FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Yardeni, T
Eckhaus, M
Morris, HD
Huizing, M
Hoogstraten-Miller, S
AF Yardeni, Tal
Eckhaus, Michael
Morris, H. Douglas
Huizing, Marjan
Hoogstraten-Miller, Shelley
TI Retro-orbital injections in mice
SO LAB ANIMAL
LA English
DT Article
ID TAIL VEIN; ROUTES; CELLS
AB Intravenous vascular access is technically challenging in the adult mouse and even more challenging in neonatal mice. The authors describe the technique of retro-orbital. injection of the venous sinus in the adult and neonatal mouse. This technique is a useful alternative to tail vein injection for the administration of non-tumorigenic compounds. The authors report that they have routinely used this technique in the adult mouse to administer volumes up to 150 mu l without incident. Administration of retro-orbital injections is more challenging in neonatal mice but can reliably deliver volumes up to 10 mu l.
C1 [Hoogstraten-Miller, Shelley] NHGRI, Off Lab Anim Med, NIH, Bethesda, MD 20892 USA.
[Yardeni, Tal; Huizing, Marjan] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Yardeni, Tal] Tel Aviv Univ, Sackler Sch Med, Grad Partner Program, IL-69978 Tel Aviv, Israel.
[Eckhaus, Michael] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA.
[Morris, H. Douglas] NINDS, Mouse Imaging Facil, NIH, Bethesda, MD 20892 USA.
RP Hoogstraten-Miller, S (reprint author), NHGRI, Off Lab Anim Med, NIH, Bethesda, MD 20892 USA.
EM shoogstr@mail.nih.gov
FU NHGRI, the National Institutes of Health
FX We thank Brenda Klaunberg and Danielle Donahue from the NIH Mouse
Imaging Facility and Darryl Leja from the NHGRI Intramural Publication
Support Office for their assistance with this project. This work was
carried out in partial fulfillment of the requirements for a PhD degree
for T.Y. (Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv,
Israel). This research was supported in part by the Intramural Research
Program of the NHGRI, the National Institutes of Health.
NR 18
TC 83
Z9 84
U1 2
U2 12
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0093-7355
J9 LAB ANIMAL
JI Lab Anim.
PD MAY
PY 2011
VL 40
IS 5
BP 155
EP 160
PG 6
WC Veterinary Sciences
SC Veterinary Sciences
GA 756GB
UT WOS:000289998600017
PM 21508954
ER
PT J
AU Colantonio, S
Simpson, JT
Fisher, RJ
Yavlovich, A
Belanger, JM
Puri, A
Blumenthal, R
AF Colantonio, Simona
Simpson, John T.
Fisher, Robert J.
Yavlovich, Amichai
Belanger, Julie M.
Puri, Anu
Blumenthal, Robert
TI Quantitative Analysis of Phospholipids Using Nanostructured Laser
Desorption Ionization Targets
SO LIPIDS
LA English
DT Article
DE NALDI; MALDI; Mass spectrometry; Lipids; Quantitation; Drug delivery
ID FLIGHT MASS-SPECTROMETRY; MALDI-TOF-MS; SMALL MOLECULES; CARBON
NANOTUBES; FATTY-ACIDS; PHYSICAL-PROPERTIES; POROUS SILICON;
DRUG-DELIVERY; DESORPTION/IONIZATION; MATRIX
AB Since its introduction as an ionization technique in mass spectrometry, matrix-assisted laser desorption ionization (MALDI) has been applied to a wide range of applications. Quantitative small molecule analysis by MALDI, however, is limited due to the presence of intense signals from the matrix coupled with non-homogeneous surfaces. The surface used in nano-structured laser desorption ionization (NALDI) eliminates the need for a matrix and the resulting interferences, and allows for quantitative analysis of small molecules. This study was designed to analyze and quantitate phospholipid components of liposomes. Here we have developed an assay to quantitate the DPPC and DC8,9PC in liposomes by NALDI following various treatments. To test our method we chose to analyze a liposome system composed of DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) and DC8,9PC (1,2-bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine), as DC8,9PC is known to undergo cross-linking upon treatment with UV (254 nm) and this reaction converts the monomer into a polymer. First, calibration curves for pure lipids (DPPC and DC8,9PC) were created using DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) as an internal standard. The calibration curve for both DPPC and DC8,9PC showed an R-2 of 0.992, obtained using the intensity ratio of analyte and internal standard. Next, DPPC:DC8,9PC liposomes were treated with UV radiation (254 nm). Following this treatment, lipids were extracted from the liposomes and analyzed. The analysis of the lipids before and after UV exposure confirmed a decrease in the signal of DC8,9PC of about 90%. In contrast, there was no reduction in DPPC signal.
C1 [Colantonio, Simona; Simpson, John T.; Fisher, Robert J.] NCI Frederick, Prot Chem Lab, Adv Technol Program, SAIC Frederick, Frederick, MD 21702 USA.
[Yavlovich, Amichai; Belanger, Julie M.; Puri, Anu; Blumenthal, Robert] NCI Frederick, Membrane Struct & Funct Sect, Ctr Canc Res, Nanobiol Program,NIH, Frederick, MD 21702 USA.
RP Colantonio, S (reprint author), NCI Frederick, Prot Chem Lab, Adv Technol Program, SAIC Frederick, POB B,Bldg 469,Rm 237, Frederick, MD 21702 USA.
EM colantos@mail.nih.gov
RI Belanger, Julie/A-5734-2009
OI Belanger, Julie/0000-0002-7236-2778
FU NIH, National Cancer Institute, Center for Cancer Research; National
Cancer Institute, National Institutes of Health [HHSN261200800001E]
FX This research was supported (in part) by federal funds from the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research. This project has been funded in part with
federal funds from the National Cancer Institute, National Institutes of
Health, under Contract No. HHSN261200800001E. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the US
government.
NR 64
TC 7
Z9 7
U1 0
U2 17
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0024-4201
J9 LIPIDS
JI Lipids
PD MAY
PY 2011
VL 46
IS 5
BP 469
EP 477
DI 10.1007/s11745-010-3493-1
PG 9
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA 755SC
UT WOS:000289955700011
PM 21327726
ER
PT J
AU Casanova, R
Espeland, MA
Goveas, JS
Davatzikos, C
Gaussoin, SA
Maldjian, JA
Brunner, RL
Kuller, LH
Johnson, KC
Mysiw, WJ
Wagner, B
Resnick, SM
AF Casanova, Ramon
Espeland, Mark A.
Goveas, Joseph S.
Davatzikos, Christos
Gaussoin, Sarah A.
Maldjian, Joseph A.
Brunner, Robert L.
Kuller, Lewis H.
Johnson, Karen C.
Mysiw, W. Jerry
Wagner, Benjamin
Resnick, Susan M.
CA Women's Hlth Initiative Memory St
TI Application of machine learning methods to describe the effects of
conjugated equine estrogens therapy on region-specific brain volumes
SO MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE Hormone therapy; MRI; Random forest; WHIMS
ID MILD COGNITIVE IMPAIRMENT; POSTMENOPAUSAL HORMONE-THERAPY; HEALTH
INITIATIVE MEMORY; RANDOMIZED CONTROLLED-TRIAL; ENTORHINAL CORTEX
NEURONS; ALZHEIMERS-DISEASE; WHIMS-MRI; EXPRESSION DATA; WOMEN; ATROPHY
AB Use of conjugated equine estrogens (CEE) has been linked to smaller regional brain volumes in women aged >= 65 years; however, it is unknown whether this results in a broad-based characteristic pattern of effects. Structural magnetic resonance imaging was used to assess regional volumes of normal tissue and ischemic lesions among 513 women who had been enrolled in a randomized clinical trial of CEE therapy for an average of 6.6 years, beginning at ages 65-80 years. A multivariate pattern analysis, based on a machine learning technique that combined Random Forest and logistic regression with L(1) penalty, was applied to identify patterns among regional volumes associated with therapy and whether patterns discriminate between treatment groups. The multivariate pattern analysis detected smaller regional volumes of normal tissue within the limbic and temporal lobes among women that had been assigned to CEE therapy. Mean decrements ranged as high as 7% in the left entorhinal cortex and 5% in the left perirhinal cortex, which exceeded the effect sizes reported previously in frontal lobe and hippocampus. Overall accuracy of classification based on these patterns, however, was projected to be only 54.5%. Prescription of CEE therapy for an average of 6.6 years is associated with lower regional brain volumes, but it does not induce a characteristic spatial pattern of changes in brain volumes of sufficient magnitude to discriminate users and nonusers. (c) 2011 Elsevier Inc. All rights reserved.
C1 [Casanova, Ramon; Espeland, Mark A.; Gaussoin, Sarah A.] Wake Forest Univ, Sch Med, Dept Biostat Sci, Winston Salem, NC 27109 USA.
[Goveas, Joseph S.] Med Coll Wisconsin, Dept Psychiat, Milwaukee, WI 53226 USA.
[Davatzikos, Christos] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
[Maldjian, Joseph A.; Wagner, Benjamin] Wake Forest Univ, Sch Med, Dept Radiol, Winston Salem, NC 27109 USA.
[Brunner, Robert L.] Univ Nevada, Sch Med, Reno, NV 89557 USA.
[Kuller, Lewis H.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Johnson, Karen C.] Univ Tennessee, Memphis, TN USA.
[Mysiw, W. Jerry] Ohio State Univ, Sch Med, Dept Phys Med & Rehabil, Columbus, OH 43210 USA.
[Resnick, Susan M.] NIA, Lab Personal & Cognit, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Casanova, R (reprint author), Wake Forest Univ, Sch Med, Dept Biostat Sci, Winston Salem, NC 27109 USA.
EM casanova@wfubmc.edu
RI Mysiw, Walter/E-3724-2011
FU National Heart, Lung, and Blood Institute of the National Institutes of
Health, US Department of Health and Human Services; Wyeth
Pharmaceuticals, St. Davids, PA, USA; NIA, National Institutes of Health
FX WHIMS-MRI Clinical Centers: Albert Einstein College of Medicine: Sylvia
Wassertheil-Smoller; Medical College of Wisconsin, Milwaukee: Jane
Morley Kotchen; Stanford Center for Research in Disease Prevention:
Marcia L. Stefanick; The Ohio State University: Rebecca Jackson;
University of California at Davis: John Robbins; University of
California at Los Angeles: Lauren Nathan; University of Florida: Marian
Limacher; University of Iowa: Jennifer Robinson; University of
Massachusetts: Judith Ockene; University of Minnesota: Karen Margolis;
University of Nevada: Robert Brunner; University of North Carolina,
Chapel Hill: Carol Murphy; University of Pittsburgh: Lewis Kuller.
WHIMS-MRI Clinical Coordinating Center: Wake Forest University Health
Sciences: Sally Shumaker. WHIMS-MRI Quality Control Center: University
of Pennsylvania: Nick Bryan. US National Institutes of Health: National
Institute on Aging: Neil Buckholtz, Susan Molchan, Susan Resnick;
National Heart, Lung, and Blood Institute: Jacques Rossouw, Linda
Pottern. Funding: The Women's Health Initiative is funded by the
National Heart, Lung, and Blood Institute of the National Institutes of
Health, US Department of Health and Human Services. WHIMS was funded in
part by Wyeth Pharmaceuticals, St. Davids, PA, USA. S.M.R. is supported
by the Intramural Research Program, NIA, National Institutes of Health.
NR 36
TC 11
Z9 11
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0730-725X
J9 MAGN RESON IMAGING
JI Magn. Reson. Imaging
PD MAY
PY 2011
VL 29
IS 4
BP 546
EP 553
DI 10.1016/j.mri.2010.12.001
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 756GS
UT WOS:000290000300009
PM 21292420
ER
PT J
AU Reiter, DA
Peacock, A
Spencer, RG
AF Reiter, David A.
Peacock, Andrew
Spencer, Richard G.
TI Effects of frozen storage and sample temperature on water
compartmentation and multiexponential transverse relaxation in cartilage
SO MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE Multicomponent; T-2; Bovine nasal cartilage; CPMG; NNLS
ID MULTICOMPONENT T-2 RELAXATION; RAT SPINAL-CORD; MYELIN WATER; H-1-NMR
RELAXOMETRY; ARTICULAR-CARTILAGE; MAGNETIC-RESONANCE; NMR RELAXATION;
WHITE-MATTER; TISSUE; DIFFUSION
AB Multiexponential transverse relaxation in tissue has been interpreted as a marker of water compartmentation. Articular cartilage has been reported to exhibit such relaxation in several studies, with the relative contributions of tissue heterogeneity and tissue microstructure remaining unspecified. In bovine nasal cartilage, conflicting data regarding the existence of multiexponential relaxation have been reported. Imaging and analysis artifacts as well as rapid chemical exchange between tissue compartments have been identified as potential causes for this discrepancy. Here, we find that disruption of cartilage microstructure by freeze-thawing can greatly alter the character of transverse relaxation in this tissue. We conclude that fresh cartilage exhibits multiexponential relaxation based upon its microstructural water compartments, but that multiexponentiality can be lost or rendered undetectable by freeze-thawing. In addition, we find that increasing chemical exchange by raising sample temperature from 4 degrees C to 37 degrees C does not substantially limit the ability to detect multiexponential relaxation. Published by Elsevier Inc.
C1 [Reiter, David A.; Peacock, Andrew; Spencer, Richard G.] NIA, Magnet Resonance Imaging & Spect Sect, NIH, Baltimore, MD 21224 USA.
RP Reiter, DA (reprint author), NIA, Magnet Resonance Imaging & Spect Sect, NIH, GRC 4D-08, Baltimore, MD 21224 USA.
EM reiterda@mail.nih.gov
FU NIH, National Institute on Aging
FX This work was supported by the Intramural Program of the NIH, National
Institute on Aging.
NR 31
TC 12
Z9 12
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0730-725X
J9 MAGN RESON IMAGING
JI Magn. Reson. Imaging
PD MAY
PY 2011
VL 29
IS 4
BP 561
EP 567
DI 10.1016/j.mri.2010.10.011
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 756GS
UT WOS:000290000300011
PM 21277724
ER
PT J
AU Nelson, LM
AF Nelson, Lawrence M.
TI One world, one woman: a transformational leader's approach to primary
ovarian insufficiency
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Article
DE Menopause; Premature menopause; Premature ovarian failure; Primary
ovarian insufficiency; Integrated care; Community-based participatory
research; Patient registries
ID EARLY EMBRYONIC-DEVELOPMENT; FRAGILE-X PREMUTATION; TREMOR/ATAXIA
SYNDROME; AUTOIMMUNE OOPHORITIS; FMR1 PREMUTATION; YOUNG-WOMEN; FAILURE;
GENE; KYOSEI; NEEDS
AB Lectureship endowment funds are created to honor major contributions that have clearly advanced a field. Such was the case in the creation of the Wulf H. Utian Endowed Lectureship Fund. In some select cases, they recognize the contributions of a transformational leader. The express purpose of the fund is to provide travel to the Annual Meeting by a lecturer selected by The North American Menopause Society Scientific Program Committee. Wulf H. Utian changed the paradigm for menopause by creating an organization whose major purpose was to use an integrated approach to the condition. Such an approach would benefit many areas of health care. This report summarizes my thoughts on how such an integrated approach might advance the field of primary ovarian insufficiency.
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Integrat Reprod Med Grp, Intramural Res Program Reprod & Adult Endocrinol, NIH,CRC, Bethesda, MD 20892 USA.
RP Nelson, LM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Integrat Reprod Med Grp, Intramural Res Program Reprod & Adult Endocrinol, NIH,CRC, Room 1-3140,10 Ctr Dr,MSC-1109, Bethesda, MD 20892 USA.
EM Lawrence_Nelson@nih.gov
FU Intramural NIH HHS [ZIA HD000633-20]
NR 44
TC 2
Z9 2
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-3714
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD MAY
PY 2011
VL 18
IS 5
BP 480
EP 487
DI 10.1097/gme.0b013e318213f250
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 755YT
UT WOS:000289978500006
PM 21686065
ER
PT J
AU Carmi-Levy, I
Motzik, A
Ofir-Birin, Y
Yagil, Z
Yang, CM
Kemeny, DM
Han, JM
Kim, S
Kay, G
Nechushtan, H
Suzuki, R
Rivera, J
Razin, E
AF Carmi-Levy, Irit
Motzik, Alex
Ofir-Birin, Yifat
Yagil, Zohar
Yang, Christopher Maolin
Kemeny, David Michael
Han, Jung Min
Kim, Sunghoon
Kay, Gillian
Nechushtan, Hovav
Suzuki, Ryo
Rivera, Juan
Razin, Ehud
TI Importin Beta Plays an Essential Role in the Regulation of the
LysRS-Ap(4)A Pathway in Immunologically Activated Mast Cells
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID NUCLEAR IMPORT; TRANSCRIPTION FACTOR; NUCLEOCYTOPLASMIC TRANSPORT;
PROTEIN-KINASE; IDENTIFICATION; EXPRESSION; COMPLEXES; HYDROLASE;
SEQUENCE; DOMAINS
AB We recently reported that diadenosine tetraphosphate hydrolase (Ap(4)A hydrolase) plays a critical role in gene expression via regulation of intracellular Ap(4)A levels. This enzyme serves as a component of our newly described lysyl tRNA synthetase (LysRS)-Ap(4)A biochemical pathway that is triggered upon immunological challenge. Here we explored the mechanism of this enzyme's translocation into the nucleus and found its immunologically dependent association with importin beta. Silencing of importin beta prevented Ap(4)A hydrolase nuclear translocation and affected the local concentration of Ap(4)A, which led to an increase in microphthalmia transcription factor (MITF) transcriptional activity. Furthermore, immunological activation of mast cells resulted in dephosphorylation of Ap(4)A hydrolase, which changed the hydrolytic activity of the enzyme.
C1 [Carmi-Levy, Irit; Motzik, Alex; Ofir-Birin, Yifat; Yagil, Zohar; Kay, Gillian; Razin, Ehud] Hebrew Univ Jerusalem, Hadassah Med Sch, Inst Med Res Israel Canada, Dept Biochem & Mol Biol, IL-91120 Jerusalem, Israel.
[Yang, Christopher Maolin; Kemeny, David Michael] Natl Univ Singapore, Ctr Life Sci, Program Immunol, Singapore 117597, Singapore.
[Yang, Christopher Maolin; Kemeny, David Michael] Natl Univ Singapore, Ctr Life Sci, Dept Microbiol, Singapore 117597, Singapore.
[Han, Jung Min] Seoul Natl Univ, Coll Pharm, Ctr Med Prot Network & Syst Biol, Seoul 151742, South Korea.
[Han, Jung Min] Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Seoul 151742, South Korea.
[Kim, Sunghoon] Seoul Natl Univ, Coll Pharm, Natl Creat Res Initiat, Ctr ARS Network, Seoul 151742, South Korea.
[Nechushtan, Hovav] Hadassah Hebrew Univ Med Ctr, Dept Oncol, IL-91120 Jerusalem, Israel.
[Suzuki, Ryo; Rivera, Juan] NIAMSD, Immunogenet Mol Lab, NIH, Bethesda, MD 20892 USA.
RP Razin, E (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Inst Med Res Israel Canada, Dept Biochem & Mol Biol, POB 12272, IL-91120 Jerusalem, Israel.
EM ehudr@ekmd.huji.ac.il
RI Kay, Gillian/F-3474-2014
OI Kay, Gillian/0000-0003-0966-2388
FU United States Binational Science Foundation; Israeli Academy of Science;
German- Israel Foundation for Scientific Research and Development; DKFZ-
MOST cooperation; National Medical Research Council of Singapore;
Morasha Foundation; Acceleration Research of KOSEF; 21st Frontier
Functional Proteomics Research; National Research Foundation of
Singapore
FX This work was supported by the United States Binational Science
Foundation (E.R.), the Israeli Academy of Science (E.R.), the German-
Israel Foundation for Scientific Research and Development (E.R.), DKFZ-
MOST cooperation (E.R.), the National Medical Research Council of
Singapore (D.M.K. and E.R.), the Morasha Foundation Fund (H.N.), the
Acceleration Research of KOSEF (S.K.), the 21st Frontier Functional
Proteomics Research (S.K.), and the CREATE project of the National
Research Foundation of Singapore (E.R. and M.K.). I.C.- L. and Z.Y. were
supported by the Canadian Friends of Hebrew University.
NR 39
TC 5
Z9 5
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD MAY
PY 2011
VL 31
IS 10
BP 2111
EP 2121
DI 10.1128/MCB.01159-10
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 755MQ
UT WOS:000289936600016
PM 21402779
ER
PT J
AU Koshimizu, H
Cawley, NX
Kim, T
Yergey, AL
Loh, YP
AF Koshimizu, Hisatsugu
Cawley, Niamh X.
Kim, Taeyoon
Yergey, Alfred L.
Loh, Y. Peng
TI Serpinin: A Novel Chromogranin A-Derived, Secreted Peptide Up-Regulates
Protease Nexin-1 Expression and Granule Biogenesis in Endocrine Cells
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID GENE-EXPRESSION; PHOSPHATIDYLINOSITOL 3-KINASE; TARGETED ABLATION;
CLEAVAGE SITES; BETA-CELLS; SP1; PHOSPHORYLATION; TRANSCRIPTION;
PROMOTER; PROTEINS
AB Previously we demonstrated that chromogranin A (CgA) promoted secretory granule biogenesis in endocrine cells by stabilizing and preventing granule protein degradation in the Golgi, through up-regulation of expression of the protease inhibitor, protease nexin-1 (PN-1). However, the mechanism by which CgA signals the increase of PN-1 expression is unknown. Here we identified a 2.9-kDa CgA-C-terminus peptide, which we named serpinin, in conditioned media from AtT-20 cells, a corticotroph cell line, which up-regulated PN-1 mRNA expression. Serpinin was secreted from AtT-20 cells upon high potassium stimulation and increased PN-1 mRNA transcription in these cells, in an actinomycin D-inhibitable manner. CgA itself and other CgA-derived peptides, when added to AtT-20 cell media, had no effect on PN-1 expression. Treatment of AtT-20 cells with 10 nM serpinin elevated cAMP levels and PN-1 mRNA expression, and this effect was inhibited by a protein kinase A inhibitor, 6-22 amide. Serpinin and a cAMP analog, 8-bromo-cAMP, promoted the translocation of the transcription factor Sp1 into the nucleus, which is known to drive PN-1 expression. Additionally, an Sp1 inhibitor, mithramycin A inhibited the serpinin-induced PN-1 mRNA up-regulation. Furthermore, a luciferase reporter assay demonstrated serpinin-induced up-regulation of PN-1 promoter activity in an Sp1-dependent manner. When added to CgB-transfected 6T3 cells, a mutant AtT20 cell line, serpinin induced granule biogenesis as evidenced by the presence of CgB puncta accumulation in the processes and tips. Our findings taken together show that serpinin, a novel CgA-derived peptide, is secreted upon stimulation of corticotrophs and plays an important autocrine role in up-regulating PN-1-dependent granule biogenesis via a cAMP-protein kinase A-Sp1 pathway to replenish released granules. (Molecular Endocrinology 25:732-744,2011)
C1 [Koshimizu, Hisatsugu; Cawley, Niamh X.; Kim, Taeyoon; Loh, Y. Peng] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bethesda, MD USA.
[Yergey, Alfred L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Metab Anal & Mass Spectrometry, NIH, Bethesda, MD USA.
RP Loh, YP (reprint author), NICHHD, NIH, Bldg 49,Room 5A22,49 Convent Dr, Bethesda, MD 20892 USA.
EM lohp@mail.noh.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health
FX This work was supported by the Intramural Research Program of Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health.
NR 37
TC 16
Z9 19
U1 0
U2 0
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0888-8809
J9 MOL ENDOCRINOL
JI Mol. Endocrinol.
PD MAY
PY 2011
VL 25
IS 5
BP 732
EP 744
DI 10.1210/me.2010-0124
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 755MM
UT WOS:000289936100002
PM 21436258
ER
PT J
AU Koh, J
Dar, M
Untch, BR
Dixit, D
Shi, YH
Yang, Z
Adam, MA
Dressman, H
Wang, XJ
Gesty-Palmer, D
Marks, JR
Spurney, R
Druey, KM
Olson, JA
AF Koh, James
Dar, Moahad
Untch, Brian R.
Dixit, Darshana
Shi, Yuhong
Yang, Zhao
Adam, Mohamed Abdelgadir
Dressman, Holly
Wang, Xiaojuan
Gesty-Palmer, Diane
Marks, Jeffrey R.
Spurney, Robert
Druey, Kirk M.
Olson, John A., Jr.
TI Regulator of G Protein Signaling 5 Is Highly Expressed in Parathyroid
Tumors and Inhibits Signaling by the Calcium-Sensing Receptor
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID GENE-EXPRESSION; PRIMARY HYPERPARATHYROIDISM; DECREASED EXPRESSION;
BLOOD-PRESSURE; MAP KINASE; ACTIVATION; RGS5; DESENSITIZATION; ADENOMAS;
PATHWAY
AB The molecular mechanisms responsible for aberrant calcium signaling in parathyroid disease are poorly understood. The loss of appropriate calcium-responsive modulation of PTH secretion observed in parathyroid disease is commonly attributed to decreased expression of the calcium-sensing receptor (CaSR), a G protein-coupled receptor. However, CaSR expression is highly variable in parathyroid adenomas, and the lack of correlation between CaSR abundance and calcium-responsive PTH kinetics indicates that mechanisms independent of CaSR expression may contribute to aberrant calcium sensing in parathyroid disease. To gain a better understanding of parathyroid tumors and the molecular determinants that drive parathyroid adenoma development, we performed gene expression profiling on a panel of 64 normal and neoplastic parathyroid tissues. The microarray data revealed high-level expression of genes known to be involved in parathyroid biology (PTH, VDR, CGA, CaSR, and GCM2). Moreover, our screen identified regulator of G protein signaling 5 (RGS5) as a candidate inhibitor of CaSR signaling. We confirmed RGS5 to be highly expressed in parathyroid adenomas relative to matched-pair normal glands. Transient expression of RGS5 in cells stably expressing CaSR resulted in dose-dependent abrogation of calcium-stimulated inositol trisphosphate production and ERK1/2 phosphorylation. Furthermore, we found that RGS5-nullizygous mice display reduced plasma PTH levels, an outcome consistent with attenuated opposition to CaSR activity. Collectively, these data suggest that RGS5 can act as a physiological regulator of calcium sensing by CaSR in the parathyroid gland. The abnormally elevated expression of RGS5 observed in parathyroid adenomas could thus represent a novel mechanism of CaSR desensitization in patients with primary hyperparathyroidism. (Molecular Endocrinology 25: 867-876, 2011)
C1 [Koh, James; Untch, Brian R.; Dixit, Darshana; Shi, Yuhong; Adam, Mohamed Abdelgadir; Marks, Jeffrey R.; Olson, John A., Jr.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
[Wang, Xiaojuan; Gesty-Palmer, Diane; Spurney, Robert] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Dressman, Holly; Olson, John A., Jr.] Duke Univ, Med Ctr, Inst Genome Sci & Policy, Durham, NC 27710 USA.
[Dar, Moahad] E Carolina Univ, Dept Med, Brody Sch Med, Greenville, NC 27858 USA.
[Yang, Zhao; Druey, Kirk M.] NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Olson, JA (reprint author), Duke Univ, Med Ctr, Dept Surg, Box 3873DUMC, Durham, NC 27710 USA.
EM jaomd@duke.edu
RI Shi, Yuhong/I-3987-2014
FU National Institutes of Health [1R01DK088188-01]; Arthritis Foundation
FX This work was supported by National Institutes of Health Grant
1R01DK088188-01 (to J.A.O. and J.K.) and by a grant from the Arthritis
Foundation (to D.G.P.).
NR 29
TC 19
Z9 20
U1 0
U2 2
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0888-8809
J9 MOL ENDOCRINOL
JI Mol. Endocrinol.
PD MAY
PY 2011
VL 25
IS 5
BP 867
EP 876
DI 10.1210/me.2010-0277
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 755MM
UT WOS:000289936100014
PM 21393447
ER
PT J
AU Hollingworth, P
Harold, D
Sims, R
Gerrish, A
Lambert, JC
Carrasquillo, MM
Abraham, R
Hamshere, ML
Pahwa, JS
Moskvina, V
Dowzell, K
Jones, N
Stretton, A
Thomas, C
Richards, A
Ivanov, D
Widdowson, C
Chapman, J
Lovestone, S
Powell, J
Proitsi, P
Lupton, MK
Brayne, C
Rubinsztein, DC
Gill, M
Lawlor, B
Lynch, A
Brown, KS
Passmore, PA
Craig, D
McGuinness, B
Todd, S
Holmes, C
Mann, D
Smith, AD
Beaumont, H
Warden, D
Wilcock, G
Love, S
Kehoe, PG
Hooper, NM
Vardy, ERLC
Hardy, J
Mead, S
Fox, NC
Rossor, M
Collinge, J
Maier, W
Jessen, F
Ruther, E
Schurmann, B
Heun, R
Kolsch, H
van den Bussche, H
Heuser, I
Kornhuber, J
Wiltfang, J
Dichgans, M
Frolich, L
Hampel, H
Gallacher, J
Hull, M
Rujescu, D
Giegling, I
Goate, AM
Kauwe, JSK
Cruchaga, C
Nowotny, P
Morris, JC
Mayo, K
Sleegers, K
Bettens, K
Engelborghs, S
De Deyn, PP
Van Broeckhoven, C
Livingston, G
Bass, NJ
Gurling, H
McQuillin, A
Gwilliam, R
Deloukas, P
Al-Chalabi, A
Shaw, CE
Tsolaki, M
Singleton, AB
Guerreiro, R
Muhleisen, TW
Nothen, MM
Moebus, S
Jockel, KH
Klopp, N
Wichmann, HE
Pankratz, VS
Sando, SB
Aasly, JO
Barcikowska, M
Wszolek, ZK
Dickson, DW
Graff-Radford, NR
Petersen, RC
van Duijn, CM
Breteler, MMB
Ikram, MA
DeStefano, AL
Fitzpatrick, AL
Lopez, O
Launer, LJ
Seshadri, S
Berr, C
Campion, D
Epelbaum, J
Dartigues, JF
Tzourio, C
Alperovitch, A
Lathrop, M
Feulner, TM
Friedrich, P
Riehle, C
Krawczak, M
Schreiber, S
Mayhaus, M
Nicolhaus, S
Wagenpfeil, S
Steinberg, S
Stefansson, H
Stefansson, K
Snaedal, J
Bjornsson, S
Jonsson, PV
Chouraki, V
Genier-Boley, B
Hiltunen, M
Soininen, H
Combarros, O
Zelenika, D
Delepine, M
Bullido, MJ
Pasquier, F
Mateo, I
Frank-Garcia, A
Porcellini, E
Hanon, O
Coto, E
Alvarez, V
Bosco, P
Siciliano, G
Mancuso, M
Panza, F
Solfrizzi, V
Nacmias, B
Sorbi, S
Bossu, P
Piccardi, P
Arosio, B
Annoni, G
Seripa, D
Pilotto, A
Scarpini, E
Galimberti, D
Brice, A
Hannequin, D
Licastro, F
Jones, L
Holmans, PA
Jonsson, T
Riemenschneider, M
Morgan, K
Younkin, SG
Owen, MJ
O'Donovan, M
Amouyel, P
Williams, J
AF Hollingworth, Paul
Harold, Denise
Sims, Rebecca
Gerrish, Amy
Lambert, Jean-Charles
Carrasquillo, Minerva M.
Abraham, Richard
Hamshere, Marian L.
Pahwa, Jaspreet Singh
Moskvina, Valentina
Dowzell, Kimberley
Jones, Nicola
Stretton, Alexandra
Thomas, Charlene
Richards, Alex
Ivanov, Dobril
Widdowson, Caroline
Chapman, Jade
Lovestone, Simon
Powell, John
Proitsi, Petroula
Lupton, Michelle K.
Brayne, Carol
Rubinsztein, David C.
Gill, Michael
Lawlor, Brian
Lynch, Aoibhinn
Brown, Kristelle S.
Passmore, Peter A.
Craig, David
McGuinness, Bernadette
Todd, Stephen
Holmes, Clive
Mann, David
Smith, A. David
Beaumont, Helen
Warden, Donald
Wilcock, Gordon
Love, Seth
Kehoe, Patrick G.
Hooper, Nigel M.
Vardy, Emma R. L. C.
