham, NC) for sharing reagents and PCR methods; S. Perfetto, R.
Nguyen, and D. Ambrozak for assistance with cell sorting; E. Lybarger
for neutralization assays; J. Stuckey and B. Hartman for assistance with
figures; A. Tislerics for manuscript preparation; D. Follman for
statistical advice; C. Carrico for discussions on resurfacing; Y.-E.A.
Ban and L. Kong for glycan modeling; P. Chattopadhyay and J. Yu for
fluorescent antibody production and qualification; C. Williamson
(University of Capetown, Capetown, South Africa), M. Thomson (Instituto
de Salud Carlos III, Madrid, Spain), J. Overbaugh (Fred Hutchinson
Cancer Research Center, Seattle, WA), and S. Tovanabutra and E.
Sanders-Buell (Henry M. Jackson Foundation and the U. S. Military HIV
Research Program, Rockville, MD) for contributing HIV-1 Env plasmids for
pseudovirus production.
NR 33
TC 762
Z9 781
U1 16
U2 110
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD AUG 13
PY 2010
VL 329
IS 5993
BP 856
EP 861
DI 10.1126/science.1187659
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 637ID
UT WOS:000280809900055
PM 20616233
ER
PT J
AU Zhou, S
Mody, D
DeRavin, SS
Hauer, J
Lu, TH
Ma, ZJ
Abina, SHB
Gray, JT
Greene, MR
Cavazzana-Calvo, M
Malech, HL
Sorrentino, BP
AF Zhou, Sheng
Mody, Disha
DeRavin, Suk See
Hauer, Julia
Lu, Taihe
Ma, Zhijun
Abina, Salima Hacein-Bey
Gray, John T.
Greene, Michael R.
Cavazzana-Calvo, Marina
Malech, Harry L.
Sorrentino, Brian P.
TI A self-inactivating lentiviral vector for SCID-X1 gene therapy that does
not activate LMO2 expression in human T cells
SO BLOOD
LA English
DT Article
ID SEVERE COMBINED IMMUNODEFICIENCY; HEMATOPOIETIC STEM-CELLS;
RECEPTOR-GAMMA-CHAIN; BONE-MARROW-TRANSPLANTATION; RETROVIRAL VECTORS;
BETA-GLOBIN; MOUSE MODEL; INSERTIONAL MUTAGENESIS; LYMPHOID DEVELOPMENT;
PROGENITOR CELLS
AB To develop safer and more effective vectors for gene therapy of X-linked severe combined immunodeficiency (SCID-X1), we have evaluated new self-inactivating lentiviral vectors based on the HIV virus. The CL20i4-h gamma(c)-Revgen vector contains the entire human common gamma chain (gamma(c)) genomic sequence driven by the gamma(c) promoter. The CL20i4-EF1 alpha-h gamma(c)OPT vector uses a promoter fragment from the eukaryotic elongation factor alpha (EF1 alpha) gene to express a codon-optimized human gamma(c) cDNA. Both vectors contain a 400-bp insulator fragment from the chicken beta-globin locus within the self-inactivating long-terminal repeat. Transduction of bone marrow cells using either of these vectors restored T, B, and natural killer lymphocyte development and function in a mouse SCID-X1 transplantation model. Transduction of human CD34(+) bone marrow cells from SCID-X1 patients with either vector restored T-cell development in an in vitro assay. In safety studies using a Jurkat LMO2 activation assay, only the CL20i4-EF1 alpha-h gamma(c)OPT vector lacked the ability to transactivate LMO2 protein expression, whereas the CL20i4-h gamma(c)-Revgen vector significantly activated LMO2 protein expression. In addition, the CL20i4-EF1 alpha-h gamma(c)OPT vector has not caused any tumors in transplanted mice. We conclude that the CL20i4-EF1 alpha-h gamma(c)OPT vector may be suitable for testing in a clinical trial based on these preclinical demonstrations of efficacy and safety. (Blood. 2010;116(6):900-908)
C1 [Zhou, Sheng; Mody, Disha; Lu, Taihe; Ma, Zhijun; Gray, John T.; Greene, Michael R.; Sorrentino, Brian P.] St Jude Childrens Hosp, Div Expt Hematol, Dept Hematol, Memphis, TN 38105 USA.
[DeRavin, Suk See; Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
[Hauer, Julia; Abina, Salima Hacein-Bey; Cavazzana-Calvo, Marina] Univ Paris 05, INSERM, U768, Paris, France.
[Hauer, Julia; Abina, Salima Hacein-Bey; Cavazzana-Calvo, Marina] Hop Necker Enfants Malad, Paris, France.
RP Zhou, S (reprint author), St Jude Childrens Hosp, Div Expt Hematol, Dept Hematol, 262 Danny Thomas Pl, Memphis, TN 38105 USA.
EM sheng.zhou@stjude.org
OI Malech, Harry/0000-0001-5874-5775
FU National Heart, Lung, and Blood Institute [P01 HL 53749]; Cancer Center
[P30 CA 21765]; Assisi Foundation of Memphis; American Lebanese Syrian
Associated Charities
FX This work was supported by the National Heart, Lung, and Blood Institute
(grant P01 HL 53749), Cancer Center (support grant P30 CA 21765), the
Assisi Foundation of Memphis, and the American Lebanese Syrian
Associated Charities.
NR 49
TC 55
Z9 55
U1 0
U2 5
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 12
PY 2010
VL 116
IS 6
BP 900
EP 908
DI 10.1182/blood-2009-10-250209
PG 9
WC Hematology
SC Hematology
GA 638GO
UT WOS:000280881700011
PM 20457870
ER
PT J
AU Hartmann, EM
Campo, E
Wright, G
Lenz, G
Salaverria, I
Jares, P
Xiao, WM
Braziel, RM
Rimsza, LM
Chan, WC
Weisenburger, DD
Delabie, J
Jaffe, ES
Gascoyne, RD
Dave, SS
Mueller-Hermelink, HK
Staudt, LM
Ott, G
Bea, S
Rosenwald, A
AF Hartmann, Elena M.
Campo, Elias
Wright, George
Lenz, Georg
Salaverria, Itziar
Jares, Pedro
Xiao, Wenming
Braziel, Rita M.
Rimsza, Lisa M.
Chan, Wing-Chung
Weisenburger, Dennis D.
Delabie, Jan
Jaffe, Elaine S.
Gascoyne, Randy D.
Dave, Sandeep S.
Mueller-Hermelink, Hans-Konrad
Staudt, Louis M.
Ott, German
Bea, Silvia
Rosenwald, Andreas
TI Pathway discovery in mantle cell lymphoma by integrated analysis of
high-resolution gene expression and copy number profiling
SO BLOOD
LA English
DT Article
ID HOMOZYGOUS DELETIONS; ORGAN SIZE; DNA; IDENTIFICATION; HYBRIDIZATION;
PROLIFERATION; PROGNOSIS; CANCER; ARRAY; PROX1
AB The genome of mantle cell lymphoma (MCL) is, in addition to the translocation t(11;14), characterized by a high number of secondary chromosomal gains and losses that probably account for the various survival times of MCL patients. We investigated 77 primary MCL tumors with available clinical information using high-resolution RNA expression and genomic profiling and applied our recently developed gene expression and dosage integrator algorithm to identify novel genes and pathways that may be of relevance for the pathobiology of MCL. We show that copy number neutral loss of heterozygosity is common in MCL and targets regions that are frequently affected by deletions. The molecular consequences of genomic copy number changes appear complex, even in genomic loci with identified tumor suppressors, such as the region 9p21 containing the CDKN2A locus. Moreover, the deregulation of novel genes, such as CUL4A, ING1, and MCPH1, may affect the 2 crucial pathogenetic mechanisms in MCL, the disturbance of the proliferation, and DNA damage response pathways. Deregulation of the Hippo pathway may have a pathogenetic role in MCL because decreased expression of its members MOBKL2A, MOBKL2B, and LATS2 was associated with inferior outcome, including an independent validation series of 32 MCLs. (Blood. 2010;116(6):953-961)
C1 [Hartmann, Elena M.; Mueller-Hermelink, Hans-Konrad; Rosenwald, Andreas] Univ Wurzburg, Inst Pathol, D-97080 Wurzburg, Germany.
[Campo, Elias; Salaverria, Itziar; Jares, Pedro; Bea, Silvia] Univ Barcelona, Dept Pathol, Hosp Clin, Barcelona, Spain.
[Wright, George] NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA.
[Lenz, Georg] Charite Univ Med Berlin, Dept Hematol Oncol & Tumor Immunol, Berlin, Germany.
[Salaverria, Itziar] Univ Kiel, Inst Human Genet, Kiel, Germany.
[Xiao, Wenming] NIH, Bioinformat & Mol Anal Sect, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Braziel, Rita M.] Oregon Hlth & Sci Univ, SW Oncol Grp, Portland, OR 97201 USA.
[Rimsza, Lisa M.] Univ Arizona, Dept Pathol, Tucson, AZ USA.
[Chan, Wing-Chung; Weisenburger, Dennis D.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA.
[Delabie, Jan] Norwegian Radium Hosp, Oslo, Norway.
[Jaffe, Elaine S.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
[Dave, Sandeep S.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Staudt, Louis M.] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
[Ott, German] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany.
[Ott, German] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-7000 Stuttgart, Germany.
RP Rosenwald, A (reprint author), Univ Wurzburg, Inst Pathol, Josef Schneider Str 2, D-97080 Wurzburg, Germany.
EM Rosenwald@mail.uni-wuerzburg.de
RI Lenz, Georg/I-6844-2012; SALAVERRIA, ITZIAR/L-2246-2015; Bea,
Silvia/K-7699-2014;
OI SALAVERRIA, ITZIAR/0000-0002-2427-9822; Bea, Silvia/0000-0001-7192-2385;
Delabie, Jan/0000-0001-5023-0689; Jaffe, Elaine/0000-0003-4632-0301;
Campo, elias/0000-0001-9850-9793
FU Instituto de Salud Carlos III; Fondo Investigaciones Sanitarias
[FIS06/0150, PI08/0077]; Comision Interministerial de Ciencia y
Tecnologia Espanola [SAF08/3630]; Instituto de Salud Carlos III Red
Tematica de Investigacion Cooperativa de Cancer [2006RET2039]; National
Institutes of Health [5 U01 CA114778-03]; Lymphoma Research Foundation
[LRFMCLI-05-023]; Interdisciplinary Center for Clinical Research,
University of Wurzburg, Wurzburg, Germany; Robert-Bosch-Stiftung GmbH
FX This work was supported by the Instituto de Salud Carlos III, Fondo
Investigaciones Sanitarias (FIS06/0150 and PI08/0077; S. B.), Comision
Interministerial de Ciencia y Tecnologia Espanola (SAF08/3630; E. C.),
Instituto de Salud Carlos III Red Tematica de Investigacion Cooperativa
de Cancer (2006RET2039; E. C.), National Institutes of Health (SPECS
grant 5 U01 CA114778-03; E. C., A. R.), and the Lymphoma Research
Foundation (LRFMCLI-05-023; E. C., A. R.). A. R. and E. M. H. were
supported by the Interdisciplinary Center for Clinical Research,
University of Wurzburg, Wurzburg, Germany. G.O. was supported by the
Robert-Bosch-Stiftung GmbH.
NR 45
TC 55
Z9 57
U1 1
U2 5
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 12
PY 2010
VL 116
IS 6
BP 953
EP 961
DI 10.1182/blood-2010-01-263806
PG 9
WC Hematology
SC Hematology
GA 638GO
UT WOS:000280881700017
PM 20421449
ER
PT J
AU Bies, J
Sramko, M
Fares, J
Rosu-Myles, M
Zhang, S
Koller, R
Wolff, L
AF Bies, Juraj
Sramko, Marek
Fares, Joanna
Rosu-Myles, Michael
Zhang, Steven
Koller, Richard
Wolff, Linda
TI Myeloid-specific inactivation of p15Ink4b results in monocytosis and
predisposition to myeloid leukemia
SO BLOOD
LA English
DT Article
ID CHRONIC MYELOMONOCYTIC LEUKEMIA; MOLONEY MURINE LEUKEMIA; C-MYB;
TUMOR-SUPPRESSOR; MYELODYSPLASTIC SYNDROME; BETHESDA PROPOSALS; LYMPHOID
NEOPLASMS; P15(INK4B) GENE; POOR-PROGNOSIS; DIFFERENTIATION
AB Inactivation of p15INK4b, an inhibitor of cyclin-dependent kinases, through DNA methylation is one of the most common epigenetic abnormalities in myeloid leukemia. Although this suggests a key role for this protein in myeloid disease suppression, experimental evidence to support this has not been reported. To address whether this event is critical for premalignant myeloid disorders and leukemia development, mice were generated that have loss of p15Ink4b specifically in myeloid cells. The p15Ink4b(fl/fl)-LysMcre mice develop nonreactive monocytosis in the peripheral blood accompanied by increased numbers of myeloid and monocytic cells in the bone marrow resembling the myeloproliferative form of chronic myelomonocytic leukemia. Spontaneous progression from chronic disease to acute leukemia was not observed. Nevertheless, MOL4070LTR retrovirus integrations provided cooperative genetic mutations resulting in a high frequency of myeloid leukemia in knockout mice. Two common retrovirus insertion sites near c-myb and Sox4 genes were identified, and their transcript up-regulated in leukemia, suggesting a collaborative role of their protein products with p15Ink4b-deficiency in promoting malignant disease. This new animal model demonstrates experimentally that p15Ink4b is a tumor suppressor for myeloid leukemia, and its loss may play an active role in the establishment of preleukemic conditions. (Blood. 2010;116(6):979-987)
C1 [Bies, Juraj; Sramko, Marek; Fares, Joanna; Rosu-Myles, Michael; Zhang, Steven; Koller, Richard; Wolff, Linda] NCI, Cellular Oncol Lab, NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
[Bies, Juraj; Sramko, Marek] Slovak Acad Sci, Canc Res Inst, Mol Oncol Lab, Bratislava, Slovakia.
[Fares, Joanna] Georgetown Univ, Med Ctr, Dept Biochem & Mol & Cellular Biol, Washington, DC 20007 USA.
[Rosu-Myles, Michael] Hlth Canada, Ctr Biol Res, Biol & Genet Therapies Directorate, Ottawa, ON K1A 0L2, Canada.
RP Bies, J (reprint author), NCI, Cellular Oncol Lab, NIH, Ctr Canc Res, Bldg 37-4124,37 Convent Dr,MSC 4263, Bethesda, MD 20892 USA.
EM biesj@mail.nih.gov; wolffl@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 40
TC 26
Z9 26
U1 0
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 12
PY 2010
VL 116
IS 6
BP 979
EP 987
DI 10.1182/blood-2009-08-238360
PG 9
WC Hematology
SC Hematology
GA 638GO
UT WOS:000280881700020
PM 20457873
ER
PT J
AU Andreani, A
Bellini, S
Burnelli, S
Granaiola, M
Leoni, A
Locatelli, A
Morigi, R
Rambaldi, M
Varoli, L
Calonghi, N
Cappadone, C
Zini, M
Stefanelli, C
Masotti, L
Shoemaker, RH
AF Andreani, Aldo
Bellini, Stefania
Burnelli, Silvia
Granaiola, Massimiliano
Leoni, Alberto
Locatelli, Alessandra
Morigi, Rita
Rambaldi, Mirella
Varoli, Lucilla
Calonghi, Natalia
Cappadone, Concettina
Zini, Maddalena
Stefanelli, Claudio
Masotti, Lanfranco
Shoemaker, Robert H.
TI Substituted E-3-(3-Indolylmethylene)-1,3-dihydroindo1-2-ones with
Antitumor Activity. In Depth Study of the Effect on Growth of Breast
Cancer Cells
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID POTENTIAL COANTHRACYCLINIC ACTIVITY; MITOMYCIN ANTIBIOTICS; DERIVATIVES;
DEATH; APOPTOSIS; CASPASES; KINASES; PATHWAY; P53
AB The synthesis of new substituted E-3-(3-indolylmethylene)-1,3-dihydroindo1-2-ones is reported. The antitumor activity was evaluated according to protocols available at the National Cancer Institute (NCI), Bethesda, MD. Structure activity relationships are discussed. The action of selected compounds was investigated in MCF-7 breast cancer cells. The ability of these derivatives to inhibit cellular proliferation was accompanied by increased level of p53 and its transcriptional targets p21 and Bax, interference in the cell cycle progression with cell accumulation in the G2/M phase, and activation of apoptosis.
C1 [Andreani, Aldo; Bellini, Stefania; Burnelli, Silvia; Granaiola, Massimiliano; Leoni, Alberto; Locatelli, Alessandra; Morigi, Rita; Rambaldi, Mirella; Varoli, Lucilla] Univ Bologna, Dipartimento Sci Farmaceut, I-40126 Bologna, Italy.
[Calonghi, Natalia; Cappadone, Concettina; Zini, Maddalena; Stefanelli, Claudio; Masotti, Lanfranco] Univ Bologna, Dipartimento Biochim G Moruzzi, I-40126 Bologna, Italy.
[Shoemaker, Robert H.] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA.
RP Andreani, A (reprint author), Univ Bologna, Dipartimento Sci Farmaceut, Via Belmeloro 6, I-40126 Bologna, Italy.
EM aldo.andreani@unibo.it
FU University of Bologna, Italy
FX This work was supported by a grant from the University of Bologna, Italy
(RFO). We are grateful to the National Cancer Institute (Bethesda, MD)
for the anticancer tests.
NR 38
TC 12
Z9 12
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD AUG 12
PY 2010
VL 53
IS 15
BP 5567
EP 5575
DI 10.1021/jm1007165
PG 9
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 633RV
UT WOS:000280523300016
PM 20684599
ER
PT J
AU Morieux, P
Salome, C
Park, KD
Stables, JP
Kohn, H
AF Morieux, Pierre
Salome, Christophe
Park, Ki Duk
Stables, James P.
Kohn, Harold
TI The Structure-Activity Relationship of the 3-Oxy Site in the
Anticonvulsant (R)-N-Benzyl 2-Acetamido-3-methoxypropionamide
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID ANTIEPILEPTIC DRUG DEVELOPMENT; AMINO-ACID-DERIVATIVES; GATED
SODIUM-CHANNELS; RING-OPENING REACTION; 2-AZIRIDINECARBOXYLIC ACID;
EPILEPSY; LACOSAMIDE; DIETHOXYTRIPHENYLPHOSPHORANE; STEREOSPECIFICITY;
CYCLODEHYDRATION
AB Lacosamide ((R)-N-benzyl 2-acetamido-3-methoxypropionamide, (R)-1) is a low molecular weight anticonvulsant recently introduced in the United States and Europe for adjuvant treatment of partial-onset seizures in adults. In this study, we define the structure-activity relationship (SAR) for the compound's 3-oxy site, Placement of small nonpolar, nonbulky substituents at the 3-oxy site provided compounds with pronounced seizure protection in the maximal electroshock (MES) seizure test with activities similar to (R)-1. The anticonvulsant activity loss that accompanied introduction of larger moieties at the 3-oxy site in (R)-1 was offset, in part, by including unsaturated groups at this position. Our findings were similar to a recently reported SAR study of the 4'-benzylamide site in (R)-1 (J. Med. Chem. 2010, 53, 1288-1305). Together, these results indicate that both the 3-oxy and 4'-benzylamide positions in (R)-1 can accommodate nonbulky, hydrophobic groups and still retain pronounced anticonvulsant activities in rodents in the MES seizure model.
C1 [Morieux, Pierre; Salome, Christophe; Park, Ki Duk; Kohn, Harold] Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA.
[Stables, James P.] NINDS, Epilepsy Branch, NIH, Rockville, MD 20892 USA.
[Kohn, Harold] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA.
RP Kohn, H (reprint author), Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA.
EM harold_kohn@unc.edu
FU National Institute of Neurological Disorders and Stroke [R01NS054112,
F31NS060358]; Korean Government [KRF-2006-352-000042]
FX We thank the NINDS and the ASP at the National Institutes of Health with
Drs. Tracy Chen and Jeffrey Jiang, for kindly performing the
pharmacological studies via the ASP's contract site at the University of
Utah with Drs. H. Wolfe, H. S. White, and K. Wilcox. The project was
supported by grants R01NS054112 (H.K.) and F31NS060358 (P.M.) from the
National Institute of Neurological Disorders and Stroke, and by the
Korean Research Foundation Grant funded by the Korean Government
(MOEHRD) grant KRF-2006-352-000042 (K.D.P.). The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institute of Neurological Disorders and
Stroke or the National Institutes of Health. Harold Kohn has a
royalty-stake position in (R)-1.
NR 66
TC 16
Z9 16
U1 0
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD AUG 12
PY 2010
VL 53
IS 15
BP 5716
EP 5726
DI 10.1021/jm100508m
PG 11
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 633RV
UT WOS:000280523300031
PM 20614888
ER
PT J
AU Liu, F
Chen, X
Allali-Hassani, A
Quinn, AM
Wigle, TJ
Wasney, GA
Dong, AP
Senisterra, G
Chau, I
Siarheyeva, A
Norris, JL
Kireev, DB
Jadhav, A
Herold, JM
Janzen, WP
Arrowsmith, CH
Frye, SV
Brown, PJ
Simeonov, A
Vedadi, M
Jin, JA
AF Liu, Feng
Chen, Xin
Allali-Hassani, Abdellah
Quinn, Amy M.
Wigle, Tim J.
Wasney, Gregory A.
Dong, Aiping
Senisterra, Guillermo
Chau, Irene
Siarheyeva, Alena
Norris, Jacqueline L.
Kireev, Dmitri B.
Jadhav, Ajit
Herold, J. Martin
Janzen, William P.
Arrowsmith, Cheryl H.
Frye, Stephen V.
Brown, Peter J.
Simeonov, Anton
Vedadi, Masoud
Jin, Jian
TI Protein Lysine Methyltransferase G9a Inhibitors: Design, Synthesis, and
Structure Activity Relationships of
2,4-Diamino-7-aminoalkoxy-quinazolines.
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID PLURIPOTENT STEM-CELLS; HISTONE METHYLTRANSFERASE; CHROMATIN-STRUCTURE;
CANCER; METHYLATION; STABILITY; GENES
AB Protein lysine methyltransferase G9a, which catalyzes methylation of lysine 9 of histone H3 (H3K9) and lysine 373 (K373) of p53, is overexpressed in human cancers. Genetic knockdown of G9a inhibits cancer cell growth, and the dimethylation of p53 K373 results in the inactivation of p53. Initial SAR exploration of the 2,4-diamino-6,7-dimethoxyquinazoline template represented by 3a (BIX01294), a selective small molecule inhibitor of G9a and GLP, led to the discovery of 10 (UNC0224) as a potent G9a inhibitor with excellent selectivity. A high resolution X-ray crystal structure of the G9a-10 complex, the first cocrystal structure of G9a with a small molecule inhibitor, was obtained. On the basis of the structural insights revealed by this cocrystal structure, optimization of the 7-dimethylaminopropoxy side chain of 10 resulted in the discovery of 29 (UNC0321) (Morrison K(i) = 63 pM), which is the first G9a inhibitor with picomolar potency and the most potent G9a inhibitor to date.
C1 [Liu, Feng; Chen, Xin; Wigle, Tim J.; Norris, Jacqueline L.; Kireev, Dmitri B.; Herold, J. Martin; Janzen, William P.; Frye, Stephen V.; Jin, Jian] Univ N Carolina, Ctr Integrat Chem Biol & Drug Discovery, Div Med Chem & Nat Prod, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA.
[Allali-Hassani, Abdellah; Wasney, Gregory A.; Dong, Aiping; Senisterra, Guillermo; Chau, Irene; Siarheyeva, Alena; Arrowsmith, Cheryl H.; Brown, Peter J.; Vedadi, Masoud] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada.
[Quinn, Amy M.; Jadhav, Ajit; Simeonov, Anton] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
RP Jin, JA (reprint author), Univ N Carolina, Ctr Integrat Chem Biol & Drug Discovery, Div Med Chem & Nat Prod, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA.
EM jianjin@unc.edu
RI Kireev, Dmitri/B-7225-2012; liu, feng/J-4669-2013
OI Kireev, Dmitri/0000-0001-8479-8555;
FU National Institute Of General Medical Sciences of NIH [RC1GM090732];
Carolina Partnership; NIH; NHGRI of NIH; Ontario Research Fund; Canadian
Institutes for Health Research [1097737]; Canada Foundation for
Innovation; Genome Canada, Ontario Genomics Institute; GlaxoSmithKline;
Karolinska Institutet; Knut and Alice Wallenberg Foundation; Ontario
Innovation Trust; Ontario Ministry for Research and Innovation; Merck
Co., Inc.; Novartis Research Foundation; Swedish Agency for Innovation
Systems; Swedish Foundation for Strategic Research; Wellcome Trust
FX We thank Dr. Yizhou Dong and Professor K. H. Lee for HRMS and HPLC
support and Dr. Stanley Ng for supplying the JMJD2E enzyme. The research
described here was supported by the grant RC1GM090732 from the National
Institute Of General Medical Sciences of NIH, the Carolina Partnership,
the Molecular Libraries Initiative of the NIH Roadmap for Medical
Research, the Intramural Research Program of NHGRI of NIH, the Ontario
Research Fund and the Structural Genomics Consortium, a registered
charity (number 1097737) that receives funds from the Canadian
Institutes for Health Research, the Canada Foundation for Innovation,
Genome Canada through the Ontario Genomics Institute, GlaxoSmithKline,
Karolinska Institutet, the Knut and Alice Wallenberg Foundation, the
Ontario Innovation Trust, the Ontario Ministry for Research and
Innovation, Merck & Co., Inc., the Novartis Research Foundation, the
Swedish Agency for Innovation Systems, the Swedish Foundation for
Strategic Research, and the Wellcome Trust.
NR 40
TC 91
Z9 95
U1 2
U2 25
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD AUG 12
PY 2010
VL 53
IS 15
BP 5844
EP 5857
DI 10.1021/jm100478y
PG 14
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 633RV
UT WOS:000280523300042
PM 20614940
ER
PT J
AU Bazhenov, M
Stopfer, M
AF Bazhenov, Maxim
Stopfer, Mark
TI Forward and Back: Motifs of Inhibition in Olfactory Processing
SO NEURON
LA English
DT Editorial Material
AB The remarkable performance of the olfactory system in classifying and categorizing the complex olfactory environment is built upon several basic neural circuit motifs. These include forms of inhibition that may play comparable roles in widely divergent species. In this issue of Neuron, a new study by Stokes and Isaacson sheds light on how elementary types of inhibition dynamically interact.
C1 [Stopfer, Mark] NICHD, NIH, Bethesda, MD 20892 USA.
[Bazhenov, Maxim] Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA.
RP Stopfer, M (reprint author), NICHD, NIH, Bethesda, MD 20892 USA.
EM stopferm@mail.nih.gov
FU NIDCD NIH HHS [R01 DC012943]
NR 7
TC 9
Z9 9
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD AUG 12
PY 2010
VL 67
IS 3
BP 357
EP 358
DI 10.1016/j.neuron.2010.07.023
PG 2
WC Neurosciences
SC Neurosciences & Neurology
GA 639AJ
UT WOS:000280942900004
PM 20696373
ER
PT J
AU Bromberg-Martin, ES
Matsumoto, M
Nakahara, H
Hikosaka, O
AF Bromberg-Martin, Ethan S.
Matsumoto, Masayuki
Nakahara, Hiroyuki
Hikosaka, Okihide
TI Multiple Timescales of Memory in Lateral Habenula and Dopamine Neurons
SO NEURON
LA English
DT Article
ID VENTRAL TEGMENTAL AREA; MIXED-STRATEGY GAME; PREFRONTAL CORTEX;
PREDICTION ERROR; REWARD SIGNALS; SHORT-TERM; RESPONSES; RAT; MONKEY;
ADAPTATION
AB Midbrain dopamine neurons are thought to signal predictions about future rewards based on the memory of past rewarding experience. Little is known about the source of their reward memory and the factors that control its timescale. Here we recorded from dopamine neurons, as well as one of their sources of input, the lateral habenula, while animals predicted upcoming rewards based on the past reward history. We found that lateral habenula and dopamine neurons accessed two distinct reward memories: a short-timescale memory expressed at the start of the task and a near-optimal long-timescale memory expressed when a future reward outcome was revealed. The short- and long-timescale memories were expressed in different forms of reward-oriented eye movements. Our data show that the habenula-dopamine pathway contains multiple timescales of memory and provide evidence for their role in motivated behavior.
C1 [Bromberg-Martin, Ethan S.; Matsumoto, Masayuki; Hikosaka, Okihide] NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA.
[Matsumoto, Masayuki] Kyoto Univ, Primate Res Inst, Aichi 4848506, Japan.
[Nakahara, Hiroyuki] RIKEN, Brain Sci Inst, Lab Integrated Theoret Neurosci, Wako, Saitama 3510198, Japan.
[Nakahara, Hiroyuki] Tokyo Inst Technol, Dept Computat Intelligence & Syst Sci, Yokohama, Kanagawa 227, Japan.
RP Bromberg-Martin, ES (reprint author), NEI, Sensorimotor Res Lab, Bldg 10, Bethesda, MD 20892 USA.
EM bromberge@mail.nih.gov
RI Nakahara, Hiroyuki/N-5411-2015
OI Nakahara, Hiroyuki/0000-0001-6891-1175
FU JSPS [21300129]; MEXT [20020034]; National Eye Institute
FX We thank K. Nakamura, B.J. Richmond, D. Lee, A. Lerchner, M. Ahmadi, P.
Dayan, S. Kaveri, and D. L. Sheinberg for valuable discussions. H.N. is
partially supported by JSPS KAKENHI 21300129 and MEXT KAKENHI 20020034.
This research was supported by the Intramural Research Program at the
National Eye Institute.
NR 51
TC 30
Z9 31
U1 1
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD AUG 12
PY 2010
VL 67
IS 3
BP 499
EP 510
DI 10.1016/j.neuron.2010.06.031
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 639AJ
UT WOS:000280942900016
PM 20696385
ER
PT J
AU Orszag, PR
Emanuel, EJ
AF Orszag, Peter R.
Emanuel, Ezekiel J.
TI Health Care Reform and Cost Control
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Orszag, Peter R.; Emanuel, Ezekiel J.] White House Off Management & Budget, Washington, DC USA.
[Emanuel, Ezekiel J.] NIH, Dept Bioeth, Bethesda, MD 20892 USA.
RP Orszag, PR (reprint author), White House Off Management & Budget, Washington, DC USA.
NR 5
TC 107
Z9 108
U1 1
U2 8
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD AUG 12
PY 2010
VL 363
IS 7
BP 601
EP 603
DI 10.1056/NEJMp1006571
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 636TN
UT WOS:000280764600001
PM 20554975
ER
PT J
AU Cushman, WC
Simons-Morton, DG
Cutler, JG
AF Cushman, William C.
Simons-Morton, Denise G.
Cutler, Jeffrey G.
CA ACCORD Study Grp
TI Blood Pressure Control in Type 2 Diabetes REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Cushman, William C.] Memphis Vet Affairs Med Ctr, Memphis, TN USA.
[Simons-Morton, Denise G.; Cutler, Jeffrey G.] NHLBI, Bethesda, MD 20892 USA.
RP Cushman, WC (reprint author), Memphis Vet Affairs Med Ctr, Memphis, TN USA.
EM william.cushman@va.gov
NR 4
TC 1
Z9 1
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD AUG 12
PY 2010
VL 363
IS 7
BP 697
EP 697
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 636TN
UT WOS:000280764600025
ER
PT J
AU Porras, C
Bennett, C
Safaeian, M
Coseo, S
Rodriguez, AC
Gonzalez, P
Hutchinson, M
Jimenez, S
Sherman, ME
Wacholder, S
Solomon, D
van Doorn, LJ
Bougelet, C
Quint, W
Schiffman, M
Herrero, R
Hildesheim, A
AF Porras, Carolina
Bennett, Christina
Safaeian, Mahboobeh
Coseo, Sarah
Cecilia Rodriguez, Ana
Gonzalez, Paula
Hutchinson, Martha
Jimenez, Silvia
Sherman, Mark E.
Wacholder, Sholom
Solomon, Diane
van Doorn, Leen-Jan
Bougelet, Catherine
Quint, Wim
Schiffman, Mark
Herrero, Rolando
Hildesheim, Allan
CA Costa Rica HPV Vaccine Trial CVT G
TI Determinants of seropositivity among HPV-16/18 DNA positive young women
SO BMC INFECTIOUS DISEASES
LA English
DT Article
ID HUMAN-PAPILLOMAVIRUS INFECTION; VIRUS-LIKE PARTICLES; CERVICAL-CANCER;
ANTIBODY-RESPONSE; HPV INFECTION; SOUTH-KOREA; COSTA-RICA; TYPE-16;
VACCINE; PCR
AB Background: Not all women infected with HPV-16/18 have detectable levels of HPV-16/18 antibodies, those who seroconvert develop low antibody levels, and seroconversion occurs typically several months post-infection. We evaluated determinants of seropositivity among 646 women infected with HPV-16 and/or HPV-18.
Methods: Data are from the enrollment visit of the NCI-sponsored Costa Rica HPV Vaccine Trial. Sera were tested for HPV-16/18 antibodies by ELISA; cervical specimens were tested for HPV DNA using HC2 and SPF10/LiPA(25). Odds ratios (OR) and 95% confidence intervals (CI) were computed.
Results: Among HPV-16/18 DNA positives, seropositivity was 63.0% and 57.5%, respectively. Among HPV-16 DNA positives, seropositivity increased with lifetime number of sexual partners (p-trend = 0.01). Women with abnormal cytology and/or high viral load had a 1.63-2.79-fold increase in the detection of antibodies compared to women with normal cytology/low viral load. Current users of oral contraceptives had a 1.88-fold (95% CI, 1.14-3.09) increased detection of antibodies and current users of injectables had a 3.38-fold (95% CI, 1.39-8.23) increased detection compared to never users. Among HPV-18 DNA positive women, seropositivity was associated with current oral contraceptive use (OR 2.47; 95% CI 1.08-5.65).
Conclusions: Factors associated with sustained HPV exposure (abnormal cytology, elevated HPV viral load, increasing lifetime partners) were predictive of HPV-16 seropositivity. Hormonal contraceptive use was associated with seropositivity suggesting an effect of hormones on immune responses to HPV. Patterns were less consistent for HPV-18. Follow up of incident HPV infections to evaluate seroconversion and their determinants is needed.
C1 [Porras, Carolina; Bennett, Christina; Safaeian, Mahboobeh; Coseo, Sarah; Sherman, Mark E.; Wacholder, Sholom; Solomon, Diane; Schiffman, Mark; Hildesheim, Allan; Costa Rica HPV Vaccine Trial CVT G] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Cecilia Rodriguez, Ana; Gonzalez, Paula; Jimenez, Silvia; Herrero, Rolando] Fdn INCIENSA, Liberia, Costa Rica.
[Hutchinson, Martha] Brown Univ, Women & Infants Hospl, Providence, RI USA.
[van Doorn, Leen-Jan; Quint, Wim] DDL Diagnost Lab, Voorburg, Netherlands.
[Bougelet, Catherine] GlaxoSmithKline Biol, Rixensart, Belgium.
RP Porras, C (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM cporras@proyectoguanacaste.org
RI Hildesheim, Allan/B-9760-2015
OI Hildesheim, Allan/0000-0003-0257-2363
FU NCI, NIH Office for Research on Women's Health [N01-CP-11005]; Ministry
of Health of Costa Rica; GammaDA [BB-IND 7920]; National Institutes of
Health
FX The Costa Rican Vaccine Trial is a longstanding collaboration between
investigators in Costa Rica and NCI. The trial is sponsored and funded
by NCI (N01-CP-11005) with support from the NIH Office for Research on
Women's Health and conducted in agreement with the Ministry of Health of
Costa Rica. Vaccine was provided for our trial by GSK Biologicals, under
a Clinical Trials Agreement with NCI. GSK also provided support for
aspects of the trial associated with the regulatory submission needs of
the company under FDA BB-IND 7920. NCI and Costa Rican investigators
make final editorial decisions on this presentation and subsequent
publications. CP was supported by an appointment to the senior
fellowship programme at the National Institutes of Health. The programme
is administered by the Oak Ridge Institute for Science and Education
through an interagency agreement between the US Department of Energy and
the National Institutes of Health
NR 26
TC 17
Z9 18
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2334
J9 BMC INFECT DIS
JI BMC Infect. Dis.
PD AUG 11
PY 2010
VL 10
AR 238
DI 10.1186/1471-2334-10-238
PG 10
WC Infectious Diseases
SC Infectious Diseases
GA 666TG
UT WOS:000283142300001
PM 20698998
ER
PT J
AU Zhang, XZ
Saaddine, JB
Chou, CF
Cotch, MF
Cheng, YJ
Geiss, LS
Gregg, EW
Albright, AL
Klein, BEK
Klein, R
AF Zhang, Xinzhi
Saaddine, Jinan B.
Chou, Chin-Fang
Cotch, Mary Frances
Cheng, Yiling J.
Geiss, Linda S.
Gregg, Edward W.
Albright, Ann L.
Klein, Barbara E. K.
Klein, Ronald
TI Prevalence of Diabetic Retinopathy in the United States, 2005-2008
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID MICROVASCULAR COMPLICATIONS; RISK-FACTORS; EYE CARE; DIAGNOSIS;
MELLITUS; AGE; PROGRESSION; POPULATION; DISEASE; PEOPLE
AB Context The prevalence of diabetes in the United States has increased. People with diabetes are at risk for diabetic retinopathy. No recent national population-based estimate of the prevalence and severity of diabetic retinopathy exists.
Objectives To describe the prevalence and risk factors of diabetic retinopathy among US adults with diabetes aged 40 years and older.
Design, Setting, and Participants Analysis of a cross-sectional, nationally representative sample of the National Health and Nutrition Examination Survey 2005-2008 (N=1006). Diabetes was defined as a self-report of a previous diagnosis of the disease (excluding gestational diabetes mellitus) or glycated hemoglobin A(1c) of 6.5% or greater. Two fundus photographs were taken of each eye with a digital nonmydriatic camera and were graded using the Airlie House classification scheme and the Early Treatment Diabetic Retinopathy Study severity scale. Prevalence estimates were weighted to represent the civilian, noninstitutionalized US population aged 40 years and older.
Main Outcome Measurements Diabetic retinopathy and vision-threatening diabetic retinopathy.
Results The estimated prevalence of diabetic retinopathy and vision-threatening diabetic retinopathy was 28.5% (95% confidence interval [Cl], 24.9%-32.5%) and 4.4% (95% Cl, 3.5%-5.7%) among US adults with diabetes, respectively. Diabetic retinopathy was slightly more prevalent among men than women with diabetes (31.6%; 95% Cl, 26.8%-36.8%; vs 25.7%; 95% Cl, 21.7%-30.1%; P=.04). Non-Hispanic black individuals had a higher crude prevalence than non-Hispanic white individuals of diabetic retinopathy (38.8%; 95% Cl, 31.9%-46.1%; vs 26.4%; 95% Cl, 21.4%-32.2%; P=.01) and vision-threatening diabetic retinopathy (9.3%; 95% Cl, 5.9%-14.4%; vs 3.2%; 95% Cl, 2.0%-5.1%; P=.01). Male sex was independently associated with the presence of diabetic retinopathy (odds ratio [OR], 2.07; 95% Cl, 1.39-3.10), as well as higher hemoglobin A(1c) level (OR, 1.45; 95% Cl, 1.20-1.75), longer duration of diabetes (OR, 1.06 per year duration; 95% Cl, 1.03-1.10), insulin use (OR, 3.23; 95% Cl, 1.99-5.26), and higher systolic blood pressure (OR, 1.03 per mm Hg; 95% Cl, 1.02-1.03).
Conclusion In a nationally representative sample of US adults with diabetes aged 40 years and older, the prevalence of diabetic retinopathy and vision-threatening diabetic retinopathy was high, especially among Non-Hispanic black individuals. JAMA. 2010;304(6):649-656
C1 [Zhang, Xinzhi; Saaddine, Jinan B.; Chou, Chin-Fang; Cheng, Yiling J.; Geiss, Linda S.; Gregg, Edward W.; Albright, Ann L.] Ctr Dis Control & Prevent, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA.
[Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Klein, Barbara E. K.; Klein, Ronald] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA.
RP Zhang, XZ (reprint author), Ctr Dis Control & Prevent, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Hwy,NE K-10, Atlanta, GA 30341 USA.
EM XZhang4@cdc.gov
OI Cotch, Mary Frances/0000-0002-2046-4350; Klein,
Ronald/0000-0002-4428-6237
FU National Center for Health Statistics (NCHS), Centers for Disease
Control and Prevention (CDC); Division of Diabetes Translation, CDC
[05FED47304]; National Eye Institute, National Institutes of Health
[Z01EY000402]; Division of Diabetes Translation
FX This study was supported by the National Center for Health Statistics
(NCHS), Centers for Disease Control and Prevention (CDC). Funding for
the National Health and Nutrition Examination Survey (NHANES) retinal
component was provided by the Intra Agency Agreement 05FED47304 from the
Division of Diabetes Translation, CDC. Funding for the vision component
was provided by the National Eye Institute, National Institutes of
Health, Intramural Research Program grant Z01EY000402.; The NCHS was
involved in the design and conduct of the NHANES study and in data
collection, but was not involved in the analysis or interpretation of
the study results or in the preparation of the manuscript. The Division
of Diabetes Translation provided funding support for the retinal
component and was involved in the design and conduct of the study; in
the collection, analysis, and interpretation of the data; and in the
preparation, review, and approval of this article before submission.
NR 42
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U1 1
U2 21
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 AUG 11
PY 2010
VL 304
IS 6
BP 649
EP 656
DI 10.1001/jama.2010.1111
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 637PA
UT WOS:000280829200020
PM 20699456
ER
PT J
AU Cardwell, CR
Abnet, CC
Cantwell, MM
Murray, LJ
AF Cardwell, Chris R.
Abnet, Christian C.
Cantwell, Marie M.
Murray, Liam J.
TI Exposure to Oral Bisphosphonates and Risk of Esophageal Cancer
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID GASTROESOPHAGEAL-REFLUX; ALENDRONATE; ADENOCARCINOMA; OSTEOPOROSIS;
VALIDATION; APOPTOSIS; FEATURES; THERAPY
AB Context Use of oral bisphosphonates has increased dramatically in the United States and elsewhere. Esophagitis is a known adverse effect of bisphosphonate use; and recent reports suggest a link between bisphosphonate use and esophageal cancer, but this has not been robustly investigated.
Objective To investigate the association between bisphosphonate use and esophageal cancer.
Design, Setting, and Participants Data were extracted from the UK General Practice Research Database to compare the incidence of esophageal and gastric cancer in a cohort of patients treated with oral bisphosphonates between January 1996 and December 2006 with incidence in a control cohort. Cancers were identified from relevant Read/Oxford Medical Information System codes in the patient's clinical files. Cox proportional hazards modeling was used to calculate hazard ratios and 95% confidence intervals for risk of esophageal and gastric cancer in bisphosphonate users compared with nonusers, with adjustment for potential confounders.
Main Outcome Measure Hazard ratio for the risk of esophageal and gastric cancer in the bisphosphonate users compared with the bisphosphonate nonusers.
Results Mean follow-up time was 4.5 and 4.4 years in the bisphosphonate and control cohorts, respectively. Excluding patients with less than 6 months' follow-up, there were 41 826 members in each cohort (81% women; mean age, 70.0 (SD, 11.4) years). One hundred sixteen esophageal or gastric cancers (79 esophageal) occurred in the bisphosphonate cohort and 115 (72 esophageal) in the control cohort. The incidence of esophageal and gastric cancer combined was 0.7 per 1000 person-years of risk in both the bisphosphonate and control cohorts; the incidence of esophageal cancer alone in the bisphosphonate and control cohorts was 0.48 and 0.44 per 1000 person-years of risk, respectively. There was no difference in risk of esophageal and gastric cancer combined between the cohorts for any bisphosphonate use (adjusted hazard ratio, 0.96 [95% confidence interval, 0.74-1.25]) or risk of esophageal cancer only (adjusted hazard ratio, 1.07 [95% confidence interval, 0.77-1.49]). There also was no difference in risk of esophageal or gastric cancer by duration of bisphosphonate intake.
Conclusion Among patients in the UK General Practice Research Database, the use of oral bisphosphonates was not significantly associated with incident esophageal or gastric cancer. JAMA. 2010;304(6):657-663
C1 [Cardwell, Chris R.; Cantwell, Marie M.; Murray, Liam J.] Queens Univ Belfast, Ctr Publ Hlth, Belfast BT12 6BJ, Antrim, North Ireland.
[Abnet, Christian C.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
RP Cardwell, CR (reprint author), Queens Univ Belfast, Ctr Publ Hlth, Grosvenor Rd, Belfast BT12 6BJ, Antrim, North Ireland.
EM c.cardwell@qub.ac.uk
RI Research Datalink, Clinical Practice/H-2477-2013; Abnet,
Christian/C-4111-2015; CPRD, CPRD/B-9594-2017;
OI Abnet, Christian/0000-0002-3008-7843; Cardwell,
Chris/0000-0002-2689-4335
FU Medical Research Council; UK Medicines and Healthcare Products
Regulatory Agency
FX Access to the GPRD database was funded through the Medical Research
Council's license agreement with the UK Medicines and Healthcare
Products Regulatory Agency. However, the interpretation and conclusions
contained in this study are those of the authors alone.
NR 24
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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 AUG 11
PY 2010
VL 304
IS 6
BP 657
EP 663
DI 10.1001/jama.2010.1098
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 637PA
UT WOS:000280829200021
PM 20699457
ER
PT J
AU Cheng, AW
Scott, AL
Ladenheim, B
Chen, K
Ouyang, X
Lathia, JD
Mughal, M
Cadet, JL
Mattson, MP
Shih, JC
AF Cheng, Aiwu
Scott, Anna L.
Ladenheim, Bruce
Chen, Kevin
Ouyang, Xin
Lathia, Justin D.
Mughal, Mohamed
Cadet, Jean Lud
Mattson, Mark P.
Shih, Jean C.
TI Monoamine Oxidases Regulate Telencephalic Neural Progenitors in Late
Embryonic and Early Postnatal Development
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; PRIMATE CEREBRAL WALL; CELL-PROLIFERATION;
STEM-CELLS; CORTICAL DEVELOPMENT; SUBVENTRICULAR ZONE;
DOPAMINE-RECEPTORS; BASAL PROGENITORS; BRAIN-DEVELOPMENT;
GENE-EXPRESSION
AB Monoamine neurotransmitters play major roles in regulating a range of brain functions in adults and increasing evidence suggests roles for monoamines in brain development. Here we show that mice lacking the monoamine metabolic enzymes MAO A and MAO B (MAO AB-deficient mice) exhibit diminished proliferation of neural stem cells (NSC) in the developing telencephalon beginning in late gestation [embryonic day (E) 17.5], a deficit that persists in neonatal and adult mice. These mice showed significantly increased monoamine levels and anxiety-like behaviors as adults. Assessments of markers of intermediate progenitor cells (IPC) and mitosis showed that NSC in the subventricular zone (SVZ), but not in the ventricular zone, are reduced in MAO AB-deficient mice. A developmental time course of monoamines in frontal cortical tissues revealed increased serotonin levels as early as E14.5, and a further large increase was found between E17.5 and postnatal day 2. Administration of an inhibitor of serotonin synthesis (parachlorophenylalanine) between E14.5 and E19.5 restored the IPC numbers and SVZ thickness, suggesting the role of serotonin in the suppression of IPC proliferation. Studies of neurosphere cultures prepared from the telencephalon at different embryonic and postnatal ages showed that serotonin stimulates proliferation in wild-type, but not in MAO AB-deficient, NSC. Together, these results suggest that a MAO-dependent long-lasting alteration in the proliferation capacity of NSC occurs late in embryonic development and is mediated by serotonin. Our findings reveal novel roles for MAOs and serotonin in the regulation of IPC proliferation in the developing brain.
C1 [Cheng, Aiwu; Ouyang, Xin; Lathia, Justin D.; Mughal, Mohamed; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Scott, Anna L.; Chen, Kevin; Shih, Jean C.] Univ So Calif, Sch Pharm, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA 90089 USA.
[Ladenheim, Bruce; Cadet, Jean Lud] NIDA, Mol Neuropsychiat Branch, Baltimore, MD 21224 USA.
[Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
[Shih, Jean C.] Univ So Calif, Keck Sch Med, Dept Cell & Neurobiol, Los Angeles, CA 90089 USA.
RP Cheng, AW (reprint author), NIA, Neurosci Lab, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM chengai@mail.nih.gov; mattsonm@grc.nia.nih; jcshih@usc.edu
RI Mattson, Mark/F-6038-2012
FU National Institute on Aging and National Institute on Drug Abuse;
National Institute of Mental Health [R37 MH39085, R01 MH39085]
FX This work was supported by the Intramural Research Programs of the
National Institute on Aging and National Institute on Drug Abuse, and by
National Institute of Mental Health Grants R37 MH39085 (MERIT Award) and
R01 MH39085 (to J.C.S.).
NR 69
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U1 0
U2 0
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 AUG 11
PY 2010
VL 30
IS 32
BP 10752
EP 10762
DI 10.1523/JNEUROSCI.2037-10.2010
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 637DL
UT WOS:000280795900016
PM 20702706
ER
PT J
AU Yao, LS
Grishaev, A
Cornilescu, G
Bax, A
AF Yao, Lishan
Grishaev, Alexander
Cornilescu, Gabriel
Bax, Ad
TI The Impact of Hydrogen Bonding on Amide H-1 Chemical Shift Anisotropy
Studied by Cross-Correlated Relaxation and Liquid Crystal NMR
Spectroscopy
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID NUCLEAR-MAGNETIC-RESONANCE; DENSITY-FUNCTIONAL CALCULATIONS;
PROTEIN-STRUCTURE VALIDATION; STATE C-13 NMR; SOLID-STATE;
MICROCRYSTALLINE PROTEIN; CONSERVATIVE MUTAGENESIS; DIPOLAR COUPLINGS;
BINDING DOMAIN; L-ALANINE
AB Site-specific H-1 chemical shift anisotropy (CSA) tensors have been derived for the well-ordered backbone amide moieties in the B3 domain of protein G (GB3). Experimental input data include residual chemical shift anisotropy (RCSA), measured in six mutants that align differently relative to the static magnetic field when dissolved in a liquid crystalline Pf1 suspension, and cross-correlated relaxation rates between the H-1(N) CSA tensor and either the H-1-N-15, the H-1-C-13', or the H-1-C-13(alpha) dipolar interactions. Analyses with the assumption that the H-1(N) CSA tensor is symmetric with respect to the peptide plane (three-parameter fit) or without this premise (five-parameter fit) yield very similar results, confirming the robustness of the experimental input data, and that, to a good approximation, one of the principal components orients orthogonal to the peptide plane. H-1(N) CSA tensors are found to deviate strongly from axial symmetry, with the most shielded tensor component roughly parallel to the N-H vector, and the least shielded component orthogonal to the peptide plane. DFT calculations on pairs of N-methyl acetamide and acetamide in H-bonded geometries taken from the GB3 X-ray structure correlate with experimental data and indicate that H-bonding effects dominate variations in the H-1(N) CSA. Using experimentally derived H-1(N) CSA tensors, the optimal relaxation interference effect needed for narrowest H-1(N) TROSY line widths is found at similar to 1200 MHz.
C1 [Yao, Lishan; Grishaev, Alexander; Bax, Ad] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Yao, Lishan] Chinese Acad Sci, Qingdao Inst Bioenergy & Bioproc Technol, Qingdao 266061, Peoples R China.
[Cornilescu, Gabriel] Natl Magnet Resonance Facil, Madison, WI 53706 USA.
RP Bax, A (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,Room 126, Bethesda, MD 20892 USA.
EM bax@nih.gov
RI yao, lishan/H-3662-2012; zheng, yonghong/H-3700-2012; Cornilescu,
Gabriel/H-3113-2011
OI yao, lishan/0000-0003-1797-922X; Cornilescu, Gabriel/0000-0002-1204-8904
FU NIDDK, NIH; NIH [P41RR02301, P41GM66326]
FX We thank Dennis A. Torchia and Jinfa Ying for helpful discussions, and
Werner Maas and Jochem Struppe (Bruker Instruments) for help with the
MAS measurements. This work was supported in part by the Intramural
Research Program of the NIDDK, NIH, by the Intramural AIDS-Targeted
Antiviral Program of the Office of the Director, NIH, and by NIH Grants
P41RR02301 (BRTP/NCRR) and P41GM66326 (NIGMS) to G.C.
NR 68
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Z9 32
U1 3
U2 24
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD AUG 11
PY 2010
VL 132
IS 31
BP 10866
EP 10875
DI 10.1021/ja103629e
PG 10
WC Chemistry, Multidisciplinary
SC Chemistry
GA 635XW
UT WOS:000280692200047
PM 20681720
ER
PT J
AU Kunin, M
Dmitrieva, NI
Gallazzini, M
Shen, RF
Wang, GH
Burg, MB
Ferraris, JD
AF Kunin, Margarita
Dmitrieva, Natalia I.
Gallazzini, Morgan
Shen, Rong-Fong
Wang, Guanghui
Burg, Maurice B.
Ferraris, Joan D.
TI Mediator of DNA Damage Checkpoint 1 (MDC1) Contributes to High
NaCl-Induced Activation of the Osmoprotective Transcription Factor
TonEBP/OREBP
SO PLOS ONE
LA English
DT Article
ID ELEMENT-BINDING PROTEIN; STIMULATES TRANSCRIPTION; NUCLEAR-LOCALIZATION;
INDUCIBLE KINASE; IN-VIVO; CHROMATIN; PHOSPHORYLATION; ATM;
HYPERTONICITY; PATHWAYS
AB Background: Hypertonicity, such as induced by high NaCl, increases the activity of the transcription factor TonEBP/OREBP whose target genes increase osmoprotective organic osmolytes and heat shock proteins.
Methodology: We used mass spectrometry to analyze proteins that coimmunoprecipitate with TonEBP/OREBP in order to identify ones that might contribute to its high NaCl-induced activation.
Principal Findings: We identified 20 unique peptides from Mediator of DNA Damage Checkpoint 1 (MDC1) with high probability. The identification was confirmed by Western analysis. We used small interfering RNA knockdown of MDC1 to characterize its osmotic function. Knocking down MDC1 reduces high NaCl-induced increases in TonEBP/OREBP transcriptional and transactivating activity, but has no significant effect on its nuclear localization. We confirm six previously known phosphorylation sites in MDC1, but do not find evidence that high NaCl increases phosphorylation of MDC1. It is suggestive that MDC1 acts as a DNA damage response protein since hypertonicity reversibly increases DNA breaks, and other DNA damage response proteins, like ATM, also associate with TonEBP/OREBP and contribute to its activation by hypertonicity.
Conclusions/Significance: MDC1 associates with TonEBP/OREBP and contributes to high NaCl-induced increase of that factor's transcriptional activity.
C1 [Kunin, Margarita; Dmitrieva, Natalia I.; Gallazzini, Morgan; Burg, Maurice B.; Ferraris, Joan D.] NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA.
[Shen, Rong-Fong; Wang, Guanghui] NHLBI, Prote Core Facil, Bethesda, MD 20892 USA.
RP Kunin, M (reprint author), Chaim Sheba Med Ctr, Dept Hypertens & Nephrol, IL-52621 Tel Hashomer, Israel.
EM maurice_burg@nih.gov
RI Gallazzini, Morgan/E-5465-2011; Dmitrieva, Natalia/A-2924-2013
OI Dmitrieva, Natalia/0000-0001-8074-6950
FU National Heart, Lung and Blood Institute
FX This work was supported by the Intramural Research Program of the
National Heart, Lung and Blood Institute. 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 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 11
PY 2010
VL 5
IS 8
AR e12108
DI 10.1371/journal.pone.0012108
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 637WJ
UT WOS:000280849100027
PM 20711462
ER
PT J
AU Radaev, S
Zou, Z
Tolar, P
Nguyen, K
Nguyen, A
Krueger, PD
Stutzman, N
Pierce, S
Sun, PD
AF Radaev, Sergei
Zou, Zhongcheng
Tolar, Pavel
Nguyen, Khanh
Nguyen, AnhThao
Krueger, Peter D.
Stutzman, Nicole
Pierce, Susan
Sun, Peter D.
TI Structural and Functional Studies of Ig alpha beta and Its Assembly with
the B Cell Antigen Receptor
SO STRUCTURE
LA English
DT Article
ID CRYSTAL-STRUCTURE; MONOCLONAL-ANTIBODY; COMPLEX; EXPRESSION; SURFACE;
SYSTEM; GENE; FORM; REFINEMENT; SELECTION
AB The B cell antigen receptor (BCR) plays an essential role in all phases of B cell development. Here we show that the extracellular domains of murine and human Ig beta form an I-set immunoglobulin-like structure with an interchain disulfide between cysteines on their G strands. Structural and sequence analysis suggests that Ig alpha displays a similar fold as Ig beta. An Ig alpha beta heterodimer model was generated based on the unique disulfide-bonded Ig beta dimer. Solution binding studies showed that the extracellular domains of Ig alpha beta preferentially recognize the constant region of BCR with chain specificity, suggesting a role for Ig alpha beta to enhance BCR mu chain signaling. Cluster mutations on Ig alpha, Ig beta, and a membrane-bound form of immunoglobulin (mIgM) based on the structural model identified distinct areas of potential contacts involving charged residues on both subunits of the coreceptor and the C mu 4 domain of mIgM. These studies provide the first structural model for understanding BCR function.
C1 [Radaev, Sergei; Zou, Zhongcheng; Nguyen, Khanh; Nguyen, AnhThao; Stutzman, Nicole; Sun, Peter D.] NIAID, Struct Immunol Sect, NIH, Rockville, MD 20852 USA.
[Tolar, Pavel; Krueger, Peter D.; Pierce, Susan] NIAID, Immunogenet Lab, Lymphocyte Activat Sect, NIH, Rockville, MD 20852 USA.
RP Sun, PD (reprint author), NIAID, Struct Immunol Sect, NIH, 12441 Pk Lawn Dr, Rockville, MD 20852 USA.
EM psun@nih.gov
FU U.S. Department of Energy, Basic Energy Sciences, Office of Science
[W-31-109-Eng-38]; National Institute of Allergy and Infectious Diseases
FX We would like to thank Marina Zhuravleva and M. Gordon Joyce for their
help in data collection. The use of the Advanced Photon Source was
supported by the U.S. Department of Energy, Basic Energy Sciences,
Office of Science, under contract W-31-109-Eng-38. This work is
supported by intramural research funding from the National Institute of
Allergy and Infectious Diseases.
NR 53
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U1 0
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0969-2126
J9 STRUCTURE
JI Structure
PD AUG 11
PY 2010
VL 18
IS 8
BP 934
EP 943
DI 10.1016/j.str.2010.04.019
PG 10
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 639DG
UT WOS:000280950400008
PM 20696394
ER
PT J
AU Yang, D
Hurley, JH
AF Yang, Dong
Hurley, James H.
TI Structural Role of the Vps4-Vta1 Interface in ESCRT-III Recycling
SO STRUCTURE
LA English
DT Article
ID AAA-ATPASE VPS4; MULTIVESICULAR BODY; SACCHAROMYCES-CEREVISIAE; MEMBRANE
ASSOCIATION; PROTEIN INTERACTIONS; ENDOSOMAL TRANSPORT; YEAST; COMPLEX;
VTA1P; MECHANISMS
AB The ESCRT complexes are required for multivesicular body biogenesis, macroautophagy, cytokinesis, and the budding of HIV-1. The final step in the ESCRT cycle is the disassembly of the ESCRT-III lattice by the AAA+ ATPase Vps4. Vps4 assembles on its membrane-bound ESCRT-III substrate with its cofactor, Vta1 The crystal structure of the dimeric VSL domain of yeast Vta1 with the small ATPase and the beta domains of Vps4 was determined. Residues involved in structural interactions are conserved and are required for binding in vitro and for Cps1 sorting in vivo. Modeling of the Vta1 complex in complex with the lower hexameric ring of Vps4 indicates that the two-fold axis of the Vta1 VSL domain is parallel to within similar to 20 degrees of the six-fold axis of the hexamer. This suggests that Vta1 might not crosslink the two hexameric rings of Vps4, but rather stabilizes an array of Vps4-Vta1 complexes for ESCRT-III disassembly.
C1 [Yang, Dong; Hurley, James H.] US Dept HHS, Mol Biol Lab, NIDDKD, NIH, Bethesda, MD 20892 USA.
RP Hurley, JH (reprint author), US Dept HHS, Mol Biol Lab, NIDDKD, NIH, Bethesda, MD 20892 USA.
EM hurley@helix.nih.gov
FU NCI [Y1-CO-1020]; NIGMS [Y1-GM-1104]; U.S. Department of Energy, Basic
Energy Sciences, Office of Science [DE-AC02-06CH11357]; NIDDK; NIH
FX We thank B. Baibokov, X. Ren, and Y. Im for assistance with microscopy,
J. Dean for microscope access, and D. Katzmann for helpful discussions.
GM/CA CAT has been funded in whole or in part with Federal funds from
the NCI (Y1-CO-1020) and the NIGMS (Y1-GM-1104). Use of the Advanced
Photon Source was supported by the U.S. Department of Energy, Basic
Energy Sciences, Office of Science, under contract No.
DE-AC02-06CH11357. This work was supported by the NIDDK and IATAP
programs of the NIH intramural research program.
NR 38
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U1 1
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0969-2126
J9 STRUCTURE
JI Structure
PD AUG 11
PY 2010
VL 18
IS 8
BP 976
EP 984
DI 10.1016/j.str.2010.04.014
PG 9
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 639DG
UT WOS:000280950400012
PM 20696398
ER
PT J
AU Enoch, MA
Zhou, Z
Mash, DC
Yuan, Q
Goldman, D
AF Enoch, M. A.
Zhou, Z.
Mash, D. C.
Yuan, Q.
Goldman, D.
TI CHRONIC ALCOHOL AND COCAINE EXPOSURE IN THE HUMAN BRAIN: EFFECTS ON
EXPRESSION OF STRESS RESPONSE GENES
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT World Congress on
International-Society-for-Biomedical-Research-on-Alcoholism
CY SEP 13-16, 2010
CL Paris, FRANCE
SP Int Soc Biomed Res Alcoholism, Soc Francaise Alcoolog
C1 [Enoch, M. A.; Zhou, Z.; Mash, D. C.; Yuan, Q.; Goldman, D.] NIAAA, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD AUG 10
PY 2010
VL 34
IS 8
SU S
BP 29A
EP 29A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 630DN
UT WOS:000280252600063
ER
PT J
AU Brooks, PJ
AF Brooks, P. J.
TI THE ROLE OF ACETALDEHYDE-DNA ADDUCTS IN ALCOHOL MEDIATED CARCINOGENESIS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT World Congress on
International-Society-for-Biomedical-Research-on-Alcoholism
CY SEP 13-16, 2010
CL Paris, FRANCE
SP Int Soc Biomed Res Alcoholism, Soc Francaise Alcoolog
C1 [Brooks, P. J.] NIAAA, NIH, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD AUG 10
PY 2010
VL 34
IS 8
SU S
BP 35A
EP 35A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 630DN
UT WOS:000280252600085
ER
PT J
AU Schank, J
Thorsell, A
Rice, KC
Heilig, M
AF Schank, J.
Thorsell, A.
Rice, K. C.
Heilig, M.
TI NEUROKININ 1 RECEPTOR (NK1R) ANTAGONISM A NOVEL TARGET FOR TREATMENT OF
ALCOHOLISM
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT World Congress on
International-Society-for-Biomedical-Research-on-Alcoholism
CY SEP 13-16, 2010
CL Paris, FRANCE
SP Int Soc Biomed Res Alcoholism, Soc Francaise Alcoolog
C1 [Schank, J.; Thorsell, A.; Rice, K. C.; Heilig, M.] NIAAA, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD AUG 10
PY 2010
VL 34
IS 8
SU S
BP 39A
EP 39A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 630DN
UT WOS:000280252600102
ER
PT J
AU Barr, CS
Yuan, Q
Zhou, Z
Lindell, SG
Schwandt, ML
Higley, JD
Suomi, SJ
Goldman, D
AF Barr, C. S.
Yuan, Q.
Zhou, Z.
Lindell, S. G.
Schwandt, M. L.
Higley, J. D.
Suomi, S. J.
Goldman, D.
TI GENOME-WIDE IDENTIFICATION OF EPIGENETIC MARKERS OF EARLY STRESS IN
PRIMATE BRAIN - RELEVANCE TO G X E INTERACTIONS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT World Congress on
International-Society-for-Biomedical-Research-on-Alcoholism
CY SEP 13-16, 2010
CL Paris, FRANCE
SP Int Soc Biomed Res Alcoholism, Soc Francaise Alcoolog
C1 [Barr, C. S.; Yuan, Q.; Zhou, Z.; Lindell, S. G.; Schwandt, M. L.; Higley, J. D.; Suomi, S. J.; Goldman, D.] NIAAA, NIH, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD AUG 10
PY 2010
VL 34
IS 8
SU S
BP 43A
EP 43A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 630DN
UT WOS:000280252600118
ER
PT J
AU Ramchandani, VA
Cooke, ME
Vatsalya, V
Issa, JE
Zimmermann, US
O'Connor, S
Hommer, DW
Heilig, M
AF Ramchandani, V. A.
Cooke, M. E.
Vatsalya, V.
Issa, J. E.
Zimmermann, U. S.
O'Connor, S.
Hommer, D. W.
Heilig, M.
TI RECENT DRINKING HISTORY PREDICTS INTRAVENOUS ALCOHOL SELF-ADMINISTRATION
IN SOCIAL DRINKERS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT World Congress on
International-Society-for-Biomedical-Research-on-Alcoholism
CY SEP 13-16, 2010
CL Paris, FRANCE
SP Int Soc Biomed Res Alcoholism, Soc Francaise Alcoolog
C1 [Ramchandani, V. A.; Cooke, M. E.; Vatsalya, V.; Issa, J. E.; Zimmermann, U. S.; O'Connor, S.; Hommer, D. W.; Heilig, M.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD AUG 10
PY 2010
VL 34
IS 8
SU S
BP 44A
EP 44A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 630DN
UT WOS:000280252600121
ER
PT J
AU Zakhari, S
AF Zakhari, S.
TI ALCOHOL METABOLISM BY HEPATIC AND EXTRAHEPATIC TISSUES
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT World Congress on
International-Society-for-Biomedical-Research-on-Alcoholism
CY SEP 13-16, 2010
CL Paris, FRANCE
SP Int Soc Biomed Res Alcoholism, Soc Francaise Alcoolog
C1 [Zakhari, S.] NIAAA, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD AUG 10
PY 2010
VL 34
IS 8
SU S
BP 51A
EP 51A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 630DN
UT WOS:000280252600150
ER
PT J
AU Veech, R
AF Veech, R.
TI THE UTILIZATION OF ACETATE BY BRAIN DECREASES PHOSPHORYLATION POTENTIAL
AND REDOX STATES COMPATIBLE WITH THE OPENING OF THE MITOCHONDRIAL
PERMIABILITY TRANSITION PORE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT World Congress on
International-Society-for-Biomedical-Research-on-Alcoholism
CY SEP 13-16, 2010
CL Paris, FRANCE
SP Int Soc Biomed Res Alcoholism, Soc Francaise Alcoolog
C1 [Veech, R.] NIAAA, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD AUG 10
PY 2010
VL 34
IS 8
SU S
BP 52A
EP 52A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 630DN
UT WOS:000280252600152
ER
PT J
AU Gao, B
Miller, A
Ki, SH
Park, O
AF Gao, B.
Miller, A.
Ki, S. H.
Park, O.
TI MOLECULAR MECHANISMS OF ALCOHOLIC LIVER DISEASE: ROLES OF CYTOKINES
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT World Congress on
International-Society-for-Biomedical-Research-on-Alcoholism
CY SEP 13-16, 2010
CL Paris, FRANCE
SP Int Soc Biomed Res Alcoholism, Soc Francaise Alcoolog
C1 [Gao, B.; Miller, A.; Ki, S. H.; Park, O.] NIAAA, Neuroendocrinol Sect, Lab Physiol Studies, NIH, Bethesda, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD AUG 10
PY 2010
VL 34
IS 8
SU S
BP 53A
EP 53A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 630DN
UT WOS:000280252600159
ER
PT J
AU Kunos, G
Tam, J
Vemuri, VK
Gao, B
Makriyannis, A
AF Kunos, G.
Tam, J.
Vemuri, V. K.
Gao, B.
Makriyannis, A.
TI TARGETING PERIPHERAL CB1 CANNABINOID RECEPTORS FOR THE TREATMENT OF
ALCOHOLIC FATTY LIVER DISEASE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT World Congress on
International-Society-for-Biomedical-Research-on-Alcoholism
CY SEP 13-16, 2010
CL Paris, FRANCE
SP Int Soc Biomed Res Alcoholism, Soc Francaise Alcoolog
C1 [Kunos, G.; Tam, J.; Vemuri, V. K.; Gao, B.; Makriyannis, A.] NIAAA, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD AUG 10
PY 2010
VL 34
IS 8
SU S
BP 54A
EP 54A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 630DN
UT WOS:000280252600161
ER
PT J
AU Heilig, M
AF Heilig, M.
TI IMAGING BASED SURROGATE MARKERS AS TRANSLATIONAL TOOLS IN MEDICATIONS
DEVELOPMENT FOR ALCOHOLISM
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT World Congress on
International-Society-for-Biomedical-Research-on-Alcoholism
CY SEP 13-16, 2010
CL Paris, FRANCE
SP Int Soc Biomed Res Alcoholism, Soc Francaise Alcoolog
C1 [Heilig, M.] NIAAA, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD AUG 10
PY 2010
VL 34
IS 8
SU S
BP 64A
EP 64A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 630DN
UT WOS:000280252600200
ER
PT J
AU Lovinger, DM
Moykkynen, T
Korpi, ER
Talani, G
Jun, S
AF Lovinger, D. M.
Moykkynen, T.
Korpi, E. R.
Talani, G.
Jun, S.
TI DESENSITIZATION INVOLVEMENT IN OPPOSING ETHANOL EFFECTS ON
AMPA/GLUTAMATE AND 5-HT3 RECEPTORS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT World Congress on
International-Society-for-Biomedical-Research-on-Alcoholism
CY SEP 13-16, 2010
CL Paris, FRANCE
SP Int Soc Biomed Res Alcoholism, Soc Francaise Alcoolog
C1 [Lovinger, D. M.; Moykkynen, T.; Korpi, E. R.; Talani, G.; Jun, S.] NIAAA, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD AUG 10
PY 2010
VL 34
IS 8
SU S
BP 74A
EP 74A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 630DN
UT WOS:000280252600242
ER
PT J
AU Goldman, D
AF Goldman, D.
TI DISCOVERY OF A COMMON STOP CODON AFFECTING SEROTONIN SIGNALING:
IMPLICATIONS FOR ALCOHOLISM AND IMPULSIVITY
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT World Congress on
International-Society-for-Biomedical-Research-on-Alcoholism
CY SEP 13-16, 2010
CL Paris, FRANCE
SP Int Soc Biomed Res Alcoholism, Soc Francaise Alcoolog
C1 [Goldman, D.] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD AUG 10
PY 2010
VL 34
IS 8
SU S
BP 78A
EP 78A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 630DN
UT WOS:000280252600257
ER
PT J
AU Rajesh, M
Ki, SH
Mukhopadhyay, P
Park, O
Wang, H
Gao, YR
Yin, S
Miller, AM
Pacher, P
AF Rajesh, M.
Ki, S. H.
Mukhopadhyay, P.
Park, O.
Wang, H.
Gao, Y. R.
Yin, S.
Miller, A. M.
Pacher, P.
TI TGF-beta ENHANCES ADVERSE ALCOHOL EFFECTS AND HEPATOCELLULAR DAMAGE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT World Congress on
International-Society-for-Biomedical-Research-on-Alcoholism
CY SEP 13-16, 2010
CL Paris, FRANCE
SP Int Soc Biomed Res Alcoholism, Soc Francaise Alcoolog
C1 [Rajesh, M.; Ki, S. H.; Mukhopadhyay, P.; Park, O.; Wang, H.; Gao, Y. R.; Yin, S.; Miller, A. M.; Pacher, P.] NIAAA, NIH, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD AUG 10
PY 2010
VL 34
IS 8
SU S
BP 84A
EP 84A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 630DN
UT WOS:000280252600282
ER
PT J
AU Murray, MM
AF Murray, M. M.
TI USING DISSEMINATION SCIENCE TO INCREASE PHYSICIAN IDENTIFICATION AND
TREATMENT OF ALCOHOL PROBLEMS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT World Congress on
International-Society-for-Biomedical-Research-on-Alcoholism
CY SEP 13-16, 2010
CL Paris, FRANCE
SP Int Soc Biomed Res Alcoholism, Soc Francaise Alcoolog
C1 [Murray, M. M.] NIAAA, NIH, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD AUG 10
PY 2010
VL 34
IS 8
SU S
BP 86A
EP 86A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 630DN
UT WOS:000280252600289
ER
PT J
AU Falk, DE
Wang, X
Liu, L
Fertig, J
Mattson, M
Ryan, M
Johnson, B
Stout, R
Litten, RZ
AF Falk, D. E.
Wang, X.
Liu, L.
Fertig, J.
Mattson, M.
Ryan, M.
Johnson, B.
Stout, R.
Litten, R. Z.
TI PERCENTAGE OF SUBJECTS WITH NO HEAVY DRINKING DAYS: EVALUATION AS AN
EFFICACY ENDPOINT FOR ALCOHOL CLINICAL TRIALS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT World Congress on
International-Society-for-Biomedical-Research-on-Alcoholism
CY SEP 13-16, 2010
CL Paris, FRANCE
SP Int Soc Biomed Res Alcoholism, Soc Francaise Alcoolog
C1 [Falk, D. E.; Wang, X.; Liu, L.; Fertig, J.; Mattson, M.; Ryan, M.; Johnson, B.; Stout, R.; Litten, R. Z.] NIH, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD AUG 10
PY 2010
VL 34
IS 8
SU S
BP 87A
EP 87A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 630DN
UT WOS:000280252600294
ER
PT J
AU Litten, RZ
AF Litten, R. Z.
TI NEW STRATEGIES AND APPROACHES TO IMPROVE ALCOHOL CLINICAL TRIALS AND
INFORM REGULATORY GUIDANCE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT World Congress on
International-Society-for-Biomedical-Research-on-Alcoholism
CY SEP 13-16, 2010
CL Paris, FRANCE
SP Int Soc Biomed Res Alcoholism, Soc Francaise Alcoolog
C1 [Litten, R. Z.] NIAAA, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD AUG 10
PY 2010
VL 34
IS 8
SU S
BP 88A
EP 88A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 630DN
UT WOS:000280252600296
ER
PT J
AU Camp, MC
Feyder, M
Palachick, B
Ihne, J
Coba, MP
Grant, SG
Holmes, A
AF Camp, M. C.
Feyder, M.
Palachick, B.
Ihne, J.
Coba, M. P.
Grant, S. G.
Holmes, A.
TI A ROLE FOR POST-SYNAPTIC DENSITY 95 (PSD-95) IN MEDIATING THE BEHAVIORAL
EFFECTS OF ETHANOL
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT World Congress on
International-Society-for-Biomedical-Research-on-Alcoholism
CY SEP 13-16, 2010
CL Paris, FRANCE
SP Int Soc Biomed Res Alcoholism, Soc Francaise Alcoolog
C1 [Camp, M. C.; Feyder, M.; Palachick, B.; Ihne, J.; Coba, M. P.; Grant, S. G.; Holmes, A.] NIH, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD AUG 10
PY 2010
VL 34
IS 8
SU S
BP 92A
EP 92A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 630DN
UT WOS:000280252600305
ER
PT J
AU Goldman, D
Zhou, Z
Yuan, Q
Mash, DC
AF Goldman, D.
Zhou, Z.
Yuan, Q.
Mash, D. C.
TI EPIGENETICS OF CHRONIC ALCOHOL AND COCAINE EXPOSURE IN THE HUMAN BRAIN
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT World Congress on
International-Society-for-Biomedical-Research-on-Alcoholism
CY SEP 13-16, 2010
CL Paris, FRANCE
SP Int Soc Biomed Res Alcoholism, Soc Francaise Alcoolog
C1 [Goldman, D.; Zhou, Z.; Yuan, Q.; Mash, D. C.] NIAAA, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD AUG 10
PY 2010
VL 34
IS 8
SU S
BP 115A
EP 115A
PG 1
WC Substance Abuse
SC Substance Abuse
GA 630DN
UT WOS:000280252600400
ER
PT J
AU Wilson, NA
Sheehan, FT
AF Wilson, Nicole A.
Sheehan, Frances T.
TI Dynamic in vivo quadriceps lines-of-action
SO JOURNAL OF BIOMECHANICS
LA English
DT Article
DE Quadriceps muscle; Patellofemoral pain; Knee; Moment arms; Modeling;
Force directions
ID PATELLOFEMORAL PAIN; EXTENSOR MECHANISM; PATELLAR TRACKING; VASTUS
MEDIALIS; MOMENT ARMS; HUMAN KNEE; JOINT; MODEL; TENDON; WALKING
AB Tissue stresses and quadriceps forces are crucial factors when considering knee joint biomechanics. However, it is difficult to obtain direct, in vivo, measurements of these quantities. The primary purpose of this study was to provide the first complete description of quadriceps geometry (force directions and moment arms) of individual quadriceps components using in vivo, 3D data collected during volitional knee extension. A secondary purpose was to determine if 3D quadriceps geometry is altered in patients with patellofemoral pain and maltracking. After obtaining informed consent, cine-phase contrast (PC) MRI sets (x,y,z velocity and anatomic images) were acquired from 25 asymptomatic knees and 15 knees with patellofemoral pain during active knee extension. Using a sagittal-oblique and two coronaloblique imaging planes, the origins and insertions of each quadriceps line-of-action were identified and tracked throughout the motion by integrating the cine-PC velocity data. The force direction and relative moment (RM) were calculated for each line-of-action. All quadriceps lines-of-action were oriented primarily in the superior direction. There were no significant differences in quadriceps geometry between asymptomatic and subjects with patellofemoral pain. However, patellofemoral kinematics were significantly different between the two populations. This study will improve the ability of musculoskeletal models to closely match in vivo human performance by providing accurate 3D quadriceps geometry and associated patellofemoral kinematics during dynamic knee motion. Furthermore, determination that quadriceps geometry is not altered in patellofemoral pain supports the use of generalized a knee model based on asymptomatic quadriceps architecture. Published by Elsevier Ltd.
C1 [Wilson, Nicole A.; Sheehan, Frances T.] NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, Bethesda, MD 20892 USA.
RP Sheehan, FT (reprint author), NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, Bldg 10 CRC RM 1-1469,10 Ctr Dr MSC 1604, Bethesda, MD 20892 USA.
EM fsheehan@cc.nih.gov
RI sheehan, frances/B-6962-2009; Wilson, Nicole/C-4049-2008
OI Wilson, Nicole/0000-0002-0844-1885
FU NIH
FX This research was supported by the Intramural Research Program of the
NIH, and the Clinical Center at the NIH. We thank Abrahm Behnam,
Jacqueline Feenster, Bonnie Damaska, and the Diagnostic Radiology
Department at the National Institutes of Health for their support and
research time. Any opinions, findings, and conclusions or
recommendations expressed in this material are those of the authors and
do not necessarily reflect the views of the National Institutes of
Health or the US Public Health Service.
NR 35
TC 7
Z9 7
U1 0
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0021-9290
EI 1873-2380
J9 J BIOMECH
JI J. Biomech.
PD AUG 10
PY 2010
VL 43
IS 11
BP 2106
EP 2113
DI 10.1016/j.jbiomech.2010.04.002
PG 8
WC Biophysics; Engineering, Biomedical
SC Biophysics; Engineering
GA 646IU
UT WOS:000281534000009
PM 20451912
ER
PT J
AU Gunderson, LL
Jessup, JM
Sargent, DJ
Greene, FL
Stewart, A
Compton, CA
Sobin, LH
AF Gunderson, Leonard L.
Jessup, J. Milburn
Sargent, Daniel J.
Greene, Frederick L.
Stewart, Andrew
Compton, Carolyn A.
Sobin, Leslie H.
TI Revised Staging: Is It Really Better, or Do We Not Know? Reply
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
ID ADJUVANT RECTAL-CANCER; POOLED ANALYSIS; SURVIVAL; CATEGORIZATION;
OUTCOMES; RELAPSE; IMPACT; TUMOR
C1 [Gunderson, Leonard L.] Mayo Clin, Ctr Canc, Scottsdale, AZ USA.
[Jessup, J. Milburn; Compton, Carolyn A.] NCI, Bethesda, MD 20892 USA.
[Sargent, Daniel J.] Mayo Clin, Ctr Canc, Rochester, MN USA.
[Greene, Frederick L.] Carolinas Med Ctr, Charlotte, NC 28203 USA.
[Stewart, Andrew] Amer Coll Surg, Chicago, IL USA.
[Sobin, Leslie H.] Int Union Canc, Geneva, Switzerland.
RP Gunderson, LL (reprint author), Mayo Clin, Ctr Canc, Scottsdale, AZ USA.
NR 8
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
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD AUG 10
PY 2010
VL 28
IS 23
BP E399
EP E400
DI 10.1200/JCO.2010.28.7250
PG 2
WC Oncology
SC Oncology
GA 641LX
UT WOS:000281129000025
ER
PT J
AU Veytsman, I
Fojo, T
AF Veytsman, Irina
Fojo, Tito
TI Adjuvant Therapy in Patients With Adrenocortical Carcinoma: A Position
of an International Panel Reply
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
C1 [Veytsman, Irina] Washington Hosp Ctr, Washington, DC 20010 USA.
[Fojo, Tito] NCI, Bethesda, MD 20892 USA.
RP Veytsman, I (reprint author), Washington Hosp Ctr, Washington, DC 20010 USA.
NR 1
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
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD AUG 10
PY 2010
VL 28
IS 23
BP E403
EP E403
DI 10.1200/JCO.2010.28.0321
PG 1
WC Oncology
SC Oncology
GA 641LX
UT WOS:000281129000027
ER
PT J
AU Hartz, AMS
Madole, EK
Miller, DS
Bauer, B
AF Hartz, A. M. S.
Madole, E. K.
Miller, D. S.
Bauer, B.
TI Estrogen Receptor beta Signaling through Phosphatase and Tensin
Homolog/Phosphoinositide 3-Kinase/Akt/Glycogen Synthase Kinase 3
Down-Regulates Blood-Brain Barrier Breast Cancer Resistance Protein
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID NECROSIS-FACTOR-ALPHA; P-GLYCOPROTEIN; ER-BETA; HORMONAL-REGULATION;
TRANSPORT ACTIVITY; ABC TRANSPORTERS; BCRP EXPRESSION; UP-REGULATION;
CELLS; PENETRATION
AB Breast cancer resistance protein (BCRP) is an ATP-driven efflux pump at the blood-brain barrier that limits central nervous system pharmacotherapy. Our previous studies showed rapid loss of BCRP transport activity in rat brain capillaries exposed to low concentrations of 17-beta-estradiol (E2); this occurred without acute change in BCRP protein expression. Here, we describe a pathway through which sustained, extended exposure to E2 signals down-regulation of BCRP at the blood-brain barrier. Six-hour exposure of isolated rat and mouse brain capillaries to E2 reduced BCRP transport activity and BCRP monomer and dimer expression. Experiments with brain capillaries from estrogen receptor (ER)alpha and ER beta knockout mice and with ER agonists and antagonists showed that E2 signaled through ER beta to down-regulate BCRP expression. In rat brain capillaries, E2 increased unphosphorylated, active phosphatase and tensin homolog (PTEN); decreased phosphorylated, active Akt; and increased phosphorylated, active glycogen synthase kinase (GSK)3. Consistent with this, inhibition of phosphoinositide 3-kinase (PI3K) or Akt decreased BCRP activity and protein expression, and inhibition of PTEN or GSK3 reversed the E2 effect on BCRP. Lactacystin, a proteasome inhibitor, abolished E2-mediated BCRP down-regulation, suggesting internalization followed by transporter degradation. Dosing mice with E2 reduced BCRP activity in brain capillaries within 1 h; this reduction persisted for 24 h. BCRP protein expression in brain capillaries was unchanged 1 h after E2 dosing but was substantially reduced 6 and 24 h after dosing. Thus, E2 signals through ER beta, PTEN/PI3K/Akt/GSK3 to stimulate proteasomal degradation of BCRP. These in vitro and in vivo findings imply that E2-mediated down-regulation of blood-brain barrier BCRP has the potential to increase brain uptake of chemotherapeutics that are BCRP substrates.
C1 [Madole, E. K.; Bauer, B.] Univ Minnesota, Coll Pharm Duluth, Dept Pharmaceut Sci, Duluth, MN 55812 USA.
[Hartz, A. M. S.] Univ Minnesota, Med Sch Duluth, Dept Biochem & Mol Biol, Duluth, MN 55812 USA.
[Miller, D. S.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
RP Bauer, B (reprint author), Univ Minnesota, Coll Pharm, 1110 Kirby Dr,232 Life Sci, Duluth, MN 55812 USA.
EM bjbauer@d.umn.edu
FU National Institutes of Health National Institute of Environmental Health
Sciences; University of Minnesota College of Pharmacy Melendy Research;
Whiteside Institute for Clinical Research; University of Minnesota
College of Pharmacy
FX This work was supported by the Intramural Research Program at the
National Institutes of Health National Institute of Environmental Health
Sciences (to D. S. M.); a University of Minnesota College of Pharmacy
Melendy Research Scholarship (to E. K. M.); a research grant from the
Whiteside Institute for Clinical Research (to A. M. S. H. and B. B.);
and University of Minnesota College of Pharmacy startup funds (to B.
B.).
NR 43
TC 33
Z9 38
U1 0
U2 1
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD AUG 10
PY 2010
VL 334
IS 2
BP 467
EP 476
DI 10.1124/jpet.110.168930
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 626TT
UT WOS:000279990700013
PM 20460386
ER
PT J
AU Schneider, EH
Strasser, A
Thurmond, RL
Seifert, R
AF Schneider, Erich H.
Strasser, Andrea
Thurmond, Robin L.
Seifert, Roland
TI Structural Requirements for Inverse Agonism and Neutral Antagonism of
Indole-, Benzimidazole-, and Thienopyrrole-Derived Histamine H-4
Receptor Ligands
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID HIGH CONSTITUTIVE ACTIVITY; PROTEIN-COUPLED RECEPTORS; ACTIVATION
MECHANISM; CRYSTAL-STRUCTURE; 1ST POTENT; H-2-RECEPTOR; H-4-RECEPTOR;
BINDING; CELLS
AB The human histamine H 4 receptor (hH(4)R), coexpressed with G alpha(i2) and G beta(1)gamma(2) in Sf9 insect cells, is highly constitutively active, and thioperamide [THIO; N-cyclohexyl-4-(imidazol-4yl)-1-piperidinecarbothioamide] is one of the most efficacious hH(4)R inverse agonists. High constitutive hH(4)R activity may have pathophysiological implications in which case inverse agonists may behave differently than neutral antagonists. To learn more about the structural requirements for hH(4)R inverse agonism, we investigated 25 compounds (indole, benzimidazole, and thienopyrrole derivatives) structurally related to the standard antagonist JNJ-7777120 [1-[(5chloro- 1H-indol-2-yl) carbonyl]-4-methyl-piperazine]. We characterized the compounds in radioligand binding assays by using [H-3] histamine ([H-3] HA) and in steady-state GTPase assays in the presence (antagonist mode) and absence (inverse agonist mode) of the agonist HA, yielding the following results: 1) Twenty-two compounds were inverse agonists (efficacy: 15-62% of the THIO effect), and only three compounds (12%) showed neutral antagonism. Thus, inverse agonism is far more common than neutral antagonism. 2) The inverse agonistic efficacy of the R5-monosubstituted indolederived compounds increased with the volume of R5. R5 may interact with Trp6.48 of the rotamer toggle switch and stabilize the inactive receptor conformation. 3) A subset of compounds showed large differences between the K i value ;from [H-3] HA competition binding and the EC50 value from steady-state GTPase assays, whereas the K-b values were closer to the K i values. Thus, the two-state model should be extended to a model comprising a constitutively active hH(4)R state, which can be discriminated by inverse agonists from a structurally distinct HA-stabilized active state.
C1 [Schneider, Erich H.] Univ Regensburg, Dept Pharmacol & Toxicol, Regensburg, Germany.
[Strasser, Andrea] Univ Regensburg, Dept Pharmaceut Med Chem, Regensburg, Germany.
[Thurmond, Robin L.] Johnson & Johnson Res & Dev LLC, San Diego, CA USA.
[Seifert, Roland] Hannover Med Sch, Inst Pharmacol, D-3000 Hannover, Germany.
RP Schneider, EH (reprint author), NIAID, Lab Mol Immunol, NIH, Bldg 10,Room 11N107,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM schneidere@mail.nih.gov
RI Schneider, Erich/B-9051-2016; Strasser, Andrea/F-9661-2016
OI Schneider, Erich/0000-0002-7905-4276;
FU German Research Foundation (Deutsche Forschungsgemeinschaft) [GRK 760]
FX This work was supported by the Research Training Program
(Graduierten-kolleg) "Medicinal Chemistry: Molecular
Recognition-Ligand-Receptor Interactions" of the German Research
Foundation (Deutsche Forschungsgemeinschaft) [Grant GRK 760]; and the
European Cooperation in the Field of Scientific and Technical Research
Action BM0806 (" Recent Advances in Histamine Receptor H4R
Research")
NR 39
TC 27
Z9 27
U1 0
U2 0
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD AUG 10
PY 2010
VL 334
IS 2
BP 513
EP 521
DI 10.1124/jpet.110.165977
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 626TT
UT WOS:000279990700017
PM 20484153
ER
PT J
AU Achat-Mendes, C
Grundt, P
Cao, JJ
Platt, DM
Newman, AH
Spealman, RD
AF Achat-Mendes, Cindy
Grundt, Peter
Cao, Jianjing
Platt, Donna M.
Newman, Amy Hauck
Spealman, Roger D.
TI Dopamine D3 and D2 Receptor Mechanisms in the Abuse-Related Behavioral
Effects of Cocaine: Studies with Preferential Antagonists in Squirrel
Monkeys
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID D-3 RECEPTOR; SELECTIVE ANTAGONISTS; SEEKING BEHAVIOR; PD 128907;
IN-VIVO; AGONIST; ANALOGS; LIGANDS; BINDING; BRAIN
AB Dopamine (DA) D3 and D2 receptor mechanisms are implicated in cocaine's abuse-related behavioral effects, but the relative contribution of the two receptor subtypes is only partially characterized. This study investigated the role of D3 and D2 subtype mechanisms by determining the degree to which the D3-preferring antagonist PG01037 [N-{4-[4-(2,3-dichlorophenyl)-piperazinl-yl]-trans-but-2-enyl}-4-pyridine-2-yl-benzamide HCl] and the D2-preferring antagonist L-741626 [3-[4-(4-chlorophenyl)-4hydroxypiperidin- 1-yl] methyl-1H-indole] attenuated several behavioral effects of cocaine in squirrel monkeys. Quantitative observational studies established doses of each antagonist that did not produce untoward effects, which were used in subsequent comparisons. In addition, the ability of the D3-preferring agonist PD128907 [(R-(+)-trans-3,4a, 10b-tetrahydro-4-propyl-2H, 5H[ 1] benzopyrano[4,3-b]-1,4-oxazin-9-ol)] and the D2-preferring agonist sumanirole [(R)-5,6-dihydro-5-(methylamino)-4H-imidazo[4,5,1-ij] quinolin-2(1H)-one(Z)-2-butenedioate] to reproduce cocaine's discriminative stimulus (DS) and priming effects were compared. In monkeys trained to discriminate cocaine from vehicle, both DA antagonists attenuated and both DA agonists partially reproduced cocaine's DS effects. PG01037 also selectively attenuated the cocaine-like DS effects of PD128907, whereas L-741626 attenuated the cocaine-like DS effects of both agonists. In self-administration studies, L-741626 nonselectively reduced cocaine-and food-maintained responding, whereas PG01037 was ineffective against either reinforcer. In studies involving reinstatement of extinguished cocaine seeking, both antagonists attenuated cocaine-induced reinstatement of responding, and both agonists induced at least partial reinstatement of cocaine seeking. L-741626 also attenuated sumanirole-induced, but not PD128907-induced, reinstatement of responding, whereas PG01037 was ineffective against either DA agonist. The results are consistent with a role for D3 and D2 receptor mechanisms in cocaine's DS effects and cocaine-induced reinstatement of drug seeking, but provide no evidence for a major role of D3 receptors in the direct reinforcing effects of cocaine.
C1 [Achat-Mendes, Cindy; Platt, Donna M.; Spealman, Roger D.] Harvard Univ, Sch Med, New England Primate Res Ctr, Div Neurosci, Southborough, MA 01772 USA.
[Grundt, Peter; Cao, Jianjing; Newman, Amy Hauck] NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD USA.
RP Achat-Mendes, C (reprint author), Harvard Univ, Sch Med, New England Primate Res Ctr, Div Neurosci, 1 Pine Hill Dr,POB 9102, Southborough, MA 01772 USA.
EM Cindy_Achat-Mendes@hms.harvard.edu
FU National Institutes of Health National Institute on Drug Abuse; National
Institutes of Health National Institute on Drug Abuse [DA011054,
DA01770]; National Institutes of Health National Center for Research
Resources [RR00168]
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health National Institute on Drug Abuse; the
National Institutes of Health National Institute on Drug Abuse [Grants
DA011054, DA01770]; the National Institutes of Health National Center
for Research Resources [Grant RR00168].
NR 35
TC 34
Z9 34
U1 0
U2 2
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD AUG 10
PY 2010
VL 334
IS 2
BP 556
EP 565
DI 10.1124/jpet.110.167619
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 626TT
UT WOS:000279990700022
PM 20494958
ER
PT J
AU Amar, MJA
D'Souza, W
Turner, S
Demosky, S
Sviridov, D
Stonik, J
Luchoomun, J
Voogt, J
Hellerstein, M
Sviridov, D
Remaley, AT
AF Amar, Marcelo J. A.
D'Souza, Wilissa
Turner, Scott
Demosky, Stephen
Sviridov, Denis
Stonik, John
Luchoomun, Jayraz
Voogt, Jason
Hellerstein, Marc
Sviridov, Dmitri
Remaley, Alan T.
TI 5A Apolipoprotein Mimetic Peptide Promotes Cholesterol Efflux and
Reduces Atherosclerosis in Mice
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID HIGH-DENSITY-LIPOPROTEIN; RANDOMIZED CONTROLLED-TRIAL; A-I; APOA-I;
LIPID EFFLUX; CORONARY ATHEROSCLEROSIS; DEFICIENT MICE; HDL; BINDING;
MACROPHAGES
AB Intravenous administration of apolipoprotein (apo) A-I complexed with phospholipid has been shown to rapidly reduce plaque size in both animal models and humans. Short synthetic amphipathic peptides can mimic the antiatherogenic properties of apoA-I and have been proposed as alternative therapeutic agents. In this study, we investigated the atheroprotective effect of the 5A peptide, a bihelical amphipathic peptide that specifically effluxes cholesterol from cells by ATP-binding cassette transporter 1 (ABCA1). 5A stimulated a 3.5-fold increase in ABCA1-mediated efflux from cells and an additional 2.5-fold increase after complexing it with phospholipid (1:7 mol/mol). 5A-palmitoyl oleoyl phosphatidyl choline (POPC), but not free 5A, was also found to promote cholesterol efflux by ABCG1. When incubated with human serum, 5A-POPC bound primarily to high-density lipoprotein (HDL) but also to low-density lipoprotein (LDL) and promoted the transfer of cholesterol from LDL to HDL. Twenty-four hours after intravenous injection of 5A-POPC (30 mg/kg) into apoE-knockout (KO) mice, both the cholesterol (181%) and phospholipid (219%) content of HDL significantly increased. By an in vivo cholesterol isotope dilution study and monitoring of the flux of cholesterol from radiolabeled macrophages to stool, 5A-POPC treatment was observed to increase reverse cholesterol transport. In three separate studies, 5A when complexed with various phospholipids reduced aortic plaque surface area by 29 to 53% (n = 8 per group; p < 0.02) in apoE-KO mice. No signs of toxicity from the treatment were observed during these studies. In summary, 5A promotes cholesterol efflux both in vitro and in vivo and reduces atherosclerosis in apoE-KO mice, indicating that it may be a useful alternative to apoA-I for HDL therapy.
C1 [Amar, Marcelo J. A.; Demosky, Stephen; Sviridov, Denis; Stonik, John; Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA.
[D'Souza, Wilissa; Sviridov, Dmitri] Baker Heart Res Inst, Melbourne, Vic, Australia.
[Turner, Scott; Luchoomun, Jayraz; Voogt, Jason] KineMed Inc, Emeryville, CA USA.
[Hellerstein, Marc] Univ Calif San Francisco, Gen Hosp, Dept Med, San Francisco, CA 94143 USA.
[Hellerstein, Marc] Univ Calif San Francisco, Dept Nutr Sci & Toxicol, San Francisco, CA 94143 USA.
RP Amar, MJA (reprint author), NHLBI, Lipoprot Metab Sect, Pulm & Vasc Med Branch, NIH, Bldg 10,Room 8N-228,10 Ctr Dr,MSC 1666, Bethesda, MD 20892 USA.
EM ma90x@nih.gov
RI Sviridov, Dmitri/E-7943-2010; 应, 宁宁/G-9472-2011
FU National Institutes of Health, National Heart, Lung, and Blood
Institute; National Health and Medical Research Council of Australia
[526709]; Health and Medical Research Council of Australia [586607]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Heart, Lung, and Blood
Institute. W.D. was supported by the National Health and Medical
Research Council of Australia [Australian Postgraduate Award 526709].
D.S. is a Fellow of the Health and Medical Research Council of Australia
[Award 586607].
NR 40
TC 47
Z9 48
U1 0
U2 4
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD AUG 10
PY 2010
VL 334
IS 2
BP 634
EP 641
DI 10.1124/jpet.110.167890
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 626TT
UT WOS:000279990700030
PM 20484557
ER
PT J
AU Graham, BS
McElrath, MJ
Keefer, MC
Rybczyk, K
Berger, D
Weinhold, KJ
Ottinger, J
Ferarri, G
Montefiori, DC
Stablein, D
Smith, C
Ginsberg, R
Eldridge, J
Duerr, A
Fast, P
Haynes, BF
AF Graham, Barney S.
McElrath, M. Juliana
Keefer, Michael C.
Rybczyk, Kyle
Berger, David
Weinhold, Kent J.
Ottinger, Janet
Ferarri, Guido
Montefiori, David C.
Stablein, Don
Smith, Carol
Ginsberg, Richard
Eldridge, John
Duerr, Ann
Fast, Pat
Haynes, Barton F.
CA AIDS Vaccine Evaluation Grp
TI Immunization with Cocktail of HIV-Derived Peptides in Montanide ISA-51
Is Immunogenic, but Causes Sterile Abscesses and Unacceptable
Reactogenicity
SO PLOS ONE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTES; NEUTRALIZING
ANTIBODIES; SYNTHETIC PEPTIDES; RHESUS-MONKEYS; ENVELOPE PEPTIDES;
VACCINE; GP120; ADJUVANT; SAFETY
AB Background: A peptide vaccine was produced containing B and T cell epitopes from the V3 and C4 Envelope domains of 4 subtype B HIV-1 isolates (MN, RF, CanO, & Ev91). The peptide mixture was formulated as an emulsion in incomplete Freund's adjuvant (IFA).
Methods: Low-risk, healthy adult subjects were enrolled in a randomized, placebo-controlled dose-escalation study, and selected using criteria specifying that 50% in each study group would be HLA-B7+. Immunizations were scheduled at 0, 1, and 6 months using a total peptide dose of 1 or 4 mg. Adaptive immune responses in 16 vaccine recipients and two placebo recipients after the 2 nd immunization were evaluated using neutralization assays of sera, as well as ELISpot and ICS assays of cryopreserved PBMCs to assess CD4 and CD8 T-cell responses. In addition, (51)Cr release assays were performed on fresh PBMCs following 14-day stimulation with individual vaccine peptide antigens.
Results: 24 subjects were enrolled; 18 completed 2 injections. The study was prematurely terminated because 4 vaccinees developed prolonged pain and sterile abscess formation at the injection site-2 after dose 1, and 2 after dose 2. Two other subjects experienced severe systemic reactions consisting of headache, chills, nausea, and myalgia. Both reactions occurred after the second 4 mg dose. The immunogenicity assessments showed that 6/8 vaccinees at each dose level had detectable MN-specific neutralizing (NT) activity, and 2/7 HLA-B7+ vaccinees had classical CD8 CTL activity detected. However, using both ELISpot and ICS, 8/16 vaccinees (5/7 HLA-B7+) and 0/2 controls had detectable vaccine-specific CD8 T-cell responses. Subjects with moderate or severe systemic or local reactions tended to have more frequent T cell responses and higher antibody responses than those with mild or no reactions.
Conclusions: The severity of local responses related to the formulation of these four peptides in IFA is clinically unacceptable for continued development. Both HIV-specific antibody and T cell responses were induced and the magnitude of response correlated with the severity of local and systemic reactions. If potent adjuvants are necessary for subunit vaccines to induce broad and durable immune responses, careful, incremental clinical evaluation is warranted to minimize the risk of adverse events.
C1 [Graham, Barney S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[McElrath, M. Juliana; Berger, David; Duerr, Ann] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA.
[Keefer, Michael C.] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
[Rybczyk, Kyle] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
[Weinhold, Kent J.; Ottinger, Janet; Ferarri, Guido; Montefiori, David C.; Haynes, Barton F.] Duke Univ, Sch Med, Durham, NC USA.
[Stablein, Don; Smith, Carol] EMMES Corp, Rockville, MD USA.
[Eldridge, John] Profectus Biosci Inc, Tarrytown, NY USA.
[Fast, Pat] Int AIDS Vaccine Initiat, New York, NY USA.
RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM bgraham@nih.gov
FU Division of AIDS; National Institute of Allergy and Infectious Diseases,
University of Rochester [NO1-AI-45208]; National Institute of Allergy
and Infectious Diseases, University of Washington at Seattle
[NO1-AI-45209]; National Institute of Allergy and Infectious Diseases,
Vanderbilt University [NO1-AI-45210]
FX This study was supported by the following National Institute of Allergy
and Infectious Diseases (http://www.niaid.nih.gov) contracts:
NO1-AI-45208 (University of Rochester), NO1-AI-45209 (University of
Washington at Seattle), and NO1-AI-45210 (Vanderbilt University).
Scientists from NIAID, Division of AIDS, participated in the study
design of the trial. The EMMES Corporation was the data coordinating and
statistical center operating under a Division of AIDS-sponsored
contract. John Eldridge now works at Profectus Biosciences, Inc., which
did not exist at the time of this study and had no role in the design or
funding of this work.
NR 24
TC 24
Z9 24
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 10
PY 2010
VL 5
IS 8
AR e11995
DI 10.1371/journal.pone.0011995
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 637IW
UT WOS:000280811900002
PM 20706632
ER
PT J
AU Mocellin, S
Shrager, J
Scolyer, R
Pasquali, S
Verdi, D
Marincola, FM
Briarava, M
Gobbel, R
Rossi, C
Nitti, D
AF Mocellin, Simone
Shrager, Jeff
Scolyer, Richard
Pasquali, Sandro
Verdi, Daunia
Marincola, Francesco M.
Briarava, Marta
Gobbel, Randy
Rossi, Carlo
Nitti, Donato
TI Targeted Therapy Database (TTD): A Model to Match Patient's Molecular
Profile with Current Knowledge on Cancer Biology
SO PLOS ONE
LA English
DT Article
ID PERSONALIZED MEDICINE; METASTATIC MELANOMA; CUTANEOUS MELANOMA;
TRANSLATIONAL RESEARCH; SYSTEMS BIOLOGY; DRUG TARGETS; METAANALYSIS;
CHEMOTHERAPY; ASSOCIATION; PERSPECTIVE
AB Background: The efficacy of current anticancer treatments is far from satisfactory and many patients still die of their disease. A general agreement exists on the urgency of developing molecularly targeted therapies, although their implementation in the clinical setting is in its infancy. In fact, despite the wealth of preclinical studies addressing these issues, the difficulty of testing each targeted therapy hypothesis in the clinical arena represents an intrinsic obstacle. As a consequence, we are witnessing a paradoxical situation where most hypotheses about the molecular and cellular biology of cancer remain clinically untested and therefore do not translate into a therapeutic benefit for patients.
Objective: To present a computational method aimed to comprehensively exploit the scientific knowledge in order to foster the development of personalized cancer treatment by matching the patient's molecular profile with the available evidence on targeted therapy.
Methods: To this aim we focused on melanoma, an increasingly diagnosed malignancy for which the need for novel therapeutic approaches is paradigmatic since no effective treatment is available in the advanced setting. Relevant data were manually extracted from peer-reviewed full-text original articles describing any type of anti-melanoma targeted therapy tested in any type of experimental or clinical model. To this purpose, Medline, Embase, Cancerlit and the Cochrane databases were searched.
Results and Conclusions: We created a manually annotated database (Targeted Therapy Database, TTD) where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method developed to fully exploit the available knowledge on cancer biology with the ultimate goal of fruitfully driving both preclinical and clinical research on anticancer targeted therapy. In the light of its theoretical nature, the prediction performance of this model must be validated before it can be implemented in the clinical setting.
C1 [Mocellin, Simone; Pasquali, Sandro; Verdi, Daunia; Briarava, Marta; Rossi, Carlo; Nitti, Donato] Univ Padua, Clin Chirurg Gen, Padua, Italy.
[Shrager, Jeff; Gobbel, Randy] Univ Padua, Dept Oncol & Surg Sci, Padua, Italy.
[Scolyer, Richard] Stanford Univ, Symbol Syst Program, Palo Alto, CA 94304 USA.
[Shrager, Jeff; Gobbel, Randy] CollabRx Inc, Palo Alto, CA USA.
[Scolyer, Richard] Royal Prince Alfred Hosp, Sydney, NSW, Australia.
[Scolyer, Richard] Melanoma Inst Australia, Sydney, NSW, Australia.
[Scolyer, Richard] Univ Sydney, Discipline Pathol, Sydney, NSW 2006, Australia.
[Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Marincola, Francesco M.] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA.
RP Mocellin, S (reprint author), Univ Padua, Clin Chirurg Gen, Padua, Italy.
EM simone.mocellin@unipd.it
RI Pasquali, Sandro/L-1790-2016; Rossi, Carlo Riccardo/A-7685-2010;
OI Pasquali, Sandro/0000-0003-4815-6293; Rossi, Carlo
Riccardo/0000-0001-7875-5655; Scolyer, Richard/0000-0002-8991-0013
NR 56
TC 6
Z9 6
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 10
PY 2010
VL 5
IS 8
AR e11965
DI 10.1371/journal.pone.0011965
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 637IW
UT WOS:000280811900001
PM 20706624
ER
PT J
AU Radjainia, M
Hyun, JK
Leysath, CE
Leppla, SH
Mitra, AK
AF Radjainia, Mazdak
Hyun, Jae-Kyung
Leysath, Clinton E.
Leppla, Stephen H.
Mitra, Alok K.
TI Anthrax toxin-neutralizing antibody reconfigures the protective antigen
heptamer into a supercomplex
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE anthrax toxin; neutralizing antibody 1G3; passive immunization; protein
therapeutics; single-particle analysis
ID BACILLUS-ANTHRACIS; CRYSTAL-STRUCTURE; LETHAL FACTOR;
MONOCLONAL-ANTIBODIES; ELECTRON-MICROSCOPY; CELL-RECEPTOR; PROPHYLAXIS;
COMPONENT; BINDING
AB The tripartite protein exotoxin secreted by Bacillus anthracis, a major contributor to its virulence and anthrax pathogenesis, consists of binary complexes of the protective antigen (PA) heptamer (PA63h), produced by proteolytic cleavage of PA, together with either lethal factor or edema factor. The mouse monoclonal anti-PA antibody 1G3 was previously shown to be a potent antidote that shares F(C) domain dependency with the human monoclonal antibody MDX-1303 currently under clinical development. Here we demonstrate that 1G3 instigates severe perturbation of the PA63h structure and creates a PA supercomplex as visualized by electron microscopy. This phenotype, produced by the unconventional mode of antibody action, highlights the feasibility for optimization of vaccines based on analogous structural modification of PA63h as an additional strategy for future remedies against anthrax.
C1 [Radjainia, Mazdak; Hyun, Jae-Kyung; Mitra, Alok K.] Univ Auckland, Sch Biol Sci, Auckland 1010, New Zealand.
[Leysath, Clinton E.; Leppla, Stephen H.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Mitra, AK (reprint author), Univ Auckland, Sch Biol Sci, Auckland 1010, New Zealand.
EM a.mitra@auckland.ac.nz
RI Mitra, alok/P-7800-2016
OI Mitra, alok/0000-0003-0891-5697
FU University of Auckland; University of Texas; National Institute of
Diabetes and Digestive and Kidney Diseases [R21 DK060827]; National
Institutes of Health, National Institute of Allergy and Infectious
Diseases
FX M.R. and J.-K.H. acknowledge University of Auckland doctoral
scholarships. We would like to thank Jennifer A. Maynard at the
University of Texas at Austin for the sequence of 1G3 scFv. We thank A.
Turner for maintaining the microscopes, Y. Halytskyy for support with
the BeSTGRID and CERES computer cluster at University of Auckland, and
David Waite for help with image digitization and particle selection. The
work was supported in part by an R21 DK060827 grant from the National
Institute of Diabetes and Digestive and Kidney Diseases (to A.K.M.) and
in part by the Intramural Research Program of the National Institutes of
Health, National Institute of Allergy and Infectious Diseases.
NR 27
TC 11
Z9 11
U1 0
U2 4
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 AUG 10
PY 2010
VL 107
IS 32
BP 14070
EP 14074
DI 10.1073/pnas.1006473107
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 636UD
UT WOS:000280767700020
PM 20660775
ER
PT J
AU Miller, Y
Ma, BY
Tsai, CJ
Nussinov, R
AF Miller, Yifat
Ma, Buyong
Tsai, Chung-Jung
Nussinov, Ruth
TI Hollow core of Alzheimer's A beta(42) amyloid observed by cryoEM is
relevant at physiological pH
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE amyloid fibril structures; polymorphism; self-assembly
ID X-RAY-DIFFRACTION; BETA FIBRIL FORMATION; ELECTRON-MICROSCOPY;
STRUCTURAL BASIS; POLYMORPHISM; A-BETA(1-40); CONFORMATION; AGGREGATION;
FILAMENTS; PEPTIDES
AB Recent cryoEM density maps of A beta(42) fibrils obtained at low pH revealed two protofilaments winding around a hollow core raising the question if such tubular structures also exist at physiological pH. Based on the cryoEM measurements and on NMR data, we probe amyloid fibril organizations corresponding to the observed cryoEM density map. Our study demonstrates that the tubular A beta(42) fibril models exist at both acidic and physiological pH; however, the relative populations of the polymorphic models shift with pH. At acidic pH, the hollow core model exhibits higher population than the other models; at physiological pH, although it is less populated compared to the other models, structurally, it is stable and represents 8% of the population. We observe that only models with C termini facing the external surface of the fibril retain the hollow core under acidic and physiological conditions with dimensions similar to those observed by cryoEM; on the other hand, the hydrophobic effect shrinks the tubular cavity in the alternative organization. The existence of the hollow core fibril at physiological pH emphasizes the need to examine toxic effects of minor oligomeric species with unique organizations.
C1 [Ma, Buyong; Tsai, Chung-Jung; Nussinov, Ruth] NCI, Ctr Canc Res Nanobiol, Basic Sci Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA.
[Miller, Yifat] NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
RP Ma, BY (reprint author), NCI, Ctr Canc Res Nanobiol, Basic Sci Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA.
EM mabuyong@mail.nih.gov; ruthnu@helix.nih.gov
RI Ma, Buyong/F-9491-2011
OI Ma, Buyong/0000-0002-7383-719X
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research
FX All simulations had been performed using the high-performance
computational facilities of the Biowulf PC/Linux cluster at the National
Institutes of Health (NIH), Bethesda, MD (http://biowulf.nih.gov). This
project has been funded in whole or in part with federal funds from the
National Cancer Institute, National Institutes of Health, under Contract
HHSN261200800001E. This research was supported (in part) by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
NR 33
TC 50
Z9 50
U1 2
U2 16
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 AUG 10
PY 2010
VL 107
IS 32
BP 14128
EP 14133
DI 10.1073/pnas.1004704107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 636UD
UT WOS:000280767700030
PM 20660780
ER
PT J
AU Ma, T
Jham, BC
Hu, JD
Friedman, ER
Basile, JR
Molinolo, A
Sodhi, A
Montaner, S
AF Ma, Tao
Jham, Bruno C.
Hu, Jiadi
Friedman, Eitan R.
Basile, John R.
Molinolo, Alfredo
Sodhi, Akrit
Montaner, Silvia
TI Viral G protein-coupled receptor up-regulates Angiopoietin-like 4
promoting angiogenesis and vascular permeability in Kaposi's sarcoma
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE Kaposi's sarcoma-associated herpesvirus; human herpesvirus-8; Rho
GTPase; endothelial cell
ID ENDOTHELIAL GROWTH-FACTOR; CHEMOKINE RECEPTOR; HERPESVIRUS;
HUMAN-HERPESVIRUS-8; INHIBITION; TUMORS; CELLS; METASTASIS; ACTIVATION;
EXPRESSION
AB Kaposi's sarcoma (KS) is an enigmatic vascular tumor thought to be a consequence of dysregulated expression of the human herpesvirus-8 (HHV-8 or KSHV)-encoded G protein-coupled receptor (vGPCR). Indeed, transgenic animals expressing vGPCR manifest vascular tumors histologically identical to human KS, with expression of the viral receptor limited to a few cells, suggestive of a paracrine mechanism for vGPCR tumorigenesis. Both human and vGPCR experimental KS lesions are characterized by prominent angiogenesis and vascular permeability attributed to the release of angiogenic molecules, most notably vascular endothelial growth factor. However, the relative contribution of these paracrine mediators to the angiogenic and exudative phenotype of KS lesions remains unclear. Here we show that vGPCR up-regulation of Angiopoietin-like 4 (ANGPTL4) plays a prominent role in promoting the angiogenesis and vessel permeability observed in KS. Indeed, ANGPTL4 expression is a hallmark of vGPCR experimental and human KS lesions. Inhibition of ANGPTL4 effectively blocks vGPCR promotion of the angiogenic switch and vascular leakage in vitro and tumorigenesis in vivo. These observations suggest that ANGPTL4 is a previously unrecognized target for the treatment of patients with KS. As angiogenesis and increased vessel permeability are common themes in all solid tumors, these findings may have a broad impact on our understanding and treatment of cancer.
C1 [Ma, Tao; Jham, Bruno C.; Hu, Jiadi; Friedman, Eitan R.; Basile, John R.; Montaner, Silvia] Univ Maryland, Dept Oncol & Diagnost Sci, Baltimore, MD 21201 USA.
[Basile, John R.; Montaner, Silvia] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Molinolo, Alfredo] Natl Inst Craniofacial & Dent Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Sodhi, Akrit] Johns Hopkins Univ, Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
RP Montaner, S (reprint author), Univ Maryland, Dept Oncol & Diagnost Sci, Baltimore, MD 21201 USA.
EM smontaner@umaryland.edu
RI Jham, Bruno/F-1596-2013
FU National Cancer Institute, National Institutes of Health [R01CA119911];
CNPq-Brazil
FX We thank Drs. J. Silvio Gutkind (NIDCR, NIH, Bethesda, MD), Stephane
Germain (INSERM, Paris, France), Gary S. Hayward (Johns Hopkins
University, Baltimore, MD) for kindly providing valuable reagents for
this manuscript, and Youngmi Ji for her help with the microarrays
experiments. This work was supported by National Cancer Institute,
National Institutes of Health Grant R01CA119911. B.C.J. received a
predoctoral fellowship from CNPq-Brazil.
NR 38
TC 55
Z9 58
U1 0
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 AUG 10
PY 2010
VL 107
IS 32
BP 14363
EP 14368
DI 10.1073/pnas.1001065107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 636UD
UT WOS:000280767700070
PM 20660728
ER
PT J
AU Budde, MD
Frank, JA
AF Budde, Matthew D.
Frank, Joseph A.
TI Neurite beading is sufficient to decrease the apparent diffusion
coefficient after ischemic stroke
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE acute ischemia; diffusion-weighted MRI; cell swelling; Monte Carlo
simulation
ID MYELINATED NERVE-FIBERS; WATER DIFFUSION; RAT-BRAIN; IN-VIVO; AXONAL
INJURY; SPINAL-CORD; SPREADING DEPRESSION; CEREBRAL-ISCHEMIA;
THEORETICAL-MODEL; WHITE-MATTER
AB Diffusion-weighted MRI (DWI) is a sensitive and reliable marker of cerebral ischemia. Within minutes of an ischemic event in the brain, the microscopic motion of water molecules measured with DWI, termed the apparent diffusion coefficient (ADC), decreases within the infarcted region. However, although the change is related to cell swelling, the precise pathological mechanism remains elusive. We show that focal enlargement and constriction, or beading, in axons and dendrites are sufficient to substantially decrease ADC. We first derived a biophysical model of neurite beading, and we show that the beaded morphology allows a larger volume to be encompassed within an equivalent surface area and is, therefore, a consequence of osmotic imbalance after ischemia. The DWI experiment simulated within the model revealed that intracellular ADC decreased by 79% in beaded neurites compared with the unbeaded form. To validate the model experimentally, excised rat sciatic nerves were subjected to stretching, which induced beading but did not cause a bulk shift of water into the axon (i.e., swelling). Beading-induced changes in cell-membrane morphology were sufficient to significantly hinder water mobility and thereby decrease ADC, and the experimental measurements were in excellent agreement with the simulated values. This is a demonstration that neurite beading accurately captures the diffusion changes measured in vivo. The results significantly advance the specificity of DWI in ischemia and other acute neurological injuries and will greatly aid the development of treatment strategies to monitor and repair damaged brain in both clinical and experimental settings.
C1 [Budde, Matthew D.; Frank, Joseph A.] Natl Inst Biomed Imaging & Bioengn, Ctr Clin, NIH, Bethesda, MD 20892 USA.
[Frank, Joseph A.] Natl Inst Biomed Imaging & Bioengn, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Budde, MD (reprint author), Natl Inst Biomed Imaging & Bioengn, Ctr Clin, NIH, Bethesda, MD 20892 USA.
EM buddem@mail.nih.gov
FU National Institutes of Health [U24-CA83060]; Clinical Center at the
National Institutes of Health
FX We thank the Biomedical Magnetic Resonance Laboratory at Washington
University in St. Louis, MO, for use of their computational resources
supported in part by National Institutes of Health Grant U24-CA83060
(J.J.H. Ackerman, PI) and Dr. Matt Hall for assistance with the Camino
software. This work was supported by the Intramural Research Program of
Clinical Center at the National Institutes of Health and an National
Institutes of Health Predoctoral National Research Service Award
fellowship (to M. D. B).
NR 51
TC 52
Z9 53
U1 0
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 AUG 10
PY 2010
VL 107
IS 32
BP 14472
EP 14477
DI 10.1073/pnas.1004841107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 636UD
UT WOS:000280767700089
PM 20660718
ER
PT J
AU Simard, EP
Pfeiffer, RM
Engels, EA
AF Simard, Edgar P.
Pfeiffer, Ruth M.
Engels, Eric A.
TI Spectrum of Cancer Risk Late After AIDS Onset in the United States
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-INFECTED PERSONS; ANAL
INTRAEPITHELIAL NEOPLASIA; HODGKIN-LYMPHOMA; HUMAN-PAPILLOMAVIRUS;
POSITIVE MEN; LUNG-CANCER; ADULTS; INDIVIDUALS; PEOPLE
AB Background: Persons living with AIDS today remain at elevated cancer risk. Highly active antiretroviral therapy (HAART), widely available since 1996, prolongs life, but immune function is not fully restored. We conducted this study to assess long-term cancer risk among persons with AIDS relative to the general population and the impact of HAART on cancer incidence.
Methods: Records of 263 254 adults and adolescents with AIDS (1980-2004) from 15 US regions were matched to cancer registries to capture incident cancers during years 3 through 5 and 6 through 10 after AIDS onset. Standardized incidence ratios (SIRs) were used to assess risks relative to the general population. Rate ratios (RRs) were used to compare cancer incidence before and after 1996 to assess the impact of availability of HAART.
Results: Risk was elevated for the 2 major AIDS-defining cancers: Kaposi sarcoma (SIRs, 5321 and 1347 in years 3-5 and 6-10, respectively) and non-Hodgkin lymphoma (SIRs, 32 and 15). Incidence of both malignancies declined in the HAART era (1996-2006). Risk was elevated for all non AIDS-defining cancers combined (SIRs, 1.7 and 1.6 in years 3-5 and 6-10, respectively) and for the following specific non AIDS-defining cancers: Hodgkin lymphoma and cancers of the oral cavity and/or pharynx, tongue, anus, liver, larynx, lung and/or bronchus, and penis. Anal cancer incidence increased between 1990-1995 and 1996-2006 (RR, 2.9; 95% confidence interval [CI], 2.1-4.0), as did that of Hodgkin lymphoma (RR, 2.0; 95% CI, 1.3-2.9).
Conclusion: Among people who survived for several years or more after an AIDS diagnosis, we observed high risks of AIDS-defining cancers and increasing incidence of anal cancer and Hodgkin lymphoma.
C1 [Engels, Eric A.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA.
[Simard, Edgar P.] Univ Med & Dent New Jersey, Dept Epidemiol, Sch Publ Hlth, Piscataway, NJ 08854 USA.
RP Engels, EA (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 7076, Rockville, MD 20892 USA.
EM engelse@mail.nih.gov
RI Simard, Edgar/G-4552-2010
OI Simard, Edgar/0000-0001-8093-2067
FU National Cancer Institute, National Institutes of Health, Bethesda,
Maryland
FX This study was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health, Bethesda,
Maryland.
NR 41
TC 51
Z9 51
U1 1
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD AUG 9
PY 2010
VL 170
IS 15
BP 1337
EP 1345
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 635JN
UT WOS:000280651500008
PM 20696958
ER
PT J
AU Vang, AG
Ben-Sasson, SZ
Dong, HL
Kream, B
DeNinno, MP
Claffey, MM
Housley, W
Clark, RB
Epstein, PM
Brocke, S
AF Vang, Amanda G.
Ben-Sasson, Shlomo Z.
Dong, Hongli
Kream, Barbara
DeNinno, Michael P.
Claffey, Michelle M.
Housley, William
Clark, Robert B.
Epstein, Paul M.
Brocke, Stefan
TI PDE8 Regulates Rapid Teff Cell Adhesion and Proliferation Independent of
ICER
SO PLOS ONE
LA English
DT Article
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CYCLIC-NUCLEOTIDE
PHOSPHODIESTERASES; PROTEIN-KINASE-A; RELAPSING MULTIPLE-SCLEROSIS;
CENTRAL-NERVOUS-SYSTEM; BLOOD-BRAIN-BARRIER; CAMP-SPECIFIC
PHOSPHODIESTERASE; DIFFERENTIAL EXPRESSION; ADENOSINE RECEPTORS;
LEUKOCYTE ADHESION
AB Background: Abolishing the inhibitory signal of intracellular cAMP by phosphodiesterases (PDEs) is a prerequisite for effector T (Teff) cell function. While PDE4 plays a prominent role, its control of cAMP levels in Teff cells is not exclusive. T cell activation has been shown to induce PDE8, a PDE isoform with 40- to 100-fold greater affinity for cAMP than PDE4. Thus, we postulated that PDE8 is an important regulator of Teff cell functions.
Methodology/Principal Findings: We found that Teff cells express PDE8 in vivo. Inhibition of PDE8 by the PDE inhibitor dipyridamole (DP) activates cAMP signaling and suppresses two major integrins involved in Teff cell adhesion. Accordingly, DP as well as the novel PDE8-selective inhibitor PF-4957325-00 suppress firm attachment of Teff cells to endothelial cells. Analysis of downstream signaling shows that DP suppresses proliferation and cytokine expression of Teff cells from Crem(-/-) mice lacking the inducible cAMP early repressor (ICER). Importantly, endothelial cells also express PDE8. DP treatment decreases vascular adhesion molecule and chemokine expression, while upregulating the tight junction molecule claudin-5. In vivo, DP reduces CXCL12 gene expression as determined by in situ probing of the mouse microvasculature by cell-selective laser-capture microdissection.
Conclusion/Significance: Collectively, our data identify PDE8 as a novel target for suppression of Teff cell functions, including adhesion to endothelial cells.
C1 [Vang, Amanda G.; Housley, William; Clark, Robert B.; Brocke, Stefan] Univ Connecticut, Ctr Hlth, Dept Immunol, Farmington, CT USA.
[Vang, Amanda G.; Dong, Hongli; Epstein, Paul M.; Brocke, Stefan] Univ Connecticut, Ctr Hlth, Dept Pharmacol, Farmington, CT USA.
[Ben-Sasson, Shlomo Z.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Dong, Hongli; Epstein, Paul M.] Univ Connecticut, Ctr Hlth, Dept Cell Biol, Farmington, CT USA.
[Kream, Barbara; Clark, Robert B.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA.
[Kream, Barbara] Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, Farmington, CT USA.
[DeNinno, Michael P.; Claffey, Michelle M.] Pfizer Global Res & Dev, Groton Labs, Groton, CT USA.
RP Vang, AG (reprint author), Univ Connecticut, Ctr Hlth, Dept Immunol, Farmington, CT USA.