Hardy, John
Mead, Simon
Fox, Nick C.
Rossor, Martin
Collinge, John
Maier, Wolfgang
Jessen, Frank
Ruether, Eckart
Schuermann, Britta
Heun, Reiner
Koelsch, Heike
van den Bussche, Hendrik
Heuser, Isabella
Kornhuber, Johannes
Wiltfang, Jens
Dichgans, Martin
Froelich, Lutz
Hampel, Harald
Gallacher, John
Huell, Michael
Rujescu, Dan
Giegling, Ina
Goate, Alison M.
Kauwe, John S. K.
Cruchaga, Carlos
Nowotny, Petra
Morris, John C.
Mayo, Kevin
Sleegers, Kristel
Bettens, Karolien
Engelborghs, Sebastiaan
De Deyn, Peter P.
Van Broeckhoven, Christine
Livingston, Gill
Bass, Nicholas J.
Gurling, Hugh
McQuillin, Andrew
Gwilliam, Rhian
Deloukas, Panagiotis
Al-Chalabi, Ammar
Shaw, Christopher E.
Tsolaki, Magda
Singleton, Andrew B.
Guerreiro, Rita
Muehleisen, Thomas W.
Noethen, Markus M.
Moebus, Susanne
Joeckel, Karl-Heinz
Klopp, Norman
Wichmann, H-Erich
Pankratz, V. Shane
Sando, Sigrid B.
Aasly, Jan O.
Barcikowska, Maria
Wszolek, Zbigniew K.
Dickson, Dennis W.
Graff-Radford, Neill R.
Petersen, Ronald C.
van Duijn, Cornelia M.
Breteler, Monique M. B.
Ikram, M. Arfan
DeStefano, Anita L.
Fitzpatrick, Annette L.
Lopez, Oscar
Launer, Lenore J.
Seshadri, Sudha
Berr, Claudine
Campion, Dominique
Epelbaum, Jacques
Dartigues, Jean-Francois
Tzourio, Christophe
Alperovitch, Annick
Lathrop, Mark
Feulner, Thomas M.
Friedrich, Patricia
Riehle, Caterina
Krawczak, Michael
Schreiber, Stefan
Mayhaus, Manuel
Nicolhaus, S.
Wagenpfeil, Stefan
Steinberg, Stacy
Stefansson, Hreinn
Stefansson, Kari
Snaedal, Jon
Bjornsson, Sigurbjorn
Jonsson, Palmi V.
Chouraki, Vincent
Genier-Boley, Benjamin
Hiltunen, Mikko
Soininen, Hilkka
Combarros, Onofre
Zelenika, Diana
Delepine, Marc
Bullido, Maria J.
Pasquier, Florence
Mateo, Ignacio
Frank-Garcia, Ana
Porcellini, Elisa
Hanon, Olivier
Coto, Eliecer
Alvarez, Victoria
Bosco, Paolo
Siciliano, Gabriele
Mancuso, Michelangelo
Panza, Francesco
Solfrizzi, Vincenzo
Nacmias, Benedetta
Sorbi, Sandro
Bossu, Paola
Piccardi, Paola
Arosio, Beatrice
Annoni, Giorgio
Seripa, Davide
Pilotto, Alberto
Scarpini, Elio
Galimberti, Daniela
Brice, Alexis
Hannequin, Didier
Licastro, Federico
Jones, Lesley
Holmans, Peter A.
Jonsson, Thorlakur
Riemenschneider, Matthias
Morgan, Kevin
Younkin, Steven G.
Owen, Michael J.
O'Donovan, Michael
Amouyel, Philippe
Williams, Julie
CA Alzheimer's Dis Neuroimaging
CHARGE Consortium
EADI1 Consortium
TI Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are
associated with Alzheimer's disease
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; RECEPTOR TYROSINE KINASE; IDENTIFIES VARIANTS;
GENE-EXPRESSION; CLU; PICALM; CR-1; RISK; LOCI; APOE
AB We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P <= 1 x 10(-5). We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 x 10(-17); including ADGC data, meta P = 5.0 x 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 x 10(-14); including ADGC data, meta P = 1.2 x 10(-16)) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 x 10(-4); including ADGC data, meta P = 8.6 x 10(-9)), CD33 (GERAD+, P = 2.2 x 10(-4); including ADGC data, meta P = 1.6 x 10(-9)) and EPHA1 (GERAD+, P = 3.4 x 10(-4); including ADGC data, meta P = 6.0 x 10(-10)).
C1 [Hollingworth, Paul; Harold, Denise; Sims, Rebecca; Gerrish, Amy; Abraham, Richard; Hamshere, Marian L.; Pahwa, Jaspreet Singh; Moskvina, Valentina; Dowzell, Kimberley; Jones, Nicola; Stretton, Alexandra; Thomas, Charlene; Richards, Alex; Ivanov, Dobril; Widdowson, Caroline; Chapman, Jade; Jones, Lesley; Holmans, Peter A.; Owen, Michael J.; O'Donovan, Michael; Williams, Julie] Cardiff Univ, MRC, Ctr Neuropsychiat Genet,Dept Psychol Med & Neurol, Neurosci & Mental Hlth Res Inst,Sch Med, Cardiff, S Glam, Wales.
[Lambert, Jean-Charles; Chouraki, Vincent; Genier-Boley, Benjamin; Amouyel, Philippe] INSERM, U744, F-59019 Lille, France.
[Lambert, Jean-Charles; Chouraki, Vincent; Genier-Boley, Benjamin; Amouyel, Philippe] Inst Pasteur, F-59019 Lille, France.
[Lambert, Jean-Charles; Chouraki, Vincent; Genier-Boley, Benjamin; Pasquier, Florence; Amouyel, Philippe] Univ Lille Nord France, F-59000 Lille, France.
[Carrasquillo, Minerva M.; Dickson, Dennis W.; Graff-Radford, Neill R.; Younkin, Steven G.] Mayo Clin, Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA.
[Lovestone, Simon] Kings Coll London, Natl Inst Hlth Res, Biomed Res Ctr Mental Hlth, S London & Maudsley Natl Hlth Serv Fdn Trust, London WC2R 2LS, England.
[Lovestone, Simon; Powell, John; Proitsi, Petroula; Lupton, Michelle K.] Kings Coll London, Inst Psychiat, Dept Neurosci, London WC2R 2LS, England.
[Brayne, Carol] Univ Cambridge, Inst Publ Hlth, Cambridge, England.
[Rubinsztein, David C.] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England.
[Gill, Michael; Lawlor, Brian; Lynch, Aoibhinn] St James Hosp, Mercers Inst Res Aging, Dublin 8, Ireland.
[Gill, Michael; Lawlor, Brian; Lynch, Aoibhinn] Trinity Coll Dublin, Dublin, Ireland.
[Brown, Kristelle S.; Morgan, Kevin] Univ Nottingham, Inst Genet, Queens Med Ctr, Nottingham NG7 2RD, England.
[Passmore, Peter A.; Craig, David; McGuinness, Bernadette; Todd, Stephen] Queens Univ Belfast, Ageing Grp, Ctr Publ Hlth, Sch Med Dent & Biomed Sci, Belfast, Antrim, North Ireland.
[Holmes, Clive] Univ Southampton, Div Clin Neurosci, Sch Med, Southampton, Hants, England.
[Mann, David; Vardy, Emma R. L. C.] Univ Manchester, Hope Hosp, Neurodegenerat & Mental Hlth Res Grp, Sch Community Based Med, Manchester, Lancs, England.
[Smith, A. David; Beaumont, Helen; Warden, Donald] Univ Oxford, John Radcliffe Hosp, Oxford Project Investigate Memory & Ageing OPTIMA, Oxford OX3 9DU, England.
[Wilcock, Gordon] Univ Oxford, Nuffield Dept Clin Med, Div Med Sci, Oxford, England.
[Love, Seth; Kehoe, Patrick G.] Univ Bristol, Inst Clin Neurosci, Frenchay Hosp, Dementia Res Grp, Bristol, Avon, England.
[Hooper, Nigel M.; Vardy, Emma R. L. C.] Univ Leeds, Inst Mol & Cellular Biol, Fac Biol Sci, LIGHT Labs, Leeds, W Yorkshire, England.
[Vardy, Emma R. L. C.] Salford Royal Natl Hlth Serv NHS Trust, Cerebral Funct Unit, Salford, Lancs, England.
[Hardy, John] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
[Hardy, John] Inst Neurol, Reta Lilla Weston Labs, London WC1N 3BG, England.
[Mead, Simon; Fox, Nick C.; Rossor, Martin; Collinge, John] UCL, Inst Neurol, Dept Neurodegenerat Dis, London, England.
[Maier, Wolfgang; Jessen, Frank; Schuermann, Britta; Heun, Reiner; Koelsch, Heike] Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany.
[Maier, Wolfgang; Ruether, Eckart] German Ctr Neurodegenerat Dis, Bonn, Germany.
[Ruether, Eckart; Noethen, Markus M.] Univ Bonn, Inst Mol Psychiat, D-5300 Bonn, Germany.
[Ruether, Eckart; Schuermann, Britta] Univ Gottingen, Dept Psychiat, Gottingen, Germany.
[Heun, Reiner] Royal Derby Hosp, Dept Psychiat, Derby, England.
[van den Bussche, Hendrik] Univ Med Ctr Hamburg Eppendorf, Inst Primary Med Care, Hamburg, Germany.
[Heuser, Isabella] Charite, Dept Psychiat, Berlin, Germany.
[Kornhuber, Johannes] Univ Erlangen Nurnberg, Dept Psychiat & Psychotherapy, Nurnberg, Germany.
[Wiltfang, Jens] Univ Duisburg Essen, Landschaftsverband Rheinland Hosp Essen, Dept Psychiat & Psychotherapy, Essen, Germany.
[Dichgans, Martin] Klinikum Univ Munchen, Dept Neurol, Munich, Germany.
[Dichgans, Martin] Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany.
[Froelich, Lutz] Univ Heidelberg, Dept Geriatr Psychiat, Cent Inst Mental Hlth, Med Fac Mannheim, D-6800 Mannheim, Germany.
[Hampel, Harald] Goethe Univ Frankfurt, Dept Psychiat Psychsomat Med & Psychotherapy, Frankfurt, Germany.
[Gallacher, John; Giegling, Ina] Cardiff Univ, Dept Primary Care & Publ Hlth, Sch Med, Cardiff, S Glam, Wales.
[Huell, Michael; Rujescu, Dan] Univ Freiburg, Ctr Geriatr Med, Freiburg, Germany.
[Huell, Michael; Rujescu, Dan] Univ Freiburg, Sect Gerontopsychiat & Neuropsychol, Freiburg, Germany.
[Goate, Alison M.; Cruchaga, Carlos; Nowotny, Petra; Mayo, Kevin] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Morris, John C.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Goate, Alison M.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Kauwe, John S. K.] Brigham Young Univ, Dept Biol, Provo, UT 84602 USA.
[Sleegers, Kristel; Bettens, Karolien; Engelborghs, Sebastiaan; De Deyn, Peter P.; Van Broeckhoven, Christine] Univ Antwerp, Inst Born Bunge, B-2020 Antwerp, Belgium.
[Sleegers, Kristel; Bettens, Karolien; Van Broeckhoven, Christine] Univ Antwerp VIB, Dept Mol Genet, Neurodegenerat Brain Dis Grp, B-2610 Antwerp, Belgium.
[Engelborghs, Sebastiaan; De Deyn, Peter P.] ZiekenhuisNetwerk Antwerpen, Memory Clin, Antwerp, Belgium.
[Engelborghs, Sebastiaan; De Deyn, Peter P.] ZiekenhuisNetwerk Antwerpen, Dept Neurol, Antwerp, Belgium.
[Livingston, Gill; Bass, Nicholas J.; Gurling, Hugh; McQuillin, Andrew] UCL, Dept Mental Hlth Sci, London, England.
[Gwilliam, Rhian; Deloukas, Panagiotis] Wellcome Trust Sanger Inst, Cambridge, England.
[Al-Chalabi, Ammar; Shaw, Christopher E.] Kings Coll London, MRC, Inst Psychiat, Ctr Neurodegenerat Res,Dept Clin Neurosci, London WC2R 2LS, England.
[Tsolaki, Magda] Aristotle Univ Thessaloniki, Dept Neurol 3, GR-54006 Thessaloniki, Greece.
[Singleton, Andrew B.; Guerreiro, Rita] NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA.
[Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Dept Genom, Life & Brain Ctr, D-5300 Bonn, Germany.
[Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany.
[Moebus, Susanne; Joeckel, Karl-Heinz] Univ Duisburg Essen, Inst Med Informat Biometry & Epidemiol, Univ Hosp Essen, Essen, Germany.
[Klopp, Norman; Wichmann, H-Erich] German Res Ctr Environm Hlth, Inst Med Informat, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Pankratz, V. Shane] Univ Munich, Div Biomed Stat, Munich, Germany.
[Sando, Sigrid B.; Aasly, Jan O.] St Olavs Hosp, Dept Neurol, Trondheim, Norway.
[Sando, Sigrid B.; Aasly, Jan O.] Norwegian Univ Sci & Technol, NTNU, Dept Neurosci, N-7491 Trondheim, Norway.
[Barcikowska, Maria] Polish Acad Sci, Med Res Ctr, Dept Neurodegenerat Disorders, Warsaw, Poland.
[Lopez, Oscar] Mayo Clin, Coll Med, Dept Neurol, Jacksonville, FL 32224 USA.
[Petersen, Ronald C.] Mayo Clin, Coll Med, Dept Neurol, Rochester, MN USA.
[Petersen, Ronald C.] Mayo Clin, Coll Med, Mayo Alzheimer Dis Res Ctr, Rochester, MN USA.
[van Duijn, Cornelia M.; Breteler, Monique M. B.; Ikram, M. Arfan] Univ Med Ctr, Dept Epidemiol, Erasmus Med Ctr, Rotterdam, Netherlands.
[van Duijn, Cornelia M.; Breteler, Monique M. B.; Ikram, M. Arfan] Netherlands Consortium Healthy Aging, Leiden, Netherlands.
[DeStefano, Anita L.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[DeStefano, Anita L.] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA.
[DeStefano, Anita L.; Seshadri, Sudha] NHLBI, Framingham, MA USA.
[Fitzpatrick, Annette L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Lopez, Oscar] Univ Pittsburgh, Sch Med, Dept Neurol, Alzheimers Dis Res Ctr, Pittsburgh, PA 15261 USA.
[Lopez, Oscar] Univ Pittsburgh, Sch Med, Dept Psychiat, Alzheimers Dis Res Ctr, Pittsburgh, PA 15261 USA.
[Launer, Lenore J.] NIA, Neuroepidemiol Sect, Lab Epidemiol Demog & Biometry LJL, Washington, DC USA.
[Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Berr, Claudine] Hop Colombiere, INSERM, U888, Montpellier, France.
[Campion, Dominique] Fac Med Pharm Rouen, INSERM, U614, Rouen, France.
[Epelbaum, Jacques] Univ Paris 05, INSERM, Fac Med, Unite Mixte Rech 894, Paris, France.
[Dartigues, Jean-Francois] Victor Segalen Univ, INSERM, U897, Bordeaux, France.
[Tzourio, Christophe; Alperovitch, Annick] INSERM, U708, Paris, France.
[Lathrop, Mark] Comis Energia Atom, Ctr Natl Genotypage, Inst Genom, Evry, France.
[Lathrop, Mark] Fdn Jean Dausset, Ctr Etud Polymorphisme Humain, Paris, France.
[Feulner, Thomas M.; Friedrich, Patricia; Riehle, Caterina; Mayhaus, Manuel; Riemenschneider, Matthias] Univ Saarland, Dept Psychiat & Psychotherapy, Univ Klinikum Saarlandes, Saarbrucken, Germany.
[Krawczak, Michael] Univ Kiel, Inst Med Informat & Stat, Kiel, Germany.
[Krawczak, Michael; Schreiber, Stefan] Univ Kiel, Biobank Popgen, Inst Expt Med, Epidemiol Sect, Kiel, Germany.
[Krawczak, Michael; Schreiber, Stefan; Nicolhaus, S.] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany.
[Wagenpfeil, Stefan] Tech Univ Munich, Klinikum Rechts Isar, Inst Med Stat & Epidemiol, D-8000 Munich, Germany.
[Steinberg, Stacy; Stefansson, Hreinn; Stefansson, Kari; Jonsson, Thorlakur] DeCODE Genet, Reykjavik, Iceland.
[Stefansson, Kari; Snaedal, Jon; Bjornsson, Sigurbjorn; Jonsson, Palmi V.] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Hiltunen, Mikko; Soininen, Hilkka] Univ Eastern Finland, Dept Neurol, Kuopio, Finland.
[Hiltunen, Mikko; Soininen, Hilkka] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Combarros, Onofre; Mateo, Ignacio] Univ Cantabria, Neurol Serv, Marques de Valdecilla Univ Hosp, E-39005 Santander, Spain.
[Combarros, Onofre; Bullido, Maria J.; Mateo, Ignacio; Frank-Garcia, Ana] Univ Cantabria, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Marques de Valdecilla Univ Hosp, E-39005 Santander, Spain.
[Zelenika, Diana; Delepine, Marc] Comis Energia Atom, Ctr Natl Genotypage, Inst Genom, Evry, France.
[Bullido, Maria J.; Amouyel, Philippe] Univ Autonoma Madrid, Ctr Biol Mol Severo Ochoa, Madrid, Spain.
[Pasquier, Florence] Univ Lille, Ctr Hosp Reg, Lille, France.
[Frank-Garcia, Ana] Hosp Univ La Paz UAM, Serv Neurol, Madrid, Spain.
[Porcellini, Elisa; Licastro, Federico] Univ Bologna, Dept Expt Pathol, Sch Med, Bologna, Italy.
[Hanon, Olivier] Univ Paris 05, Dept Geriatr, Broca Hosp, Paris, France.
[Coto, Eliecer; Alvarez, Victoria] Hosp Univ Cent Asturias, Genet Mol Unit, Oviedo, Spain.
[Bosco, Paolo] Ist Di Ricovero & Cura Carattere Sci Oasi Maria S, Troina, Italy.
[Siciliano, Gabriele; Mancuso, Michelangelo] Univ Pisa, Dept Neurosci, Neurol Clin, I-56100 Pisa, Italy.
[Panza, Francesco; Solfrizzi, Vincenzo] Univ Bari, Dept Geriatr, Ctr Aging Brain, Memory Unit, Bari, Italy.
[Nacmias, Benedetta; Sorbi, Sandro] Univ Florence, Dept Neurol & Psychiat Sci, Florence, Italy.
[Bossu, Paola] IRCCS Santa Lucia Fdn, Dept Clin & Behav Neurol, Rome, Italy.
[Piccardi, Paola] Univ Cagliari, Lab Mol Genet, Clin Pharmacol Sect, Dept Neurosci, Cagliari, Italy.
[Arosio, Beatrice] Univ Milan, Dept Internal Med, Fdn IRCCS, Osped Maggiore Mangiagalli & Regina Elena, Milan, Italy.
[Annoni, Giorgio] Univ Milano Bicocca, Dept Clin Med & Prevent, Monza, Italy.
[Seripa, Davide; Pilotto, Alberto] IRCCS Casa Sollievo Sofferenza, Geriatr Unit, San Giovanni Rotondo, Italy.
[Seripa, Davide; Pilotto, Alberto] IRCCS Casa Sollievo Sofferenza, Gerontol Geriatr Res Lab, Dept Med Sci, San Giovanni Rotondo, Italy.
[Scarpini, Elio; Galimberti, Daniela] Univ Milan, Dept Neurol Sci, Fdn IRCCS, Osped Maggiore Mangiagalli & Regina Elena, Milan, Italy.
[Brice, Alexis] Hop La Pitie Salpetriere, INSERM, UMR S679, Paris, France.
[Hannequin, Didier] Fac Med Pharm Rouen, INSERM, U614, Rouen, France.
RP Owen, MJ (reprint author), Cardiff Univ, MRC, Ctr Neuropsychiat Genet,Dept Psychol Med & Neurol, Neurosci & Mental Hlth Res Inst,Sch Med, Cardiff, S Glam, Wales.
EM owenmj@cardiff.ac.uk; williamsj@cardiff.ac.uk
RI Bullido, Maria/C-8509-2014; Lambert, jean-charles/A-9553-2014;
Porcellini, Elisa/K-5346-2016; Siciliano, Gabriele/K-7259-2016; Smith,
Anthony/A-4233-2010; McQuillin, Andrew/C-1623-2008; Deloukas,
Panos/B-2922-2013; Gurling, Hugh/A-5029-2010; Epelbaum,
Jacques/B-2263-2013; Kornhuber, Johannes/B-9613-2014; berr,
Claudine/D-5238-2014; Bosso, Paola/E-4832-2014; Tzourio,
christophe/B-4015-2009; Fox, Nick/B-1319-2009; lambert,
jean-charles/F-8787-2013; Holmans, Peter/F-4518-2015; LICEND,
CEMND/F-1296-2015; Breteler, Monique /J-5058-2014; Frank Garcia,
Ana/I-5159-2015; Hull, Michael/F-2618-2012; Guerreiro, Rita/A-1327-2011;
Schreiber, Stefan/B-6748-2008; Al-Chalabi, Ammar/E-5361-2010;
Livingston, Gill/C-7081-2008; Singleton, Andrew/C-3010-2009; Mead,
Simon/E-9414-2011; Powell, John/G-4412-2011; Krawczak,
Michael/A-8964-2010; Kauwe, John/B-2034-2009; Morris, John/A-1686-2012;
Hardy, John/C-2451-2009; Love, Seth/E-6545-2012; Jessen,
Frank/E-7655-2012;
OI sorbi, sandro/0000-0002-0380-6670; Arosio, Beatrice/0000-0002-0615-3580;
Chouraki, Vincent/0000-0002-4698-1794; scarpini,
elio/0000-0002-6395-2119; Gill, Michael/0000-0003-0206-5337; Wiltfang,
Jens/0000-0003-1492-5330; Harold, Denise/0000-0001-5195-0143; Bullido,
Maria/0000-0002-6477-1117; Lambert, jean-charles/0000-0003-0829-7817;
Porcellini, Elisa/0000-0003-3991-5294; Siciliano,
Gabriele/0000-0002-6142-2384; Smith, Anthony/0000-0002-1095-6722;
McQuillin, Andrew/0000-0003-1567-2240; Ikram, Mohammad
Arfan/0000-0003-0372-8585; Seshadri, Sudha/0000-0001-6135-2622;
galimberti, daniela/0000-0002-9284-5953; O'Donovan,
Michael/0000-0001-7073-2379; Dickson, Dennis W/0000-0001-7189-7917;
Deloukas, Panos/0000-0001-9251-070X; Kornhuber,
Johannes/0000-0002-8096-3987; berr, Claudine/0000-0001-5254-7655; Bosso,
Paola/0000-0002-1432-0078; Tzourio, christophe/0000-0002-6517-2984; Fox,
Nick/0000-0002-6660-657X; Holmans, Peter/0000-0003-0870-9412; Frank
Garcia, Ana/0000-0003-3858-9116; Schreiber, Stefan/0000-0003-2254-7771;
Al-Chalabi, Ammar/0000-0002-4924-7712; Mead, Simon/0000-0002-4326-1468;
Powell, John/0000-0001-6124-439X; Krawczak, Michael/0000-0003-2603-1502;
Kauwe, John/0000-0001-8641-2468; NACMIAS, Benedetta/0000-0001-9338-9040;
Livingston, Gill/0000-0001-6741-5516; Ivanov,
Dobril/0000-0001-6271-6301; Cruchaga, Carlos/0000-0002-0276-2899; Panza,
Francesco/0000-0002-7220-0656; Stefansson, Hreinn/0000-0002-9331-6666;
Escott-Price, Valentina/0000-0003-1784-5483; Nothen,
Markus/0000-0002-8770-2464; Todd, Stephen/0000-0002-2312-9195
FU Wellcome Trust; Medical Research Council (UK); Alzheimer's Research UK;
Welsh Assembly Government; Mercer's Institute for Research on Ageing;
Alzheimer's Society; Ulster Garden Villages; Northern Ireland RD Office;
Royal College of Physicians; Dunhill Medical Trust; Bristol Research
into Alzheimer's and Care of the Eldery; US National Institutes of
Health; Barnes Jewish Foundation; Charles and Joanne Knight Alzheimer's
Research Initiative; University College London (UCL) Hospital/UCL
Biomedical Centre; Lundbeck; German Federal Ministry of Education and
Research Competence Network Dementia and Competence Network Degenerative
Dementia; Alfried Krupp von Bohlen und Halbach-Stiftung; National
Institute of Ageing Department of Health and Human Services; University
of Antwerp; Fund for Scientific Research-Flanders; Foundation for
Alzheimer Research; Methusalem Excellence grant; Federal Science Policy
Office; Mayo AD Research Center; National Institute of Neurological
Disorders and Stroke; Robert and Clarice Smith Postdoctoral Fellowship
and AD Research Program; Palumbo Professorship in AD Research; Carl
Edward and Susan Bass Bolch Gift; Institut Pasteur de Lille; Centre
National de Genotypage; Fondation pour la Recherche Medicale Caisse;
Nationale Maladie des Travailleurs Salaries, Direction Generale de la
Sant; Institut de la Longevite; Agence Francaise de Securite Sanitaire
des Produits de Sante; Aquitaine and Bourgogne Regional Councils;
Fondation de France; French Ministry of Research/Institute national de
la sante et de la recherche medicale; Eisai; Health Research Council of
the Academy of Finland; Nordic Centre of Excellence in
Neurodegeneration; Italian Ministry of Research; Carimonte Foundation;
Italian Ministry of Health; Fondazione Monzino; Ministerio de Educacion
y Ciencia the Ministerio de Sanidad y Consumo; Fundacion Ramon Areces;
National Institute of Biomedical Imaging Bioengineering; Abbott;
AstraZeneca; Bayer Schering Pharma; Bristol-Myers Squibb; Elan;
Genentech; GE; GlaxoSmithKline; Innogenetics; Johnson and Johnson; Eli
Lilly; Medpace; Merck; Novartis; Pfizer; Hoffman-La Roche;
Schering-Plough; Synarc; Wyeth; Alzheimer's Association; Alzheimer's
Drug Discovery Foundation; US Food and Drug Administration; Foundation
for the National Institutes of Health Northern California Institute for
Research and Education; Dana Foundation; German National Genome Research
Network; German Ministry for Education and Research; National Institute
on Deafness and Other Communication Disorders; Hjartavernd; Althingi;
National Heart Lung and Blood Institute; National Institute of Diabetes
and Digestive and Kidney Diseases; Robert Dawson Evans Endowment;
Netherlands Organisation of Scientific Research; Netherlands Genomics
Initiative; Erasmus Medical Center; Netherlands organization for
scientific research; Netherlands Organization for the Health Research
and Development; Research Institute for Diseases in the Elderly;
Ministry of Education, Culture and Science; Ministry for Health, Welfare
and Sports; European Commission; Municipality of Rotterdam; NIHR
Biomedical Research Centre, Oxford; Health Foundation
FX For complete acknowledgments, please see the Supplementary Note. We
thank the individuals and families who took part in this research and
those who funded the groups who contributed to this study: Wellcome
Trust; Medical Research Council (UK); Alzheimer's Research UK; the Welsh
Assembly Government; Mercer's Institute for Research on Ageing;
Alzheimer's Society; Ulster Garden Villages; Northern Ireland R&D
Office; Royal College of Physicians; Dunhill Medical Trust; Bristol
Research into Alzheimer's and Care of the Eldery; US National Institutes
of Health, the Barnes Jewish Foundation; Charles and Joanne Knight
Alzheimer's Research Initiative; University College London (UCL)
Hospital/UCL Biomedical Centre; Lundbeck; German Federal Ministry of
Education and Research Competence Network Dementia and Competence
Network Degenerative Dementia; Alfried Krupp von Bohlen und
Halbach-Stiftung; Intramural Research Program of the National Institute
of Ageing Department of Health and Human Services; University of
Antwerp, Fund for Scientific Research-Flanders; Foundation for Alzheimer
Research; Methusalem Excellence grant; Federal Science Policy Office
Interuniversity Attraction Poles program; Mayo AD Research Center;
National Institute of Neurological Disorders and Stroke; Robert and
Clarice Smith Postdoctoral Fellowship and AD Research Program; Palumbo
Professorship in AD Research; Carl Edward and Susan Bass Bolch Gift;
Institut Pasteur de Lille; Centre National de Genotypage; Fondation pour
la Recherche Medicale Caisse; Nationale Maladie des Travailleurs
Salaries, Direction Generale de la Sant; Institut de la Longevite;
Agence Francaise de Securite Sanitaire des Produits de Sante; Aquitaine
and Bourgogne Regional Councils; Fondation de France; French Ministry of
Research/Institute national de la sante et de la recherche medicale;
Eisai; Health Research Council of the Academy of Finland; Nordic Centre
of Excellence in Neurodegeneration; Italian Ministry of Research;
Carimonte Foundation; Italian Ministry of Health; Fondazione Monzino;
Ministerio de Educacion y Ciencia the Ministerio de Sanidad y Consumo;
Fundacion Ramon Areces; National Institute of Biomedical Imaging
Bioengineering; Abbott; AstraZeneca, Bayer Schering Pharma;
Bristol-Myers Squibb; Elan; Genentech; GE; GlaxoSmithKline;
Innogenetics; Johnson and Johnson; Eli Lilly; Medpace; Merck; Novartis;
Pfizer; Hoffman-La Roche; Schering-Plough; Synarc; Wyeth; Alzheimer's
Association; Alzheimer's Drug Discovery Foundation; US Food and Drug
Administration; Foundation for the National Institutes of Health
Northern California Institute for Research and Education; Dana
Foundation; German National Genome Research Network; German Ministry for
Education and Research; National Institute on Deafness and Other
Communication Disorders; Hjartavernd; Althingi; National Heart Lung and
Blood Institute; National Institute of Diabetes and Digestive and Kidney
Diseases; Robert Dawson Evans Endowment; Netherlands Organisation of
Scientific Research; Netherlands Genomics Initiative; Erasmus Medical
Center; Netherlands organization for scientific research; Netherlands
Organization for the Health Research and Development; the Research
Institute for Diseases in the Elderly; Ministry of Education, Culture
and Science; Ministry for Health, Welfare and Sports; European
Commission and the Municipality of Rotterdam. G.W. was partly funded by
the NIHR Biomedical Research Centre Programme, Oxford. The Leeds sample
collection was funded by the Health Foundation.
NR 38
TC 697
Z9 711
U1 12
U2 131
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD MAY
PY 2011
VL 43
IS 5
BP 429
EP +
DI 10.1038/ng.803
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 755XF
UT WOS:000289972600011
PM 21460840
ER
PT J
AU Wei, XM
Walia, V
Lin, JC
Teer, JK
Prickett, TD
Gartner, J
Davis, S
Stemke-Hale, K
Davies, MA
Gershenwald, JE
Robinson, W
Robinson, S
Rosenberg, SA
Samuels, Y
AF Wei, Xiaomu
Walia, Vijay
Lin, Jimmy C.
Teer, Jamie K.
Prickett, Todd D.
Gartner, Jared
Davis, Sean
Stemke-Hale, Katherine
Davies, Michael A.
Gershenwald, Jeffrey E.
Robinson, William
Robinson, Steven
Rosenberg, Steven A.
Samuels, Yardena
CA NISC Comparative Sequencing Progra
TI Exome sequencing identifies GRIN2A as frequently mutated in melanoma
SO NATURE GENETICS
LA English
DT Article
ID HUMAN CANCER; GLUTAMATE RECEPTORS; COLORECTAL CANCERS; MUTATIONS; GENE;
EXPRESSION; SUBUNIT; REVEALS; GENOME; GROWTH
AB The incidence of melanoma is increasing more than any other cancer, and knowledge of its genetic alterations is limited. To systematically analyze such alterations, we performed whole-exome sequencing of 14 matched normal and metastatic tumor DNAs. Using stringent criteria, we identified 68 genes that appeared to be somatically mutated at elevated frequency, many of which are not known to be genetically altered in tumors. Most importantly, we discovered that TRRAP harbored a recurrent mutation that clustered in one position (p. Ser722Phe) in 6 out of 167 affected individuals (similar to 4%), as well as a previously unidentified gene, GRIN2A, which was mutated in 33% of melanoma samples. The nature, pattern and functional evaluation of the TRRAP recurrent mutation suggest that TRRAP functions as an oncogene. Our study provides, to our knowledge, the most comprehensive map of genetic alterations in melanoma to date and suggests that the glutamate signaling pathway is involved in this disease.