EM sbrocke@uchc.edu
FU Connecticut Breast Health Initiative; Connecticut Department of Public
Health; Smart Family Foundation; National Institutes of Health (NIH)
[1R56 AI 072533-01 A1]; National Multiple Sclerosis Society [RG
4070-A-6]
FX This work was supported by institutional start up funds to S.B., the
Connecticut Breast Health Initiative (P.E. and S.B.), the Connecticut
Department of Public Health (P.E. and S.B.), the Smart Family Foundation
(P.E.), National Institutes of Health (NIH) grant 1R56 AI 072533-01 A1
(R.C.), and National Multiple Sclerosis Society grant RG 4070-A-6
(R.C.). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 72
TC 24
Z9 26
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 9
PY 2010
VL 5
IS 8
AR e12011
DI 10.1371/journal.pone.0012011
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 636XC
UT WOS:000280776800009
PM 20711499
ER
PT J
AU Zen, A
Micheletti, C
Keskin, O
Nussinov, R
AF Zen, Andrea
Micheletti, Cristian
Keskin, Ozlem
Nussinov, Ruth
TI Comparing interfacial dynamics in protein-protein complexes: an elastic
network approach
SO BMC STRUCTURAL BIOLOGY
LA English
DT Article
ID NORMAL-MODE CALCULATIONS; HOT-SPOTS; CONFORMATIONAL-CHANGES; DECOMPOSING
PROTEINS; MOLECULAR-DYNAMICS; CONSERVED RESIDUES; INTRINSIC MOTIONS;
RESOURCE UNIPROT; ADENYLATE KINASE; SINGLE-PARAMETER
AB Background: The transient, or permanent, association of proteins to form organized complexes is one of the most common mechanisms of regulation of biological processes. Systematic physico-chemical studies of the binding interfaces have previously shown that a key mechanism for the formation/stabilization of dimers is the steric and chemical complementarity of the two semi-interfaces. The role of the fluctuation dynamics at the interface of the interacting subunits, although expectedly important, proved more elusive to characterize. The aim of the present computational study is to gain insight into salient dynamics-based aspects of protein-protein interfaces.
Results: The interface dynamics was characterized by means of an elastic network model for 22 representative dimers covering three main interface types. The three groups gather dimers sharing the same interface but with good (type I) or poor (type II) similarity of the overall fold, or dimers sharing only one of the semi-interfaces (type III). The set comprises obligate dimers, which are complexes for which no structural representative of the free form (s) is available. Considerations were accordingly limited to bound and unbound forms of the monomeric subunits of the dimers. We proceeded by first computing the mobility of amino acids at the interface of the bound forms and compare it with the mobility of (i) other surface amino acids (ii) interface amino acids in the unbound forms. In both cases different dynamic patterns were observed across interface types and depending on whether the interface belongs to an obligate or non-obligate complex.
Conclusions: The comparative investigation indicated that the mobility of amino acids at the dimeric interface is generally lower than for other amino acids at the protein surface. The change in interfacial mobility upon removing "in silico" the partner monomer (unbound form) was next found to be correlated with the interface type, size and obligate nature of the complex. In particular, going from the unbound to the bound forms, the interfacial mobility is noticeably reduced for dimers with type I interfaces, while it is largely unchanged for type II ones. The results suggest that these structurally-and biologically-different types of interfaces are stabilized by different balancing mechanisms between enthalpy and conformational entropy.
C1 [Zen, Andrea; Micheletti, Cristian] SISSA, Democritos CNR IOM, I-34136 Trieste, Italy.
[Zen, Andrea; Micheletti, Cristian] Italian Inst Technol, I-34136 Trieste, Italy.
[Keskin, Ozlem] Koc Univ, Ctr Computat Biol & Bioinformat, TR-34450 Rumelifeneri Yolu, Sariyer Istanbu, Turkey.
[Keskin, Ozlem] Koc Univ, Coll Engn, TR-34450 Rumelifeneri Yolu, Sariyer Istanbu, Turkey.
[Nussinov, Ruth] NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
RP Micheletti, C (reprint author), SISSA, Democritos CNR IOM, Via Bonomea 265, I-34136 Trieste, Italy.
EM michelet@sissa.it
OI Zen, Andrea/0000-0002-7648-4078
FU Italian Ministry of Education
FX This project has been funded in part by the Italian Ministry of
Education, by Democritos CNR-IOM and in part with Federal funds from the
National Cancer Institute, National Institutes of Health, under contract
number HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U. S. Government.
This research was supported (in part) by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research. O.K.
acknowledges funds from TUBITAK Research Grant No: 109T343.
NR 72
TC 18
Z9 18
U1 0
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6807
J9 BMC STRUCT BIOL
JI BMC Struct. Biol.
PD AUG 8
PY 2010
VL 10
AR 26
DI 10.1186/1472-6807-10-26
PG 13
WC Biophysics
SC Biophysics
GA 655MV
UT WOS:000282255000001
PM 20691107
ER
PT J
AU Newman, ZL
Crown, D
Leppla, SH
Moayeri, M
AF Newman, Zachary L.
Crown, Devorah
Leppla, Stephen H.
Moayeri, Mahtab
TI Anthrax lethal toxin activates the inflammasome in sensitive rat
macrophages
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Anthrax; Lethal toxin; Inflammasome; Caspase-1; Nlrp1
ID CASPASE-1 ACTIVATION; NALP1; INTERNALIZATION; SUSCEPTIBILITY; VITILIGO;
DISEASE; SHOCK
AB Anthrax lethal toxin (LT) is an important virulence factor for Bacillus anthracis. In mice, LT lyses macrophages from certain inbred strains in less than 2 h by activating the Nlrp1b inflammasome and caspase-1, while macrophages from other strains remain resistant to the toxin's effects. We analyzed LT effects in toxin-sensitive and resistant rat macrophages to test if a similar pathway was involved in rat macrophage death. LT activates caspase-1 in rat macrophages from strains harboring LT-sensitive macrophages in a manner similar to that in toxin-sensitive murine macrophages. This activation of caspase-1 is dependent on proteasome activity, and sensitive macrophages are protected from LT's lytic effects by lactacystin. Proteasome inhibition also delayed the death of rats in response to LT, confirming our previous data implicating the rat Nlrp1 inflammasome in animal death. Quinidine, caspase-1 inhibitors, the cathepsin B inhibitor CA-074Me, and heat shock also protected rat macrophages from LT toxicity. These data support the existence of an active functioning LT-responsive Nlrp1 inflammasome in rat macrophages. The activation of the rat Nlrp1 inflammasome is required for LT-mediated rat macrophage lysis and contributes to animal death. Published by Elsevier Inc.
C1 [Newman, Zachary L.; Crown, Devorah; Leppla, Stephen H.; Moayeri, Mahtab] NIAID, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA.
RP Moayeri, M (reprint author), NIAID, Lab Bacterial Dis, NIH, 33 North Dr,Bldg 33,Room 1W20B, Bethesda, MD 20892 USA.
EM newmanz@niaid.nih.gov; crownd@niaid.nih.gov; sleppla@niaid.nih.gov;
mmoayeri@niaid.nih.gov
FU NIH, National Institute of Allergy and Infectious Diseases
FX We thank Rasem Fattah for toxin preparation. This research was supported
by the Intramural Research Program of the NIH, National Institute of
Allergy and Infectious Diseases.
NR 24
TC 20
Z9 22
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
EI 1090-2104
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD AUG 6
PY 2010
VL 398
IS 4
BP 785
EP 789
DI 10.1016/j.bbrc.2010.07.039
PG 5
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 638NJ
UT WOS:000280901300029
PM 20638366
ER
PT J
AU Ton-Hoang, B
Pastemak, C
Siguier, P
Guynet, C
Hickman, AB
Dyda, F
Sommer, S
Chandler, M
AF Ton-Hoang, Bao
Pastemak, Cecile
Siguier, Patricia
Guynet, Catherine
Hickman, Alison Burgess
Dyda, Fred
Sommer, Suzanne
Chandler, Michael
TI Single-Stranded DNA Transposition Is Coupled to Host Replication
SO CELL
LA English
DT Article
ID ESCHERICHIA-COLI MUTANTS; DEINOCOCCUS-RADIODURANS; YERSINIA-PESTIS;
INSERTION-SEQUENCE; GENOME SEQUENCE; IN-VITRO; ARREST; PROTEIN; FORK;
TRANSCRIPTION
AB DNA transposition has contributed significantly to evolution of eukaryotes and prokaryotes. Insertion sequences (ISs) are the simplest prokaryotic trans-posons and are divided into families on the basis of their organization and transposition mechanism. Here, we describe a link between transposition of IS608 and ISDra2, both members of the IS200/IS605 family, which uses obligatory single-stranded DNA intermediates, and the host replication fork. Replication direction through the IS plays a crucial role in excision: activity is maximal when the "top'' IS strand is located on the lagging-strand template. Excision is stimulated upon transient inactivation of replicative helicase function or inhibition of Okazaki fragment synthesis. IS608 insertions also exhibit an orientation preference for the lagging-strand template and insertion can be specifically directed to stalled replication forks. An in silico genomic approach provides evidence that dissemination of other IS200/IS605 family members is also linked to host replication.
C1 [Ton-Hoang, Bao; Siguier, Patricia; Guynet, Catherine; Chandler, Michael] CNRS, Lab Microbiol & Genet Mol, UMR 5100, F-31062 Toulouse, France.
[Pastemak, Cecile; Sommer, Suzanne] Univ Paris 11, CNRS, Inst Genet & Microbiol,UMR 8621, Lab Rech Correspondant Commissariat Energie Atom, F-91405 Orsay, France.
[Hickman, Alison Burgess; Dyda, Fred] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Ton-Hoang, B (reprint author), CNRS, Lab Microbiol & Genet Mol, UMR 5100, 118 Route Narbonne, F-31062 Toulouse, France.
EM bao.tonhoang@ibcg.biotoul.fr; michael.chandler@ibcg.biotoul.fr
RI Guynet, Catherine/A-4815-2011;
OI Chandler, Michael/0000-0002-0292-6662
FU Centre National de Recherche Scientifique (France); ANR; European
contract [LSHM-CT-2005-019023]; Commissariat a l'Energie Atomique and
Electricite de France (France); National Institute of Diabetes and
Digestive and Kidney Diseases
FX We would like to thank members of the "Mobile Genetic Elements'' group,
A. Bailone, P. Polard, and D. Lane for discussions, G. Coste and B.
Marty for expert technical assistance, L. Lavatine for guiding us
through the mysteries of statistics, A. Varani for identifying a
representative oligonucleotide sequence used in the PCR mapping for the
D. radiodurans genome, and the Institut Curie for the use of the
137Cs irradiation system. This work was supported by:
intramural funding from the Centre National de Recherche Scientifique
(France), in its later stages by ANR grant Mobigen (M.C. and S.S.),
European contract LSHM-CT-2005-019023 (M.C.), and the Commissariat a
l'Energie Atomique and Electricite de France (France; S.S.). At the
National Institutes of Health, this work was supported by the Intramural
Program of the National Institute of Diabetes and Digestive and Kidney
Diseases.
NR 52
TC 34
Z9 35
U1 0
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD AUG 6
PY 2010
VL 142
IS 3
BP 398
EP 408
DI 10.1016/j.cell.2010.06.034
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 634TS
UT WOS:000280609100017
PM 20691900
ER
PT J
AU Wang, G
Chen, HW
Oktay, Y
Zhang, J
Allen, EL
Smith, GM
Fan, KC
Hong, JS
French, SW
McCaffery, JM
Lightowlers, RN
Morse, HC
Koehler, CM
Teitell, MA
AF Wang, Geng
Chen, Hsiao-Wen
Oktay, Yavuz
Zhang, Jin
Allen, Eric L.
Smith, Geoffrey M.
Fan, Kelly C.
Hong, Jason S.
French, Samuel W.
McCaffery, J. Michael
Lightowlers, Robert N.
Morse, Herbert C., III
Koehler, Carla M.
Teitell, Michael A.
TI PNPASE Regulates RNA Import into Mitochondria
SO CELL
LA English
DT Article
ID HUMAN POLYNUCLEOTIDE PHOSPHORYLASE; HELA-CELL MITOCHONDRIA;
INTERMEMBRANE SPACE; POLY(A) POLYMERASE; RIBOSOMAL-RNA; P-ACTIVITY;
PROTEIN; LIVER; MACHINERY; CONTAINS
AB RNA import into mammalian mitochondria is considered essential for replication, transcription, and translation of the mitochondrial genome but the pathway(s) and factors that control this import are poorly understood. Previously, we localized polynucleotide phosphorylase (PNPASE), a 3' -> 5' exoribonuclease and poly-A polymerase, in the mitochondrial intermembrane space, a location lacking resident RNAs. Here, we show a new role for PNPASE in regulating the import of nuclear-encoded RNAs into the mitochondrial matrix. PNPASE reduction impaired mitochondrial RNA processing and polycistronic transcripts accumulated. Augmented import of RNase P, 5S rRNA, and MRP RNAs depended on PNPASE expression and PNPASE-imported RNA interactions were identified. PNPASE RNA processing and import activities were separable and a mitochondrial RNA targeting signal was isolated that enabled RNA import in a PNPASE-dependent manner. Combined, these data strongly support an unanticipated role for PNPASE in mediating the translocation of RNAs into mitochondria.
C1 [Wang, Geng; Oktay, Yavuz; Koehler, Carla M.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA.
[Koehler, Carla M.; Teitell, Michael A.] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA.
[Teitell, Michael A.] Univ Calif Los Angeles, Calif NanoSyst Inst, Broad Stem Cell Res Ctr, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA.
[Teitell, Michael A.] Univ Calif Los Angeles, Ctr Cell Control, Los Angeles, CA 90095 USA.
[Chen, Hsiao-Wen] Univ Calif Irvine, Ctr Mol & Mitochondrial Med & Genet, Irvine, CA 92697 USA.
[Zhang, Jin; Allen, Eric L.; Smith, Geoffrey M.; Fan, Kelly C.; Hong, Jason S.; French, Samuel W.; Teitell, Michael A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
[McCaffery, J. Michael] Johns Hopkins Univ, Dept Biol, Integrated Imaging Ctr, Baltimore, MD 21218 USA.
[Lightowlers, Robert N.] Newcastle Univ, Inst Ageing & Hlth, Mitochondrial Res Grp, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Morse, Herbert C., III] NIAID, Immunopathol Lab, NIH, Rockville, MD 20852 USA.
RP Koehler, CM (reprint author), Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA.
EM koehler@chem.ucla.edu; mteitell@mednet.ucla.edu
RI Oktay, Yavuz/F-2703-2015; Oktay, Yavuz/G-4794-2015;
OI Oktay, Yavuz/0000-0002-0158-2693; Morse, Herbert/0000-0002-9331-3705
FU NIH [R01GM061721, R01GM073981, R01CA90571, PN2EY018228, K22CA120147];
NIH, National Institute of Allergy and Infectious Diseases; Muscular
Dystrophy Association [022398]; American Heart Association [0640076N];
California Institute of Regenerative Medicine [RS1-00313, RB1-01397]
FX We thank Michelle Husain for expertise in TEM. Supported by NIH grants
R01GM061721 and R01GM073981 (C.M.K.), R01CA90571 (M.A.T.) and
PN2EY018228 (Roadmap for Medical Research Nanomedicine Initiative)
(M.A.T.), and K22CA120147 (S.W.F.), the Intramural Research Program of
the NIH, National Institute of Allergy and Infectious Diseases (H.C.M.
III), the Muscular Dystrophy Association 022398 (C.M.K.), the American
Heart Association 0640076N (C.M.K.), and the California Institute of
Regenerative Medicine (RS1-00313 and RB1-01397, M.A.T.). C.M.K. is an
Established Investigator of the American Heart Association and M.A.T. is
a Scholar of the Leukemia and Lymphoma Society.
NR 37
TC 117
Z9 123
U1 4
U2 24
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD AUG 6
PY 2010
VL 142
IS 3
BP 456
EP 467
DI 10.1016/j.cell.2010.06.035
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 634TS
UT WOS:000280609100022
PM 20691904
ER
PT J
AU Iglesias-Bartolome, R
Gutkind, JS
AF Iglesias-Bartolome, Ramiro
Gutkind, J. Silvio
TI Keeping the Epidermal Stem Cell Niche in Shape
SO CELL STEM CELL
LA English
DT Editorial Material
ID SERUM RESPONSE FACTOR; ACTIN
C1 [Iglesias-Bartolome, Ramiro; Gutkind, J. Silvio] NIDR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
RP Gutkind, JS (reprint author), NIDR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
EM sg39v@nih.gov
RI Gutkind, J. Silvio/A-1053-2009; Iglesias-Bartolome, Ramiro/H-4460-2014
OI Iglesias-Bartolome, Ramiro/0000-0002-0792-1254
NR 10
TC 5
Z9 5
U1 0
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
J9 CELL STEM CELL
JI Cell Stem Cell
PD AUG 6
PY 2010
VL 7
IS 2
BP 143
EP 145
DI 10.1016/j.stem.2010.07.008
PG 3
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA 641EK
UT WOS:000281107400005
PM 20682441
ER
PT J
AU Maunakea, AK
Chepelev, I
Zhao, KJ
AF Maunakea, Alika K.
Chepelev, Iouri
Zhao, Keji
TI Epigenome Mapping in Normal and Disease States
SO CIRCULATION RESEARCH
LA English
DT Article
DE epigenetics; genetics; gene expression; gene regulation
ID TRANSGENERATIONAL EPIGENETIC INHERITANCE; ENDOCRINE DISRUPTOR
VINCLOZOLIN; EUKARYOTIC DNA METHYLATION; HISTONE MODIFICATIONS; HUMAN
GENOME; GENE-EXPRESSION; MAMMALIAN DEVELOPMENT; CHROMATIN SIGNATURES;
BLOOD-PRESSURE; HUMAN-CELLS
AB Epigenomes are comprised, in part, of all genome-wide chromatin modifications, including DNA methylation and histone modifications. Unlike the genome, epigenomes are dynamic during development and differentiation to establish and maintain cell type-specific gene expression states that underlie cellular identity and function. Chromatin modifications are particularly labile, providing a mechanism for organisms to respond and adapt to environmental cues. Results from studies in animal models clearly demonstrate that epigenomic variability leads to phenotypic variability, including susceptibility to disease that is not recognized at the DNA sequence level. Thus, capturing epigenomic information is invaluable for comprehensively understanding development, differentiation, and disease. Herein, we provide a brief overview of epigenetic processes, how they are relevant to human health, and review studies using technologies that enable epigenome mapping. We conclude by describing feasible applications of epigenome mapping, focusing on epigenome-wide association studies (eGWAS), which have the potential to revolutionize current studies of human diseases and will likely promote the discovery of novel diagnostic, preventative, and treatment strategies. (Circ Res. 2010;107:327-339.)
C1 [Maunakea, Alika K.; Chepelev, Iouri; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
RP Zhao, KJ (reprint author), NHLBI, Lab Mol Immunol, NIH, 9000 Rockville Pike,Bldg 10,Room 7B04, Bethesda, MD 20892 USA.
EM zhaok@nhlbi.nih.gov
FU NIH; National Heart, Lung, and Blood Institute
FX This work was supported by the Division of Intramural Research Program
of the NIH, National Heart, Lung, and Blood Institute.
NR 173
TC 67
Z9 70
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD AUG 6
PY 2010
VL 107
IS 3
BP 327
EP 339
DI 10.1161/CIRCRESAHA.110.222463
PG 13
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 634RX
UT WOS:000280603000004
PM 20689072
ER
PT J
AU Cavanaugh, NA
Beard, WA
Wilson, SH
AF Cavanaugh, Nisha A.
Beard, William A.
Wilson, Samuel H.
TI DNA Polymerase beta Ribonucleotide Discrimination INSERTION,
MISINSERTION, EXTENSION, AND CODING
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HIV-1 REVERSE-TRANSCRIPTASE; I KLENOW FRAGMENT; ESCHERICHIA-COLI;
NUCLEOTIDE INCORPORATION; TERNARY COMPLEXES; SINGLE RESIDUE;
MINOR-GROOVE; ABASIC SITE; FIDELITY; REPLICATION
AB DNA polymerases must select nucleotides that preserve Watson-Crick base pairing rules and choose substrates with the correct (deoxyribose) sugar. Sugar discrimination represents a great challenge because ribonucleotide triphosphates are present at much higher cellular concentrations than their deoxy-counterparts. Although DNA polymerases discriminate against ribonucleotides, many therapeutic nucleotide analogs that target polymerases have sugar modifications, and their efficacy depends on their ability to be incorporated into DNA. Here, we investigate the ability of DNA polymerase beta to utilize nucleotides with modified sugars. DNA polymerase beta readily inserts dideoxynucleoside triphosphates but inserts ribonucleotides nearly 4 orders of magnitude less efficiently than natural deoxynucleotides. The efficiency of ribonucleotide insertion is similar to that reported for other DNA polymerases. The poor polymerase-dependent insertion represents a key step in discriminating against ribonucleotides because, once inserted, a ribonucleotide is easily extended. Likewise, a templating ribonucleotide has little effect on insertion efficiency or fidelity. In contrast to insertion and extension of a ribonucleotide, the chemotherapeutic drug arabinofuranosylcytosine triphosphate is efficiently inserted but poorly extended. These results suggest that the sugar pucker at the primer terminus plays a crucial role in DNA synthesis; a 3'-endo sugar pucker facilitates nucleotide insertion, whereas a 2'-endo conformation inhibits insertion.
C1 [Cavanaugh, Nisha A.; Beard, William A.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Beard, WA (reprint author), NIEHS, Struct Biol Lab, NIH, 111 TW Alexander Dr,POB 12233,MD F1-12, Res Triangle Pk, NC 27709 USA.
EM wilson5@niehs.nih.gov
FU National Institutes of Health [Z01-ES050158, P41 RR-01081]; NIEHS
[Z01-ES050161, 1U19CA105010]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants Z01-ES050158 and Z01-ES050161 Intramural Research Program,
NIEHS (to S. H. W.), and was in association with Grant 1U19CA105010.;
Molecular graphics images were produced using the Chimera package (58)
from the Resource for Biocomputing, Visualization, and Informatics at
the University of California, San Francisco (supported by National
Institutes of Health Grant P41 RR-01081).
NR 63
TC 33
Z9 33
U1 0
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 6
PY 2010
VL 285
IS 32
BP 24457
EP 24465
DI 10.1074/jbc.M110.132407
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 633YB
UT WOS:000280542100018
PM 20519499
ER
PT J
AU Watashi, K
Yeung, ML
Starost, MF
Hosmane, RS
Jeang, KT
AF Watashi, Koichi
Yeung, Man Lung
Starost, Matthew F.
Hosmane, Ramachandra S.
Jeang, Kuan-Teh
TI Identification of Small Molecules That Suppress MicroRNA Function and
Reverse Tumorigenesis
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID BINDING PROTEIN TRBP; RNA-INTERFERENCE; BREAST-CANCER; EXPRESSION;
CELLS; GENE; DICER; HIV-1; TRANSFORMATION; COMPLEX
AB MicroRNAs (miRNAs) act in post-transcriptional gene silencing and are proposed to function in a wide spectrum of pathologies, including cancers and viral diseases. Currently, to our knowledge, no detailed mechanistic characterization of small molecules that interrupt miRNA pathways have been reported. In screening a small chemical library, we identified compounds that suppress RNA interference activity in cultured cells. Two compounds were characterized; one impaired Dicer activity while the other blocked small RNA-loading into an Argonaute 2 (AGO2) complex. We developed a cell-based model of miRNA-dependent tumorigenesis, and using this model, we observed that treatment of cells with either of the two compounds effectively neutralized tumor growth. These findings indicate that miRNA pathway-suppressing small molecules could potentially reverse tumorigenesis.
C1 NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Starost, Matthew F.] NIH, Div Vet Resources, Bethesda, MD 20892 USA.
[Hosmane, Ramachandra S.] Univ Maryland, Dept Chem & Biochem, Baltimore, MD 21250 USA.
RP Jeang, KT (reprint author), 9000 Rockville Pike,Bldg 4,Rm 303A, Bethesda, MD 20892 USA.
EM kjeang@niaid.nih.gov
RI Jeang, Kuan-Teh/A-2424-2008
FU National Institutes of Health [1R01 GM087738-01A1]; NIAID; NIH; Japan
Society for the Promotion of Science
FX This work was supported, in whole or in part, by National Institutes of
Health Grant 1R01 GM087738-01A1 (to R. S. H.) and by intramural funds
from NIAID, NIH and the Intramural AIDS Targeted Antiviral Program from
the office of the Director, NIH (to K.-T. J.).; A recipient of a
Postdoctoral Fellowship for Research Abroad from the Japan Society for
the Promotion of Science.
NR 52
TC 52
Z9 52
U1 1
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 6
PY 2010
VL 285
IS 32
BP 24707
EP 24716
DI 10.1074/jbc.M109.062976
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 633YB
UT WOS:000280542100043
PM 20529860
ER
PT J
AU Singh, K
Gitti, RK
Diouf, A
Zhou, H
Gowda, DC
Miura, K
Ostazeski, SA
Fairhurst, RM
Garboczi, DN
Long, CA
AF Singh, Kavita
Gitti, Rossitza K.
Diouf, Ababacar
Zhou, Hong
Gowda, D. Channe
Miura, Kazutoyo
Ostazeski, Stanley A.
Fairhurst, Rick M.
Garboczi, David N.
Long, Carole A.
TI Subdomain 3 of Plasmodium falciparum VAR2CSA DBL3x Is Identified as a
Minimal Chondroitin Sulfate A-binding Region
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ADHESION-BLOCKING ANTIBODIES; PREGNANCY-ASSOCIATED MALARIA; VARIANT
SURFACE-ANTIGENS; N-TERMINAL DOMAIN; INFECTED ERYTHROCYTES; PARASITE
ADHESION; PLACENTAL MALARIA; VAR GENE; RECEPTOR; NMR
AB Molecular interactions between the VAR2CSA protein, expressed on the surface of Plasmodium falciparum-infected erythrocytes, and placental chondroitin sulfate A (CSA) are primarily responsible for pregnancy-associated malaria (PAM). Interrupting these interactions may prevent or ameliorate the severity of PAM. Several of the Duffy binding-like (DBL) domains of VAR2CSA, including the DBL3x domain, have been shown to bind CSA in vitro, but a more detailed understanding of how DBL domains bind CSA is needed. In this study, we demonstrate that subdomain 3 (S3), one of the three subdomains of VAR2CSA DBL3x by itself, is the major contributor toward CSA binding. NMR spectroscopy and flow cytometry analyses show that S3 and the intact DBL3x domain bind CSA similarly. Mutations within the S3 portion of DBL3x markedly affect CSA binding. Both recombinant molecules, S3 and DBL3x, are recognized by antibodies in the plasma of previously pregnant women living in malaria-endemic regions of Mali, but much less so by plasma from men of the same regions. As the S3 sequence is highly conserved in all known VAR2CSA proteins expressed by different parasite isolates obtained from various malaria endemic areas of the world, the identification of S3 as an independent CSA-binding region provides a compelling molecular basis for designing interventions against PAM.
C1 [Garboczi, David N.] NIAID, Struct Biol Sect, Res Technol Branch, NIH, Rockville, MD 20852 USA.
[Gitti, Rossitza K.; Ostazeski, Stanley A.] Edgewood Chem Biol Ctr, Forens Analyt Branch, Aberdeen Proving Ground, MD 21010 USA.
[Diouf, Ababacar; Zhou, Hong; Miura, Kazutoyo; Fairhurst, Rick M.; Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Gowda, D. Channe] Penn State Univ, Coll Med, Dept Biochem & Mol Biol, Hershey, PA 17033 USA.
EM ksingh@niaid.nih.gov; clong@niaid.nih.gov
FU NIAID, National Institutes of Health [AI45086]
FX This work was supported, in whole or in part, by Grant AI45086 from
NIAID, National Institutes of Health and the Division of Intramural
Research of the NIAID, National Institutes of Health.
NR 39
TC 17
Z9 17
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD AUG 6
PY 2010
VL 285
IS 32
BP 24855
EP 24862
DI 10.1074/jbc.M110.118612
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 633YB
UT WOS:000280542100058
PM 20529864
ER
PT J
AU Shaikh, AG
Wong, AL
Optican, LM
Miura, K
Solomon, D
Zee, DS
AF Shaikh, Aasef G.
Wong, Aaron L.
Optican, Lance M.
Miura, Kenichiro
Solomon, David
Zee, David S.
TI Sustained eye closure slows saccades
SO VISION RESEARCH
LA English
DT Article
DE Omnipause neurons; Burst neurons; Oscillations; Ballistic movement;
Post-inhibitory rebound
ID PONTINE RETICULAR-FORMATION; EXCITATORY BURST NEURONS; SUPERIOR
COLLICULUS; OMNIPAUSE NEURONS; HORIZONTAL SACCADES; MOVEMENTS;
OSCILLATIONS; MONKEY; IDENTIFICATION; CEREBELLUM
AB Saccadic eye movements rapidly orient the line of sight towards the object of interest. Pre-motor burst neurons (BNs) controlling saccades receive excitation from superior colliculus and cerebellum, but inhibition by omnipause neurons (OPNs) prevents saccades. When the OPNs pause, BNs begin to fire. It has been presumed that part of the BN burst comes from post-inhibitory rebound (PIR). We hypothesized that in the absence of prior inhibition from OPNs there would be no PIR, and thus the increase in initial firing rate of BNs would be reduced. Consequently, saccade acceleration would be reduced. We measured eye movements and showed that sustained eye closure, which inhibits the activity of OPNs and thus hypothetically should weaken PIR, reduced the peak velocity, acceleration, and deceleration of saccades in healthy human subjects. Saccades under closed eyelids also had irregular trajectories; the frequency of the oscillations underlying this irregularity was similar to that of high-frequency ocular flutter (back-to-back saccades) often seen in normal subjects during attempted fixation at straight ahead while eyes are closed. Saccades and quick phases of nystagmus are generated by the same pre-motor neurons, and we found that the quick-phase velocity of nystagmus was also reduced by lid closure. These changes were not due to a mechanical hindrance to the eyes, because lid closure did not affect the peak velocities or accelerations of the eyes in the "slow-phase" response to rapid head movements of comparable speeds to those of saccades. These results indicate a role for OPNs in generating the abrupt onset and high velocities of saccades. We hypothesize that the mechanism involved is PIR in pre-motor burst neurons. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Shaikh, Aasef G.; Solomon, David; Zee, David S.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA.
[Wong, Aaron L.] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21287 USA.
[Optican, Lance M.] NEI, Sensorimotor Res Lab, NIH, DHHS, Bethesda, MD 20892 USA.
[Miura, Kenichiro] Kyoto Univ, Grad Sch Med, Dept Integrat Brain Sci, Kyoto, Japan.
[Zee, David S.] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD 21287 USA.
[Zee, David S.] Johns Hopkins Univ, Dept Otolaryngol, Baltimore, MD 21287 USA.
RP Shaikh, AG (reprint author), Johns Hopkins Univ, Dept Neurol, 600 N Wolfe St,Path 2-210, Baltimore, MD 21287 USA.
EM ashaikh@dizzy.med.jhu.edu
FU Gustavus and Louise Pfeiffer Foundation; Leon Levy Foundation; NIH
[EY01849]
FX This work was supported by grants from the Gustavus and Louise Pfeiffer
Foundation, NIH EY01849, and Leon Levy Foundation.
NR 34
TC 11
Z9 11
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0042-6989
J9 VISION RES
JI Vision Res.
PD AUG 6
PY 2010
VL 50
IS 17
BP 1665
EP 1675
DI 10.1016/j.visres.2010.05.019
PG 11
WC Neurosciences; Ophthalmology
SC Neurosciences & Neurology; Ophthalmology
GA 638OS
UT WOS:000280904800006
PM 20573593
ER
PT J
AU Nikolov, NP
Shimizu, M
Cleland, S
Bailey, D
Aoki, J
Strom, T
Schwartzberg, PL
Candotti, F
Siegel, RM
AF Nikolov, Nikolay P.
Shimizu, Masaki
Cleland, Sophia
Bailey, Daniel
Aoki, Joseph
Strom, Ted
Schwartzberg, Pamela L.
Candotti, Fabio
Siegel, Richard M.
TI Systemic autoimmunity and defective Fas ligand secretion in the absence
of the Wiskott-Aldrich syndrome protein
SO BLOOD
LA English
DT Article
ID REGULATORY T-CELLS; CUTTING EDGE; APOPTOSIS; DEATH; LYMPHOCYTES;
EXPRESSION; DEFICIENT; RECEPTOR; WASP; HOMEOSTASIS
AB Autoimmunity is a surprisingly common complication of primary immunodeficiencies, yet the molecular mechanisms underlying this clinical observation are not well understood. One widely known example is provided by Wiskott-Aldrich syndrome (WAS), an X-linked primary immunodeficiency disorder caused by mutations in the gene encoding the WAS protein (WASp) with a high incidence of autoimmunity in affected patients. WASp deficiency affects T-cell antigen receptor (TCR) signaling and T-cell cytokine production, but its role in TCR-induced apoptosis, one of the mechanisms of peripheral immunologic tolerance, has not been investigated. We find that WASp-deficient mice produce autoantibodies and develop proliferative glomerulonephritis with immune complex deposition as they age. We also find that CD4(+) T lymphocytes from WASp-deficient mice undergo reduced apoptosis after restimulation through the TCR. While Fas-induced cell death is normal, WASp deficiency affects TCR-induced secretion of Fas ligand (FasL) and other components of secretory granules by CD4(+) T cells. These results describe a novel role of WASp in regulating TCR-induced apoptosis and FasL secretion and suggest that WASp-deficient mice provide a good model for the study of autoimmune manifestations of WAS and the development of more specific therapies for these complications. (Blood. 2010;116(5):740-747)
C1 [Nikolov, Nikolay P.; Cleland, Sophia; Bailey, Daniel; Siegel, Richard M.] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Nikolov, Nikolay P.] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, Immunoregulat Grp, Autoimmun Branch, NIH, Bethesda, MD 20892 USA.
[Shimizu, Masaki; Candotti, Fabio] NHGRI, Disorders Immun Sect, GMBB, NIH, Bethesda, MD 20892 USA.
[Aoki, Joseph; Schwartzberg, Pamela L.] NHGRI, Cell Signaling Sect, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Strom, Ted] Univ Tennessee Hlth Sci, Memphis VA Med Ctr, Pathol & Lab Med Serv, Memphis, TN USA.
[Strom, Ted] Univ Tennessee Hlth Sci, Dept Pathol, Memphis, TN USA.
RP Siegel, RM (reprint author), Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, Off Clin Director, NIH, 10 Ctr Dr,Bldg 10,Rm 13C103, Bethesda, MD 20892 USA.
EM siegelr@mail.nih.gov
OI Siegel, Richard/0000-0001-5953-9893
FU NIH; NIH Office of Rare Diseases; NHGRI; NIAMS
FX This work was supported by intramural research program of NIAMS and
NHGRI at the NIH, and also by a Bench-to-Bedside award funded by the NIH
Office of Rare Diseases, NHGRI, and NIAMS. J.A. was a Howard Hughes
Medical Institute-NIH scholar.
NR 50
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U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 5
PY 2010
VL 116
IS 5
BP 740
EP 747
DI 10.1182/blood-2009-08-237560
PG 8
WC Hematology
SC Hematology
GA 634PX
UT WOS:000280596500013
PM 20457871
ER
PT J
AU Engram, JC
Cervasi, B
Borghans, JAM
Klatt, NR
Gordon, SN
Chahroudi, A
Else, JG
Mittler, RS
Sodora, DL
de Boer, RJ
Brenchley, JM
Silvestri, G
Paiardini, M
AF Engram, Jessica C.
Cervasi, Barbara
Borghans, Jose A. M.
Klatt, Nichole R.
Gordon, Shari N.
Chahroudi, Ann
Else, James G.
Mittler, Robert S.
Sodora, Donald L.
de Boer, Rob J.
Brenchley, Jason M.
Silvestri, Guido
Paiardini, Mirko
TI Lineage-specific T-cell reconstitution following in vivo CD4(+) and
CD8(+) lymphocyte depletion in nonhuman primates
SO BLOOD
LA English
DT Article
ID IMMUNODEFICIENCY VIRUS-INFECTION; SOOTY MANGABEYS; AIDS PATHOGENESIS;
PERIPHERAL-BLOOD; HIV-1 INFECTION; SIV INFECTION; HOMEOSTASIS; IL-7;
MEMORY; FAILURE
AB Many features of T-cell homeostasis in primates are still unclear, thus limiting our understanding of AIDS pathogenesis, in which T-cell homeostasis is lost. Here, we performed experiments of in vivo CD4(+) or CD8(+) lymphocyte depletion in 2 nonhuman primate species, rhesus macaques (RMs) and sooty mangabeys (SMs). Whereas RMs develop AIDS after infection with simian immunodeficiency virus (SIV), SIV-infected SMs are typically AIDS-resistant. We found that, in both species, most CD4(+) or CD8(+) T cells in blood and lymph nodes were depleted after treatment with their respective antibodies. These CD4(+) and CD8(+) lymphocyte depletions were followed by a largely lineage-specific CD4(+) and CD8(+) T-cell proliferation, involving mainly memory T cells, which correlated with interleukin-7 plasma levels. Interestingly, SMs showed a faster repopulation of naive CD4(+) T cells than RMs. In addition, in both species CD8(+) T-cell repopulation was faster than that of CD4(+) T cells, with CD8(+) T cells reconstituting a normal pool within 60 days and CD4(+) T cells remaining below baseline levels up to day 180 after depletion. While this study revealed subtle differences in CD4(+) T-cell repopulation in an AIDS-sensitive versus an AIDS-resistant species, such differences may have particular relevance in the presence of active SIV replication, where CD4(+) T-cell destruction is chronic. (Blood. 2010;116(5):748-758)
C1 [Else, James G.; Mittler, Robert S.; Silvestri, Guido; Paiardini, Mirko] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA.
[Engram, Jessica C.; Cervasi, Barbara; Chahroudi, Ann; Silvestri, Guido; Paiardini, Mirko] Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA.
[Borghans, Jose A. M.] Utrecht Med Ctr, Dept Immunol, Utrecht, Netherlands.
[Klatt, Nichole R.; Brenchley, Jason M.] NCI, Viral Pathogenesis & Vaccine Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Gordon, Shari N.] NCI, Anim Models & Retroviral Vaccine Sect, NIH, Bethesda, MD 20892 USA.
[Sodora, Donald L.] Seattle Biomed Res Inst, Seattle, WA USA.
[de Boer, Rob J.] Univ Utrecht, Utrecht, Netherlands.
RP Paiardini, M (reprint author), Emory Univ, Yerkes Natl Primate Res Ctr, 954 Gatewood Rd NE, Atlanta, GA 30329 USA.
EM mirko.paiardini@emory.edu
RI De Boer, Rob/B-6050-2011
OI De Boer, Rob/0000-0002-2130-691X
FU [R21-AI-54 234]; [R01-HL075766]
FX This work was supported by grants R21-AI-54 234 and R01-HL075766 (to
G.S).
NR 53
TC 18
Z9 18
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 5
PY 2010
VL 116
IS 5
BP 748
EP 758
DI 10.1182/blood-2010-01-263814
PG 11
WC Hematology
SC Hematology
GA 634PX
UT WOS:000280596500014
PM 20484087
ER
PT J
AU Valent, P
Arock, M
Akin, C
Sperr, WR
Reiter, A
Sotlar, K
Hartmann, K
George, TI
Brockow, K
Kluin-Nelemans, HC
Gotlib, J
Metcalfe, DD
Horny, HP
AF Valent, Peter
Arock, Michel
Akin, Cem
Sperr, Wolfgang R.
Reiter, Andreas
Sotlar, Karl
Hartmann, Karin
George, Tracy I.
Brockow, Knut
Kluin-Nelemans, Hanneke C.
Gotlib, Jason
Metcalfe, Dean D.
Horny, Hans-Peter
TI The classification of systemic mastocytosis should include mast cell
leukemia (MCL) and systemic mastocytosis with a clonal hematologic
non-mast cell lineage disease (SM-AHNMD)
SO BLOOD
LA English
DT Letter
ID CRITERIA; PROPOSAL
C1 [Valent, Peter; Sperr, Wolfgang R.] Med Univ Vienna, Dept Internal Med 1, Div Hematol & Hemostaseol, A-1090 Vienna, Austria.
[Arock, Michel] Ecole Normale Super, Lab Biol & Pharmacol Appl, Cachan, France.
[Akin, Cem] Harvard Univ, Sch Med, Boston, MA USA.
[Reiter, Andreas] Univ Med Mannheim, Med Klin 3, Mannheim, Germany.
[Sotlar, Karl] Univ Munich, Inst Pathol, D-8000 Munich, Germany.
[Hartmann, Karin] Univ Cologne, Dept Dermatol, D-5000 Cologne, Germany.
[George, Tracy I.; Gotlib, Jason] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Brockow, Knut] Biederstein Tech Univ, Dept Dermatol & Allergy, Munich, Germany.
[Kluin-Nelemans, Hanneke C.] Univ Groningen, Univ Med Ctr Groningen, Dept Hematol, Groningen, Netherlands.
[Metcalfe, Dean D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Horny, Hans-Peter] Inst Pathol Ansbach, Ansbach, Germany.
RP Valent, P (reprint author), Med Univ Vienna, Dept Internal Med 1, Div Hematol & Hemostaseol, Wahringer Gurtel 18-20, A-1090 Vienna, Austria.
EM peter.valent@meduniwien.ac.at
RI Hartmann, Karin/N-4865-2015
OI Hartmann, Karin/0000-0002-4595-8226
NR 9
TC 11
Z9 11
U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 5
PY 2010
VL 116
IS 5
BP 850
EP 851
PG 2
WC Hematology
SC Hematology
GA 634PX
UT WOS:000280596500027
PM 20688965
ER
PT J
AU Gladwin, MT
Barst, RJ
Castro, OL
Gordeuk, VR
Hillery, CA
Kato, GJ
Kim-Shapiro, DB
Machado, R
Morris, CR
Steinberg, MH
Vichinsky, EP
AF Gladwin, Mark T.
Barst, Robyn J.
Castro, Oswaldo L.
Gordeuk, Victor R.
Hillery, Cheryl A.
Kato, Gregory J.
Kim-Shapiro, Daniel B.
Machado, Roberto
Morris, Claudia R.
Steinberg, Martin H.
Vichinsky, Elliott P.
TI Pulmonary hypertension and NO in sickle cell
SO BLOOD
LA English
DT Letter
ID NITRIC-OXIDE BIOAVAILABILITY; DISEASE; HEMOLYSIS; DEATH; HEMOGLOBIN;
RISK; DYSFUNCTION; PRIAPISM; MODEL; MICE
C1 [Gladwin, Mark T.] Univ Pittsburgh, Vasc Med Inst, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15213 USA.
[Barst, Robyn J.] Columbia Univ, New York, NY USA.
[Castro, Oswaldo L.; Gordeuk, Victor R.] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA.
[Hillery, Cheryl A.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Hillery, Cheryl A.] Blood Ctr Wisconsin, Milwaukee, WI USA.
[Kato, Gregory J.] NIH, Bethesda, MD 20892 USA.
[Kim-Shapiro, Daniel B.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Machado, Roberto] Univ Illinois Chicago, Chicago, IL USA.
[Morris, Claudia R.; Vichinsky, Elliott P.] Childrens Hosp & Res Ctr Oakland, Oakland, CA 94609 USA.
[Steinberg, Martin H.] Boston Univ, Boston, MA 02215 USA.
RP Gladwin, MT (reprint author), Univ Pittsburgh, Vasc Med Inst, Div Pulm Allergy & Crit Care Med, NW 628 Montefiore Hosp,3459 5th Ave, Pittsburgh, PA 15213 USA.
EM gladwinmt@upmc.edu
RI Vichinsky, Elliott/F-8541-2011; Kato, Gregory/I-7615-2014
OI Vichinsky, Elliott/0000-0002-0500-9579; Kato,
Gregory/0000-0003-4465-3217
FU Intramural NIH HHS [ZIA HL006014-01, ZIA HL006012-01, ZIA HL006014-02,
ZIA HL006012-02]; NHLBI NIH HHS [R37 HL058091]
NR 18
TC 28
Z9 29
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD AUG 5
PY 2010
VL 116
IS 5
BP 852
EP 854
PG 4
WC Hematology
SC Hematology
GA 634PX
UT WOS:000280596500029
PM 20688967
ER
PT J
AU Garcia-Villada, L
Drake, JW
AF Garcia-Villada, Libertad
Drake, John W.
TI Mutational clusters generated by non-processive polymerases: A case
study using DNA polymerase beta in vitro
SO DNA REPAIR
LA English
DT Article
DE DNA polymerase beta; Mutational clusters; Polymerase processivity
ID BASE SUBSTITUTION; ESCHERICHIA-COLI; FIDELITY; MECHANISM; MUTANTS;
SHOWERS; ERRORS
AB Available DNA mutational spectra reveal that the number of mutants with multiple mutations ("multiples") is usually greater than expected from a random distribution of mutations among mutants. These overloads imply the occurrence of non-random clusters of mutations. probably generated during episodes of low-fidelity DNA synthesis. Excess multiples have been reported not only for viruses, bacteria, and eukaryotic cells but also for the DNA polymerases of phages T4 and RB69 in vitro. In the simplest case of a purified polymerase, non-random clusters may be generated by a subfraction of phenotypic variants able to introduce more errors per cycle of DNA synthesis than the normal enzyme. According to this hypothesis, excess multiples are not expected with non-processive polymerases even if they harbor rare mutator variants. DNA polymerase beta (Pol beta) is a mammalian DNA-repair polymerase with very low processivity. Although several Pol beta mutational spectra have been described, there is conflicting evidence on whether or not excess multiples occur, with spectra based on the HSV-tk system tending to show excess multiples. Excess multiples generated by Pol beta or any of its mutants might imply that the excesses of multiples observed in numerous other systems, especially those with processive polymerases, could be artifactual. Here. the distributions of mutations generated by native and recombinant rat Pol beta and by the Pol beta(Y265C) mutator were analyzed in the M13mp2 lacZ alpha system. Our results present no evidence for a significant excess of multiples over the expected numbers with any of the Pol beta enzymes tested in this system. The reported excess of Pol beta-generated multiples in the HSV-tk system may reflect a reduced efficiency of detection of base substitutions that cause weak phenotypes, which in turn may artifactually increase the frequency of multiples. Published by Elsevier B.V.
C1 [Garcia-Villada, Libertad; Drake, John W.] Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
RP Drake, JW (reprint author), Natl Inst Environm Hlth Sci, Mol Genet Lab, POB 12233,111 S Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM garciavitlal@niehs.nih.gov; drake@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences [Z01ES065016]
FX We thank Sam Bennett, the Sam Wilson lab, and Joann Sweasy for gifts of
purified Pol beta preparations; Kasia Bebenek, Stephanie Nick McElhinny,
Dinh Nguyen and Tom Kunkel for advice on the properties and use of the
lacZ alpha system; and Kasia Bebenek and Bill Beard for critical
readings of the manuscript. This research was supported by funds
allocated to project number Z01ES065016 of the Intramural Research
Program of the NIH, National Institute of Environmental Health Sciences.
NR 30
TC 1
Z9 1
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD AUG 5
PY 2010
VL 9
IS 8
BP 871
EP 878
DI 10.1016/j.dnarep.2010.05.002
PG 8
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 642AJ
UT WOS:000281174700004
PM 20627824
ER
PT J
AU Yang, Y
Gordenin, DA
Resnick, MA
AF Yang, Yong
Gordenin, Dmitry A.
Resnick, Michael A.
TI A single-strand specific lesion drives MMS-induced hyper-mutability at a
double-strand break in yeast
SO DNA REPAIR
LA English
DT Article
DE Localized hyper-mutability; Double-strand break; Single-strand DNA; DNA
polymerase zeta; Methyl methanesulfonate
ID SITE-DIRECTED MUTAGENESIS; SACCHAROMYCES-CEREVISIAE; ALKYLATION DAMAGE;
ESCHERICHIA-COLI; DNA-POLYMERASE; IN-VIVO; PYRIMIDINE DIMERS; ABASIC
SITES; REPAIR; RNA
AB Localized hyper-mutability (LHM) can be important in evolution, immunity, and genetic diseases. We previously reported that single-strand DNA (ssDNA) can be an important source of damage-induced LHM in yeast. Here, we establish that the generation of LHM by methyl methanesulfonate (MMS) during repair of a chromosomal double-strand break (DSB) can result in over 0.2 mutations/kb, which is similar to 20,000-fold higher than the MMS-induced mutation density without a DSB. The MMS-induced mutations associated with DSB repair were primarily due to substitutions via translesion DNA synthesis at damaged cytosines, even though there are nearly 10 times more MMS-induced lesions at other bases. Based on this mutation bias, the promutagenic lesion dominating LHM is likely 3-methylcytosine. which is single-strand specific. Thus, the dramatic increase in mutagenesis at a DSB is concluded to result primarily from the generation of non-repairable lesions in ssDNA associated with DSB repair along with efficient induction of highly mutagenic ssDNA-specific lesions. These findings with MMS-induced LHM have broad biological implications for unrepaired damage generated in ssDNA and possibly ssRNA. Published by Elsevier B.V.
C1 [Yang, Yong; Gordenin, Dmitry A.; Resnick, Michael A.] Natl Inst Environm Hlth Sci, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Resnick, MA (reprint author), Natl Inst Environm Hlth Sci, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
EM gordenin@niehs.nih.gov; resnick@niehs.nih.gov
OI Gordenin, Dmitry/0000-0002-8399-1836
FU NIH, National Institute of Environmental Health Sciences [ES065073]
FX We thank Dr. Shay Covo and other members of the lab for many helpful
discussions. We are grateful to Drs. Julie Horton, Jana Stone, Steven
Roberts and Thomas Kunkel for critical reading of the manuscript and
helpful suggestions. This work was supported by the Intramural Research
Program of the NIH, National Institute of Environmental Health Sciences
(Project ES065073 to M.A.R.).
NR 49
TC 25
Z9 25
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD AUG 5
PY 2010
VL 9
IS 8
BP 914
EP 921
DI 10.1016/j.dnarep.2010.06.005
PG 8
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 642AJ
UT WOS:000281174700009
PM 20663718
ER
PT J
AU Heacock, ML
Stefanick, DF
Horton, JK
Wilson, SH
AF Heacock, Michelle L.
Stefanick, Donna F.
Horton, Julie K.
Wilson, Samuel H.
TI Alkylation DNA damage in combination with PARP inhibition results in
formation of S-phase-dependent double-strand breaks
SO DNA REPAIR
LA English
DT Article
DE PARP-1; PARP inhibitor; Methyl methanesulfonate; Cell cycle;
Double-strand breaks; gamma-H2A.X
ID POLY(ADP-RIBOSE) POLYMERASE-ACTIVITY; FIELD GEL-ELECTROPHORESIS;
BASE-EXCISION-REPAIR; MAMMALIAN-CELLS; CANCER-THERAPY; ATM; DEFECT;
FIBROBLASTS; REQUIREMENT; RADIATION
AB The combination of poly(ADP-ribose)polymerase (PARP) inhibitors and alkylating agents is currently being investigated in cancer therapy clinical trials. However, the DNA lesions producing the synergistic cell killing effect in tumors are not fully understood. Treatment of human and mouse fibroblasts with the monofunctional DNA methylating agent methyl methanesulfonate (MMS) in the presence of a PARP inhibitor has been shown to trigger a cell cycle checkpoint response. Among other changes, this DNA damage response to combination treatment includes activation of ATM/Chk2 and phosphorylation of histone H2A.X. These changes are consistent with DNA double-strand break (DSB) formation during the response, but the measurement of DSBs has not been addressed. Such DSB evaluation is important in understanding this DNA damage response because events other than DSB formation are known to lead to ATM/Chk2 activation and H2A.X phosphorylation. Here, we examined the structural integrity of genomic DNA after the combined treatment of cells with MMS and a PARP inhibitor, i.e., exposure to a sub-lethal dose of MMS in the presence of the PARP inhibitor 4-amino-1,8-napthalimide (4-AN). We used pulsed field gel electrophoresis (PFGE) for measurement of DSBs in both human and mouse embryonic fibroblasts, and flow cytometry to follow the phosphorylated form of H2A.X (gamma-H2A.X). The results indicate that DSBs are formed with the combination treatment, but not following treatment with either agent alone. Our data also show that formation of gamma-H2A.X correlates with PARP-1-expressing cells in S-phase of the cell cycle. The observations support the model that persistence of PARP-1 at base excision repair intermediates, as cells move into S-phase, leads to DSBs and the attendant checkpoint responses. Published by Elsevier B.V.
C1 [Heacock, Michelle L.; Stefanick, Donna F.; Horton, Julie K.; Wilson, Samuel H.] NIEHS, NIH, Struct Biol Lab, Res Triangle Pk, NC 27709 USA.
RP Wilson, SH (reprint author), NIEHS, NIH, Struct Biol Lab, 111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA.
EM wilson5@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences [Z01-ES050159]
FX We thank Jennifer Zeng for technical assistance, Michael Carrozza for
discussion and critical reading of this manuscript and Bonnie Mesmer for
careful editing. We thank Carl Bortner and the Flow Cytometry Center for
assistance. We are also grateful to the Michael Resnick laboratory for
use of their Bio-Rad CHEF-mapper XA PFGE system, as well as for
technical assistance from Wenjian Ma and Jim Westmoreland. This research
was supported by Research Project Number Z01-ES050159 in the intramural
Research Program of the NIH, National Institute of Environmental Health
Sciences.
NR 48
TC 30
Z9 30
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD AUG 5
PY 2010
VL 9
IS 8
BP 929
EP 936
DI 10.1016/j.dnarep.2010.05.007
PG 8
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 642AJ
UT WOS:000281174700011
PM 20573551
ER
PT J
AU Teslovich, TM
Musunuru, K
Smith, AV
Edmondson, AC
Stylianou, IM
Koseki, M
Pirruccello, JP
Ripatti, S
Chasman, DI
Willer, CJ
Johansen, CT
Fouchier, SW
Isaacs, A
Peloso, GM
Barbalic, M
Ricketts, SL
Bis, JC
Aulchenko, YS
Thorleifsson, G
Feitosa, MF
Chambers, J
Orho-Melander, M
Melander, O
Johnson, T
Li, XH
Guo, XQ
Li, MY
Cho, YS
Go, MJ
Kim, YJ
Lee, JY
Park, T
Kim, K
Sim, X
Ong, RTH
Croteau-Chonka, DC
Lange, LA
Smith, JD
Song, K
Zhao, JH
Yuan, X
Luan, JA
Lamina, C
Ziegler, A
Zhang, W
Zee, RYL
Wright, AF
Witteman, JCM
Wilson, JF
Willemsen, G
Wichmann, HE
Whitfield, JB
Waterworth, DM
Wareham, NJ
Waeber, G
Vollenweider, P
Voight, BF
Vitart, V
Uitterlinden, AG
Uda, M
Tuomilehto, J
Thompson, JR
Tanaka, T
Surakka, I
Stringham, HM
Spector, TD
Soranzo, N
Smit, JH
Sinisalo, J
Silander, K
Sijbrands, EJG
Scuteri, A
Scott, J
Schlessinger, D
Sanna, S
Salomaa, V
Saharinen, J
Sabatti, C
Ruokonen, A
Rudan, I
Rose, LM
Roberts, R
Rieder, M
Psaty, BM
Pramstaller, PP
Pichler, I
Perola, M
Penninx, BWJH
Pedersen, NL
Pattaro, C
Parker, AN
Pare, G
Oostra, BA
O'Donnell, CJ
Nieminen, MS
Nickerson, DA
Montgomery, GW
Meitinger, T
McPherson, R
McCarthy, MI
McArdle, W
Masson, D
Martin, NG
Marroni, F
Mangino, M
Magnusson, PKE
Lucas, G
Luben, R
Loos, RJF
Lokki, ML
Lettre, G
Langenberg, C
Launer, LJ
Lakatta, EG
Laaksonen, R
Kyvik, KO
Kronenberg, F
Konig, IR
Khaw, KT
Kaprio, J
Kaplan, LM
Johansson, A
Jarvelin, MR
Janssens, ACJW
Ingelsson, E
Igi, W
Hovingh, GK
Hottenga, JJ
Hofman, A
Hicks, AA
Hengstenberg, C
Heid, IM
Hayward, C
Havulinna, AS
Hastie, ND
Harris, TB
Haritunians, T
Hall, AS
Gyllensten, U
Guiducci, C
Groop, LC
Gonzalez, E
Gieger, C
Freimer, NB
Ferrucci, L
Erdmann, J
Elliott, P
Ejebe, KG
Doering, A
Dominiczak, AF
Demissie, S
Deloukas, P
de Geus, EJC
de Faire, U
Crawford, G
Collins, FS
Chen, YDI
Caulfield, MJ
Campbell, H
Burtt, NP
Bonnycastle, LL
Boomsma, DI
Boekholdt, SM
Bergman, RN
Barroso, I
Bandinelli, S
Ballantyne, CM
Assimes, TL
Quertermous, T
Altshuler, D
Seielstad, M
Wong, TY
Tai, ES
Feranil, AB
Kuzawa, CW
Adair, LS
Taylor, HA
Borecki, IB
Gabriel, SB
Wilson, JG
Holm, H
Thorsteinsdottir, U
Gudnason, V
Krauss, RM
Mohlke, KL
Ordovas, JM
Munroe, PB
Kooner, JS
Tall, AR
Hegele, RA
Kastelein, JJP
Schadt, EE
Rotter, JI
Boerwinkle, E
Strachan, DP
Mooser, V
Stefansson, K
Reilly, MP
Samani, NJ
Schunkert, H
Cupples, LA
Sandhu, MS
Ridker, PM
Rader, DJ
van Duijn, CM
Peltonen, L
Abecasis, GR
Boehnke, M
Kathiresan, S
AF Teslovich, Tanya M.
Musunuru, Kiran
Smith, Albert V.
Edmondson, Andrew C.
Stylianou, Ioannis M.
Koseki, Masahiro
Pirruccello, James P.
Ripatti, Samuli
Chasman, Daniel I.
Willer, Cristen J.
Johansen, Christopher T.
Fouchier, Sigrid W.
Isaacs, Aaron
Peloso, Gina M.
Barbalic, Maja
Ricketts, Sally L.
Bis, Joshua C.
Aulchenko, Yurii S.
Thorleifsson, Gudmar
Feitosa, Mary F.
Chambers, John
Orho-Melander, Marju
Melander, Olle
Johnson, Toby
Li, Xiaohui
Guo, Xiuqing
Li, Mingyao
Cho, Yoon Shin
Go, Min Jin
Kim, Young Jin
Lee, Jong-Young
Park, Taesung
Kim, Kyunga
Sim, Xueling
Ong, Rick Twee-Hee
Croteau-Chonka, Damien C.
Lange, Leslie A.
Smith, Joshua D.
Song, Kijoung
Zhao, Jing Hua
Yuan, Xin
Luan, Jian'an
Lamina, Claudia
Ziegler, Andreas
Zhang, Weihua
Zee, Robert Y. L.
Wright, Alan F.
Witteman, Jacqueline C. M.
Wilson, James F.
Willemsen, Gonneke
Wichmann, H. -Erich
Whitfield, John B.
Waterworth, Dawn M.
Wareham, Nicholas J.
Waeber, Gerard
Vollenweider, Peter
Voight, Benjamin F.
Vitart, Veronique
Uitterlinden, Andre G.
Uda, Manuela
Tuomilehto, Jaakko
Thompson, John R.
Tanaka, Toshiko
Surakka, Ida
Stringham, Heather M.
Spector, Tim D.
Soranzo, Nicole
Smit, Johannes H.
Sinisalo, Juha
Silander, Kaisa
Sijbrands, Eric J. G.
Scuteri, Angelo
Scott, James
Schlessinger, David
Sanna, Serena
Salomaa, Veikko
Saharinen, Juha
Sabatti, Chiara
Ruokonen, Aimo
Rudan, Igor
Rose, Lynda M.
Roberts, Robert
Rieder, Mark
Psaty, Bruce M.
Pramstaller, Peter P.
Pichler, Irene
Perola, Markus
Penninx, Brenda W. J. H.
Pedersen, Nancy L.
Pattaro, Cristian
Parker, Alex N.
Pare, Guillaume
Oostra, Ben A.
O'Donnell, Christopher J.
Nieminen, Markku S.
Nickerson, Deborah A.
Montgomery, Grant W.
Meitinger, Thomas
McPherson, Ruth
McCarthy, Mark I.
McArdle, Wendy
Masson, David
Martin, Nicholas G.
Marroni, Fabio
Mangino, Massimo
Magnusson, Patrik K. E.
Lucas, Gavin
Luben, Robert
Loos, Ruth J. F.
Lokki, Marja-Liisa
Lettre, Guillaume
Langenberg, Claudia
Launer, Lenore J.
Lakatta, Edward G.
Laaksonen, Reijo
Kyvik, Kirsten O.
Kronenberg, Florian
Koenig, Inke R.
Khaw, Kay-Tee
Kaprio, Jaakko
Kaplan, Lee M.
Johansson, Asa
Jarvelin, Marjo-Riitta
Janssens, A. Cecile J. W.
Ingelsson, Erik
Igi, Wilmar
Hovingh, G. Kees
Hottenga, Jouke-Jan
Hofman, Albert
Hicks, Andrew A.
Hengstenberg, Christian
Heid, Iris M.
Hayward, Caroline
Havulinna, Aki S.
Hastie, Nicholas D.
Harris, Tamara B.
Haritunians, Talin
Hall, Alistair S.
Gyllensten, Ulf
Guiducci, Candace
Groop, Leif C.
Gonzalez, Elena
Gieger, Christian
Freimer, Nelson B.
Ferrucci, Luigi
Erdmann, Jeanette
Elliott, Paul
Ejebe, Kenechi G.
Doering, Angela
Dominiczak, Anna F.
Demissie, Serkalem
Deloukas, Panagiotis
de Geus, Eco J. C.
de Faire, Ulf
Crawford, Gabriel
Collins, Francis S.
Chen, Yii-der I.
Caulfield, Mark J.
Campbell, Harry
Burtt, Noel P.
Bonnycastle, Lori L.
Boomsma, Dorret I.
Boekholdt, S. Matthijs
Bergman, Richard N.
Barroso, Ines
Bandinelli, Stefania
Ballantyne, Christie M.
Assimes, Themistocles L.
Quertermous, Thomas
Altshuler, David
Seielstad, Mark
Wong, Tien Y.
Tai, E-Shyong
Feranil, Alan B.
Kuzawa, Christopher W.
Adair, Linda S.
Taylor, Herman A., Jr.
Borecki, Ingrid B.
Gabriel, Stacey B.
Wilson, James G.
Holm, Hilma
Thorsteinsdottir, Unnur
Gudnason, Vilmundur
Krauss, Ronald M.
Mohlke, Karen L.
Ordovas, Jose M.
Munroe, Patricia B.
Kooner, Jaspal S.
Tall, Alan R.
Hegele, Robert A.
Kastelein, John J. P.
Schadt, Eric E.
Rotter, Jerome I.
Boerwinkle, Eric
Strachan, David P.
Mooser, Vincent
Stefansson, Kari
Reilly, Muredach P.
Samani, Nilesh J.
Schunkert, Heribert
Cupples, L. Adrienne
Sandhu, Manjinder S.
Ridker, Paul M.
Rader, Daniel J.
van Duijn, Cornelia M.
Peltonen, Leena
Abecasis, Goncalo R.
Boehnke, Michael
Kathiresan, Sekar
TI Biological, clinical and population relevance of 95 loci for blood
lipids
SO NATURE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; DISEASE; RISK; TRAITS; TRIGLYCERIDES;
CHOLESTEROL; HUMANS
AB Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P<5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
C1 [Musunuru, Kiran; Pirruccello, James P.; Voight, Benjamin F.; Bandinelli, Stefania; Altshuler, David; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Teslovich, Tanya M.; Willer, Cristen J.; Stringham, Heather M.; Bergman, Richard N.; Abecasis, Goncalo R.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Musunuru, Kiran; Ballantyne, Christie M.; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Musunuru, Kiran; Pirruccello, James P.; Voight, Benjamin F.; Guiducci, Candace; Gonzalez, Elena; Ejebe, Kenechi G.; Crawford, Gabriel; Burtt, Noel P.; Altshuler, David; Wong, Tien Y.; Gabriel, Stacey B.; Kathiresan, Sekar] Broad Inst, Cambridge, MA 02142 USA.
[Musunuru, Kiran; Chasman, Daniel I.; Zee, Robert Y. L.; O'Donnell, Christopher J.; Assimes, Themistocles L.; Quertermous, Thomas; Altshuler, David; Ridker, Paul M.; Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Musunuru, Kiran; Pirruccello, James P.; Tai, E-Shyong] Johns Hopkins Univ, Sch Med, Baltimore, MD 21287 USA.
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[Edmondson, Andrew C.; Li, Mingyao; Adair, Linda S.; Reilly, Muredach P.; Rader, Daniel J.] Univ Penn, Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
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[Ripatti, Samuli; Surakka, Ida; Silander, Kaisa; Saharinen, Juha; Perola, Markus; Kaprio, Jaakko] Univ Helsinki, FIMM, FI-00014 Helsinki, Finland.
[Ripatti, Samuli; Surakka, Ida; Silander, Kaisa; Perola, Markus; Kaprio, Jaakko] Natl Inst Hlth & Welf, FI-00251 Helsinki, Finland.
[Chasman, Daniel I.; Zee, Robert Y. L.; Rose, Lynda M.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA.
[Johansen, Christopher T.; Hegele, Robert A.] Univ Western Ontario, Robarts Res Inst, London, ON N6A 5K8, Canada.
[Fouchier, Sigrid W.; Hovingh, G. Kees; Kastelein, John J. P.] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands.
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[Orho-Melander, Marju; Melander, Olle; Groop, Leif C.] Lund Univ, Dept Clin Sci, SE-20502 Malmo, Sweden.
[Johnson, Toby; Caulfield, Mark J.] Queen Mary Univ London, Clin Pharmacol & Barts & London Genome Ctr, William Harvey Res Inst, Barts & London Sch Med, London EC1M 6BQ, England.
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[Lamina, Claudia; Kronenberg, Florian] Innsbruck Med Univ, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, A-6020 Innsbruck, Austria.
[Ziegler, Andreas; Koenig, Inke R.] Med Univ Lubeck, Inst Med Biometrie & Stat, D-23562 Lubeck, Germany.
[Wright, Alan F.; Vitart, Veronique; Hayward, Caroline; Hastie, Nicholas D.] Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
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[Tanaka, Toshiko] NIA, Clin Res Branch, NIH, Baltimore, MD 21225 USA.
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[Spector, Tim D.; Soranzo, Nicole; Mangino, Massimo] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.
[Soranzo, Nicole; Deloukas, Panagiotis; Barroso, Ines; Sandhu, Manjinder S.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
[Smit, Johannes H.; Penninx, Brenda W. J. H.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst, Dept Psychiat, NL-1007 MB Amsterdam, Netherlands.
[Sinisalo, Juha; Nieminen, Markku S.] HUCH, Dept Med, Div Cardiol, FI-00029 Helsinki, Finland.
[Scuteri, Angelo] IRCCS, INRCA, Unita Operat Geriatria, I-00189 Rome, Italy.
[Scott, James; Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Natl Heart & Lung Inst, London W12 0NN, England.
[Schlessinger, David; Lakatta, Edward G.] NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA.
[Sabatti, Chiara] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Ruokonen, Aimo] Univ Oulu, Dept Clin Chem, FI-90220 Oulu, Finland.
[Tanaka, Toshiko] Univ Ottawa, John & Jennifer Ruddy Canadian Cardiovasc Gen Ctr, Ottawa, ON K1Y 4W7, Canada.
[Psaty, Bruce M.] Univ Washington, Dept Med, Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA 98101 USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA 98101 USA.
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[Pramstaller, Peter P.; Pichler, Irene; Pattaro, Cristian; Hicks, Andrew A.] Univ Lubeck, European Acad Bozen Bolzano EURAC, Inst Med Genet, Lubeck, Germany.
[Pedersen, Nancy L.; Magnusson, Patrik K. E.; Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden.
[Parker, Alex N.] Amgen Inc, Thousand Oaks, CA 91320 USA.
[Pare, Guillaume] McMaster Univ, Genet & Mol Epidemiol Lab, Hamilton, ON L8N 3Z5, Canada.
[Oostra, Ben A.] Erasmus Univ, Med Ctr, Dept Clin Genet, NL-3000 CA Rotterdam, Netherlands.
[Meitinger, Thomas] Deutsch Forsch Zentrum Umwelt & Gesundheit, Helmholtz Zentrum Munchen, Inst Humangenet, D-85764 Neuherberg, Germany.
[Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-81675 Munich, Germany.
[McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
[McCarthy, Mark I.] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Med, Oxford OX3 7LJ, England.
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[McArdle, Wendy] Univ Bristol, Avon Longitudinal Study Parents & Children, Bristol BS8 2BN, Avon, England.
[Marroni, Fabio] Inst Appl Genom, I-33100 Udine, Italy.
[Lucas, Gavin] Inst Municipal Invest Med, E-08003 Barcelona, Spain.
[Lokki, Marja-Liisa] Univ Helsinki, Haartman Inst, Transplantat Lab, FI-00014 Helsinki, Finland.
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[Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, Fac Med, FI-00014 Helsinki, Finland.
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[Johansson, Asa; Igi, Wilmar; Gyllensten, Ulf] Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden.
[Jarvelin, Marjo-Riitta; Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London W2 1PG, England.
[Jarvelin, Marjo-Riitta] Univ Oulu, Dept Publ Hlth Sci & Gen Practice, FI-90220 Oulu, Finland.
[Hengstenberg, Christian] Univ Regensburg, Klin & Poliklin Innere Med 2, D-93053 Regensburg, Germany.
[Heid, Iris M.] Univ Regensburg, Med Ctr, Dept Epidemiol & Prevent Med, D-93053 Regensburg, Germany.
[Havulinna, Aki S.] Aalto Univ, Sch Sci & Technol, Dept Biomed Engn & Computat Sci, FI-00076 Aalto, Finland.
[Hall, Alistair S.] Univ Leeds, Fac Med & Hlth, LIGHT Res Inst, Leeds LS2 9JT, W Yorkshire, England.
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[Erdmann, Jeanette; Schunkert, Heribert] Med Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany.
[Elliott, Paul] Univ London Imperial Coll Sci Technol & Med, MRC HPA Ctr Environm & Hlth, London W2 1PG, England.
[Dominiczak, Anna F.] Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Glasgow G12 8TA, Lanark, Scotland.
[de Faire, Ulf] Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, SE-17177 Stockholm, Sweden.
[Collins, Francis S.; Bonnycastle, Lori L.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Boekholdt, S. Matthijs] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands.
[Boekholdt, S. Matthijs] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands.
[Bergman, Richard N.] Univ So Calif, Dept Physiol & Biophys, Los Angeles, CA 90033 USA.
[Bandinelli, Stefania] ASF, Geriatr Unit, I-50125 Florence, Italy.
[Ballantyne, Christie M.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
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[Wong, Tien Y.] Natl Univ Singapore, Singapore Eye Res Inst, Singapore 168751, Singapore.
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[Tai, E-Shyong] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Epidemiol, Singapore 117597, Singapore.
[Tai, E-Shyong] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Publ Hlth, Singapore 117597, Singapore.
[Feranil, Alan B.] Univ San Carlos, Off Populat Studies Fdn, Cebu 6000, Philippines.
[Kuzawa, Christopher W.] Northwestern Univ, Dept Anthropol, Evanston, IL 60208 USA.
[Adair, Linda S.] Univ N Carolina, Carolina Populat Ctr, Dept Nutr, Chapel Hill, NC 27516 USA.
[Taylor, Herman A., Jr.; Wilson, James G.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39126 USA.
[Krauss, Ronald M.] Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA.
[Ordovas, Jose M.] Ctr Nacl Invest Cardiovasc, Dept Cardiovasc Epidemiol & Populat Genet, Madrid 28029, Spain.
[Ordovas, Jose M.] Tufts Univ, Nutr & Genom Lab, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Munroe, Patricia B.] Queen Mary Univ London, Clin Pharmacol & Barts & London Genome Ctr, William Harvey Res Inst, Barts & London Sch Med & Dent, London EC1M 6BQ, England.
[Schadt, Eric E.] Sage Bionetworks, Seattle, WA 98109 USA.
[Strachan, David P.] St Georges Univ London, Div Community Hlth Sci, London SW17 0RE, England.
[Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, NIHR Biomed Res Unit Cardiovasc Dis, Glenfield Hosp, Leicester LE3 9QP, Leics, England.
RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
EM skathiresan@partners.org
RI Aulchenko, Yurii/M-8270-2013; Laaksonen, Reijo/D-6323-2014; Boekholdt,
Matthijs/G-7562-2014; Pramstaller, Peter/C-2357-2008; Fouchier,
Sigrid/A-8310-2011; Gudnason, Vilmundur/K-6885-2015; Ripatti,
Samuli/H-9446-2014; Wilson, James F/A-5704-2009; de Geus,
Eco/M-9318-2015; Montgomery, Grant/B-7148-2008; Meitinger,
Thomas/O-1318-2015; Hegele, Robert/G-3301-2011; Ejebe,
Kenechi/I-9238-2016; Smith, Albert/K-5150-2015; Kyvik, Kirsten
/K-5680-2016; mangino, massimo/F-5134-2011; Hayward,
Caroline/M-8818-2016; Konig, Inke/A-4544-2009; Erdmann,
Jeanette/A-4417-2009; Magnusson, Patrik/C-4458-2017; Feitosa,
Mary/K-8044-2012; Hicks, Andrew/E-9518-2017; Erdmann,
Jeanette/P-7513-2014; Abecasis, Goncalo/B-7840-2010; Altshuler,
David/A-4476-2009; Kronenberg, Florian/B-1736-2008; Voight,
Benjamin/F-1775-2011; Stylianou, Ioannis/C-6061-2012; Lucas,
Gavin/D-4346-2012; Spector, Tim/F-6533-2012; Lamina,
Claudia/F-7608-2010; Rudan, Igor/I-1467-2012; Johansson,
Asa/G-5270-2011; Deloukas, Panos/B-2922-2013; Colaus,
PsyColaus/K-6607-2013;
OI Aulchenko, Yurii/0000-0002-7899-1575; Gudnason,
Vilmundur/0000-0001-5696-0084; Ripatti, Samuli/0000-0002-0504-1202;
Wilson, James F/0000-0001-5751-9178; de Geus, Eco/0000-0001-6022-2666;
Montgomery, Grant/0000-0002-4140-8139; Ejebe,
Kenechi/0000-0002-6090-8657; Smith, Albert/0000-0003-1942-5845; Kyvik,
Kirsten /0000-0003-2981-0245; mangino, massimo/0000-0002-2167-7470;
Hayward, Caroline/0000-0002-9405-9550; Feitosa,
Mary/0000-0002-0933-2410; Hicks, Andrew/0000-0001-6320-0411; Pichler,
Irene/0000-0001-8251-0757; Cupples, L. Adrienne/0000-0003-0273-7965;
Marroni, Fabio/0000-0002-1556-5907; Soranzo, Nicole/0000-0003-1095-3852;
Willer, Cristen/0000-0001-5645-4966; Seielstad,
Mark/0000-0001-5783-1401; Sijbrands, Eric/0000-0001-8857-7389; sanna,
serena/0000-0002-3768-1749; Johnson, Toby/0000-0002-5998-3270; Abecasis,
Goncalo/0000-0003-1509-1825; Erdmann, Jeanette/0000-0002-4486-6231;
Luben, Robert/0000-0002-5088-6343; Gieger,
Christian/0000-0001-6986-9554; Ziegler, Andreas/0000-0002-8386-5397;
Janssens, A Cecile/0000-0002-6153-4976; Jarvelin,
Marjo-Riitta/0000-0002-2149-0630; Ordovas, Jose/0000-0002-7581-5680;
Kaprio, Jaakko/0000-0002-3716-2455; Altshuler,
David/0000-0002-7250-4107; Kronenberg, Florian/0000-0003-2229-1120;
Rudan, Igor/0000-0001-6993-6884; Johansson, Asa/0000-0002-2915-4498;
Deloukas, Panos/0000-0001-9251-070X; Tai, E Shyong/0000-0003-2929-8966;
Martin, Nicholas/0000-0003-4069-8020
FU British Heart Foundation [PG/02/128, PG/08/094, PG/08/094/26019,
RG/07/005/23633, SP/08/005/25115]; CCR NIH HHS [RC1 HL099634-02]; Chief
Scientist Office [CZB/4/710]; FIC NIH HHS [TW05596]; Intramural NIH HHS;
Medical Research Council [G0801056, G0000934, G0401527, G0601966,
G0700931, G0701863, G0801566, G9521010, G9521010D, MC_QA137934,
MC_U106179471, MC_U106188470, MC_U127561128]; NCI NIH HHS [CA 047988];
NCRR NIH HHS [M01-RR00425, RR20649, U54 RR020278, UL1RR025005]; NHGRI
NIH HHS [1Z01 HG000024, N01-HG-65403, T32 HG00040, U01HG004402]; NHLBI
NIH HHS [5R01HL087679-02, 5R01HL08770003, 5R01HL08821502, HL 04381, HL
080467, HL-54776, HL085144, K99 HL098364, K99 HL098364-01, K99HL094535,
N01 HC-15103, N01 HC-55222, N01-HC-25195, N01-HC-35129, N01-HC-45133,
N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020,
N01-HC-55021, N01-HC-55022, N01-HC-75150, N01-HC-85079, N01-HC-85080,
N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085,
N01-HC-85086, N02-HL-6-4278, R01 HL087647, R01 HL087676, R01 HL089650,
R01HL086694, R01HL087641, R01HL087652, R01HL59367, RC1 HL099634, RC1
HL099634-02, RC1 HL099793, RC2 HL101864,, RC2 HL102419, T32HL007208, U01
HL069757, U01 HL080295]; NIA NIH HHS [N01-AG-12100]; NICHD NIH HHS [R24
HD050924]; NIDDK NIH HHS [5R01DK06833603, 5R01DK07568102, DK062370,
DK063491, DK072193, DK078150, DK56350, R01 DK072193, R01 DK078150, U01
DK062370, U01 DK062418]; NIEHS NIH HHS [ES10126]; NIGMS NIH HHS [T32
GM007092]; PHS HHS [HHSN268200625226C]; Wellcome Trust [068545/Z/02,
076113/B/04/Z, 077016/Z/05/Z, 079895]
NR 20
TC 1524
Z9 1557
U1 22
U2 219
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD AUG 5
PY 2010
VL 466
IS 7307
BP 707
EP 713
DI 10.1038/nature09270
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 634EN
UT WOS:000280562500029
PM 20686565
ER
PT J
AU Musunuru, K
Strong, A
Frank-Kamenetsky, M
Lee, NE
Ahfeldt, T
Sachs, KV
Li, XY
Li, H
Kuperwasser, N
Ruda, VM
Pirruccello, JP
Muchmore, B
Prokunina-Olsson, L
Hall, JL
Schadt, EE
Morales, CR
Lund-Katz, S
Phillips, MC
Wong, J
Cantley, W
Racie, T
Ejebe, KG
Orho-Melander, M
Melander, O
Koteliansky, V
Fitzgerald, K
Krauss, RM
Cowan, CA
Kathiresan, S
Rader, DJ
AF Musunuru, Kiran
Strong, Alanna
Frank-Kamenetsky, Maria
Lee, Noemi E.
Ahfeldt, Tim
Sachs, Katherine V.
Li, Xiaoyu
Li, Hui
Kuperwasser, Nicolas
Ruda, Vera M.
Pirruccello, James P.
Muchmore, Brian
Prokunina-Olsson, Ludmila
Hall, Jennifer L.
Schadt, Eric E.
Morales, Carlos R.
Lund-Katz, Sissel
Phillips, Michael C.
Wong, Jamie
Cantley, William
Racie, Timothy
Ejebe, Kenechi G.
Orho-Melander, Marju
Melander, Olle
Koteliansky, Victor
Fitzgerald, Kevin
Krauss, Ronald M.
Cowan, Chad A.
Kathiresan, Sekar
Rader, Daniel J.
TI From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol
locus
SO NATURE
LA English
DT Article
ID DENSITY-LIPOPROTEIN CHOLESTEROL; GENOME-WIDE ASSOCIATION;
CORONARY-ARTERY-DISEASE; PROTEIN; GENE; SORTILIN; TRANSCRIPTION;
POPULATION; TRANSPORT; DESIGN
AB Recent genome-wide association studies (GWASs) have identified a locus on chromosome 1p13 strongly associated with both plasma low-density lipoprotein cholesterol (LDL-C) and myocardial infarction (MI) in humans. Here we show through a series of studies in human cohorts and human-derived hepatocytes that a common noncoding polymorphism at the 1p13 locus, rs12740374, creates a C/EBP (CCAAT/enhancer binding protein) transcription factor binding site and alters the hepatic expression of the SORT1 gene. With small interfering RNA (siRNA) knockdown and viral overexpression in mouse liver, we demonstrate that Sort1 alters plasma LDL-C and very low-density lipoprotein (VLDL) particle levels by modulating hepatic VLDL secretion. Thus, we provide functional evidence for a novel regulatory pathway for lipoprotein metabolism and suggest that modulation of this pathway may alter risk for MI in humans. We also demonstrate that common noncoding DNA variants identified by GWASs can directly contribute to clinical phenotypes.
C1 [Strong, Alanna; Sachs, Katherine V.; Li, Xiaoyu; Li, Hui; Rader, Daniel J.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA.
[Strong, Alanna; Sachs, Katherine V.; Li, Xiaoyu; Li, Hui; Rader, Daniel J.] Univ Penn, Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.
[Strong, Alanna; Sachs, Katherine V.; Li, Xiaoyu; Li, Hui; Rader, Daniel J.] Univ Penn, Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Musunuru, Kiran; Lee, Noemi E.; Ahfeldt, Tim; Kuperwasser, Nicolas; Ruda, Vera M.; Pirruccello, James P.; Ejebe, Kenechi G.; Cowan, Chad A.; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Musunuru, Kiran; Lee, Noemi E.; Ahfeldt, Tim; Kuperwasser, Nicolas; Ruda, Vera M.; Pirruccello, James P.; Ejebe, Kenechi G.; Cowan, Chad A.; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Musunuru, Kiran; Lee, Noemi E.; Kuperwasser, Nicolas; Ruda, Vera M.; Pirruccello, James P.; Ejebe, Kenechi G.; Cowan, Chad A.; Kathiresan, Sekar] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Musunuru, Kiran; Pirruccello, James P.; Hall, Jennifer L.; Ejebe, Kenechi G.; Cowan, Chad A.; Kathiresan, Sekar] Broad Inst, Cambridge, MA 02142 USA.
[Musunuru, Kiran] Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD 21287 USA.
[Frank-Kamenetsky, Maria; Wong, Jamie; Cantley, William; Racie, Timothy; Koteliansky, Victor; Fitzgerald, Kevin] Alnylam Pharmaceut Inc, Cambridge, MA 02142 USA.
[Ahfeldt, Tim] Univ Med Ctr Hamburg Eppendorf, Dept Biochem & Mol Biol Mol Cell Biol 2, D-20246 Hamburg, Germany.
[Muchmore, Brian; Prokunina-Olsson, Ludmila] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Hall, Jennifer L.] Univ Minnesota, Program Cardiovasc Translat Genom, Lillehei Heart Inst, Minneapolis, MN 55455 USA.
[Schadt, Eric E.] Sage Bionetworks, Seattle, WA 98109 USA.
[Morales, Carlos R.] McGill Univ, Dept Anat & Cell Biol, Montreal, PQ H3A 2B2, Canada.
[Lund-Katz, Sissel; Phillips, Michael C.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA.
[Orho-Melander, Marju; Melander, Olle] Lund Univ, Skania Univ Hosp, Dept Clin Sci, SE-20502 Malmo, Sweden.
[Krauss, Ronald M.] Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA.
RP Rader, DJ (reprint author), Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA.
EM skathiresan@partners.org; rader@mail.med.upenn.edu
RI Morales, Carlos/H-1055-2011; Ejebe, Kenechi/I-9238-2016; Ahfeldt,
Tim/E-2935-2017;
OI Ejebe, Kenechi/0000-0002-6090-8657; Prokunina-Olsson,
Ludmila/0000-0002-9622-2091
FU United States National Institutes of Health (NIH); NIH [K99-HL098364,
U01-HL069757, RC2-HL101864, P01-HL059407]; Harvard Stem Cell Institute;
Division of Cancer Epidemiology & Genetics, National Cancer Institute,
NIH; Swedish Medical Research Council; Heart-Lung Foundation; Pahlsson
Foundation; Quest Diagnostics, Inc.; Bristol-Myers Squibb
FX We thank D. Altshuler, E. Fisher and J. Maraganore for advice and
guidance, and A. Akinc, J. Billheimer, R. Brown, R. Camahort, D.
Cromley, E. Eduoard, I. Fuki, C. Geaney, G. Hinkle, I. Kohaar, S.
Kuchimanchi, W. Lagor, F. Lau, D. Lum, M. Maier, D. Marchadier, R.
Meyers, J. Millar, S. Milstein, D. Nguyen, D. Perez, D. Peters, V.
Redon, A. Rigamonti, R. Schinzel, M.-S. Sun, S.-A. Toh, A. Wilson and K.
Wojnoonski for assistance and suggestions. We acknowledge the National
Heart, Lung, and Blood Institute (NHLBI) Gene Therapy Resource Program
for providing support for viral vector production as well as the Vector
Core laboratory of the University of Pennsylvania for producing the
vectors. We acknowledge the members of the NHLBI Candidate Gene
Association Resource (CARe) lipids working group for the contribution of
association data in African Americans. This work was supported in part
by a T32 grant in Cell and Molecular Training for Cardiovascular Biology
from the United States National Institutes of Health (NIH), K99-HL098364
from the NIH, and the Clinician Scientist Program of the Harvard Stem
Cell Institute (K. M.); a Medical Scientist Training Program grant from
the NIH (A. S.); the intramural research program of the Division of
Cancer Epidemiology & Genetics, National Cancer Institute, NIH
(L.P.-O.); the Swedish Medical Research Council, Heart-Lung Foundation,
and Pahlsson Foundation (M.O.-M., O.M.); U01-HL069757 from the NIH and
research support from Quest Diagnostics, Inc. (R. M. K.); RC2-HL101864
from the NIH (S. K.); and P01-HL059407 and RC2-HL101864 from the NIH and
a "Freedom to Discover'' Unrestricted Cardiovascular Research Grant from
Bristol-Myers Squibb (D.J.R.).
NR 35
TC 431
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U1 3
U2 43
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD AUG 5
PY 2010
VL 466
IS 7307
BP 714
EP U2
DI 10.1038/nature09266
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 634EN
UT WOS:000280562500030
PM 20686566
ER
PT J
AU Liu, J
Nussinov, R
AF Liu, Jin
Nussinov, Ruth
TI Rbx1 Flexible Linker Facilitates Cullin-RING Ligase Function Before
Neddylation and After Deneddylation
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID SCF UBIQUITIN LIGASE; MOLECULAR-DYNAMICS; BINDING CASCADES; PROTEIN;
NEDD8; ACTIVATION; ALLOSTERY; INSIGHTS; RECOGNITION; CONJUGATION
AB In ubiquitination, cullin-RING E3 ubiquitin ligases (CRLs) assist in ubiquitin transfer from ubiquitin-conjugating enzyme E2 to the substrate. Neddylation, which involves NEDD8 transfer from E2 to E3-cullin, stimulates ubiquitination by inducing conformational change in CRLs. However, deneddylation, which removes NEDD8 from cullin, does not suppress ubiquitination in vivo, raising the question of how neddylation/deneddylation exerts its effects. Using molecular-dynamics simulations, we demonstrate that before neddylation occurs, the linker flexibility of Rbx1, a CAL component, leads to conformational changes in CRLs that allow neddylation and initiation of ubiquitination. These large NEDD8-induced conformational changes are retained after deneddylation, allowing both initiation of the ubiquitination process and ubiquitin chain elongation after deneddylation. Furthermore, mutation of lysine, the cullin residue to which NEDD8 covalently attaches, dramatically reduces CAL conformational changes, suggesting that the acceptor lysine allosterically regulates CRLs. Thus, our results imply that neddylation stimulates ubiquitination by CAL conformational control via lysine modification.
C1 [Liu, Jin; Nussinov, Ruth] NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
RP Nussinov, R (reprint author), NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA.
EM ruthnu@helix.nih.gov
FU National Cancer Institute, National Institutes of Health (NW)
[HHSN261200800001E]; Center for Cancer Research, National Cancer
Institute, NIH
FX This project was funded in whole or in part by federal funds from the
National Cancer Institute, National Institutes of Health (NW), under
contract number HHSN261200800001E. The content of this publication does
not necessarily reflect the views or policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
Support was also provided by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, NIH. This study
used the high-performance computational capabilities of the Biowulf
Linux cluster at the NIH, Bethesda, MD (http://biowulf.nih.gov).
NR 33
TC 19
Z9 19
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD AUG 4
PY 2010
VL 99
IS 3
BP 736
EP 744
DI 10.1016/j.bpj.2010.05.021
PG 9
WC Biophysics
SC Biophysics
GA 635YE
UT WOS:000280693100008
PM 20682250
ER
PT J
AU Nestorovich, EM
Karginov, VA
Bezrukov, SM
AF Nestorovich, Ekaterina M.
Karginov, Vladimir A.
Bezrukov, Sergey M.
TI Polymer Partitioning and Ion Selectivity Suggest Asymmetrical Shape for
the Membrane Pore Formed by Epsilon Toxin
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID PLANAR LIPID-BILAYERS; PROTECTIVE ANTIGEN; ESCHERICHIA-COLI;
ALPHA-HEMOLYSIN; LETHAL TOXIN; MDCK CELLS; CHANNEL; CONDUCTANCE;
GEOMETRY; OMPF
AB Using poly-(ethylene glycol)s of different molecular weights, we probe the channels formed in planar lipid bilayers by epsilon toxin secreted by the anaerobic bacterium Clostridium perfringens. We find that the pore is highly asymmetric. The cutoff size of polymers entering the pore through its opening from the cis side, the side of toxin addition, is similar to 500 Da, whereas the cutoff size for the polymers entering from the trans side is similar to 2300 Da. Comparing these characteristic molecular weights with those reported earlier for OmpF porin and the alpha-Hemolysin channel, we estimate the radii of cis and trans openings as 0.4 nm and 1.0 nm, respectively. The simplest geometry corresponding to these findings is that of a truncated cone. The asymmetry of the pore is also confirmed by measurements of the reversal potential at oppositely directed salt gradients. The moderate anionic selectivity of the channel is salted-out more efficiently when the salt concentration is higher at the trans side of the pore.
C1 [Nestorovich, Ekaterina M.; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
[Karginov, Vladimir A.] Innovat Biol, Herndon, VA USA.
RP Nestorovich, EM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
EM nestoroe@mail.nih.gov
FU National Institutes of Health [2R44AI074105-02]; Eunice Kennedy Shriver
National Institute of Child Health and Human Development; National
Institutes of Health; National Institute of Allergy and Infectious
Diseases (NIAID)
FX V.A.K. was supported by grant No. 2R44AI074105-02 from the National
Institutes of Health. E.M.N. and S.M.B. were supported by the Intramural
Research Program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development, National Institutes of Health, and
the National Institute of Allergy and Infectious Diseases (NIAID)
intramural biodefense research grant for an institute other than NIAID.
V.A.K. is an employee and shareholder of Innovative Biologics.
NR 57
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Z9 24
U1 0
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD AUG 4
PY 2010
VL 99
IS 3
BP 782
EP 789
DI 10.1016/j.bpj.2010.05.014
PG 8
WC Biophysics
SC Biophysics
GA 635YE
UT WOS:000280693100013
PM 20682255
ER
PT J
AU Soubias, O
Teague, WE
Hines, KG
Mitchell, DC
Gawrisch, K
AF Soubias, Olivier
Teague, Walter E., Jr.
Hines, Kirk G.
Mitchell, Drake C.
Gawrisch, Klaus
TI Contribution of Membrane Elastic Energy to Rhodopsin Function
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID DEUTERIUM MAGNETIC-RESONANCE; POLYUNSATURATED FATTY-ACIDS;
LIPID-BILAYERS; METARHODOPSIN-II; PHOSPHOLIPID BILAYER;
PHYSICAL-PROPERTIES; BENDING ELASTICITY; ACYL CHAINS; CURVATURE;
HYDRATION
AB We considered the issue of whether shifts in the metarhodopsin I (MI)-metarhodopsin II (MII) equilibrium from lipid composition are fully explicable by differences in bilayer curvature elastic stress. A series of six lipids with known spontaneous radii of monolayer curvature and bending elastic moduli were added at increasing concentrations to the matrix lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and the MI-MII equilibrium measured by flash photolysis followed by recording UV-vis spectra. The average area-per-lipid molecule and the membrane hydrophobic thickness were derived from measurements of the (2)H NMR order parameter profile of the palmitic acid chain in POPC. For the series of ethanolamines with different levels of headgroup methylation, shifts in the MI-MII equilibrium correlated with changes in membrane elastic properties as expressed by the product of spontaneous radius of monolayer curvature, bending elastic modulus, and lateral area per molecule. However, for the entire series of lipids, elastic energy explained the shifts only partially. Additional contributions correlated with the capability of the ethanolamine headgroups to engage in hydrogen bonding with the protein, independent of the state of ethanolamine methylation, with introduction of polyunsaturated sn-2 hydrocarbon chains, and with replacement of the palmitic acid sn-1 chains by oleic acid. The experiments point to the importance of interactions of rhodopsin with particular lipid species in the first layer of lipids surrounding the protein as well as to membrane elastic stress in the lipid-protein domain.
C1 [Soubias, Olivier; Teague, Walter E., Jr.; Hines, Kirk G.; Gawrisch, Klaus] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA.
[Mitchell, Drake C.] Portland State Univ, Dept Phys, Portland, OR 97207 USA.
RP Gawrisch, K (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA.
EM gawrisch@helix.nih.gov
FU National Institute on Alcohol Abuse and Alcoholism, of the National
Institutes of Health, Bethesda, Maryland
FX This work was supported by the Intramural Research Program of National
Institute on Alcohol Abuse and Alcoholism, of the National Institutes of
Health, Bethesda, Maryland.
NR 39
TC 60
Z9 60
U1 2
U2 17
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD AUG 4
PY 2010
VL 99
IS 3
BP 817
EP 824
DI 10.1016/j.bpj.2010.04.068
PG 8
WC Biophysics
SC Biophysics
GA 635YE
UT WOS:000280693100017
PM 20682259
ER
PT J
AU Jiao, M
Li, HT
Chen, J
Minton, AP
Liang, Y
AF Jiao, Ming
Li, Hong-Tao
Chen, Jie
Minton, Allen P.
Liang, Yi
TI Attractive Protein-Polymer Interactions Markedly Alter the Effect of
Macromolecular Crowding on Protein Association Equilibria
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID SUPEROXIDE-DISMUTASE; SELF-ASSOCIATION; EXCLUDED-VOLUME; INTRACELLULAR
ENVIRONMENTS; PHYSIOLOGICAL CONSEQUENCES; CU,ZN-SUPEROXIDE DISMUTASE;
GLOBULAR-PROTEINS; OSMOTIC-PRESSURE; HYALURONIC ACID; LIVER CATALASE
AB The dependence of the fluorescence of catalase upon the concentration of added superoxide dismutase (SOD) indicates that SOD binds to saturable sites on catalase. The affinity of SOD for these sites varies with temperature, and with the concentration of each of three nominally inert polymeric additives-dextran 70, Ficoll 70, and polyethylene glycol 2000. At room temperature (25.0 degrees C) and higher, the addition of high concentrations of polymer is found to significantly enhance the affinity of SOD for catalase, but with decreasing temperature the enhancing effect of polymer addition diminishes, and at 8.0 degrees C, addition of polymer has little or no effect on the affinity of SOD for catalase. The results presented here provide the first experimental evidence for the existence of competition between a repulsive excluded volume interaction between protein and polymer, which tends to enhance association of dilute protein, and an attractive interaction between protein and polymer, which tends to inhibit protein association. The net effect of high concentrations of polymer upon protein associations depends upon the relative strength of these two types of interactions at the temperature of measurement, and may vary significantly between different proteins and/or polymers.
C1 [Jiao, Ming; Li, Hong-Tao; Chen, Jie; Liang, Yi] Wuhan Univ, Coll Life Sci, State Key Lab Virol, Wuhan 430072, Peoples R China.
[Minton, Allen P.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
RP Liang, Y (reprint author), Wuhan Univ, Coll Life Sci, State Key Lab Virol, Wuhan 430072, Peoples R China.
EM minton@helix.nih.gov; liangyi@whu.edu.cn
OI Minton, Allen/0000-0001-8459-1247
FU National Key Basic Research Foundation of China [2006CB910301]; National
Natural Science Foundation of China [30770421, 30970599]; Chinese 111
Project [B06018]; National Institute of Diabetes and Digestive and
Kidney Diseases
FX Research of Y.L., M.J., H-T.L., and J.C. is supported by National Key
Basic Research Foundation of China (Grant 2006CB910301 to Y.L.),
National Natural Science Foundation of China (Grants 30770421 and
30970599 to Y.L.), and Chinese 111 Project Grant B06018. The research of
A.P.M. is supported by the Intramural Research Program of the National
Institute of Diabetes and Digestive and Kidney Diseases.
NR 59
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U1 3
U2 38
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 AUG 4
PY 2010
VL 99
IS 3
BP 914
EP 923
DI 10.1016/j.bpj.2010.05.013
PG 10
WC Biophysics
SC Biophysics
GA 635YE
UT WOS:000280693100028
PM 20682270
ER
PT J
AU Li, FQ
Xue, YX
Wang, JS
Fang, Q
Li, YQ
Zhu, WL
He, YY
Liu, JF
Xue, LF
Shaham, Y
Lu, L
AF Li, Fang-qiong
Xue, Yan-xue
Wang, Ji-shi
Fang, Qin
Li, Yan-qin
Zhu, Wei-Li
He, Ying-ying
Liu, Jian-feng
Xue, Li-fen
Shaham, Yavin
Lu, Lin
TI Basolateral Amygdala Cdk5 Activity Mediates Consolidation and
Reconsolidation of Memories for Cocaine Cues
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID CYCLIN-DEPENDENT KINASE-5; CONDITIONED PLACE PREFERENCE; DRUG-SEEKING
BEHAVIOR; NUCLEUS-ACCUMBENS; REINFORCING EFFICACY; SIGNALING PATHWAY;
CONTEXTUAL FEAR; NMDA RECEPTORS; REWARD; INCUBATION
AB Cocaine use and relapse involves learned associations between cocaine-associated environmental contexts and discrete stimuli and cocaine effects. Initially, these contextual and discrete cues undergo memory consolidation after being paired with cocaine exposure. During abstinence, cocaine cue memories can undergo memory reconsolidation after cue exposure without the drug. We used a conditioned place preference (CPP) procedure in rats to study the role of neuronal protein kinase cyclin-dependent kinase 5 (Cdk5) in consolidation and reconsolidation of cocaine cue memories. We found that the expression of cocaine CPP in drug-free tests 1 d after CPP training (four pairings of 10 mg/kg cocaine with one context and four pairings of saline with a different context) increased Cdk5 activity, and levels of the Cdk5 activator p35 in basolateral but not central amygdala. We also found that basolateral (but not central) amygdala injections of the Cdk5 inhibitor beta-butyrolactone (100 ng/side) immediately (but not 6 h) after cocaine-context pairings during training prevented subsequent cocaine CPP expression. After training, acute basolateral (but not central) amygdala beta-butyrolactone injections immediately before testing prevented the expression of cocaine CPP; this effect was also observed on a second test performed 1 d later, suggesting an effect on reconsolidation of cocaine cue memories. In support, basolateral beta-butyrolactone injections, given immediately (but not 6 h) after a single exposure to the cocaine-paired context, prevented cocaine CPP expression 1 and 14 d after the injections. Results indicate that basolateral amygdala Cdk5 activity is critical for consolidation and reconsolidation of the memories of cocaine-associated environmental cues.
C1 [Li, Fang-qiong; Wang, Ji-shi; Fang, Qin; He, Ying-ying] Guiyang Med Univ, Sch Pharm, Guiyang 550004, Peoples R China.
[Li, Fang-qiong; Wang, Ji-shi; Fang, Qin; He, Ying-ying] Guiyang Med Univ, Affiliated Hosp, Guiyang 550004, Peoples R China.
[Li, Fang-qiong; Xue, Yan-xue; Li, Yan-qin; Zhu, Wei-Li; Liu, Jian-feng; Xue, Li-fen; Lu, Lin] Peking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China.
[Shaham, Yavin] Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Wang, JS (reprint author), Guiyang Med Univ, Sch Pharm, Guiyang 550004, Peoples R China.
EM jswang_yg@yahoo.com; linlu@bjmu.edu.cn
RI Xue, Yan-Xue/B-7245-2011; shaham, yavin/G-1306-2014;
OI Liu, Jianfeng/0000-0002-3464-6462
FU National Basic Research Program of China [2007CB512302]; Natural Science
Foundation of Beijing Municipality [09G0762, 7092058]; Natural Science
Foundation of Guizhou Province [2008-59]
FX This work was supported in part by National Basic Research Program of
China Grant 2007CB512302, Natural Science Foundation of Beijing
Municipality Grants 09G0762 and 7092058, and Natural Science Foundation
of Guizhou Province Grant 2008-59.
NR 62
TC 48
Z9 52
U1 1
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 AUG 4
PY 2010
VL 30
IS 31
BP 10351
EP 10359
DI 10.1523/JNEUROSCI.2112-10.2010
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 637BP
UT WOS:000280789600009
PM 20685978
ER
PT J
AU Miquelajauregui, A
Varela-Echavarria, A
Ceci, ML
Garcia-Moreno, F
Ricano, I
Hoang, K
Frade-Perez, D
Portera-Cailliau, C
Tamariz, E
De Carlos, JA
Westphal, H
Zhao, YG
AF Miquelajauregui, Amaya
Varela-Echavarria, Alfredo
Laura Ceci, M.
Garcia-Moreno, Fernando
Ricano, Itzel
Hoang, Kimmi
Frade-Perez, Daniela
Portera-Cailliau, Carlos
Tamariz, Elisa
De Carlos, Juan A.
Westphal, Heiner
Zhao, Yangu
TI LIM-Homeobox Gene Lhx5 Is Required for Normal Development of
Cajal-Retzius Cells
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID MARGINAL ZONE; HIPPOCAMPAL MORPHOGENESIS; CEREBRAL-CORTEX; EXPRESSION;
NEURONS; REELIN; DIFFERENTIATION; SPECIFICATION; GENERATION; MIGRATION
AB Cajal-Retzius (C-R) cells play important roles in the lamination of the mammalian cortex via reelin secretion. The genetic mechanisms underlying the development of these neurons have just begun to be unraveled. Here, we show that two closely related LIM-homeobox genes Lhx1 and Lhx5 are expressed in reelin(+) cells in various regions in the mouse telencephalon at or adjacent to sites where the C-R cells are generated, including the cortical hem, the mantle region of the septal/retrobulbar area, and the ventral pallium. Whereas Lhx5 is expressed in all of these reelin-expressing domains, Lhx1 is preferentially expressed in the septal area and in a continuous domain spanning from lateral olfactory region to caudomedial territories. Genetic ablation of Lhx5 results in decreased reelin(+) and p73(+) cells in the neocortical anlage, in the cortical hem, and in the septal, olfactory, and caudomedial telencephalic regions. The overall reduction in number of C-R cells in Lhx5 mutants is accompanied by formation of ectopic reelin(+) cell clusters at the caudal telencephalon. Based on differential expression of molecular markers and by fluorescent cell tracing in cultured embryos, we located the origin of reelin(+) ectopic cell clusters at the caudomedial telencephalic region. We also confirmed the existence of a normal migration stream of reelin(+) cells from the caudomedial area to telencephalic olfactory territories in wild-type embryos. These results reveal a complex role for Lhx5 in regulating the development and normal distribution of C-R cells in the developing forebrain.
C1 [Miquelajauregui, Amaya; Varela-Echavarria, Alfredo; Ricano, Itzel; Frade-Perez, Daniela; Tamariz, Elisa] Univ Nacl Autonoma Mexico, Inst Neurobiol, Queretaro 76230, Mexico.
[Laura Ceci, M.; Garcia-Moreno, Fernando; De Carlos, Juan A.] CSIC, Inst Cajal, E-28002 Madrid, Spain.
[Hoang, Kimmi; Westphal, Heiner; Zhao, Yangu] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Mammalian Genes & Dev, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[Portera-Cailliau, Carlos] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
RP Varela-Echavarria, A (reprint author), Univ Nacl Autonoma Mexico, Inst Neurobiol, Campus Juriquilla, Queretaro 76230, Mexico.
EM avarela@unam.mx; yzhao@helix.nih.gov
OI De Carlos, Juan Andres/0000-0001-9096-5372; Garcia-Moreno,
Fernando/0000-0001-9048-4237
FU National Institute of Child Health and Human Development-National
Institutes of Health (NIH); Wellcome Trust [GR071174AIA]; Agencia
Espanola de Cooperacion Internacional [A/010585/07]; Spanish Ministerio
de Ciencia e Innovacion [BFU2007-60351/BFI]; Mexican Consejo Nacional de
Ciencia y Tecnologia (CONACYT) [40286M]; Direccion General de Asuntos
del Personal Academico-Universidad Nacional Autonoma de Mexico;
Comunidad Autonoma de Madrid-OLFACTOSENSE Consortium [P-SEM-0255-2006];
Spanish predoctoral I3P fellowship; National Research Council
FX This work was supported by funds from the intramural research program of
National Institute of Child Health and Human Development-National
Institutes of Health (NIH), The Wellcome Trust (GR071174AIA), Agencia
Espanola de Cooperacion Internacional (A/010585/07), BFU2007-60351/BFI
from Spanish Ministerio de Ciencia e Innovacion, and Mexican Consejo
Nacional de Ciencia y Tecnologia (CONACYT) (40286M). A. M. was supported
by a fellowship from Direccion General de Asuntos del Personal
Academico-Universidad Nacional Autonoma de Mexico, D. F.-P. by a
fellowship from CONACYT, F. G.-M. by a postdoctoral contract from the
Comunidad Autonoma de Madrid-OLFACTOSENSE Consortium P-SEM-0255-2006,
and M. L. C. by a Spanish predoctoral I3P fellowship. Part of this
research was performed at the laboratory of Heiner Westphal at the
National Institute of Child Health and Human Development-NIH (Bethesda,
MD), by A. V.-E. with the support of a National Research Council
Associateship Award. Technical support was provided by Anaid Antaramian,
Adriana Gonzalez, Pilar Galarza, Martin Garcia, Cristina Gonzalez, Nydia
Hernandez, Alberto Lara, and Omar Gonzalez. Lhx1tlz/+ founder
mice were kindly donated by Tom Jessell. We thank Tom Curran, Antonello
Mallamaci, and Magdalena Gotz for providing probes and Richard Behringer
for the rabbit Lhx1 antibody.
NR 43
TC 15
Z9 15
U1 1
U2 2
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 AUG 4
PY 2010
VL 30
IS 31
BP 10551
EP 10562
DI 10.1523/JNEUROSCI.5563-09.2010
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 637BP
UT WOS:000280789600029
PM 20685998
ER
PT J
AU Oku, N
Takada, K
Fuller, RW
Wilson, JA
Peach, ML
Pannell, LK
McMahon, JB
Gustafson, KR
AF Oku, Naoya
Takada, Kentaro
Fuller, Richard W.
Wilson, Jennifer A.
Peach, Megan L.
Pannell, Lewis K.
McMahon, James B.
Gustafson, Kirk R.
TI Isolation, Structural Elucidation, and Absolute Stereochemistry of
Enigmazole A, a Cytotoxic Phosphomacrolide from the Papua New Guinea
Marine Sponge Cinachyrella enigmatica
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID PHOSPHOLIPID FATTY-ACIDS; NATURAL-PRODUCTS; DISCODERMIA-CALYX; PROTEIN
PHOSPHATASE-1; BACILLUS-SUBTILIS; ECTEINASCIDIA-TURBINATA;
COUPLING-CONSTANTS; GENUS CINACHYRELLA; DELTA-LACTONE; CALYCULIN-A
AB Enigmazole A (1), a novel phosphate-containing macrolide, was isolated from a Papua New Guinea collection of the marine sponge Cinachyrella enigmatica. The structure of 1, including the absolute stereochemistry at all eight chiral centers, was determined by a combination of spectroscopic analyses and a series of microscale chemical derivatization studies. Compound 1 is comprised of an 18-membered phosphomacrolide that contains an embedded exomethylene-substituted tetrahydropyran ring and an acyclic portion that spans an embedded oxazole moiety. Two additional analogues, 15-O-methylenigmazole A and 13-hydroxy-15-O-methylenigmazole A, were also isolated and assigned. The enigmazoles are the first phosphomacrolides from a marine source and 1 exhibited significant cytotoxicity in the NCI 60-cell line antitumor screen, with a mean GI(50) of 1.7 mu M.
C1 NCI, Mol Targets Lab, Ctr Canc Res, NCI Frederick, Frederick, MD 21701 USA.
SAIC Frederick Inc, NCI Frederick, Biol Chem Lab, Frederick, MD 21702 USA.
NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA.
RP Gustafson, KR (reprint author), NCI, Mol Targets Lab, Ctr Canc Res, NCI Frederick, Bldg 1052,Room 121, Frederick, MD 21701 USA.
EM gustafki@mail.nih.gov
OI zaraat, javad/0000-0001-5341-7481
FU NIH, National Cancer Institute, Center for Cancer Research; National
Cancer Institute, National Institutes of Health [HHSN261200800001E]
FX We thank D. Newman (Natural Products Branch, NCI) for arranging sample
collections, Patrick Colin (Coral Reef Research Foundation) for making
collections, Michelle Kelly (NIWA, New Zealand) for taxonomic
identifications, and T. McCloud (SAIC-Frederick) for extractions. This
research was supported in part by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research, and in part
with federal funds from the National Cancer Institute, National
Institutes of Health, under contract HHSN261200800001E. Credit for the
sponge image on the cover goes to Coral Reef Research Foundation/Patrick
L. Colin, and we are grateful to J. Molinski for assistance with
rendering.
NR 74
TC 26
Z9 26
U1 2
U2 26
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD AUG 4
PY 2010
VL 132
IS 30
BP 10278
EP 10285
DI 10.1021/ja1016766
PG 8
WC Chemistry, Multidisciplinary
SC Chemistry
GA 632VC
UT WOS:000280456100025
PM 20590096
ER
PT J
AU Annunziata, CM
Birrer, MJ
AF Annunziata, Christina M.
Birrer, Michael J.
TI CD157 in Ovarian Carcinoma: How Does It Help Us?
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
C1 [Annunziata, Christina M.; Birrer, Michael J.] Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA 02114 USA.
[Annunziata, Christina M.] Natl Canc Inst, Med Oncol Branch, Bethesda, MD USA.
RP Birrer, MJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Med, 55 Fruit St, Boston, MA 02114 USA.
EM mbirrer@partners.org
RI Annunziata, Christina/L-3219-2016
OI Annunziata, Christina/0000-0003-2033-6532
NR 5
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD AUG 4
PY 2010
VL 102
IS 15
BP 1004
EP 1005
DI 10.1093/jnci/djq269
PG 2
WC Oncology
SC Oncology
GA 636CL
UT WOS:000280705500002
ER
PT J
AU Rutten, LF
Davis, K
Squiers, L
Blake, KD
AF Rutten, Lila Finney
Davis, Kia
Squiers, Linda
Blake, Kelly D.
TI Low Awareness of and Referral to National Cancer Information Resources
Among Physicians
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Letter
C1 [Rutten, Lila Finney; Davis, Kia] SAIC Frederick Inc, Natl Canc Inst Frederick, Clin Monitoring Res Program, Frederick, MD 21704 USA.
[Squiers, Linda] Res Triangle Inst, Res Triangle Pk, NC 27709 USA.
[Blake, Kelly D.] NCI, Hlth Commun & Informat Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Rutten, LF (reprint author), SAIC Frederick Inc, Natl Canc Inst Frederick, Clin Monitoring Res Program, Frederick, MD 21704 USA.
EM finneyl@mail.nih.gov
OI Davis, Kia/0000-0002-1338-3018
NR 6
TC 1
Z9 1
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD AUG 4
PY 2010
VL 102
IS 15
BP 1206
EP U115
DI 10.1093/jnci/djq244
PG 2
WC Oncology
SC Oncology
GA 636CL
UT WOS:000280705500014
PM 20581334
ER
PT J
AU Fojo, T
Grady, C
AF Fojo, Tito
Grady, Christine
TI Re: How Much Is Life Worth: Cetuximab, Non-Small Cell Lung Cancer, and
the $440 Billion Question Response
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Letter
ID PHASE-III TRIAL; METASTATIC COLORECTAL-CANCER; PLUS GEMCITABINE;
BEVACIZUMAB; CARCINOMA; CHEMOTHERAPY; SORAFENIB; PACLITAXEL; ERLOTINIB;
EFFICACY
C1 [Grady, Christine] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
[Fojo, Tito] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Fojo, T (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bldg 10,Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM fojot@mail.nih.gov
NR 19
TC 1
Z9 1
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD AUG 4
PY 2010
VL 102
IS 15
BP 1207
EP U121
DI 10.1093/jnci/djq247
PG 4
WC Oncology
SC Oncology
GA 636CL
UT WOS:000280705500016
ER
PT J
AU Kutty, RK
Samuel, W
Jaworski, C
Duncan, T
Nagineni, CN
Raghavachari, N
Wiggert, B
Redmond, TM
AF Kutty, R. Krishnan
Samuel, William
Jaworski, Cynthia
Duncan, Todd
Nagineni, Chandrasekharam N.
Raghavachari, Nalini
Wiggert, Barbara
Redmond, T. Michael
TI MicroRNA expression in human retinal pigment epithelial (ARPE-19) cells:
Increased expression of microRNA-9 by N-(4-Hydroxyphenyl)retinamide
SO MOLECULAR VISION
LA English
DT Article
ID GENE-EXPRESSION; MIRNA EXPRESSION; OXIDATIVE DAMAGE; MAMMALIAN EYE;
DIFFERENTIATION; CANCER; ACID; INDUCTION; BINDING; IDENTIFICATION
AB Purpose: MicroRNAs (miRNAs) are important regulators of many cellular functions due to their ability to target mRNAs for degradation or translational inhibition. Previous studies have reported that the expression of microRNA-9 (miR-9) is regulated by retinoic acid and reactive oxygen species (ROS). We have previously shown that N-(4-hydoxyphenyl)retinamide (4HPR), a retinoic acid derivative, induces ROS generation and apoptosis in cultured human retinal pigment epithelial (RPE) cells, known as ARPE-19 cells. The aim of the present study was to investigate the expression of miR-9 in ARPE-19 cells in response to 4HPR treatment, and to identify other miRNAs normally expressed in these cells.
Methods: ARPE-19 cells in culture were treated with 4HPR, the total RNA fractions were isolated, and the expression of various miRNAs and mRNAs was analyzed using real-time PCR. The miRNA expression profile of ARPE-19 cells was analyzed using microarray hybridization.
Results: Treatment of ARPE-19 cells with 4HPR resulted in apoptosis characterized by the increased expression of HMOX1 and GADD153 genes. A twofold increase in the expression of miR-9 was also observed during this response. Potential binding sites for the transcription factors encoded by CEBPA and CEBPB genes were found to be present in the putative promoter regions of all three genes encoding miR-9. 4HPR-induced miR-9 expression was associated with parallel increases in the expression of these transcription factor genes. 5-Aza-2'-deoxycytidine, a methyl transferase inhibitor, also increased the expression of miR-9 in ARPE-19 cells. Microarray hybridization analysis identified let-7b, let-7a, miR-125b, miR-24, miR-320, miR-23b, let-7e, and let-7d as the most abundant miRNAs normally expressed in ARPE-19 cells. These miRNAs are known to regulate cell growth, differentiation or development. The 4HPR treatment increased the expression of miR-16, miR-26b, miR-23a, and miR-15b in ARPE-19 cells, although these increases were modest when compared to the increase in the expression of miR-9.
Conclusions: Our studies demonstrate that miR-9 is expressed in the RPE cell line ARPE-19, and its expression is increased by a retinoic acid derivative and by an inhibitor of promoter hypermethylation. Several miRNAs with inherent ability to regulate cell growth, differentiation and development are also normally expressed in ARPE-19 cells. Thus, miR-9 and other miRNAs could be important in maintaining RPE cell function.
C1 [Kutty, R. Krishnan; Samuel, William; Jaworski, Cynthia; Duncan, Todd; Wiggert, Barbara; Redmond, T. Michael] NEI, Lab Retinal Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Raghavachari, Nalini] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Raghavachari, Nalini] NHLBI, Genom Core Facil, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA.
RP Kutty, RK (reprint author), NEI, Lab Retinal Cell & Mol Biol, NIH, Bldg 6,Room 112,6 Ctr Dr,MSC 0608, Bethesda, MD 20892 USA.
EM kuttyk@nei.nih.gov
RI Xie, Huangming/B-2260-2012
FU National Eye Institute; National Heart Lung and Blood Institute,
National Institutes of Health
FX This study was supported by the Intramural Research Programs of the
National Eye Institute and the National Heart Lung and Blood Institute,
National Institutes of Health. Note: While this manuscript was under
review, Wang et al. [56] reported on the expression of miRNAs in fetal
human RPE and the possible role of miR-204 and miR-211 in regulating
epithelial physiology.
NR 56
TC 31
Z9 32
U1 0
U2 6
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD AUG 4
PY 2010
VL 16
IS 160-62
BP 1475
EP 1486
PG 12
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA 643QS
UT WOS:000281314100002
PM 20806079
ER
PT J
AU Croswell, JM
Kramer, BS
AF Croswell, Jennifer M.
Kramer, Barnett S.
TI Misleading Statement in Trial on False-Positive Results in Lung Cancer
Screening RESPONSE
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Letter
C1 [Croswell, Jennifer M.; Kramer, Barnett S.] NIH, Bethesda, MD 20892 USA.
RP Croswell, JM (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD AUG 3
PY 2010
VL 153
IS 3
BP 210
EP 210
DI 10.7326/0003-4819-153-3-201008030-00020
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 634CR
UT WOS:000280557600017
ER
PT J
AU Jones, RH
White, H
Velazquez, EJ
Shaw, LK
Pietrobon, R
Panza, JA
Bonow, RO
Sopko, G
O'Connor, CM
Rouleau, JL
AF Jones, Robert H.
White, Harvey
Velazquez, Eric J.
Shaw, Linda K.
Pietrobon, Ricardo
Panza, Julio A.
Bonow, Robert O.
Sopko, George
O'Connor, Christopher M.
Rouleau, Jean-Lucien
TI STICH (Surgical Treatment for Ischemic Heart Failure) Trial Enrollment
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
ID CORONARY-ARTERY DISEASE; BYPASS-SURGERY; SURVIVAL
AB Objectives The aim of this study was to assess the influence of enrolling site location and enrollment performance on the generalizability of STICH ( Surgical Treatment for Ischemic Heart Failure) trial results.
Background The international STICH trial seeks to define the role of cardiac surgery for patients with ischemic cardiomyopathy.
Methods Baseline characteristics of 2,136 randomized STICH patients were entered into a multivariate equation created using the Duke Databank for Cardiovascular Diseases to predict their 5-year risk for death without cardiac surgery. Patients ordered by increasing predicted risk were assigned to 1 of 32 risk at randomization (RAR) groups created to share one-thirty-second of total predicted deaths. Numbers of patients sharing the same RAR group were compared between higher and lower enrolling site groupings and for countries tending to enroll high-or low-risk patients.
Results Country of enrollment was a stronger determinant of risk diversity than site enrollment performance among patients enrolled at 127 sites in 26 countries. Mean RAR differences among countries ranged from 9.4 (Singapore) to 18.6 (Germany). However, 1,614 of 2,136 patients (76%) from countries enrolling lower-risk patients shared the same RAR group with patients from countries enrolling higher-risk patients. Baseline characteristics responsible for risk differences of patients enrolled in the 2 country groupings were sufficiently similar to exert little influence on clinical decision making.
Conclusions STICH randomized patients are characterized by a continuous spectrum of risk, without discordant dominance from any site or country. Clinical site diversity promises to enhance the generalization of STICH trial results to a broad population of patients with ischemic cardiomyopathy. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease; NCT00023595) (J Am Coll Cardiol 2010; 56: 490-8) (C) 2010 by the American College of Cardiology Foundation
C1 [Jones, Robert H.] Duke Univ, Med Ctr, Dept Surg, Div Cardiothorac Surg, Durham, NC 27710 USA.
[Velazquez, Eric J.; O'Connor, Christopher M.] Duke Univ, Dept Med, Div Cardiovasc Med, Durham, NC 27710 USA.
[Shaw, Linda K.] Duke Clin Res Inst, Durham, NC USA.
[White, Harvey] Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.
[Pietrobon, Ricardo] Duke NUS, Dept Hlth Serv Res, Singapore, Singapore.
[Panza, Julio A.] Washington Hosp Ctr, Dept Med Cardiovasc Dis, Washington, DC 20010 USA.
[Bonow, Robert O.] Northwestern Univ, NW Mem Hosp, Feinberg Sch Med, Div Cardiol, Chicago, IL 60611 USA.
[Sopko, George] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Rouleau, Jean-Lucien] Univ Montreal, Inst Cardiol Montreal, Montreal, PQ, Canada.
RP Jones, RH (reprint author), Duke Univ, Med Ctr, Dept Surg, Div Cardiothorac Surg, POB 2986, Durham, NC 27710 USA.
EM jones060@mc.duke.edu
FU National Heart, Lung, and Blood Institute, National Institutes of Health
[U01-HL69015]
FX Institut de Cardiologie de Montreal, University of Montreal, Montreal,
Quebec, Canada. This study was supported by grant U01-HL69015 from the
National Heart, Lung, and Blood Institute, National Institutes of
Health.
NR 10
TC 22
Z9 24
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD AUG 3
PY 2010
VL 56
IS 6
BP 490
EP 498
DI 10.1016/j.jacc.2009.11.102
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 631TZ
UT WOS:000280373400007
PM 20670760
ER
PT J
AU Read, SW
DeGrezia, M
Ciccone, EJ
DerSimonian, R
Higgins, J
Adelsberger, JW
Starling, JM
Rehm, C
Sereti, I
AF Read, Sarah W.
DeGrezia, Mary
Ciccone, Emily J.
DerSimonian, Rebecca
Higgins, Jeanette
Adelsberger, Joseph W.
Starling, Judith M.
Rehm, Catherine
Sereti, Irini
TI The Effect of Leflunomide on Cycling and Activation of T-Cells in
HIV-1-Infected Participants
SO PLOS ONE
LA English
DT Article
ID ACTIVE ANTIRETROVIRAL THERAPY; PLASMACYTOID DENDRITIC CELLS; LYMPHATIC
TISSUE FIBROSIS; HIV-INFECTED PATIENTS; IMMUNE ACTIVATION;
MYCOPHENOLATE-MOFETIL; LYMPHOCYTE-ACTIVATION; RHEUMATOID-ARTHRITIS;
DISEASE PROGRESSION; IMMUNODEFICIENCY
AB Background: The pathogenesis of immunodeficiency due to human immunodeficiency virus (HIV)-1 is incompletely understood, but immune activation is believed to play a central role. Immunomodulatory agents that decrease immune activation may be useful in the treatment of HIV-1 infection.
Methodology: A randomized, double blind, placebo-controlled pilot study of leflunomide for 28 days was performed in participants with HIV-1 infection who were not receiving antiretroviral therapy. Participants randomized to leflunomide were subsequently treated with cholestyramine until leflunomide levels were below detection limit.
Findings: Treatment with leflunomide was well tolerated with mostly low-grade adverse events. Leflunomide administration reduced cycling of CD4 T cells (by ex vivo bromodeoxyuridine uptake and Ki67 expression) and decreased expression of activation markers (HLA-DR/CD38 co-expression) on CD8 T cells in peripheral blood. In addition, decreased expression of HIV-1 co-receptors was observed in both CD4 and CD8 T cells in the leflunomide group. There were no significant changes in naive and memory T cell subsets, apoptosis of T cells or markers of microbial translocation.
Conclusions: Leflunomide was effective in reducing immune activation in the setting of chronic HIV-1 infection suggesting that targeting immune activation with immunomodulatory agents may be a feasible strategy.
C1 [Read, Sarah W.] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
[DerSimonian, Rebecca] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA.
[Higgins, Jeanette; Adelsberger, Joseph W.] NCI, Sci Applicat Int Corp Frederick, Frederick, MD 21701 USA.
[Starling, Judith M.] NIH, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA.
[DeGrezia, Mary; Ciccone, Emily J.; Rehm, Catherine; Sereti, Irini] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Read, SW (reprint author), NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
EM isereti@niaid.nih.gov
FU National Cancer Institute, National Institutes of Health (NIH)
[N01-CO-12400]; NIH, National Institute of Allergy and Infectious
Diseases
FX This project has been funded in part with federal funds from the
National Cancer Institute, National Institutes of Health (NIH), under
contract N01-CO-12400. This research was also supported in part by the
Intramural Program of NIH, National Institute of Allergy and Infectious
Diseases. 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. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 36
TC 22
Z9 22
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 3
PY 2010
VL 5
IS 8
AR e11937
DI 10.1371/journal.pone.0011937
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 633RB
UT WOS:000280520500005
PM 20689824
ER
PT J
AU Tsao, D
Minton, AP
Dokholyan, NV
AF Tsao, Douglas
Minton, Allen P.
Dokholyan, Nikolay V.
TI A Didactic Model of Macromolecular Crowding Effects on Protein Folding
SO PLOS ONE
LA English
DT Article
ID DISCRETE MOLECULAR-DYNAMICS; COARSE-GRAINED STRATEGY; EXCLUDED-VOLUME;
PHYSIOLOGICAL CONSEQUENCES; CONCENTRATED-SOLUTIONS; BINDING STABILITY;
THERMODYNAMICS; AGGREGATION; SIMULATIONS; CONFINEMENT
AB A didactic model is presented to illustrate how the effect of macromolecular crowding on protein folding and association is modeled using current analytical theory and discrete molecular dynamics. While analytical treatments of crowding may consider the effect as a potential of average force acting to compress a polypeptide chain into a compact state, the use of simulations enables the presence of crowding reagents to be treated explicitly. Using an analytically solvable toy model for protein folding, an approximate statistical thermodynamic method is directly compared to simulation in order to gauge the effectiveness of current analytical crowding descriptions. Both methodologies are in quantitative agreement under most conditions, indication that both current theory and simulation methods are capable of recapitulating aspects of protein folding even by utilizing a simplistic protein model.