C1 [Wei, Xiaomu; Walia, Vijay; Prickett, Todd D.; Gartner, Jared; Samuels, Yardena] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
[Lin, Jimmy C.] Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD USA.
[Lin, Jimmy C.] Johns Hopkins Kimmel Canc Ctr, Howard Hughes Med Inst, Baltimore, MD USA.
[Teer, Jamie K.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Davis, Sean] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
[NISC Comparative Sequencing Progra] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
[Stemke-Hale, Katherine; Davies, Michael A.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
[Davies, Michael A.] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA.
[Gershenwald, Jeffrey E.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA.
[Gershenwald, Jeffrey E.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA.
[Robinson, William; Robinson, Steven] Univ Colorado, Denver Sch Med, Div Med Oncol, Aurora, CO USA.
[Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Samuels, Y (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
EM samuelsy@mail.nih.gov
RI Walia, Vijay/F-1647-2013; Stemke-Hale, Katherine/K-9113-2013;
OI Stemke-Hale, Katherine/0000-0002-1231-4192; Davis,
Sean/0000-0002-8991-6458
FU National Human Genome Research Institute; National Cancer Institute,
National Institutes of Health, USA; University of Texas MD Anderson
Cancer Center [P50 CA93459]
FX We thank V. Maduro, H. Abaan, P. Cruz and J. Mullikin for generating the
sequence data analyzed here. We thank V.G. Prieto for pathologic review
of the biospecimens from MelCore at MD Anderson. We thank T. Wolfsberg
for bioinformatics help and J. Fekecs and D. Leja for graphical
assistance. This work was supported by the Intramural Research Programs
of the National Human Genome Research Institute, the National Cancer
Institute, National Institutes of Health, USA and The University of
Texas MD Anderson Cancer Center Melanoma SPORE (P50 CA93459).
NR 30
TC 262
Z9 275
U1 1
U2 22
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD MAY
PY 2011
VL 43
IS 5
BP 442
EP +
DI 10.1038/ng.810
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 755XF
UT WOS:000289972600013
PM 21499247
ER
PT J
AU Spurdle, AB
Thompson, DJ
Ahmed, S
Ferguson, K
Healey, CS
O'Mara, T
Walker, LC
Montgomery, SB
Dermitzakis, ET
Fahey, P
Montgomery, GW
Webb, PM
Fasching, PA
Beckmann, MW
Ekici, AB
Hein, A
Lambrechts, D
Coenegrachts, L
Vergote, I
Amant, F
Salvesen, HB
Trovik, J
Njolstad, TS
Helland, H
Scott, RJ
Ashton, K
Proietto, T
Otton, G
Tomlinson, I
Gorman, M
Howarth, K
Hodgson, S
Garcia-Closas, M
Wentzensen, N
Yang, HN
Chanock, S
Hall, P
Czene, K
Liu, JJ
Li, JM
Shu, XO
Zheng, W
Long, JR
Xiang, YB
Shah, M
Morrison, J
Michailidou, K
Pharoah, PD
Dunning, AM
Easton, DF
AF Spurdle, Amanda B.
Thompson, Deborah J.
Ahmed, Shahana
Ferguson, Kaltin
Healey, Catherine S.
O'Mara, Tracy
Walker, Logan C.
Montgomery, Stephen B.
Dermitzakis, Emmanouil T.
Fahey, Paul
Montgomery, Grant W.
Webb, Penelope M.
Fasching, Peter A.
Beckmann, Matthias W.
Ekici, Arif B.
Hein, Alexander
Lambrechts, Diether
Coenegrachts, Lieve
Vergote, Ignace
Amant, Frederic
Salvesen, Helga B.
Trovik, Jone
Njolstad, Tormund S.
Helland, Harald
Scott, Rodney J.
Ashton, Katie
Proietto, Tony
Otton, Geoffrey
Tomlinson, Ian
Gorman, Maggie
Howarth, Kimberley
Hodgson, Shirley
Garcia-Closas, Montserrat
Wentzensen, Nicolas
Yang, Hannah
Chanock, Stephen
Hall, Per
Czene, Kamila
Liu, Jianjun
Li, Jingmei
Shu, Xiao-Ou
Zheng, Wei
Long, Jirong
Xiang, Yong-Bing
Shah, Mitul
Morrison, Jonathan
Michailidou, Kyriaki
Pharoah, Paul D.
Dunning, Alison M.
Easton, Douglas F.
CA Australian Natl Endometrial Canc
Natl Study Endometrial Canc Geneti
TI Genome-wide association study identifies a common variant associated
with risk of endometrial cancer
SO NATURE GENETICS
LA English
DT Article
ID HEPATOCYTE NUCLEAR FACTOR-1-BETA; CLEAR-CELL CARCINOMA; PROSTATE-CANCER;
SUSCEPTIBILITY LOCI; DIABETES-MELLITUS; EXPRESSION; METAANALYSIS;
REPLICATION; YOUNGER; FAMILY
AB Endometrial cancer is the most common malignancy of the female genital tract in developed countries. To identify genetic variants associated with endometrial cancer risk, we performed a genome-wide association study involving 1,265 individuals with endometrial cancer (cases) from Australia and the UK and 5,190 controls from the Wellcome Trust Case Control Consortium. We compared genotype frequencies in cases and controls for 519,655 SNPs. Forty seven SNPs that showed evidence of association with endometrial cancer in stage 1 were genotyped in 3,957 additional cases and 6,886 controls. We identified an endometrial cancer susceptibility locus close to HNF1B at 17q12 (rs4430796, P = 7.1 x 10(-10)) that is also associated with risk of prostate cancer and is inversely associated with risk of type 2 diabetes.
C1 [Spurdle, Amanda B.; Ferguson, Kaltin; O'Mara, Tracy; Walker, Logan C.; Fahey, Paul; Montgomery, Grant W.; Webb, Penelope M.; Australian Natl Endometrial Canc] Queensland Inst Med Res, Div Genet & Populat Hlth, Brisbane, Qld 4006, Australia.
[Thompson, Deborah J.; Morrison, Jonathan; Michailidou, Kyriaki; Pharoah, Paul D.; Easton, Douglas F.] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge, England.
[Ahmed, Shahana; Healey, Catherine S.; Shah, Mitul; Pharoah, Paul D.; Dunning, Alison M.; Easton, Douglas F.] Univ Cambridge, Strangeways Res Lab, Dept Oncol, Cambridge, England.
[O'Mara, Tracy] Queensland Univ Technol, Hormone Dependent Canc Program, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia.
[Montgomery, Stephen B.; Dermitzakis, Emmanouil T.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland.
[Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Beckmann, Matthias W.; Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, D-8520 Erlangen, Germany.
[Hein, Alexander] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Gynecol & Obstet, D-8520 Erlangen, Germany.
[Hein, Alexander] Ctr Comprehens Canc, Univ Gynecol Oncol Ctr, Erlangen, Germany.
[Lambrechts, Diether] Vlaams Inst Biotechnol, Vesalius Res Ctr, Louvain, Belgium.
[Lambrechts, Diether] Katholieke Univ Leuven, Vesalius Res Ctr, Louvain, Belgium.
[Coenegrachts, Lieve; Vergote, Ignace; Amant, Frederic] Katholieke Univ Leuven Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol, Louvain, Belgium.
[Salvesen, Helga B.; Trovik, Jone; Njolstad, Tormund S.; Helland, Harald] Haukeland Hosp, Dept Obstet & Gynecol, N-5021 Bergen, Norway.
[Salvesen, Helga B.; Trovik, Jone; Njolstad, Tormund S.] Univ Bergen, Dept Clin Med, Bergen, Norway.
[Scott, Rodney J.; Ashton, Katie] Univ Newcastle, Ctr Informat Based Med, Callaghan, NSW 2308, Australia.
[Scott, Rodney J.; Ashton, Katie] Univ Newcastle, Discipline Med Genet, Sch Biomed Sci & Pharm, Fac Hlth, Callaghan, NSW 2308, Australia.
[Scott, Rodney J.; Ashton, Katie] John Hunter Hosp, Hunter Med Res Inst, Newcastle, NSW, Australia.
[Scott, Rodney J.] John Hunter Hosp, Hunter Area Pathol Serv, Div Genet, Newcastle, NSW, Australia.
[Scott, Rodney J.] John Hunter Hosp, Hunter Ctr Gynaecol, Newcastle, NSW, Australia.
[Proietto, Tony; Otton, Geoffrey] Univ Newcastle, Sch Med & Publ Hlth, Fac Hlth, Callaghan, NSW 2308, Australia.
[Tomlinson, Ian; Gorman, Maggie; Howarth, Kimberley; Natl Study Endometrial Canc Geneti] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Hodgson, Shirley] St George Hosp, Sch Med, Dept Clin Genet, London, England.
[Garcia-Closas, Montserrat; Wentzensen, Nicolas; Yang, Hannah; Chanock, Stephen] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Garcia-Closas, Montserrat] Inst Canc Res, London SW3 6JB, England.
[Hall, Per; Czene, Kamila; Li, Jingmei] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Liu, Jianjun; Li, Jingmei] Genome Inst Singapore, Singapore, Singapore.
[Shu, Xiao-Ou; Zheng, Wei; Long, Jirong] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN USA.
[Xiang, Yong-Bing] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
RP Spurdle, AB (reprint author), Queensland Inst Med Res, Div Genet & Populat Hlth, Brisbane, Qld 4006, Australia.
EM amanda.spurdle@qimr.edu.au
RI Spurdle, Amanda/A-4978-2011; Verdrengh, Evelien/H-4571-2012; Li,
Jingmei/I-2904-2012; Dermitzakis, Emmanouil/B-7687-2013; Fahey,
Paul/B-7985-2013; Hein, Alexander/F-6999-2010; Montgomery,
Grant/B-7148-2008; O'Mara, Tracy/M-7508-2016; salvesen,
Helga/C-1187-2017; Ekici, Arif/C-3971-2013; Garcia-Closas, Montserrat
/F-3871-2015;
OI Spurdle, Amanda/0000-0003-1337-7897; Dunning, Alison
Margaret/0000-0001-6651-7166; Njolstad, Tormund/0000-0003-4024-3819; Li,
Jingmei/0000-0001-8587-7511; Fahey, Paul/0000-0002-6351-9876; Hein,
Alexander/0000-0003-2601-3398; Montgomery, Grant/0000-0002-4140-8139;
O'Mara, Tracy/0000-0002-5436-3232; salvesen, Helga/0000-0002-4438-8831;
Czene, Kamila/0000-0002-3233-5695; Garcia-Closas, Montserrat
/0000-0003-1033-2650; Webb, Penelope/0000-0003-0733-5930
FU National Health and Medical Research Council (NHMRC) [552402, 339435];
Wellcome Trust [068545/Z/02, 085475]; Cancer Research UK [C1287/A10118,
C490/A1021, C8197/A10865, C8197/A10123, C490/A10124]; Australian
Postgraduate Award; Institute of Health and Biomedical Innovation;
Joseph Mitchell Trust; Dr. Mildred Scheel Stiftung of the Deutsche
Krebshilfe (German Cancer Aid); Medical Research Council [G0000934];
Cancer Council Queensland [4196615]; Cancer Council Tasmania [403031,
457636]; University of Erlangen; Verelst Foundation for endometrial
cancer; Helse Vest Grant; University of Bergen; Melzer Foundation;
Norwegian Cancer Society (Harald Andersens legat); Research Council of
Norway; Haukeland University Hospital; Oxford Comprehensive Biomedical
Research Centre [075491/Z/04]; US National Cancer Institute, Division of
Cancer Epidemiology and Genetics in the Hormonal and Reproductive
Epidemiology Branch; Agency for Science, Technology and Research of
Singapore (A*STAR); US National Institutes of Health (NIH); Susan G.
Komen Breast Cancer Foundation; National Cancer Institute of the United
States Public Health Service [RO1 CA 092585, R01 CA90899, R01 CA64277]
FX This work was supported by the National Health and Medical Research
Council (NHMRC; ID 552402), the Wellcome Trust and by Cancer Research UK
grants C1287/A10118, C490/A1021, C8197/A10865 and C8197/A10123. A.B.S.
and P.M.W. are NHMRC Senior Research Fellows, and G.M. is an NHMRC
Senior Principle Research Fellow. T.O. is supported by an Australian
Postgraduate Award, an Institute of Health and Biomedical Innovation PhD
Top-Up and a Smart State PhD Award. L.C.W. is a John Gavin Postdoctoral
Fellow (Genesis Oncology Trust, New Zealand). D.F.E. is a Principal
Research Fellow of Cancer Research UK. A.M.D. is supported by the Joseph
Mitchell Trust. I.T. is supported by Cancer Research UK and the Oxford
Comprehensive Biomedical Research Centre. P.A.F. was partly funded by
the Dr. Mildred Scheel Stiftung of the Deutsche Krebshilfe (German
Cancer Aid).; This study makes use of data generated by the Wellcome
Trust Case Control Consortium (WTCCC) 2. A full list of the
investigators who contributed to the generation of the data is available
from the WTCCC website. We acknowledge use of DNA from the British 1958
Birth Cohort collection, funded by the Medical Research Council grant
G0000934 and the Wellcome Trust grant 068545/Z/02. Funding for this
project was provided by the Wellcome Trust under award 085475.; We thank
the study participants and collaborators and the research teams involved
in the design and implementation of the individual studies included (see
Supplementary Note for full list of collaborators and specific
acknowledgments). Australian National Endometrial Cancer Study (ANECS)
recruitment was supported by project grants from the National Health and
Medical Research Council of Australia (ID#339435), The Cancer Council
Queensland (ID#4196615) and Cancer Council Tasmania (ID#403031 and
ID#457636). The Bavarian Endometrial Cancer Study (BECS) was partly
funded by the Erlanger Leistungsbezogene Anschubfinanzierung und
Nachwuchsforderung Fond (ELAN fund) of the University of Erlangen. The
Leuven Endometrium Study (LES) was supported by the Verelst Foundation
for endometrial cancer. Molecular Markers in Treatment of Endometrial
Cancer (MoMaTEC) received financial support from a Helse Vest Grant, the
University of Bergen, Melzer Foundation, the Norwegian Cancer Society
(Harald Andersens legat), the Research Council of Norway and Haukeland
University Hospital. The Newcastle Endometrial Cancer Study (NECS)
acknowledges contributions from the University of Newcastle, the
National Broadcasting Network (NBN) Children's Cancer Research Group,
Jennie Thomas and the Hunter Medical Research Institute. The National
Study of Endometrial Cancer Genetics (NSECG) Group was supported
principally by Cancer Research UK and by funds from the Oxford
Comprehensive Biomedical Research Centre, with core infrastructure
support to the Wellcome Trust Centre for Human Genetics, Oxford provided
by grant 075491/Z/04. The Polish Endometrial Cancer Study (PECS) was
funded by the intramural research program at the US National Cancer
Institute, Division of Cancer Epidemiology and Genetics in the Hormonal
and Reproductive Epidemiology Branch. The Singapore and Swedish
Breast/Endometrial Cancer Study (SASBAC) was supported by funding from
the Agency for Science, Technology and Research of Singapore (A*STAR),
the US National Institutes of Health (NIH) and the Susan G. Komen Breast
Cancer Foundation. The Shanghai Endometrial Cancer Genetic Study (SECGS)
was supported by grants from the National Cancer Institute of the United
States Public Health Service (RO1 CA 092585 and R01 CA90899, R01
CA64277). SEARCH is funded by a program grant from Cancer Research UK
(C490/A10124).
NR 44
TC 69
Z9 69
U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD MAY
PY 2011
VL 43
IS 5
BP 451
EP +
DI 10.1038/ng.812
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA 755XF
UT WOS:000289972600015
PM 21499250
ER
PT J
AU McCoy, JP
AF McCoy, J. Philip, Jr.
TI High-content screening: getting more from less
SO NATURE METHODS
LA English
DT Editorial Material
C1 NHLBI, NIH, Bethesda, MD 20892 USA.
RP McCoy, JP (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM mccoyj@nhlbi.nih.gov
FU Intramural NIH HHS [ZIC HL005905-02]
NR 6
TC 6
Z9 6
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1548-7091
J9 NAT METHODS
JI Nat. Methods
PD MAY
PY 2011
VL 8
IS 5
BP 390
EP 391
PG 3
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 756BQ
UT WOS:000289987100014
PM 21527930
ER
PT J
AU Planchon, TA
Gao, L
Milkie, DE
Davidson, MW
Galbraith, JA
Galbraith, CG
Betzig, E
AF Planchon, Thomas A.
Gao, Liang
Milkie, Daniel E.
Davidson, Michael W.
Galbraith, James A.
Galbraith, Catherine G.
Betzig, Eric
TI Rapid three-dimensional isotropic imaging of living cells using Bessel
beam plane illumination
SO NATURE METHODS
LA English
DT Article
ID FLUORESCENCE MICROSCOPY; STRUCTURED-ILLUMINATION; LIGHT; FIELD
AB A key challenge when imaging living cells is how to noninvasively extract the most spatiotemporal information possible. Unlike popular wide-field and confocal methods, plane-illumination microscopy limits excitation to the information-rich vicinity of the focal plane, providing effective optical sectioning and high speed while minimizing out-of-focus background and premature photobleaching. Here we used scanned Bessel beams in conjunction with structured illumination and/or two-photon excitation to create thinner light sheets (< 0.5 mu m) better suited to three-dimensional (3D) subcellular imaging. As demonstrated by imaging the dynamics of mitochondria, filopodia, membrane ruffles, intracellular vesicles and mitotic chromosomes in live cells, the microscope currently offers 3D isotropic resolution down to similar to 0.3 mu m, speeds up to nearly 200 image planes per second and the ability to noninvasively acquire hundreds of 3D data volumes from single living cells encompassing tens of thousands of image frames.
C1 [Planchon, Thomas A.; Gao, Liang; Betzig, Eric] Howard Hughes Med Inst, Ashburn, VA USA.
[Milkie, Daniel E.] Coleman Technol Inc, Chadds Ford, PA USA.
[Davidson, Michael W.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32306 USA.
[Davidson, Michael W.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA.
[Galbraith, James A.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
[Galbraith, Catherine G.] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Betzig, E (reprint author), Howard Hughes Med Inst, Janelia Farm Res Campus, Ashburn, VA USA.
EM betzige@janelia.hhmi.org
RI Planchon, Thomas/C-5234-2013
FU National Institute of Neurological Disorders and Stroke
FX We thank D. Cabaniss and S. Bassin for machining services, H. White and
S. Michael for sample preparation; A. Arnold for confocal microscopy
support; H. Shroff for early instrumentation development; and M.
Gustafsson, L. Shao, R. Fiolka, P. Keller and N. Ji for valuable
discussions. mCerulean3 was a gift of M.A. Rizzo (University of
Maryland) and Neptune was a gift of M.Z. Lin (Stanford University).
Partial support was provided by the intramural program of the National
Institute of Neurological Disorders and Stroke.
NR 24
TC 347
Z9 357
U1 20
U2 192
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1548-7091
J9 NAT METHODS
JI Nat. Methods
PD MAY
PY 2011
VL 8
IS 5
BP 417
EP U68
DI 10.1038/NMETH.1586
PG 10
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 756BQ
UT WOS:000289987100020
PM 21378978
ER
PT J
AU Taylor, CE
Camargo, CA
AF Taylor, Christopher E.
Camargo, Carlos A., Jr.
TI Impact of micronutrients on respiratory infections
SO NUTRITION REVIEWS
LA English
DT Review
DE immune response; micronutrients; respiratory infection
ID PLACEBO-CONTROLLED TRIAL; A VIRUS-INFECTION; VITAMIN-D LEVELS;
MYCOBACTERIUM-TUBERCULOSIS; TRACT INFECTION; INFLUENZA-A; FOLIC-ACID;
25-HYDROXYVITAMIN-D LEVELS; DIETARY REQUIREMENT; DOUBLE-BLIND
AB Several studies have documented the impact of vitamin D and other micronutrients on host responses to upper and lower respiratory tract infections, such as influenza and tuberculosis. These studies include observational as well as micronutrient intervention studies. Other studies have been conducted to understand the mechanisms by which micronutrients alter immune responses. However, critical information gaps and challenges remain. An immediate need exists for randomized controlled trials of vitamin D supplementation in high-risk populations, such as infants, children, and patients with immunocompromised health. Other important areas of research include vitamin D genetics, the impact of other micronutrient deficiencies on innate and adaptive immunity, the 25(OH)D threshold for insufficiency, the need for valuable reliable markers, standardization of assays to detect 25(OH)D, novel functional markers beyond serum 25(OH)D, and further development of in vitro and animal models that could be useful for preclinical studies. Lastly, a new systems biology approach is needed to address the complexity of micronutrient effects and regulation.
C1 [Taylor, Christopher E.] NIAID, Resp Dis Branch, Div Microbiol & Infect Dis, Bethesda, MD 20852 USA.
[Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Taylor, CE (reprint author), NIAID, Resp Dis Branch, Div Microbiol & Infect Dis, 6610 Rockledge Dr,Room 5045, Bethesda, MD 20852 USA.
EM ctaylor@niaid.nih.gov
RI Osborne, Nicholas/N-4915-2015
OI Osborne, Nicholas/0000-0002-6700-2284
NR 71
TC 20
Z9 20
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0029-6643
J9 NUTR REV
JI Nutr. Rev.
PD MAY
PY 2011
VL 69
IS 5
BP 259
EP 269
DI 10.1111/j.1753-4887.2011.00386.x
PG 11
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 754XV
UT WOS:000289892100002
PM 21521228
ER
PT J
AU Bergman, RN
Stefanovski, D
Buchanan, TA
Sumner, AE
Reynolds, JC
Sebring, NG
Xiang, AH
Watanabe, RM
AF Bergman, Richard N.
Stefanovski, Darko
Buchanan, Thomas A.
Sumner, Anne E.
Reynolds, James C.
Sebring, Nancy G.
Xiang, Anny H.
Watanabe, Richard M.
TI A Better Index of Body Adiposity
SO OBESITY
LA English
DT Article
ID GESTATIONAL DIABETES-MELLITUS; DISEASE RISK; WAIST CIRCUMFERENCE;
METABOLIC SYNDROME; AFRICAN-AMERICANS; HEART-DISEASE; MASS INDEX;
OBESITY; PREVALENCE; CHILDREN
AB Obesity is a growing problem in the United States and throughout the world. It is a risk factor for many chronic diseases. The BMI has been used to assess body fat for almost 200 years. BMI is known to be of limited accuracy, and is different for males and females with similar %body adiposity. Here, we define an alternative parameter, the body adiposity index (BAI = ((hip circumference)/((height)(1.5))-18)). The BAI can be used to reflect %body fat for adult men and women of differing ethnicities without numerical correction. We used a population study, the "BetaGene" study, to develop the new index of body adiposity. %Body fat, as measured by the dual-energy X-ray absorptiometry (DXA), was used as a "gold standard" for validation. Hip circumference (R = 0.602) and height (R = -0.524) are strongly correlated with %body fat and therefore chosen as principal anthropometric measures on which we base BAI. The BAI measure was validated in the "Triglyceride and Cardiovascular Risk in African-Americans (TARA)" study of African Americans. Correlation between DXA-derived %adiposity and the BAI was R = 0.85 for TARA with a concordance of C_b = 0.95. BAI can be measured without weighing, which may render it useful in settings where measuring accurate body weight is problematic. In summary, we have defined a new parameter, the BAI, which can be calculated from hip circumference and height only. It can be used in the clinical setting even in remote locations with very limited access to reliable scales. The BAI estimates %adiposity directly.
C1 [Bergman, Richard N.; Stefanovski, Darko] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA.
[Buchanan, Thomas A.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA.
[Buchanan, Thomas A.] Univ So Calif, Keck Sch Med, Dept Ob Gyn & Physiol & Biophys, Los Angeles, CA 90033 USA.
[Sumner, Anne E.] Natl Inst Diabet & Digest & Kidney Dis NIDDK, Clin & Endocrinol Branch, NIH, Bethesda, MD USA.
[Reynolds, James C.] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Xiang, Anny H.] Kaiser Permanente So Calif Med Grp, Dept Res & Evaluat, Pasadena, CA USA.
[Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Div Biostat, Los Angeles, CA 90033 USA.
RP Bergman, RN (reprint author), Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA.
EM rbergman@usc.edu
OI Xiang, Anny/0000-0003-2786-1268
FU NIH [DK27619, DK29867, DKR01-61628]; American Diabetes Association
[7-04DCS]; USC GCRC [M01-RR-0043]; NIDDK at the NIH
FX R.N.B. is supported by the NIH DK27619 (M.E.R.I.T) and DK29867, and by
two Mentor Awards from the American Diabetes Association. R.N.B. had
full access to all of the data in the study and takes responsibility for
the integrity of the data and the accuracy of the data analysis. T.A.B.
and R.M.W. are supported by the NIH (DKR01-61628), and T.A.B. is also
supported with the ADA Distinguished Clinical Science Award (7-04DCS).
We thank the families who participated in the BetaGene Study, the
recruitment and technical staff, and the support of the USC GCRC
(M01-RR-0043). A.E.S. was supported by the Intramural Program of NIDDK
at the NIH. We are indebted to Drs. Marilyn Ader and Viorica Ionut for
improving the manuscript prior to publication.
NR 29
TC 219
Z9 234
U1 4
U2 30
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 MAY
PY 2011
VL 19
IS 5
BP 1083
EP 1089
DI 10.1038/oby.2011.38
PG 7
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 755LS
UT WOS:000289933300030
PM 21372804
ER
PT J
AU Jonasson, F
Arnarsson, A
Eiriksdottir, G
Harris, TB
Launer, LJ
Meuer, SM
Klein, BE
Klein, R
Gudnason, V
Cotch, MF
AF Jonasson, Fridbert
Arnarsson, Arsaell
Eiriksdottir, Gudny
Harris, Tamara B.
Launer, Lenore J.
Meuer, Stacy M.
Klein, Barbara E.
Klein, Ronald
Gudnason, Vilmundur
Cotch, Mary Frances
TI Prevalence of Age-related Macular Degeneration in Old Persons: Age,
Gene/Environment Susceptibility Reykjavik Study
SO OPHTHALMOLOGY
LA English
DT Article
ID BLUE MOUNTAINS EYE; RACIAL-DIFFERENCES; VISUAL IMPAIRMENT; MACULOPATHY;
BLINDNESS; POPULATION; BALTIMORE; ROTTERDAM; AUSTRALIA; RISK
AB Purpose: To describe the prevalence and signs of early and late age-related macular degeneration (AMD) in an old cohort.
Design: Population-based cohort study.
Participants: We included 5272 persons aged >= 66 years, randomly sampled from the Reykjavik area.
Methods: Fundus images were taken through dilated pupils using a 45-degree digital camera and graded for drusen size, type, area, increased retinal pigment, retinal pigment epithelial depigmentation, neovascular lesions, and geographic atrophy (GA) using the modified Wisconsin Age-Related Maculopathy Grading System.
Main Outcome Measures: Age-related macular degeneration in an elderly cohort.
Results: The mean age of participants was 76 years. The prevalence of early AMD was 12.4% (95% confidence interval [CI], 11.0-13.9) for those aged 66 to 74 years and 36% (95% CI, 30.9-41.1) for those aged >= 85 years. The prevalence of exudative AMD was 3.3% (95% CI, 2.8-3.8). The prevalence of pure GA was 2.4% (95% CI, 2.0-2.8). The highest prevalence of late AMD was among those aged >= 85 years: 11.4% (95% CI, 8.2-14.5) for exudative AMD and 7.6% (95% CI, 4.8-10.4) for pure GA.
Conclusions: Persons aged >= 85 years have a 10-fold higher prevalence of late AMD than those aged 70 to 74 years. The high prevalence of late AMD in the oldest age group and expected increase of elderly people in the western world in coming years call for improved preventive measures and novel treatments.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2011; 118: 825-830 (C) 2011 by the American Academy of Ophthalmology.
C1 [Jonasson, Fridbert; Gudnason, Vilmundur] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
[Jonasson, Fridbert] Landspitali Univ Hosp, Reykjavik, Iceland.
[Arnarsson, Arsaell] Univ Akureyri, Akureyri, Iceland.
[Eiriksdottir, Gudny] Iceland Heart Assoc, Kopavogur, Iceland.
[Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
[Meuer, Stacy M.; Klein, Barbara E.; Klein, Ronald] Univ Wisconsin, Madison, WI USA.
[Cotch, Mary Frances] NEI, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA.
RP Jonasson, F (reprint author), Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
EM fridbert@landspitali.is
RI Gudnason, Vilmundur/K-6885-2015;
OI Gudnason, Vilmundur/0000-0001-5696-0084; Cotch, Mary
Frances/0000-0002-2046-4350; Klein, Ronald/0000-0002-4428-6237
FU National Institutes of Health, National Institute on Ageing and the
National Eye Institute [Z01-EY00401, N01-AG-1-2100]; IHA; Icelandic
Parliament; University of Iceland
FX Supported by the National Institutes of Health (Intramural Research
Program of the National Institute on Ageing and the National Eye
Institute, Z01-EY00401 National Institutes of Health contract number
N01-AG-1-2100), the IHA, the Icelandic Parliament, and the University of
Iceland Research Fund.
NR 28
TC 43
Z9 43
U1 1
U2 11
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 MAY
PY 2011
VL 118
IS 5
BP 825
EP 830
DI 10.1016/j.ophtha.2010.08.044
PG 6
WC Ophthalmology
SC Ophthalmology
GA 757MM
UT WOS:000290090300006
PM 21126770
ER
PT J
AU Kawasaki, R
Cheung, N
Islam, FMA
Klein, R
Klein, BEK
Cotch, MF
Sharrett, AR
O'Leary, D
Wong, TY
AF Kawasaki, Ryo
Cheung, Ning
Islam, F. M. Amirul
Klein, Ronald
Klein, Barbara E. K.
Cotch, Mary Frances
Sharrett, A. Richey
O'Leary, Daniel
Wong, Tien Y.
CA Multiethnic Study Atherosclerosis
TI Is Diabetic Retinopathy Related to Subclinical Cardiovascular Disease?
SO OPHTHALMOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; RETINAL VASCULAR CALIBER; RISK-FACTORS;
CORONARY CALCIFICATION; MYOCARDIAL-INFARCTION; ATHEROSCLEROSIS RISK;
EVENTS; INDEX; ASSOCIATION; COMMUNITIES
AB Objective: Persons with diabetic retinopathy (DR) have an increased risk of clinical cardiovascular events. This study aimed to determine whether DR is associated with a range of measures of subclinical cardiovascular disease (CVD) in persons without clinical CVD.
Design: Population-based, cross-sectional epidemiologic study.
Participants: Nine hundred twenty-seven persons with diabetes without clinical CVD in the Multi-Ethnic Study of Atherosclerosis.
Methods: Diabetic retinopathy was ascertained from retinal photographs according to modification of the Airlie House Classification system. Vision-threatening DR (VTDR) was defined as severe nonproliferative DR, proliferative DR, or clinically significant macular edema. Subclinical CVD measures were assessed and defined as follows: high coronary artery calcium (CAC) score, defined as CAC score of 400 or more; low ankle-brachial index (ABI), defined as ABI of less than 0.9; high ABI, defined as ABI of 1.4 or more; high carotid intima-media thickness (IMT), defined as highest 25% of IMT; and carotid stenosis, defined as more than 25% stenosis or presence of carotid plaque.
Main Outcome Measures: Associations between DR and subclinical CVD measures.
Results: The prevalence of DR and VTDR in this sample was 30.0% and 7.2%, respectively, and VTDR was associated with a high CAC score (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.15-4.73), low ABI (OR, 2.54; 95% CI, 1.08-5.99), and high ABI (OR, 12.6; 95% CI, 1.14-140.6) after adjusting for risk factors including hemoglobin A1c level and duration of diabetes. The association between VTDR and high CAC score remained significant after further adjustment for hypoglycemic, antihypertensive, and cholesterol-lowering medications. Diabetic retinopathy was not significantly associated with measures of carotid artery disease.
Conclusions: In persons with diabetes without a history of clinical CVD, the presence of advanced-stage DR is associated with subclinical coronary artery disease. These findings emphasize the need to be careful about the use of anti-vascular endothelial growth factor for the treatment of DR.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2011; 118: 860-865 (C) 2011 by the American Academy of Ophthalmology.