C1 [Tsao, Douglas] Univ N Carolina, Dept Chem, Chapel Hill, NC 27515 USA.
[Minton, Allen P.] NIDDKD, Sect Phys Biochem, Lab Biochem & Genet, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Dokholyan, Nikolay V.] Univ N Carolina, Sch Med, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
RP Tsao, D (reprint author), Univ N Carolina, Dept Chem, Chapel Hill, NC 27515 USA.
EM dokh@med.unc.edu
OI Dokholyan, Nikolay/0000-0002-8225-4025; Minton,
Allen/0000-0001-8459-1247
FU National Institutes of Health [R01GM080742]
FX National Institutes of Health grant R01GM080742. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 53
TC 7
Z9 7
U1 1
U2 18
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 3
PY 2010
VL 5
IS 8
AR e11936
DI 10.1371/journal.pone.0011936
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 633RB
UT WOS:000280520500004
PM 20689808
ER
PT J
AU Wang, XT
Chorley, BN
Pittman, GS
Kleeberger, SR
Brothers, J
Liu, G
Spira, A
Bell, DA
AF Wang, Xuting
Chorley, Brian N.
Pittman, Gary S.
Kleeberger, Steven R.
Brothers, John, II
Liu, Gang
Spira, Avrum
Bell, Douglas A.
TI Genetic Variation and Antioxidant Response Gene Expression in the
Bronchial Airway Epithelium of Smokers at Risk for Lung Cancer
SO PLOS ONE
LA English
DT Article
ID ELEMENT-DEPENDENT GENES; OXIDATIVE STRESS; CIGARETTE-SMOKE; NEGATIVE
REGULATION; HUMAN GENOME; NRF2; POLYMORPHISMS; ASSOCIATION; ACTIVATION;
SUSCEPTIBILITY
AB Prior microarray studies of smokers at high risk for lung cancer have demonstrated that heterogeneity in bronchial airway epithelial cell gene expression response to smoking can serve as an early diagnostic biomarker for lung cancer. As a first step in applying functional genomic analysis to population studies, we have examined the relationship between gene expression variation and genetic variation in a central molecular pathway (NRF2-mediated antioxidant response) associated with smoking exposure and lung cancer. We assessed global gene expression in histologically normal airway epithelial cells obtained at bronchoscopy from smokers who developed lung cancer (SC, n = 20), smokers without lung cancer (SNC, n = 24), and never smokers (NS, n = 8). Functional enrichment analysis showed that the NRF2-mediated, antioxidant response element (ARE)-regulated genes, were significantly lower in SC, when compared with expression levels in SNC. Importantly, we found that the expression of MAFG (a binding partner of NRF2) was correlated with the expression of ARE genes, suggesting MAFG levels may limit target gene induction. Bioinformatically we identified single nucleotide polymorphisms (SNPs) in putative ARE genes and to test the impact of genetic variation, we genotyped these putative regulatory SNPs and other tag SNPs in selected NRF2 pathway genes. Sequencing MAFG locus, we identified 30 novel SNPs and two were associated with either gene expression or lung cancer status among smokers. This work demonstrates an analysis approach that integrates bioinformatics pathway and transcription factor binding site analysis with genotype, gene expression and disease status to identify SNPs that may be associated with individual differences in gene expression and/or cancer status in smokers. These polymorphisms might ultimately contribute to lung cancer risk via their effect on the airway gene expression response to tobacco-smoke exposure.
C1 [Wang, Xuting; Chorley, Brian N.; Pittman, Gary S.; Bell, Douglas A.] NIEHS, Environm Genom Sect, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Kleeberger, Steven R.] NIEHS, Environm Genet Sect, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
[Brothers, John, II; Liu, Gang; Spira, Avrum] Boston Univ, Sect Computat Biomed, Dept Med, Boston, MA 02215 USA.
[Brothers, John, II; Liu, Gang; Spira, Avrum] Boston Univ, Ctr Pulm, Boston, MA 02215 USA.
RP Wang, XT (reprint author), NIEHS, Environm Genom Sect, Mol Genet Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM BELL1@niehs.nih.gov
OI Wang, Xuting/0000-0001-6781-8008
FU National Institute of Environmental Health Sciences, National Institutes
of Health [Z01 ES100475]; National Institute of Health [U01ES016035,
R01CA124640]
FX The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript. This work was
funded by the Intramural Research Program of the National Institute of
Environmental Health Sciences, National Institutes of Health (Z01
ES100475) and grants to Avrum Spira from the National Institute of
Health (U01ES016035, R01CA124640).
NR 42
TC 25
Z9 27
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 3
PY 2010
VL 5
IS 8
AR e11934
DI 10.1371/journal.pone.0011934
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 633RB
UT WOS:000280520500003
PM 20689807
ER
PT J
AU Tost, H
Kolachana, B
Hakimi, S
Lemaitre, H
Verchinski, BA
Mattay, VS
Weinberger, DR
Meyer-Lindenberg, A
AF Tost, Heike
Kolachana, Bhaskar
Hakimi, Shabnam
Lemaitre, Herve
Verchinski, Beth A.
Mattay, Venkata S.
Weinberger, Daniel R.
Meyer-Lindenberg, Andreas
TI A common allele in the oxytocin receptor gene (OXTR) impacts prosocial
temperament and human hypothalamic-limbic structure and function
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE imaging genetics; neuroimaging; social behavior; prosocial
neuropeptides; autism
ID AUTISM SPECTRUM DISORDERS; SOCIAL COGNITION; NEURAL CIRCUITRY; AMYGDALA
VOLUME; HUMAN BRAIN; WILLIAMS-SYNDROME; FRONTAL DAMAGE; GAZE-FIXATION;
VASOPRESSIN; CHILDREN
AB The evolutionarily highly conserved neuropeptide oxytocin is a key mediator of social and emotional behavior in mammals, including humans. A common variant (rs53576) in the oxytocin receptor gene (OXTR) has been implicated in social-behavioral phenotypes, such as maternal sensitivity and empathy, and with neuropsychiatric disorders associated with social impairment, but the intermediate neural mechanisms are unknown. Here, we used multimodal neuroimaging in a large sample of healthy human subjects to identify structural and functional alterations in OXTR risk allele carriers and their link to temperament. Activation and interregional coupling of the amygdala during the processing of emotionally salient social cues was significantly affected by genotype. In addition, evidence for structural alterations in key oxytocinergic regions emerged, particularly in the hypothalamus. These neural characteristics predicted lower levels of reward dependence, specifically in male risk allele carriers. Our findings identify sex-dependent mechanisms impacting the structure and function of hypothalamic-limbic circuits that are of potential clinical and translational significance.
C1 [Tost, Heike; Kolachana, Bhaskar; Hakimi, Shabnam; Lemaitre, Herve; Verchinski, Beth A.; Mattay, Venkata S.; Weinberger, Daniel R.; Meyer-Lindenberg, Andreas] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Meyer-Lindenberg, Andreas] Cent Inst Mental Hlth, Dept Psychiat & Psychotherapy, D-68159 Mannheim, Germany.
RP Tost, H (reprint author), NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM tosth@mail.nih.gov; a.meyer-lindenberg@zi-mannheim.de
RI Meyer-Lindenberg, Andreas/H-1076-2011;
OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123; Lemaitre,
Herve/0000-0002-5952-076X; Hakimi, Shabnam/0000-0003-4122-6041
FU National Institute of Mental Health, National Institutes of Health;
Deutsche Forschungsgemeinschaft-National Institutes of Health [To539/1]
FX We thank Lucas Kempf, Tajvar Alam, Dwight Dickinson, and Krista Wisner
for help in performing the analyses. This research was supported by the
Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health, and a Deutsche
Forschungsgemeinschaft-National Institutes of Health scholarship grant
To539/1 (to H.T.).
NR 94
TC 214
Z9 218
U1 12
U2 66
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 AUG 3
PY 2010
VL 107
IS 31
BP 13936
EP 13941
DI 10.1073/pnas.1003296107
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 634SP
UT WOS:000280605900069
PM 20647384
ER
PT J
AU Kwon, J
Shatynski, KE
Chen, H
Morand, S
de Deken, X
Miot, F
Leto, TL
Williams, MS
AF Kwon, Jaeyul
Shatynski, Kristen E.
Chen, Haiyan
Morand, Stanislas
de Deken, Xavier
Miot, Francoise
Leto, Thomas L.
Williams, Mark S.
TI The Nonphagocytic NADPH Oxidase Duox1 Mediates a Positive Feedback Loop
During T Cell Receptor Signaling
SO SCIENCE SIGNALING
LA English
DT Article
ID PROTEIN-TYROSINE PHOSPHATASES; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR;
PHOSPHOLIPASE C-GAMMA-1 PLC-GAMMA-1; ANTIGEN RECEPTOR;
HYDROGEN-PEROXIDE; IN-VIVO; KINASE ACTIVATION; STRUCTURAL BASIS;
BINDING-SITE; ZAP-70
AB Production of reactive oxygen species, often by NADPH(reduced form of nicotinamide adenine dinucleotide phosphate) oxidases, plays a role in the signaling responses of cells to many receptor stimuli. Here, we describe the function of the calcium-dependent, nonphagocytic NADPH oxidase Duox1 in primary human CD4(+) T cells and cultured T cell lines. Duox1 bound to inositol 1,4,5-trisphosphate receptor 1 and was required for early T cell receptor (TCR)-stimulated production of hydrogen peroxide (H(2)O(2)) through a pathway that was dependent on TCR-proximal kinases. Transient or stable knockdown of Duox1 inhibited TCR signaling, especially phosphorylation of tyrosine-319 of zeta chain-associated protein kinase of 70 kilodaltons (ZAP-70), store-operated entry of calcium ions (Ca(2+)), and activation of extracellular signal-regulated kinase. The production of cytokines was also inhibited by knockdown of Duox1. Duox1-mediated inactivation of Src homology 2 domain-containing protein tyrosine phosphatase 2 promoted the phosphorylation of ZAP-70 and its association with the Src family tyrosine kinase Lck and the CD3 zeta chain of the TCR complex. Thus, we suggest that activation of Duox1, downstream of proximal TCR signals, generates H(2)O(2) that acts in a positive feedback loop to enhance and sustain further TCR signaling.
C1 [Kwon, Jaeyul; Shatynski, Kristen E.; Chen, Haiyan; Williams, Mark S.] Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
[Kwon, Jaeyul; Morand, Stanislas; Leto, Thomas L.] NIAID, Host Def Lab, NIH, Rockville, MD 20852 USA.
[de Deken, Xavier; Miot, Francoise] Univ Libre Bruxelles, Inst Rech Interdisciplinaire Biol Humaine & Mol, B-1070 Brussels, Belgium.
RP Kwon, J (reprint author), Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Dept Microbiol & Immunol, 800 W Baltimore St, Baltimore, MD 21201 USA.
EM kwonja@niaid.nih.gov; marwilliams@som.umaryland.edu
FU Intramural NIH HHS [ZIA AI001060-02]; NIAID NIH HHS [AI070823, R01
AI070823]
NR 59
TC 43
Z9 43
U1 0
U2 2
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD AUG 3
PY 2010
VL 3
IS 133
AR ra59
DI 10.1126/scisignal.2000976
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 635JF
UT WOS:000280650700002
PM 20682913
ER
PT J
AU Aravind, L
de Souza, RF
Iyer, LM
AF Aravind, L.
de Souza, Robson F.
Iyer, Lakshminarayan M.
TI Predicted class-I aminoacyl tRNA synthetase-like proteins in
non-ribosomal peptide synthesis
SO BIOLOGY DIRECT
LA English
DT Article
ID FORMING ENZYMES; BIOSYNTHESIS; EVOLUTION; PEPTIDOGLYCAN; SUPERFAMILY;
REVEALS; DOMAINS; LIGASE; ACID
AB Background: Recent studies point to a great diversity of non-ribosomal peptide synthesis systems with major roles in amino acid and co factor biosynthesis, secondary metabolism, and post-translational modifications of proteins by peptide tags. The least studied of these systems are those utilizing tRNAs or aminoacyl-tRNA synthetases (AAtRS) in non-ribosomal peptide ligation.
Results: Here we describe novel examples of AAtRS related proteins that are likely to be involved in the synthesis of widely distributed peptide-derived metabolites. Using sensitive sequence profile methods we show that the cyclodipeptide synthases (CDPSs) are members of the HUP class of Rossmannoid domains and are likely to be highly derived versions of the class I AAtRS catalytic domains. We also identify the first eukaryotic CDPSs in fungi and in animals; they might be involved in immune response in the latter organisms. We also identify a paralogous version of the methionyl-tRNA synthetase, which is widespread in bacteria, and present evidence using contextual information that it might function independently of protein synthesis as a peptide ligase in the formation of a peptide- derived secondary metabolite. This metabolite is likely to be heavily modified through multiple reactions catalyzed by a metal-binding cupin domain and a lysine N6 monooxygenase that are strictly associated with this paralogous methionyl-tRNA synthetase (MtRS). We further identify an analogous system wherein the MtRS has been replaced by more typical peptide ligases with the ATP-grasp or modular condensation-domains.
Conclusions: The prevalence of these predicted biosynthetic pathways in phylogenetically distant, pathogenic or symbiotic bacteria suggests that metabolites synthesized by them might participate in interactions with the host. More generally, these findings point to a complete spectrum of recruitment of AAtRS to various non-ribosomal biosynthetic pathways, ranging from the conventional AAtRS, through closely related paralogous AAtRS dedicated to certain pathways, to highly derived versions of the class-I AAtRS catalytic domain like the CDPSs. Both the conventional AAtRS and their closely related paralogs often provide aminoacylated tRNAs for peptide ligations by MprF/Fem/MurM-type acetyltransferase fold ligases in the synthesis of peptidoglycan, N-end rule modifications of proteins, lipid aminoacylation or biosynthesis of antibiotics, such as valinamycin. Alternatively they might supply aminoacylated tRNAs for other biosynthetic pathways like that for tetrapyrrole or directly function as peptide ligases as in the case of mycothiol and those identified here.
Reviewers: This article was reviewed by Andrei Osterman and Igor Zhulin.
C1 [Aravind, L.; de Souza, Robson F.; Iyer, Lakshminarayan M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM aravind@ncbi.nlm.nih.gov
FU National Library of Medicine at the National Institutes of Health, USA
FX Work by the authors is supported by the intramural funds of the National
Library of Medicine at the National Institutes of Health, USA.
NR 28
TC 21
Z9 22
U1 3
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 AUG 2
PY 2010
VL 5
AR 48
DI 10.1186/1745-6150-5-48
PG 11
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 645DD
UT WOS:000281430200001
PM 20678224
ER
PT J
AU Salcedo, R
Worschech, A
Cardone, M
Jones, Y
Gyulai, Z
Dai, RM
Wang, EN
Ma, W
Haines, D
O'hUigin, C
Marincola, FM
Trinchieri, G
AF Salcedo, Rosalba
Worschech, Andrea
Cardone, Marco
Jones, Yava
Gyulai, Zsofia
Dai, Ren-Ming
Wang, Ena
Ma, Winnie
Haines, Diana
O'hUigin, Colm
Marincola, Francesco M.
Trinchieri, Giorgio
TI MyD88-mediated signaling prevents development of adenocarcinomas of the
colon: role of interleukin 18
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID CHRONIC INTESTINAL INFLAMMATION; COLITIS-ASSOCIATED CANCER;
SODIUM-SULFATE COLITIS; EXPRESSION PATTERNS; INNATE IMMUNITY;
BOWEL-DISEASE; BETA-CATENIN; MUTANT MICE; CELL LINES; TUMORIGENESIS
AB Signaling through the adaptor protein myeloid differentiation factor 88 (MyD88) promotes carcinogenesis in several cancer models. In contrast, MyD88 signaling has a protective role in the development of azoxymethane (AOM)/dextran sodium sulfate (DSS) colitis-associated cancer (CAC). The inability of Myd88(-/-) mice to heal ulcers generated upon injury creates an altered inflammatory environment that induces early alterations in expression of genes encoding proinflammatory factors, as well as pathways regulating cell proliferation, apoptosis, and DNA repair, resulting in a dramatic increase in adenoma formation and progression to infiltrating adenocarcinomas with frequent clonal mutations in the beta-catenin gene. Others have reported that toll-like receptor (Tlr) 4-deficient mice have a similar susceptibility to colitis to Myd88-deficient mice but, unlike the latter, are resistant to CAC. We have observed that mice deficient for Tlr2 or Il1r do not show a differential susceptibility to colitis or CAC. However, upon AOM/DSS treatment Il18(-/-) and Il18r1(-/-) mice were more susceptible to colitis and polyp formation than wild-type mice, suggesting that the phenotype of Myd88(-/-) mice is, in part, a result of their inability to signal through the IL-18 receptor. This study revealed a previously unknown level of complexity surrounding MyD88 activities downstream of different receptors that impact tissue homeostasis and carcinogenesis.
C1 [Salcedo, Rosalba; Cardone, Marco; Jones, Yava; Gyulai, Zsofia; Dai, Ren-Ming; Ma, Winnie; O'hUigin, Colm; Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
[Haines, Diana] Pathol Histotechnol Lab, Frederick, MD 21701 USA.
[Salcedo, Rosalba; Dai, Ren-Ming; O'hUigin, Colm] SAIC Frederick Inc, Frederick, MD 21701 USA.
[Worschech, Andrea; Wang, Ena; Marincola, Francesco M.] NIH, Dept Transfus Med, Infect Dis & Immunogenet Sect, Bethesda, MD 20892 USA.
RP Trinchieri, G (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
EM trinchig@mail.nih.gov
RI Worschech, Andrea/I-3919-2012
OI Worschech, Andrea/0000-0002-4303-8653
FU National Cancer Institute; National Cancer Institute, National
Institutes of Health [HHSN261200800001E]
FX This Research was supported by the Intramural Research Program National
Cancer Institute and by funds from the National Cancer Institute,
National Institutes of Health, under contract HHSN261200800001E. Mention
of trade names, commercial products, services, or organizations does not
imply endorsement by the U.S. Government.
NR 41
TC 170
Z9 175
U1 2
U2 16
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD AUG 2
PY 2010
VL 207
IS 8
BP 1625
EP 1636
DI 10.1084/jem.20100199
PG 12
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 636EB
UT WOS:000280709900007
PM 20624890
ER
PT J
AU Kim, SJ
Zhang, ZJ
Saha, A
Sarkar, C
Zhao, ZW
Xu, Y
Mukherjee, AB
AF Kim, Sung-Jo
Zhang, Zhongjian
Saha, Arjun
Sarkar, Chinmoy
Zhao, Zhenwen
Xu, Yan
Mukherjee, Anil B.
TI Omega-3 and omega-6 fatty acids suppress ER- and oxidative stress in
cultured neurons and neuronal progenitor cells from mice lacking PPT1
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE INCL; Palmitoyl-protein thioesterase-1; Batten disease;
Neurodegeneration; ER-stress; Oxidative stress; Apoptosis; PUFA
ID PALMITOYL-PROTEIN THIOESTERASE; CEROID-LIPOFUSCINOSIS; DOCOSAHEXAENOIC
ACID; MOUSE MODEL; RAT-BRAIN; NEURODEGENERATION; ACTIVATION; APOPTOSIS;
LIPIDS; INCL
AB Reactive oxygen species (ROS) damage brain lipids, carbohydrates, proteins, as well as DNA and may contribute to neurodegeneration. We previously reported that ER- and oxidative stress cause neuronal apoptosis in infantile neuronal ceroid lipofuscinosis (INCL), a lethal neurodegenerative storage disease, caused by palmitoyl-protein thioesterase-1 (PPT1) deficiency. Polyunsaturated fatty acids (PUFA) are essential components of cell membrane phospholipids in the brain and excessive ROS may cause oxidative damage of PUFA leading to neuronal death. Using cultured neurons and neuroprogenitor cells from mice lacking PUFA, which mimic INCL, we demonstrate that Ppt1-deficient neurons and neuroprogenitor cells contain high levels of ROS, which may cause peroxidation of PUFA and render them incapable of providing protection against oxidative stress. We tested whether treatment of these cells with omega-3 or omega-6 PUFA protects the neurons and neuroprogenitor cells from oxidative stress and suppress apoptosis. We report here that both omega-3 and omega-6 fatty acids protect the Ppt1-deficient cells from ER- as well as oxidative stress and suppress apoptosis. Our results suggest that PUFA supplementation may have neuroprotective effects in INCL Published by Elsevier Ireland Ltd.
C1 [Kim, Sung-Jo; Zhang, Zhongjian; Saha, Arjun; Sarkar, Chinmoy; Mukherjee, Anil B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Dev Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Zhao, Zhenwen; Xu, Yan] Indiana Univ Sch Med, Dept Obstet & Gynecol, Indianapolis, IN 46202 USA.
RP Mukherjee, AB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Dev Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
EM mukherja@exchange.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health
FX We thank Dr. Sandra L. Hofmann for the generous gift of the Ppt1-KO mice
generated in her laboratory [see reference 10]. Extensive backcross
experiments to obtain homogeneous C57 genetic background of these mice
were carried out in the laboratory of Dr. Mark Sands. We thank Dr. Sands
for providing a mating pair to establish our Ppt1-KO mouse colony. We
also thank Drs. J.Y. Chou and I. Owens for critical review of the
manuscript and helpful suggestions. This research was supported in whole
by the Intramural Research Program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development, National
Institutes of Health.
NR 29
TC 26
Z9 26
U1 1
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3940
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD AUG 2
PY 2010
VL 479
IS 3
BP 292
EP 296
DI 10.1016/j.neulet.2010.05.083
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 628FR
UT WOS:000280100600024
PM 20561933
ER
PT J
AU Taioli, E
Im, A
Xu, X
Veenstra, TD
Ahrendt, G
Garte, S
AF Taioli, Emanuela
Im, Annie
Xu, Xia
Veenstra, Timothy D.
Ahrendt, Gretchen
Garte, Seymour
TI Comparison of estrogens and estrogen metabolites in human breast tissue
and urine
SO REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY
LA English
DT Article
ID CHROMATOGRAPHY-MASS SPECTROMETRY; POSTMENOPAUSAL WOMEN;
2-HYDROXYESTRONE/16-ALPHA-HYDROXYESTRONE RATIO; ESTRADIOL METABOLITES;
CANCER; RISK; CARCINOGENESIS; HYDROXYESTROGENS; PREMENOPAUSAL;
PROLIFERATION
AB Background: An important aspect of the link between estrogen and breast cancer is whether urinary estrogen levels are representative of the intra-tissue levels of bioavailable estrogens.
Methods: This study compares 15 estrogen and estrogen metabolite levels in breast tissue and urine of 9 women with primary breast cancer using a quantitative liquid chromatography-mass spectrometry method.
Results: The average levels of estrogens (estrone, 17 beta-estradiol) were significantly higher in breast tissue than in urine. Both the 2 and the 16-hydroxylation pathways were less represented in breast tissue than urine; no components of the 4-hydroxypathway were detected in breast tissue, while 4-hydroxyestrone was measured in urine. However, the 2/16 ratio was similar in urine and breast tissue. Women carrying the variant CYP1B1 genotype (Leu/Val and Val/Val) showed significantly lower overall estrogen metabolite, estrogen, and 16-hydroxylation pathway levels in breast tissue in comparison to women carrying the wild type genotype. No effect of the CYP1B1 polymorphism was observed in urinary metabolites.
Conclusions: The urinary 2/16 ratio seems a good approximation of the ratio observed in breast tissue. Metabolic genes may have an important role in the estrogen metabolism locally in tissues where the gene is expressed, a role that is not readily observable when urinary measurements are performed.
C1 [Taioli, Emanuela] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA.
[Im, Annie; Ahrendt, Gretchen] Univ Pittsburgh, Div Surg Oncol, Dept Surg, Pittsburgh, PA 15232 USA.
[Taioli, Emanuela; Garte, Seymour] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15232 USA.
[Xu, Xia; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Taioli, E (reprint author), Suny Downstate Med Ctr, Brooklyn, NY 11203 USA.
EM emanuela.taioli@downstate.edu
OI Garte, Seymour/0000-0003-3284-5975
NR 36
TC 11
Z9 11
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1477-7827
J9 REPROD BIOL ENDOCRIN
JI Reprod. Biol. Endocrinol.
PD AUG 2
PY 2010
VL 8
AR 93
DI 10.1186/1477-7827-8-93
PG 7
WC Endocrinology & Metabolism; Reproductive Biology
SC Endocrinology & Metabolism; Reproductive Biology
GA 659GV
UT WOS:000282555900001
PM 20678202
ER
PT J
AU Overton, ET
Kang, M
Peters, MG
Umbleja, T
Alston-Smith, BL
Bastow, B
Demarco-Shaw, D
Koziel, MJ
Mong-Kryspin, L
Sprenger, HL
Yu, JY
Aberg, JA
AF Overton, E. T.
Kang, M.
Peters, M. G.
Umbleja, T.
Alston-Smith, B. L.
Bastow, B.
Demarco-Shaw, D.
Koziel, M. J.
Mong-Kryspin, L.
Sprenger, H. L.
Yu, J. Y.
Aberg, J. A.
TI Immune response to hepatitis B vaccine in HIV-infected subjects using
granulocyte-macrophage colony-stimulating factor (GM-CSF) as a vaccine
adjuvant: ACTG study 5220
SO VACCINE
LA English
DT Article
DE HIV; HBV vaccination; GM-CSF; Adjuvant
ID HEMODIALYSIS-PATIENTS; DISEASES SOCIETY; MEDICINE ASSOCIATION; IMPAIRED
RESPONSE; RANDOMIZED-TRIAL; VIRUS INFECTION; GUIDELINES; MANAGEMENT;
EFFICACY; AMERICA
AB HIV-infected persons are at risk for HBV co-infection which is associated with increased morbidity and mortality. Unfortunately, protective immunity following HBV vaccination in HIV-infected persons is poor. This randomized, phase II, open-label study aimed to evaluate efficacy and safety of 40 mcg HBV vaccine with or without 250 mcg GM-CSF administered at day 0, weeks 4 and 12. HIV-infected individuals >= 18 years of age, CD4 count >= 200 cells/mm(3), seronegative for HBV and HCV, and nave to HBV vaccination were eligible. Primary endpoints were quantitative HBsAb titers and adverse events. The study enrolled 48 subjects. Median age and baseline CD4 were 41 years and 446 cells/mm(3), 37 were on ART, and 26 subjects had undetectable VL Vaccination was well tolerated. Seven subjects in the GM-CSF arm reported transient grade >= 2 signs/symptoms (six grade 2, one grade 3), mostly aches and nausea. GM-CSF had no significant effect on VL or CD4. Four weeks after vaccination, 26 subjects (59%) developed a protective antibody response (HBsAb >= 10 mIU/mL; 52% in the GM-CSF arm and 65% in the control arm) without improved Ab titer in the GM-CSF vs. control arm (median 11 mIU/mL vs. 92 mIU/mL, respectively). Response was more frequent in those with CD4 >= 350 cells/mm(3) (64%) than with CD4 <350 cells/mm(3) (50%), though not statistically significant. GM-CSF as an adjuvant did not improve the Ab titer or the development of protective immunity to HBV vaccination in those receiving an accelerated vaccine schedule. Given the common routes of transmission for HIV and HBV, additional HBV vaccine research is warranted. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Overton, E. T.] Washington Univ, Div Infect Dis, Sch Med, St Louis, MO 63110 USA.
[Kang, M.; Umbleja, T.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Peters, M. G.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Alston-Smith, B. L.] NIH, Bethesda, MD 20892 USA.
[Bastow, B.] ACTG, Silver Spring, MD USA.
[Koziel, M. J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Mong-Kryspin, L.] Ohio State Univ, Columbus, OH 43210 USA.
[Sprenger, H. L.; Yu, J. Y.] Frontier Sci, Amherst, NY USA.
[Aberg, J. A.] NYU, New York, NY USA.
RP Overton, ET (reprint author), Washington Univ, Div Infect Dis, Sch Med, 660 S Euclid Ave,Campus Box 8011, St Louis, MO 63110 USA.
EM toverton@dom.wustl.edu
FU Merck; GlaxoSmithKline; Gilead; Abbott; Tibotec; Boehinger Ingelheim
through Washington University; Abbott Laboratories; Boehringer
Ingelheim; Bristol Myers Squib; Gilead Sciences; Glaxo-Smith Kline;
Merck Co., Inc.; Pfizer, Inc; Schering-Plough; Tibotec Therapeutics;
National Institute of Allergy and Infectious Diseases [AI 68636, AI
68634, AI069495, AI038855, AI068634, AIO27665, AI069532, AI 69495, AI
69434, AI 69532, AI 69474, AI 69471, AI 69501, AI69513, AI 69511, AI
69484-02]; NIH [RR 024160]; Washington University; New York
University/NYC HHC at Bellevue Hospital Center; Ohio State University;
Northwestern University; Case Western Reserve University; University of
Cincinnati College of Medicine; Rush University Medical Center;
Rochester; Duke University Medical Center; MetroHealth Medical Center
FX ETO received research grants from Merck, GlaxoSmithKline, Gilead,
Abbott, Tibotec, and Boehinger Ingelheim through Washington University;
served as a consultant for Tibotec and GlaxoSmithKline; and served on
speakers' bureau or received honoraria from Merck, Tibotec,
GlaxoSmithKline, Bristol-Myers Squibb, GlaxoSmithKline, Monogram
Sciences, and Gilead. JA has received honoraria, research support and/or
served on the advisory boards of Abbott Laboratories, Boehringer
Ingelheim, Bristol Myers Squib, Gilead Sciences, Glaxo-Smith Kline,
Merck & Co., Inc., Pfizer, Inc, Schering-Plough and Tibotec
Therapeutics. MP has served as a consultant for Merck, Pharmasset,
Cinical Care Options and Hoffman LaRoche. MJK moved from Beth Israel
Deaconess to Novartis after the completion of the study. All other
authors: no conflicts.; This research was supported in part by the AIDS
Clinical Trials Group funded by the National Institute of Allergy and
Infectious Diseases (Grants: AI 68636 and AI 68634) and by the
institutions listed below. HBV vaccine was donated by Merck and GM-CSF
by Bayer. Neither pharmaceutical company was involved in the design,
conduct or analysis of data from this study, or in the writing of this
paper; however we thank Rafael Munoz, Bayer for his scientific guidance
during the design of this study. Grant support was provided, in part, to
Dr. Overton from NIH AI069495; Dr. Kang from NIH AI038855 and AI068634;
and Dr. Aberg from NIH AIO27665 and AI069532.; The following persons and
institutions participated in the conduct of this trial: Teresa Spitz, RN
and Geyoul Kim, RN (Washington University (Site 2101) CTU Grant# AI
69495); Janet Forcht, RN and Karen Cavanagh, RN (New York University/NYC
HHC at Bellevue Hospital Center (Site 0401) CTU Grant# AI 69532);
William E. Maher, MD and Laura Laughlin, RN (Ohio State University (Site
2301) CTU Grant# AI 69474); Babafemi Taiwo, M.B.B.S., M.D. and Karen
Coleman, R.N. (Northwestern University (Site 2701) CTU Grant# AI 69471);
Benigno Rodriguez, MD and Trisha Walton, RN (Case Western Reserve
University (Site 2501) CTU Grant# AI 69501); Shelia Dunaway, MD and
Sheryl Storey, PA-C (University of Washington (Site 1401) CTU Grant# AI
69434); Judith Feinberg MD and Tammy Mansfield RN ACRN (University of
Cincinnati College of Medicine (Site 2401) CTU Grant# AI69513); Allan
R.Tenorio, MD and Beverly E. Sha, MD (Rush University Medical Center
(Site 2702) CTU Grant# AI 69471); Jane Reid RN, MS, APN-BC and Carol
Greisberger RN BSN CCRC (Rochester (Site 1101) CTU Grant# AI 69511; GCRC
Grant# RR 024160); Nathan M. Thielman, MD and Martha Silberman, RN (Duke
University Medical Center (Site 1601) CTU Grant# AI 69484-02); Ann Marie
Anderson, R.N. and Robert C Kalayjian, M.D. (MetroHealth Medical Center
(Site 2503) CTU Grant# AI 69501).
NR 36
TC 14
Z9 17
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD AUG 2
PY 2010
VL 28
IS 34
BP 5597
EP 5604
DI 10.1016/j.vaccine.2010.06.030
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 639DZ
UT WOS:000280952300011
PM 20600512
ER
PT J
AU Summers, RM
Liu, JM
Rehani, B
Stafford, P
Brown, L
Louie, A
Barlow, DS
Jensen, DW
Cash, B
Choi, JR
Pickhardt, PJ
Petrick, N
AF Summers, Ronald M.
Liu, Jiamin
Rehani, Bhavya
Stafford, Phillip
Brown, Linda
Louie, Adeline
Barlow, Duncan S.
Jensen, Donald W.
Cash, Brooks
Choi, J. Richard
Pickhardt, Perry J.
Petrick, Nicholas
TI CT Colonography Computer-Aided Polyp Detection: Effect on Radiologist
Observers of Polyp Identification by CAD on Both the Supine and Prone
Scans
SO ACADEMIC RADIOLOGY
LA English
DT Article
DE CT; colon; CT; virtual imaging; colon cancer; image processing;
automated detection; observer performance
ID TOMOGRAPHIC VIRTUAL COLONOSCOPY; MAMMOGRAPHIC VIEWS; READER PARADIGM;
2ND READER; PERFORMANCE; SENSITIVITY; SCHEME
AB Rationale and Objectives: To determine whether the display of computer-aided detection (CAD) marks on individual polyps on both the supine and prone scans leads to improved polyp detection by radiologists compared to the display of CAD marks on individual polyps on either the supine or the prone scan, but not both.
Materials and Methods: The acquisition of patient data for this study was approved by the Institutional Review Board and was Health Insurance Portability and Accountability Act-compliant. Subsequently, the use of the data was declared exempt from further institutional review board review. Four radiologists interpreted 33 computed tomography colonography cases, 21 of which had one adenoma 6-9 mm in size, with the assistance of a CAD system in the first reader mode (ie, the radiologists reviewed only the CAD marks). The radiologists were shown each case twice, with different sets of CAD marks for each of the two readings. In one reading, a true-positive CAD mark for the same polyp was displayed on both the supine and prone scans (a double-mark reading). In the other reading, a true-positive CAD mark was displayed either on the supine or prone scan, but not both (a single-mark reading). True-positive marks were randomized between readings and there was at least a 1-month delay between readings to minimize recall bias. Sensitivity and specificity were determined and receiver operating characteristic (ROC) and multiple-reader multiple-case analyses were performed.
Results: The average per polyp sensitivities were 60% (38%-81%) versus 71% (52%-91%) (P = .03) for single-mark and double-mark readings, respectively. The areas (95% confidence intervals) under the ROC curves were 0.76 (0.62-0.88) and 0.79 (0.58-0.96), respectively (P = NS). Specificities were similar for the single-mark compared with the double-mark readings.
Conclusion: The display of CAD marks on a polyp on both the supine and prone scans led to more frequent detection of polyps by radiologists without adversely affecting specificity for detecting 6-9 mm adenomas.
C1 [Summers, Ronald M.; Liu, Jiamin; Rehani, Bhavya; Stafford, Phillip; Brown, Linda; Louie, Adeline] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA.
[Barlow, Duncan S.; Jensen, Donald W.; Cash, Brooks] Natl Naval Med Ctr, Colon Hlth Initiat, Bethesda, MD USA.
[Choi, J. Richard] Walter Reed Army Med Ctr, Washington, DC 20307 USA.
[Pickhardt, Perry J.] Univ Wisconsin, Sch Med, Dept Radiol, Madison, WI USA.
[Petrick, Nicholas] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10,Room 1C368X MSC 1182, Bethesda, MD 20892 USA.
EM rms@nih.gov
FU National Institutes of Health (NIH); National Institute of Biomedical
Imaging and Bioengineering
FX From the Imaging Biomarkers and Computer-Aided Diagnosis Laboratory,
Radiology and Imaging Sciences, National Institutes of Health Clinical
Center, Bldg. 10, Room 1C368X MSC 1182, Bethesda, MD 20892-1182 (R.M.S.,
J.L., B.R., P.S., LB., A.L.); Colon Health Initiative, National Naval
Medical Center, Bethesda, MD (D.S.B., D.W.J., B.C.); Walter Reed Army
Medical Center, Washington, DC (J.R.C.); Department of Radiology,
University of Wisconsin Medical School, Madison, WI (P.J.P); Center for
Devices and Radiological Health, U.S. Food and Drug Administration,
Silver Spring, MD (NP.) Received February 15, 2010; accepted March 26,
2010. Presented in part at the 2008 meeting of CARS, Barcelona, Spain.
Supported in part by the Intramural Research Program of the National
Institutes of Health (NIH) Clinical Center and the National Institute of
Biomedical Imaging and Bioengineering (NP.). R.M.S. has pending and/or
awarded patents for the subject matter described in the manuscript and
receives royalty income for a patent license from iCAD. His lab is
supported in part by a Cooperative Research and Development Agreement
with iCAD. Viatronix supplied the V3D Colon software to NIH free of
charge. P.J.P. is on the medical advisory boards of Viatronix, Inc, and
Medicsight, Inc, a consultant to Covidien and co-founder of VirtuoCTC.
J.R.C. is on the medical advisory boards of Viatronix, Inc, and QI and
has received research support from E-Z-EM. The views expressed in this
article are those of the authors and do not necessarily reflect the
official policy or position of the Department of the Navy, Department of
Defense, nor the U.S. Government and no official endorsement of any
equipment or product of any company mentioned in the publication should
be inferred. Address correspondence to: R.M.S. e-mail: rms@nih.gov
NR 31
TC 9
Z9 9
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1076-6332
EI 1878-4046
J9 ACAD RADIOL
JI Acad. Radiol.
PD AUG
PY 2010
VL 17
IS 8
BP 948
EP 959
DI 10.1016/j.acra.2010.03.024
PG 12
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 627IO
UT WOS:000280032900002
PM 20542452
ER
PT J
AU Banerjee, A
Panosian, TD
Mukherjee, K
Ravindra, R
Gal, S
Sackett, DL
Bane, S
AF Banerjee, Abhijit
Panosian, Timothy D.
Mukherjee, Kamalika
Ravindra, Rudravajhala
Gal, Susannah
Sackett, Dan L.
Bane, Susan
TI Site-Specific Orthogonal Labeling of the Carboxy Terminus of
alpha-Tubulin
SO ACS CHEMICAL BIOLOGY
LA English
DT Article
ID TYROSINE-LIGASE; POSTTRANSLATIONAL MODIFICATIONS; GENETIC INCORPORATION;
POOR-PROGNOSIS; AMINO-ACIDS; MICROTUBULES; MECHANISM; PROTEINS; CELLS;
DETYROSINATION
AB A fluorescent probe has been attached to the carboxy terminus of the a-subunit of alpha,beta-tubulin by an enzymatic reaction followed by a chemical reaction. The unnatural amino acid 3-formyltyrosine is attached to the carboxy terminus of alpha-tubulin through the use of the enzyme tubulin tyrosine ligase. The aromatic aldehyde of the unnatural amino acid serves as an orthogonal electrophile that specifically reacts with a fluorophore containing an aromatic hydrazine functional group, which in this case is 7-hydrazino-4-methyl coumarin. Conditions for covalent bond formation between the unnatural amino acid and the fluorophore are mild, allowing fluorescently labeled tubulin to retain its ability to assemble into microtubules. A key feature of the labeling reaction is that it produces a red shift in the fluorophore's absorption and emission maxima, accompanied by an increase in its quantum yield; thus, fluorescently labeled protein can be observed in the presence of unreacted fluorophore. Both the enzymatic and coupling reaction can occur in living cells. The approach presented here should be applicable to a wide variety of in vitro systems.
C1 [Banerjee, Abhijit; Panosian, Timothy D.; Mukherjee, Kamalika; Ravindra, Rudravajhala; Bane, Susan] SUNY Binghamton, Dept Chem, Binghamton, NY 13902 USA.
[Gal, Susannah] SUNY Binghamton, Dept Biol Sci, Binghamton, NY 13902 USA.
[Sackett, Dan L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Integrat & Med Biophys, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
RP Bane, S (reprint author), SUNY Binghamton, Dept Chem, Binghamton, NY 13902 USA.
EM sbane@binghamton.edu
RI Bane, Susan/C-1414-2013
OI Bane, Susan/0000-0002-4270-6314
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; NIH [R01 CA-69571, R15 GM-093941]
FX This work was supported in part by the Intramural Research Program of
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development and by NIH Grants R01 CA-69571 and R15 GM-093941. We are
grateful to Prof. Dr. J. Wehland and Dr. C. Erck for their initial gift
of TTL. We thank Mr. B. Cowen for the first synthesis of
3-formyltyrosine, Dr. R. Kissling for assistance in the synthetic
chemistry, and Mr. D. Tuttle for photography.
NR 44
TC 22
Z9 22
U1 0
U2 14
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1554-8929
J9 ACS CHEM BIOL
JI ACS Chem. Biol.
PD AUG
PY 2010
VL 5
IS 8
BP 777
EP 785
DI 10.1021/cb100060v
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 640DW
UT WOS:000281029500008
PM 20545322
ER
PT J
AU Mccoy, JG
Marugan, JJ
Liu, K
Zheng, W
Southall, N
Huang, WW
Heilig, M
Austin, CP
AF McCoy, Joshua G.
Marugan, Juan J.
Liu, Ke
Zheng, Wei
Southall, Noel
Huang, Wenwei
Heilig, Markus
Austin, Christopher P.
TI Selective Modulation of Gq/Gs pathways by Naphtho Pyrano Pyrimidines As
Antagonists of the Neuropeptide S Receptor
SO ACS CHEMICAL NEUROSCIENCE
LA English
DT Article
DE Neuropeptide S receptor antagonist; sleep disorders; addiction
disorders; naphtho pyrano pyrimidines; homogeneous time-resolved
fluorescence; neuropeptide S radiolabel displacement assay
ID AROUSAL; MICE
AB Antagonists of the neuropeptide S receptor have been postulated as promising therapeutics in the treatment of respiratory, sleep, anxiety, and addictive disorders. Here, we present the SA R of a new series of orthosteric antagonists. Neuropeptide S receptor signaling is coupled to both Gq and Gs proteins, and we observe that different analogues in this structural series can selectively antagonize these two pathways. Many G-protein coupled receptors transduce signals through multiple pathways. Selective antagonism of these pathways may lead the way to the development of more targeted pharmacological profiles and therapies.
C1 [McCoy, Joshua G.; Marugan, Juan J.; Liu, Ke; Zheng, Wei; Southall, Noel; Huang, Wenwei; Austin, Christopher P.] NHGRI, NIH Chem Genom Ctr, NIH, Rockville, MD 20850 USA.
[Heilig, Markus] NIAAA, NIH, Bethesda, MD 20892 USA.
RP Marugan, JJ (reprint author), NHGRI, NIH Chem Genom Ctr, NIH, 9800 Med Ctr Dr, Rockville, MD 20850 USA.
EM maruganj@mail.nih.gov
RI Southall, Noel/H-8991-2012;
OI Southall, Noel/0000-0003-4500-880X; Heilig, Markus/0000-0003-2706-2482;
Zheng, Wei/0000-0003-1034-0757
FU NIH; National Human Genome Research Institute, National Institutes of
Health
FX This research was supported by the Molecular Libraries Initiative of the
NIH Roadmap for Medical Research and the Intramural Research Program of
the National Human Genome Research Institute, National Institutes of
Health.
NR 15
TC 12
Z9 13
U1 0
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-7193
J9 ACS CHEM NEUROSCI
JI ACS Chem. Neurosci.
PD AUG
PY 2010
VL 1
IS 8
BP 559
EP 574
DI 10.1021/cn100040h
PG 16
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences
& Neurology
GA 640LJ
UT WOS:000281052400006
PM 21116448
ER
PT J
AU Frankowski, KJ
Ghosh, P
Setola, V
Tran, TB
Roth, BL
Aube, J
AF Frankowski, Kevin J.
Ghosh, Partha
Setola, Vincent
Tran, Thuy B.
Roth, Bryan L.
Aube, Jeffrey
TI N-Alkyl-octahydroisoquinolin-1-one-8-carboxamides: Selective and
Nonbasic kappa-Opioid Receptor Ligands
SO ACS MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE kappa-Opioid receptor; isoquinolones
ID FORCED-SWIM TEST; MU-OPIOIDS; ANTAGONISTS; RATS; PRESSURE
AB Herein, we report that N-alkyl-octahydroisoquinolin-1-one-8-carboxamides are a novel class of readily synthesized, selective K-opioid receptor (KOR) ligands. A striking feature of this class of compounds is the absence of any basic nitrogen atoms. Many of these compounds have demonstrated exclusive affinity for the KOR over not only the delta-opioid receptor and the mu-opioid receptor but also 38 other G protein-coupled receptor targets. The general binding affinity of this class of compounds for the KOR combined with a streamlined route for analogue synthesis provide strong motivation for pursuing this interesting new scaffold as a basis toward new probes targeting the KOR.
C1 [Frankowski, Kevin J.; Ghosh, Partha; Aube, Jeffrey] Univ Kansas, Dept Med Chem, Lawrence, KS 66047 USA.
[Setola, Vincent; Tran, Thuy B.; Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27514 USA.
[Setola, Vincent; Tran, Thuy B.; Roth, Bryan L.] Univ N Carolina, NIMH Psychoact Drug Screening Program CB 7365, Chapel Hill, NC 27514 USA.
RP Aube, J (reprint author), Univ Kansas, Dept Med Chem, 2121 Simons Dr, Lawrence, KS 66047 USA.
EM jaube@ku.edu
RI Roth, Bryan/F-3928-2010;
OI Aube, Jeffrey/0000-0003-1049-5767
FU National Institute of General Medical Sciences [GM-49093,
PO50-GM069663]; National Institute of Mental Health (NIMH-PDSP)
[HHSN-271-2008-000025-C, RO1 DA-017204]
FX We thank the National Institute of General Medical Sciences (GM-49093
and PO50-GM069663), the National Institute of Mental Health's
Psychoactive Drug Screening Program [Contract #HHSN-271-2008-000025-C
(NIMH-PDSP)] and RO1 DA-017204 for financial support.
NR 20
TC 12
Z9 12
U1 1
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-5875
J9 ACS MED CHEM LETT
JI ACS Med. Chem. Lett.
PD AUG
PY 2010
VL 1
IS 5
BP 189
EP 193
DI 10.1021/ml100040t
PG 5
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 638TL
UT WOS:000280919100001
PM 20729985
ER
PT J
AU Li, M
Gustchina, A
Rasulova, FS
Melnikov, EE
Maurizi, MR
Rotanova, TV
Dauter, Z
Wlodawer, A
AF Li, Mi
Gustchina, Alla
Rasulova, Fatima S.
Melnikov, Edward E.
Maurizi, Michael R.
Rotanova, Tatyana V.
Dauter, Zbigniew
Wlodawer, Alexander
TI Structure of the N-terminal fragment of Escherichia coli Lon protease
SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
LA English
DT Article
ID CRYSTAL-STRUCTURE; DEPENDENT PROTEASES; LIMITED PROTEOLYSIS; CATALYTIC
DOMAIN; ACTIVE-SITES; PROTEINS; CHAPERONE; AAA(+); CLASSIFICATION;
RECOGNITION
AB The structure of a recombinant construct consisting of residues 1-245 of Escherichia coli Lon protease, the prototypical member of the A-type Lon family, is reported. This construct encompasses all or most of the N-terminal domain of the enzyme. The structure was solved by SeMet SAD to 2.6 angstrom resolution utilizing trigonal crystals that contained one molecule in the asymmetric unit. The molecule consists of two compact subdomains and a very long C-terminal alpha-helix. The structure of the first subdomain (residues 1-117), which consists mostly of beta-strands, is similar to that of the shorter fragment previously expressed and crystallized, whereas the second subdomain is almost entirely helical. The fold and spatial relationship of the two subdomains, with the exception of the C-terminal helix, closely resemble the structure of BPP1347, a 203-amino-acid protein of unknown function from Bordetella parapertussis, and more distantly several other proteins. It was not possible to refine the structure to satisfactory convergence; however, since almost all of the Se atoms could be located on the basis of their anomalous scattering the correctness of the overall structure is not in question. The structure reported here was also compared with the structures of the putative substrate-binding domains of several proteins, showing topological similarities that should help in defining the binding sites used by Lon substrates.
C1 [Li, Mi; Gustchina, Alla; Wlodawer, Alexander] NCI, Protein Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA.
[Li, Mi] SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA.
[Rasulova, Fatima S.; Maurizi, Michael R.] NCI, Cell Biol Lab, Bethesda, MD 20892 USA.
[Melnikov, Edward E.; Rotanova, Tatyana V.] Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia.
[Dauter, Zbigniew] Argonne Natl Lab, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, NCI, Argonne, IL 60439 USA.
RP Wlodawer, A (reprint author), NCI, Protein Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA.
EM wlodawer@nih.gov
FU Russian Foundation for Basic Research [08-04-00977]; NIH, National
Cancer Institute, Center for Cancer Research; US Department of Energy,
Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38];
National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX We thank Gerald G. Leffers (NCI) for constructing the pET30a clone of E.
coli Lon with the synonymous mutation eliminating the endogenous NdeI
restriction enzyme site. We acknowledge the use of beamline 22-ID of the
Southeast Regional Collaborative Access Team (SER-CAT), located at the
Advanced Photon Source, Argonne National Laboratory. Use of the APS was
supported by the US Department of Energy, Office of Science, Office of
Basic Energy Sciences under Contract No. W-31-109-Eng-38. This work was
supported in part by a grant from the Russian Foundation for Basic
Research (Project No. 08-04-00977) to TVR, by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research and by Federal funds from the National Cancer Institute,
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 the
mention of trade names, commercial products or organizations imply
endorsement by the US Government.
NR 52
TC 15
Z9 15
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0907-4449
J9 ACTA CRYSTALLOGR D
JI Acta Crystallogr. Sect. D-Biol. Crystallogr.
PD AUG
PY 2010
VL 66
BP 865
EP 873
DI 10.1107/S0907444910019554
PN 8
PG 9
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA 627ZQ
UT WOS:000280083900002
PM 20693685
ER
PT J
AU Lauretani, F
Cepollaro, C
Bandinelli, S
Cherubini, A
Gozzini, A
Masi, L
Falchetti, A
Del Monte, F
Carbonell-Sala, S
Marini, F
Tanini, A
Corsi, AM
Ceda, GP
Brandi, ML
Ferrucci, L
AF Lauretani, Fulvio
Cepollaro, Chiara
Bandinelli, Stefania
Cherubini, Antonio
Gozzini, Alessia
Masi, Laura
Falchetti, Alberto
Del Monte, Francesca
Carbonell-Sala, Silvia
Marini, Francesca
Tanini, Annalisa
Corsi, Anna Maria
Ceda, Gian Paolo
Brandi, Maria Luisa
Ferrucci, Luigi
TI LRP5 gene polymorphism and cortical bone
SO AGING CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Cortical bone area; LRP5 gene polymorphism; osteoporosis; peripheral
bone quantitative computed tomography (pQCT); volumetric BMD
ID RECEPTOR-RELATED PROTEIN-5; MINERAL DENSITY; FRACTURE RISK; ASSOCIATION;
WOMEN; MEN; MASS; OSTEOPOROSIS; MUTATIONS; BMD
AB Background and aims: There is evidence that distinct genetic polymorphisms of LRP5 are associated with low Bone Mineral Density (BMD) and the risk of fracture. However, relationships between LRP5 polymorphisms and micro- and macro-architectural bone characteristics assessed by pQCT have not been studied. The aim of the present study was to investigate the association of Ala1330Val and Va1667Met polymorphisms in LRP5 gene with volumetric BMD (vBMD) and macro-architectural bone parameters in a population-based sample of men and women. Methods: We studied 959 participants of the InCHIANTI study (451 men and 508 women, age range: 21-94 yrs). Trabecular vBMD (vBMDt, mg/cm(3)), cortical vBMD (vBMDc, mg/cm(3)), cortical bone area (CBA, mm(2)) and cortical thickness (Ct.Th, mm) at the level of the tibia were assessed by peripheral quantitative computed tomography (pQCT). Ala1330Val and Va1667Met genotypes were determined on genomic DNA by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: In age-adjusted analyses both LRP 1330-valine and LRP 667-metionin variants were associated with lower vBMDt in men (p<0.05), and lower vBMDt (p<0.05), Ct.Th (p<0.05) and CBA (p<0.05) in women. After adjusting for multiple confounders, only the association of LRP5 1330-valine and 667-metionin with CBA remained statistically significant (p=0.04 and p=0.01, respectively) in women. Conclusion: These findings suggest that both Ala1330Val and Va1667Met LRP5 polymorphisms may affect the determination of geometric bone parameters in women. (Aging Clin Exp Res 2010; 22: 281-288) (C) 2010, Editrice Kurtis
C1 [Lauretani, Fulvio] Univ Hosp Parma, Dept Geriatr Rehabil, Geriatr Unit, I-40130 Parma, Italy.
[Cepollaro, Chiara; Gozzini, Alessia; Masi, Laura; Falchetti, Alberto; Del Monte, Francesca; Carbonell-Sala, Silvia; Marini, Francesca; Tanini, Annalisa; Brandi, Maria Luisa] Univ Florence, Dept Internal Med & Spin Off DeGene, Florence, Italy.
[Bandinelli, Stefania] Azienda Sanitaria Firenze, Geriatr Unit, Florence, Italy.
[Cherubini, Antonio] Univ Perugia, Sch Med, Inst Gerontol & Geriatr, I-06100 Perugia, Italy.
[Ceda, Gian Paolo] Univ Hosp Parma, Geriatr Clin, Parma, Italy.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
RP Lauretani, F (reprint author), Univ Hosp Parma, Dept Geriatr Rehabil, Geriatr Unit, I-40130 Parma, Italy.
EM flauretani@ao.pr.it
RI FALCHETTI, ALBERTO/Q-1787-2016; Lauretani, Fulvio/K-5115-2016;
OI FALCHETTI, ALBERTO/0000-0002-6739-4417; Lauretani,
Fulvio/0000-0002-5287-9972; Ceda, Gian Paolo/0000-0002-9648-8295;
Cherubini, Antonio/0000-0003-0261-9897
FU Italian Ministry of Health [ICS 110.1\RS97.71]; U.S. National Institute
on Aging [N01-AG-916413, N01-AG-821336, 263 MD 9164 13, 263 MD 821336];
MIUR [RB-NE01C5S2]; FIRB [RB-NE01C5S2, 4AF/F10]; Agenzia Spaziale
Italiana
FX The InCHIANTI study was supported as a "targeted project" (ICS
110.1\RS97.71) by the Italian Ministry of Health and in part by the U.S.
National Institute on Aging (Contracts N01-AG-916413 and N01-AG-821336),
and by U.S. National Institute on Aging (Contracts 263 MD 9164 13 and
263 MD 821336). This work was also supported by MIUR 2003 to MLB
"Genetic Markers of Osteoporosis in the Italian population", FIRB PNR
2001-2003 (protocol RB-NE01C5S2) (to MLB) "Identification of Genetic
Susceptibility to Multifactorial Diseases in the Italian Population, ISS
2003 SARA project no. 4AF/F10 (to MLB) "Correlation Study between
Endocrine Estrogenic Activity and Genetic Polymorphisms", and the Ente
Cassa di Risparmio di Firenze (to MLB). Dr. Chiara Cepollaro received an
unrestricted grant from the Agenzia Spaziale Italiana. We thank Dr.
Cosimo Roberto Russo for assistance in the methodological aspects of
performing pQCT scans. The authors report no conflict of interest.
NR 35
TC 0
Z9 0
U1 0
U2 0
PU EDITRICE KURTIS S R L
PI MILAN
PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY
SN 1594-0667
J9 AGING CLIN EXP RES
JI Aging Clin. Exp. Res.
PD AUG
PY 2010
VL 22
IS 4
BP 281
EP 288
PG 8
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 697ET
UT WOS:000285496100002
PM 21116122
ER
PT J
AU Schensul, JJ
Singh, SK
Gupta, K
Bryant, K
Verma, R
AF Schensul, Jean J.
Singh, S. K.
Gupta, Kamla
Bryant, Kendall
Verma, Ravi
TI Alcohol and HIV in India: A Review of Current Research and Intervention
SO AIDS AND BEHAVIOR
LA English
DT Editorial Material
ID SEXUALLY-TRANSMITTED INFECTIONS; FEMALE SEX WORKERS; RISK BEHAVIORS;
ANDHRA-PRADESH; SUBSTANCE USE; SOUTH-INDIA; PREVENTION; POPULATION;
CHENNAI; MEN
C1 [Schensul, Jean J.] Inst Community Res, Hartford, CT 06106 USA.
[Singh, S. K.; Gupta, Kamla] Int Inst Populat Sci, Mumbai, Maharashtra, India.
[Bryant, Kendall] NIAAA, Bethesda, MD USA.
[Verma, Ravi] Asia Reg Off, Int Ctr Res Women, New Delhi, India.
RP Schensul, JJ (reprint author), Inst Community Res, 2 Hartford Sq W,Ste 100, Hartford, CT 06106 USA.
EM Jean.schensul@icrweb.org
NR 23
TC 5
Z9 5
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
J9 AIDS BEHAV
JI AIDS Behav.
PD AUG
PY 2010
VL 14
SU 1
BP 1
EP 7
DI 10.1007/s10461-010-9740-x
PG 7
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 622RA
UT WOS:000279681300001
ER
PT J
AU Papas, RK
Sidle, JE
Wamalwa, ES
Okumu, TO
Bryant, KL
Goulet, JL
Maisto, SA
Braithwaite, RS
Justice, AC
AF Papas, Rebecca K.
Sidle, John E.
Wamalwa, Emmanuel S.
Okumu, Thomas O.
Bryant, Kendall L.
Goulet, Joseph L.
Maisto, Stephen A.
Braithwaite, R. Scott
Justice, Amy C.
TI Estimating Alcohol Content of Traditional Brew in Western Kenya Using
Culturally Relevant Methods: The Case for Cost Over Volume
SO AIDS AND BEHAVIOR
LA English
DT Article
DE Alcohol; Traditional brew; HIV; Kenya; Cognitive behavioral treatment
ID COLLABORATIVE PROJECT; HIV-INFECTION; CONSUMPTION; RISK; NIGERIA; WOMEN
AB Traditional homemade brew is believed to represent the highest proportion of alcohol use in sub-Saharan Africa. In Eldoret, Kenya, two types of brew are common: chang'aa, spirits, and busaa, maize beer. Local residents refer to the amount of brew consumed by the amount of money spent, suggesting a culturally relevant estimation method. The purposes of this study were to analyze ethanol content of chang'aa and busaa; and to compare two methods of alcohol estimation: use by cost, and use by volume, the latter the current international standard. Laboratory results showed mean ethanol content was 34% (SD = 14%) for chang'aa and 4% (SD = 1%) for busaa. Standard drink unit equivalents for chang'aa and busaa, respectively, were 2 and 1.3 (US) and 3.5 and 2.3 (Great Britain). Using a computational approach, both methods demonstrated comparable results. We conclude that cost estimation of alcohol content is more culturally relevant and does not differ in accuracy from the international standard.
C1 [Papas, Rebecca K.; Goulet, Joseph L.; Braithwaite, R. Scott; Justice, Amy C.] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA.
[Sidle, John E.] Moi Univ, Fac Hlth Sci, Dept Med, Eldoret, Kenya.
[Okumu, Thomas O.] Kenya Bur Stand, Nairobi, Kenya.
[Bryant, Kendall L.] Natl Inst Alcohol Abuse & Alcoholism, Rockville, MD USA.
[Maisto, Stephen A.] Syracuse Univ, Dept Psychol, Syracuse, NY USA.
RP Papas, RK (reprint author), Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA.
EM Rebecca.papas@yale.edu
OI Goulet, Joseph/0000-0002-0842-804X
FU NIAAA NIH HHS [R21 AA016884-02, R21 AA016884, R21AA016884]
NR 28
TC 15
Z9 15
U1 4
U2 7
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
J9 AIDS BEHAV
JI AIDS Behav.
PD AUG
PY 2010
VL 14
IS 4
BP 836
EP 844
DI 10.1007/s10461-008-9492-z
PG 9
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 629UW
UT WOS:000280226400012
PM 19015972
ER
PT J
AU Gopal, DM
Kalogeropoulos, AP
Georgiopoulou, VV
Tang, WWH
Methvin, A
Smith, AL
Bauer, DC
Newman, AB
Kim, L
Harris, TB
Kritchevsky, SB
Butler, J
AF Gopal, Deepa M.
Kalogeropoulos, Andreas P.
Georgiopoulou, Vasiliki V.
Tang, Wilson W. H.
Methvin, Amanda
Smith, Andrew L.
Bauer, Douglas C.
Newman, Anne B.
Kim, Lauren
Harris, Tamara B.
Kritchevsky, Stephen B.
Butler, Javed
CA Hlth ABC Study
TI Serum albumin concentration and heart failure risk: The Health, Aging,
and Body Composition Study
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID EXPERIMENTAL DIABETIC CARDIOMYOPATHY; TUMOR-NECROSIS-FACTOR; C-REACTIVE
PROTEIN; CARDIOVASCULAR MORTALITY; DIASTOLIC DYSFUNCTION;
HEMODIALYSIS-PATIENTS; ALL-CAUSE; DISEASE; INTERLEUKIN-6; INFLAMMATION
AB Background How serum albumin levels are associated with risk for heart failure (HF) in the elderly is unclear.
Methods We evaluated 2,907 participants without HF (age 73.6 +/- 2.9 years, 48.0% male, 58.7% white) from the community-based Health ABC Study. The association between baseline albumin and incident HF was assessed with standard and competing risks proportional hazards models controlling for HF predictors, inflammatory markers, and incident coronary events.
Results During a median follow-up of 9.4 years, 342 (11.8%) participants developed HF. Albumin was a time-dependent predictor of HF, with significance retained for up to 6 years (baseline hazard ratio [HR] per - 1 g/L 1.14, 95% CI 1.06-1.22, P < .001; annual rate of HR decline 2.1%, 95% CI 0.8%-3.3%, P = .001). This association persisted in models controlling for HF predictors, inflammatory markers, and incident coronary events (baseline HR per - 1 g/L 1.13, 95% CI 1.05-1.22, P = .001; annual rate of HR decline 1.8%, 95% CI 0.5%-3.0%, P = .008) and when mortality was accounted for in adjusted competing risks models (baseline HR per - 1 g/L 1.13, 95% CI 1.05-1.21, P = .001; annual rate of HR decline 1.9%, 95% CI 0.7%-3.1%, P = .002). The association of albumin with HF risk was similar in men (HR per - 1 g/L 1.13, 95% CI 1.05-1.23, P = .002) and women (HR per - 1 g/L 1.12, 95% CI 1.04-1.22, P = .005) and in whites and blacks (HR per - 1 g/L 1.13, 95% CI 1.04-1.22, P< .01 for both races) in adjusted models.