C1 [Kawasaki, Ryo; Cheung, Ning; Islam, F. M. Amirul; Wong, Tien Y.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic 3002, Australia.
[Kawasaki, Ryo] St Vincent Hosp, Ctr Clin Res Excellence Diabet, Melbourne, Vic, Australia.
[Klein, Ronald; Klein, Barbara E. K.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA.
[Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Sharrett, A. Richey] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[O'Leary, Daniel] Caritas Carney Hosp, Dorchester, MA USA.
[Wong, Tien Y.] Natl Univ Singapore, Singapore Eye Res Inst, Singapore 117548, Singapore.
RP Wong, TY (reprint author), Univ Melbourne, Ctr Eye Res Australia, 32 Gisborne St, Melbourne, Vic 3002, Australia.
EM twong@unimelb.edu.au
RI Cheung, Ning Danny/F-2043-2013;
OI Cotch, Mary Frances/0000-0002-2046-4350; Klein,
Ronald/0000-0002-4428-6237
FU National Heart, Lung and Blood Institute, National Institutes of Health
[N01-HC-95159, N01-HC-95165, N01-HC-95169, R01HL69979]; National
Institutes of Health [HL69979-03]; National Eye Institute, National
Institutes of Health, Bethesda, Maryland [Z01EY00403]
FX Supported by the National Heart, Lung and Blood Institute, National
Institutes of Health (contract nos.: N01-HC-95159 through N01-HC-95165
and N01-HC-95169; and grant no.: R01HL69979 [RK and TYW]), the National
Institutes of Health (grant no.: HL69979-03 [RK and TYW]), and a
National Eye Institute, National Institutes of Health Intramural
Research Award (no.: Z01EY00403 [MFC]), Bethesda, Maryland; Dr. O'Leary
is a consultant for Pfizer and an equity owner in Medpace.
NR 26
TC 24
Z9 25
U1 0
U2 3
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 MAY
PY 2011
VL 118
IS 5
BP 860
EP 865
DI 10.1016/j.ophtha.2010.08.040
PG 6
WC Ophthalmology
SC Ophthalmology
GA 757MM
UT WOS:000290090300011
PM 21168222
ER
PT J
AU Yuan, PX
Tragon, T
Xia, MH
LeClair, CA
Skoumbourdis, AP
Zheng, W
Thomas, CJ
Huang, RL
Austin, CP
Chen, G
Guitart, X
AF Yuan, Peixiong
Tragon, Tyson
Xia, Menghang
LeClair, Christopher A.
Skoumbourdis, Amanda P.
Zheng, Wei
Thomas, Craig J.
Huang, Ruili
Austin, Christopher P.
Chen, Guang
Guitart, Xavier
TI Phosphodiesterase 4 inhibitors enhance sexual pleasure-seeking activity
in rodents
SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
LA English
DT Article
DE PDE4; Postmortem human brain; Depression; Pleasure-seeking activity
ID MAJOR DEPRESSIVE DISORDER; BIPOLAR DISORDER; PDE4 INHIBITORS;
MOUSE-BRAIN; ROLIPRAM; MODELS; RATS; ANTIDEPRESSANTS; INVOLVEMENT;
EXPRESSION
AB Pleasure-seeking deficits, including lack of libido, are a core feature of depression. Animal and preliminary clinical studies both suggest that phosphodiesterase 4 (PDE4) is a target for developing novel antidepressants. This study examined the potential involvement of PDE4 in the pathology of depression in both animal models and human postmortem brains. In humans, PDE4B and PDE4D levels were elevated in cingulate cortical tissue from individuals with major depressive disorder (MDD) compared to controls. Using the female urine smelling test (FUST), a recently refined method for monitoring sexual pleasure-seeking activity in mice, we found that icy infusion of selective potent PDE4 inhibitors enhanced sexual pleasure-seeking activity in male mice that underwent the learned helplessness or serotonin depletion paradigms. The infusion also increased sexual pleasure-seeking activity in naive male mice. The results suggest that PDE4 may be a plausible contributor to the sexual pleasure-seeking deficits seen in depressed patients; inhibiting PDE4 may restore these deficits. Published by Elsevier Inc.
C1 [Yuan, Peixiong; Guitart, Xavier] NIMH, Biomarker Lab, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
[Tragon, Tyson; Chen, Guang] NIMH, Mol Pharmacol Lab, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
[Xia, Menghang; LeClair, Christopher A.; Skoumbourdis, Amanda P.; Zheng, Wei; Thomas, Craig J.; Huang, Ruili; Austin, Christopher P.] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
RP Chen, G (reprint author), Johnson & Johnson Pharmaceut Res & Dev LLC, Neurosci Drug Discovery, 3210 Merryfield Row, San Diego, CA 92121 USA.
EM PeixiongYuan@mail.nih.gov; tragont@mail.nih.gov; mxia@mail.nih.gov;
leclairc@mail.nih.gov; Amanda.skoumbourdis@gmail.com;
wzheng@mail.nih.gov; craigt@mail.nih.gov; huangru@mail.nih.gov;
austinc@mail.nih.gov; GChen13@its.jnj.com; guitartx@mail.nih.gov
RI Chen, Guang/A-2570-2017;
OI Zheng, Wei/0000-0003-1034-0757
FU National Institute of Mental Health, National Institutes of Health;
Department of Health and Human Services (IRP-NIMH-NIH-DHHS)
FX This study was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health, and
Department of Health and Human Services (IRP-NIMH-NIH-DHHS). Ioline
Henter provided invaluable editorial assistance.
NR 29
TC 1
Z9 1
U1 0
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0091-3057
J9 PHARMACOL BIOCHEM BE
JI Pharmacol. Biochem. Behav.
PD MAY
PY 2011
VL 98
IS 3
BP 349
EP 355
DI 10.1016/j.pbb.2011.02.001
PG 7
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 756KV
UT WOS:000290011000004
PM 21296104
ER
PT J
AU Imayama, I
Alfano, CM
Bertram, LAC
Wang, CC
Xiao, LR
Duggan, C
Campbell, KL
Foster-Schubert, KE
McTiernan, A
AF Imayama, Ikuyo
Alfano, Catherine M.
Bertram, Lisa A. Cadmus
Wang, Chiachi
Xiao, Liren
Duggan, Catherine
Campbell, Kristin L.
Foster-Schubert, Karen E.
McTiernan, Anne
TI Effects of 12-month exercise on health-related quality of life: A
randomized controlled trial
SO PREVENTIVE MEDICINE
LA English
DT Article
DE Exercise; Health-related quality of life; Exercise self-efficacy;
Physical activity
ID PHYSICAL-ACTIVITY; OLDER-ADULTS; SELF-EFFICACY; MENTAL-HEALTH;
CARDIOVASCULAR-DISEASE; CANCER SURVIVORS; RISK-FACTORS; ADHERENCE;
WOMEN; WEIGHT
AB Objective. We investigated exercise effects on health-related quality of life (HRQOL) and exercise self-efficacy, and tested effect modification by baseline body mass index (BMI) and gender.
Methods. Middle-aged women (n = 100) and men (n = 102) were randomly assigned to either exercise (360 min/week of moderate-to-vigorous aerobic exercise) or control in Seattle, WA, from 2001 to 2004. Demographics, anthropometrics, exercise self-efficacy (5-item self-efficacy questionnaire) and HRQOL (SF-36) were assessed at baseline and 12 months. Analysis of covariance adjusting for baseline scores was used to compare HRQOL and exercise self-efficacy scores between the exercise and control groups.
Results. At 12 months, exercisers demonstrated higher exercise self-efficacy than controls (percent change from baseline: -6.5% vs. -15.0%, p < 0.01), without differences in HRQOL Baseline BMI category and gender did not modify these effects. In exploratory analyses comparing exercisers and controls within subgroups defined by gender and BMI, 12-month HRQOL scores [role-physical ( +7.0% vs. -13.1%), vitality ( +15.6% vs. -4.2%), social functioning (+10.0% vs. -3.5%), and mental health (+6.8% vs. -2.9%)] were higher only among overweight male exercisers (p < 0.05, vs. control).
Conclusion. Three hundred and sixty minutes per week of exercise, recommended for weight maintenance, did not have negative effects on exercise self-efficacy or HRQOL This level of exercise may increase HRQOL among overweight men.
Trial registration. NCT00668161. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Imayama, Ikuyo; Wang, Chiachi; Xiao, Liren; Duggan, Catherine; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Alfano, Catherine M.] NCI, Off Canc Survivorship, NIH, Bethesda, MD 20892 USA.
[Bertram, Lisa A. Cadmus] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.
[Campbell, Kristin L.] Univ British Columbia, Fac Med, Vancouver, BC V6T 1Z3, Canada.
[Foster-Schubert, Karen E.; McTiernan, Anne] Univ Washington, Sch Med, Seattle, WA 98108 USA.
[McTiernan, Anne] Univ Washington, Sch Publ Hlth, Seattle, WA 98108 USA.
RP McTiernan, A (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,Mail Stop M4-B874,POB 19024, Seattle, WA 98109 USA.
EM iimayama@fhcrc.org; alfanoc@mail.nih.gov; lcadmus@ucsd.edu;
cwan2@fhcrc.org; lxiao@fhcrc.org; cduggan@fhcrc.org;
kristin.campbell@ubc.ca; kfoster@u.washington.edu; amctiern@fhcrc.org
RI Duggan, Catherine/F-9414-2015
OI Duggan, Catherine/0000-0001-7369-4021
FU National Cancer Institute [R01 CA77572, U54 CA116847]; National
Institutes of Health [5KL2RR025015-03]; Canadian Institutes of Health
Research (CIHR)
FX This study was funded by grants from the National Cancer Institute (R01
CA77572 and U54 CA116847, Transdisciplinary Research on Energetics and
Cancer). K.E.F. was supported by National Institutes of Health
(5KL2RR025015-03). K.L.C. received support from a Canadian Institutes of
Health Research (CIHR) fellowship.
NR 50
TC 9
Z9 10
U1 3
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0091-7435
EI 1096-0260
J9 PREV MED
JI Prev. Med.
PD MAY 1
PY 2011
VL 52
IS 5
BP 344
EP 351
DI 10.1016/j.ypmed.2011.02.016
PG 8
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 757CO
UT WOS:000290062000009
PM 21371498
ER
PT J
AU Spector, D
DeRoo, LA
Sandler, DP
AF Spector, Denise
DeRoo, Lisa A.
Sandler, Dale P.
TI Lifestyle behaviors in Black and White women with a family history of
breast cancer
SO PREVENTIVE MEDICINE
LA English
DT Article
DE Breast cancer risk; Lifestyle behaviors; Physical activity;
Overweight/obesity; Diet
ID PHYSICAL-ACTIVITY; POSTMENOPAUSAL WOMEN; RISK; EXERCISE
AB Objectives. To examine lifestyle behaviors among non-Hispanic Black and White women with a family history of breast cancer and determine the extent to which they meet American Cancer Society (ACS) Nutrition and Physical Activity Recommendations for Breast Cancer Prevention.
Method. Cross-sectional data from 44,364 women enrolled in the Sister Study (2009), a study of sisters of women with breast cancer within the U.S., were analyzed. Descriptive statistics and chi-square analyses were used to examine body mass index and lifestyle behaviors (e.g., exercise, diet, and smoking) and to determine percentages of women meeting ACS recommendations.
Results. Black women consumed a lower percentage of calories from fat (mean 36.90% vs. 37.17%) and were more likely to meet ACS alcohol recommendations than Whites. White women consumed more fruits and vegetables/day (mean 4.81 vs. 4.41) than Black women and were more likely to meet ACS guidelines for physical activity (26.4% vs. 18.2%) and body mass index (42.5% vs. 16.7%).
Conclusion. Despite an elevated risk for breast cancer due to a family history of breast cancer, the majority of women were no more likely than women in the general population to engage in healthy lifestyle behaviors. These women may benefit from lifestyle behavior risk-reduction counseling. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Spector, Denise] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA.
[DeRoo, Lisa A.; Sandler, Dale P.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
RP Spector, D (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, CB 8615,3433 Country Club Dr, Chapel Hill, NC 27599 USA.
EM dspector@email.unc.edu; DerooL@niehs.nih.gov; sandler@niehs.nih.gov
OI Sandler, Dale/0000-0002-6776-0018
FU American Cancer Society [DSCN-07-132-01]; NIH, National Institute of
Environmental Health Sciences [Z01 ES0044005]
FX The first author would like to acknowledge the American Cancer Society
for their support through a Doctoral Degree Scholarship in Cancer
Nursing (grant number DSCN-07-132-01). This work was also funded, in
part, by the Intramural Research Program of the NIH, National Institute
of Environmental Health Sciences (Z01 ES0044005). A special thanks to
the supportive staff of the Sister Study, especially Dan Scharf for
programming assistance.
NR 19
TC 15
Z9 16
U1 3
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0091-7435
J9 PREV MED
JI Prev. Med.
PD MAY 1
PY 2011
VL 52
IS 5
BP 394
EP 397
DI 10.1016/j.ypmed.2011.03.001
PG 4
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 757CO
UT WOS:000290062000020
PM 21396953
ER
PT J
AU McCoy, MT
Jayanthi, S
Wulu, JA
Beauvais, G
Ladenheim, B
Martin, TA
Krasnova, IN
Hodges, AB
Cadet, JL
AF McCoy, Michael T.
Jayanthi, Subramaniam
Wulu, Jacqueline A.
Beauvais, Genevieve
Ladenheim, Bruce
Martin, Tracey A.
Krasnova, Irina N.
Hodges, Amber B.
Cadet, Jean Lud
TI Chronic methamphetamine exposure suppresses the striatal expression of
members of multiple families of immediate early genes (IEGs) in the rat:
normalization by an acute methamphetamine injection
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Addiction; Arc; Preprotachykinin; Dynorphin; Molecular neuroadaptations
ID MESSENGER-RNA EXPRESSION; ELEMENT-BINDING PROTEIN; INDUCED
UP-REGULATION; INDUCED BEHAVIORAL SENSITIZATION; INDUCED STRUCTURAL
PLASTICITY; CHRONIC COCAINE TREATMENT; C-FOS EXPRESSION; TRANSCRIPTION
FACTORS; NGFI-A; CHRONIC AMPHETAMINE
AB Repeated injections of cocaine cause blunted responses to acute cocaine challenge-induced increases in the expression of immediate early genes (IEGs).
The aim of this study was to test if chronic methamphetamine (METH) exposure might cause similar blunting of acute METH-induced increases in IEG expression.
Repeated saline or METH injections were given to rats over 14 days. After 1 day of withdrawal, they received a single injection of saline or METH (5 mg/kg). Acute injection of METH increased c-fos, fosB, fra2, junB, Egr1-3, Nr4a1 (Nur77), and Nr4a3 (Nor-1) mRNA levels in the striatum of saline-pretreated rats. Chronic METH treatment alone reduced the expression of AP1, Erg1-3, and Nr4a1 transcription factors below control levels. Acute METH challenge normalized these values in METH-pretreated rats. Unexpectedly, acute METH challenge to METH-pretreated animals caused further decreases in Nr4a2 (Nurr1) mRNA levels. In contrast, the METH challenge caused significant but blunted increases in Nr4a3 and Arc expression in METH-pretreated rats. There were also chronic METH-associated decreases in the expression of cAMP responsive element binding protein (CREB) which modulates IEG expression via activation of the cAMP/PKA/CREB signal transduction pathway. Chronic METH exposure also caused significant decreases in preprotachykinin, but not in prodynorphin, mRNA levels.
These results support the accumulated evidence that chronic administration of psychostimulants is associated with blunting of their acute stimulatory effects on IEG expression. The METH-induced renormalization of the expression of several IEGs in rats chronically exposed to METH hints to a potential molecular explanation for the recurrent self-administration of the drug by human addicts.
C1 [McCoy, Michael T.; Jayanthi, Subramaniam; Wulu, Jacqueline A.; Beauvais, Genevieve; Ladenheim, Bruce; Martin, Tracey A.; Krasnova, Irina N.; Hodges, Amber B.; Cadet, Jean Lud] NIDA, Mol Neuropsychiat Res Branch, DHHS, NIH,Intramural Res Program, Baltimore, MD 21224 USA.
[Hodges, Amber B.] Morgan State Univ, Dept Psychol, Baltimore, MD 21239 USA.
RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Res Branch, DHHS, NIH,Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM jcadet@intra.nida.nih.gov
FU DHHS/NIH/NIDA
FX This research was supported by funds of the Intramural Research Program
of the DHHS/NIH/NIDA.
NR 107
TC 25
Z9 25
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD MAY
PY 2011
VL 215
IS 2
BP 353
EP 365
DI 10.1007/s00213-010-2146-7
PG 13
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 756BE
UT WOS:000289985700015
PM 21229349
ER
PT J
AU Gogtay, N
Vyas, NS
Testa, R
Wood, SJ
Pantelis, C
AF Gogtay, Nitin
Vyas, Nora S.
Testa, Renee
Wood, Stephen J.
Pantelis, Christos
TI Age of Onset of Schizophrenia: Perspectives From Structural Neuroimaging
Studies
SO SCHIZOPHRENIA BULLETIN
LA English
DT Article
DE schizophrenia; adolescent; brain development; high risk; neural
circuitry; prefrontal cortex
ID ULTRA-HIGH-RISK; BRAIN DEVELOPMENTAL TRAJECTORIES; ANTERIOR CINGULATE
CORTEX; SUPERIOR TEMPORAL GYRUS; HUMAN CEREBRAL-CORTEX; GRAY-MATTER
VOLUME; MAGNETIC-RESONANCE; PREFRONTAL CORTEX; WHITE-MATTER; DEVELOPING
PSYCHOSIS
AB Many of the major neuropsychiatric illnesses, including schizophrenia, have a typical age of onset in late adolescence. Late adolescence may reflect a critical period in brain development making it particularly vulnerable for the onset of psychopathology. Neuroimaging studies that focus on this age range may provide unique insights into the onset and course of psychosis. In this review, we examine the evidence from 2 unique longitudinal cohorts that span the ages from early childhood through young adulthood; a study of childhood-onset schizophrenia where patients and siblings are followed from ages 6 through to their early twenties, and an ultra-high risk study where subjects (mean age of 19 years) are studied before and after the onset of psychosis. From the available evidence, we make an argument that subtle, regionally specific, and genetically influenced alterations during developmental age windows influence the course of psychosis and the resultant brain phenotype. The importance of examining trajectories of development and the need for future combined approaches, using multimodal imaging together with molecular studies is discussed.
C1 [Pantelis, Christos] Univ Melbourne, Melbourne Neuropsychiat Ctr, Natl Neurosci Facil, Dept Psychiat, Carlton, Vic 3053, Australia.
[Testa, Renee; Wood, Stephen J.; Pantelis, Christos] Melbourne Hlth, Melbourne, Vic, Australia.
[Gogtay, Nitin; Vyas, Nora S.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA.
[Wood, Stephen J.] Univ Birmingham, Sch Psychol, Birmingham B15 2TT, W Midlands, England.
RP Pantelis, C (reprint author), Univ Melbourne, Melbourne Neuropsychiat Ctr, Natl Neurosci Facil, Dept Psychiat, 161 Barry St, Carlton, Vic 3053, Australia.
EM cpant@unimelb.edu.au
RI Gogtay, Nitin/A-3035-2008; Wood, Stephen/M-8652-2014; Pantelis,
Christos/H-7722-2014
OI Wood, Stephen/0000-0003-4186-5919; Pantelis,
Christos/0000-0002-9565-0238
FU US-UK Fulbright Commission; NHMRC [ID: 628386, ID: 350241, 566529]
FX N.S.V. is supported by the Fulbright Distinguished Scholar Award by the
US-UK Fulbright Commission. C. P. is supported by a NHMRC Senior
Principal Research Fellowship (ID: 628386) and NHMRC Program Grants (ID:
350241, 566529).
NR 131
TC 66
Z9 68
U1 11
U2 27
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0586-7614
EI 1745-1701
J9 SCHIZOPHRENIA BULL
JI Schizophr. Bull.
PD MAY
PY 2011
VL 37
IS 3
BP 504
EP 513
DI 10.1093/schbul/sbr030
PG 10
WC Psychiatry
SC Psychiatry
GA 753UF
UT WOS:000289804500012
PM 21505117
ER
PT J
AU Takahashi, K
Kamijo, Y
Hora, K
Hashimoto, K
Higuchi, M
Nakajima, T
Ehara, T
Shigematsu, H
Gonzalez, FJ
Aoyama, T
AF Takahashi, Kyoko
Kamijo, Yuji
Hora, Kazuhiko
Hashimoto, Koji
Higuchi, Makoto
Nakajima, Takero
Ehara, Takashi
Shigematsu, Hidekazu
Gonzalez, Frank J.
Aoyama, Toshifumi
TI Pretreatment by low-dose fibrates protects against acute free fatty
acid-induced renal tubule toxicity by counteracting PPAR alpha
deterioration
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Free fatty acid toxicity; Fibrates; Kidney disease; Proximal tubule;
PPAR
ID ACTIVATED RECEPTOR-ALPHA; COENZYME-A SYNTHETASE; RAT-LIVER PEROXISOMES;
EPITHELIAL-CELLS; MICE; EXPRESSION; DISEASE; GENE; DEHYDROGENASE;
MITOCHONDRIAL
AB Development of a preventive strategy against tubular damage associated with proteinuria is of great importance. Recently, free fatty acid (FFA) toxicities accompanying proteinuria were found to be a main cause of tubular damage, which was aggravated by insufficiency of peroxisome proliferator-activated receptor alpha (PPAR alpha), suggesting the benefit of PPAR alpha activation. However, an earlier study using a murine acute tubular injury model, FFA-overload nephropathy, demonstrated that high-dose treatment of PPAR alpha agonist (0.5% clofibrate diet) aggravated the tubular damage as a consequence of excess serum accumulation of clofibrate metabolites due to decreased kidney elimination. To induce the renoprotective effects of PPAR alpha agonists without drug accumulation, we tried a pretreatment study using low-dose clofibrate (0.1% clofibrate diet) using the same murine model. Low-dose clofibrate pretreatment prevented acute tubular injuries without accumulation of its metabolites. The tubular protective effects appeared to be associated with the counteraction of PPAR alpha deterioration, resulting in the decrease of FFAs influx to the kidney, maintenance of fatty acid oxidation, diminution of intracellular accumulation of undigested FFAs, and attenuation of disease developmental factors including oxidative stress, apoptosis, and NF kappa B activation. These effects are common to other fibrates and dependent on PPAR alpha function. Interestingly, however, clofibrate pretreatment also exerted PPAR alpha-independent tubular toxicities in PPAR alpha-null mice with FFA-overload nephropathy. The favorable properties of fibrates are evident when PPAR alpha-dependent tubular protective effects outweigh their PPAR alpha-independent tubular toxicities. This delicate balance seems to be easily affected by the drug dose. It will be important to establish the appropriate dosage of fibrates for treatment against kidney disease and to develop a novel PPAR alpha activator that has a steady serum concentration regardless of kidney dysfunction. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Takahashi, Kyoko; Kamijo, Yuji; Hora, Kazuhiko; Hashimoto, Koji; Higuchi, Makoto] Shinshu Univ, Sch Med, Dept Nephrol Internal Med, Matsumoto, Nagano 3908621, Japan.
[Takahashi, Kyoko; Kamijo, Yuji; Hashimoto, Koji; Nakajima, Takero; Aoyama, Toshifumi] Shinshu Univ, Sch Med, Inst Aging & Adaptat, Dept Metab Regulat, Matsumoto, Nagano 3908621, Japan.
[Ehara, Takashi; Shigematsu, Hidekazu] Shinshu Univ, Sch Med, Dept Pathol, Matsumoto, Nagano 3908621, Japan.
[Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA.
RP Kamijo, Y (reprint author), Shinshu Univ, Sch Med, Dept Nephrol Internal Med, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan.
EM yujibeat@shinshu-u.ac.jp
NR 42
TC 10
Z9 10
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD MAY 1
PY 2011
VL 252
IS 3
BP 237
EP 249
DI 10.1016/j.taap.2011.02.012
PG 13
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 757CQ
UT WOS:000290062200004
PM 21338618
ER
PT J
AU Xia, MH
Shahane, SA
Huang, RL
Titus, SA
Shum, E
Zhao, Y
Southall, N
Zheng, W
Witt, KL
Tice, RR
Austin, CP
AF Xia, Menghang
Shahane, Sampada A.
Huang, Ruili
Titus, Steven A.
Shum, Enoch
Zhao, Yong
Southall, Noel
Zheng, Wei
Witt, Kristine L.
Tice, Raymond R.
Austin, Christopher P.
TI Identification of quaternary ammonium compounds as potent inhibitors of
hERG potassium channels
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Cardiotoxicity; hERG; Long QT syndrome; NTP 1408 library; Patch clamp;
qHTS; Tetra-n-octylammonium bromide; Thallium influx
ID K+ CHANNELS; 1,3-DIPHENYLGUANIDINE; PHARMACOLOGY; HEALTH; DRUGS;
ELECTROPHYSIOLOGY; PROLONGATION; RESISTANCE; TOXICOLOGY; TAMOXIFEN
AB The human ether-a-go-go-related gene (hERG) channel, a member of a family of voltage-gated potassium (K(+)) channels, plays a critical role in the repolarization of the cardiac action potential. The reduction of hERG channel activity as a result of adverse drug effects or genetic mutations may cause QT interval prolongation and potentially leads to acquired long QT syndrome. Thus, screening for hERG channel activity is important in drug development. Cardiotoxicity associated with the inhibition of hERG channels by environmental chemicals is also a public health concern. To assess the inhibitory effects of environmental chemicals on hERG channel function, we screened the National Toxicology Program (NIP) collection of 1408 compounds by measuring thallium influx into cells through hERG channels. Seventeen compounds with hERG channel inhibition were identified with IC(50) potencies ranging from 0.26 to 22 mu M. Twelve of these compounds were confirmed as hERG channel blockers in an automated whole cell patch clamp experiment. In addition, we investigated the structure-activity relationship of seven compounds belonging to the quaternary ammonium compound (QAC) series on hERG channel inhibition. Among four active QAC compounds, tetra-n-octylammonium bromide was the most potent with an IC(50) value of 260 nM in the thallium influx assay and 80 nM in the patch clamp assay. The potency of this class of hERG channel inhibitors appears to depend on the number and length of their aliphatic side-chains surrounding the charged nitrogen. Profiling environmental compound libraries for hERG channel inhibition provides information useful in prioritizing these compounds for cardiotoxicity assessment in vivo. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Xia, Menghang; Shahane, Sampada A.; Huang, Ruili; Titus, Steven A.; Southall, Noel; Zheng, Wei; Austin, Christopher P.] NIH, NIH Chem Genom Ctr, Bethesda, MD 20892 USA.
[Shum, Enoch; Zhao, Yong] Cerep Inc, Redmond, WA USA.
[Witt, Kristine L.; Tice, Raymond R.] Natl Inst Environm Hlth Sci, Natl Toxicol Program, Res Triangle Pk, NC USA.
RP Xia, MH (reprint author), NIH, NIH Chem Genom Ctr, 9800 Med Ctr Dr, Bethesda, MD 20892 USA.
EM mxia@mail.nih.gov
RI Southall, Noel/H-8991-2012;
OI Southall, Noel/0000-0003-4500-880X; Zheng, Wei/0000-0003-1034-0757
FU National Institute of Environmental Health Sciences [Y2-ES-7020-01];
National Human Genome Research Institute, National Institutes of Health
(NIH); NIH
FX This work was supported by the Intramural Research Programs (Interagency
agreement #Y2-ES-7020-01) of the National Toxicology Program, National
Institute of Environmental Health Sciences, and the National Human
Genome Research Institute, National Institutes of Health (NIH), and the
NIH Roadmap for Medical Research Molecular Libraries Program. This
article is the work product of employees of the National Institute of
Environmental Health Sciences and the National Human Genome Research
Institute, NIH. The statements, opinions, or conclusions contained
therein do not necessarily represent the statements, opinions, or
conclusions of NIH or the United States government.
NR 48
TC 15
Z9 16
U1 3
U2 11
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD MAY 1
PY 2011
VL 252
IS 3
BP 250
EP 258
DI 10.1016/j.taap.2011.02.016
PG 9
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 757CQ
UT WOS:000290062200005
PM 21362439
ER
PT J
AU Nita-Lazar, A
AF Nita-Lazar, Aleksandra
TI Quantitative analysis of phosphorylation-based protein signaling
networks in the immune system by mass spectrometry
SO WILEY INTERDISCIPLINARY REVIEWS-SYSTEMS BIOLOGY AND MEDICINE
LA English
DT Article
ID METAL AFFINITY-CHROMATOGRAPHY; T-CELL-RECEPTOR;
TYROSINE-PHOSPHORYLATION; PHOSPHOPROTEOMIC ANALYSIS;
SACCHAROMYCES-CEREVISIAE; IN-VIVO; PHOSPHOPEPTIDES; ENRICHMENT; SITES;
PEPTIDES
AB Dynamic modification of cell proteins with phosphate is one of the key regulators of the cellular response to external stimuli. Phosphorylation-based signaling networks mediate cell proliferation, differentiation, and migration, and their dysregulation is the basis of multiple diseases. However, the transient nature of the regulatory protein phosphorylation and low site occupancy mean that only a fraction of the protein is phosphorylated at a given time, and it is a challenge to measure the degree and dynamics of phosphorylation using traditional biochemical means. Technological advances in the field of mass spectrometry (MS) made it possible to generate large sets of phosphoproteomics data, probing the phosphoproteome with great depth, sensitivity, and accuracy. Therefore, quantitative phosphoproteomics emerged as one of the essential components of the systems biology approach for profiling of complex biological networks. Nowadays, the challenge lies in validation of the information and in its integration into the comprehensive models of cell decision processes. This article reviews the role of phosphoproteomics in systems biology, the MS-based approach, and technical details of the methods. Recent examples of quantitative measurements and methodologies as well as applications to the studies of the immune system and infectious diseases are presented and discussed. (C) 2010 John Wiley & Sons, Inc. WIREs Syst Biol Med 2011 3368-376 DOI: 10.1002/wsbm.123
C1 NIAID, Program Syst Immunol & Infect Dis Modeling, NIH, Bethesda, MD 20892 USA.
RP Nita-Lazar, A (reprint author), NIAID, Program Syst Immunol & Infect Dis Modeling, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM nitalazarau@niaid.nih.gov
NR 57
TC 6
Z9 6
U1 0
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1939-5094
EI 1939-005X
J9 WIRES SYST BIOL MED
JI Wiley Interdiscip. Rev.-Syst. Biol
PD MAY-JUN
PY 2011
VL 3
IS 3
BP 368
EP 376
DI 10.1002/wsbm.123
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 757YN
UT WOS:000290125100011
PM 20836078
ER
PT J
AU Larsen, M
Yamada, KM
Musselmann, K
AF Larsen, Melinda
Yamada, Kenneth M.
Musselmann, Kurt
TI Systems analysis of salivary gland development and disease (vol 2, pg
670, 2010)
SO WILEY INTERDISCIPLINARY REVIEWS-SYSTEMS BIOLOGY AND MEDICINE
LA English
DT Correction
C1 [Larsen, Melinda] SUNY Albany, Albany, NY 12222 USA.
[Yamada, Kenneth M.; Musselmann, Kurt] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD USA.
RP Larsen, M (reprint author), SUNY Albany, Albany, NY 12222 USA.
EM mlarsen@albany.edu; kyamada@mail.nih.gov; Musselmannk@mail.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1939-5094
J9 WIRES SYST BIOL MED
JI Wiley Interdiscip. Rev.-Syst. Biol
PD MAY-JUN
PY 2011
VL 3
IS 3
BP 377
EP 377
DI 10.1002/wsbm.152
PG 1
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 757YN
UT WOS:000290125100012
ER
PT J
AU Heilig, M
AF Heilig, Markus
TI A WELCOME CHANGE THAT STOPS SHORT OF BEING FULLY SATISFYING
SO ADDICTION
LA English
DT Editorial Material
DE Addiction; decision making; dependence; neuroadaptation; reward; stress
ID CORTICOTROPIN-RELEASING-FACTOR; DEPENDENCE; ADDICTION
C1 NIAAA, Lab Clin & Translat Studies, Bethesda, MD 20892 USA.