Conclusions Low serum albumin levels are associated with increased risk for HF in the elderly in a time-dependent manner independent of inflammation and incident coronary events. (Am Heart J 2010;160:279-85.)
C1 [Kalogeropoulos, Andreas P.; Georgiopoulou, Vasiliki V.; Methvin, Amanda; Smith, Andrew L.; Butler, Javed] Emory Univ Hosp, Atlanta, GA 30322 USA.
[Gopal, Deepa M.] Boston Univ, Boston, MA 02215 USA.
[Tang, Wilson W. H.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Bauer, Douglas C.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Newman, Anne B.] Univ Pittsburgh, Pittsburgh, PA USA.
[Kim, Lauren; Harris, Tamara B.] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Kritchevsky, Stephen B.] Wake Forest Univ, Sticht Ctr Aging, Winston Salem, NC 27109 USA.
RP Butler, J (reprint author), Emory Univ Hosp, 1365 Clifton Rd NE,Suite AT430, Atlanta, GA 30322 USA.
EM javed.butler@emory.edu
RI Library, Woodruff Health/A-6096-2012; Newman, Anne/C-6408-2013;
Kalogeropoulos, Andreas/A-9494-2009;
OI Newman, Anne/0000-0002-0106-1150; Kalogeropoulos,
Andreas/0000-0002-1284-429X; Gopal, Deepa/0000-0003-3534-9360;
Kritchevsky, Stephen/0000-0003-3336-6781
FU Intramural NIH HHS [Z01 AG007390-02]
NR 28
TC 29
Z9 31
U1 0
U2 6
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD AUG
PY 2010
VL 160
IS 2
BP 279
EP 285
DI 10.1016/j.ahj.2010.05.022
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 635NM
UT WOS:000280662400011
PM 20691833
ER
PT J
AU Lin, YH
Llanos, A
Mena, P
Uauy, R
Salem, N
Pawlosky, RJ
AF Lin, Yu Hong
Llanos, Adolfo
Mena, Patricia
Uauy, Ricardo
Salem, Norman, Jr.
Pawlosky, Robert J.
TI Compartmental analyses of H-2(5)-alpha-linolenic acid and
C-13-U-eicosapentaenoic acid toward synthesis of plasma labeled 22:6-23
in newborn term infants
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID POLYUNSATURATED FATTY-ACIDS; ARACHIDONIC-ACID; DOCOSAHEXAENOIC ACIDS;
VISUAL-ACUITY; HUMAN-MILK; METABOLISM; FORMULAS; GROWTH; LIPIDS; MEN
AB Background: During early postnatal development, the nervous system accretes docosahexaenoic acid (DHA; 22:6n-3), a highly unsaturated n-3 (omega-3) fatty acid (FA) used in the formation of neural cell membranes. DHA, which is present in human breast milk, may also be biosynthesized from n-3 FAs such as 18:3n-3 [alpha-linolenic acid (ALA)] or 20: 5n-3 [eicosapentaenoic acid (EPA)]. An important concern is to what extent these precursors can supply DHA to the developing infant.
Objective: We analyzed measurements of fractional percentages of plasma H-2(5)-ALA and C-13-U-EPA directed toward the synthesis of labeled 22: 6n-3 in 11 newborn infants by using compartmental modeling procedures.
Design: One-week-old infants received doses of H-2(5)-ALA and (CU)-C-13-EPA ethyl esters enterally. We drew blood from the infants periodically and analyzed the plasma for endogenous and labeled n-3 FAs. From the time-course concentrations of the labeled FAs, we determined rate constant coefficients, fractional synthetic rates, and plasma turnover rates of n-3 FAs.
Results: In infants, approximate to 0.04% of the H-2(5)-ALA dose converted to plasma H-2(5)-EPA. Plasma H-2(5)-EPA and H-2(5)-22: 5n-3 [docosapentaenoic acid (DPA)] efficiently converted to H-2(5)-DPA and (2)H(5)DHA, respectively. The percentage of plasma C-13-U-EPA directed toward the synthesis of C-13-DHA was lower than the percentage of plasma H-2(5)-EPA that originated from H-2(5)-ALA.
Conclusions: Endogenously synthesized EPA was efficiently converted to DHA. In comparison, preformed EPA was less efficiently used for DHA biosynthesis, which suggests a differential metabolism of endogenous EPA compared with exogenous EPA. However, on a per mole basis, preformed EPA was 3.6 times more effective toward DHA synthesis than was ALA. Newborns required an intake of approximate to 5 mg preformed DHA . kg(-1).d(-1) to maintain plasma DHA homeostasis. Am J Clin Nutr 2010; 92: 284-93.
C1 [Lin, Yu Hong; Salem, Norman, Jr.] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA.
[Pawlosky, Robert J.] NIAAA, Lab Metab Control, NIH, Bethesda, MD USA.
[Llanos, Adolfo; Mena, Patricia; Uauy, Ricardo] Inst Nutr & Food Technol, Santiago, Chile.
[Llanos, Adolfo; Mena, Patricia] Hosp Dr Sotero del Rio, Neonatol Unit, Santiago, Chile.
[Uauy, Ricardo] London Sch Hyg & Trop Med, London WC1, England.
RP Pawlosky, RJ (reprint author), Room 1S-22,5625 Fishers Lane, Bethesda, MD 20892 USA.
EM bpawl@mail.nih.gov
FU National Institute on Alcohol Abuse and Alcoholism, NIH;
Fondecyt/Chilean National Scientific and Technological Fund [1990078]
FX Supported, in part, by the Intramural Research Program of the National
Institute on Alcohol Abuse and Alcoholism, NIH. Clinical research and
nonisotope biochemical analysis related to this work were supported by
Fondecyt/Chilean National Scientific and Technological Fund grant no.
1990078 to RU and PM.
NR 27
TC 18
Z9 20
U1 0
U2 4
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD AUG
PY 2010
VL 92
IS 2
BP 284
EP 293
DI 10.3945/ajcn.2009.28779
PG 10
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 628UZ
UT WOS:000280149700005
PM 20534748
ER
PT J
AU Bailey, RL
McDowell, MA
Dodd, KW
Gahche, JJ
Dwyer, JT
Picciano, MF
AF Bailey, Regan L.
McDowell, Margaret A.
Dodd, Kevin W.
Gahche, Jaime J.
Dwyer, Johanna T.
Picciano, Mary Frances
TI Total folate and folic acid intakes from foods and dietary supplements
of US children aged 1-13 y
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID NEURAL-TUBE DEFECTS; COMPLEX SURVEY DATA; UNITED-STATES; INTAKE
DISTRIBUTIONS; FORTIFICATION; NUTRITION; VITAMIN; PREVENTION; NUTRIENTS;
ENERGY
AB Background: Total folate intake includes naturally occurring food folate and folic acid from fortified foods and dietary supplements. Recent reports have focused on total folate intakes of persons aged >= 14 y. Information on total folate intakes of young children, however, is limited.
Objective: The objective was to compute total folate and total folic acid intakes of US children aged 1-13 y by using a statistical method that adjusts for within-person variability and to compare these intakes with the Dietary Reference Intake guidelines for adequacy and excess.
Design: Data from the 2003-2006 National Health and Nutrition Examination Survey, a nationally representative cross-sectional survey, were analyzed. Total folate intakes were derived by combining intakes of food folate (naturally occurring and folic acid from fortified foods) on the basis of 24-h dietary recall results and folic acid intakes from dietary supplements on the basis of a 30-d questionnaire.
Results: More than 95% of US children consumed at least the Estimated Average Requirement (EAR) for folate from foods alone. More than one-third (35%) of US children aged 1-13 y used dietary supplements, and 28% used dietary supplements containing folic acid. Supplement users had significantly higher total folate and folic acid intakes than did nonusers. More than half (53%) of dietary supplement users exceeded the Tolerable Upper Intake Level (UL) for total folic acid (fortified food + supplements) as compared with 5% of nonusers.
Conclusions: Total folate intakes of most US children aged 1-13 y meet the EAR. Children who used dietary supplements had significantly higher total folate intakes and exceeded the UL by >50%. Am J Clin Nutr 2010; 92: 353-8.
C1 [Bailey, Regan L.; Dwyer, Johanna T.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[McDowell, Margaret A.] NIH, Div Nutr Res Coordinat, Bethesda, MD 20892 USA.
[Dodd, Kevin W.] NCI, NIH, Bethesda, MD 20892 USA.
[Gahche, Jaime J.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
RP Bailey, RL (reprint author), 6100 Execut Blvd,2B03, Bethesda, MD 20892 USA.
EM baileyr@mail.nih.gov
OI Dwyer, Johanna/0000-0002-0783-1769
FU National Institutes of Health, Office of Dietary Supplements
FX Supported by the National Institutes of Health, Office of Dietary
Supplements.
NR 37
TC 27
Z9 27
U1 0
U2 3
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD AUG
PY 2010
VL 92
IS 2
BP 353
EP 358
DI 10.3945/ajcn.2010.29652
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 628UZ
UT WOS:000280149700013
PM 20534747
ER
PT J
AU Timpson, NJ
Forouhi, NG
Brion, MJ
Harbord, RM
Cook, DG
Johnson, P
McConnachie, A
Morris, RW
Rodriguez, S
Luan, J
Ebrahim, S
Padmanabhan, S
Watt, G
Bruckdorfer, KR
Wareham, NJ
Whincup, PH
Chanock, S
Sattar, N
Lawlor, DA
Smith, GD
AF Timpson, Nicholas J.
Forouhi, Nita G.
Brion, Marie-Jo
Harbord, Roger M.
Cook, Derek G.
Johnson, Paul
McConnachie, Alex
Morris, Richard W.
Rodriguez, Santiago
Luan, Jian'an
Ebrahim, Shah
Padmanabhan, Sandosh
Watt, Graham
Bruckdorfer, K. Richard
Wareham, Nicholas J.
Whincup, Peter H.
Chanock, Steve
Sattar, Naveed
Lawlor, Debbie A.
Smith, George Davey
TI Genetic variation at the SLC23A1 locus is associated with circulating
concentrations of L-ascorbic acid (vitamin C): evidence from 5
independent studies with > 15,000 participants
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID LOW-DENSITY-LIPOPROTEIN; GAMMA-LACTONE OXIDASE; BRITISH WOMENS HEART;
MENDELIAN RANDOMIZATION; DIABETES-MELLITUS; TRANSPORTER SVCT1;
EPIC-NORFOLK; RAT-KIDNEY; RISK; HEALTH
AB Background: L-Ascorbic acid is an essential part of the human diet and has been associated with a wide range of chronic complex diseases, including cardiovascular outcomes. To date, there are no confirmed genetic correlates of circulating concentrations of L-ascorbic acid.
Objective: We aimed to confirm the existence of an association between common variation at the SLC23A1 gene locus and circulating concentrations of L-ascorbic acid.
Design: We used a 2-stage design, which included a discovery cohort (the British Women's Heart and Health Study), a series of follow-up cohorts, and meta-analysis (totaling 15,087 participants) to assess the relation between variation at SLC23A1 and circulating concentrations of L-ascorbic acid.
Results: In the discovery cohort, variation at rs33972313 was associated with a reduction in circulating concentrations of L-ascorbic acid (-4.15 mu mol/L; 95% CI: -0.49, -7.81 mu mol/L; P = 0.03 reduction per minor allele). Pooled analysis of the relation between rs33972313 and circulating L-ascorbic acid across all studies confirmed this and showed that each additional rare allele was associated with a reduction in circulating concentrations of L-ascorbic acid of -5.98 mu mol/L (95% CI: -8.23, -3.73 mu mol/L; P = 2.0 x 10(-7) per minor allele).
Conclusions: A genetic variant (rs33972313) in the SLC23A1 vitamin C active transporter locus was identified that is reliably associated with circulating concentrations of L-ascorbic acid in the general population. This finding has implications more generally for the epidemiologic investigation of relations between circulating L-ascorbic acid and health outcomes. Am J Clin Nutr 2010; 92: 375-82.
C1 [Timpson, Nicholas J.] Univ Bristol, MRC, Ctr Causal Anal Translat Epidemiol, Dept Social Med, Bristol BS8 2BN, Avon, England.
[Forouhi, Nita G.; Luan, Jian'an; Wareham, Nicholas J.] Addenbrookes Hosp, MRC, Epidemiol Unit, Inst Metab Sci, Cambridge, England.
[Cook, Derek G.; Whincup, Peter H.] St Georges Univ London, Div Community Hlth Sci, London, England.
[Johnson, Paul; McConnachie, Alex] Univ Glasgow, Fac Med, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
[Padmanabhan, Sandosh; Sattar, Naveed] Univ Glasgow, Fac Med, British Heart Fdn, Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland.
[Morris, Richard W.] UCL, Dept Primary Care & Populat Hlth, London, England.
[Ebrahim, Shah] London Sch Hyg & Trop Med, London WC1, England.
[Watt, Graham] Univ Glasgow, Div Community Based Sci, Glasgow, Lanark, Scotland.
[Chanock, Steve] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Timpson, NJ (reprint author), Univ Bristol, MRC, Ctr Causal Anal Translat Epidemiol, Dept Social Med, Oakfield House, Bristol BS8 2BN, Avon, England.
EM n.j.timpson@bris.ac.uk
RI Harbord, Roger/A-8699-2008; Brion, Marie-Jo/O-6825-2014; Johnson,
Paul/O-9695-2014; Fox, Laura /C-6249-2016; Padmanabhan,
Sandosh/S-3963-2016;
OI Timpson, Nicholas/0000-0002-7141-9189; Lawlor, Debbie
A/0000-0002-6793-2262; Morris, Richard/0000-0001-7240-4563; Davey Smith,
George/0000-0002-1407-8314; Forouhi, Nita/0000-0002-5041-248X; Harbord,
Roger/0000-0002-2257-8271; Brion, Marie-Jo/0000-0002-9030-2103; Johnson,
Paul/0000-0001-6663-7520; Whincup, Peter/0000-0002-5589-4107; Monsalve,
Beatriz Elena/0000-0002-5994-866X; Padmanabhan,
Sandosh/0000-0003-3869-5808
FU MRC CAiTE Centre [G0600705]; MRC [G0601625, G9900686]; BHF
[FS/05/095/19937, PG97012, PG97027, FS05/125]; Department of Health
Policy Research Division; Wellcome Trust [051187/Z/97/A]; NHS; British
Heart Foundation Research Group; Cancer Research Campaign, the Medical
Research Council; Stroke Association; Department of Health; Europe
Against Cancer Programme Commission of the European Union; Ministry of
Agriculture, Fisheries and Food
FX NJT is supported by MRC CAiTE Centre grant G0600705; GDS and DAL work
within the MRC CAiTE Centre, which is capacity funded by grant G0600705;
RMH is supported in part by MRC project grant G0601625; SP was supported
by a BHF Intermediate Research Fellowship FS/05/095/19937; the British
Women's Heart and Health Study is supported by grants from the British
Heart Foundation and the Department of Health Policy Research Division;
The Offspring Study in MIDSPAN was supported by grants from the Wellcome
Trust and the NHS Research and Development Programme; The Ten Towns
Heart Health Study was supported by a project grant from The Wellcome
Trust (051187/Z/97/A) and the genetic studies by a grant from the
Medical Research Council (G9900686); The British Regional Heart Study is
a British Heart Foundation Research Group; the measurements and
laboratory analyses reported here were supported by British Heart
Foundation project grants PG97012 and PG97027; and the DNA extraction
was supported in part by British Heart Foundation Senior Research
Fellowship FS05/125. The EPIC Norfolk study is supported by grant
funding from the Cancer Research Campaign, the Medical Research Council,
the Stroke Association, the British Heart Foundation, the Department of
Health, the Europe Against Cancer Programme Commission of the European
Union and the Ministry of Agriculture, Fisheries and Food.
NR 49
TC 38
Z9 40
U1 0
U2 5
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD AUG
PY 2010
VL 92
IS 2
BP 375
EP 382
DI 10.3945/ajcn.2010.29438
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 628UZ
UT WOS:000280149700016
PM 20519558
ER
PT J
AU Bailey, RL
Mills, JL
Yetley, EA
Gahche, JJ
Pfeiffer, CM
Dwyer, JT
Dodd, KW
Sempos, CT
Betz, JM
Picciano, MF
AF Bailey, Regan L.
Mills, James L.
Yetley, Elizabeth A.
Gahche, Jaime J.
Pfeiffer, Christine M.
Dwyer, Johanna T.
Dodd, Kevin W.
Sempos, Christopher T.
Betz, Joseph M.
Picciano, Mary Frances
TI Unmetabolized serum folic acid and its relation to folic acid intake
from diet and supplements in a nationally representative sample of
adults aged >= 60 y in the United States
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID RANDOMIZED CLINICAL-TRIAL; DIHYDROFOLATE-REDUCTASE; FOLATE
FORTIFICATION; MASS-SPECTROMETRY; BLOOD FOLATE; CANCER-RISK; PLASMA;
WOMEN; QUANTIFICATION; VITAMIN-B-12
AB Background: Unmetabolized serum folic acid (UMFA) has been detected in adults. Previous research indicates that high folic acid intakes may be associated with risk of cancer.
Objective: The objective was to examine UMFA concentrations in relation to dietary and supplemental folate and status biomarkers in the US population aged >= 60 y.
Design: Surplus sera were analyzed with the use of data from the National Health and Nutrition Examination Survey (NHANES) 2001-2002, a cross-sectional, nationally representative survey (n = 1121).
Results: UMFA was detected in 38% of the population, with a mean concentration of 4.4 +/- 0.6 nmol/L (median: 1.2 +/- 0.2 nmol/L). The group with UMFA (UMFA+) had a significantly higher proportion of folic acid supplement users than did the group without UMFA (60% compared with 41%). UMFA+ men and women also had higher supplemental and total (food + supplements) folic acid intakes than did their counterparts without UMFA. Forty percent of the UMFA+ group was in the highest quartile of total folic acid intake, but total folic acid intake was only moderately related to UMFA concentrations (r(2) = 0.07). Serum folate concentrations were significantly higher in the UMFA+ group and were predictive of UMFA concentrations (r(2) = 0.15). Serum 5-methyltetrahydrofolate and vitamin B-12 concentrations were higher in the UMFA+ group, whereas there was no difference between the 2 UMFA groups in red blood cell folate, serum homocysteine, or methylmalonic acid concentrations.
Conclusions: Approximately 40% of older adults in the United States have UMFA that persists after a fast, and the presence of UMFA is not easily explained in NHANES by folic acid intakes alone. Given the possibility that excessive folic acid exposure may relate to cancer risk, monitoring of UMFA may be warranted. Am J Clin Nutr 2010; 92: 383-9.
C1 [Bailey, Regan L.; Yetley, Elizabeth A.; Dwyer, Johanna T.; Sempos, Christopher T.; Betz, Joseph M.; Picciano, Mary Frances] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Mills, James L.] Eunice Kennedy Shriver Natl Inst Child & Human De, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA.
[Dodd, Kevin W.] NCI, NIH, Bethesda, MD 20892 USA.
[Gahche, Jaime J.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
[Pfeiffer, Christine M.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA.
RP Bailey, RL (reprint author), 6100 Execut Blvd,2B03, Bethesda, MD 20892 USA.
EM baileyr@mail.nih.gov
OI Dwyer, Johanna/0000-0002-0783-1769
FU National Institutes of Health, Office of Dietary Supplements
FX Supported by the National Institutes of Health, Office of Dietary
Supplements.
NR 30
TC 48
Z9 48
U1 0
U2 4
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD AUG
PY 2010
VL 92
IS 2
BP 383
EP 389
DI 10.3945/ajcn.2010.29499
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 628UZ
UT WOS:000280149700017
PM 20573790
ER
PT J
AU Zeliadt, SB
Ramsey, SD
Van Den Eeden, SK
Hamilton, AS
Oakley-Girvan, I
Penson, DF
Fairweather, ME
Arora, NK
Potosky, AL
AF Zeliadt, Steven B.
Ramsey, Scott D.
Van Den Eeden, Stephen K.
Hamilton, Ann S.
Oakley-Girvan, Ingrid
Penson, David F.
Fairweather, Megan E.
Arora, Neeraj K.
Potosky, Arnold L.
TI Patient Recruitment Methods to Evaluate Treatment Decision Making for
Localized Prostate Cancer
SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS
LA English
DT Article
DE prostate cancer; decision making; recruitment; registry
ID BREAST-CANCER; STRATEGIES; MANAGEMENT; TRIAL; MEN; SURVEILLANCE;
CARCINOMA
AB Objective: To examine methods for identifying and recruiting prostate cancer patients prior to initiating treatment to gain insight into the treatment decision process and avoid recall bias.
Study Design and Setting: One recruitment strategy involved providers and nursing staff approaching patients in community and academic urology clinics. The second recruitment strategy used electronic pathology reports to identify newly diagnosed cases in real time in an integrated health system. Our recruitment goal was to have patients complete the survey about the decision-making process prior to initiating therapy.
Results: The two recruitment methods yielded different response rates. Of the 226 eligible participants approached in urology clinics, 187 (83%) returned a completed baseline survey. Of the 1177 surveys mailed to potentially eligible participants at KPNC, 617 (52%) returned a completed baseline survey. The number of surveys completed prior to treatment was 125 (67%) for the clinic recruitment approach and 437 (71%) for the electronic medical record approach. Younger participants and patients with less aggressive clinical characteristics were more likely to complete the survey before initiating treatment. Other patient demographic and clinical factors were not associated with the timing of survey return.
Conclusions: Recruiting newly diagnosed patients prior to initiating treatment is feasible with both approach methods. The use of electronic medical records to identify subjects was more cost efficient, although it results in a lower response rate.
C1 [Zeliadt, Steven B.; Ramsey, Scott D.; Fairweather, Megan E.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Zeliadt, Steven B.] VA Puget Sound Hlth Care Syst, Hlth Serv Res, Seattle, WA USA.
[Zeliadt, Steven B.] VA Puget Sound Hlth Care Syst, Dev Ctr Excellence, Seattle, WA USA.
[Van Den Eeden, Stephen K.] Kaiser Permanente, Div Res, Oakland, CA USA.
[Hamilton, Ann S.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Oakley-Girvan, Ingrid] No Calif Canc Ctr, Fremont, CA USA.
[Penson, David F.] Vanderbilt Univ, Med Ctr, Vanderbilt Inst Med & Publ Hlth, Nashville, TN USA.
[Arora, Neeraj K.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Potosky, Arnold L.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
RP Ramsey, SD (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,Box 19024,M3-B232, Seattle, WA 98109 USA.
EM sramsey@fhcrc.org
FU National Cancer Institute [N01-PC-35142, N01-PC-35139, N01-PC-35136]
FX Supported by the National Cancer Institute contracts: N01-PC-35142,
N01-PC-35139, and N01-PC-35136.
NR 33
TC 3
Z9 3
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0277-3732
EI 1537-453X
J9 AM J CLIN ONCOL-CANC
JI Am. J. Clin. Oncol.-Cancer Clin. Trials
PD AUG
PY 2010
VL 33
IS 4
BP 381
EP 386
DI 10.1097/COC.0b013e3181b215d5
PG 6
WC Oncology
SC Oncology
GA 635OX
UT WOS:000280666200011
PM 20010079
ER
PT J
AU Kinney, W
Stoler, MH
Castle, PE
AF Kinney, Walter
Stoler, Mark H.
Castle, Philip E.
TI Special Commentary Patient Safety and the Next Generation of HPV DNA
Tests
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Editorial Material
DE Cytology; Cervical cancer; Human papillomavirus; HPV; HPV DNA testing
ID HUMAN-PAPILLOMAVIRUS DNA; CERVICAL INTRAEPITHELIAL NEOPLASIA;
QUALITY-CONTROL; UNITED-STATES; CANCER; WOMEN; CYTOLOGY; RISK; TRIAL;
REPRODUCIBILITY
AB Human papillomavirus (HPV) testing is more Sensitive for the detection of cervical precancer and cancer than cervical cytology. The increased sensitivity of HPV testing and cytology combined ("cotesting") compared to cytology alone permitted professional societies to recommend 3-year screening intervals among the cotest-negative results. However, there is an increasing recognition that both clinical sensitivity and specificity of cervical cancer screening are important to patient safety and must be considered in the context of using current and future HPV DIVA tests. Exquisite analytic sensitivity for HPV does not increase clinical sensitivity of an HPV test but does result in excessive test positivity and decreased clinical specificity A recent US Food and Drug Administration (FDA)-approved HPV test, Cervista (Hologic. Bedford, MA), demonstrated excessive test positivity-2 to 4 times more positive than the other FDA-approved HPV test-from its premarketing approval trial. The poor specificity of Cervista raises questions about the safety and applicability of using this test in routine cervical cancer screening. These data provide a didactic example of the potential dangers of in excellent analytic sensitivity and even clinical sensitivity for good clinical performance.
C1 [Castle, Philip E.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Kinney, Walter] Kaiser Permanente Med Care Program, Div Gynecol Oncol, Oakland, CA USA.
[Stoler, Mark H.] Univ Virginia, Dept Pathol, Charlottesville, VA 22903 USA.
RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, 6120 Execut Blvd,Room 5026,MSC 7234, Bethesda, MD 20892 USA.
FU Intramural NIH HHS
NR 41
TC 61
Z9 61
U1 0
U2 3
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0002-9173
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD AUG
PY 2010
VL 134
IS 2
BP 193
EP 199
DI 10.1309/AJCPRI8XPQUEAA3K
PG 7
WC Pathology
SC Pathology
GA 627UE
UT WOS:000280067600003
PM 20660320
ER
PT J
AU Shi, JJ
Long, JR
Gao, YT
Lu, W
Cai, QY
Wen, WQ
Zheng, Y
Yu, K
Xiang, YB
Hu, FB
Zheng, W
Shu, XO
AF Shi, Jiajun
Long, Jirong
Gao, Yu-Tang
Lu, Wei
Cai, Qiuyin
Wen, Wanqing
Zheng, Ying
Yu, Kai
Xiang, Yong-Bing
Hu, Frank B.
Zheng, Wei
Shu, Xiao-Ou
TI Evaluation of Genetic Susceptibility Loci for Obesity in Chinese Women
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE body mass index; genome-wide association study; linkage disequilibrium;
obesity; polymorphism; genetic; women
ID GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; EARLY-ONSET OBESITY; FTO GENE;
FAT MASS; ADULT OBESITY; DIABETES RISK; EUROPEAN POPULATIONS; ASIAN
POPULATIONS; VARIANTS CONFER
AB Recent genome-wide association (GWA) studies have identified 18 genetic loci for obesity. Using directly observed and imputed GWA genotyping data on approximately 5,000 Chinese women (1996-2007), the authors evaluated 17 single nucleotide polymorphisms (SNPs) that represent 17 distinct obesity loci. Two SNPs near the BAT2 and MC4R genes and 3 SNPs within the FTO, SEC16B, and SH2B1 genes were significantly associated with body mass index (weight (kg)/height (m)(2)), body weight, and the prevalence of obesity. The per-allele increase in body mass index ranged from 0.16 units (BAT2) to 0.38 units (SH2B1). Odds ratios for obesity ranged from 1.46 (95% confidence interval (CI): 1.12, 1.92) for BAT2 to 2.16 (95% CI: 1.39, 3.37) for MC4R. A genetic risk score calculated by summing the number of risk-increasing alleles that each woman carried at these 5 loci was significantly associated with the prevalence of obesity. Women carrying 5 or more risk alleles had a 3.13-fold (95% CI: 2.06, 4.77) higher prevalence of obesity than women carrying 1 or no risk alleles. Results from this study extend some previous GWA findings to Chinese women and show the need for additional studies to identify susceptibility loci in Chinese and other Asian populations.
C1 [Shi, Jiajun; Long, Jirong; Cai, Qiuyin; Wen, Wanqing; Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Sch Med, Dept Med, Div Epidemiol, Nashville, TN 37212 USA.
[Shi, Jiajun; Long, Jirong; Cai, Qiuyin; Wen, Wanqing; Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA.
[Gao, Yu-Tang; Xiang, Yong-Bing] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Lu, Wei; Zheng, Ying] Shanghai Inst Prevent Med, Shanghai Ctr Dis Prevent & Control, Shanghai, Peoples R China.
[Yu, Kai] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
RP Shu, XO (reprint author), Vanderbilt Epidemiol Ctr, 2525 W End Ave,Suite 600, Nashville, TN 37230 USA.
EM xiao-ou.shu@vanderbilt.edu
FU US National Institutes of Health [R01CA124558, R01CA64277, R01CA70867,
R01CA90899]; Allen Foundation; National Center for Research
Resources/National Institutes of Health [1 UL1 RR024975]
FX This study was supported in part by the US National Institutes of Health
(grants R01CA124558, R01CA64277, R01CA70867, and R01CA90899), Ingram
professorship funds and research award funds to Drs. Wei Zheng and
Xiao-Ou Shu, Allen Foundation funds to Dr. Xiao-Ou Shu, and a Vanderbilt
University Clinical and Translational Science Award (grant 1 UL1
RR024975) from the National Center for Research Resources/National
Institutes of Health to Dr. Jirong Long.
NR 57
TC 29
Z9 32
U1 2
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 1
PY 2010
VL 172
IS 3
BP 244
EP 254
DI 10.1093/aje/kwq129
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 633UB
UT WOS:000280531100002
PM 20616199
ER
PT J
AU Lee, KM
Baris, D
Zhang, YW
Hosgood, HD
Menashe, I
Yeager, M
Zahm, SH
Wang, SS
Purdue, MP
Chanock, S
Zheng, TZ
Rothman, N
Lan, Q
AF Lee, Kyoung-Mu
Baris, Dalsu
Zhang, Yawei
Hosgood, H. Dean, III
Menashe, Idan
Yeager, Meredith
Zahm, Shelia Hoar
Wang, Sophia S.
Purdue, Mark P.
Chanock, Stephen
Zheng, Tongzhang
Rothman, Nathaniel
Lan, Qing
TI Common single nucleotide polymorphisms in immunoregulatory genes and
multiple myeloma risk among women in Connecticut
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID T-CELLS; CD4; ASSOCIATION; EXPRESSION; CANCER
AB In light of the relationship between immune system dysregulation and multiple myeloma (MM) risk, we investigated whether genetic variation in 92 immune function genes among 77 gene regions are associated with MM susceptibility in a population-based case-control study (108 cases and 482 controls) conducted among Caucasian women in Connecticut. Tagging single-nucleotide polymorphisms (SNPs; N = 870) were selected using a pairwise linkage-disequilibrium based algorithm. Odds ratios (ORs) and 95% confidence intervals (CIs) for SNP genotypes were estimated using unconditional logistic regression. Tests of association for gene regions were conducted using the minP test. We applied the false discovery rate (FDR) method to the minP test results as a means of controlling for multiple comparisons. The CD4 gene region located on 12p13-q13 (minP = 0.0009), had an FOR value <0.1. In this region, a total of six tag SNPs in two genes (CD4 and LAG3) were significantly associated with MM risk (P(trend)<0.05), with the strongest association observed for the C04 variant rs11064392 (OR(AG/GG) = 2.53, 95% CI = 1.59-4.02). Our findings suggest that genetic variation in CD4 may influence susceptibility to MM. Additional studies are needed to replicate these findings and, more generally, to explore the manner in which genes and receptors may influence the pathogenesis of this poorly understood malignancy. Am. J. Hematol. 85:560-563, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Lee, Kyoung-Mu; Baris, Dalsu; Hosgood, H. Dean, III; Menashe, Idan; Yeager, Meredith; Zahm, Shelia Hoar; Purdue, Mark P.; Chanock, Stephen; Rothman, Nathaniel; Lan, Qing] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Zhang, Yawei; Zheng, Tongzhang] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
[Wang, Sophia S.] City Hope Natl Med Ctr, City Hope Comprehens Canc Ctr, Canc Control & Populat Sci Program, Duarte, CA USA.
RP Lee, KM (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM kmlee92@snu.ac.kr
RI Zahm, Shelia/B-5025-2015; Purdue, Mark/C-9228-2016
OI Purdue, Mark/0000-0003-1177-3108
FU NCI NIH HHS [N01 CO012400]
NR 28
TC 9
Z9 10
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0361-8609
J9 AM J HEMATOL
JI Am. J. Hematol.
PD AUG
PY 2010
VL 85
IS 8
BP 560
EP 563
DI 10.1002/ajh.21760
PG 4
WC Hematology
SC Hematology
GA 634EQ
UT WOS:000280562800003
PM 20568250
ER
PT J
AU Desmond, R
Lynch, K
Gleeson, M
Farrell, M
Murphy, P
AF Desmond, Ronan
Lynch, Karen
Gleeson, Mary
Farrell, Michael
Murphy, Philip
TI Progressive multifocal leukencephalopathy and cerebral toxoplasmosis in
a patient with CLL
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Editorial Material
C1 [Desmond, Ronan] NHLBI, Mol Hematopoesis Sect, Hematol Branch, Bethesda, MD 20892 USA.
[Desmond, Ronan; Murphy, Philip] Beaumont Hosp, Dept Haematol, Dublin 9, Ireland.
[Lynch, Karen; Farrell, Michael] Beaumont Hosp, Dept Histopathol, Dublin 9, Ireland.
[Gleeson, Mary] Waterford Reg Hosp, Dept Haematol, Waterford, Ireland.
RP Desmond, R (reprint author), NHLBI, Mol Hematopoesis Sect, Hematol Branch, Bldg 10, Bethesda, MD 20892 USA.
EM ronandesmond@ireland.com
NR 2
TC 6
Z9 6
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0361-8609
J9 AM J HEMATOL
JI Am. J. Hematol.
PD AUG
PY 2010
VL 85
IS 8
BP 607
EP 607
DI 10.1002/ajh.21589
PG 1
WC Hematology
SC Hematology
GA 634EQ
UT WOS:000280562800012
PM 20029990
ER
PT J
AU Ballas, SK
Bauserman, RL
McCarthy, WF
Castro, OL
Smith, WR
Waclawiw, MA
AF Ballas, Samir K.
Bauserman, Robert L.
McCarthy, William F.
Castro, Oswaldo L.
Smith, Wally R.
Waclawiw, Myron A.
CA Investigators Multictr Study Hydro
TI Utilization of analgesics in the multicenter study of hydroxyurea in
sickle cell anemia: Effect of sex, age, and geographical location
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Letter
ID PHARMACOLOGICAL MANAGEMENT; MORPHINE ANALGESIA; PAINFUL EPISODES;
PERSISTENT PAIN; DISEASE; FREQUENCY; CRISIS
AB Several factors affect the severity and duration of sickle cell pain and its response to treatment with analgesics [1,2]. Sex has been one of the factors reported to influence the pain experience and the response to therapy [3]. Several chronic pain disorders, such as fibromyalgia, occur more frequently in females than in males [4,5]. Moreover, women seem to be more sensitive to painful stimuli than men [6]. However, whether differences in analgesic use by sex occur in patients with sickle cell anemia (SS) is unknown. Age also has been related to pain experience in many studies [7-9]. Moreover, we and others recently found an effect of geographic location and climatic conditions on frequency and severity of sickle cell pain [10,11]. Studies at single sites and anecdotal reports showed that climatic conditions, especially temperature can precipitate or exacerbate pain in sickle cell disease [12-14]. However, to the best of our knowledge, there are no multicenter, randomized, and placebo-controlled studies that relate all of these factors to pain management in sickle cell disease (SCD). The Multicenter Study of Hydroxyurea (MSH) in SS [15] gave us art opportunity to report on these aspects of sickle cell pain.
C1 [Ballas, Samir K.] Thomas Jefferson Univ, Cardeza Fdn Hematol Res, Dept Med, Jefferson Med Coll, Philadelphia, PA 19107 USA.
[Bauserman, Robert L.; McCarthy, William F.] Maryland Med Res Inst, Baltimore, MD USA.
[Castro, Oswaldo L.] Howard Univ, Dept Med Hematol, Washington, DC 20059 USA.
[Smith, Wally R.] Virginia Commonwealth Univ, Richmond, VA USA.
[Waclawiw, Myron A.] NHLBI, Bethesda, MD 20892 USA.
RP Ballas, SK (reprint author), Thomas Jefferson Univ, Cardeza Fdn, Dept Med, Jefferson Med Coll, 1015 Walnut St, Philadelphia, PA 19107 USA.
EM samir.ballas@jefferson.edu
FU NHLBI NIH HHS [U54 HL090516]
NR 30
TC 5
Z9 5
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0361-8609
J9 AM J HEMATOL
JI Am. J. Hematol.
PD AUG
PY 2010
VL 85
IS 8
BP 613
EP 616
DI 10.1002/ajh.21750
PG 4
WC Hematology
SC Hematology
GA 634EQ
UT WOS:000280562800016
PM 20568300
ER
PT J
AU Gold, LS
Milliken, K
Stewart, P
Purdue, M
Severson, R
Seixas, N
Blair, A
Davis, S
Hartge, P
De Roos, AJ
AF Gold, Laura S.
Milliken, Kevin
Stewart, Patricia
Purdue, Mark
Severson, Richard
Seixas, Noah
Blair, Aaron
Davis, Scott
Hartge, Patricia
De Roos, Anneclaire J.
TI Occupation and Multiple Myeloma: An Occupation and Industry Analysis
SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE
LA English
DT Article
DE multiple myeloma; lymphoma; machinery operators; occupation; painters;
service occupations
ID HAIR DYE USE; RETROSPECTIVE COHORT MORTALITY; REPORTED WORK HISTORY;
LONG-TERM EXPOSURE; HEPATITIS-C VIRUS; CANCER INCIDENCE; LYMPHOID
NEOPLASMS; ORGANIC-SOLVENTS; UNITED-STATES; HEMATOPOIETIC CANCER
AB Background Multiple myeloma (MM) is an incurable plasma cell malignancy with a poorly understood etiology. The purpose of our research was to examine the relationships between lifetime occupations and MM in a relatively large case-control study.
Methods MM cases (n = 180) were identified through cancer registries in the Seattle-Puget Sound area and Detroit. Population-based controls (n = 481) were identified using random digit dialing and Medicare and Medicaid Services files. In-person interviews were conducted to ascertain occupational histories. Standard occupational classification (SO C) and standard industrial classification (SIC) codes were assigned to each job held by each participant. Unconditional logistic regression was used to generate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between MM and having ever worked in each occupation/industry and according to duration of employment in an occupation/industry.
Results The risk of MM was associated with several manufacturing occupations and industries, including machine operators and tenders, not elsewhere classified (SOC 76) (OR = 1.8, CI = 1.0-3.3); textile, apparel, and furnishing machine operators and tenders (SOC 765) (OR = 6.0, CI = 1.7-21); and machinery manufacturing, except electrical (SIC 35) (OR = 3.3, CI = 1.7-6.7). Several service occupations and industries, such as food and beverage preparation (SOC 521) (OR = 2.0, CI = 1.1-3.8), were also associated with MM. One occupation that has been associated with MM in several previous studies, painters, paperhangers, and plasterers (SOC 644) was associated with a non-significantly elevated risk (OR = 3.6, CI = 0.7-19).
Conclusions We found associations between the risk of MM and employment in several manufacturing and service-related occupations and industries. Am. J. Ind. Med. 53:768-779, 2010. (C) 2010 Wiley-Liss, Inc.
C1 [Gold, Laura S.; Milliken, Kevin; Davis, Scott; De Roos, Anneclaire J.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98109 USA.
[Gold, Laura S.; Milliken, Kevin; Davis, Scott; De Roos, Anneclaire J.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Stewart, Patricia] Stewart Exposure Assessments LLC, Arlington, VA USA.
[Purdue, Mark; Blair, Aaron; Hartge, Patricia] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Severson, Richard] Wayne State Univ, Karmanos Canc Inst, Dept Family Med & Publ Hlth Sci, Detroit, MI USA.
[Seixas, Noah] Univ Washington, Sch Publ Hlth, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA.
RP Gold, LS (reprint author), Fred Hutchinson Canc Res Ctr, Program Epidemiol, 1100 Fairview Ave N,POB 19024, Seattle, WA 98109 USA.
EM lgold@fhcrc.org
FU National Occupational Research Agenda (NORA) [5 T42 0H008433-03];
National Institute for Occupational Safety and Health (NIOSH) [5 T42
0H008433-03]
FX Contract grant sponsor: National Occupational Research Agenda (NORA);
Contract grant number: 5 T42 0H008433-03.; The authors are very grateful
to the National Institute for Occupational Safety and Health (NIOSH) for
Grant Number 5 T42 0H008433-03 that contributed to the completion of
this project.
NR 50
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U1 2
U2 10
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0271-3586
J9 AM J IND MED
JI Am. J. Ind. Med.
PD AUG
PY 2010
VL 53
IS 8
BP 768
EP 779
DI 10.1002/ajim.20857
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 630MJ
UT WOS:000280277100002
PM 20623662
ER
PT J
AU Allanson, JE
Bohring, A
Dorr, HG
Dufke, A
Gillessen-Kaesbach, G
Horn, D
Konig, R
Kratz, CP
Kutsche, K
Pauli, S
Raskin, S
Rauch, A
Turner, A
Wieczorek, D
Zenker, M
AF Allanson, Judith E.
Bohring, Axel
Dorr, Helmuth-Guenther
Dufke, Andreas
Gillessen-Kaesbach, Gabrielle
Horn, Denise
Koenig, Rainer
Kratz, Christian P.
Kutsche, Kerstin
Pauli, Silke
Raskin, Salmo
Rauch, Anita
Turner, Anne
Wieczorek, Dagmar
Zenker, Martin
TI The Face of Noonan Syndrome: Does Phenotype Predict Genotype
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE Noonan syndrome; PTPN11; SOS1; RAF1; KRAS; facial phenotype;
genotype-phenotype correlation
ID PROTEIN-TYROSINE-PHOSPHATASE; MUTATIONS CAUSE NOONAN; OF-FUNCTION
MUTATIONS; GERMLINE MUTATIONS; CUTANEOUS SYNDROME; COSTELLO-SYNDROME;
LEOPARD SYNDROMES; PTPN11 MUTATIONS; KRAS; SOS1
AB The facial photographs of 81 individuals with Noonan syndrome, from infancy to adulthood, have been evaluated by two dysmorphologists (JA and MZ), each of whom has considerable experience with disorders of the Ras/MAPK pathway. Thirty-two of this cohort have PTPN11 mutations, 21 SOS1 mutations, 11 RAF1 mutations, and 17 KRAS mutations. The facial appearance of each person was judged to be typical of Noonan syndrome or atypical. In each gene category both typical and unusual faces were found. We determined that some individuals with mutations in the most commonly affected gene, PTPN11, which is correlated with the cardinal physical features, may have a quite atypical face. Conversely, some individuals with KRAS mutations, which may be associated with a less characteristic intellectual phenotype and a resemblance to Costello and cardio-facio-cutaneous syndromes, can have a very typical face. Thus, the facial phenotype, alone, is insufficient to predict the genotype, but certain facial features may facilitate an educated guess in some cases. (C) 2010 Wiley-Liss, Inc.
C1 [Allanson, Judith E.] Childrens Hosp Eastern Ontario, Dept Genet, Ottawa, ON K1H 8L1, Canada.
[Allanson, Judith E.] Univ Ottawa, Ottawa, ON, Canada.
[Bohring, Axel] Univ Munster, Inst Humangenet, Munster, Germany.
[Dorr, Helmuth-Guenther] Univ Childrens Hosp, Dept Pediat Endocrinol & Pediat Cardiol, Erlangen, Germany.
[Dufke, Andreas] Univ Hosp Tuebingen, Dept Med Genet, Tubingen, Germany.
[Gillessen-Kaesbach, Gabrielle] Med Univ Lubeck, Inst Humangenet, D-23538 Lubeck, Germany.
[Horn, Denise] Charite, Inst Med Genet, D-13353 Berlin, Germany.
[Koenig, Rainer] Goethe Univ Frankfurt, Inst Human Genet, Frankfurt, Germany.
[Kratz, Christian P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Kutsche, Kerstin] Univ Klinikum Hamburg Eppendorf, Inst Humangenet, Hamburg, Germany.
[Pauli, Silke] Univ Gottingen, Inst Human Genet, D-3400 Gottingen, Germany.
[Raskin, Salmo] Genet Lab, Curitiba, Parana, Brazil.
[Rauch, Anita] Univ Zurich, Inst Med Genet, Zurich, Switzerland.
[Turner, Anne] Sydney Childrens Hosp, Dept Med Genet, Randwick, NSW, Australia.
[Wieczorek, Dagmar] Univ Duisburg Essen, Inst Humangenet, Essen, Germany.
[Zenker, Martin] Univ Hosp, Inst Human Genet, Magdeburg, Germany.
RP Allanson, JE (reprint author), Childrens Hosp Eastern Ontario, Dept Genet, 401 Smyth Rd, Ottawa, ON K1H 8L1, Canada.
EM allanson@cheo.on.ca
RI Rauch, Anita/C-5568-2014
OI Rauch, Anita/0000-0003-2930-3163
FU US National Cancer Institute, National Institutes of Health; German
Research Foundation (DFG) [ZE 524/4-1]
FX C.P.K.'s work was supported by the Intramural Research Program of the US
National Cancer Institute, National Institutes of Health. M.Z. was
supported by the German Research Foundation (DFG; ZE 524/4-1).
NR 27
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U1 2
U2 3
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD AUG
PY 2010
VL 152A
IS 8
BP 1960
EP 1966
DI 10.1002/ajmg.a.33518
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 638VO
UT WOS:000280925800010
PM 20602484
ER
PT J
AU Koo, G
Conley, SK
Wassif, CA
Porter, FD
AF Koo, Grace
Conley, Sandra K.
Wassif, Christopher A.
Porter, Forbes D.
TI Discordant Phenotype and Sterol Biochemistry in Smith-Lemli-Opitz
Syndrome
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE Smith-Lemli-Optiz syndrome; SLOS; malformations; 7-dehydrocholesterol
(7DHC); cholesterol; inborn errors
ID 7-DEHYDROCHOLESTEROL REDUCTASE GENE; CARRIER FREQUENCY; MUTATIONS;
CHOLESTEROL; DIAGNOSIS; DELTA(7)-REDUCTASE; FIBROBLASTS
AB Smith-Lemli-Opitz syndrome (SLOS) is a malformation syndrome resulting from mutations of the 7-dehydrocholesterol reductase (DHCR7) gene. During cholesterol biosynthesis, DHCR7 catalyzes the conversion of 7-dehydrocholesterol (7DHC) to cholesterol. A clinical diagnosis of SLOS is confirmed biochemically by the presence of elevated levels of 7DHC. Phenotypic severity of SLOS has previously been shown to correlate with the 7DHC/cholesterol ratio. We describe a patient with a severe SLOS phenotype, but a very low serum 7DHC/cholesterol ratio. We show that this discordance is due to alternative splicing of a previously unreported IVS5+3 A>T mutation. This mutation results in the transcription of both normal and mutant mRNA transcripts. We postulate that alternative splicing of the IVS5+3 A>T results in insufficient DHCR7 activity during embryogenesis, but sufficient DHCR7 activity once cholesterol synthetic rates decrease postnatally. This unique case underscores the adjunctive use of fibroblast and molecular testing in ambiguous cases of SLOS and may provide insight into the potential efficacy of therapeutic interventions altering postnatal cholesterol biosynthesis. Published 2010 Wiley-Liss, Inc.(dagger)
C1 [Koo, Grace; Conley, Sandra K.; Wassif, Christopher A.; Porter, Forbes D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Dysmorphol, Program Dev Endocrinol & Genet, DHHS, Bethesda, MD USA.
RP Porter, FD (reprint author), NICHD, PDGEN, NIH, Bld 10,Rm 9D42,10 Ctr Dr, Bethesda, MD 20892 USA.
EM fdporter@mail.nih.gov
OI Wassif, Christopher/0000-0002-2524-1420
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX This work was supported by the intramural research program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development.
NR 20
TC 5
Z9 8
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD AUG
PY 2010
VL 152A
IS 8
BP 2094
EP 2098
DI 10.1002/ajmg.a.33540
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA 638VO
UT WOS:000280925800034
PM 20635399
ER
PT J
AU Brooks, EL
Preis, SR
Hwang, SJ
Murabito, JM
Benjamin, EJ
Kelly-Hayes, M
Sorlie, P
Levy, D
AF Brooks, Erica L.
Preis, Sarah Rosner
Hwang, Shih-Jen
Murabito, Joanne M.
Benjamin, Emelia J.
Kelly-Hayes, Margaret
Sorlie, Paul
Levy, Daniel
TI Health Insurance and Cardiovascular Disease Risk Factors
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
DE Cardiovascular risk factors; Health disparities; Health insurance;
Hypertension
ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; INSURED ADULTS; CARE;
HYPERTENSION; CHOLESTEROL; DESIGN; ACCESS; HEART
AB BACKGROUND: Compared with those with health insurance, the uninsured receive less care for chronic conditions, such as hypertension and diabetes, and experience higher mortality.
METHODS: We investigated the relations of health insurance status to the prevalence, treatment, and control of major cardiovascular disease risk factors-hypertension and elevated low-density lipoprotein (LDL) cholesterol-among Framingham Heart Study (FHS) participants in gender-specific, age-adjusted analyses. Participants who attended the seventh Offspring cohort examination cycle (1998-2001) or the first Third Generation cohort examination cycle (2002-2005) were studied.
RESULTS: Among 6098 participants, 3.8% were uninsured at the time of the FHS clinic examination and ages ranged from 19 to 64 years. The prevalence of hypertension and elevated LDL cholesterol was similar for the insured and uninsured; however, the proportion of those who obtained treatment and achieved control of these risk factors was lower among the uninsured. Uninsured men and women were less likely to be treated for hypertension with odds ratios for treatment of 0.19 (95% confidence interval [CI], 0.07-0.56) for men and 0.31 (95% CI, 0.12-0.79) for women. Among men, the uninsured were less likely to receive treatment or achieve control of elevated LDL cholesterol than the insured, with odds ratios of 0.12 (95% CI, 0.04-0.38) for treatment and 0.17 (95% CI, 0.05-0.56) for control.
CONCLUSION: The treatment and control of hypertension and hypercholesterolemia are lower among uninsured adults. Increasing the proportion of insured individuals may be a means to improve the treatment and control of cardiovascular disease risk factors and to reduce health disparities. Published by Elsevier Inc. The American Journal of Medicine (2010) 123, 741-747
C1 [Brooks, Erica L.; Preis, Sarah Rosner; Hwang, Shih-Jen; Murabito, Joanne M.; Benjamin, Emelia J.; Kelly-Hayes, Margaret; Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Brooks, Erica L.] Tufts Med Ctr, Dept Med, Div Cardiol, Boston, MA USA.
[Preis, Sarah Rosner; Hwang, Shih-Jen] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Murabito, Joanne M.] Boston Univ, Gen Internal Med Sect, Boston, MA 02215 USA.
[Murabito, Joanne M.; Benjamin, Emelia J.; Kelly-Hayes, Margaret] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA.
[Kelly-Hayes, Margaret] Boston Univ, Dept Neurol, Boston, MA 02215 USA.
[Sorlie, Paul] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA.
RP Levy, D (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA.
EM levyd@nih.gov
OI Preis, Sarah/0000-0002-9360-4166; Murabito, Joanne/0000-0002-0192-7516;
Benjamin, Emelia/0000-0003-4076-2336
FU National Institutes of Health [N01-HC-25195]
FX The Framingham Heart Study is funded through National Institutes of
Health contract N01-HC-25195.
NR 23
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U1 1
U2 1
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 AUG
PY 2010
VL 123
IS 8
BP 741
EP 747
DI 10.1016/j.amjmed.2010.02.013
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 631UG
UT WOS:000280374200016
PM 20670729
ER
PT J
AU Wiggins, CL
Harlan, LC
Nelson, HE
Stevens, JL
Willman, CL
Libby, EN
Hromas, RA
AF Wiggins, Charles L.
Harlan, Linda C.
Nelson, Harold E.
Stevens, Jennifer L.
Willman, Cheryl L.
Libby, Edward N.
Hromas, Robert A.
TI Age Disparity in the Dissemination of Imatinib for Treating Chronic
Myeloid Leukemia
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
DE Age discrimination; Chronic myeloid leukemia; Imatinib; Socioeconomic
status
ID CHRONIC MYELOGENOUS LEUKEMIA; CANCER-TREATMENT TRIALS; ABL TYROSINE
KINASE; PHILADELPHIA-CHROMOSOME; CLINICAL-TRIALS; BREAST-CANCER;
GERIATRIC ONCOLOGY; POSITIVE CELLS; OLDER PATIENTS; INHIBITOR
AB BACKGROUND: Imatinib is a highly effective treatment for chronic myeloid leukemia. It was approved by the Food and Drug Administration in 2001 and thereafter rapidly became front-line therapy. This study characterized the prevailing chronic myeloid leukemia therapies in the United States and assessed the impact of imatinib on chronic myeloid leukemia survival and mortality rates in the general population.
METHODS: Investigators with the National Cancer Institute's Patterns of Care study reviewed medical records and queried physicians regarding therapy for 423 patients with chronic myeloid leukemia diagnosed in 2003 who were randomly selected from cancer registries in the Surveillance, Epidemiology, and End Results Program. Characteristics associated with the receipt of imatinib were documented, as were survival differences between those who received imatinib and those who did not. Population-based data were used to assess chronic myeloid leukemia survival and mortality rates in time periods before and after the introduction of imatinib.
RESULTS: Imatinib was administered to 76% of patients in the Patterns of Care study. Imatinib use was inversely associated with age: 90%, 75%, and 46% for patients ages 20 to 59 years, 60 to 79 years, and 80 or more years, respectively. Elderly patients who received imatinib survived significantly longer than those who did not. After adjusting for age, imatinib use did not vary significantly by race/ethnicity, socioeconomic status, urban/rural residence, presence of comorbid conditions, or insurance status. Overall, chronic myeloid leukemia survival in the Surveillance, Epidemiology, and End Results population improved, and mortality in the United States declined dramatically during the period when imatinib became widely available; these improvements diminished with increasing age.
CONCLUSION: Age disparities in treatment with imatinib likely contributed to worse survival for many elderly patients with chronic myeloid leukemia. (C) 2010 Elsevier Inc. All rights reserved. The American Journal of Medicine (2010) 123, 764. e1-764. e9
C1 [Wiggins, Charles L.; Willman, Cheryl L.; Libby, Edward N.; Hromas, Robert A.] Univ New Mexico, Ctr Canc, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
[Wiggins, Charles L.; Nelson, Harold E.] Univ New Mexico, New Mexico Tumor Registry, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
[Harlan, Linda C.] NCI, Bethesda, MD 20892 USA.
[Stevens, Jennifer L.] Informat Management Syst Inc, Rockville, MD USA.
RP Hromas, RA (reprint author), 1 Univ New Mexico, UNM Canc Ctr, MSC 08 4630, Albuquerque, NM 87131 USA.
EM rhromas@salud.unm.edu
FU National Cancer Institute (NCI) of the National Institutes of Health
(NIH) [NO1-PC-35138, N01-PC-35133, N01-PC-35135, N01-PC-35141,
N01-PC-35136, N01-PC-35137, N01-PC-35139, N01-PC-35142, N01-PC-35143,
N01-PC-35145, N01-PC-54402, N01-PC-54404, N01-PC-54405, 5UO1 CA88361];
Leukemia and Lymphoma Society; University of New Mexico Cancer Center;
NCI Cancer Center [P30-CA118100]; LLS [SCOR 7388-06, 7388-06]; NIH
[CA139429, CA100862, CA140442, HL075783]
FX The National Cancer Institute (NCI) of the National Institutes of Health
(NIH) and the Leukemia and Lymphoma Society supported this study. Dr
Wiggins acknowledges the support of NCI Contracts NO1-PC-35138,
N01-PC-35133, N01-PC-35135, N01-PC-35141, N01-PC-35136, N01-PC-35137,
N01-PC-35139, N01-PC-35142, N01-PC-35143, N01-PC-35145, N01-PC-54402,
N01-PC-54404, and N01-PC-54405, and the University of New Mexico Cancer
Center, a recipient of NCI Cancer Center Support Grant P30-CA118100. Dr
Willman was supported by LLS SCOR 7388-06 and the NCI 5UO1 CA88361, and
Dr Hromas was supported by LLS 7388-06, NIH CA139429, NIH CA100862, NIH
CA140442, and NIH HL075783.
NR 50
TC 4
Z9 4
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
J9 AM J MED
JI Am. J. Med.
PD AUG
PY 2010
VL 123
IS 8
AR 764.e1
DI 10.1016/j.amjmed.2010.03.018
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 631UG
UT WOS:000280374200019
PM 20670732
ER
PT J
AU Galanaud, D
Haik, S
Linguraru, MG
Ranjeva, JP
Faucheux, B
Kaphan, E
Ayache, N
Chiras, J
Cozzone, P
Dormont, D
Brandel, JP
AF Galanaud, D.
Haik, S.
Linguraru, M. G.
Ranjeva, J. -P.
Faucheux, B.
Kaphan, E.
Ayache, N.
Chiras, J.
Cozzone, P.
Dormont, D.
Brandel, J. -P.
TI Combined Diffusion Imaging and MR Spectroscopy in the Diagnosis of Human
Prion Diseases
SO AMERICAN JOURNAL OF NEURORADIOLOGY
LA English
DT Article
ID CREUTZFELDT-JAKOB-DISEASE; MAGNETIC-RESONANCE SPECTROSCOPY; HUMAN-BRAIN
INVIVO; WEIGHTED MRI; INTEROBSERVER AGREEMENT; WHITE-MATTER;
ABNORMALITIES; MYOINOSITOL; INCREASE
AB BACKGROUND AND PURPOSE: The physiopathologic bases underlying the signal intensity changes and reduced diffusibility observed in prion diseases (TSEs) are still poorly understood. We evaluated the interest of MRS combined with DWI both as a diagnostic tool and a way to understand the mechanism underlying signal intensity and ADC changes in this setting.
MATERIALS AND METHODS: We designed a prospective study of multimodal MR imaging in patients with suspected TSEs. Forty-five patients with a suspicion of TSE and 11 age-matched healthy volunteers were included. The MR imaging protocol included T1, FLAIR, and DWI sequences. MRS was performed on the cerebellum, pulvinar, right lenticular nucleus, and frontal cortex. MR images were assessed visually, and ADC values were calculated.
RESULTS: Among the 45 suspected cases, 31 fulfilled the criteria for probable or definite TSEs (19 sCJDs, 3 iCJDs, 2 vCJDs, and 7 genetic TSEs); and 14 were classified as AltDs. High signals in the cortex and/or basal ganglia were observed in 26/31 patients with TSEs on FLAIR and 29/31 patients on DWI. In the basal ganglia, high DWI signals corresponded to a decreased ADC. Metabolic alterations, increased mlns, and decreased NAA were observed in all patients with TSEs. ADC values and metabolic changes were not correlated; this finding suggests that neuronal stress (vacuolization), neuronal loss, and astrogliosis do not alone explain the decrease of ADC.
CONCLUSIONS: MRS combined with other MR imaging is of interest in the diagnosis of TSE and provides useful information for understanding physiopathologic processes underlying prion diseases.
C1 [Galanaud, D.; Chiras, J.; Dormont, D.] Hop La Pitie Salpetriere, Dept Neuroradiol, F-75013 Paris, France.
[Haik, S.; Faucheux, B.] Hop La Pitie Salpetriere, Dept Pathol, F-75013 Paris, France.
[Haik, S.; Brandel, J. -P.] Hop La Pitie Salpetriere, Dept Cellule Reference Malad Prions, F-75013 Paris, France.
[Galanaud, D.; Haik, S.; Faucheux, B.; Dormont, D.; Brandel, J. -P.] Hop La Pitie Salpetriere, INSERM, CNRS,UMR 7225, Ctr Rech,Inst Cerveau & Moelle Epiniere,UMRS 975, F-75013 Paris, France.
[Galanaud, D.; Chiras, J.; Dormont, D.] Univ Paris 06, F-75252 Paris 05, France.
[Ranjeva, J. -P.; Cozzone, P.] La Timone Hosp, CNRS, CRMBM CEMEREM, UMR 6612, Marseille, France.
[Kaphan, E.] La Timone Hosp, Fac Med La Timone, Marseille, France.
[Kaphan, E.] La Timone Hosp, Dept Neurol, Marseille, France.
[Linguraru, M. G.; Ayache, N.] Inst Natl Rech Informat & Automat, Epidaure Asclepios Res Grp, Sophia Antipolis, France.
[Linguraru, M. G.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
RP Galanaud, D (reprint author), Hop La Pitie Salpetriere, Dept Neuroradiol, 47 Blvd Hop, F-75013 Paris, France.
EM galanaud@dat.org
RI Dormont, Didier/F-5492-2012
FU Groupement d'interet specifique "Prions"; French Ministry of Research;
Centre National de la Recherche Scientifique; Institut Universitaire de
France
FX This work was supported by a grant from the Groupement d'interet
specifique "Prions." Other financial support for this work was provided
by the French Ministry of Research, the Centre National de la Recherche
Scientifique, and the Institut Universitaire de France.
NR 36
TC 18
Z9 18
U1 0
U2 3
PU AMER SOC NEURORADIOLOGY
PI OAK BROOK
PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA
SN 0195-6108
J9 AM J NEURORADIOL
JI Am. J. Neuroradiol.
PD AUG
PY 2010
VL 31
IS 7
BP 1311
EP 1318
DI 10.3174/ajnr.A2069
PG 8
WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 641ED
UT WOS:000281106700029
PM 20430851
ER
PT J
AU Conde-Agudelo, A
Romero, R
Hassan, SS
Yeo, L
AF Conde-Agudelo, Agustin
Romero, Roberto
Hassan, Sonia S.
Yeo, Lami
TI Transvaginal sonographic cervical length for the prediction of
spontaneous preterm birth in twin pregnancies: a systematic review and
metaanalysis
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE cervical length; metaanalysis; prediction; preterm birth; systematic
review
ID DIAGNOSTIC-TEST; FETAL FIBRONECTIN; IDENTIFY TWINS; LOW-RISK; DELIVERY;
GESTATIONS; ULTRASONOGRAPHY; ACCURACY; BIAS; ULTRASOUND
AB OBJECTIVE: To assess the accuracy of transvaginal sonographic cervical length (CL) in predicting spontaneous preterm birth in women with twin pregnancies.
STUDY DESIGN: Systematic review and metaanalysis of predictive test accuracy.
RESULTS: Twenty-one studies (16 in asymptomatic women and 5 in symptomatic women) with a total of 3523 women met the inclusion criteria. Among asymptomatic women, a CL <= 20 mm at 20-24 weeks' gestation was the most accurate in predicting preterm birth <32 and <34 weeks' gestation (pooled sensitivities, specificities, and positive and negative likelihood ratios of 39% and 29%, 96% and 97%, 10.1 and 9.0, and 0.64 and 0.74, respectively). A CL <= 25 mm at 20-24 weeks' gestation had a pooled positive likelihood ratio of 9.6 to predict preterm birth <28 weeks' gestation. The predictive accuracy of CL for preterm birth was low in symptomatic women.
CONCLUSION: Transvaginal sonographic CL at 20-24 weeks' gestation is a good predictor of spontaneous preterm birth in asymptomatic women with twin pregnancies.
C1 [Conde-Agudelo, Agustin; Romero, Roberto; Hassan, Sonia S.; Yeo, Lami] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept HHS, Bethesda, MD USA.