RP Heilig, M (reprint author), NIAAA, Lab Clin & Translat Studies, 10 Ctr Dr,10-1E-5334, Bethesda, MD 20892 USA.
EM markus.heilig@mail.nih.gov
OI Heilig, Markus/0000-0003-2706-2482
NR 7
TC 2
Z9 2
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0965-2140
J9 ADDICTION
JI Addiction
PD MAY
PY 2011
VL 106
IS 5
BP 874
EP 875
DI 10.1111/j.1360-0443.2010.03233.x
PG 2
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 747CC
UT WOS:000289296900007
PM 21477231
ER
PT J
AU Heilig, M
Schank, JR
Thorsell, A
Rice, KC
AF Heilig, Markus
Schank, Jesse R.
Thorsell, Annika
Rice, Kenner C.
TI Preclinical validation of the neurokinin 1 receptor (NK1R) as a target
for treatment of alcoholism
SO ALCOHOL
LA English
DT Meeting Abstract
CT Conference on Alcoholism and Stress - A Framework for Future Treatment
Strategies
CY MAY 06-08, 2008
CL Volterra, ITALY
C1 [Heilig, Markus; Schank, Jesse R.; Thorsell, Annika] NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA.
[Rice, Kenner C.] NIDA, Chem Biol Branch, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-8329
EI 1873-6823
J9 ALCOHOL
JI Alcohol
PD MAY
PY 2011
VL 45
IS 3
BP 271
EP 271
PG 1
WC Substance Abuse; Pharmacology & Pharmacy; Toxicology
SC Substance Abuse; Pharmacology & Pharmacy; Toxicology
GA 750HX
UT WOS:000289538300028
ER
PT J
AU Alvarez, VA
Carlson, VCC
Sherazee, N
Seabold, GK
Sprow, G
Helms, C
Thiele, T
Lovinger, DM
Grant, KA
AF Alvarez, Veronica A.
Carlson, Verginia C. Cuzon
Sherazee, Nyssa
Seabold, Gail K.
Sprow, Gretchen
Helms, Christa
Thiele, Todd
Lovinger, David M.
Grant, Kathleen A.
TI Morphological and functional changes at striatal synapses after
prolonged ethanol self-administration in monkeys and rodents
SO ALCOHOL
LA English
DT Meeting Abstract
CT Conference on Alcoholism and Stress - A Framework for Future Treatment
Strategies
CY MAY 06-08, 2008
CL Volterra, ITALY
C1 [Alvarez, Veronica A.; Sherazee, Nyssa; Seabold, Gail K.] NIAAA208, Sect Neuronal Struct, NIH, Bethesda, MD 20892 USA.
[Carlson, Verginia C. Cuzon; Lovinger, David M.] NIAAA, Sect Synapt Pharmacol, NIH, Bethesda, MD 20892 USA.
[Sprow, Gretchen; Thiele, Todd] Univ N Carolina, Dept Psychol, Chapel Hill, NC 27515 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-8329
EI 1873-6823
J9 ALCOHOL
JI Alcohol
PD MAY
PY 2011
VL 45
IS 3
BP 281
EP 281
PG 1
WC Substance Abuse; Pharmacology & Pharmacy; Toxicology
SC Substance Abuse; Pharmacology & Pharmacy; Toxicology
GA 750HX
UT WOS:000289538300069
ER
PT J
AU Dias-Ferreira, E
Sousa, JC
Jin, X
Cerqueira, JJ
Sousa, N
Costa, RM
AF Dias-Ferreira, Eduardo
Sousa, Joao C.
Jin, Xin
Cerqueira, Joao J.
Sousa, Nuno
Costa, Rui M.
TI Stressing out Decisions
SO ALCOHOL
LA English
DT Meeting Abstract
CT Conference on Alcoholism and Stress - A Framework for Future Treatment
Strategies
CY MAY 06-08, 2008
CL Volterra, ITALY
C1 [Dias-Ferreira, Eduardo; Costa, Rui M.] Inst Gulbenkian Ciencias, Champalimaud Neurosci Programme, Oeiras, Portugal.
[Dias-Ferreira, Eduardo; Sousa, Joao C.; Cerqueira, Joao J.; Sousa, Nuno] Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst ICVS, Braga, Portugal.
[Dias-Ferreira, Eduardo; Jin, Xin; Costa, Rui M.] NIAAA, NIH, Sect Vivo Neural Funct, Lab Integrat Neurosci, Bethesda, MD USA.
[Dias-Ferreira, Eduardo] Univ Coimbra, Ctr Neurosci & Cell Biol, PhD Programme Expt Biol & Biomed PDBEB, Coimbra, Portugal.
RI Cerqueira, Joao/B-4579-2008
OI Cerqueira, Joao/0000-0003-3155-2775
NR 0
TC 0
Z9 0
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-8329
EI 1873-6823
J9 ALCOHOL
JI Alcohol
PD MAY
PY 2011
VL 45
IS 3
BP 281
EP 281
PG 1
WC Substance Abuse; Pharmacology & Pharmacy; Toxicology
SC Substance Abuse; Pharmacology & Pharmacy; Toxicology
GA 750HX
UT WOS:000289538300066
ER
PT J
AU Mason, B
Heilig, M
AF Mason, Barbara
Heilig, Markus
TI Clinical Treatments Roundtable
SO ALCOHOL
LA English
DT Meeting Abstract
CT Conference on Alcoholism and Stress - A Framework for Future Treatment
Strategies
CY MAY 06-08, 2008
CL Volterra, ITALY
C1 [Mason, Barbara] Scripps Res Inst, La Jolla, CA 92037 USA.
[Heilig, Markus] NIAAA, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-8329
EI 1873-6823
J9 ALCOHOL
JI Alcohol
PD MAY
PY 2011
VL 45
IS 3
BP 285
EP 285
PG 1
WC Substance Abuse; Pharmacology & Pharmacy; Toxicology
SC Substance Abuse; Pharmacology & Pharmacy; Toxicology
GA 750HX
UT WOS:000289538300083
ER
PT J
AU Camp, MC
Debrouse, L
Holmes, A
AF Camp, Marguerite C.
Debrouse, Lauren
Holmes, Andrew
TI Chronic intermittent ethanol vapor exposure as a tool for modeling major
diagnostic criteria for alcohol dependence in mice
SO ALCOHOL
LA English
DT Meeting Abstract
CT Conference on Alcoholism and Stress - A Framework for Future Treatment
Strategies
CY MAY 06-08, 2008
CL Volterra, ITALY
C1 [Camp, Marguerite C.; Debrouse, Lauren; Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-8329
EI 1873-6823
J9 ALCOHOL
JI Alcohol
PD MAY
PY 2011
VL 45
IS 3
BP 292
EP 292
PG 1
WC Substance Abuse; Pharmacology & Pharmacy; Toxicology
SC Substance Abuse; Pharmacology & Pharmacy; Toxicology
GA 750HX
UT WOS:000289538300108
ER
PT J
AU Carlson, VCC
Gremel, CM
Lovinger, DM
AF Carlson, V. C. Cuzon
Gremel, C. M.
Lovinger, D. M.
TI Prenatal ethanol exposure causes dynamic changes in the synaptic
transmission in the dorsal striatum and disrupts subsequent habit
formation in the adult mouse
SO ALCOHOL
LA English
DT Meeting Abstract
CT Conference on Alcoholism and Stress - A Framework for Future Treatment
Strategies
CY MAY 06-08, 2008
CL Volterra, ITALY
C1 [Carlson, V. C. Cuzon; Gremel, C. M.; Lovinger, D. M.] NIAAA, Lab Integrat Neurosci, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-8329
EI 1873-6823
J9 ALCOHOL
JI Alcohol
PD MAY
PY 2011
VL 45
IS 3
BP 293
EP 293
PG 1
WC Substance Abuse; Pharmacology & Pharmacy; Toxicology
SC Substance Abuse; Pharmacology & Pharmacy; Toxicology
GA 750HX
UT WOS:000289538300110
ER
PT J
AU Cifani, C
Navarre, BM
Nair, SG
Pickens, CL
Bossert, JM
Shaham, Y
AF Cifani, C.
Navarre, B. M.
Nair, S. G.
Pickens, C. L.
Bossert, J. M.
Shaham, Y.
TI Stress-induced reinstatement of palatable food seeking: Role of Dorsal
Medial Prefrontal Cortex Dopamine D1-Family Receptors
SO ALCOHOL
LA English
DT Meeting Abstract
CT Conference on Alcoholism and Stress - A Framework for Future Treatment
Strategies
CY MAY 06-08, 2008
CL Volterra, ITALY
C1 [Cifani, C.; Navarre, B. M.; Nair, S. G.; Pickens, C. L.; Bossert, J. M.; Shaham, Y.] NIDA, Behav Neurosci Branch, NIH, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-8329
EI 1873-6823
J9 ALCOHOL
JI Alcohol
PD MAY
PY 2011
VL 45
IS 3
BP 297
EP 297
PG 1
WC Substance Abuse; Pharmacology & Pharmacy; Toxicology
SC Substance Abuse; Pharmacology & Pharmacy; Toxicology
GA 750HX
UT WOS:000289538300125
ER
PT J
AU Vendruscolo, LF
Misra, KK
Barbier, E
Heilig, M
Zorrilla, EP
Koob, GF
AF Vendruscolo, Leandro F.
Misra, Kaushik K.
Barbier, Estelle
Heilig, Markus
Zorrilla, Eric P.
Koob, George F.
TI Antecedent anxiety predicts compulsive-like alcohol drinking in rats
SO ALCOHOL
LA English
DT Meeting Abstract
CT Conference on Alcoholism and Stress - A Framework for Future Treatment
Strategies
CY MAY 06-08, 2008
CL Volterra, ITALY
C1 [Vendruscolo, Leandro F.; Misra, Kaushik K.; Zorrilla, Eric P.; Koob, George F.] Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA 92037 USA.
[Barbier, Estelle; Heilig, Markus] NIAAA, Bethesda, MD USA.
RI koob, george/P-8791-2016
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-8329
EI 1873-6823
J9 ALCOHOL
JI Alcohol
PD MAY
PY 2011
VL 45
IS 3
BP 297
EP 297
PG 1
WC Substance Abuse; Pharmacology & Pharmacy; Toxicology
SC Substance Abuse; Pharmacology & Pharmacy; Toxicology
GA 750HX
UT WOS:000289538300128
ER
PT J
AU Schwandt, ML
Issa, JE
Smith, AR
Doty, L
Lionetti, T
Spero, D
Geyer, C
Hommer, DW
Heilig, M
George, DT
Ramchandani, VA
AF Schwandt, M. L.
Issa, J. E.
Smith, A. R.
Doty, L.
Lionetti, T.
Spero, D.
Geyer, C.
Hommer, D. W.
Heilig, M.
George, D. T.
Ramchandani, V. A.
TI Relationship between adverse childhood experiences and alcohol-related
outcomes in recently detoxified alcoholics
SO ALCOHOL
LA English
DT Meeting Abstract
CT Conference on Alcoholism and Stress - A Framework for Future Treatment
Strategies
CY MAY 06-08, 2008
CL Volterra, ITALY
C1 [Schwandt, M. L.; Issa, J. E.; Smith, A. R.; Doty, L.; Lionetti, T.; Spero, D.; Geyer, C.; Hommer, D. W.; Heilig, M.; George, D. T.; Ramchandani, V. A.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-8329
EI 1873-6823
J9 ALCOHOL
JI Alcohol
PD MAY
PY 2011
VL 45
IS 3
BP 301
EP 301
PG 1
WC Substance Abuse; Pharmacology & Pharmacy; Toxicology
SC Substance Abuse; Pharmacology & Pharmacy; Toxicology
GA 750HX
UT WOS:000289538300142
ER
PT J
AU Blasbalg, TL
Hibbeln, JR
Ramsden, CE
Majchrzak, SF
Rawlings, RR
AF Blasbalg, Tanya L.
Hibbeln, Joseph R.
Ramsden, Christopher E.
Majchrzak, Sharon F.
Rawlings, Robert R.
TI Changes in consumption of omega-3 and omega-6 fatty acids in the United
States during the 20th century
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID CORONARY-HEART-DISEASE; HUMAN DEPOT FAT; EICOSAPENTAENOIC ACID;
DOCOSAHEXAENOIC ACID; LINOLEIC-ACID; N-3; HEALTH; RISK; DIET; PLASMA
AB Background: The consumption of omega-3 (n-3) and omega-6 (n-6) essential fatty acids in Western diets is thought to have changed markedly during the 20th century.
Objective: We sought to quantify changes in the apparent consumption of essential fatty acids in the United States from 1909 to 1999.
Design: We calculated the estimated per capita consumption of food commodities and availability of essential fatty acids from 373 food commodities by using economic disappearance data for each year from 1909 to 1999. Nutrient compositions for 1909 were modeled by using current foods (1909-C) and foods produced by traditional early 20th century practices (1909-T).
Results: The estimated per capita consumption of soybean oil increased >1000-fold from 1909 to 1999. The availability of linoleic acid (LA) increased from 2.79% to 7.21% of energy (P < 0.000001), whereas the availability of a-linolenic acid (ALA) increased from 0.39% to 0.72% of energy by using 1909-C modeling. By using 1909-T modeling, LA was 2.23% of energy, and ALA was 0.35% of energy. The ratio of LA to ALA increased from 6.4 in 1909 to 10.0 in 1999. The 1909-T but not the 1909-C data showed substantial declines in dietary availability (percentage of energy) of n-6 arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Predicted net effects of these dietary changes included declines in tissue n-3 highly unsaturated fatty acid status (36.81%, 1909-T; 31.28%, 1909-C; 22.95%, 1999) and declines in the estimated omega-3 index (8.28, 1909-T; 6.51, 1909-C; 3.84, 1999).
Conclusion: The apparent increased consumption of LA, which was primarily from soybean oil, has likely decreased tissue concentrations of EPA and DHA during the 20th century. Am J Clin Nutr 2011;93:950-62.
C1 [Blasbalg, Tanya L.; Hibbeln, Joseph R.; Ramsden, Christopher E.; Majchrzak, Sharon F.] NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, Bethesda, MD USA.
[Rawlings, Robert R.] NIAAA, Lab Clin Translat Studies, NIH, Bethesda, MD USA.
RP Hibbeln, JR (reprint author), 5625 Fishers Lane,Room 3N-07, Rockville, MD 20852 USA.
EM jhibbeln@mail.nih.gov
FU National Institute on Alcohol Abuse and Alcoholism
FX Supported by a gift from John M Davis and the Intramural Research
Program of the National Institute on Alcohol Abuse and Alcoholism.
NR 43
TC 224
Z9 230
U1 7
U2 49
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 MAY
PY 2011
VL 93
IS 5
BP 950
EP 962
DI 10.3945/ajcn.110.006643
PG 13
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 753KC
UT WOS:000289770500008
PM 21367944
ER
PT J
AU Heikens, MJ
Gorbach, AM
Eden, HS
Savastano, DM
Chen, KY
Skarulis, MC
Yanovski, JA
AF Heikens, Marc J.
Gorbach, Alexander M.
Eden, Henry S.
Savastano, David M.
Chen, Kong Y.
Skarulis, Monica C.
Yanovski, Jack A.
TI Core body temperature in obesity
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID MEN; THERMOGENESIS; THERMOMETER; MICE
AB Background: A lower core body temperature set point has been suggested to be a factor that could potentially predispose humans to develop obesity.
Objective: We tested the hypothesis that obese individuals have lower core temperatures than those in normal-weight individuals.
Design: In study 1, nonobese [body mass index (BMI; in kg/m(2)) <30] and obese (BMI >= 30) adults swallowed wireless core temperature-sensing capsules, and we measured core temperatures continuously for 24 h. In study 2, normal-weight (BMI of 18-25) and obese subjects swallowed temperature-sensing capsules to measure core temperatures continuously for >= 48 h and kept activity logs. We constructed daily, 24-h core temperature profiles for analysis.
Results: Mean (+/- SE) daily core body temperature did not differ significantly between the 35 nonobese and 46 obese subjects (36.92 +/- 0.03 degrees C compared with 36.89 +/- 0.03 degrees C; P = 0.44). Core temperature 24-h profiles did not differ significantly between 11 normal-weight and 19 obese subjects (P = 0.274). Women had a mean core body temperature approximate to 0.23 degrees C greater than that of men (36.99 +/- 0.03 degrees C compared with 36.76 +/- 0.03 degrees C; P < 0.0001).
Conclusions: Obesity is not generally associated with a reduced core body temperature. It may be necessary to study individuals with function-altering mutations in core temperature-regulating genes to determine whether differences in the core body temperature set point affect the regulation of human body weight. These trials were registered at clinicaltrials.gov as NCT00428987 and NCT00266500. Am J Clin Nutr 2011;93:963-7.
C1 [Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Growth & Obes, Program Dev Endocrinol & Genet, NIH,Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
[Gorbach, Alexander M.; Eden, Henry S.] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA.
[Chen, Kong Y.; Skarulis, Monica C.] NIDDKD, Clin Endocrinol Branch, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Yanovski, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Growth & Obes, Program Dev Endocrinol & Genet, NIH,Hatfield Clin Res Ctr, 9000 Rockville Pike,Room 1-3330,MSC 1103, Bethesda, MD 20892 USA.
EM jy15i@nih.gov
OI Yanovski, Jack/0000-0001-8542-1637; Chen, Kong/0000-0002-0306-1904
FU National Institute of Child Health and Human Development, National
Institutes of Health (NIH); National Institute of Diabetes, Digestive
and Kidney Diseases, NIH; National Institute of Biomedical Imaging and
Bioengineering, NIH; NIH; Pfizer Inc
FX Supported by the Intramural Research Programs of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development,
National Institutes of Health (NIH); the National Institute of Diabetes,
Digestive and Kidney Diseases, NIH; and the National Institute of
Biomedical Imaging and Bioengineering, NIH. The research year for MJH
was made possible through the Clinical Research Training Program, which
is a public-private partnership supported jointly by the NIH and Pfizer
Inc (via a grant to the Foundation for NIH from Pfizer Inc).
NR 24
TC 15
Z9 17
U1 1
U2 19
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 MAY
PY 2011
VL 93
IS 5
BP 963
EP 967
DI 10.3945/ajcn.110.006270
PG 5
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 753KC
UT WOS:000289770500009
PM 21367952
ER
PT J
AU O'Grady, NP
Alexander, M
Burns, LA
Dellinger, EP
Garland, J
Heard, SO
Lipsett, PA
Masur, H
Mermel, LA
Pearson, ML
Raad, II
Randolph, AG
Rupp, ME
Saint, S
AF O'Grady, Naomi P.
Alexander, Mary
Burns, Lillian A.
Dellinger, E. Patchen
Garland, Jeffrey
Heard, Stephen O.
Lipsett, Pamela A.
Masur, Henry
Mermel, Leonard A.
Pearson, Michele L.
Raad, Issam I.
Randolph, Adrienne G.
Rupp, Mark E.
Saint, Sanjay
CA HICPAC
TI Guidelines for the prevention of intravascular catheter-related
infections
SO AMERICAN JOURNAL OF INFECTION CONTROL
LA English
DT Article
ID CENTRAL VENOUS CATHETERS; BLOOD-STREAM INFECTION; INTENSIVE-CARE-UNIT;
RANDOMIZED CONTROLLED-TRIAL; PULMONARY-ARTERY CATHETERS; CRITICALLY-ILL
PATIENTS; TOTAL PARENTERAL-NUTRITION; COAGULASE-NEGATIVE STAPHYLOCOCCI;
PERIPHERAL INTRAVENOUS CATHETERS; CUFFED HEMODIALYSIS CATHETERS
C1 [O'Grady, Naomi P.; Masur, Henry] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Alexander, Mary] Infus Nurses Soc, Norwood, MA USA.
[Burns, Lillian A.] Staten Isl Univ Hosp, Staten Isl, NY USA.
[Dellinger, E. Patchen] Univ Washington, Dept Surg, Seattle, WA 98195 USA.
[Garland, Jeffrey] Wheaton Franciscan Healthcare St Joseph, Dept Pediat, Milwaukee, WI USA.
[Heard, Stephen O.] Univ Massachusetts, Sch Med, Dept Anesthesiol, Worcester, MA USA.
[Lipsett, Pamela A.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA.
[Mermel, Leonard A.] Brown Univ, Div Infect Dis, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Mermel, Leonard A.] Rhode Isl Hosp, Providence, RI USA.
[Pearson, Michele L.] CDC, Off Infect Dis, Atlanta, GA 30333 USA.
[Raad, Issam I.] Univ Texas MD Anderson Canc Ctr, Dept Infect Dis, Houston, TX 77030 USA.
[Randolph, Adrienne G.] Childrens Hosp, Dept Anesthesiol, Boston, MA 02115 USA.
[Rupp, Mark E.] Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE USA.
[Saint, Sanjay] Univ Michigan, Ann Arbor, MI 48109 USA.
[Saint, Sanjay] Ann Arbor VA Med Ctr, Dept Internal Med, Ann Arbor, MI USA.
RP O'Grady, NP (reprint author), NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
EM nogrady@mail.cc.nih.gov
OI Randolph, Adrienne/0000-0002-3084-3071
FU NIH; Merck; Medscape; ASHP; IDSA; ASM; American College of Surgeons;
NQF; SHEA/CDC; SHEA/CDC, HHS; Trauma Shock Inflammation and Sepsis
Meeting (Munich); University of Minnesota; Angiotech; Astellas;
Theravance; Pfizer; Catheter Connections; Cubist; Cubist, Enzon;
Basilea; Eisai Pharmaceuticals, Discovery Laboratories; Molnlycke;
Cardinal Healthcare Foundation; Sanofi-Pasteur; 3M
FX E.P.D. Grant support through the NIH.; Potential conflicts of interest.
N.P. O'G. served as a board member for the ABIM Subspecialty Board for
Critical Care Medicine. M.A. is an employee of the Infusion Nurses
Society, Honoraria from 3M, Becton Dickinson, Smiths Medical. L.A.B. is
a consultant for Institute of Healthcare Improvement, Board membership
for Theradoc, Medline. Honoraria from APIC, Clorox. E.P.D. consulting
from Merck, Baxter, Ortho-McNeil, Targanta, Schering-Plough, Optimer,
Cadence, Cardinal, BDGeneOhm, WebEx, Cerebrio, and Tyco. Grant support
through the NIH. Payment for lecture from Merck. Payment for development
of educational presentation from Medscape. Travel and meeting expenses
paid for by ASHP, IDSA, ASM, American College of Surgeons, NQF,
SHEA/CDC, HHS, Trauma Shock Inflammation and Sepsis Meeting (Munich),
University of Minnesota. J.G. Honoria from Ethicon. S.O.H. provides
research support from Angiotech; Honoraria from Angiotech, Merck. L.A.M
provides research support from Astellas, Theravance, Pfizer; Consulting
for Ash Access, Cadence, Cor-Medix, Catheter Connections, Carefusion,
Sage, Bard, Teleflex; Payment for manuscript preparation from Catheter
Connections. I.I.R. provides research support from Cubist, Enzon, and
Basilea; Consulting for Clorox; Stock Equity or Options in Great Lakes
Pharmaceuticalsand Inventive Protocol; Speakers Bureau for Cook, Inc.;
Royalty income (patents owned by MD Anderson on which Dr. Raad in an
inventor: American Medical Systems, Cook, Inc., Cook urological,
Teleflex, TyRx, Medtronic, Biomet, Great Lakes Pharmaceuticals. A.R.
consulting income from Eisai Pharmaceuticals, Discovery Laboratories.
M.E.R. provides research support from Molnlycke, Cardinal Healthcare
Foundation, Sanofi-Pasteur, 3M, and Cubist; Consulting from Semprus;
Honorarium for lectures from 3M, Carefusion, Baxter and Becton
Dickinson. Previously served on Board of Directors for Society for
Healthcare Epidemiology of America. All other authors: no conflicts.
NR 371
TC 328
Z9 355
U1 7
U2 68
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-6553
EI 1527-3296
J9 AM J INFECT CONTROL
JI Am. J. Infect. Control
PD MAY
PY 2011
VL 39
IS 4
SU 1
BP S1
EP S34
DI 10.1016/j.ajic.2011.01.003
PG 34
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 752TI
UT WOS:000289716700001
PM 21511081
ER
PT J
AU Atienza, AA
Patrick, K
AF Atienza, Audie A.
Patrick, Kevin
TI Mobile Health The Killer App for Cyberinfrastructure and Consumer Health
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID BEHAVIOR-CHANGE
C1 [Atienza, Audie A.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20982 USA.
[Patrick, Kevin] Univ Calif San Diego, Calif Inst Telecommun & Informat Technol, Dept Family & Prevent Med, San Diego, CA 92103 USA.
RP Atienza, AA (reprint author), NCI, Div Canc Control & Populat Sci, NIH, 6130 Execut Blvd,EPN 4082, Bethesda, MD 20982 USA.
EM atienzaa@mail.nih.gov
FU National Institutes of Health
FX Publication of this article was supported by the National Institutes of
Health.
NR 15
TC 25
Z9 25
U1 0
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 MAY
PY 2011
VL 40
IS 5
SU 2
BP S151
EP S153
DI 10.1016/j.amepre.2011.01.008
PG 3
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 754DR
UT WOS:000289833200009
PM 21521588
ER
PT J
AU Chismar, W
Horan, TA
Hesse, BW
Feldman, SS
Shaikh, AR
AF Chismar, William
Horan, Thomas A.
Hesse, Bradford W.
Feldman, Sue S.
Shaikh, Abdul R.
TI Health Cyberinfrastructure for Collaborative Use-Inspired Research and
Practice
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID TEAM SCIENCE; FIELD
AB Rapid advances in information and networking technologies have greatly expanded the modes for conducting business and science. For the past two decades, the National Science Foundation (NSF) has been supporting efforts to develop a comprehensive cyberinfrastructure with the goal of transforming the nature of scientific investigations. More recently, the NIH began supporting efforts to develop a cyberinfrastructure of healthcare research and practice. However, the best structure and applications of cyberinfrastructure in health care have yet to be defined. To address these issues, the NIH and the Kay Center for E-Health Research at Claremont Graduate University sponsored a symposium on "Cyberinfrastructure for Public Health and Health Services: Research and Funding Directions." The symposium convened researchers, practitioners, and federal funders to discuss how to further cyberinfrastructure systems and research in the public health and health services sectors.
This paper synthesizes findings of the symposium, the goals of which were to determine the dynamics necessary for executing and utilizing cyberinfrastructure in public health and health services; examine the requirements of transdisciplinary collaboration; and identify future research directions. A multi-faceted conception of use-inspired research for cyberinfrastructure is developed. Use-inspired research aims to further basic theory but is grounded, inspired, and informed by practical problems. A cyberinfrastructure framework is presented that incorporates three intersecting dimensions: research-practice, health services-public health, and social-technical dimensions. Within this framework, this paper discusses the ways in which cyberinfrastructure provides opportunities to integrate across these dimensions to develop research and actions that can improve both clinical outcomes and public health. (Am J Prev Med 2011;40(5S2):S108-S114) (C) 2011 American Journal of Preventive Medicine
C1 [Horan, Thomas A.; Feldman, Sue S.] Claremont Grad Univ, Kay Ctr E Hlth Res, Claremont, CA 91711 USA.
[Chismar, William] Univ Hawaii Manoa, Shidler Coll Business, Honolulu, HI 96822 USA.
[Chismar, William] Univ Hawaii Manoa, Outreach Coll, Honolulu, HI 96822 USA.
[Hesse, Bradford W.; Shaikh, Abdul R.] NCI, Hlth Commun & Informat Res Branch, NIH, Bethesda, MD 20892 USA.
RP Feldman, SS (reprint author), Claremont Grad Univ, Kay Ctr E Hlth Res, 130 E 9th St, Claremont, CA 91711 USA.
EM Sue.feldman@cgu.edu
OI Hesse, Bradford/0000-0003-1142-1161
FU National Cancer Institute; Kay Center for E-Health Research; National
Institutes of Health
FX The authors acknowledge Dr. Ralph Sprague, Jr., Department of
Information Technology Management, Shidler College of Business,
University of Hawai'i at Manoa, and HICSS-42 Conference Chair for the
opportunity to develop the Cyberinfrastructure Symposium, and the
National Cancer Institute and Kay Center for E-Health Research for their
co-sponsorship of the symposium. The authors further acknowledge the
editorial contributions of Olivia Patterson and Richard Moser.;
Publication of this article was supported by the National Institutes of
Health.
NR 18
TC 9
Z9 10
U1 0
U2 11
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 MAY
PY 2011
VL 40
IS 5
SU 2
BP S108
EP S114
DI 10.1016/j.amepre.2011.01.002
PG 7
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 754DR
UT WOS:000289833200004
PM 21521583
ER
PT J
AU Hesse, BW
Croyle, RT
Buetow, KH
AF Hesse, Bradford W.
Croyle, Robert T.
Buetow, Kenneth H.
TI Cyberinfrastructure and the Biomedical Sciences
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID ELECTRONIC HEALTH RECORDS; INFORMATION-TECHNOLOGY; CANCER CARE; TEAM
SCIENCE; BIG DATA; QUALITY; INFRASTRUCTURE; POPULATION; IMPROVE;
COLLABORATION
C1 [Hesse, Bradford W.] NCI, Hlth Commun & Informat Res Branch, NIH, Bethesda, MD 20892 USA.
[Croyle, Robert T.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Buetow, Kenneth H.] NCI, Ctr Biomed Informat & Informat Technol, NIH, Bethesda, MD 20892 USA.
RP Hesse, BW (reprint author), NCI, Hlth Commun & Informat Res Branch, NIH, 6130 Execut Blvd,MSC 7365, Bethesda, MD 20892 USA.
EM hesseb@mail.nih.gov
OI Hesse, Bradford/0000-0003-1142-1161
FU National Institutes of Health
FX Publication of this article was supported by the National Institutes of
Health.
NR 63
TC 4
Z9 4
U1 3
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
EI 1873-2607
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD MAY
PY 2011
VL 40
IS 5
SU 2
BP S97
EP S102
DI 10.1016/j.amepre.2011.01.006
PG 6
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 754DR
UT WOS:000289833200002
PM 21521604
ER
PT J
AU Mabry, PL
AF Mabry, Patricia L.
TI Making Sense of the Data Explosion The Promise of Systems Science
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID HEALTH
C1 NIH, Off Behav & Social Sci Res, Off Director, Bethesda, MD 20892 USA.
RP Mabry, PL (reprint author), NIH, Off Behav & Social Sci Res, Off Director, 31 Ctr Dr,Bldg 31,B1-C19,MSC 2027, Bethesda, MD 20892 USA.
EM mabryp@od.nih.gov
FU National Institutes of Health
FX Publication of this article was supported by the National Institutes of
Health.
NR 9
TC 7
Z9 7
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD MAY
PY 2011
VL 40
IS 5
SU 2
BP S159
EP S161
DI 10.1016/j.amepre.2011.02.001
PG 3
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 754DR
UT WOS:000289833200011
PM 21521590
ER
PT J
AU Madhavan, S
Sanders, AE
Chou, WYS
Shuster, A
Boone, KW
Dente, MA
Shad, AT
Hesse, BW
AF Madhavan, Subha
Sanders, Amy E.
Chou, Wen-Ying Sylvia
Shuster, Alex
Boone, Keith W.
Dente, Mark A.
Shad, Aziza T.
Hesse, Bradford W.
TI Pediatric Palliative Care and eHealth Opportunities for Patient-Centered
Care
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID ELECTRONIC HEALTH RECORDS; CANCER CARE; KAISER PERMANENTE; SUPPORT;
QUALITY; INFORMATION; INTERFACES; PHYSICIANS; SURVIVORS; IMPROVE
AB Background: Pediatric palliative care currently faces many challenges including unnecessary pain from insufficiently personalized treatment, doctor-patient communication breakdowns, and a paucity of usable patient-centric information. Recent advances in informatics for consumer health through eHealth initiatives have the potential to bridge known communication gaps, but overall these technologies remain under-utilized in practice.
Purpose: This paper seeks to identify effective uses of existing and developing health information technology (HIT) to improve communications and care within the clinical setting.
Methods: A needs analysis was conducted by surveying seven pediatric oncology patients and their extended support network at the Lombardi Pediatric Clinic at Georgetown University Medical Center in May and June of 2010. Needs were mapped onto an existing inventory of emerging HIT technologies to assess what existing informatics solutions could effectively bridge these gaps.