[Romero, Roberto; Hassan, Sonia S.; Yeo, Lami] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
RP Conde-Agudelo, A (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept HHS, Bethesda, MD USA.
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Department of Health and
Human Services
FX This research was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Department of Health and
Human Services.
NR 46
TC 25
Z9 28
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD AUG
PY 2010
VL 203
IS 2
AR 128.e1
DI 10.1016/j.ajog.2010.02.064
PG 12
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 629XN
UT WOS:000280234500015
PM 20576253
ER
PT J
AU Bianco, C
Rangel, MC
Castro, NP
Nagaoka, T
Rollman, K
Gonzales, M
Salomon, DS
AF Bianco, Caterina
Rangel, Maria Cristina
Castro, Nadia P.
Nagaoka, Tadahiro
Rollman, Kelly
Gonzales, Monica
Salomon, David S.
TI Role of Cripto-1 in Stem Cell Maintenance and Malignant Progression
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Review
ID EPITHELIAL-MESENCHYMAL TRANSITION; HYPOXIA-INDUCIBLE FACTORS; LEFT-RIGHT
ASYMMETRY; NODAL EXPRESSION; GENE-EXPRESSION; MAMMARY-GLAND;
EMBRYONIC-DEVELOPMENT; REGULATORY CIRCUITRY; TRANSGENIC MICE;
SELF-RENEWAL
AB Cripto-1 is critical for early embryonic development and, together with its ligand Nodal, has been found to be associated with the undifferentiated status of mouse and human embryonic stem cells. Like other embryonic genes, Cripto-1 performs important roles in the formation and progression of several types of human tumors, stimulating cell proliferation, migration, epithelial to mesenchymal transition, and tumor angiogenesis. Several studies have demonstrated that cell fate regulation during embryonic development and cell transformation during oncogenesis share common signaling pathways, suggesting that uncontrolled activation of embryonic signaling pathways might drive cell transformation and tumor progression in adult tissues. Here we review our current understanding of how Cripto-1 controls stem cell biology and how it integrates with other major embryonic signaling pathways. Because many cancers are thought to derive from a subpopulation of cancer stem-like cells, which may re-express embryonic genes, Cripto-1 signaling may drive tumor growth through the generation or expansion of tumor initiating cells bearing stem-like characteristics. Therefore, the Cripto-1/Nodal signaling may represent an attractive target for treatment in cancer, leading to the elimination of undifferentiated stem-like tumor initiating cells. (Am J Pathol 2010, 177:532-540; DOI: 10.2353/ajpath.2010.100102)
C1 [Bianco, Caterina; Rangel, Maria Cristina; Castro, Nadia P.; Nagaoka, Tadahiro; Rollman, Kelly; Gonzales, Monica; Salomon, David S.] NCI, Mammary Biol & Tumorigenesis Lab, NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Bianco, C (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, NIH, Ctr Canc Res, 37 Convent Dr,Bldg 37,Room 1112, Bethesda, MD 20892 USA.
EM biancoc@mail.nih.gov; salomond@mail.nih.gov
RI Rangel, Maria Cristina/P-7216-2014;
OI Rangel, Maria Cristina/0000-0002-8002-9617; Nagaoka,
Tadahiro/0000-0002-9391-0243
FU National Institutes of Health, National Cancer Institute
FX Supported by Intramural Research Program of the National Institutes of
Health, National Cancer Institute.
NR 69
TC 43
Z9 47
U1 0
U2 7
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD AUG
PY 2010
VL 177
IS 2
BP 532
EP 540
DI 10.2353/ajpath.2010.100102
PG 9
WC Pathology
SC Pathology
GA 638KU
UT WOS:000280894600003
PM 20616345
ER
PT J
AU Refuerzo, JS
Momirova, V
Peaceman, AM
Sciscione, A
Rouse, DJ
Caritis, SN
Spong, CY
Varner, MW
Malone, FD
Iams, JD
Mercer, BM
Thorp, JM
Sorokin, Y
Carpenter, MW
Lo, J
Harper, M
AF Refuerzo, Jerrie S.
Momirova, Valerija
Peaceman, Alan M.
Sciscione, Anthony
Rouse, Dwight J.
Caritis, Steve N.
Spong, Catherine Y.
Varner, Michael W.
Malone, Fergal D.
Iams, Jay D.
Mercer, Brian M.
Thorp, John M., Jr.
Sorokin, Yoram
Carpenter, Marshall W.
Lo, Julie
Harper, Margaret
CA Eunice Kennedy Shriver Natl Inst
TI Neonatal Outcomes in Twin Pregnancies Delivered Moderately Preterm, Late
Preterm, and Term
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article; Proceedings Paper
CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine
CY JAN 26-31, 2009
CL San Diego, CA
SP Soc Maternal Fetal Med
DE Twin pregnancy; late preterm birth; neonatal morbidities
ID GESTATIONAL-AGE; INFANTS; MORBIDITY; BIRTHS; RISK; PREMATURITY;
MORTALITY; PARADIGM; IMPACT; RATES
AB We compared neonatal outcomes in twin pregnancies following moderately preterm birth (MPTB), late preterm birth (LPTB), and term birth. A secondary analysis of a multicenter, randomized controlled trial of multiple gestations was conducted. MPTB was defined as delivery between 32(0)/(7) and 33(6)/(7) weeks and LPTB between 34(0)/(7) and 36(6)/(7) weeks. Primary outcome was a neonatal outcome composite consisting of one or more of the following: neonatal death, respiratory distress syndrome, early onset culture-proven sepsis, stage 2 or 3 necrotizing enterocolitis, bronchopulmonary dysplasia, grade 3 or 4 intraventricular hemorrhage, periventricular leukomalacia, pneumonia, or severe retinopathy of prematurity. Among 552 twin pregnancies, the MPTB rate was 14.5%, LPTB 49 8%, and term birth rate 35.7%. The rate of the primary outcome was different between groups: 30.0% for MPTB, 12.8% for LPTB, 0.5% for term birth (p < 0.001). Compared with term neonates, the primary neonatal outcome composite was increased following MPTB (relative risk [RR] 58.5; 95% confidence interval [CI] 11 3 to 1693.0) and LPTB (RR 24.9, 95% CI 4.8 to 732.2). Twin pregnancies born moderately and late preterm encounter higher rates of neonatal morbidities compared with twins born at term
C1 [Refuerzo, Jerrie S.] Univ Texas Hlth Sci Ctr Houston, Dept Obstet & Gynecol, Div Maternal Fetal Med, Houston, TX 77030 USA.
[Momirova, Valerija] Northwestern Univ, Chicago, IL 60611 USA.
[Peaceman, Alan M.] Drexel Univ, Philadelphia, PA 19104 USA.
[Sciscione, Anthony] Univ Alabama, Birmingham, AL USA.
[Rouse, Dwight J.] Univ Pittsburgh, Pittsburgh, PA USA.
[Caritis, Steve N.] Univ Utah, Salt Lake City, UT USA.
[Spong, Catherine Y.] Columbia Univ, New York, NY USA.
[Varner, Michael W.] Ohio State Univ, Columbus, OH 43210 USA.
[Malone, Fergal D.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Iams, Jay D.] Univ N Carolina, Chapel Hill, NC USA.
[Mercer, Brian M.] Wayne State Univ, Detroit, MI USA.
[Thorp, John M., Jr.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Sorokin, Yoram] Brown Univ, Providence, RI 02912 USA.
[Carpenter, Marshall W.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
[Lo, Julie] George Washington Univ, Ctr Biostat, Washington, DC USA.
[Harper, Margaret] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Refuerzo, JS (reprint author), Univ Texas Hlth Sci Ctr Houston, Dept Obstet & Gynecol, Div Maternal Fetal Med, 6431 Fannin St 3 270, Houston, TX 77030 USA.
RI Malone, Fergal/D-6233-2012; Varner, Michael/K-9890-2013
OI caritis, steve/0000-0002-2169-0712; Peaceman, Alan/0000-0002-4515-4850;
Varner, Michael/0000-0001-9455-3973
FU NCATS NIH HHS [UL1 TR000005]; NICHD NIH HHS [U10 HD040545, HD21410,
HD27860, HD27869, HD27915, HD27917, HD34116, HD34136, HD34208, HD36801,
HD40485, HD40500, HD40512, HD40544, HD40545, HD40560, R24 HD050924, U01
HD036801, U10 HD021410, U10 HD021410-22, U10 HD027860, U10 HD027860-15,
U10 HD027869, U10 HD027869-10, U10 HD027915, U10 HD027915-19, U10
HD027917, U10 HD027917-18, U10 HD034116, U10 HD034116-13, U10 HD034136,
U10 HD034136-10, U10 HD034208, U10 HD034208-12, U10 HD036801, U10
HD036801-11, U10 HD040485, U10 HD040485-11, U10 HD040500, U10
HD040500-08, U10 HD040512, U10 HD040512-11, U10 HD040544, U10
HD040544-11, U10 HD040545-11, U10 HD040560, U10 HD040560-11, UG1
HD027869, UG1 HD027915, UG1 HD034116, UG1 HD034208, UG1 HD040485, UG1
HD040500, UG1 HD040512, UG1 HD040544, UG1 HD040545, UG1 HD040560]
NR 16
TC 26
Z9 30
U1 1
U2 3
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
J9 AM J PERINAT
JI Am. J. Perinatol.
PD AUG
PY 2010
VL 27
IS 7
BP 537
EP 542
DI 10.1055/s-0030-1248940
PG 6
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 633CJ
UT WOS:000280476800005
PM 20175042
ER
PT J
AU Barber, M
Blaisdell, CJ
AF Barber, Melissa
Blaisdell, Carol J.
TI Respiratory Causes of Infant Mortality: Progress and Challenges
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article
DE Bronchopulmonary dysplasia; meconium aspiration syndrome; pulmonary
vascular disease
ID UNITED-STATES; BIRTH-WEIGHT; DISTRESS-SYNDROME; BRONCHOPULMONARY
DYSPLASIA; NEONATAL-MORTALITY; ANTENATAL CORTICOSTEROIDS; SURFACTANT
THERAPY; RACIAL-DIFFERENCES; PRETERM DELIVERY; GESTATIONAL-AGE
AB A marked reduction in infant mortality due to respiratory distress syndrome (RDS) has been reported in previous studies; however, deaths due to RDS are still more common in black infants than white infants Because advances in respiratory care may have impacted non-RDS respiratory causes of infant mortality as well, the objective of this study was to determine if specific and total non-RDS respiratory causes of infant mortality have changed over time, and if health disparities exist. We analyzed and compared infant deaths due to RDS and other respiratory diseases from 1980 to 2005 in the United States and evaluated outcomes by race and gender Infant mortality due to non-RDS causes declined more than twofold over this time frame, but not as dramatically as the fivefold decline in RDS deaths. Black compared with white Infants had twice the mortality rate due to non-RDS respiratory causes. The most common non-RDS respiratory cause of infant mortality was due to congenital malformations of the respiratory tract, which did not change dramatically over the 25 years studied.
C1 [Barber, Melissa; Blaisdell, Carol J.] NHLBI, Div Lung Dis, NIH, Bethesda, MD 20892 USA.
RP Blaisdell, CJ (reprint author), NHLBI, Div Lung Dis, NIH, 6701 Rockledge Dr, Bethesda, MD 20892 USA.
NR 36
TC 9
Z9 10
U1 0
U2 4
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
J9 AM J PERINAT
JI Am. J. Perinatol.
PD AUG
PY 2010
VL 27
IS 7
BP 549
EP 558
DI 10.1055/s-0030-1248942
PG 10
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 633CJ
UT WOS:000280476800007
PM 20175045
ER
PT J
AU Grewal, J
Zhang, J
Mikolajczyk, RT
Ford, J
AF Grewal, Jagteshwar
Zhang, Jun
Mikolajczyk, Rafael T.
Ford, Jessie
TI Risk of Cesarean Delivery When Second-Trimester Ultrasound Dating
Disagrees with Definite Last Menstrual Period
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article
DE Gestational age; last menstrual period; cesarean section; low birth
weight
ID INTRAUTERINE GROWTH-RETARDATION; GESTATIONAL-AGE; BIPARIETAL DIAMETER;
LABOR PROGRESSION; FETAL GROWTH; PREGNANCY; DISCREPANCY; PRETERM;
SMALLER; WEIGHT
AB Estimates of gestational age based on early second-trimester ultrasound often differ from that based on the last menstrual period (LMP) even when a woman is certain about her LMP. Discrepancies in these gestational age estimates may be associated with an increased risk of cesarean section and low birth weight. We analyzed 7228 singleton, low-risk, white women from The Routine Antenatal Diagnostic Imaging with Ultrasound trial. The women were recruited at less than 14 weeks of gestation and received ultrasound exams between 15 and 22 weeks. Our results indicate that among nulliparous women, the risk of cesarean section increased from 10% when the ultrasound-based gestational age exceeded the LMP-based estimate by 4 days to 60% when the discrepancy increased to 21 clays. Moreover, for each additional day the ultrasound-based estimate exceeded the LMP-based estimate, birth weight was higher by 9.6 g. Our findings indicate that a positive discrepancy (i.e., ultrasound-based estimate exceeds LMP-based estimate) in gestational age is associated with an increased risk of cesarean section. A. negative discrepancy, by contrast, may reflect early intrauterine growth restriction and an increased risk of low birth weight
C1 [Grewal, Jagteshwar] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, NIH, Rockville, MD 20852 USA.
[Mikolajczyk, Rafael T.] Univ Bremen, Dept Clin Epidemiol, Bremen Inst Prevent Res & Social Med, Bremen, Germany.
RP Grewal, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, NIH, 6100 Execut Blvd,Room 7B03G, Rockville, MD 20852 USA.
OI Mikolajczyk, Rafael/0000-0003-1271-7204; Grewal,
Jagteshwar/0000-0002-0141-4876
FU NIH, Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX This research was supported by the Intramural Research Program of the
NIH, Eunice Kennedy Shriver National Institute of Child Health and Human
Development
NR 25
TC 0
Z9 0
U1 0
U2 1
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
J9 AM J PERINAT
JI Am. J. Perinatol.
PD AUG
PY 2010
VL 27
IS 7
BP 587
EP 593
DI 10.1055/s-0030-1249359
PG 7
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 633CJ
UT WOS:000280476800012
PM 20232279
ER
PT J
AU Abe, Y
Sakairi, T
Kajiyama, H
Shrivastav, S
Beeson, C
Kopp, JB
AF Abe, Yoshifusa
Sakairi, Toru
Kajiyama, Hiroshi
Shrivastav, Shashi
Beeson, Craig
Kopp, Jeffrey B.
TI Bioenergetic characterization of mouse podocytes
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Article
DE mitochondria; oxygen consumption rate; extracellular acidification rate
ID MONOCARBOXYLATE TRANSPORTERS; MITOCHONDRIAL; EXPRESSION; KIDNEY; CELLS;
NEPHROPATHY; RESPIRATION; OXIDATION; MEMBRANE; FAMILY
AB Abe Y, Sakairi T, Kajiyama H, Shrivastav S, Beeson C, Kopp JB. Bioenergetic characterization of mouse podocytes. Am J Physiol Cell Physiol 299: C464-C476, 2010. First published May 5, 2010; doi: 10.1152/ajpcell.00563.2009.-Mitochondrial dysfunction contributes to podocyte injury, but normal podocyte bioenergetics have not been characterized. We measured oxygen consumption rates (OCR) and extracellular acidification rates (ECAR), using a transformed mouse podocyte cell line and the Seahorse Bioscience XF24 Extracellular Flux Analyzer. Basal OCR and ECAR were 55.2 +/- 9.9 pmol/min and 3.1 +/- 1.9 milli-pH units/min, respectively. The complex V inhibitor oligomycin reduced OCR to similar to 45% of baseline rates, indicating that similar to 55% of cellular oxygen consumption was coupled to ATP synthesis. Rotenone, a complex I inhibitor, reduced OCR to similar to 25% of the baseline rates, suggesting that mitochondrial respiration accounted for similar to 75% of the total cellular respiration. Thus similar to 75% of mitochondrial respiration was coupled to ATP synthesis and similar to 25% was accounted for by proton leak. Carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), which uncouples electron transport from ATP generation, increased OCR and ECAR to similar to 360% and 840% of control levels. FCCP plus rotenone reduced ATP content by 60%, the glycolysis inhibitor 2-deoxyglucose reduced ATP by 35%, and 2-deoxyglucose in combination with FCCP or rotenone reduced ATP by >85%. The lactate dehydrogenase inhibitor oxamate and 2-deoxyglucose did not reduce ECAR, and 2-deoxyglucose had no effect on OCR, although 2-deoxyglucose reduced ATP content by 25%. Mitochondrial uncoupling induced by FCCP was associated with increased OCR with certain substrates, including lactate, glucose, pyruvate, and palmitate. Replication of these experiments in primary mouse podocytes yielded similar data. We conclude that mitochondria play the primary role in maintaining podocyte energy homeostasis, while glycolysis makes a lesser contribution.
C1 [Abe, Yoshifusa; Sakairi, Toru; Shrivastav, Shashi; Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA.
[Abe, Yoshifusa] Showa Univ, Sch Med, Dept Pediat, Tokyo 142, Japan.
[Kajiyama, Hiroshi] Saitama Med Univ, Dept Rheumatol & Appl Immunol, Saitama, Japan.
[Beeson, Craig] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA.
RP Kopp, JB (reprint author), NIDDK, Kidney Dis Sect, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM jbkopp@nih.gov
OI Kopp, Jeffrey/0000-0001-9052-186X
FU NIDDK [ZO1-DK-043308]
FX This study was supported by the NIDDK Intramural Research Program, under
project ZO1-DK-043308.
NR 27
TC 54
Z9 54
U1 2
U2 16
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6143
J9 AM J PHYSIOL-CELL PH
JI Am. J. Physiol.-Cell Physiol.
PD AUG
PY 2010
VL 299
IS 2
BP C464
EP C476
DI 10.1152/ajpcell.00563.2009
PG 13
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 632CK
UT WOS:000280397600030
PM 20445170
ER
PT J
AU Cawley, NX
Yanik, T
Woronowicz, A
Chang, WZ
Marini, JC
Loh, YP
AF Cawley, Niamh X.
Yanik, Tulin
Woronowicz, Alicja
Chang, Weizhong
Marini, Joan C.
Loh, Y. Peng
TI Obese carboxypeptidase E knockout mice exhibit multiple defects in
peptide hormone processing contributing to low bone mineral density
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
ID AMPHETAMINE-REGULATED TRANSCRIPT; ACTIVITY-DEPENDENT SECRETION;
SYMPATHETIC-NERVOUS-SYSTEM; HIPPOCAMPAL-NEURONS; ENERGY-METABOLISM; CART
DEFICIENCY; BODY-WEIGHT; MASS; LEADS; GENE
AB Cawley NX, Yanik T, Woronowicz A, Chang W, Marini JC, Loh YP. Obese carboxypeptidase E knockout mice exhibit multiple defects in peptide hormone processing contributing to low bone mineral density. Am J Physiol Endocrinol Metab 299: E189-E197, 2010. First published May 11, 2010; doi:10.1152/ajpendo.00516.2009.-Carboxypeptidase E (CPE) is a prohormone/proneuropeptide processing enzyme, and mice bearing CPE mutations exhibit an obese and diabetic phenotype. Studies on CPE knockout (KO) mice revealed poor prohormone processing, resulting in deficiencies in peptide hormones/neuropeptides such as insulin, gonadotropin-releasing hormone, and cocaine-and amphetamine-regulated transcript (CART). Here, we show that CPE KO mice, an obese animal model, have low bone mineral density (BMD) accompanied by elevated plasma CTX-1 (carboxy-terminal collagen crosslinks), and osteocalcin, indicators of increased bone turnover. Receptor activator for NF-kappa B ligand (RANKL) expression was elevated similar to 2-fold relative to osteoprotegerin in the femur of KO animals, suggesting increased osteoclastic activity in the KO mice. In the hypothalamus, mature CART, a peptide involved in eating behavior and implicated in bone metabolism, was undetectable. The melanocortin and neuropeptide Y (NPY) systems in the hypothalamus have also been implicated in bone remodeling, since MC4R KO and NPY KO mice have increased BMD. However, reduction of alpha-MSH, the primary ligand of MC4R by up to 94% and the lack of detectable NPY in the hypothalamus of CPE KO do not recapitulate the single-gene KO phenotypes. This study highlights the complex physiological interplay between peptides involved in energy metabolism and bone formation and furthermore suggests the possibility that patients, bearing CPE and CART mutations leading to inactive forms of these molecules, may be at a higher risk of developing osteoporosis.
C1 [Cawley, Niamh X.; Yanik, Tulin; Woronowicz, Alicja; Loh, Y. Peng] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Chang, Weizhong; Marini, Joan C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA.
RP Loh, YP (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bldg 49,Rm 5A-22,49 Convent Dr, Bethesda, MD 20892 USA.
EM lohp@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Bethesda, MD
FX This research was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Bethesda, MD.
NR 40
TC 21
Z9 22
U1 0
U2 1
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD AUG
PY 2010
VL 299
IS 2
BP E189
EP E197
DI 10.1152/ajpendo.00516.2009
PG 9
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA 622IG
UT WOS:000279654600006
PM 20460579
ER
PT J
AU Li, JH
Rosenblatt-Velin, N
Loukili, N
Pacher, P
Feihl, F
Waeber, B
Liaudet, L
AF Li Jianhui
Rosenblatt-Velin, Nathalie
Loukili, Noureddine
Pacher, Pal
Feihl, Francois
Waeber, Bernard
Liaudet, Lucas
TI Endotoxin impairs cardiac hemodynamics by affecting loading conditions
but not by reducing cardiac inotropism
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE cardiac function; contractility; mice
ID NITRIC-OXIDE SYNTHASE; LEFT-VENTRICULAR VOLUME; INDUCED MYOCARDIAL
DYSFUNCTION; CANINE LEFT-VENTRICLE; CONDUCTANCE CATHETER; SEPTIC SHOCK;
HEART-RATE; PARALLEL CONDUCTANCE; CONSCIOUS DOGS; VENOUS RETURN
AB Jianhui L, Rosenblatt-Velin N, Loukili N, Pacher P, Feihl F, Waeber B, Liaudet L. Endotoxin impairs cardiac hemodynamics by affecting loading conditions but not by reducing cardiac inotropism. Am J Physiol Heart Circ Physiol 299: H492-H501, 2010. First published June 4, 2010; doi:10.1152/ajpheart.01135.2009.-Acute myocardial dysfunction is a typical manifestation of septic shock. Experimentally, the administration of endotoxin [lipopolysacharride (LPS)] to laboratory animals is frequently used to study such dysfunction. However, a majority of studies used load-dependent indexes of cardiac function [including ejection fraction (EF) and maximal systolic pressure increment (dP/dt(max))], which do not directly explore cardiac inotropism. Therefore, we evaluated the direct effects of LPS on myocardial contractility, using left ventricular (LV) pressure-volume catheters in mice. Male BALB/c mice received an intraperitoneal injection of E. coli LPS (1, 5, 10, or 20 mg/kg). After 2, 6, or 20 h, cardiac function was analyzed in anesthetized, mechanically ventilated mice. All doses of LPS induced a significant drop in LV stroke volume and a trend toward reduced cardiac output after 6 h. Concomitantly, there was a significant decrease of LV preload (LV end-diastolic volume), with no apparent change in LV afterload (evaluated by effective arterial elastance and systemic vascular resistance). Load-dependent indexes of LV function were markedly reduced at 6 h, including EF, stroke work, and dP/dt(max). In contrast, there was no reduction of load-independent indexes of LV contractility, including end-systolic elastance (ejection phase measure of contractility) and the ratio dP/dt(max)/end-diastolic volume (isovolumic phase measure of contractility), the latter showing instead a significant increase after 6 h. All changes were transient, returning to baseline values after 20 h. Therefore, the alterations of cardiac function induced by LPS are entirely due to altered loading conditions, but not to reduced contractility, which may instead be slightly increased.
C1 [Li Jianhui; Loukili, Noureddine; Liaudet, Lucas] Univ Hosp Ctr, Dept Intens Care Med, CH-1011 Lausanne, Switzerland.
[Rosenblatt-Velin, Nathalie; Feihl, Francois; Waeber, Bernard; Liaudet, Lucas] Univ Hosp Ctr, Div Clin Pathophysiol, CH-1011 Lausanne, Switzerland.
[Rosenblatt-Velin, Nathalie; Feihl, Francois; Waeber, Bernard; Liaudet, Lucas] Fac Biol & Med, CH-1011 Lausanne, Switzerland.
[Li Jianhui] Zhejiang Univ, Coll Med, Affiliated Hosp 1, Dept Hepatobiliary Surg, Hangzhou 310003, Zhejiang, Peoples R China.
[Pacher, Pal] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA.
RP Liaudet, L (reprint author), Univ Hosp Ctr, Dept Intens Care Med, CHUV BH 08-621, CH-1011 Lausanne, Switzerland.
EM lucas.liaudet@chuv.ch
RI Pacher, Pal/B-6378-2008; Liaudet, Lucas/E-1322-2017
OI Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930
FU Swiss National Fund for Scientific Research [320000/118174]; CARDIOMET
Foundation, University of Lausanne [2007-R07-15]
FX This work was supported, in part, by a grant from the Swiss National
Fund for Scientific Research (Nr 320000/118174) and a grant from the
CARDIOMET Foundation, University of Lausanne (Grant Nr 2007-R07-15) to
L. Liaudet.
NR 57
TC 0
Z9 0
U1 0
U2 0
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD AUG
PY 2010
VL 299
IS 2
BP H492
EP H501
DI 10.1152/ajpheart.01135.2009
PG 10
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA 633GZ
UT WOS:000280491100030
ER
PT J
AU Dunton, GF
Berrigan, D
Ballard-Barbash, R
Perna, FM
Graubard, BI
Atienza, AA
AF Dunton, Genevieve Fridlund
Berrigan, David
Ballard-Barbash, Rachel
Perna, Frank M.
Graubard, Barry I.
Atienza, Audie A.
TI Adolescents' Sports and Exercise Environments in a US Time Use Survey
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID CHILDRENS PHYSICAL-ACTIVITY; SCHOOL GIRLS; YOUTH; CONTEXTS; PREDICTORS;
SUPPORT; OBESITY; WALKING; HEALTH; SPACE
AB Background: Studies examining environmental influences on adolescent physical activity largely measure the presence and availability of social resources and built environment facilities. Unfortunately, this research approach provides limited information about adolescents' social company during exercise or the extent to which adolescents actually use physical settings for physical activity.
Purpose: The current study used data from the nationally representative American Time Use Survey (2003-2006) to describe demographic and temporal patterns in the social and physical contexts of physical activity among adolescents.
Methods: The sample consisted of high school students (aged 15-18 years) reporting at least one bout of sports or exercise (N=867). During the interview, participants reported where (e.g., outdoors, home, work) and with whom (e.g., alone, family, friends) each bout occurred. Sample-weighted multinomial logistic regression analyses compared the proportion of bouts occurring in each environment by age, gender, family income, season, weekend/weekday, and time of day, controlling for race/ethnicity. Data were analyzed in 2009.
Results: Girls were more likely to exercise with family (22% vs 16%), and less likely to exercise with friends/acquaintances/others (47% vs 52%) and outdoors (18% vs 24%) than boys. Compared with those aged 15 years, a larger proportion of exercise bouts among those aged 18 years occurred alone (23% vs 18%); and a smaller proportion occurred at home (14% vs 20%), at someone else's house (5% vs 12%), and at school (14% vs 27%) (p's<0.001).
Conclusions: Information about the social and physical contexts of adolescents' sports and exercise can help guide the selection of future environmental targets for investigation and intervention. (Am J Prey Med 2010;39(2):122-129) (C) 2010 American Journal of Preventive Medicine
C1 [Dunton, Genevieve Fridlund] Univ So Calif, Dept Prevent Med, Alhambra, CA 91803 USA.
[Berrigan, David; Ballard-Barbash, Rachel; Perna, Frank M.] NCI, Off Associate Director, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Graubard, Barry I.] NCI, Biostat Branch, Epidemiol & Biostat Program, Div Canc Epidemiol & Biostat, Bethesda, MD 20892 USA.
[Atienza, Audie A.] NCI, Hlth Promot Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Dunton, GF (reprint author), Univ So Calif, Dept Prevent Med, 1000 S Fremont Ave,Unit 8,Bldg 5,Room 5229, Alhambra, CA 91803 USA.
EM dunton@usc.edu
NR 34
TC 5
Z9 5
U1 5
U2 14
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD AUG
PY 2010
VL 39
IS 2
BP 122
EP 129
DI 10.1016/j.amepre.2010.03.022
PG 8
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 632MP
UT WOS:000280429100003
PM 20621259
ER
PT J
AU Khoury, MJ
Feero, WG
Valdez, R
AF Khoury, Muin J.
Feero, William G.
Valdez, Rodolfo
TI Family History and Personal Genomics As Tools for Improving Health in an
Era of Evidence-Based Medicine
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID NATIONAL-INSTITUTES; COMMON DISEASES; RISK; PREVENTION; RECOMMENDATIONS;
PRIORITIES; STATEMENT; PROFILES; SCIENCE
C1 [Khoury, Muin J.; Valdez, Rodolfo] CDC, Natl Off Publ Hlth Genom, Atlanta, GA 30333 USA.
[Feero, William G.] Maine Dartmouth Family Med Residency Program, Augusta, ME USA.
[Feero, William G.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Khoury, MJ (reprint author), CDC, Natl Off Publ Hlth Genom, 1600 Clifton Rd, Atlanta, GA 30333 USA.
EM muk1@cdc.gov
NR 28
TC 21
Z9 22
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD AUG
PY 2010
VL 39
IS 2
BP 184
EP 188
DI 10.1016/j.amepre.2010.03.019
PG 5
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 632MP
UT WOS:000280429100011
PM 20621267
ER
PT J
AU Kay, DB
Marsiske, M
Suomi, SJ
Higley, JD
AF Kay, D. B.
Marsiske, M.
Suomi, S. J.
Higley, J. D.
TI CONFIRMATORY FACTOR ANALYSIS OF THE THREE-FACTOR MODEL OF TEMPERAMENT IN
THE RHESUS MONKEY
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the American-Society-of-Primatologists
CY JUN 16-19, 2010
CL Louisville, KY
SP Amer Soc Primatologists, Louisville Zoo, Centre Coll, Bellarmine Univ
C1 [Kay, D. B.; Marsiske, M.] Univ Florida, Gainesville, FL 32610 USA.
[Suomi, S. J.] NICHHD, NIH, Anim Ctr, Bethesda, MD 20892 USA.
[Higley, J. D.] Brigham Young Univ, Provo, UT 84602 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD AUG
PY 2010
VL 72
SU 1
MA 20
BP 32
EP 32
PG 1
WC Zoology
SC Zoology
GA 636GS
UT WOS:000280720400021
ER
PT J
AU Paukner, A
Ferrari, PF
Suomi, SJ
AF Paukner, A.
Ferrari, P. F.
Suomi, S. J.
TI DELAYED IMITATION OF LIPSMACKING IN INFANT RHESUS MACAQUES
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the American-Society-of-Primatologists
CY JUN 16-19, 2010
CL Louisville, KY
SP Amer Soc Primatologists, Louisville Zoo, Centre Coll, Bellarmine Univ
C1 [Paukner, A.; Suomi, S. J.] NIH, Comparat Ethol Lab, Anim Ctr, Poolesville, MD 20837 USA.
[Ferrari, P. F.] Univ Parma, Dipartimento Neurosci, I-43100 Parma, Italy.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD AUG
PY 2010
VL 72
SU 1
MA 21
BP 32
EP 32
PG 1
WC Zoology
SC Zoology
GA 636GS
UT WOS:000280720400022
ER
PT J
AU Suomi, SJ
AF Suomi, S. J.
TI RISK, RESILIENCE, AND GENE X ENVIRONMENT INTERACTIONS IN PRIMATES
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the American-Society-of-Primatologists
CY JUN 16-19, 2010
CL Louisville, KY
SP Amer Soc Primatologists, Louisville Zoo, Centre Coll, Bellarmine Univ
C1 [Suomi, S. J.] NICHD, LCE, NIH, DHHS, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD AUG
PY 2010
VL 72
SU 1
MA 23
BP 33
EP 33
PG 1
WC Zoology
SC Zoology
GA 636GS
UT WOS:000280720400024
ER
PT J
AU Dettmer, AM
Novak, MA
Meyer, JS
Vallender, EJ
Miller, GM
Suomi, SJ
AF Dettmer, A. M.
Novak, M. A.
Meyer, J. S.
Vallender, E. J.
Miller, G. M.
Suomi, S. J.
TI INFLUENCES OF MU-OPIOID RECEPTOR AND TPH2 GENOTYPES ON HPA AXIS ACTIVITY
AND SOCIAL BEHAVIOR IN DIFFERENTLY REARED MONKEYS ACROSS THE FIRST TWO
YEARS OF LIFE
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the American-Society-of-Primatologists
CY JUN 16-19, 2010
CL Louisville, KY
SP Amer Soc Primatologists, Louisville Zoo, Centre Coll, Bellarmine Univ
C1 [Dettmer, A. M.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
[Novak, M. A.; Meyer, J. S.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA.
[Vallender, E. J.; Miller, G. M.] Harvard Univ, Sch Med, New England Primate Res Ctr, Div Neurochem, Southborough, MA 01772 USA.
[Suomi, S. J.] Eunice Kennedy Shriver NICHD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD AUG
PY 2010
VL 72
SU 1
MA 43
BP 39
EP 39
PG 1
WC Zoology
SC Zoology
GA 636GS
UT WOS:000280720400044
ER
PT J
AU Miller, ML
Ruggiero, A
Hansman, C
Sun, M
Heckman, J
Suomi, S
AF Miller, M. L.
Ruggiero, A.
Hansman, C.
Sun, M.
Heckman, J.
Suomi, S.
TI THE EFFECTS OF MATERNAL REARING CONDITION ON INFANT BIRTH WEIGHT IN A
CAPTIVE COLONY OF RHESUS MACAQUES (MACACA MULATTA)
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the American-Society-of-Primatologists
CY JUN 16-19, 2010
CL Louisville, KY
SP Amer Soc Primatologists, Louisville Zoo, Centre Coll, Bellarmine Univ
C1 [Miller, M. L.; Ruggiero, A.; Suomi, S.] NICHHD, Comparat Ethol Lab, NIH, Anim Ctr, Poolesville, MD 20827 USA.
[Hansman, C.; Sun, M.; Heckman, J.] Univ Chicago, Chicago, IL 60637 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD AUG
PY 2010
VL 72
SU 1
MA 45
BP 39
EP 39
PG 1
WC Zoology
SC Zoology
GA 636GS
UT WOS:000280720400046
ER
PT J
AU Kirton, JW
Blocker, DJ
Orgad, K
Suomi, SJ
Higley, JD
AF Kirton, J. W.
Blocker, D. J.
Orgad, K.
Suomi, S. J.
Higley, J. D.
TI CONSISTENCY OF TEMPERAMENT OF IN GROUP-HOUSED INFANT RHESUS MONKEYS
(MACACA MULATTA) DURING THE FIRST MONTHS OF LIFE
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the American-Society-of-Primatologists
CY JUN 16-19, 2010
CL Louisville, KY
SP Amer Soc Primatologists, Louisville Zoo, Centre Coll, Bellarmine Univ
C1 [Kirton, J. W.; Blocker, D. J.; Orgad, K.; Higley, J. D.] Brigham Young Univ, Dept Psychol, Provo, UT 84057 USA.
[Suomi, S. J.] NICHD, LCE, Poolesville, MD USA.
[Higley, J. D.] NIAAA, LCTS, Poolesville, MD 20837 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD AUG
PY 2010
VL 72
SU 1
MA 46
BP 40
EP 40
PG 1
WC Zoology
SC Zoology
GA 636GS
UT WOS:000280720400047
ER
PT J
AU Bower, S
Paukner, A
Suomi, SJ
AF Bower, S.
Paukner, A.
Suomi, S. J.
TI FAMILY FACES: RELATEDNESS AND FACIAL SIMILARITY IN RHESUS MACAQUES
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the American-Society-of-Primatologists
CY JUN 16-19, 2010
CL Louisville, KY
SP Amer Soc Primatologists, Louisville Zoo, Centre Coll, Bellarmine Univ
C1 [Bower, S.; Paukner, A.; Suomi, S. J.] NIH Anim Ctr, Comparat Ethol Lab, Poolesville, MD 20837 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD AUG
PY 2010
VL 72
SU 1
MA 55
BP 43
EP 43
PG 1
WC Zoology
SC Zoology
GA 636GS
UT WOS:000280720400056
ER
PT J
AU Herman, KN
McLaughlin, SM
Cummins, A
Delaney, D
Vaughan, K
Noble, P
Suomi, SJ
Winslow, JT
Nelson, EE
AF Herman, K. N.
McLaughlin, S. M.
Cummins, A.
Delaney, D.
Vaughan, K.
Noble, P.
Suomi, S. J.
Winslow, J. T.
Nelson, E. E.
TI RH5-HTTLPR AND PEER REARING COMPROMISE SOCIAL BUFFERING OF AROUSAL AND
FEAR IN JUVENILE RHESUS MACAQUES (MACACA MULATTA)
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the American-Society-of-Primatologists
CY JUN 16-19, 2010
CL Louisville, KY
SP Amer Soc Primatologists, Louisville Zoo, Centre Coll, Bellarmine Univ
C1 [Herman, K. N.; Suomi, S. J.] NIH Anim Ctr, Comparat Ethol Lab, Poolesville, MD 20842 USA.
[Herman, K. N.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA.
[McLaughlin, S. M.; Nelson, E. E.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
[Cummins, A.; Delaney, D.; Vaughan, K.; Noble, P.; Winslow, J. T.] NIMH, Primate Core Facil, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD AUG
PY 2010
VL 72
SU 1
MA 69
BP 47
EP 47
PG 1
WC Zoology
SC Zoology
GA 636GS
UT WOS:000280720400070
ER
PT J
AU Songrady, JC
Novak, MFSX
Ruggiero, AM
Mallott, EK
Bowling, N
Miller, ML
Kerschner, EA
Synnestvedt, K
Suomi, SJ
AF Songrady, J. C.
Novak, M. F. S. X.
Ruggiero, A. M.
Mallott, E. K.
Bowling, N.
Miller, M. L.
Kerschner, E. A.
Synnestvedt, K.
Suomi, S. J.
TI TEMPERAMENT DEVELOPMENT AND SEX DIFFERENCES IN RHESUS MACAQUE INFANTS
(MACACA MULATTA) ACROSS DIFFERENT TESTING ENVIRONMENTS
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the American-Society-of-Primatologists
CY JUN 16-19, 2010
CL Louisville, KY
SP Amer Soc Primatologists, Louisville Zoo, Centre Coll, Bellarmine Univ
C1 [Songrady, J. C.; Novak, M. F. S. X.; Ruggiero, A. M.; Mallott, E. K.; Bowling, N.; Miller, M. L.; Kerschner, E. A.; Synnestvedt, K.; Suomi, S. J.] NICHD, NIH, Comparat Ethol Lab, NIH Anim Ctr, Poolesville, MD 20837 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD AUG
PY 2010
VL 72
SU 1
MA 89
BP 53
EP 54
PG 2
WC Zoology
SC Zoology
GA 636GS
UT WOS:000280720400090
ER
PT J
AU Chaffin, AC
Higley, JD
Schwandt, ML
Lindell, SG
Suomi, SJ
Barr, CS
AF Chaffin, A. C.
Higley, J. D.
Schwandt, M. L.
Lindell, S. G.
Suomi, S. J.
Barr, C. S.
TI TEMPERAMENTAL BEHAVIORS MEASURED DURING THE FIRST MONTHS OF LIFE ARE
PREDICTIVE OF AGGRESSION IN GROUP HOUSED RHESUS MACAQUES (MACACA
MULATTA)
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the American-Society-of-Primatologists
CY JUN 16-19, 2010
CL Louisville, KY
SP Amer Soc Primatologists, Louisville Zoo, Centre Coll, Bellarmine Univ
C1 [Chaffin, A. C.; Higley, J. D.] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA.
[Schwandt, M. L.; Lindell, S. G.; Barr, C. S.] NIAA, LCTS, NIH, Bethesda, MD 20892 USA.
[Suomi, S. J.] NICHD, LCE, NIH, Poolesville, MD 20837 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD AUG
PY 2010
VL 72
SU 1
MA 90
BP 54
EP 54
PG 1
WC Zoology
SC Zoology
GA 636GS
UT WOS:000280720400091
ER
PT J
AU Johnson, E
Brockett, A
Herman, KN
Vaughan, K
Delaney, D
Cummins, A
Fellows, D
Noble, P
Suomi, SJ
Winslow, JT
Nelson, EE
AF Johnson, E.
Brockett, A.
Herman, K. N.
Vaughan, K.
Delaney, D.
Cummins, A.
Fellows, D.
Noble, P.
Suomi, S. J.
Winslow, J. T.
Nelson, E. E.
TI HOW VARIANT REARING PATTERNS AND FLUOXETINE AFFECTS STRESS AND FEAR
RESPONSE BEHAVIORS IN ADOLESCENT RHESUS MACAQUES (MACACA MULATTA)
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the American-Society-of-Primatologists
CY JUN 16-19, 2010
CL Louisville, KY
SP Amer Soc Primatologists, Louisville Zoo, Centre Coll, Bellarmine Univ
C1 [Johnson, E.; Brockett, A.; Vaughan, K.; Delaney, D.; Cummins, A.; Fellows, D.; Noble, P.; Winslow, J. T.; Nelson, E. E.] NIMH, Dickerson, MD 20842 USA.
[Herman, K. N.] Univ Maryland, College Pk, MD 20742 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD AUG
PY 2010
VL 72
SU 1
MA 98
BP 56
EP 56
PG 1
WC Zoology
SC Zoology
GA 636GS
UT WOS:000280720400099
ER
PT J
AU Mallott, EK
Bowling, NA
Ionica, CS
Kerschner, EA
Miller, ML
Novak, MFSX
Robbins, KL
Suomi, SJ
AF Mallott, E. K.
Bowling, N. A.
Ionica, C. S.
Kerschner, E. A.
Miller, M. L.
Novak, M. F. S. X.
Robbins, K. L.
Suomi, S. J.
TI EFFECTS OF NUMBER OF CLOSE RELATIVES ON INFANT DEVELOPMENTAL MILESTONES
IN SOCIALLY HOUSED MACACA MULATTA
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the American-Society-of-Primatologists
CY JUN 16-19, 2010
CL Louisville, KY
SP Amer Soc Primatologists, Louisville Zoo, Centre Coll, Bellarmine Univ
C1 [Mallott, E. K.; Bowling, N. A.; Ionica, C. S.; Kerschner, E. A.; Miller, M. L.; Novak, M. F. S. X.; Robbins, K. L.; Suomi, S. J.] NICHD, Comparat Ethol Lab, NIH, NIH Anim Ctr, Poolesville, MD 20837 USA.
RI Ionica, Consuel/A-5186-2009
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD AUG
PY 2010
VL 72
SU 1
MA 104
BP 58
EP 58
PG 1
WC Zoology
SC Zoology
GA 636GS
UT WOS:000280720400105
ER
PT J
AU Higley, J
Roberg, B
Schwandt, M
Lindell, S
Bari, C
Suomi, S
AF Higley, J.
Roberg, B.
Schwandt, M.
Lindell, S.
Bari, C.
Suomi, S.
TI VIOLENT AGGRESSION AND THE SEROTONIN TRANSPORTER GENE: A
PERSONAL-GENOTYPE X PARTNER-GENOTYPE INTERACTION
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the American-Society-of-Primatologists
CY JUN 16-19, 2010
CL Louisville, KY
SP Amer Soc Primatologists, Louisville Zoo, Centre Coll, Bellarmine Univ
C1 [Higley, J.; Roberg, B.] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA.
[Higley, J.; Schwandt, M.; Lindell, S.; Bari, C.] NIAAA, LCTS, NIH, Anim Ctr, Bethesda, MD 20892 USA.
[Higley, J.; Suomi, S.] NICHD, LCE, NIH, Anim Ctr, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0275-2565
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD AUG
PY 2010
VL 72
SU 1
MA 136
BP 69
EP 69
PG 1
WC Zoology
SC Zoology
GA 636GS
UT WOS:000280720400137
ER
PT J
AU Wu, JM
Takahashi, DL
Ingram, DK
Mattison, JA
Roth, G
Ottinger, MA
Zelinski, MB
AF Wu, Julie M.
Takahashi, Diana L.
Ingram, Donald K.
Mattison, Julie A.
Roth, George
Ottinger, Mary Ann
Zelinski, Mary B.
TI Ovarian Reserve Tests and Their Utility in Predicting Response to
Controlled Ovarian Stimulation in Rhesus Monkeys
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Article
DE inhibin; ovarian reserve; follicular response; peri-menopause; hormone
predictors of fertility
ID ANTI-MULLERIAN HORMONE; DIMERIC INHIBIN; CLOMIPHENE CITRATE; OVULATORY
WOMEN; MARKER; SERUM; RISE; PERIMENOPAUSE; SECRETION; CYCLES
AB Controlled ovarian stimulation (COS) is an alternative to natural breeding in nonhuman primates; however, these protocols are costly with no guarantee of success. Toward the objective of predicting COS outcome in rhesus monkeys, this study evaluated three clinically used ovarian reserve tests (ORTs): day 3 (d3) follicle-stimulating hormone (FSH) with d3 inhibin B (INHB), the clomiphene citrate challenge test (CCCT), and the exogenous FSH Ovarian Reserve Test. A COS was also performed and response was classified as either successful (COS+) or unsuccessful (COS-) and retrospectively compared with ORT predictions. FSH and INHB were assessed for best hormonal index in conjunction with the aforementioned tests. INHB was consistently more accurate than FSH in all the ORTs used. Overall, a modified version of the CCCT using INHB values yielded the best percentage of correct predictions. This is the first report of ORT evaluation in rhesus monkeys and may provide a useful diagnostic test before costly follicle stimulations, as well as predicting the onset of menopause. Am. J. Primatol. 72:672-680, 2010. (c) 2010 Wiley-Liss, Inc.
C1 [Wu, Julie M.; Ottinger, Mary Ann] Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA.
[Takahashi, Diana L.; Zelinski, Mary B.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Reprod Sci, Beaverton, OR USA.
[Ingram, Donald K.] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA USA.
[Mattison, Julie A.] NIA, Lab Expt Gerontol, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA.
[Roth, George] GeroScience Inc, Pylesville, MD USA.
RP Ottinger, MA (reprint author), Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA.
EM maottinger@umresearch.umd.edu
FU NIH [AG21382-01, HD 18185, RR00163]; National Institute on Aging;
University of Maryland Department of Animal and Avian Sciences; Sigma Xi
Grants in Aid of Research
FX Contract grant sponsor: NIH; Contract grant number: AG21382-01 vertical
bar HD 18185 vertical bar RR00163; Contract grant sponsors: Intramural
Research Program of the NIH; National Institute on Aging; University of
Maryland Department of Animal and Avian Sciences; Sigma Xi Grants in Aid
of Research.
NR 20
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0275-2565
EI 1098-2345
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD AUG
PY 2010
VL 72
IS 8
BP 672
EP 680
DI 10.1002/ajp.20823
PG 9
WC Zoology
SC Zoology
GA 625PG
UT WOS:000279906800002
PM 20336797
ER
PT J
AU Lewis, CM
Ng, MY
Butler, AW
Cohen-Woods, S
Uher, R
Pirlo, K
Weale, ME
Schosser, A
Paredes, UM
Rivera, M
Craddock, N
Owen, MJ
Jones, L
Jones, I
Korszun, A
Aitchison, KJ
Shi, JX
Quinn, JP
MacKenzie, A
Vollenweider, P
Waeber, G
Heath, S
Lathrop, M
Muglia, P
Barnes, MR
Whittaker, JC
Tozzi, F
Holsboer, F
Preisig, M
Farmer, AE
Breen, G
Craig, IW
McGuffin, P
AF Lewis, Cathryn M.
Ng, Mandy Y.
Butler, Amy W.
Cohen-Woods, Sarah
Uher, Rudolf
Pirlo, Katrina
Weale, Michael E.
Schosser, Alexandra
Paredes, Ursula M.
Rivera, Margarita
Craddock, Nicholas
Owen, Mike J.
Jones, Lisa
Jones, Ian
Korszun, Ania
Aitchison, Katherine J.
Shi, Jianxin
Quinn, John P.
MacKenzie, Alasdair
Vollenweider, Peter
Waeber, Gerard
Heath, Simon
Lathrop, Mark
Muglia, Pierandrea
Barnes, Michael R.
Whittaker, John C.
Tozzi, Federica
Holsboer, Florian
Preisig, Martin
Farmer, Anne E.
Breen, Gerome
Craig, Ian W.
McGuffin, Peter
TI Genome-Wide Association Study of Major Recurrent Depression in the UK
Population
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID POLYCYSTIC KIDNEY-DISEASE; BICAUDAL-C; PSYCHIATRIC-DISORDERS; UNIPOLAR
DEPRESSION; LIFETIME HISTORY; HERITABILITY; AUTISM; GENES; METHODOLOGY;
RELIABILITY
AB Objective: Studies of major depression in twins and families have shown moderate to high heritability, but extensive molecular studies have failed to identify susceptibility genes convincingly. To detect genetic variants contributing to major depression, the authors performed a genome-wide association study using 1,636 cases of depression ascertained in the U.K. and 1,594 comparison subjects screened negative for psychiatric disorders.
Method: Cases were collected from 1) a case-control study of recurrent depression (the Depression Case Control [DeCC] study; N=1346), 2) an affected sibling pair linkage study of recurrent depression (probands from the Depression Network [DeNT] study; N=332), and 3) a pharmacogenetic study (the Genome-Based Therapeutic Drugs for Depression [GENDEN study; N=88). Depression cases and comparison subjects were genotyped at Centre National de Genotypage on the Illumina Human610-Quad Bead Chip. After applying stringent quality control criteria for missing genotypes, departure from Hardy-Weinberg equilibrium, and low minor allele frequency, the authors tested for association to depression using logistic regression, correcting for population ancestry.
Results: Single nucleotide polymorphisms (SNPs) in BICC1 achieved suggestive evidence for association, which strengthened after imputation of ungeno-typed markers, and in analysis of female depression cases. A meta-analysis of U.K. data with previously published results from studies in Munich and Lausanne showed some evidence for association near neuroligin 1 (NLGN1) on chromosome 3, but did not support findings at BICC1.
Conclusion: This study identifies several signals for association worthy of further investigation but, as in previous genome-wide studies, suggests that individual gene contributions to depression are likely to have only minor effects, and very large pooled analyses will be required to identify them.
C1 [Lewis, Cathryn M.] Kings Coll London, Inst Psychiat, MRC, SGDP Ctr, London SE5 8AF, England.
Kings Coll London, Dept Med & Mol Genet, Sch Med, London, England.
Med Univ Vienna, Dept Psychiat & Psychotherapy, Div Biol Psychiat, Vienna, Austria.
Cardiff Univ, MRC, Ctr Neuropsychiatr Genet & Genom, Dept Psychol Med & Neurol,Sch Med, Cardiff, S Glam, Wales.
Univ Birmingham, Dept Psychiat, Sch Clin Expt Med, Natl Ctr Mental Hlth, Birmingham, W Midlands, England.
Queen Mary Univ London, Ctr Psychiat, Wolfson Inst Prevent Med, Barts & London Med Sch, London, England.
NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
Univ Liverpool, Physiol Lab, Sch Biomed Sci, Liverpool L69 3BX, Merseyside, England.
Sch Med Sci, Inst Med Sci, Aberdeen, Scotland.
Univ Hosp Ctr, Lausanne, Switzerland.
Univ Lausanne, Lausanne, Switzerland.
Ctr Natl Genotypage, Evry, France.
CEPH Fdn Jean Dausset, Paris, France.
GlaxoSmithKline Res & Dev Ltd, Div Genet, Drug Discovery, Verona, Italy.
Univ Toronto, Ctr Addict & Mental Hlth, Dept Psychiat, Toronto, ON M5S 1A1, Canada.
Max Planck Inst Psychiat, D-80804 Munich, Germany.
NIHR Biomed Res Ctr Mental Hlth, London, England.
Maudsley NHS Fdn Trust, London, England.
RP Lewis, CM (reprint author), Kings Coll London, Inst Psychiat, MRC, SGDP Ctr, P080 SGDP,De Crespigny Pk, London SE5 8AF, England.
EM cathryn.lewis@kcl.ac.uk
RI Breen, Gerome/A-5540-2010; Cohen-Woods, Sarah/F-8674-2014; Quinn,
John/A-2972-2010; Weale, Michael/F-2587-2010; Lewis,
Cathryn/A-5225-2010; turton, miranda/F-4682-2011; mackenzie,
Alasdair/C-8121-2012; Ng, Mandy/D-8661-2012; Heath, Simon/J-4138-2012;
Colaus, PsyColaus/K-6607-2013; McGuffin, Peter/A-1565-2012; Uher,
Rudolf/A-5477-2008; Whittaker, John/B-8609-2012; Aitchison,
Katherine/G-4476-2013;
OI Breen, Gerome/0000-0003-2053-1792; Quinn, John/0000-0003-3551-7803;
Weale, Michael/0000-0003-4593-1186; Lewis, Cathryn/0000-0002-8249-8476;
McGuffin, Peter/0000-0002-9888-2907; Uher, Rudolf/0000-0002-2998-0546;
Whittaker, John/0000-0002-3529-2379; Aitchison,
Katherine/0000-0002-1107-3024; Barnes, Michael/0000-0001-9097-7381;
Tozzi, Federica/0000-0002-3536-2920; Craig, Ian/0000-0002-4063-1005;
Cohen-Woods, Sarah/0000-0003-2199-6129
FU U.K. Medical Research Council; GlaxoSmithKline [G0701420]; Austrian
Science Funds [J2647]; National Institute for Health Research (NIHR)
Specialist Biomedical Research Centre for Mental Health at the South
London; Maudsley NHS Foundation Trust; Institute of Psychiatry, King's
College London; Postdoctoral Marie Curie Intra-European Fellowship with
the 7th European Framework Programme; European Commission
[LSHB-CT-2003-503428]; Swiss National Science Foundation [3200B0-105993,
3200B0-118308, 33CSCO-122661]; GlaxoSmithKline (Psychiatry Center of
Excellence for Drug Discovery and Genetics Division, Drug
Discovery-Verona, RD)
FX This study was funded by a joint grant from the U.K. Medical Research
Council and GlaxoSmithKline (G0701420), the Erwin-Schroedinger
Fellowship (J2647) of the Austrian Science Funds (to Dr. Schosser), and
by financial support from 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. Dr. Rivera is funded by a
Postdoctoral Marie Curie Intra-European Fellowship with the 7th European
Framework Programme. The GENDEP study was funded by a European
Commission Framework 6 grant, EC Contract Ref.: LSHB-CT-2003-503428. The
population-based study in Lausanne was supported by three grants from
the Swiss National Science Foundation (#3200B0-105993, #3200B0-118308,
#33CSCO-122661) and from GlaxoSmithKline (Psychiatry Center of
Excellence for Drug Discovery and Genetics Division, Drug
Discovery-Verona, R&D).
NR 45
TC 123
Z9 125
U1 1
U2 19
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD AUG
PY 2010
VL 167
IS 8
BP 949
EP 957
DI 10.1176/appi.ajp.2010.09091380
PG 9
WC Psychiatry
SC Psychiatry
GA 634OS
UT WOS:000280593400012
PM 20516156
ER
PT J
AU Fee, E
AF Fee, Elizabeth
TI Samuel Hopkins Adams (1871-1958): Journalist and Muckraker
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
C1 [Fee, Elizabeth] NIH, Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA.
RP Fee, E (reprint author), NIH, Natl Lib Med, Hist Med Div, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM elizabeth_fee@nlm.nih.gov
NR 3
TC 0
Z9 0
U1 0
U2 3
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD AUG
PY 2010
VL 100
IS 8
BP 1390
EP 1391
DI 10.2105/AJPH.2009.186452
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 656RR
UT WOS:000282354800011
PM 20558787
ER
PT J
AU Roth, GA
Fee, E
AF Roth, Ginny A.
Fee, Elizabeth
TI The United Nations and Global Health
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Editorial Material
C1 [Roth, Ginny A.; Fee, Elizabeth] NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20892 USA.
RP Roth, GA (reprint author), NIH, Hist Med Div, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 1
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD AUG
PY 2010
VL 100
IS 8
BP 1392
EP 1392
DI 10.2105/AJPH.2009.187195
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 656RR
UT WOS:000282354800012
PM 20558786
ER
PT J
AU Romero, R
Kadar, N
Vaisbuch, E
Hassan, SS
AF Romero, Roberto
Kadar, Nicholas
Vaisbuch, Edi
Hassan, Sonia S.
TI Maternal Death Following Cardiopulmonary Collapse After Delivery:
Amniotic Fluid Embolism or Septic Shock Due to Intrauterine Infection?
SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
LA English
DT Review
DE Bacteremia; cardiorespiratory arrest; chorioamnionitis; disseminated
intravascular coagulation; fever; intraamniotic infection; pregnancy;
preterm labor; tumor necrosis factor-alpha
ID TUMOR-NECROSIS-FACTOR; POLYMERASE-CHAIN-REACTION; RECURRENT
SPONTANEOUS-ABORTION; SERUM CYTOKINE LEVELS; C-REACTIVE PROTEIN; PRETERM
LABOR; SEVERE SEPSIS; FACTOR-ALPHA; HEMODYNAMIC-ALTERATIONS;
PULMONARY-EMBOLISM
AB Problem
The amniotic fluid embolism (AFE) syndrome is a catastrophic complication of pregnancy frequently associated with maternal death. The causes and mechanisms of disease responsible for this syndrome remain elusive.
Method of study
We report two cases of maternal deaths attributed to AFE: (1) one woman presented with spontaneous labor at term, developed intrapartum fever, and after delivery had sudden cardiovascular collapse and disseminated intravascular coagulation (DIC), leading to death; (2) another woman presented with preterm labor and foul-smelling amniotic fluid, underwent a Cesarean section for fetal distress, and also had postpartum cardiovascular collapse and DIC, leading to death.
Results
Of major importance is that in both cases, the maternal plasma concentration of tumor necrosis factor-alpha at the time of admission to the hospital and when patients had no clinical evidence of infection was in the lethal range (a lethal range is considered to be above 0.1 ng/mL).
Conclusion
We propose that subclinical intraamniotic infection may be a cause of postpartum cardiovascular collapse and DIC and resemble AFE. Thus, some patients with the clinical diagnosis of AFE may have infection/systemic inflammation as a mechanism of disease. These observations have implications for the understanding of the mechanisms of disease of patients who develop cardiovascular collapse and DIC, frequently attributed to AFE. It may be possible to identify a subset of patients who have biochemical and immunological evidence of systemic inflammation at the time of admission, and before a catastrophic event occurs.
C1 [Romero, Roberto] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp,Detroit Med Ctr, Detroit, MI 48201 USA.
[Romero, Roberto; Vaisbuch, Edi; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Romero, Roberto; Vaisbuch, Edi; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
[Vaisbuch, Edi; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Sch Med, Detroit, MI 48201 USA.
RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp,Detroit Med Ctr, 3990 John R,POB 4, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu
OI Vaisbuch, Edi/0000-0002-8400-9031
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development,; NIH; DHHS; Wayne State University School of Medicine;
Detroit Medical Center
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, NIH, DHHS, by the Wayne State University School of
Medicine and the Detroit Medical Center.
NR 134
TC 14
Z9 15
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1046-7408
EI 1600-0897
J9 AM J REPROD IMMUNOL
JI Am. J. Reprod. Immunol.
PD AUG
PY 2010
VL 64
IS 2
BP 113
EP 125
DI 10.1111/j.1600-0897.2010.00823.x
PG 13
WC Immunology; Reproductive Biology
SC Immunology; Reproductive Biology
GA 621UQ
UT WOS:000279610700006
PM 20236259
ER
PT J
AU Xu, Y
Madsen-Bouterse, SA
Romero, R
Hassan, S
Mittal, P
Elfline, M
Zhu, AP
Petty, HR
AF Xu, Yi
Madsen-Bouterse, Sally A.
Romero, Roberto
Hassan, Sonia
Mittal, Pooja
Elfline, Megan
Zhu, Aiping
Petty, Howard R.
TI Leukocyte Pyruvate Kinase Expression is Reduced in Normal Human
Pregnancy but not in Pre-eclampsia
SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
LA English
DT Article
DE Lymphocytes; neutrophils; signaling
ID AMINO-ACID-CONCENTRATIONS; PERIPHERAL-BLOOD LEUKOCYTES; T-CELL
DIFFERENTIATION; METABOLIC CHARACTERISTICS; ENDOCRINE MILIEU;
HUMAN-FETUS; NEUTROPHILS; FETAL; GRANULOCYTES; ACTIVATION
AB Problem
Emerging evidence suggests that metabolism influences immune cell signaling and immunoregulation. To examine the immunoregulatory role of glycolysis in pregnancy, we evaluated the properties of pyruvate kinase in leukocytes from non-pregnant women and those with normal pregnancy and pre-eclampsia.
Method of study
We evaluated pyruvate kinase expression in lymphocytes and neutrophils from non-pregnant, pregnant, and pre-eclampsia patients using fluorescence microscopy and flow cytometry. Leukocyte pyruvate kinase activity and pyruvate concentrations were also evaluated. To study pyruvate's effect on signaling, we labeled Jurkat T cells with Ca2+ dyes and measured cell responses in the presence of agents influencing intracellular pyruvate.
Results
The expression of pyruvate kinase is reduced in lymphocytes and neutrophils from normal pregnant women in comparison with those of non-pregnant women and pre-eclampsia patients. Similarly, the activity of pyruvate kinase and the intracellular pyruvate concentration are reduced in leukocytes of normal pregnant women in comparison with non-pregnant women and women with pre-eclampsia. Using Jurkat cells as a model of leukocyte signaling, we have shown that perturbations of intracellular pyruvate influence Ca2+ signals.
Conclusion
Normal pregnancy is characterized by reduced pyruvate kinase expression within lymphocytes and neutrophils. We speculate that reduced pyruvate kinase expression modifies immune cell responses due to reduced pyruvate concentrations.
C1 [Elfline, Megan; Zhu, Aiping; Petty, Howard R.] Univ Michigan, Sch Med, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA.
[Xu, Yi; Romero, Roberto; Hassan, Sonia; Mittal, Pooja] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Madsen-Bouterse, Sally A.; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Div Intramural Res, NIH, Bethesda, MD USA.
[Madsen-Bouterse, Sally A.; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Div Intramural Res, NIH, Detroit, MI USA.
[Romero, Roberto] Wayne State Univ, Hutzel Womens Hosp, Detroit Med Ctr, Ctr Mol Med & Genet, Detroit, MI USA.
[Petty, Howard R.] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48105 USA.
RP Petty, HR (reprint author), Univ Michigan, Sch Med, Dept Ophthalmol & Visual Sci, 1000 Wall St, Ann Arbor, MI 48105 USA.