Results: Through the patient interviews, a number of communication challenges and needs in pediatric palliative cancer care were identified from the interconnected group perspective surrounding each patient. These gaps mapped well, in most cases, to existing or emerging cyberinfrastructure. However, adoption and adaptation of appropriate technologies could improve, including for patient-provider communication, behavioral support, pain assessment, and education, all through integration within existing work flows.
Conclusions: This study provides a blueprint for more optimal use of HIT technologies, effectively utilizing HIT standards-based technology solutions to improve communication. This research aims to further stimulate the development and adoption of interoperable, standardized technologies and delivery of context-sensitive information to substantially improve the quality of care patients receive within pediatric palliative care clinics and other settings. (Am J Prev Med 2011;40(5S2):S208-S216) (C) 2011 American Journal of Preventive Medicine
C1 [Madhavan, Subha; Shuster, Alex; Shad, Aziza T.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
[Sanders, Amy E.; Chou, Wen-Ying Sylvia; Hesse, Bradford W.] NCI, NIH, Bethesda, MD 20892 USA.
[Boone, Keith W.; Dente, Mark A.] GE Healthcare Informat Technol, Boston, MA USA.
RP Madhavan, S (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, 3300 Whitehaven St NW,Suite 1200, Washington, DC 20007 USA.
EM sm696@georgetown.edu
OI Boone, Keith/0000-0003-4737-6438; Hesse, Bradford/0000-0003-1142-1161
FU National Center for Research Resources (NCRR), National Institutes of
Health (NIH) [UL1RR031975]; National Institutes of Health
FX This project has been funded in part with Federal funds (Grant
#UL1RR031975) from the National Center for Research Resources (NCRR),
National Institutes of Health (NIH), through the Clinical and
Translational Science Awards Program (CTSA), a trademark of DHHS, part
of the Roadmap Initiative, Re-Engineering the Clinical Research
Enterprise.; Publication of this article was supported by the National
Institutes of Health.
NR 47
TC 9
Z9 9
U1 3
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD MAY
PY 2011
VL 40
IS 5
SU 2
BP S208
EP S216
DI 10.1016/j.amepre.2011.01.013
PG 9
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 754DR
UT WOS:000289833200017
PM 21521596
ER
PT J
AU Moser, RP
Hesse, BW
Shaikh, AR
Courtney, P
Morgan, G
Augustson, E
Kobrin, S
Levin, KY
Helba, C
Garner, D
Dunn, M
Coa, K
AF Moser, Richard P.
Hesse, Bradford W.
Shaikh, Abdul R.
Courtney, Paul
Morgan, Glen
Augustson, Erik
Kobrin, Sarah
Levin, Kerry Y.
Helba, Cynthia
Garner, David
Dunn, Marsha
Coa, Kisha
TI Grid-Enabled Measures Using Science 2.0 to Standardize Measures and
Share Data
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID HEALTH-CARE; INFRASTRUCTURE; INFORMATION; SUPPORT; CYBERINFRASTRUCTURE;
COLLABORATION; ASSOCIATION; ACCELERATE; SYSTEM
AB Scientists are taking advantage of the Internet and collaborative web technology to accelerate discovery in a massively connected, participative environment-a phenomenon referred to by some as Science 2.0. As a new way of doing science, this phenomenon has the potential to push science forward in a more efficient manner than was previously possible. The Grid-Enabled Measures (GEM) database has been conceptualized as an instantiation of Science 2.0 principles by the National Cancer Institute (NCI) with two overarching goals: (1) promote the use of standardized measures, which are tied to theoretically based constructs; and (2) facilitate the ability to share harmonized data resulting from the use of standardized measures. The first is accomplished by creating an online venue where a virtual community of researchers can collaborate together and come to consensus on measures by rating, commenting on, and viewing meta-data about the measures and associated constructs. The second is accomplished by connecting the constructs and measures to an ontological framework with data standards and common data elements such as the NCI Enterprise Vocabulary System (EVS) and the cancer Data Standards Repository (caDSR). This paper will describe the web 2.0 principles on which theGEMdatabase is based, describe its functionality, and discuss some of the important issues involved with creating the GEM database, such as the role of mutually agreed-on ontologies (i.e., knowledge categories and the relationships among these categories-for data sharing). (Am J Prev Med 2011;40(5S2):S134-S143) Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine
C1 [Moser, Richard P.; Hesse, Bradford W.; Shaikh, Abdul R.; Morgan, Glen; Augustson, Erik; Kobrin, Sarah] NCI, NIH, Bethesda, MD 20892 USA.
[Courtney, Paul] NCI Frederick, Clin Monitoring Res Program, SAIC Frederick Inc, Frederick, MD USA.
[Levin, Kerry Y.; Helba, Cynthia; Garner, David; Dunn, Marsha; Coa, Kisha] Westat Corp, Rockville, MD USA.
RP Moser, RP (reprint author), NCI, NIH, 6130 Execut Blvd,MSC 7326, Bethesda, MD 20892 USA.
EM moserr@mail.nih.gov
OI Hesse, Bradford/0000-0003-1142-1161
FU National Institutes of Health
FX Publication of this article was supported by the National Institutes of
Health.
NR 50
TC 22
Z9 22
U1 2
U2 19
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
EI 1873-2607
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD MAY
PY 2011
VL 40
IS 5
SU 2
BP S134
EP S143
DI 10.1016/j.amepre.2011.01.004
PG 10
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 754DR
UT WOS:000289833200007
PM 21521586
ER
PT J
AU Sairamesh, J
Griss, ML
Weber, PA
Hum, S
Garverick, SL
Nemana, R
Yu, W
Hosea, FW
Das, AK
Garner, H
AF Sairamesh, Jakka
Griss, Martin L.
Weber, Patricia A.
Hum, Stanley
Garverick, Steven L.
Nemana, Ravi
Yu, Wil
Hosea, Fred W.
Das, Amar K.
Garner, Harold
TI Innovation in Healthcare Intelligence Cross-Sector Convergence Beyond
Electronic Medical Records
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
C1 [Sairamesh, Jakka; Nemana, Ravi] 360Fresh Inc, Palo Alto, CA 94303 USA.
[Griss, Martin L.] Carnegie Mellon Univ, Moffett Field, CA USA.
[Garverick, Steven L.] W Wireless Hlth Inst, La Jolla, CA USA.
[Hosea, Fred W.] Kaiser Permanente, Oakland, CA USA.
[Das, Amar K.] Stanford Med Ctr, Stanford, CA USA.
[Weber, Patricia A.] NCI, NIH, Bethesda, MD 20892 USA.
[Hum, Stanley] Columbia Univ, Med Ctr, New York, NY USA.
[Yu, Wil] Off Natl Coordinator, Washington, DC USA.
[Garner, Harold] Virginia Bioinformat Inst, Blacksburg, VA USA.
RP Sairamesh, J (reprint author), 360Fresh Inc, 3600 W Bayshore Rd,Suite 102, Palo Alto, CA 94303 USA.
EM ramesh@360fresh.com
FU National Institutes of Health
FX Publication of this article was supported by the National Institutes of
Health.
NR 6
TC 3
Z9 3
U1 0
U2 9
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 MAY
PY 2011
VL 40
IS 5
SU 2
BP S234
EP S237
DI 10.1016/j.amepre.2011.02.002
PG 4
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 754DR
UT WOS:000289833200020
PM 21521599
ER
PT J
AU Shaikh, AR
Das, IP
Vinson, CA
Spring, B
AF Shaikh, Abdul R.
Das, Irene Prabhu
Vinson, Cynthia A.
Spring, Bonnie
TI Cyberinfrastructure for Consumer Health Introduction
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Editorial Material
C1 [Shaikh, Abdul R.] NCI, Hlth Commun & Informat Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, Bethesda, MD 20892 USA.
[Das, Irene Prabhu] NCI, Outcomes Res Branch, Appl Res Program, NIH, Bethesda, MD 20892 USA.
[Spring, Bonnie] Northwestern Univ, Dept Prevent Med Psychol & Psychiat, Chicago, IL 60611 USA.
RP Shaikh, AR (reprint author), NCI, Hlth Commun & Informat Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, EPN 4062,6130 Execut Blvd, Bethesda, MD 20892 USA.
EM shaikhab@mail.nih.gov
NR 43
TC 7
Z9 9
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD MAY
PY 2011
VL 40
IS 5
SU 2
BP S91
EP S96
DI 10.1016/j.amepre.2011.02.012
PG 6
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 754DR
UT WOS:000289833200001
PM 21521603
ER
PT J
AU Feber, A
Xi, LQ
Pennathur, A
Gooding, WE
Bandla, S
Wu, MX
Luketich, JD
Godfrey, TE
Litle, VR
AF Feber, Andrew
Xi, Liqiang
Pennathur, Arjun
Gooding, William E.
Bandla, Santhoshi
Wu, Maoxin
Luketich, James D.
Godfrey, Tony E.
Litle, Virginia R.
TI MicroRNA Prognostic Signature for Nodal Metastases and Survival in
Esophageal Adenocarcinoma
SO ANNALS OF THORACIC SURGERY
LA English
DT Article; Proceedings Paper
CT 57th Annual Meeting of the Southern-Thoracic-Surgical-Association
CY NOV 03-06, 2010
CL Orlando, FL
SP So Thorac Surg Assoc
ID EXPRESSION PROFILES; ENDOSCOPIC THERAPY; COLORECTAL-CANCER;
PROSTATE-CANCER; C-ELEGANS; CARCINOMA; RESOLUTION; DISEASE; MIR-143;
MIR-21
AB Background. The incidence of esophageal adenocarcinoma is rapidly increasing and is now one of the leading causes of cancer death in the western world. MicroRNAs (miRNAs) are small noncoding RNAs that regulate the expression of protein-encoding genes and are involved in the development, progression and prognosis of other malignancies. We hypothesized that global miRNA expression would predict survival and lymph node involvement in a cohort of surgically resected esophagus cancer patients.
Methods. The miRNA analysis was performed using a custom Affymetrix microarray with probes for 462 known human, 2,102 predicted human, 357 mouse, and 238 rat miRNAs. Expression of miRNA was evaluated in 45 primary tumors, and the association of miRNA expression with patient survival and lymph node metastasis was assessed. The prognostic impact of identified unique miRNAs was verified with quantitative reverse transcriptase polymerase chain reaction.
Results. Our data indicate that the expression of individual human miRNA species is significantly associated with postresection patient survival. Using data from five unique miRNAs, we were further able to generate a combined miRNA expression signature that is associated with patient survival (p = 0.005; hazard ratio 3.6) independent of node involvement and overall stage. The expression of three miRNAs (miR-99b and miR-199a_3p and _5p) was also associated with the presence of lymph node metastasis.
Conclusions. These results suggest miRNA expression profiling could provide prognostic utility in staging esophagus cancer patients and treatment planning with endoscopic and neoadjuvant therapies. The alterations of specific miRNAs may further elucidate steps in the metastatic pathway and allow for development of targeted therapy. (Ann Thorac Surg 2011;91:1556-61) (C) 2011 by The Society of Thoracic Surgeons
C1 UCL, Inst Canc, London, England.
NCI, Bethesda, MD 20892 USA.
Univ Pittsburgh, Med Ctr, Dept Cardiothorac Surg, Pittsburgh, PA USA.
Univ Pittsburgh, Dept Biostat, Pittsburgh Canc Inst, Pittsburgh, PA 15261 USA.
[Litle, Virginia R.] Univ Rochester, Sch Med & Dent, Dept Surg, Rochester, NY 14642 USA.
Mt Sinai Sch Med, Dept Pathol, New York, NY USA.
RP Litle, VR (reprint author), Univ Rochester, Sch Med & Dent, Dept Surg, Box SURG,601 Elmwood Ave, Rochester, NY 14642 USA.
EM virginia_litle@urmc.rochester.edu
RI Litle, Virginia/A-9859-2013; Godfrey, Tony/A-5572-2013;
OI Litle, Virginia/0000-0002-3107-688X; Godfrey, Tony/0000-0002-3283-6983;
Feber, Andrew/0000-0001-5282-0498
FU NCI NIH HHS [R01 CA130853]
NR 40
TC 50
Z9 53
U1 1
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-4975
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD MAY
PY 2011
VL 91
IS 5
BP 1523
EP 1530
DI 10.1016/j.athoracsur.2011.01.056
PG 8
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 754EE
UT WOS:000289835000051
PM 21420070
ER
PT J
AU Lin, Q
Yang, XP
Fang, D
Ren, XR
Zhou, HY
Fang, JZ
Liu, XL
Zhou, SY
Wen, F
Yao, XH
Wang, JM
Su, SB
AF Lin, Qing
Yang, Xiao Ping
Fang, Dan
Ren, Xiangrong
Zhou, Hongyan
Fang, Jiazhu
Liu, Xialin
Zhou, Shiyou
Wen, Feng
Yao, Xiaohong
Wang, Ji Ming
Su, Shao Bo
TI High-Mobility Group Box-1 Mediates Toll-Like Receptor 4-Dependent
Angiogenesis
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE angiogenesis; macrophages; HMGB1; inflammation; Toll-like receptor
ID ENDOTHELIAL GROWTH-FACTOR; GLYCATION END-PRODUCTS; EXPERIMENTAL
CHOROIDAL NEOVASCULARIZATION; CORNEAL NEOVASCULARIZATION; EXTRACELLULAR
HMGB1; MURINE MACROPHAGES; FACTOR EXPRESSION; PROGENITOR CELLS; INNATE
IMMUNITY; LIVER ISCHEMIA
AB Objective-Inflammation is closely linked to angiogenesis, and Toll-like receptors (TLRs) are the key mediators of inflammatory responses. However, the impact of TLRs on angiogenesis is incompletely understood. In this study, we determined the involvement of TLRs in angiogenesis.
Methods and Results-In a mouse model of alkali-induced corneal neovascularization (CNV), we found that CNV was attenuated in TLR4(-/-) but not TLR2(-/-) mice. Further study revealed that the absence of TLR4 led to decreased production of proangiogenic factors in association with reduced accumulation of macrophages at the site of wounds, which was associated with reduced expression of high-mobility group box-1 (HMGB1) protein, an endogenous ligand for TLR4. Topical application of HMGB1 to the injured cornea promoted CNV with increased macrophage accumulation in wild-type mice but not in TLR4(-/-) mice. HMGB1 treatment in vitro also promoted the production of proangiogenic factors by mouse macrophages in a TLR4-dependent manner. Furthermore, antagonists of HMGB1 and TLR4 reduced CNV and macrophage recruitment in the injured cornea of wild-type mice.
Conclusion-Our results suggest that the release of HMGB1 in the wounds initiates TLR4-dependent responses that contribute to neovascularization. Thus, targeting HMGB1-TLR4 signaling cascade may constitute a novel therapeutic approach to angiogenesis-related diseases. (Arterioscler Thromb Vasc Biol. 2011;31:1024-1032.)
C1 [Lin, Qing; Fang, Dan; Ren, Xiangrong; Zhou, Hongyan; Fang, Jiazhu; Liu, Xialin; Zhou, Shiyou; Wen, Feng; Su, Shao Bo] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China.
[Yang, Xiao Ping] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA.
[Yao, Xiaohong; Wang, Ji Ming] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
RP Su, SB (reprint author), Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, 54 S Xianlie Rd, Guangzhou 510060, Guangdong, Peoples R China.
EM shaobosu@yahoo.com
OI Lin, Qing/0000-0002-8890-800X
FU National Basic Research Program of China [2007CB512206, 2010CB529400,
2011CB966200]; National Natural Science Foundation of China [81072483]
FX This project was supported by the grants from the National Basic
Research Program of China (2007CB512206, 2010CB529400 and 2011CB966200)
and the National Natural Science Foundation of China (81072483).
NR 64
TC 46
Z9 49
U1 0
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD MAY
PY 2011
VL 31
IS 5
BP 1024
EP U174
DI 10.1161/ATVBAHA.111.224048
PG 26
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 752UR
UT WOS:000289720800015
PM 21372296
ER
PT J
AU Muller, CE
Jacobson, KA
AF Mueller, Christa E.
Jacobson, Kenneth A.
TI Recent developments in adenosine receptor ligands and their potential as
novel drugs
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
LA English
DT Review
DE Adenosine receptor; Agonist; Antagonist; Clinical trial; Medicinal
chemistry; G protein-coupled receptor
ID POSITRON-EMISSION-TOMOGRAPHY; AFFINITY ANTAGONIST RADIOLIGAND;
CENTRAL-NERVOUS-SYSTEM; A(2A) RECEPTOR; A(3) RECEPTOR; A(1) RECEPTORS;
A(2B) RECEPTOR; HIGHLY POTENT; A(3)-ADENOSINE RECEPTOR; BIOLOGICAL
EVALUATION
AB Medicinal chemical approaches have been applied to all four of the adenosine receptor (AR) subtypes (A(1), A(2A), A(2B), and A(3)) to create selective agonists and antagonists for each. The most recent class of selective AR ligands to be reported is the class of A(2B)AR agonists. The availability of these selective ligands has facilitated research on therapeutic applications of modulating the ARs and in some cases has provided clinical candidates. Prodrug approaches have been developed which improve the bioavailability of the drugs, reduce side-effects, and/or may lead to site-selective effects. The A(2A) agonist regadenoson (Lexiscan (R)), a diagnostic drug for myocardial perfusion imaging, is the first selective AR agonist to be approved. Other selective agonists and antagonists are or were undergoing clinical trials for a broad range of indications, including capadenoson and tecadenoson (A(1) agonists) for atrial fibrillation, or paroxysmal supraventricular tachycardia, respectively, apadenoson and binodenoson (A(2A) agonists) for myocardial perfusion imaging, preladenant (A(2A) antagonist) for the treatment of Parkinson's disease, and CF101 and CF102 (A(3) agonists) for inflammatory diseases and cancer, respectively. This article is part of a Special Issue entitled: "Adenosine Receptors". (C) 2010 Elsevier B.V. All rights reserved.
C1 [Mueller, Christa E.] Univ Bonn, PharmaCtr Bonn, Inst Pharmaceut, D-53121 Bonn, Germany.
[Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Muller, CE (reprint author), Univ Bonn, PharmaCtr Bonn, Inst Pharmaceut, Immenburg 4, D-53121 Bonn, Germany.
EM christa.mueller@uni-bonn.de
RI Jacobson, Kenneth/A-1530-2009; Muller, Christa/C-7748-2014
OI Jacobson, Kenneth/0000-0001-8104-1493; Muller,
Christa/0000-0002-0013-6624
FU NIH, National Institute of Diabetes & Digestive & Kidney Diseases; BMBF
(BioPharma - Neuroallianz); DFG; DAAD; European Commission (ERANET
Neuron); State of North-Rhine Westfalia (NRW International Research
Graduate Schools BIOTECH-PHARMA and Chemical Biology)
FX KAJ acknowledges support from the Intramural Research Program of the
NIH, National Institute of Diabetes & Digestive & Kidney Diseases. CEM
is grateful for support by BMBF (BioPharma - Neuroallianz), DFG, DAAD,
European Commission (ERANET Neuron), and the State of North-Rhine
Westfalia (NRW International Research Graduate Schools BIOTECH-PHARMA
and Chemical Biology).
NR 191
TC 163
Z9 163
U1 4
U2 31
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2736
J9 BBA-BIOMEMBRANES
JI Biochim. Biophys. Acta-Biomembr.
PD MAY
PY 2011
VL 1808
IS 5
SI SI
BP 1290
EP 1308
DI 10.1016/j.bbamem.2010.12.017
PG 19
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 752BW
UT WOS:000289664000007
PM 21185259
ER
PT J
AU Lev, O
AF Lev, Ori
TI WILL BIOMEDICAL ENHANCEMENTS UNDERMINE SOLIDARITY, RESPONSIBILITY,
EQUALITY AND AUTONOMY?
SO BIOETHICS
LA English
DT Article
DE biomedical enhancement; political values; solidarity; responsibility;
equality; autonomy; scenario planning
AB Prominent thinkers such as Jurgen Habermas and Michael Sandel are warning that biomedical enhancements will undermine fundamental political values. Yet whether biomedical enhancements will undermine such values depends on how biomedical enhancements will function, how they will be administered and to whom. Since only few enhancements are obtainable, it is difficult to tell whether these predictions are sound. Nevertheless, such warnings are extremely valuable. As a society we must, at the very least, be aware of developments that could have harmful consequences. Indeed, if important values were to be jeopardized, we should take appropriate measures to protect them. This paper focuses on four central values: solidarity, personal responsibility, equality and autonomy. It delineates the conditions under which biomedical enhancements would undermine these values. It also details the circumstances under which these values would be unaffected by enhancements as well as those under which they would be promoted. Specifying these conditions is valuable; it would enable society to prepare appropriate ethical guidelines and policy responses in advance.
C1 [Lev, Ori] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
[Lev, Ori] NIH, Bioeth Dept, Ctr Clin, Bethesda, MD USA.
RP Lev, O (reprint author), NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
EM levo@mail.nih.gov
FU National Human Genome Research Institute, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Human Genome Research Institute, National Institutes of Health.
I thank Ezekiel J. Emanuel, Frank Miller, Alan Wertheimer, Arnon Keren,
Joe Millum, Shlomi Segall, Ben Sachs, Colin O'Neil and Connie Rosati for
their criticisms and helpful suggestions about the manuscript.
NR 0
TC 4
Z9 4
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0269-9702
J9 BIOETHICS
JI Bioethics
PD MAY
PY 2011
VL 25
IS 4
BP 177
EP 184
DI 10.1111/j.1467-8519.2009.01779.x
PG 8
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA 748BF
UT WOS:000289364300002
PM 20002073
ER
PT J
AU Barsoum, I
Yao, HHC
AF Barsoum, Ivraym
Yao, Humphrey H. C.
TI Redundant and Differential Roles of Transcription Factors Gli1 and Gli2
in the Development of Mouse Fetal Leydig Cells
SO BIOLOGY OF REPRODUCTION
LA English
DT Article
DE developmental biology; Gli; hedgehog; Leydig cells; steroidogenesis;
testis
ID SONIC HEDGEHOG; DESERT-HEDGEHOG; TESTIS ORGANOGENESIS; NEURAL-TUBE;
PATHWAYS; OVARY; GENE; TRANSDUCTION; CYCLOPAMINE; INHIBITION
AB Appearance of mouse fetal Leydig cells requires activation of the Hedgehog pathway. Upon binding to the membrane-bound receptor patched, Hedgehog ligands induce intracellular responses via a combined effect of Gli transcription factors. Szczepny et al. (Biol Reprod 2009; 80:258-263;) found that Gli1, one of the three Gli transcription factors, is present in the fetal testis and that its expression is suppressed by the Hedgehog inhibitor cyclopamine. In this study, we investigated the involvement of the Gli1 and Gli2 factors in mouse fetal Leydig cell differentiation. The Gli1 and Gli2 transcription factors showed an overlapping expression pattern in the testis interstitium at the time when fetal Leydig cells appear. Despite their similar expression, Gli1 and Gli2 patterns were differentially regulated. Initial Gli1 and Gli2 expression depends upon an active Hedgehog pathway; however, maintenance of only Gli1, but not Gli2, expression requires activation of the pathway. Inactivation of either the Gli1 or Gli2 gene did not affect fetal Leydig cell development and testis morphology, suggesting a functional redundancy. When the transcriptional activity of both GLI1 and GLI2 was suppressed by a selective inhibitor, GANT61, in cultured fetal testes before the appearance of fetal Leydig cells, Gli1 and Gli2 expression and steroidogenic marker activity were completely abolished. However at later stages when Leydig cells were already present, GANT61 treatment inhibited Gli1 expression but had no effects on Gli2 expression and fetal Leydig cell appearance. Our results reveal overlapping and redundant Gli1 and Gli2 roles in fetal Leydig cell differentiation and a novel regulation of Gli2 expression in the fetal testis.
C1 [Yao, Humphrey H. C.] Univ Illinois, Dept Comparat Biosci, Urbana, IL 61801 USA.
[Barsoum, Ivraym] Univ Illinois, Dept Cell & Dev Biol, Urbana, IL 61801 USA.
[Yao, Humphrey H. C.] Natl Inst Environm Hlth Sci, Reprod Dev Biol Grp, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC USA.
RP Yao, HHC (reprint author), Univ Illinois, Dept Comparat Biosci, Urbana, IL 61801 USA.
EM yaoh3@niehs.nih.gov
RI Yao, Humphrey Hung-Chang/B-4795-2010
OI Yao, Humphrey Hung-Chang/0000-0003-2944-8469
FU U.S. National Institutes of Heath [NIH-HD-46861, HD-059961]; March of
Dimes Birth Defects Foundation; UIUC College of Veterinary Medicine
Billie Field; NIH, National Institute of Environmental Health Sciences
FX Supported by U.S. National Institutes of Heath grants NIH-HD-46861 and
HD-059961 to H.H.C.Y., March of Dimes Birth Defects Foundation to
H.H.C.Y., and by a UIUC College of Veterinary Medicine Billie Field
Graduate Fellowship to I.B.B. Also supported in part by the Intramural
Research Program of the NIH, National Institute of Environmental Health
Sciences.
NR 42
TC 16
Z9 17
U1 0
U2 4
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1603 MONROE ST, MADISON, WI 53711-2021 USA
SN 0006-3363
J9 BIOL REPROD
JI Biol. Reprod.
PD MAY
PY 2011
VL 84
IS 5
BP 894
EP 899
DI 10.1095/biolreprod.110.088997
PG 6
WC Reproductive Biology
SC Reproductive Biology
GA 752XK
UT WOS:000289728600008
PM 21209421
ER
PT J
AU Zou, MF
Cao, JJ
Rodriguez, AL
Conn, PJ
Newman, AH
AF Zou, Mu-Fa
Cao, Jianjing
Rodriguez, Alice L.
Conn, P. Jeffrey
Newman, Amy Hauck
TI Design and synthesis of substituted
N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides as positive allosteric
modulators of the metabotropic glutamate receptor subtype 5
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE mGluR5; MPEP; CDPPB; Allosteric modulators
ID ANTAGONISTS; POTENT; AMIDES; SITE
AB Based on SAR in the alkyne class of mGlu5 receptor negative allosteric modulators and a set of amide-based positive allosteric modulators, optimized substitution of the aryl 'b' ring was used to create substituted N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides. Results from an mGlu5 receptor functional assay, using calcium fluorescence, revealed varying efficacies and potencies that provide evidence that subtle changes in compounds within a close structural class can have marked effects on functional activity including switches in modes of efficacy (i.e., negative to positive allosteric modulation). Published by Elsevier Ltd.
C1 [Zou, Mu-Fa; Cao, Jianjing; Newman, Amy Hauck] Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Rodriguez, Alice L.; Conn, P. Jeffrey] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Vanderbilt Program Drug Discovery, Nashville, TN 37232 USA.
RP Newman, AH (reprint author), Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM anewman@intra.nida.nih.gov
RI Conn, Peter/D-7848-2012
FU NIDA; NINDS [F32 NS049865]; National Institute of Mental Health (NIMH)
[NO1MH32004]
FX This work was funded by the NIDA-Intramural Research Program and an NRSA
Fellowship F32 NS049865 awarded by NINDS to A.L.R. mGlu5 receptor
binding data were provided by the National Institute of Mental Health's
Psychoactive Drug Screening Program, Contract no. NO1MH32004 (NIMH
PDSP). We thank Dr. Tom Keck for helpful comments on an earlier version
of this manuscript.
NR 20
TC 11
Z9 11
U1 0
U2 9
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD MAY 1
PY 2011
VL 21
IS 9
BP 2650
EP 2654
DI 10.1016/j.bmcl.2010.12.110
PG 5
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 753KW
UT WOS:000289773300015
PM 21295978
ER
PT J
AU Kumar, TS
Mishra, S
Deflorian, F
Yoo, LS
Phan, K
Kecskes, M
Szabo, A
Shinkre, B
Gao, ZG
Trenkle, W
Jacobson, KA
AF Kumar, T. Santhosh
Mishra, Shilpi
Deflorian, Francesca
Yoo, Lena S.
Khai Phan
Kecskes, Miklos
Szabo, Angela
Shinkre, Bidhan
Gao, Zhan-Guo
Trenkle, William
Jacobson, Kenneth A.
TI Molecular probes for the A(2A) adenosine receptor based on a
pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine scaffold
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE SCH 442416; G protein-coupled receptor; Fluorescence; Dendrimer;
Radioligand binding
ID POSITRON-EMISSION-TOMOGRAPHY; PARKINSONS-DISEASE; RAT-BRAIN;
ANTAGONISTS; DERIVATIVES; POTENT; DEPRESSION; DISCOVERY; TARGETS; MODELS
AB Pyrazolo[4,3-e][1,2,4] triazolo[1,5-c]pyrimidin-5-amine derivatives such as SCH 442416 display high affinity and selectivity as antagonists for the human A(2A) adenosine receptor (AR). We extended ether-linked chain substituents at the p-position of the phenyl group using optimized O-alkylation. The conjugates included an ester, carboxylic acid and amines (for amide condensation), an alkyne (for click chemistry), a fluoropropyl group (for F-18 incorporation), and fluorophore reporter groups (e. g., BODIPY conjugate 14, K-i 15 nM). The potent and A(2A)AR-selective N-aminoethylacetamide 7 and N-[2-(2-aminoethyl)-aminoethyl]acetamide 8 congeners were coupled to polyamidoamine (PAMAM) G3.5 dendrimers, and the multivalent conjugates displayed high A(2A)AR affinity. Theoretical docking of an AlexaFluor conjugate to the receptor X-ray structure highlighted the key interactions between the heterocyclic core and the binding pocket of the A(2A)AR as well as the distal anchoring of the fluorophore. In conclusion, we have synthesized a family of high affinity functionalized congeners as pharmacological probes for studying the A(2A)AR. Published by Elsevier Ltd.
C1 [Kumar, T. Santhosh; Mishra, Shilpi; Deflorian, Francesca; Yoo, Lena S.; Khai Phan; Kecskes, Miklos; Szabo, Angela; Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Shinkre, Bidhan; Trenkle, William] NIDDKD, Chem Biol Unit, Lab Cell Biochem & Biol, 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 in part by the Intramural Research Program
of the NIH, National Institute of Diabetes and Digestive and Kidney
Diseases. We thank Dr. Dale Kiesewetter (NIBIB, NIH) for helpful
discussions.
NR 27
TC 17
Z9 17
U1 3
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD MAY 1
PY 2011
VL 21
IS 9
BP 2740
EP 2745
DI 10.1016/j.bmcl.2010.11.082
PG 6
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 753KW
UT WOS:000289773300034
PM 21185184
ER
PT J
AU Romagnoli, R
Baraldi, PG
Cruz-Lopez, O
Tolomeo, M
Di Cristina, A
Pipitone, RM
Grimaudo, S
Balzarini, J
Brancale, A
Hamel, E
AF Romagnoli, Romeo
Baraldi, Pier Giovanni
Cruz-Lopez, Olga
Tolomeo, Manlio
Di Cristina, Antonietta
Pipitone, Rosaria Maria
Grimaudo, Stefania
Balzarini, Jan
Brancale, Andrea
Hamel, Ernest
TI Synthesis of novel antimitotic agents based on
2-amino-3-aroyl-5-(hetero)arylethynyl thiophene derivatives
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Thiophene; Inhibition of tubulin polymerization; Inhibition of tumor
cell growth; Antiproliferative agents
ID ANTINEOPLASTIC AGENTS; BIOLOGICAL EVALUATION; MICROTUBULE DYNAMICS;
MEDICINAL CHEMISTRY; ANTITUBULIN AGENTS; NATURAL-PRODUCTS; TUBULIN;
ANALOGS; CANCER; COMBRETASTATIN-A-4
AB Microtubules are dynamic structures that play a crucial role in cellular division and are recognized as an important target for cancer therapy. In search of new compounds with strong antiproliferative activity and simple molecular structure, a new series of 2-amino-3-(3',4',5'-trimethoxybenzoyl)-5-(hetero) aryl ethynyl thiophene derivatives was prepared by the Sonogashira coupling reaction of the corresponding 5-bromothiophenes with several (hetero) aryl acetylenes. When these compounds were analyzed in vitro for their inhibition of cell proliferation, the 2- and 3-thiophenyl acetylene derivatives were the most powerful compounds, both of which exerted cytostatic effects at submicromolar concentrations. In contrast, the presence of a more flexible ethyl chain between the (hetero) aryl and the 5-position of the thiophene ring resulted in significant reduction in activity relative to the 5-(hetero)aryl acetylene substituted derivatives. The effects of a selected series of compounds on cell cycle progression correlated well with their strong antiproliferative activity and inhibition of tubulin polymerization. We found that the antiproliferative effects of the most active compounds were associated with increase of the proportion of cells in the G(2)/M and sub-G(1) phases of the cell cycle. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Romagnoli, Romeo; Baraldi, Pier Giovanni; Cruz-Lopez, Olga] Univ Ferrara, Dipartimento Sci Farmaceut, I-44100 Ferrara, Italy.
[Tolomeo, Manlio; Di Cristina, Antonietta; Pipitone, Rosaria Maria; Grimaudo, Stefania] Univ Palermo, Ctr Interdipartimentale Ric, Oncol Clin, Palermo, Italy.
[Tolomeo, Manlio; Di Cristina, Antonietta; Pipitone, Rosaria Maria; Grimaudo, Stefania] Univ Palermo, Dipartimento Biomed Med Interna & Specialist, Palermo, Italy.
[Balzarini, Jan] Katholieke Univ Leuven, Rega Inst Med Res, Lab Virol & Chemotherapy, B-3000 Louvain, Belgium.
[Brancale, Andrea] Cardiff Univ, Welsh Sch Pharm, Cardiff CF10 3XF, S Glam, Wales.
[Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA.
RP Romagnoli, R (reprint author), Univ Ferrara, Dipartimento Sci Farmaceut, I-44100 Ferrara, Italy.
EM rmr@unife.it; baraldi@unife.it
RI antonietta, di cristina/I-9251-2012; Brancale, Andrea/N-9445-2014;
Romagnoli, Romeo/G-9887-2015; Baraldi, Pier Giovanni/B-7933-2017;
Cruz-Lopez, Olga /F-3060-2017;
OI Brancale, Andrea/0000-0002-9728-3419; PIPITONE, Rosaria
Maria/0000-0002-6721-3962; Grimaudo, Stefania/0000-0003-3225-4112
FU Intramural NIH HHS [Z99 CA999999]
NR 25
TC 14
Z9 15
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD MAY 1
PY 2011
VL 21
IS 9
BP 2746
EP 2751
DI 10.1016/j.bmcl.2010.11.083
PG 6
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 753KW
UT WOS:000289773300035
PM 21146985
ER
PT J
AU Lan, Q
Wang, SS
Menashe, I
Armstrong, B
Zhang, YW
Hartge, P
Purdue, MP
Holford, TR
Morton, LM
Kricker, A
Cerhan, JR
Grulich, A
Cozen, W
Zahm, SH
Yeager, M
Vajdic, CM
Schenk, M
Leaderer, B
Yuenger, J
Severson, RK
Chatterjee, N
Chanock, SJ
Zheng, T
Rothman, N
AF Lan, Qing
Wang, Sophia S.
Menashe, Idan
Armstrong, Bruce
Zhang, Yawei
Hartge, Patricia
Purdue, Mark P.
Holford, Theodore R.
Morton, Lindsay M.
Kricker, Anne
Cerhan, James R.
Grulich, Andrew
Cozen, Wendy
Zahm, Shelia H.
Yeager, Meredith
Vajdic, Claire M.
Schenk, Maryjean
Leaderer, Brian
Yuenger, Jeff
Severson, Richard K.
Chatterjee, Nilanjan
Chanock, Stephen J.
Zheng, Tongzhang
Rothman, Nathaniel
TI Genetic variation in Th1/Th2 pathway genes and risk of non-Hodgkin
lymphoma: a pooled analysis of three population-based case-control
studies
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE Non-Hodgkin lymphoma; single nucleotide polymorphisms; immunogenetics;
case-control study
ID GENOME-WIDE ASSOCIATION; INTERLEUKIN-18 GENE; PROMOTER POLYMORPHISMS;
IMMUNOREGULATORY GENES; INTERLYMPH-CONSORTIUM; RHEUMATOID-ARTHRITIS;
FOLLICULAR LYMPHOMA; CYTOKINE; VARIANTS; CANCER
AB P>The balance between T-helper 1 (Th1) and T-helper 2 (Th2) activity is critical in lymphoid cell development and differentiation. Immune dysfunction underlies lymphomagenesis, so an alteration in the regulation of key Th1/Th2 cytokines may lead to the development of non-Hodgkin lymphoma (NHL). To study the impact of polymorphisms in Th1/Th2 cytokines on NHL risk, we analyzed 145 tag single nucleotide polymorphisms (SNPs) in 17 Th1/Th2 cytokine and related genes in three population-based case-control studies (1946 cases and 1808 controls). Logistic regression was used to compute odds ratios (OR) for NHL and four major NHL subtypes in relation to tag SNP genotypes and haplotypes. A gene-based analysis adjusting for the number of tag SNPs genotyped in each gene showed significant associations with risk of NHL combined and one or more NHL subtypes for Th1 (IL12A and IL12RB1) and Th2 (IL4, IL10RB, and IL18) genes. The strongest association was for rs485497 in IL12A, which plays a central role in bridging the cellular and humoral pathways of innate resistance and antigen-specific adaptive immune responses (allele risk OR = 1 center dot 17; P(trend) = 0 center dot 00099). This SNP was also associated specifically with risk of follicular lymphoma (allele risk OR = 1 center dot 26; P(trend) = 0 center dot 0012). These findings suggest that genetic variation in Th1/Th2 cytokine genes may contribute to lymphomagenesis.
C1 [Lan, Qing; Wang, Sophia S.; Menashe, Idan; Hartge, Patricia; Purdue, Mark P.; Morton, Lindsay M.; Zahm, Shelia H.; Chatterjee, Nilanjan; Chanock, Stephen J.; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD USA.
[Wang, Sophia S.] City Hope Natl Med Ctr, Dept Populat Sci, Div Etiol, Duarte, CA USA.
[Armstrong, Bruce; Kricker, Anne] Univ Sydney, Sydney Sch Publ Hlth, Sydney, NSW 2006, Australia.
[Zhang, Yawei; Holford, Theodore R.; Leaderer, Brian; Zheng, Tongzhang] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
[Cerhan, James R.] Mayo Clin, Coll Med, Rochester, MN USA.
[Grulich, Andrew] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia.
[Cozen, Wendy] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Yeager, Meredith; Yuenger, Jeff; Chanock, Stephen J.] NCI, Core Genotyping Facil, Adv Technol Ctr, NIH,DHHS, Gaithersburg, MD USA.
[Vajdic, Claire M.] Univ New S Wales, UNSW Canc Res Ctr, Prince Wales Clin Sch, Sydney, NSW, Australia.
[Schenk, Maryjean] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Schenk, Maryjean] Univ Washington, Seattle, WA 98195 USA.
[Severson, Richard K.] Wayne State Univ, Dept Family Med, Detroit, MI USA.
[Severson, Richard K.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
RP Lan, Q (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, MSC 7240,6120 Execut Blvd,EPS 8109, Bethesda, MD 20892 USA.
EM qingl@mail.nih.gov
RI Zahm, Shelia/B-5025-2015; Morton, Lindsay/B-5234-2015; Armstrong,
Bruce/K-9464-2015; Purdue, Mark/C-9228-2016;
OI Morton, Lindsay/0000-0001-9767-2310; Armstrong,
Bruce/0000-0001-8940-7525; Purdue, Mark/0000-0003-1177-3108; Cerhan,
James/0000-0002-7482-178X; Vajdic, Claire/0000-0002-3612-8298
FU National Institutes of Health (NIH) (National Cancer Institute (NCI));
Public Health Service (PHS) [N01-PC-65064, N01-PC-67008, N01-PC-67009,
N01-PC-67010, N02-PC-71105]; NCI [CA62006]; National Health and Medical
Research Council of Australia [990920]; The Cancer Council NSW; The
University of Sydney Medical Foundation
FX DNA extraction, genotyping and statistical analysis for this project
were supported by the Intramural Research Program of the National
Institutes of Health (NIH) (National Cancer Institute (NCI)). The
NCI-SEER study was also supported by the Intramural Research Program of
the NIH (NCI), and by Public Health Service (PHS) contracts
N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010, and
N02-PC-71105. The Connecticut study was supported by NIH grant CA62006
(TZ) from the NCI. The NSW study was supported by the National Health
and Medical Research Council of Australia Project Grant number 990920
(BA), The Cancer Council NSW, and The University of Sydney Medical
Foundation. We gratefully acknowledge the assistance of Peter Hui
(Information Management Services, Inc., Silver Spring, MD) for
programming support.
NR 38
TC 22
Z9 22
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD MAY
PY 2011
VL 153
IS 3
BP 341
EP 350
DI 10.1111/j.1365-2141.2010.08424.x
PG 10
WC Hematology
SC Hematology
GA 748BJ
UT WOS:000289364700005
PM 21418175
ER
PT J
AU Schafer, R
Schnaidt, M
Klaffschenkel, RA
Siegel, G
Schule, M
Radlein, MA
Hermanutz-Klein, U
Ayturan, M
Buadze, M
Gassner, C
Danielyan, L
Kluba, T
Northoff, H
Flegel, WA
AF Schaefer, Richard
Schnaidt, Martina
Klaffschenkel, Roland A.
Siegel, Georg
Schuele, Michael
Raedlein, Maria Anna
Hermanutz-Klein, Ursula
Ayturan, Miriam
Buadze, Marine
Gassner, Christoph
Danielyan, Lusine
Kluba, Torsten
Northoff, Hinnak
Flegel, Willy A.
TI Expression of blood group genes by mesenchymal stem cells
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE stem cell transplantation; mesenchymal cells; blood groups; H antigen;
CD173
ID VERSUS-HOST-DISEASE; BONE-MARROW; STROMAL CELLS; OSTEOGENESIS
IMPERFECTA; CLINICAL-APPLICATIONS; AMMONIA TRANSPORTER; RHC
GLYCOPROTEIN; ANTIGEN; TRANSPLANTATION; IDENTIFICATION
AB P>Incompatible blood group antigens are highly immunogenic and can cause graft rejections. Focusing on distinct carbohydrate- and protein-based membrane structures, defined by blood group antigens, we investigated human bone marrow-derived mesenchymal stem cells (MSCs) cultured in human serum. The presence of H (CD173), ABO, RhD, RhCE, RhAG, Kell, urea transporter type B (SLC14A1, previously known as JK), and Duffy antigen receptor of chemokines (DARC) was evaluated at the levels of genome, transcriptome and antigen. Fucosyltransferase-1 (FUT1), RHCE, KEL, SLC14A1 (JK) and DARC mRNA were transcribed in MSCs. FUT1 mRNA transcription was lost during differentiation. The mRNA transcription of SLC14A1 (JK) decreased during chondrogenic differentiation, while that of DARC increased during adipogenic differentiation. All MSCs synthesized SLC14A1 (JK) but no DARC protein. However, none of the protein antigens tested occurred on the surface, indicating a lack of associated protein function in the membrane. As A and B antigens are neither expressed nor adsorbed, concerns of ABO compatibility with human serum supplements during culture are alleviated. The H antigen expression by GD2dim+ MSCs identified two distinct MSC subpopulations and enabled their isolation. We hypothesize that GD2dim+ H+ MSCs retain a better 'stemness'. Because immunogenic blood group antigens are lacking, they cannot affect MSC engraftment in vivo, which is promising for clinical applications.
C1 [Flegel, Willy A.] Ctr Clin, Dept Transfus Med, NIH, Bethesda, MD 20892 USA.
[Schaefer, Richard; Schnaidt, Martina; Klaffschenkel, Roland A.; Siegel, Georg; Schuele, Michael; Raedlein, Maria Anna; Hermanutz-Klein, Ursula; Ayturan, Miriam; Buadze, Marine; Northoff, Hinnak] Univ Tubingen Hosp, Inst Clin & Expt Transfus Med IKET, Tubingen, Germany.
[Schaefer, Richard] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Buadze, Marine; Danielyan, Lusine] Univ Tubingen Hosp, Dept Clin Pharmacol, Tubingen, Germany.
[Gassner, Christoph] Blood Donat Ctr Zurich SRC, Schlieren, Switzerland.
[Kluba, Torsten] Univ Tubingen Hosp, Dept Orthopaed, Tubingen, Germany.
RP Flegel, WA (reprint author), Ctr Clin, Dept Transfus Med, NIH, Bldg 10,Room 1C711,10 Ctr Dr, Bethesda, MD 20892 USA.
EM flegelwa@cc.nih.gov
RI Gassner, Christoph/B-2171-2012;
OI Schafer, Richard/0000-0003-1530-7980
FU Intramural NIH HHS [Z99 CL999999]
NR 48
TC 18
Z9 20
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD MAY
PY 2011
VL 153
IS 4
BP 520
EP 528
DI 10.1111/j.1365-2141.2011.08652.x
PG 9
WC Hematology
SC Hematology
GA 753BJ
UT WOS:000289738900009
PM 21418181
ER
PT J
AU Liu, MM
Tuo, JS
Chan, CC
AF Liu, Melissa M.
Tuo, Jingsheng
Chan, Chi-Chao
TI Gene therapy for ocular diseases
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Review
ID EPITHELIUM-DERIVED FACTOR; CILIARY NEUROTROPHIC FACTOR; LEBER CONGENITAL
AMAUROSIS; RETINAL GANGLION-CELLS; INHIBITS CHOROIDAL
NEOVASCULARIZATION; BOVINE IMMUNODEFICIENCY VIRUS; ADENOASSOCIATED VIRAL
VECTOR; ADENOVIRUS-MEDIATED DELIVERY; RCS RAT MODEL; MOUSE MODEL
AB The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.
C1 [Liu, Melissa M.; Tuo, Jingsheng; Chan, Chi-Chao] NEI, NIH, Immunopathol Sect, Immunol Lab, Bethesda, MD 20895 USA.
RP Chan, CC (reprint author), NEI, NIH, Immunopathol Sect, Immunol Lab, 10 Ctr Dr,Bldg 10,Rm 10N103, Bethesda, MD 20895 USA.
EM chanc@nei.nih.gov
OI Tuo, Jingsheng/0000-0002-1372-7810
FU NEI; American Health Assistance Foundation [M2007037]; National
Institutes of Health
FX This work was supported by the NEI Intramural Research Program and the
American Health Assistance Foundation (M2007037). Other Funders:
National Institutes of Health.
NR 104
TC 32
Z9 33
U1 2
U2 16
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD MAY
PY 2011
VL 95
IS 5
BP 604
EP 612
DI 10.1136/bjo.2009.174912
PG 9
WC Ophthalmology
SC Ophthalmology
GA 752TN
UT WOS:000289717300004
PM 20733027
ER
PT J
AU Shirota, H
Klinman, DM
AF Shirota, Hidekazu
Klinman, Dennis M.
TI CpG-conjugated apoptotic tumor cells elicit potent tumor-specific
immunity
SO CANCER IMMUNOLOGY IMMUNOTHERAPY
LA English
DT Article
DE Cancer; Vaccine; Adjuvant; TLR9; CpG ODN
ID CANCER-IMMUNOTHERAPY; METASTATIC MELANOMA; AIRWAY EOSINOPHILIA;
DENDRITIC CELLS; BACTERIAL-DNA; ANTIGEN; OLIGODEOXYNUCLEOTIDES; VACCINE;
PROTEIN; MODEL
AB The primary goal of cancer immunotherapy is to elicit an immune response capable of eradicating established tumors and preventing tumor metastasis. One strategy to achieve this goal utilizes whole killed tumor cells as the primary immunogen. Killed tumor cells provide a comprehensive source of tumor-associated antigens (TAAs), thereby eliminating the need to identify individual antigens. Unfortunately, killed tumor cells tend to be poorly immunogenic. To overcome this limitation, we covalently conjugated immunostimulatory CpG oligodeoxynucleotides (ODN) to apoptotic tumor cells and examined their ability to induce TAA-specific immune responses. Results indicate that CpG conjugation enhances the uptake of cell-based vaccines by dendritic cells (DCs), up-regulates co-stimulatory molecule expression, and promotes the production of immunostimulatory cytokines. Vaccination with CpG-conjugated tumor cells triggers the expansion of tumor-specific cytotoxic T lymphocytes (CTL) that reduce the growth of established tumors and prevents their metastatic spread. Thus, conjugating CpG ODN to cell-based tumor vaccines is an important step toward improving cancer immunotherapy.
C1 [Shirota, Hidekazu; Klinman, Dennis M.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Shirota, Hidekazu] NCI, Basic Sci Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Klinman, DM (reprint author), NCI, Expt Immunol Lab, Canc & Inflammat Program, Bldg 567,Rm 205, Frederick, MD 21702 USA.
EM shirotah@mail.nih.gov; klinmand@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN26120080001E]
FX The authors thank Dr. Nga for advice on conjugation methods and Drs. J.
Weiss and Z. Howard for kindly providing several of the tumor cell lines
used in this study. This project was funded by the Intramural Research
Program of the National Cancer Institute, National Institutes of Health,
including 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.
NCI Frederick is accredited by AAALAC International and follows the
Public Health Service Policy for the Care and Use of Laboratory Animals.
Animal care was provided in accordance with the procedures outlined in
the "Guide for Care and Use of Laboratory Animals'' (National Research
Council; 1996; National Academy Press; Washington, DC).
NR 42
TC 19
Z9 20
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-7004
J9 CANCER IMMUNOL IMMUN
JI Cancer Immunol. Immunother.
PD MAY
PY 2011
VL 60
IS 5
BP 659
EP 669
DI 10.1007/s00262-011-0973-y
PG 11
WC Oncology; Immunology
SC Oncology; Immunology
GA 752XJ
UT WOS:000289728500006
PM 21318638
ER
PT J
AU Amos, SM
Pegram, HJ
Westwood, JA
John, LB
Devaud, C
Clarke, CJ
Restifo, NP
Smyth, MJ
Darcy, PK
Kershaw, MH
AF Amos, Sally M.
Pegram, Hollie J.
Westwood, Jennifer A.
John, Liza B.
Devaud, Christel
Clarke, Chris J.
Restifo, Nicholas P.
Smyth, Mark J.
Darcy, Phillip K.
Kershaw, Michael H.
TI Adoptive immunotherapy combined with intratumoral TLR agonist delivery
eradicates established melanoma in mice
SO CANCER IMMUNOLOGY IMMUNOTHERAPY
LA English
DT Article
DE Tumor immunology; Immunotherapy; Pmel; Toll-like receptor; Adoptive
immunotherapy; Adjuvant
ID TOLL-LIKE RECEPTORS; BLOOD MONONUCLEAR-CELLS; IN-VIVO; GENE-EXPRESSION;
DENDRITIC CELLS; T-CELLS; METASTATIC MELANOMA; CPG
OLIGODEOXYNUCLEOTIDES; INDUCIBLE PROTEIN-10; ADAPTIVE IMMUNITY
AB Toll-like receptor (TLR) agonists can trigger broad inflammatory responses that elicit rapid innate immunity and promote the activities of lymphocytes, which can potentially enhance adoptive immunotherapy in the tumor-bearing setting. In the present study, we found that Polyinosinic:Polycytidylic Acid [Poly(I:C)] and CpG oligodeoxynucleotide 1826 [CpG], agonists for TLR 3 and 9, respectively, potently activated adoptively transferred T cells against a murine model of established melanoma. Intratumoral injection of Poly(I:C) and CpG, combined with systemic transfer of activated pmel-1 T cells, specific for gp100(25-33), led to enhanced survival and eradication of 9-day established subcutaneous B16F10 melanomas in a proportion of mice. A series of survival studies in knockout mice supported a key mechanistic pathway, whereby TLR agonists acted via host cells to enhance IFN-gamma production by adoptively transferred T cells. IFN-gamma, in turn, enhanced the immunogenicity of the B16F10 melanoma line, leading to increased killing by adoptively transferred T cells. Thus, this combination approach counteracted tumor escape from immunotherapy via downregulation of immunogenicity. In conclusion, TLR agonists may represent advanced adjuvants within the setting of adoptive T-cell immunotherapy of cancer and hold promise as a safe means of enhancing this approach within the clinic.
C1 [Amos, Sally M.; Pegram, Hollie J.; Westwood, Jennifer A.; John, Liza B.; Devaud, Christel; Clarke, Chris J.; Smyth, Mark J.; Darcy, Phillip K.; Kershaw, Michael H.] Peter MacCallum Canc Ctr, Canc Immunol Res Program, Melbourne, Vic 3002, Australia.
[Restifo, Nicholas P.] NCI, Surg Branch, Bethesda, MD 20892 USA.
[Smyth, Mark J.; Darcy, Phillip K.; Kershaw, Michael H.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia.
[Smyth, Mark J.; Darcy, Phillip K.; Kershaw, Michael H.] Monash Univ, Dept Immunol, Clayton, Vic, Australia.
RP Kershaw, MH (reprint author), Peter MacCallum Canc Ctr, Canc Immunol Res Program, 14 St Andrews Pl, Melbourne, Vic 3002, Australia.
EM michael.kershaw@petermac.org
RI Restifo, Nicholas/A-5713-2008; Smyth, Mark/H-8709-2014;
OI Smyth, Mark/0000-0001-7098-7240; Kershaw, Michael/0000-0002-2697-487X;
Restifo, Nicholas P./0000-0003-4229-4580
FU National Health and Medical Research Council of Australia (NHMRC);
Cancer Council of Victoria; The Bob Parker Memorial Fund
FX This work was supported by the National Health and Medical Research
Council of Australia (NHMRC), Cancer Council of Victoria and The Bob
Parker Memorial Fund. M.K. is supported by a Senior Research Fellowship
from the NHMRC. P.D. is supported by an NHMRC Career Development Award,
M.J.S. is supported by an Australia Fellowship from the NHMRC and S.A.
is supported by a Cancer Council of Victoria Postgraduate Cancer
Research Scholarship.
NR 52
TC 29
Z9 29
U1 1
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-7004
J9 CANCER IMMUNOL IMMUN
JI Cancer Immunol. Immunother.
PD MAY
PY 2011
VL 60
IS 5
BP 671
EP 683
DI 10.1007/s00262-011-0984-8
PG 13
WC Oncology; Immunology
SC Oncology; Immunology
GA 752XJ
UT WOS:000289728500007
PM 21327636
ER
PT J
AU Yang, SC
Luca, G
Liu, F
Ji, Y
Yu, ZY
Restifo, NP
Rosenberg, SA
Morgan, RA
AF Yang, Shicheng
Luca, Gattinoni
Liu, Fang
Ji, Yun
Yu, Zhiya
Restifo, Nicholas P.
Rosenberg, Steven A.
Morgan, Richard A.
TI In vitro generated anti-tumor T lymphocytes exhibit distinct subsets
mimicking in vivo antigen-experienced cells
SO CANCER IMMUNOLOGY IMMUNOTHERAPY
LA English
DT Article
DE Gene therapy; Lentiviral vector; T-cell receptor; Central memory cells;
Effector memory cells; Tumor immunity
ID TUMOR-INFILTRATING LYMPHOCYTES; CENTRAL-MEMORY; ENGINEERED LYMPHOCYTES;
METASTATIC MELANOMA; BINDING-PROTEIN; GENE-EXPRESSION; VECTOR DESIGN;
EX-VIVO; EFFECTOR; RECEPTOR
AB The T-lymphocyte pool can be subdivided into na < ve (Tn), effector memory (Tem), and central memory (Tcm) T cells. In this study, we characterized in vitro short-term cultured anti-tumor human T lymphocytes generated by lentiviral transduction with an anti-tumor antigen TCR vector. Within 2 weeks of in vitro culture, the cultured T cells showed a Tcm-like phenotype illustrated by a high percentage of CD62L and CD45RO cells. When the cells were sorted into populations that were CD45RO+/CD62L-(Tem), CD45RO+/CD62L+(Tcm), or CD45RO(low)/CD62L+(Tn) and co-cultured with antigen-matched tumor lines, the magnitude of cytokine release from these populations for IFN gamma (Tn < Tcm < Tem) and IL-2 (Tn > Tcm > Tem) mimicked the types of immune cell responses observed in vivo. In comparing cell-mediated effector function, Tn were found to be deficient (relative to Tcm and Tem) in the ability to form conjugates with tumor cells and subsequent lytic activity. Moreover, analysis of the gene expression profiles of the in vitro cultured and sorted T-cell populations also demonstrated patterns consistent with their in vivo counterparts. When Tcm and Tem were tested for the ability to survive in vivo, Tcm displayed significantly increased engraftment and persistence in NOD/SCID/gamma c(-/-) mice. In general, a large percentage of in vitro generated anti-tumor T lymphocytes mimic a Tcm-like phenotype (based on phenotype, effector function, and increased persistence in vivo), which suggests that these Tcm-like cultured T cells may be optimal for adoptive immunotherapy.
C1 [Yang, Shicheng; Luca, Gattinoni; Liu, Fang; Ji, Yun; Yu, Zhiya; Restifo, Nicholas P.; Rosenberg, Steven A.; Morgan, Richard A.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Morgan, RA (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10,CRC 3W-3864, Bethesda, MD 20892 USA.
EM rmorgan@mail.nih.gov
RI Gattinoni, Luca/A-2281-2008; Ji, Yun/B-7245-2009; Restifo,
Nicholas/A-5713-2008;
OI Gattinoni, Luca/0000-0003-2239-3282; Ji, Yun/0000-0001-6340-7009;
Restifo, Nicholas P./0000-0003-4229-4580
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX We thank Arnold Mixon and Shawn Farid in the FACS laboratory and all
members in the TIL laboratory at the Surgery Branch for providing
technical support and maintenance of PBL and tumor cells from patients.
This work is supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 51
TC 22
Z9 23
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-7004
J9 CANCER IMMUNOL IMMUN
JI Cancer Immunol. Immunother.
PD MAY
PY 2011
VL 60
IS 5
BP 739
EP 749
DI 10.1007/s00262-011-0977-7
PG 11
WC Oncology; Immunology
SC Oncology; Immunology
GA 752XJ
UT WOS:000289728500013
PM 21305379
ER
PT J
AU Woolery, M
Sheeron, J
Jarosinski, P
AF Woolery, Myra
Sheeron, Joan
Jarosinski, Paul
TI A Multidisciplinary Approach: Improving Documentation Key to Serum Drug
Level Interpretation
SO CLINICAL NURSE SPECIALIST
LA English
DT Meeting Abstract
C1 [Woolery, Myra; Sheeron, Joan; Jarosinski, Paul] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0887-6274
J9 CLIN NURSE SPEC
JI Clin. Nurse Spec.
PD MAY-JUN
PY 2011
VL 25
IS 3
BP 140
EP 140
PG 1
WC Nursing
SC Nursing
GA 748QH
UT WOS:000289405000010
ER
PT J
AU Valeri, RM
Kotakidou, R
Michalakis, K
Andreadis, C
Kousi-Koliakou, K
Destouni, C
AF Valeri, Rosalia-Maria
Kotakidou, Rodoula
Michalakis, Konstantinos
Andreadis, Charalambos
Kousi-Koliakou, Kokkona
Destouni, Charikleia
TI Malignant Leydig-Cell Tumor of the Testis Diagnosed by Fine-Needle
Aspiration Using ThinPrep Technique
SO DIAGNOSTIC CYTOPATHOLOGY
LA English
DT Article
DE Leydig cell tumor; testicular neoplasms; biopsy; FNA;
immunohistochemistry
ID INTRANUCLEAR REINKES CRYSTALS; CYTOLOGY
AB Leydig cell tumors (LCT) are rare sex cord-stromal tumors that account for 2-3% of all testicular tumors. Approximately 10% of LCTs shows evidence of malignant behavior.
We present a case of LCT with severe atypia diagnosed by fine-needle aspiration (FNA) in a 49-year-old man who presented with gynecomastia and right testis enlargement. The FNA material on conventional and ThinPrep smears revealed a hemorrhagic and necrotic background with high cellularity, consisting of large cells, isolated or in small cohesive clusters, abundant, eosinophilic cytoplasm, round nuclei, fine chromatin, and variably conspicuous nucleoli. Occasionally, pleomorphic cells with hyperchromatic nuclei and prominent nucleoli were seen. Immunocytochemistry was positive against vimentin, inhibin, and calretinin. Histological examination of the surgical specimen was in accordance with the FNA findings.
The cytologic diagnosis of LCT of the testis, using FNA, is achievable in a preoperative setting to vitiate the need for more invasive biopsy procedures; malignancy could be considered on cytology when necrosis and marked atypia are evident. Diagn. Cytopathol. 2011;39:368-372. (C) 2010 Wiley-Liss, Inc.
C1 [Michalakis, Konstantinos] Elena Venizelou Gen Hosp, Dept Endocrinol, NIH, Bethesda, MD USA.
[Valeri, Rosalia-Maria; Destouni, Charikleia] Theageneio Canc Hosp Thessaloniki, Dept Cytopathol, Athens, Greece.
[Kotakidou, Rodoula] Gennimatas Hosp Thessaloniki, Dept Pathol, Athens, Greece.
[Andreadis, Charalambos] Theageneio Canc Hosp Thessaloniki, Dept Oncol 3, Athens, Greece.
[Kousi-Koliakou, Kokkona] Aristotle Univ Thessaloniki, Univ Dept Histol & Embryol, Athens, Greece.
RP Michalakis, K (reprint author), Elena Venizelou Gen Hosp, Dept Endocrinol, NIH, Bethesda, MD USA.
EM kostismichalakis@hotmail.com
NR 16
TC 3
Z9 3
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 8755-1039
J9 DIAGN CYTOPATHOL
JI Diagn. Cytopathol.
PD MAY
PY 2011
VL 39
IS 5
BP 368
EP 372
DI 10.1002/dc.21446
PG 5
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 751SR
UT WOS:000289638400013
PM 20730900
ER
PT J
AU Armant, DR
AF Armant, D. Randall
TI Autophagy's Expanding Role in Development: Implantation Is Next
SO ENDOCRINOLOGY
LA English
DT Editorial Material
ID MOUSE UTERUS; MECHANISMS; PATHWAYS; GENES
C1 [Armant, D. Randall] Wayne State Univ Sch Med, CS Mott Ctr Human Growth & Dev, Dept Obstet & Gynecol, Dept Anat & Cell Biol, Detroit, MI 48201 USA.
[Armant, D. Randall] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
RP Armant, DR (reprint author), Wayne State Univ Sch Med, CS Mott Ctr Human Growth & Dev, Dept Obstet & Gynecol, Dept Anat & Cell Biol, 275 E Hancock Ave, Detroit, MI 48201 USA.
EM D.Armant@wayne.edu
OI Armant, D. Randall/0000-0001-5904-9325
FU Intramural NIH HHS; NICHD NIH HHS [R01 HD045966, HD045966]
NR 17
TC 2
Z9 2
U1 1
U2 7
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD MAY
PY 2011
VL 152
IS 5
BP 1739
EP 1741
DI 10.1210/en.2011-0220
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 753OJ
UT WOS:000289788500004
PM 21511986
ER
PT J
AU Cai, T
Chen, X
Wang, RN
Xu, H
You, YH
Zhang, T
Lan, MS
Notkins, AL
AF Cai, Tao
Chen, Xiang
Wang, Rennian
Xu, Huan
You, Yuhui
Zhang, Tao
Lan, Michael S.
Notkins, Abner L.
TI Expression of Insulinoma-Associated 2 (INSM2) in Pancreatic Islet Cells
Is Regulated by the Transcription Factors Ngn3 and NeuroD1
SO ENDOCRINOLOGY
LA English
DT Article
ID NEUROENDOCRINE DIFFERENTIATION; ENDOCRINE PANCREAS; IN-VITRO; IA-1;
PROTEIN; FAMILY; MICE
AB The insulinoma-associated 2 (Insm2) gene is a member of the Snail/Gfi1/Insm1 transcriptional repressor superfamily. However, little is known about how the expression of human INSM2 or mouse Insm2 in neuroendocrine tissues is regulated. Here we report the expression of INSM2/Insm2 in human fetal pancreas and mouse embryos, as well as adult pancreatic islets, and its regulation by two major islet transcription factors. Mutagenesis and chromatin immunoprecipitation analysis demonstrated that the proximal E-boxes of the mouse Insm2 promoter are direct targets of neurogenin 3 and neurogenic differentiation 1 (NeuroD1). Furthermore, we found that endogenous Insm2 expression was activated in Ngn3/NeuroD1-transduced pancreatic epithelial duct cells. Our results suggest that Insm2 plays an important role in the differentiation cascade of Ngn3/NeuroD1 signaling in pancreatic islets. (Endocrinology 152: 1961-1969, 2011)
C1 [Cai, Tao; Notkins, Abner L.] Natl Inst Dent & Craniofacial Res, Expt Med Sect, NIH, Bethesda, MD 20892 USA.