EM hpetty@umich.edu
FU Division of Intramural Research of the Eunice Kennedy Schriver National
Institute of Child Health and Human Development; NIH; DHHS;
[N01-HD-2-3342]; [WSU04055]
FX This work was supported, in part, by the Division of Intramural Research
of the Eunice Kennedy Schriver National Institute of Child Health and
Human Development, NIH, DHHS, contract number N01-HD-2-3342 and
subcontract WSU04055. We thank L. Nikita for assistance in recruiting
patients.
NR 78
TC 5
Z9 5
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1046-7408
J9 AM J REPROD IMMUNOL
JI Am. J. Reprod. Immunol.
PD AUG
PY 2010
VL 64
IS 2
BP 137
EP 151
DI 10.1111/j.1600-0897.2010.00881.x
PG 15
WC Immunology; Reproductive Biology
SC Immunology; Reproductive Biology
GA 621UQ
UT WOS:000279610700008
PM 20560913
ER
PT J
AU Draper, DW
Madenspacher, JH
Dixon, D
King, DH
Remaley, AT
Fessler, MB
AF Draper, David W.
Madenspacher, Jennifer H.
Dixon, Darlene
King, Debra H.
Remaley, Alan T.
Fessler, Michael B.
TI ATP-binding Cassette Transporter G1 Deficiency Dysregulates Host Defense
in the Lung
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE ATP binding cassette G1; cholesterol; innate immunity; lung; pneumonia
ID PULMONARY ALVEOLAR PROTEINOSIS; TUMOR-NECROSIS-FACTOR;
NIEMANN-PICK-DISEASE; LIVER-X-RECEPTOR; HUMAN MACROPHAGES; INNATE
IMMUNITY; ABCG1; CHOLESTEROL; INFLAMMATION; MICE
AB Rationale: Mice with genetic deletion of the cholesterol efflux transporter, ATP-binding cassette (ABC) G1, have pulmonary lipidosis and chronic pulmonary inflammation. Whether ABCG1 regulates host defense is unknown.
Objectives: To determine whether ABCG1 regulates pulmonary innate immunity and host defense, and to investigate the underlying molecular/cellular mechanisms.
Methods: Abcg1(+/-) and Abcg1(-/-) mice were challenged with intrapulmonary lipopolysaccharide (LPS) or Klebsiella pneumoniae, intravenous K pneumoniae, or intra peritoneal LPS. Phenotypic responses were profiled Bone marrow chimeras and in vitro assays were used to differentiate and characterize the role of hematopoietic versus nonhematopoietic ABCG1 in host defense.
Measurements and Main Results: Unexposed Abcg1(-/-) mice had normal numbers of circulating neutrophils, but increased neutrophil recruitment to the airspace and lung parenchyma, and increased airspace cytokines and chemokines in the steady state. After intrapulmonary LPS or K. pneumoniae, Abcg1(-/-) mice displayed exaggerated further neutrophil recruitment to and degranulation in the airspace, and elevated airspace cytokine/chemokine induction. Alveolar macrophage ABCG1 was critical, as ABCG1 deficiency in hematopoietic cells was sufficient to enhance responses in vivo, and Abcg1(-/-) alveolar macrophages adopted a "foam cell" phenotype, and were hyperresponsive ex vivo. Pulmonary compartmentalization and clearance of K pneumoniae were increased in Abcg1-/- mice, indicating enhanced host defense. By contrast, Abcg1(+/+) and Abcg1(-/-) mice had equivalent responses to intravenous K pneumoniae and intraperitoneal LPS, suggesting that ABCG1 regulates innate immunity in a tissue-selective manner.
Conclusions: Abcgl1 (/-) mice have an enhanced pulmonary host defense response driven predominantly by hematopoietic cells.
C1 [Draper, David W.; Madenspacher, Jennifer H.; Fessler, Michael B.] Natl Inst Environm Hlth Sci, Lab Resp Biol, Res Triangle Pk, NC 27709 USA.
[Dixon, Darlene; King, Debra H.] Natl Inst Environm Hlth Sci, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA.
[Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, Pulm & Vasc Med Branch, Bethesda, MD 20892 USA.
RP Fessler, MB (reprint author), Natl Inst Environm Hlth Sci, Lab Resp Biol, 111 T W Alexander Dr,POB 12233,MD D2-01, Res Triangle Pk, NC 27709 USA.
FU National Institutes of Health, National Institute of Environmental
Health Sciences [Z01 ES102005]
FX Supported in part by Intramural Research Program of the National
Institutes of Health, National Institute of Environmental Health
Sciences grant; D W D is an employee of the National Institutes of
Health (NIH) I H M does not have a financial relationship with a
commercial entity that has an interest in the subject of this manuscript
D D does not have a financial relationship with a commercial entity that
has an interest in the subject of this manuscript D H K does not have a
financial relationship with a commercial entity that has an interest in
the subject of this manuscript AT R received more than 8100,001 from
KineMed Inc for a peptide drug development project-NIH-approved
cooperative research agreement (CRADA), $5,001-$10,000 from AlphaCore
Pharma for a recombinant Lecithin-cholesterol acyltransferase
development project-NIB-approved CRADA, and $5,001-$10,000 from VirxSys
Inc for a trans-splicing gene delivery project-NIH-approved CRADA M B F
does not have a financial relationship with a commercial entity that has
an interest in the subject of this manuscriptZ01 ES102005
NR 36
TC 16
Z9 18
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD AUG 1
PY 2010
VL 182
IS 3
BP 404
EP 412
DI 10.1164/rccm.200910-1580OC
PG 9
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 635ZP
UT WOS:000280697400016
PM 20395559
ER
PT J
AU Cesta, MF
Ryman-Rasmussen, JP
Wallace, DG
Masinde, T
Hurlburt, G
Taylor, AJ
Bonner, JC
AF Cesta, Mark F.
Ryman-Rasmussen, Jessica P.
Wallace, Duncan G.
Masinde, Tiwanda
Hurlburt, Geoffrey
Taylor, Alexia J.
Bonner, James C.
TI Bacterial Lipopolysaccharide Enhances PDGF Signaling and Pulmonary
Fibrosis in Rats Exposed to Carbon Nanotubes
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
DE carbon nanotubes; inflammation; lipopolysaccharide; fibrosis; growth
factors
ID GROWTH FACTOR-AA; ALVEOLAR MACROPHAGES; LUNG FIBROBLASTS; AIRWAY
DISEASE; INTRATRACHEAL INSTILLATION; CHRYSOTILE ASBESTOS;
GENE-EXPRESSION; RECEPTOR-ALPHA; INHALATION; MICE
AB Engineered multi-walled carbon nanotubes (MWCNT) represent a possible health risk for pulmonary fibrosis due to their fiber-like shape and potential for persistence in the lung. We postulated that bacterial lipopolysaccharide (LPS), a ubiquitous agent in the environment that causes lung inflammation, would enhance fibrosis caused by MWCNT. Rats were exposed to LPS and then intratracheally instilled with MWCNT or carbon black (CB) nanoparticles 24 hours later. Pulmonary fibrosis was observed 21 days after MWCNT exposure, but not with CB. LPS alone caused no fibrosis but enhanced MWCNT-induced fibrosis. LPS plus CB did not significantly increase fibrosis. MWCNT increased platelet-derived growth factor-AA (PDGF-AA), a major mediator of fibrosis. PDGF-AA production in response to MWCNT, but not CB, was synergistically enhanced by LPS. Immunostaining showed PDGF-AA in bronchiolar epithelial cells and macrophages. Since macrophages engulfed MWCNT, were positive for PDGF-AA, and mediate fibroblast responses, experiments were performed with rat lung macrophages (NR8383 cells) and rat lung fibroblasts in vitro. LPS exposure increased PDGF-A mRNA levels in NR8383 cells and enhanced MWCNT-induced PDGF-A m RNA levels. Moreover, LPS increased MWCNT- or CB-induced PDGF receptor-alpha (PDGF-R alpha) mRNA in fibroblasts. Our data suggest that LPS exacerbates MWCNT-induced lung fibrosis by amplifying production of PDGF-AA in macrophages and epithelial cells, and by increasing PDGF-R alpha on pulmonary fibroblasts. Our findings also suggest that individuals with pre-existing pulmonary inflammation are at greater risk for the potential adverse effects of MWCNT.
C1 [Cesta, Mark F.; Ryman-Rasmussen, Jessica P.; Taylor, Alexia J.; Bonner, James C.] N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA.
[Cesta, Mark F.; Ryman-Rasmussen, Jessica P.; Wallace, Duncan G.; Bonner, James C.] Hamner Inst Hlth Sci, Res Triangle Pk, NC USA.
[Cesta, Mark F.; Masinde, Tiwanda] NIEHS, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA.
[Hurlburt, Geoffrey] Pathology Associates, Charles River Labs, Durham, NC USA.
RP Bonner, JC (reprint author), N Carolina State Univ, Dept Environm & Mol Toxicol, POB 7633, Raleigh, NC 27695 USA.
EM james_bonner@ncsu.edu
FU American Chemistry Council's Long-Range Research Initiative; NIH
[R21-ES015801-01, RC2 ES018772-01]; North Carolina State University's
College of Agricultural and Life Sciences; National Institutes of
Health, National Institute of Environmental Health Sciences
FX This work was supported by The American Chemistry Council's Long-Range
Research Initiative program provided to The Hamner Institutes for Health
Sciences, NIH Grant R21-ES015801-01 and NIH Grant RC2 ES018772-01 to
J.B.; North Carolina State University's College of Agricultural and Life
Sciences; and the Intramural Research Program of the National Institutes
of Health, National Institute of Environmental Health Sciences.
NR 35
TC 37
Z9 39
U1 2
U2 7
PU AMER THORACIC SOC
PI NEW YORK
PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA
SN 1044-1549
J9 AM J RESP CELL MOL
JI Am. J. Respir. Cell Mol. Biol.
PD AUG
PY 2010
VL 43
IS 2
BP 142
EP 151
DI 10.1165/rcmb.2009-0113OC
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA 634YV
UT WOS:000280623100004
PM 19738159
ER
PT J
AU Galgano, MT
Castle, PE
Atkins, KA
Brix, WK
Nassau, SR
Stoler, MH
AF Galgano, Mary T.
Castle, Philip E.
Atkins, Kristen A.
Brix, William K.
Nassau, Sarah R.
Stoler, Mark H.
TI Using Biomarkers as Objective Standards in the Diagnosis of Cervical
Biopsies
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE CIN; HPV; p16; Ki-67; interobserver; biomarker
ID HUMAN-PAPILLOMAVIRUS DNA; ASCUS-LSIL TRIAGE; INTRAEPITHELIAL NEOPLASIA;
P16(INK4A) IMMUNOHISTOCHEMISTRY; LESIONS; RISK; CANCER; REGRESSION;
IMPACT; COHORT
AB Histopathologic diagnosis of cervical biopsies determines clinical management of patients with an abnormal cervical cancer-screening test yet is prone to poor interobserver reproducibility. Immunohistochemical staining for biomarkers related to the different stages of cervical carcinogenesis may provide objective standards to reduce diagnostic variability of cervical biopsy evaluations but systematic, rigorous evaluations of their potential clinical utility are lacking. To address diagnostic utility of human papillomavirus (HPV) L1, p16(INK4a), and Ki-67 immunohistochemical staining for improving diagnostic accuracy, we conducted a community-based and population-based evaluation using 1455 consecutive cervical biopsies submitted to the Department of Pathology at the University of Virginia during a period of 14 months. Thin-sections of each biopsy from 1451 of 1455 (99.7%) biopsies underwent evaluation of immunohistochemical stains for the 3 biomarkers, masked to the original diagnosis, and the results were compared with an adjudicated, consensus diagnosis by 3 pathologists. p16(INK4a) immunostaining, using the strongest staining as the cutpoint, was 86.7% sensitive and 82.8% specific for cervical intraepithelial neoplasia (CIN) grade 2 or more severe (CIN2(+)) diagnoses. The performance of p16(INK4a) was more sensitive (P < 0.001), less specific (P < 0.001), and of similar overall accuracy for CIN2(+) compared with the combined performance of all pathologist reviews in routine clinical diagnostic service (sensitivity = 68.9%, specificity = 97.2%). Ki-67 immunostaining was also strongly associated with a CIN2(+) diagnosis but its performance at all staining intensities was inferior to p16(INK4a) immunostaining, and did not increase the accuracy of CIN2(+) diagnosis when combined with p16(INK4a) immunostaining compared with p16(INK4a) immunostaining alone. We found no utility for L1 immunostaining in distinguishing between CIN and non-CIN. In conclusion, with a rigorous evaluation, we found immunohistochemical staining for p16INK4a to be a useful and reliable diagnostic adjunct for distinguishing biopsies with and without CIN2(+).
C1 [Galgano, Mary T.; Atkins, Kristen A.; Brix, William K.; Nassau, Sarah R.; Stoler, Mark H.] Univ Virginia Hlth Syst, Robert E Fechner Lab Surg Pathol, Charlottesville, VA 22908 USA.
[Castle, Philip E.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
RP Stoler, MH (reprint author), Univ Virginia Hlth Syst, Robert E Fechner Lab Surg Pathol, 1215 Lee St,HEP Room 3032, Charlottesville, VA 22908 USA.
EM mhs2e@virginia.edu
FU NIH, National Cancer Institute
FX Dr Castle was supported by the Intramural Research Program of the NIH,
National Cancer Institute. Antibodies for the detection of
p16INK4a were donated by mtm laboratories AG (Heidelberg,
Germany) and for the detection of L1 capsid protein by Cytoimmun
Diagnostics (Pirmasens, Germany). Dr Stoler serves as consultant for mtm
laboratories. In addition, Dr Stoler has been a consultant in clinical
trial and HPV DNA test development for Third Wave, Hologic, Qiagen,
Roche Molecular Systems, and Gen-Probe.
NR 30
TC 108
Z9 115
U1 2
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0147-5185
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD AUG
PY 2010
VL 34
IS 8
BP 1077
EP 1087
DI 10.1097/PAS.0b013e3181e8b2c4
PG 11
WC Pathology; Surgery
SC Pathology; Surgery
GA 631TV
UT WOS:000280372900001
PM 20661011
ER
PT J
AU Springman, SR
Andrei, AC
Willmann, K
Rusy, DA
Warren, ME
Han, S
Lee, M
AF Springman, S. R.
Andrei, A. -C.
Willmann, K.
Rusy, D. A.
Warren, M. E.
Han, S.
Lee, M.
TI A comparison of SNAP II (c) and bispectral index monitoring in patients
undergoing sedation
SO ANAESTHESIA
LA English
DT Article
ID AUDITORY-EVOKED POTENTIALS; PROPOFOL SEDATION; ANESTHESIA; DEPTH;
COLONOSCOPY; ENDOSCOPY; AWARENESS; ENTROPY; LEVEL
AB P>Clinical signs and patients' verbal responses have traditionally been used to assess patients' comfort and the depth of sedation. Recently, level-of-consciousness monitors have been used to guide sedation. The SNAP II(C) is a single-lead electroencephalogram device that displays a SNAP(C) Index - a derived value based on both high and low frequency electroencephalogram signals. Much of the current clinical research on monitoring during sedation involves the bispectral index monitor. We compared simultaneous readings recorded by the SNAP II and bispectral index during sedation in 51 consecutive patients undergoing surgery. The anaesthesia team was blinded to the SNAP II and bispectal index values. Concurrent SNAP II and bispectral index readings displayed similarly-shaped trajectories during sedation, but further studies are needed to establish the routine clinical utility of both these monitors.
C1 [Andrei, A. -C.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53706 USA.
[Springman, S. R.; Willmann, K.; Rusy, D. A.; Warren, M. E.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Anesthesiol, Madison, WI USA.
[Han, S.] Univ Wisconsin, Dept Stat, Madison, WI 53706 USA.
[Lee, M.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
RP Andrei, AC (reprint author), Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53706 USA.
EM andrei@biostat.wisc.edu
FU NIH [P30 CA014520-33, UL1 RR025011]; Everest Biomedical Instruments Co
Inc., Fenton, MO, USA
FX Adin-Cristian Andrei's research is supported in part by the following
NIH grants: P30 CA014520-33 and UL1 RR025011. The authors have also
received a grant from Everest Biomedical Instruments Co Inc., Fenton,
MO, USA, providing support for the institutional research nurse and the
SNAP II module and electrodes. The company was not involved in the
design of the study, the collection or analysis of the data, or the
writing of the manuscript, which it has not reviewed.
NR 30
TC 4
Z9 4
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0003-2409
J9 ANAESTHESIA
JI Anaesthesia
PD AUG
PY 2010
VL 65
IS 8
BP 815
EP 819
DI 10.1111/j.1365-2044.2010.06408.x
PG 5
WC Anesthesiology
SC Anesthesiology
GA 620WX
UT WOS:000279533800010
PM 20586747
ER
PT J
AU Zhu, AP
Romero, R
Petty, HR
AF Zhu, Aiping
Romero, Roberto
Petty, Howard R.
TI Amplex UltraRed enhances the sensitivity of fluorimetric pyruvate
detection
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Editorial Material
ID HYDROGEN-PEROXIDE
AB Pyruvate, which is produced in the final step of glycolysis, participates in anabolic metabolism, catabolic metabolism, and signal transduction. We have recently reported a new sensitive and selective fluorimetric assay for pyruvate measurement using Amplex Red as a fluorogenic dye. However, the fluorescence of the reaction product, resorufin, is pH dependent, which limits the sensitivity of the assay at pH 6.7. In this Note, we evaluate lnvitrogen's new dye, Amplex UltraRed, as a fluorogenic agent for pyruvate determination. Our results show that Amplex UltraRed improves the performance of the assay, providing brighter fluorescence and enhanced sensitivity. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Zhu, Aiping; Petty, Howard R.] Univ Michigan, Sch Med, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA.
[Romero, Roberto] Eunice Kennedy Shriver NICHHD, Perinatol Res Branch, Div Intramural Res, NICHD,NIH, Bethesda, MD USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
[Romero, Roberto] Hutzel Womens Hosp, Detroit Med Ctr, Detroit, MI 48201 USA.
[Petty, Howard R.] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48105 USA.
RP Petty, HR (reprint author), Univ Michigan, Sch Med, Dept Ophthalmol & Visual Sci, 1000 Wall St, Ann Arbor, MI 48105 USA.
EM hpetty@umich.edu
FU Intramural NIH HHS [Z01 HD002400-17]; NICHD NIH HHS [N01-HD-2-3342]; PHS
HHS [WSU04055]
NR 9
TC 12
Z9 12
U1 4
U2 18
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0003-2697
J9 ANAL BIOCHEM
JI Anal. Biochem.
PD AUG
PY 2010
VL 403
IS 1-2
BP 123
EP 125
DI 10.1016/j.ab.2010.04.008
PG 3
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 611EJ
UT WOS:000278793800019
PM 20382105
ER
PT J
AU Deans, KJ
Minneci, PC
Danner, RL
Eichacker, PQ
Natanson, C
AF Deans, Katherine J.
Minneci, Peter C.
Danner, Robert L.
Eichacker, Peter Q.
Natanson, Charles
TI Practice Misalignments in Randomized Controlled Trials: Identification,
Impact, and Potential Solutions
SO ANESTHESIA AND ANALGESIA
LA English
DT Review
ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; PLACEBO-CONTROLLED
TRIALS; CRITICALLY-ILL PATIENTS; CLINICAL-TRIAL; MECHANICAL VENTILATION;
CRITICAL-CARE; TRANSFUSION; STRATEGIES; DESIGN
AB Appropriate control group selection in a randomized controlled trial (RCT) is a critical factor in generating results, which are both interpretable and generalizable. Control groups ideally encompass and realistically reflect prevailing medical practices. This goal can be challenging in investigations of standard therapies that are routinely titrated. To eliminate the heterogeneity in clinical practice from the trial design, recent investigations of titrated therapies have randomized patients to fixed-dose regimens. Although this approach may produce statistically significant differences, the results may not be interpretable or generalizable.
In this trial design, randomization disrupts the normal relationship between clinically important characteristics and therapy titration, thereby creating subgroups of patients within each study arm that receive levels of therapy inconsistent with current practices outside of the clinical study. These misaligned subgroups may have worse outcomes than usual care. Practice misalignments can occur in any clinical trial of a preexisting therapy that is typically adjusted based on severity of illness or other patient characteristics.
In this study, we review three recent RCTs to demonstrate how practice misalignments can affect the safety, results, and conclusions of RCTs. Furthermore, we discuss methods to prospectively identify potentially important relationships between therapy titration and patient- and disease-specific characteristics. Finally, we review trial design options that may minimize the occurrence and impact of practice misalignments. Because these designs may limit the feasibility of a clinical trial, a thorough characterization of usual care is necessary to determine whether one of these designs should be used to protect patient safety. (Anesth Analg 2010;111:444-50)
C1 [Deans, Katherine J.] Childrens Hosp Philadelphia, Dept Surg, Childrens Inst Surg Sci, Abramson Res Ctr, Philadelphia, PA 19104 USA.
[Minneci, Peter C.] Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA.
[Danner, Robert L.; Eichacker, Peter Q.; Natanson, Charles] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
RP Deans, KJ (reprint author), Childrens Hosp Philadelphia, Dept Surg, Childrens Inst Surg Sci, Abramson Res Ctr, Rm 1116,34th St & Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM deansk@email.chop.edu
FU Intramural Research Division of the Critical Care Medicine Department,
Clinical Center at the NIH; NHLBI [K22HL089041-01]
FX Supported by the Intramural Research Division of the Critical Care
Medicine Department, Clinical Center at the NIH, and by extramural NHLBI
grant # K22HL089041-01.
NR 23
TC 15
Z9 15
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-2999
J9 ANESTH ANALG
JI Anesth. Analg.
PD AUG
PY 2010
VL 111
IS 2
BP 444
EP 450
DI 10.1213/ane.0b013e3181aa8903
PG 7
WC Anesthesiology
SC Anesthesiology
GA 633CZ
UT WOS:000280478400031
PM 19820238
ER
PT J
AU Deans, KJ
Minneci, P
Eichacker, PQ
Danner, RL
Natanson, C
AF Deans, Katherine J.
Minneci, Peter
Eichacker, Peter Q.
Danner, Robert L.
Natanson, Charles
TI Walk a Mile in Whose Shoes?
SO ANESTHESIA AND ANALGESIA
LA English
DT Letter
C1 [Deans, Katherine J.; Minneci, Peter] Childrens Hosp Philadelphia, Childrens Inst Surg Sci, Dept Surg, Philadelphia, PA 19104 USA.
[Minneci, Peter] Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA.
[Eichacker, Peter Q.; Danner, Robert L.; Natanson, Charles] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
RP Deans, KJ (reprint author), Childrens Hosp Philadelphia, Childrens Inst Surg Sci, Dept Surg, Philadelphia, PA 19104 USA.
EM cnatanson@nih.gov
NR 5
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-2999
J9 ANESTH ANALG
JI Anesth. Analg.
PD AUG
PY 2010
VL 111
IS 2
BP 576
EP 577
DI 10.1213/ANE.0b013e3181e63976
PG 2
WC Anesthesiology
SC Anesthesiology
GA 633CZ
UT WOS:000280478400050
PM 20664096
ER
PT J
AU Beydoun, HA
Al-Sahab, B
Beydoun, MA
Tamim, H
AF Beydoun, Hind A.
Al-Sahab, Ban
Beydoun, May A.
Tamim, Hala
TI Intimate Partner Violence as a Risk Factor for Postpartum Depression
Among Canadian Women in the Maternity Experience Survey
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
DE Intimate Partner Violence; Postpartum Depression; Pregnancy; Survey
ID POSTTRAUMATIC-STRESS-DISORDER; 18 US STATES/TERRITORIES;
AFRICAN-AMERICAN WOMEN; DOMESTIC VIOLENCE; PHYSICAL VIOLENCE;
PREGNANT-WOMEN; POSTNATAL DEPRESSION; HEALTH CONSEQUENCES; CHINESE
COMMUNITY; PRETERM BIRTH
AB PURPOSE: Intimate partner violence is a worldwide public health concern that predominantly affects women of reproductive age. The purpose of this study was to evaluate the effect of exposure to intimate partner violence before, during, or after pregnancy on postpartum depression in a nationally representative sample of Canadian women.
METHODS: A cross-sectional analysis was performed with the use of data from the Maternity Experience Survey conducted by Statistics Canada in 2006. A population-based sample of 8542 women 15 years and older who delivered singleton live births was selected from all Canadian provinces and territories; of those, 6421 completed a computer-assisted telephone interview. Recent experiences with and threats of physical or sexual violence by in intimate partner were examined in relation to postpartum depression assessed through the Edinburgh Postpartum Depression Scale.
RESULTS: The prevalence of postpartum depression was 7.5% (95% confidence interval, 6.8-8.2). Controlling for confounders, odds of postpartum depression were significantly greater among women who reported partner violence in the past two years as opposed to those who did not (adjusted odds ratio 1.61; 95% confidence interval, 1.06-2.45).
CONCLUSIONS: Intimate partner violence is positively associated with postpartum depression among Canadian women. Implications for healthcare practice are discussed. Aim Epidemiol 2010;20:575-583. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA.
[Al-Sahab, Ban; Tamim, Hala] York Univ, Sch Kinesiol & Hlth Sci, Toronto, ON M3J 2R7, Canada.
[Beydoun, May A.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
RP Beydoun, HA (reprint author), Eastern Virginia Med Sch, Grad Program Publ Hlth, 700 W Olney Rd,POB 1980, Norfolk, VA 23501 USA.
EM baydouha@evms.edu
FU NIH, National Institute on Aging
FX This research was supported in part by the intramural research program
of the NIH, National Institute on Aging.
NR 79
TC 36
Z9 38
U1 9
U2 18
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 AUG
PY 2010
VL 20
IS 8
BP 575
EP 583
DI 10.1016/j.annepidem.2010.05.011
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 628PC
UT WOS:000280131600001
PM 20609336
ER
PT J
AU Sorlie, PD
Aviles-Santa, LM
Wassertheil-Smoller, S
Kaplan, RC
Daviglus, ML
Giachello, AL
Schneiderman, N
Raij, L
Talavera, G
Allison, M
Lavange, L
Chambless, LE
Heiss, G
AF Sorlie, Paul D.
Aviles-Santa, Larissa M.
Wassertheil-Smoller, Sylvia
Kaplan, Robert C.
Daviglus, Martha L.
Giachello, Aida L.
Schneiderman, Neil
Raij, Leopoldo
Talavera, Gregory
Allison, Matthew
Lavange, Lisa
Chambless, Lloyd E.
Heiss, Gerardo
TI Design and Implementation of the Hispanic Community Health Study/Study
of Latinos
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
DE Epidemiologic Methods; Cardiovascular Disease; Risk Factors; Hispanics;
Acculturation
ID MORTALITY; PARTICIPANTS; PARADOX
AB PURPOSE: The Hispanic Community Health Study (HCHS)/Study of Latinos (SOL) is a comprehensive multicenter community based cohort study of Hispanics/Latinos in the United States.
METHODS: The Study rationale, objectives, design, and implementation are described in this report.
RESULTS: The HCHS/SOL will recruit 16,000 men and women who self-identify as Hispanic or Latino, 18 to 74 years of age, from a random sample of households in defined communities in the Bronx, Chicago, Miami, and San Diego. The sites were selected so that the overall sample would consist of at least 2000 persons in each of the following origin designations: Mexican, Puerto Rican and Dominican, Cuban, and Central and South American. The study includes research in the prevalence of and risk factors for heart, lung, blood and sleep disorders, kidney and liver function, diabetes, cognitive function, dental conditions, and hearing disorders.
CONCLUSIONS: The HCHS/SOL will (1) characterize the health status and disease burden in the largest minority population in the United Stares; (2) describe the positive and negative consequences of immigration and acculturation of Hispanics/Latinos to the mainstream United States life-styles, environment and health care opportunities; and (3) identify likely causal factors of many diseases in a population with diverse environmental exposures, genetic backgrounds, and early life experiences. Ann Epidemiol 2010;20:629-641. Published by Elsevier Inc.
C1 [Sorlie, Paul D.] NHLBI, Epidemiol Branch, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Wassertheil-Smoller, Sylvia; Kaplan, Robert C.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Daviglus, Martha L.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Giachello, Aida L.] Univ Illinois Chicago, Midw Latino Hlth Res Training & Policy Ctr, Chicago, IL USA.
[Schneiderman, Neil] Univ Miami, Dept Psychol, Miami, FL USA.
[Raij, Leopoldo] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Talavera, Gregory] San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA.
[Allison, Matthew] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Chambless, Lloyd E.; Heiss, Gerardo] Univ N Carolina, Dept Biostat, Collaborat Studies Coordinating Ctr, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
RP Sorlie, PD (reprint author), NHLBI, Epidemiol Branch, Div Cardiovasc Sci, NIH, 6701 Rockledge Dr,Room 10210,MSC 7936, Bethesda, MD 20892 USA.
EM Sorlie@mail.nih.gov
RI Kaplan, Robert/A-2526-2011;
OI Allison, Matthew/0000-0003-0777-8272
FU National Heart, Lung, and Blood Institute (NHLBI) to the University of
North Carolina [N01-HC65233]; University of Miami [N01-HC65234]; Albert
Einstein College of Medicine [N01-HC65235]; Northwestern University
[N01-HC65236]; San Diego State University [N01-HC65237]; NHLBI: National
Center on Minority Health and Health Disparities; National Institute of
Deafness and Other Communications Disorders; National Institute of
Dental and Craniofacial Research; National Institute of Diabetes and
Digestive and Kidney Diseases; National Institute of Neurological
Disorders and Stroke; Office of Dietary Supplements
FX The Hispanic Community Health Study/Study of Latinos was supported by
contracts from the National Heart, Lung, and Blood Institute (NHLBI) to
the University of North Carolina (N01-HC65233), University of Miami
(N01-HC65234), Albert Einstein College of Medicine (N01-HC65235),
Northwestern University (N01-HC65236), and San Diego State University
(N01-HC65237). The following Institutes/Centers/Offices contribute to
the HCHS/SOL through a transfer of funds to the NHLBI: National Center
on Minority Health and Health Disparities, the National Institute of
Deafness and Other Communications Disorders, the National Institute of
Dental and Craniofacial Research, the National Institute of Diabetes and
Digestive and Kidney Diseases, the National Institute of Neurological
Disorders and Stroke, and the Office of Dietary Supplements.
NR 16
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U1 1
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1047-2797
J9 ANN EPIDEMIOL
JI Ann. Epidemiol.
PD AUG
PY 2010
VL 20
IS 8
BP 629
EP 641
DI 10.1016/j.annepidem.2010.03.015
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 628PC
UT WOS:000280131600008
PM 20609343
ER
PT J
AU Lavange, LM
Kalsbeek, WD
Sorlie, PD
Aviles-Santa, LM
Kaplan, RC
Barnhart, J
Liu, KA
Giachello, A
Lee, DJ
Ryan, J
Criqui, MH
Elder, JP
AF Lavange, Lisa M.
Kalsbeek, William D.
Sorlie, Paul D.
Aviles-Santa, Larissa M.
Kaplan, Robert C.
Barnhart, Janice
Liu, Kiang
Giachello, Aida
Lee, David J.
Ryan, John
Criqui, Michael H.
Elder, John P.
TI Sample Design and Cohort Selection in the Hispanic Community Health
Study/Study of Latinos
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
DE Probability Sampling; Sampling Diverse Populations; Hispanic/Latino
Health
AB PURPOSE: The Hispanic Community Health Study (HCHS)/Study of Latinos (SQL) is a multicenter, community-based cohort study of Hispanic/Latino adults in the United States. A diverse participant sample is required that is both representative of the target population and likely to remain engaged throughout follow-up. The choice of sample design, its rationale, and benefits and challenges of design decisions are described in this study.
METHODS: The study design calls for recruitment and follow-up of a cohort of 16,000 Hispanics/Latinos 18-74 years of age, with 62.5% (10,000) over 44 years of age and adequate subgroup sample sizes to support inference by Hispanic/Latino background. Participants are recruited in community areas surrounding four field centers in the Bronx, Chicago, Miami, and San Diego. A two-stage area probability sample of households is selected with stratification and oversampling incorporated at each stage to provide a broadly diverse sample, offer efficiencies in field operations, and ensure that the target age distribution is obtained.
CONCLUSIONS: Embedding probability sampling within this traditional, multisite cohort study design enables competing research objectives to be met. However, the use of probability sampling requires developing solutions to some unique challenges in both sample selection and recruitment, as described here. Ann Epidemiol 2010;20:642-649. (C) 2010 Elsevier Inc. All rights reserved.
C1 [Lavange, Lisa M.] Univ N Carolina, Gillings Sch Global Publ Hlth, Collaborat Studies Coordinating Ctr, Dept Biostat,UNC CH, Chapel Hill, NC 27514 USA.
[Kalsbeek, William D.] Univ N Carolina, Survey Res Unit, Dept Biostat, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27514 USA.
[Sorlie, Paul D.; Aviles-Santa, Larissa M.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Kaplan, Robert C.; Barnhart, Janice] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Liu, Kiang] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Giachello, Aida] Univ Illinois, Midw Latino Hlth Res Training & Policy Ctr, Jane Addams Coll Social Work, Chicago, IL USA.
[Lee, David J.] Univ Miami, Sylvester Comprehens Ctr, Dept Epidemiol & Publ Hlth, Coral Gables, FL 33124 USA.
[Ryan, John] Univ Miami, Dept Family Med & Community Hlth, Coral Gables, FL 33124 USA.
[Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Elder, John P.] San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA.
RP Lavange, LM (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Collaborat Studies Coordinating Ctr, Dept Biostat,UNC CH, 137 E Franklin St,Suite 203, Chapel Hill, NC 27514 USA.
EM lisa_lavange@unc.edu
RI Kaplan, Robert/A-2526-2011
FU National Heart, Lung, and Blood Institute (NHLBI) to the University of
North Carolina [N01-HC65233]; University of Miami [N01-HC65234]; Albert
Einstein College of Medicine [NOD HC65235]; Northwestern University
[N01-HC65236]; San Diego State University [N01-HC65237]; NHLBI: National
Center on Minority Health and Health Disparities; National Institute of
Deafness and Other Communications Disorders; National Institute of
Dental and Craniofacial Research; National Institute of Diabetes and
Digestive and Kidney Diseases; National Institute of Neurological
Disorders and Stroke; Office of Dietary Supplements
FX The Hispanic Community Health Study/Study of Latinos is funded by
contracts from the National Heart, Lung, and Blood Institute (NHLBI) to
the University of North Carolina (N01-HC65233), University of Miami
(N01-HC65234), Albert Einstein College of Medicine (NOD HC65235),
Northwestern University (N01-HC65236), and San Diego State University
(N01-HC65237). The following Institutes/Centers/Offices contribute to
the HCHS/SOL through a transfer of funds to the NHLBI: National Center
on Minority Health and Health Disparities, the National Institute of
Deafness and Other Communications Disorders, the National Institute of
Dental and Craniofacial Research, the National Institute of Diabetes and
Digestive and Kidney Diseases, the National Institute of Neurological
Disorders and Stroke and the Office of Dietary Supplements.
NR 15
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U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1047-2797
J9 ANN EPIDEMIOL
JI Ann. Epidemiol.
PD AUG
PY 2010
VL 20
IS 8
BP 642
EP 649
DI 10.1016/j.annepidem.2010.05.006
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 628PC
UT WOS:000280131600009
PM 20609344
ER
PT J
AU Debette, S
Beiser, A
Hoffmann, U
DeCarli, C
O'Donnell, CJ
Massaro, JM
Au, R
Himali, JJ
Wolf, PA
Fox, CS
Seshadri, S
AF Debette, Stephanie
Beiser, Alexa
Hoffmann, Udo
DeCarli, Charles
O'Donnell, Christopher J.
Massaro, Joseph M.
Au, Rhoda
Himali, Jayandra J.
Wolf, Philip A.
Fox, Caroline S.
Seshadri, Sudha
TI Visceral Fat Is Associated with Lower Brain Volume in Healthy
Middle-Aged Adults
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID BODY-MASS INDEX; ADIPOSE-TISSUE VOLUMES; WHITE-MATTER LESIONS; STROKE
RISK PROFILE; FOLLOW-UP; ALZHEIMERS-DISEASE; CENTRAL OBESITY; COGNITIVE
FUNCTION; GENE-EXPRESSION; DEMENTIA
AB Objective: Mid life obesity has been associated with an increased risk of dementia. The underlying mechanisms are poorly understood. Our aim was to examine the cross-sectional association of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and computed tomography (CT)-based measurements of subcutaneous (SAT) and visceral (VAT) adipose tissue with various magnetic resonance imaging (MRI) markers of brain aging in middle-aged community adults.
Methods: Participants from the Framingham Offspring cohort were eligible if in addition to having measurements of BMI, WC, WHR, SAT, and VAT, they had undergone a volumetric brain MRI scan with measurements of total brain volume (TCBV), temporal horn volume (THV), white matter hyperintensity volume (WMHV), and MRI-defined brain infarcts (BI). All analyses were adjusted for age, sex, and time interval between abdominal CT and brain MRI.
Results: In a sample of 733 community participants (mean age, 60 years; 53% women), we observed an inverse association of BMI (estimate by standard deviation unit +/- standard error = -0.27 +/- 0.12; p = 0.02), WC (-0.30 +/- 0.12; p = 0.01), WHR (-0.37 +/- 0.12; p = 0.02), SAT (-0.23 +/- 0.11; p = 0.04), and VAT (-0.36 +/- 0.12; p = 0.002) with TCBV, independent of vascular risk factors. The association between VAT and TCBV was the strongest and most robust, and was also independent of BMI (-0.35 +/- 0.15; p = 0.02) and insulin resistance (-0.32 +/- 0.13; p = 0.01). When adjusting for C-reactive protein levels, the associations were attenuated (-0.17 +/- 0.13; p = 0.17 for VAT). No consistently significant association was observed between the anthropometric or CT-based abdominal fat measurements and THV, WMHV, or BI.
Interpretation: In middle-aged community participants, we observed a significant inverse association of anthropometric and CT-based measurements of abdominal, especially visceral, fat with total brain volume. ANN NEUROL 2010;68:136-144
C1 [Debette, Stephanie; Beiser, Alexa; Au, Rhoda; Himali, Jayandra J.; Wolf, Philip A.; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Framingham Heart Study, Boston, MA 02118 USA.
[Debette, Stephanie; Beiser, Alexa; O'Donnell, Christopher J.; Massaro, Joseph M.; Au, Rhoda; Himali, Jayandra J.; Wolf, Philip A.; Fox, Caroline S.; Seshadri, Sudha] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Beiser, Alexa; Massaro, Joseph M.; Himali, Jayandra J.] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA.
[Hoffmann, Udo; Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Metab & Diabet, Boston, MA 02115 USA.
[Hoffmann, Udo; O'Donnell, Christopher J.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[DeCarli, Charles] Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA.
RP Seshadri, S (reprint author), Boston Univ, Sch Med, Dept Neurol, Framingham Heart Study, B602,72 E Concord St, Boston, MA 02118 USA.
EM suseshad@bu.edu
RI DeCarli, Charles/B-5541-2009;
OI /0000-0003-1391-9481
FU Framingham Heart Study's National Heart, Lung, and Blood Institute
[N01-HC-25195]; National Institute of Neurological Disorders and Stroke
[R01 NS17950]; National Institute on Aging [R01 AG16495, AG08122,
AG033193, AG031287, AG033040, P30AG013846]; Bettencourt-Schueller
Foundation
FX This work was supported by the Framingham Heart Study's National Heart,
Lung, and Blood Institute contract (N01-HC-25195) and by grants from the
National Institute of Neurological Disorders and Stroke (R01 NS17950 to
PAW.) and from the National Institute on Aging (R01 AG16495 to P.A.W.,
AG08122 to P.A.W., AG033193 to S.S., AG031287 to S.S., AG033040 to
P.A.W., P30AG013846 to S.S.).; Dr Debette received an award from the
Bettencourt-Schueller Foundation.
NR 58
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U1 1
U2 11
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD AUG
PY 2010
VL 68
IS 2
BP 136
EP 144
DI 10.1002/ana.22062
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 636HD
UT WOS:000280721500007
PM 20695006
ER
PT J
AU Dolan, H
Crain, B
Troncoso, J
Resnick, SM
Zonderman, AB
OBrien, RJ
AF Dolan, Hillary
Crain, Barbara
Troncoso, Juan
Resnick, Susan M.
Zonderman, Alan B.
OBrien, Richard J.
TI Atherosclerosis, Dementia, and Alzheimer Disease in the Baltimore
Longitudinal Study of Aging Cohort
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID CORTICAL WATERSHED MICROINFARCTS; CORONARY-ARTERY-DISEASE; RISK-FACTORS;
WILLIS ATHEROSCLEROSIS; CARDIOVASCULAR-DISEASE; CEREBRAL INFARCTIONS;
OLDER PERSONS; ASSOCIATION; PATHOLOGY; INFLAMMATION
AB Objective: Although it is now accepted that asymptomatic cerebral infarcts are an important cause of dementia in the elderly, the relationship between atherosclerosis per se and dementia is controversial. Specifically, it is unclear whether atherosclerosis can cause the neuritic plaques and neurofibrillary tangles that define Alzheimer neuropathology and whether atherosclerosis, a potentially reversible risk factor, can influence cognition independent of brain infarcts.
Methods: We examined the relationship between systemic atherosclerosis, Alzheimer type pathology, and dementia in autopsies from 200 participants in the Baltimore Longitudinal Study of Aging, a prospective study of the effect of aging on cognition, 175 of whom had complete body autopsies.
Results: Using a quantitative analysis of atherosclerosis in the aorta, heart, and intracranial vessels, we found no relationship between the degree of atherosclerosis in any of these systems and the degree of Alzheimer type brain pathology. However, we found that the presence of intracranial but not coronary or aortic atherosclerosis significantly increased the odds of dementia, independent of cerebral infarction. Given the large number of individuals with intracranial atherosclerosis in this cohort (136/200), the population attributable risk of dementia related to intracranial atherosclerosis (independent of infarction) is substantial and potentially reversible.
Interpretation: Atherosclerosis of the intracranial arteries is an independent and important risk factor for dementia, suggesting potentially reversible pathways unrelated to Alzheimer pathology and stroke through which vascular changes may influence dementia risk. ANN NEUROL 2010;68:231-240
C1 [Dolan, Hillary; OBrien, Richard J.] Johns Hopkins Bayview Med Ctr, Dept Neurol, Baltimore, MD 21224 USA.
[OBrien, Richard J.] Johns Hopkins Bayview Med Ctr, Dept Med, Baltimore, MD 21224 USA.
[Crain, Barbara; Troncoso, Juan] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA.
[Resnick, Susan M.; Zonderman, Alan B.] NIA, Intramural Res Program, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA.
RP OBrien, RJ (reprint author), Johns Hopkins Bayview Med Ctr, Dept Neurol, Mason F Lord Ctr Tower,Suite 5100,5200 Eastern Av, Baltimore, MD 21224 USA.
EM robrien@jhmi.edu
OI Zonderman, Alan B/0000-0002-6523-4778
FU National Institute on Aging [P50 AG05146]; Burroughs Wellcome Fund for
Translational Research [1005227]; National Institute on Aging
FX Supported by National Institute on Aging grant P50 AG05146 RO, JT, the
Burroughs Wellcome Fund for Translational Research 1005227 RO, and the
Intramural Research Program, National Institute on Aging SR, AZ, NIH.
NR 55
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U1 1
U2 8
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD AUG
PY 2010
VL 68
IS 2
BP 231
EP 240
DI 10.1002/ana.22055
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 636HD
UT WOS:000280721500017
PM 20695015
ER
PT J
AU Bergmann, L
Berns, B
Dalgleish, AG
von Euler, M
Hecht, TT
Lappin, GL
Reed, N
Palmeri, S
Smyth, J
Embacher-Aichorn, S
Zwierzina, H
AF Bergmann, L.
Berns, B.
Dalgleish, A. G.
von Euler, M.
Hecht, T. T.
Lappin, G. L.
Reed, N.
Palmeri, S.
Smyth, J.
Embacher-Aichorn, S.
Zwierzina, H.
CA Biotherapy Dev Assoc
TI Investigator-initiated trials of targeted oncology agents: why
independent research is at risk?
SO ANNALS OF ONCOLOGY
LA English
DT Review
DE academic research; Clinical Trials Directive; drug development;
investigator-initiated trials; oncology; targeted therapies
ID CLINICAL-TRIALS; BREAST-CANCER; PERSPECTIVE; EUROPE; CHEMOTHERAPY;
THERAPIES; PRODUCTS; COSTS
AB Background: Drug development traditionally has relied upon the complementary contributions of clinicians and scientists at academic institutions and at pharmaceutical companies. Greater regulatory burdens, increased bureaucratic requirements, restricted reimbursement, and spiralling research and development costs are exerting pressure on the drug development pipeline. The result is a de-emphasis of exploratory research, particularly independent academic research, despite its proven value in identifying new drug targets and developing innovative cancer therapies.
Design: An expert panel assembled by the Biotherapy Development Association-a nonprofit international forum for academic and industry researchers, patients, and government regulatory and postregulatory agencies-examined the growing schism between academia and industry and identified several causes of declining academic research.
Results: The authors propose solutions to sustain investigator-initiated research and provide a new model whereby expert organisations provide a forum for academia and industry to plan studies within a regulatory framework to support licensure/authorisation and reimbursement for new molecularly targeted agents and biomarkers.
Conclusions: Investigator-initiated trials have led to the discovery and development of innovative, safe, and effective cancer treatments. To ensure that such research continues, action will be required on the parts of legislative and regulatory bodies, industry, universities, patient advocacy organisations, and preclinical and clinical academic scientists.
C1 [Embacher-Aichorn, S.; Zwierzina, H.] Med Univ Klin, Dept Internal Med Med Oncol, A-6020 Innsbruck, Austria.
[Bergmann, L.] Goethe Univ Frankfurt, Canc Ctr Rhein Main, Med Clin 2, Frankfurt, Germany.
[Berns, B.] Res & Dev, Ortho Biotech Oncol, High Wycombe, Bucks, England.
[Dalgleish, A. G.] Univ London, St Georges Hosp, Sch Med, Div Oncol, London WC1E 7HU, England.
[von Euler, M.] Roche, Oncol Clin Dev, Welwyn Garden City, Herts, England.
[Hecht, T. T.] NCI, NIH, Bethesda, MD 20892 USA.
[Lappin, G. L.] Xceleron Inc, Sci & Technol, Germantown, MD USA.
[Reed, N.] Western Infirm & Associated Hosp, Beatson Oncol Ctr, Glasgow G11 6NT, Lanark, Scotland.
[Palmeri, S.] Univ Palermo, Palermo, Italy.
[Smyth, J.] Univ Edinburgh, Edinburgh, Midlothian, Scotland.
RP Zwierzina, H (reprint author), Med Univ Klin, Dept Internal Med Med Oncol, Anichstr 35, A-6020 Innsbruck, Austria.
EM Heinz.Zwierzina@i-med.ac.at
NR 39
TC 6
Z9 7
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD AUG
PY 2010
VL 21
IS 8
BP 1573
EP 1578
DI 10.1093/annonc/mdq018
PG 6
WC Oncology
SC Oncology
GA 633UK
UT WOS:000280532000002
PM 20133383
ER
PT J
AU Tsai, HF
Sammons, LR
Zhang, XZ
Suffis, SD
Su, Q
Myers, TG
Marr, KA
Bennett, JE
AF Tsai, Huei-Fung
Sammons, Lindsay R.
Zhang, Xiaozhen
Suffis, Sara D.
Su, Qin
Myers, Timothy G.
Marr, Kieren A.
Bennett, John E.
TI Microarray and Molecular Analyses of the Azole Resistance Mechanism in
Candida glabrata Oropharyngeal Isolates
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID MULTIDRUG-RESISTANCE; SURVEILLANCE PROGRAM; TRANSCRIPTION FACTOR;
ANTIFUNGAL AGENTS; TRANSPORTER GENE; FLUCONAZOLE; SUSCEPTIBILITY; PDR1
AB DNA microarrays were used to analyze Candida glabrata oropharyngeal isolates from seven hematopoietic stem cell transplant recipients whose isolates developed azole resistance while the recipients received fluconazole prophylaxis. Transcriptional profiling of the paired isolates revealed 19 genes upregulated in the majority of resistant isolates compared to their paired susceptible isolates. All seven resistant isolates had greater than 2-fold upregulation of C. glabrata PDR1 (CgPDR1), a master transcriptional regulator of the pleiotropic drug resistance (PDR) network, and all seven resistant isolates showed upregulation of known CgPDR1 target genes. The altered transcriptome can be explained in part by the observation that all seven resistant isolates had acquired a single nonsynonymous mutation in their CgPDR1 open reading frame. Four mutations occurred in the regulatory domain (L280P, L344S, G348A, and S391L) and one in the activation domain (G943S), while two mutations (N764I and R772I) occurred in an undefined region. Association of azole resistance and the CgPDR1 mutations was investigated in the same genetic background by introducing the CgPDR1 sequences from one sensitive isolate and five resistant isolates into a laboratory azole-hypersusceptible strain (Cgpdr1 strain) via integrative transformation. The Cgpdr1 strain was restored to wild-type fluconazole susceptibility when transformed with CgPDR1 from the susceptible isolate but became resistant when transformed with CgPDR1 from the resistant isolates. However, despite the identical genetic backgrounds, upregulation of CgPDR1 and CgPDR1 target genes varied between the five transformants, independent of the domain locations in which the mutations occurred. In summary, gain-of-function mutations in CgPDR1 contributed to the clinical azole resistance, but different mutations had various degrees of impact on the CgPDR1 target genes.
C1 [Tsai, Huei-Fung; Sammons, Lindsay R.; Zhang, Xiaozhen; Suffis, Sara D.; Bennett, John E.] NIAID, Clin Mycol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Su, Qin; Myers, Timothy G.] NIAID, Genom Technol Sect, Res Technol Branch, NIH, Bethesda, MD 20892 USA.
[Marr, Kieren A.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
RP Bennett, JE (reprint author), NIAID, Clin Mycol Sect, Lab Clin Infect Dis, NIH, 10 Ctr Dr,Bldg 10,Room 12C103, Bethesda, MD 20892 USA.
EM Jbennett@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX This work was supported by the Intramural Research Program from the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 29
TC 30
Z9 57
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD AUG
PY 2010
VL 54
IS 8
BP 3308
EP 3317
DI 10.1128/AAC.00535-10
PG 10
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 626JW
UT WOS:000279963300029
PM 20547810
ER
PT J
AU Lestner, JM
Howard, SJ
Goodwin, J
Gregson, L
Majithiya, J
Walsh, TJ
Jensen, GM
Hope, WW
AF Lestner, Jodi M.
Howard, Susan J.
Goodwin, Joanne
Gregson, Lea
Majithiya, Jayesh
Walsh, Thomas J.
Jensen, Gerard M.
Hope, William W.
TI Pharmacokinetics and Pharmacodynamics of Amphotericin B Deoxycholate,
Liposomal Amphotericin B, and Amphotericin B Lipid Complex in an In
Vitro Model of Invasive Pulmonary Aspergillosis
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID CLINICAL-PRACTICE GUIDELINES; INFECTIOUS-DISEASES SOCIETY; ANTIFUNGAL
AGENTS; FILAMENTOUS FUNGI; THERAPY; CANDIDIASIS; FORMULATIONS;
PATHOGENESIS; NEUTROPENIA; MORTALITY
AB The pharmacodynamic and pharmacokinetic (PK-PD) properties of amphotericin B (AmB) formulations against invasive pulmonary aspergillosis (IPA) are not well understood. We used an in vitro model of IPA to further elucidate the PK-PD of amphotericin B deoxycholate (DAmB), liposomal amphotericin B (LAmB) and amphotericin B lipid complex (ABLC). The pharmacokinetics of these formulations for endovascular fluid, endothelial cells, and alveolar cells were estimated. Pharmacodynamic relationships were defined by measuring concentrations of galactomannan in endovascular and alveolar compartments. Confocal microscopy was used to visualize fungal biomass. A mathematical model was used to calculate the area under the concentration-time curve (AUC) in each compartment and estimate the extent of drug penetration. The interaction of LAmB with host cells and hyphae was visualized using sulforhodamine B-labeled liposomes. The MICs for the pure compound and the three formulations were comparable (0.125 to 0.25 mg/liter). For all formulations, concentrations of AmB progressively declined in the endovascular fluid as the drug distributed into the cellular bilayer. Depending on the formulation, the AUCs for AmB were 10 to 300 times higher within the cells than within endovascular fluid. The concentrations producing a 50% maximal effect (EC50) in the endovascular compartment were 0.12, 1.03, and 4.41 mg/liter for DAmB, LAmB, and ABLC, respectively, whereas, the EC50 in the alveolar compartment were 0.17, 7.76, and 39.34 mg/liter, respectively. Confocal microscopy suggested that liposomes interacted directly with hyphae and host cells. The PK-PD relationships of the three most widely used formulations of AmB differ markedly within an in vitro lung model of IPA.
C1 [Lestner, Jodi M.; Howard, Susan J.; Goodwin, Joanne; Gregson, Lea; Majithiya, Jayesh; Hope, William W.] Univ Manchester, Manchester Acad Hlth Sci Ctr, NIHR Translat Res Facil Resp Med, Univ Hosp S Manchester NHS Fdn Trust, Manchester M13 9PT, Lancs, England.
[Walsh, Thomas J.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Jensen, Gerard M.] Gilead Sci, San Dimas, CA USA.
RP Hope, WW (reprint author), Univ Manchester, 1-800 Stopford Bldg,Oxford Rd, Manchester M13 9PT, Lancs, England.
EM william.hope@manchester.ac.uk
OI , /0000-0003-0340-2016; Hope, William/0000-0001-6187-878X
FU Fungal Research Trust; Gilead Sciences; National Institute of Health
Research (NIHR); National Cancer Institute, National Institutes of
Health
FX This work was funded, in part, by the Fungal Research Trust and Gilead
Sciences. William Hope is supported by a National Institute of Health
Research (NIHR) Clinician Scientist Fellowship. This study was
supported, in part, by the intramural research program of the National
Cancer Institute, National Institutes of Health.
NR 27
TC 20
Z9 20
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
EI 1098-6596
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD AUG
PY 2010
VL 54
IS 8
BP 3432
EP 3441
DI 10.1128/AAC.01586-09
PG 10
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 626JW
UT WOS:000279963300045
PM 20439615
ER
PT J
AU Walsh, TJ
Goutelle, S
Jelliffe, RW
Golden, JA
Little, EA
DeVoe, C
Mickiene, D
Hayes, M
Conte, JE
AF Walsh, Thomas J.
Goutelle, Sylvain
Jelliffe, Roger W.
Golden, Jeffrey A.
Little, Emily A.
DeVoe, Catherine
Mickiene, Diana
Hayes, Maggie
Conte, John E., Jr.
TI Intrapulmonary Pharmacokinetics and Pharmacodynamics of Micafungin in
Adult Lung Transplant Patients
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID INVASIVE PULMONARY ASPERGILLOSIS; LIPOSOMAL AMPHOTERICIN-B; STEM-CELL
TRANSPLANT; HEALTHY-VOLUNTEERS; FUNGAL-INFECTIONS; STEADY-STATE; MURINE
MODEL; DOUBLE-BLIND; CANDIDIASIS; RECIPIENTS
AB Invasive pulmonary aspergillosis is a life-threatening infection in lung transplant recipients; however, no studies of the pharmacokinetics and pharmacodynamics (PKPD) of echinocandins in transplanted lungs have been reported. We conducted a single-dose prospective study of the intrapulmonary and plasma PKPD of 150 mg of micafungin administered intravenously in 20 adult lung transplant recipients. Epithelial lining fluid (ELF) and alveolar cell (AC) samples were obtained via bronchoalveolar lavage performed 3, 5, 8, 18, or 24 h after initiation of infusion. Micafungin concentrations in plasma, ELF, and ACs were determined using high-pressure liquid chromatography. Noncompartmental methods, population analysis, and multiple-dose simulations were used to calculate PKPD parameters. C-max in plasma, ELF, and ACs was 4.93, 1.38, and 17.41 mu g/ml, respectively. The elimination half-life in plasma was 12.1 h. Elevated concentrations in ELF and ACs were sustained during the 24-h sampling period, indicating prolonged compartmental half-lives. The mean micafungin concentration exceeded the MIC90 of Aspergillus fumigatus (0.0156 mu g/ml) in plasma (total and free), ELF, and ACs throughout the dosing interval. The area under the time-concentration curve from 0 to 24 h (AUC(0-24))/MIC90 ratios in plasma, ELF, and ACs were 5,077, 923.1, and 13,340, respectively. Multiple-dose simulations demonstrated that ELF and AC concentrations of micafungin would continue to increase during 14 days of administration. We conclude that a single 150-mg intravenous dose of micafungin resulted in plasma, ELF, and AC concentrations that exceeded the MIC90 of A. fumigatus for 24 h and that these concentrations would continue to increase during 14 days of administration, supporting its potential activity for prevention and early treatment of pulmonary aspergillosis.
C1 [Little, Emily A.; DeVoe, Catherine; Conte, John E., Jr.] Amer Hlth Sci, San Francisco, CA 94117 USA.
[Walsh, Thomas J.; Mickiene, Diana] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Goutelle, Sylvain] Hosp Civils Lyon, Hop A Charial, Serv Pharmaceut ADCAPT, Francheville, France.
[Goutelle, Sylvain] Univ Lyon 1, CNRS, UMR Biometrie & Biol Evolut 5558, F-69622 Villeurbanne, France.
[Jelliffe, Roger W.] Univ So Calif, USC Lab Appl Pharmacokinet, Los Angeles, CA USA.
[Golden, Jeffrey A.; Little, Emily A.; Hayes, Maggie] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Conte, John E., Jr.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
RP Conte, JE (reprint author), Amer Hlth Sci, 305,350 Parnassus Ave, San Francisco, CA 94117 USA.
EM john.conte@ucsf.edu
FU Astellas Pharma, Inc.; National Cancer Institute
FX This study was supported in part by Astellas Pharma, Inc., and by the
intramural program of the National Cancer Institute.
NR 49
TC 20
Z9 22
U1 1
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
EI 1098-6596
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD AUG
PY 2010
VL 54
IS 8
BP 3451
EP 3459
DI 10.1128/AAC.01647-09
PG 9
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 626JW
UT WOS:000279963300047
PM 20439610
ER
PT J
AU Tojo, Y
Koh, Y
Amano, M
Aoki, M
Das, D
Kulkarni, S
Anderson, DD
Ghosh, AK
Mitsuya, H
AF Tojo, Yasushi
Koh, Yasuhiro
Amano, Masayuki
Aoki, Manabu
Das, Debananda
Kulkarni, Sarang
Anderson, David D.
Ghosh, Arun K.
Mitsuya, Hiroaki
TI Novel Protease Inhibitors (PIs) Containing Macrocyclic Components and
3(R),3a(S),6a(R)-bis-Tetrahydrofuranylurethane That Are Potent against
Multi-PI-Resistant HIV-1 Variants In Vitro
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY;
REVERSE-TRANSCRIPTASE; CRYSTAL-STRUCTURES; DRUG-RESISTANCE; DISCOVERY;
P-2-LIGANDS; ZIDOVUDINE; MUTATIONS; MORTALITY
AB Natural products with macrocyclic structural features often display intriguing biological properties. Molecular design incorporating macrocycles may lead to molecules with unique protein-ligand interactions. We generated novel human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) containing a macrocycle and bis-tetrahydrofuranylurethane. Four such compounds exerted potent activity against HIV-1(LAI) and had 50% effective concentrations (EC(50)s) of as low as 0.002 mu M with minimal cytotoxicity. GRL-216 and GRL-286 blocked the replication of HIV-1(NL4-3) variants selected by up to 5 mu M saquinavir, ritonavir, nelfinavir, lopinavir, or atazanavir; they had EC(50)s of 0.020 to 0.046 mu M and potent activities against six multi-PI-resistant clinical HIV-1 (HIV(mPIr)) variants with EC(50)s of 0.027 to 0.089 mu M. GRL-216 and -286 also blocked HIV-1 protease dimerization as efficiently as darunavir. When HIV-1(NL4-3) was selected by GRL-216, it replicated progressively more poorly and failed to replicate in the presence of >0.26 mu M GRL-216, suggesting that the emergence of GRL-216-resistant HIV-1 variants is substantially delayed. At passage 50 with GRL-216 (the HIV isolate selected with GRL-216 at up to 0.16 mu M [HIV(216-0.16) mu M]), HIV-1(NL4-3) containing the L10I, L24I, M46L, V82I, and I84V mutations remained relatively sensitive to PIs, including darunavir, with the EC(50)s being 3- to 8-fold-greater than the EC(50) of each drug for HIV-1(NL4-3). Interestingly, HIV(216-0.16) mu M had 10-fold increased sensitivity to tipranavir. Analysis of the protein-ligand X-ray structures of GRL-216 revealed that the macrocycle occupied a greater volume of the binding cavity of protease and formed greater van der Waals interactions with V82 and I84 than darunavir. The present data warrant the further development of GRL-216 as a potential antiviral agent for treating individuals harboring wild-type and/or HIV(mPIr).
C1 [Tojo, Yasushi; Koh, Yasuhiro; Amano, Masayuki; Aoki, Manabu; Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Biomed Sci, Dept Hematol, Kumamoto 8608556, Japan.
[Tojo, Yasushi; Koh, Yasuhiro; Amano, Masayuki; Aoki, Manabu; Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Biomed Sci, Dept Infect Dis, Kumamoto 8608556, Japan.
[Das, Debananda; Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA.
[Kulkarni, Sarang; Anderson, David D.; Ghosh, Arun K.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
[Kulkarni, Sarang; Anderson, David D.; Ghosh, Arun K.] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA.
RP Mitsuya, H (reprint author), Kumamoto Univ, Sch Med, Dept Infect Dis, 1-1-1 Honjo, Kumamoto 8608556, Japan.
EM hmitsuya@helix.nih.gov
RI Amano, Masayuki/N-7407-2016
OI Amano, Masayuki/0000-0003-0516-9502
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health; National Institutes of Health [GM 53386]; Kumamoto
University; Global Education and Research Center Aiming at the Control
of AIDS; Ministry of Education, Culture, Sports, Science, and Technology
(Monbu-Kagakusho); Monbu-Kagakusho of Japan; Ministry of Health, Labor
and Welfare (Kosei-Rodosho) of Japan
FX This work was supported in part by the Intramural Research Program of
the Center for Cancer Research, National Cancer Institute, National
Institutes of Health; a grant from the National Institutes of Health
(grant GM 53386 to A.K.G.); a grant from the Kumamoto University Global
Center of Excellence Program, Global Education and Research Center
Aiming at the Control of AIDS, supported by the Ministry of Education,
Culture, Sports, Science, and Technology (Monbu-Kagakusho); a
Grant-in-Aid for Scientific Research (Priority Areas) from
Monbu-Kagakusho of Japan; and a Grant for Promotion of AIDS Research
from the Ministry of Health, Labor and Welfare (Kosei-Rodosho) of Japan.
NR 37
TC 16
Z9 16
U1 0
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD AUG
PY 2010
VL 54
IS 8
BP 3460
EP 3470
DI 10.1128/AAC.01766-09
PG 11
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 626JW
UT WOS:000279963300048
PM 20439612
ER
EF