[Chen, Xiang; You, Yuhui] Wenzhou Med Coll, Dept Pediat, Wenzhou 325035, Peoples R China.
[Wang, Rennian] Univ Western Ontario, Dept Physiol & Pharmacol & Med, London, ON N6A 5C1, Canada.
[Xu, Huan] Fudan Univ, Gynecol & Obstet Hosp, Shanghai 200433, Peoples R China.
[Zhang, Tao; Lan, Michael S.] Childrens Hosp, Res Inst Children, New Orleans, LA 70118 USA.
RP Cai, T (reprint author), Natl Inst Dent & Craniofacial Res, Expt Med Sect, NIH, 30 Convent Dr, Bethesda, MD 20892 USA.
EM tcai@mail.nih.gov
RI Wang, Rennian/N-3879-2015
FU National Institute of Dental and Craniofacial Research/National
Institutes of Health; Canadian Diabetes Association; Canadian Institute
of Health Research
FX This work was supported in part by the Intramural Research Program of
the National Institute of Dental and Craniofacial Research/National
Institutes of Health. The human fetal pancreas and duodenum study has
received funding from the Canadian Diabetes Association, and Dr. R. Wang
has received a New Investigator Award from the Canadian Institute of
Health Research.
NR 23
TC 1
Z9 5
U1 1
U2 3
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD MAY
PY 2011
VL 152
IS 5
BP 1961
EP 1969
DI 10.1210/en.2010-1065
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 753OJ
UT WOS:000289788500027
PM 21343251
ER
PT J
AU Olsson, AH
Ronn, T
Ladenvall, C
Parikh, H
Isomaa, B
Groop, L
Ling, C
AF Olsson, Anders H.
Ronn, Tina
Ladenvall, Claes
Parikh, Hemang
Isomaa, Bo
Groop, Leif
Ling, Charlotte
TI Two common genetic variants near nuclear-encoded OXPHOS genes are
associated with insulin secretion in vivo
SO EUROPEAN JOURNAL OF ENDOCRINOLOGY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; HUMAN SKELETAL-MUSCLE; PANCREATIC BETA-CELLS;
DIABETES-MELLITUS; SUSCEPTIBILITY LOCI; RISK LOCI; TYPE-2; MITOCHONDRIA;
RESISTANCE; REPLICATION
AB Context: Mitochondrial ATP production is important in the regulation of glucose-stimulated insulin secretion. Genetic factors may modulate the capacity of the beta-cells to secrete insulin and thereby contribute to the risk of type 2 diabetes.
Objective: The aim of this study was to identify genetic loci in or adjacent to nuclear-encoded genes of the oxidative phosphorylation (OXPHOS) pathway that are associated with insulin secretion in vivo.
Design and methods: To find polymorphisms associated with glucose-stimulated insulin secretion, data from a genome-wide association study (GWAS) of 1467 non-diabetic individuals, including the Diabetes Genetic Initiative (DGI), was examined. A total of 413 single nucleotide polymorphisms with a minor allele frequency >= 0.05 located in or adjacent to 76 OXPHOS genes were included in the DGI GWAS. A more extensive population-based study of 4323 non-diabetics, the PPP-Botnia, was used as a replication cohort. Insulinogenic index during an oral glucose tolerance test was used as a surrogate marker of glucose-stimulated insulin secretion. Multivariate linear regression analyses were used to test genotype-phenotype associations.
Results: Two common variants were identified in the DGI, where the major C-allele of rs606164, adjacent to NADH dehydrogenase (ubiquinone) 1 subunit C2 (NDUFC2), and the minor G-allele of rs1323070, adjacent to cytochrome c oxidase subunit VIIa polypeptide 2 (COX7A2), showed nominal associations with decreased glucose-stimulated insulin secretion (P=0.0009, respective P=0.003). These associations were replicated in PPP-Botnia (P=0.002 and P=0.05).
Conclusion: Our study shows that genetic variation near genes involved in OXPHOS may influence glucose-stimulated insulin secretion in vivo.
C1 [Olsson, Anders H.; Ronn, Tina; Ladenvall, Claes; Parikh, Hemang; Groop, Leif; Ling, Charlotte] Lund Univ, Scania Univ Hosp, Dept Clin Sci, Lund Univ Diabet Ctr,CRC, S-20502 Malmo, Sweden.
[Parikh, Hemang] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20877 USA.
[Isomaa, Bo] 00014 Univ Helsinki, Biomedicum Helsinki, Folkhalsan Res Ctr, Helsinki, Finland.
[Isomaa, Bo] Dept Social Serv & Hlth Care, Pietarsaari 68601, Finland.
RP Ling, C (reprint author), Lund Univ, Scania Univ Hosp, Dept Clin Sci, Lund Univ Diabet Ctr,CRC, S-20502 Malmo, Sweden.
EM charlotte.ling@med.lu.se
RI Ling, Charlotte/Q-2432-2015
OI Ling, Charlotte/0000-0003-0587-7154
FU Novartis; Swedish Research Council; Region Skane; Malmo University
Hospital; Knut and Alice Wallenberg Foundation; Diabetes Foundation;
EFSD-Lilly; Tore Nilsson; Novo Nordisk; Soderberg; Pahlsson and Linne
grant [B31 5631/2006]
FX The DGI GWAS study was supported by a grant from Novartis. The
investigation in Malmo was supported by grants from the Swedish Research
Council, Region Skane, Malmo University Hospital, Knut and Alice
Wallenberg Foundation, Diabetes Foundation, EFSD-Lilly, Tore Nilsson,
Novo Nordisk, Soderberg, Pahlsson and Linne grant (B31 5631/2006).
NR 31
TC 14
Z9 15
U1 0
U2 3
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0804-4643
J9 EUR J ENDOCRINOL
JI Eur. J. Endocrinol.
PD MAY
PY 2011
VL 164
IS 5
BP 765
EP 771
DI 10.1530/EJE-10-0995
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 754HR
UT WOS:000289846200014
PM 21325017
ER
PT J
AU Janssens, ACJW
Ioannidis, JPA
Bedrosian, S
Boffetta, P
Dolan, SM
Dowling, N
Fortier, I
Freedman, AN
Grimshaw, JM
Gulcher, J
Gwinn, M
Hlatky, MA
Janes, H
Kraft, P
Melillo, S
O'Donnell, CJ
Pencina, MJ
Ransohoff, D
Schully, SD
Seminara, D
Winn, DM
Wright, CF
van Duijn, CM
Little, J
Khoury, MJ
AF Janssens, A. Cecile J. W.
Ioannidis, John P. A.
Bedrosian, Sara
Boffetta, Paolo
Dolan, Siobhan M.
Dowling, Nicole
Fortier, Isabel
Freedman, Andrew N.
Grimshaw, Jeremy M.
Gulcher, Jeffrey
Gwinn, Marta
Hlatky, Mark A.
Janes, Holly
Kraft, Peter
Melillo, Stephanie
O'Donnell, Christopher J.
Pencina, Michael J.
Ransohoff, David
Schully, Sheri D.
Seminara, Daniela
Winn, Deborah M.
Wright, Caroline F.
van Duijn, Cornelia M.
Little, Julian
Khoury, Muin J.
TI Strengthening the reporting of genetic risk prediction studies (GRIPS):
explanation and elaboration
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; HEART-DISEASE RISK; OPERATING CHARACTERISTIC
CURVE; TYPE-2 DIABETES RISK; RECLASSIFICATION MEASURES; MACULAR
DEGENERATION; DIAGNOSTIC-ACCURACY; CARDIOVASCULAR RISK;
CONTROLLED-TRIALS; PROSTATE-CANCER
AB The rapid and continuing progress in gene discovery for complex diseases is fueling interest in the potential application of genetic risk models for clinical and public health practice. The number of studies assessing the predictive ability is steadily increasing, but they vary widely in completeness of reporting and apparent quality. Transparent reporting of the strengths and weaknesses of these studies is important to facilitate the accumulation of evidence on genetic risk prediction. A multidisciplinary workshop sponsored by the Human Genome Epidemiology Network developed a checklist of 25 items recommended for strengthening the reporting of Genetic RIsk Prediction Studies (GRIPS), building on the principles established by previous reporting guidelines. These recommendations aim to enhance the transparency, quality and completeness of study reporting, and thereby to improve the synthesis and application of information from multiple studies that might differ in design, conduct or analysis. European Journal of Human Genetics (2011) 19; doi:10.1038/ejhg.2011.27; published online 16 March 2011
C1 [Janssens, A. Cecile J. W.; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
[Ioannidis, John P. A.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece.
[Ioannidis, John P. A.] Fdn Res & Technol, Biomed Res Inst, Ioannina, Greece.
[Ioannidis, John P. A.] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA.
[Ioannidis, John P. A.] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Tufts CTSI, Boston, MA USA.
[Ioannidis, John P. A.] Ctr Genet Epidemiol & Modeling, Boston, MA USA.
[Ioannidis, John P. A.] Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA.
[Ioannidis, John P. A.; Bedrosian, Sara; Dowling, Nicole; Gwinn, Marta; Melillo, Stephanie; Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA.
[Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
[Boffetta, Paolo] Int Prevent Res Inst, Lyon, France.
[Dolan, Siobhan M.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, Bronx, NY 10467 USA.
[Fortier, Isabel] Publ Populat Project Genom P3G, Montreal, PQ, Canada.
[Freedman, Andrew N.; Schully, Sheri D.; Seminara, Daniela; Winn, Deborah M.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Grimshaw, Jeremy M.] Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada.
[Grimshaw, Jeremy M.] Univ Ottawa, Dept Med, Ottawa, ON, Canada.
[Gulcher, Jeffrey] deCODE Genet, Reykjavik, Iceland.
[Hlatky, Mark A.] Stanford Univ, Dept Hlth Res & Policy, Palo Alto, CA 94304 USA.
[Janes, Holly] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Inst, Seattle, WA 98104 USA.
[Janes, Holly] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[O'Donnell, Christopher J.] NHLBI, Framingham, MA USA.
[O'Donnell, Christopher J.] NHLBIs Framingham Heart Study, Framingham, MA USA.
[O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
[Pencina, Michael J.] Boston Univ, Dept Biostat, Boston, MA 02215 USA.
[Pencina, Michael J.] Harvard Clin Res Inst, Boston, MA USA.
[Ransohoff, David] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Wright, Caroline F.] PHG Fdn, Cambridge, England.
[Little, Julian] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON, Canada.
RP Janssens, ACJW (reprint author), Erasmus Univ, Med Ctr, Dept Epidemiol, POB 2040, NL-3000 CA Rotterdam, Netherlands.
EM a.janssens@erasmusmc.nl
RI Ioannidis, John/G-9836-2011; janssens, cecile/L-1075-2015;
OI Janssens, A Cecile/0000-0002-6153-4976; Wright,
Caroline/0000-0003-2958-5076
FU National Heart, Lung and Blood Institute; National Cancer Institute,
National Institutes of Health; Donald W. Reynolds Foundation; Leducq
Foundation
FX Examples: 'This study was supported by grants from the National Heart,
Lung and Blood Institute and National Cancer Institute, National
Institutes of Health; the Donald W. Reynolds Foundation; and the Leducq
Foundation. Additional support for DNA extraction, reagents and data
analysis was provided by Roche Diagnostics and Amgen. Genotyping of the
9p21.3 variant was performed by Celera. The funding sources had no role
in the design, conduct, or reporting of this study or the decision to
submit the manuscript for publication'.56
NR 93
TC 2
Z9 2
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD MAY
PY 2011
VL 19
IS 5
DI 10.1038/ejhg.2011.27
PG 18
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 753OR
UT WOS:000289789500001
ER
PT J
AU Yao, ZY
Wei, XY
Wu, XM
Katz, JL
Kopajtic, T
Greig, NH
Sun, HB
AF Yao, Zhangyu
Wei, Xueying
Wu, Xiaoming
Katz, Jonathan L.
Kopajtic, Theresa
Greig, Nigel H.
Sun, Hongbin
TI Preparation and evaluation of tetrabenazine enantiomers and all eight
stereoisomers of dihydrotetrabenazine as VMAT2 inhibitors
SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
DE Tetrabenazine enantiomers; Dihydrotetrabenazine stereoisomers;
Resolution; Huntington's chorea; VMAT2; Hyperkinetic disorders
ID MONOAMINE TRANSPORTER; MOVEMENT-DISORDERS; METABOLITE; EPOXIDES;
EMETINE; BINDING; DRUGS
AB Tetrabenazine (TBZ) ((+/-)-1) and dihydrotetrabenazines (DHTBZ) are potent inhibitors of VMAT2. Herein, a practical chemical resolution of (+/-)-1 and stereoselective synthesis of all eight DHTBZ stereoisomers are described. The result of VMAT2 binding assay revealed that (+)-1 (K-i = 4.47 nM) was 8000-fold more potent than ()-1 (K-i = 36,400 nM). Among all eight DHTBZ stereoisomers, (2R,3R,11bR)-DHTBZ ((+)-2: K-i= 3.96 nM) showed the greatest affinity for VMAT2. The (3R,11bR)-configuration appeared to play a key role for VMAT2 binding. In summary, (+)-1, (+)-2, and their derivatives warrant further studies in order to develop more potent and safer drugs for the treatment of chorea associated with Huntington's disease and other hyperkinetic disorders. (C) 2011 Elsevier Masson SAS. All rights reserved.
C1 [Yao, Zhangyu; Wei, Xueying; Wu, Xiaoming; Sun, Hongbin] China Pharmaceut Univ, Coll Pharm, Ctr Drug Discovery, Nanjing 210009, Peoples R China.
[Katz, Jonathan L.; Kopajtic, Theresa] Natl Inst Drug Abuse, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Greig, Nigel H.] NIA, Drug Design & Dev Sect, Lab Neurosci, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
RP Sun, HB (reprint author), China Pharmaceut Univ, Coll Pharm, Ctr Drug Discovery, 24 Tongjiaxiang, Nanjing 210009, Peoples R China.
EM hbsun2000@yahoo.com
OI Katz, Jonathan/0000-0002-1068-1159
FU Ministry of Education of China; State Administration of Foreign Expert
Affairs of China [111-2-07]; National Institute on Aging and National
Institute on Drug Abuse, NIH
FX This work was supported in part by the "111 Project" from the Ministry
of Education of China and the State Administration of Foreign Expert
Affairs of China (No. 111-2-07). It was additionally supported in part
by the Intramural Research Programs of the National Institute on Aging
and National Institute on Drug Abuse, NIH.
NR 23
TC 13
Z9 13
U1 0
U2 6
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 0223-5234
J9 EUR J MED CHEM
JI Eur. J. Med. Chem.
PD MAY
PY 2011
VL 46
IS 5
BP 1841
EP 1848
DI 10.1016/j.ejmech.2011.02.046
PG 8
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 751YW
UT WOS:000289655100044
PM 21396745
ER
PT J
AU Goldstein, DS
Sullivan, P
Holmes, C
Kopin, IJ
Basile, MJ
Mash, DC
AF Goldstein, D. S.
Sullivan, P.
Holmes, C.
Kopin, I. J.
Basile, M. J.
Mash, D. C.
TI Catechols in post-mortem brain of patients with Parkinson disease
SO EUROPEAN JOURNAL OF NEUROLOGY
LA English
DT Article
DE aldehyde dehydrogenase; dihydroxyphenylacetaldehyde;
dihydroxyphenylglycol; dopamine; norepinephrine; Parkinson disease;
putamen
ID ENDOGENOUS DOPAMINERGIC NEUROTOXIN; SUBSTANTIA-NIGRA; ALDEHYDE
DEHYDROGENASE; METABOLIC STRESS; ALPHA-SYNUCLEIN; PC12 CELLS;
3,4-DIHYDROXYPHENYLACETALDEHYDE; CHROMATOGRAPHY; PATHOGENESIS
AB Background:
Dihydroxyphenylacetaldehyde (DOPAL), a cytotoxic metabolite of dopamine, is the focus of the 'catecholaldehyde hypothesis' about the pathogenesis of Parkinson disease. This study explored whether DOPAL is detectable in human striatum - especially in the putamen (Pu), the main site of dopamine depletion in Parkinson disease - and is related to other neurochemical indices of catecholamine stores and metabolism in Parkinson disease.
Methods:
Putamen, caudate (Cd), and frontal cortex (Ctx) catechols were measured in tissue from patients with pathologically proven end-stage Parkinson disease (N = 15) and control subjects (N = 14) of similar age with similar post-mortem intervals.
Results:
Putamen DOPAL (3% of dopamine in controls) correlated with dopamine and dihydroxyphenylacetic acid both across all subjects and within the Parkinson disease and control groups. Pu dopamine was decreased by 93% and dihydroxyphenylacetic acid 95% in Parkinson disease vs. controls, with smaller decreases of DOPAL (83%) and norepinephrine (73%) in Pu and of dopamine (74%) and dihydroxyphenylacetic acid (82%) in Cd. In Parkinson disease, Pu DOPAL:dihydroxyphenylacetic acid averaged 3.4 times and DOPAL:dopamine 4.4 times control (P = 0.03 each). The main catecholamine in Ctx was norepinephrine, which was decreased by 51% in Parkinson disease patients.
Conclusions:
Correlated decreases of DOPAL, dopamine, and dihydroxyphenylacetic acid in Parkinson disease reflect severe loss of Pu dopamine stores, which seems more extensive than loss of Pu norepinephrine or Cd dopamine stores. Increased Pu DOPAL:dihydroxyphenylacetic acid ratios in Parkinson disease suggest decreased detoxification of DOPAL by aldehyde dehydrogenase. Elevated levels of cytosolic DOPAL might contribute to loss of dopaminergic neurons in Parkinson disease.
C1 [Goldstein, D. S.] NINDS, Clin Neurocardiol Sect, NIH, Clin Neurosci Program,Div Intramural Res, Bethesda, MD 20892 USA.
[Basile, M. J.; Mash, D. C.] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.
RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, Clin Neurosci Program,Div Intramural Res, 9000 Rockville Pike MSC 1620,Bldg 10,Room 5N220, Bethesda, MD 20892 USA.
EM goldsteind@ninds.nih.gov
FU NINDS
FX The research reported here was supported by the intramural research
program of the NINDS.
NR 19
TC 47
Z9 47
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1351-5101
J9 EUR J NEUROL
JI Eur. J. Neurol.
PD MAY
PY 2011
VL 18
IS 5
BP 703
EP 710
DI 10.1111/j.1468-1331.2010.03246.x
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 751OI
UT WOS:000289627000009
PM 21073636
ER
PT J
AU Popat, RA
Van Den Eeden, SK
Tanner, CM
Kamel, F
Umbach, DM
Marder, K
Mayeux, R
Ritz, B
Ross, GW
Petrovitch, H
Topol, B
McGuire, V
Costello, S
Manthripragada, AD
Southwick, A
Myers, RM
Nelson, LM
AF Popat, R. A.
Van Den Eeden, S. K.
Tanner, C. M.
Kamel, F.
Umbach, D. M.
Marder, K.
Mayeux, R.
Ritz, B.
Ross, G. W.
Petrovitch, H.
Topol, B.
McGuire, V.
Costello, S.
Manthripragada, A. D.
Southwick, A.
Myers, R. M.
Nelson, L. M.
TI Coffee, ADORA2A, and CYP1A2: the caffeine connection in Parkinson's
disease
SO EUROPEAN JOURNAL OF NEUROLOGY
LA English
DT Article
DE adenosine receptor A2A; caffeine; case-control; CYP1A2; epidemiology;
Parkinson's disease; polymorphisms
ID RISK; NEUROPROTECTION; POLYMORPHISMS; ASSOCIATION; INACTIVATION; AGE
AB Background and purpose:
In 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine animal models of Parkinson's disease (PD), caffeine protects neurons by blocking the adenosine receptor A2A (ADORA2A). Caffeine is primarily metabolized by cytochrome P450 1A2 (CYP1A2). Our objective was to examine whether ADORA2A and CYP1A2 polymorphisms are associated with PD risk or modify the caffeine-PD association.
Methods:
Parkinson's Epidemiology and Genetic Associations Studies in the United States (PEGASUS) included five population-based case-control studies. One laboratory genotyped four ADORA2A and three CYP1A2 polymorphisms in 1325 PD cases and 1735 age- and sex-matched controls. Information regarding caffeine (coffee) consumption and other lifestyle factors came from structured in-person or telephone interviews. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression.
Results:
Two ADORA2A polymorphisms were inversely associated with PD risk - rs71651683, a 5' variant (adjusted allelic OR = 0.51, 95% CI 0.33-0.80, permutation-adjusted P = 0.015) and rs5996696, a promoter region variant (adjusted OR for AC and CC genotypes compared with the AA wild-type genotype were 0.76 (95% CI 0.57-1.02) and 0.37 (95% CI 0.13-1.01), respectively (permutation-adjusted P for trend = 0.04). CYP1A2 polymorphisms were not associated with PD risk; however, the coffee-PD association was strongest among subjects homozygous for either variant allele rs762551 (P(interaction) = 0.05) or rs2470890 (P(interaction) = 0.04).
Conclusion:
In this consortium study, two ADORA2A polymorphisms were inversely associated with PD risk, but there was weak evidence of interaction with coffee consumption. In contrast, the coffee-PD association was strongest among slow metabolizers of caffeine who were homozygous carriers of the CYP1A2 polymorphisms.
C1 [Popat, R. A.; Topol, B.; McGuire, V.; Nelson, L. M.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Epidemiol, Stanford, CA 94305 USA.
[Van Den Eeden, S. K.] Kaiser Fdn Res Inst, Div Res, Oakland, CA USA.
[Tanner, C. M.] Parkinsons Inst, Sunnyvale, CA USA.
[Kamel, F.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Umbach, D. M.] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Marder, K.; Mayeux, R.] Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY USA.
[Marder, K.; Mayeux, R.] Columbia Univ, Gertrude H Sergievsky Ctr, Coll Phys & Surg, New York, NY 10027 USA.
[Marder, K.; Mayeux, R.] Columbia Univ, Coll Phys & Surg, Taub Inst, New York, NY USA.
[Ritz, B.; Manthripragada, A. D.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA.
[Ross, G. W.; Petrovitch, H.] Vet Affairs Pacific Islands Hlth Care Syst, Honolulu, HI USA.
[Ross, G. W.; Petrovitch, H.] Pacific Hlth Res Inst, Honolulu, HI USA.
[Costello, S.] Univ Calif Berkeley, Sch Publ Hlth, Dept Environm Sci, Berkeley, CA 94720 USA.
[Southwick, A.; Myers, R. M.] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA.
RP Popat, RA (reprint author), Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Epidemiol, HRP Redwood Bldg,Room T209, Stanford, CA 94305 USA.
EM rpopat@stanford.edu
RI Ritz, Beate/E-3043-2015;
OI Kamel, Freya/0000-0001-5052-6615
FU Michael J Fox Foundation for Parkinson's Research; NIH [NS R01-31964,
R01-NS32527, ES10544, UES12078]; Tobacco-Related Disease Research Fund
[8RT-0131, 11RT-0237]; NIA [PO1 AG07232, NO1-AG-4-2149]; SCEHSC [5P30
ES07048]; Parkinson's Disease Association; United States Department of
the Army [DAM.D.17-98-1-8621]; NHLBI [NO1-HC-05102]; VA Medical
Research; NIEHS [01-ES10803, U54-ES12077]; NIH, National Institute of
Environmental Health Sciences, and National Cancer Institute (Division
of Cancer Epidemiology and Genetics)
FX Funding was provided to the PEGASUS genetic consortium by the Michael J
Fox Foundation for Parkinson's Research. Additional funding to
individual investigators for the original studies was provided by: NIH
NS R01-31964 and Tobacco-Related Disease Research Fund Grants and
8RT-0131 and 11RT-0237 (Dr. Lorene Nelson,); NIH R01-NS32527 (Drs.
Richard Mayeux and Karen Marder), NIA PO1 AG07232 (Dr. Richard Mayeux);
NIH ES10544 and UES12078, pilot funding from SCEHSC # 5P30 ES07048, the
Parkinson's Disease Association (Dr. Beate Ritz); United States
Department of the Army DAM.D.17-98-1-8621, NIA NO1-AG-4-2149, NHLBI
NO1-HC-05102, and VA Medical Research funds (Dr. G. Webster Ross); NIEHS
01-ES10803 and U54-ES12077 (Drs. Caroline Tanner and Freya Kamel). The
FAME study was supported in part by the Intramural Research Program of
the NIH, National Institute of Environmental Health Sciences, and
National Cancer Institute (Division of Cancer Epidemiology and
Genetics). The information in this study does not necessarily reflect
the position or the policy of the government and no official endorsement
should be inferred.
NR 28
TC 38
Z9 39
U1 0
U2 19
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1351-5101
J9 EUR J NEUROL
JI Eur. J. Neurol.
PD MAY
PY 2011
VL 18
IS 5
BP 756
EP 765
DI 10.1111/j.1468-1331.2011.03353.x
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 751OI
UT WOS:000289627000017
PM 21281405
ER
PT J
AU Hogg, ME
Varu, VN
Vavra, AK
Popowich, DA
Banerjee, MN
Martinez, J
Jiang, Q
Saavedra, JE
Keefer, LK
Kibbe, MR
AF Hogg, Melissa E.
Varu, Vinit N.
Vavra, Ashley K.
Popowich, Daniel A.
Banerjee, Monisha N.
Martinez, Janet
Jiang, Qun
Saavedra, Joseph E.
Keefer, Larry K.
Kibbe, Melina R.
TI Effect of nitric oxide on neointimal hyperplasia based on sex and
hormone status
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Neointimal hyperplasia; Vascular smooth muscle proliferation; Nitric
oxide; Hormones; Cell cycle; Free radicals
ID SMOOTH-MUSCLE-CELLS; POSTMENOPAUSAL ESTROGEN THERAPY; PERIPHERAL
ARTERIAL-DISEASE; ACTIVATED PROTEIN-KINASE; CORONARY HEART-DISEASE;
LOWER-EXTREMITY; BALLOON INJURY; WOMENS HEALTH; PROLIFERATION; MIGRATION
AB Nitric oxide (NO)-based therapies decrease neointimal hyperplasia; however, studies have been performed only in male animal models. Thus, we sought to evaluate the effect of NO on vascular smooth muscle cells (VSMC) in vitro and neointimal hyperplasia in vivo based on sex and hormone status. In hormone-replete medium, male VSMC proliferated at greater rates than female VSMC. In hormone-depleted medium, female VSMC proliferated at greater rates than male VSMC. However, in both hormone environments, NO inhibited proliferation and migration to a greater extent in male compared to female VSMC. These findings correlated with greater G(0)/G(1) cell cycle arrest and changes in cell cycle protein expression in male compared to female VSMC after exposure to NO. Next, the rat carotid artery injury model was used to assess the effect of NO on neointimal hyperplasia in vivo. Consistent with the in vitro data, NO was significantly more effective at inhibiting neointimal hyperplasia in hormonally intact males compared to females using weight-based dosing. An increased weight-based dose of NO in females was able to achieve efficacy equal to that in males. Surprisingly. NO was less effective at inhibiting neointimal hyperplasia in castrated animals of both sexes. In conclusion, these data suggest that NO inhibits neointimal hyperplasia more effectively in males compared to females and in hormonally intact compared to castrated rats, indicating that the effects of NO in the vasculature may be sex- and hormone-dependent. Published by Elsevier Inc.
C1 [Hogg, Melissa E.; Varu, Vinit N.; Vavra, Ashley K.; Popowich, Daniel A.; Banerjee, Monisha N.; Martinez, Janet; Jiang, Qun; Kibbe, Melina R.] Northwestern Univ, Div Vasc Surg, Chicago, IL 60611 USA.
[Hogg, Melissa E.; Varu, Vinit N.; Vavra, Ashley K.; Popowich, Daniel A.; Banerjee, Monisha N.; Martinez, Janet; Jiang, Qun; Kibbe, Melina R.] Northwestern Univ, Feinberg Sch Med, Inst BioNanotechnol Med, Chicago, IL 60611 USA.
[Varu, Vinit N.] Univ Illinois, Dept Surg, Chicago, IL 60612 USA.
[Saavedra, Joseph E.] SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA.
[Keefer, Larry K.] NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA.
[Kibbe, Melina R.] Jesse Brown Vet Affairs Med Ctr, Chicago, IL 60612 USA.
RP Kibbe, MR (reprint author), Northwestern Univ, Div Vasc Surg, Chicago, IL 60611 USA.
EM mkibbe@nmh.org
RI Keefer, Larry/N-3247-2014
OI Keefer, Larry/0000-0001-7489-9555
FU Institute for Women's Health Research at the Feinberg School of
Medicine, Northwestern University (Chicago, IL); National Institutes of
Health [K08HL084203]; Department of Veterans Affairs; American Vascular
Association; American Medical Association; National Cancer Institute,
NIH [NO1-CO-12400]; SAIC-Frederick, Inc.; NIH, National Cancer
Institute, Center for Cancer Research
FX The authors express their thanks to the Feinberg Cardiovascular Research
Institute and to Edwards Lifesciences for generously providing the
Fogarty balloon catheters. This work was supported in part by funding
from the Institute for Women's Health Research at the Feinberg School of
Medicine, Northwestern University (Chicago, IL) through the Pioneer
Award competitive funding mechanism. This work was also supported in
part by funding from the National Institutes of Health (K08HL084203), a
Department of Veterans Affairs Merit Review award, the American Vascular
Association, and an American Medical Association seed grant. It was
supported in part by the generosity of Mrs. Hilda Rosenbloom and Ms.
Eleanor Baldwin. Last, this work was supported in part by funding from
the National Cancer Institute, NIH, under Contract NO1-CO-12400 with
SAIC-Frederick, Inc., and by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research. The authors also
express their thanks to the Institute for BioNanotechnology in Medicine
and Lynnette Dangerfield for her "tireless" hours.
NR 37
TC 14
Z9 15
U1 1
U2 3
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 MAY 1
PY 2011
VL 50
IS 9
BP 1065
EP 1074
DI 10.1016/j.freeradbiomed.2011.01.016
PG 10
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 752CA
UT WOS:000289664500006
PM 21256959
ER
PT J
AU Prast-Nielsen, S
Dexheimer, TS
Schultz, L
Stafford, WC
Cheng, Q
Xu, JQ
Jadhav, A
Arner, ESJ
Simeonov, A
AF Prast-Nielsen, Stefanie
Dexheimer, Thomas S.
Schultz, Lena
Stafford, William C.
Cheng, Qing
Xu, Jianqiang
Jadhav, Ajit
Arner, Elias S. J.
Simeonov, Anton
TI Inhibition of thioredoxin reductase 1 by porphyrins and other small
molecules identified by a high-throughput screening assay
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Screening assay; Thioredoxin reductase; Inhibitor; Substrate;
Protoporphyrin IX; Rottlerin; Cancer; Free radicals
ID MAMMALIAN THIOREDOXIN; MOTEXAFIN GADOLINIUM; LUNG-CARCINOMA; HUMAN
CANCER; SELENOPROTEIN; SELENOENZYME; EXPRESSION; INDUCTION; INVOLVEMENT;
APOPTOSIS
AB The selenoprotein thioredoxin reductase 1 (TrxR1) has in recent years been identified as a promising anticancer drug target. A high-throughput assay for discovery of novel compounds targeting the enzyme is therefore warranted. Herein, we describe a single-enzyme, dual-purpose assay for simultaneous identification of inhibitors and substrates of TrxR1. Using this assay to screen the LOPAC(1280) compound collection we identified several known inhibitors of TrxR1, thus validating the assay, as well as several compounds hitherto unknown to target the enzyme. These included rottlerin (previously reported as a PKC delta inhibitor and mitochondrial uncoupler) and the heme precursor protoporphyrin IX (PpIX). We found that PpIX was a potent competitive inhibitor of TrxR1, with a K-i = 2.7 mu M with regard to Trx1, and in the absence of Trx1 displayed time-dependent irreversible inhibition with an apparent second-order rate constant (k(inact)) of (0.73 +/- 0.07) x 10(-3) mu M-1 min(-1). Exogenously delivered PpIX was cytotoxic, inhibited A549 cell proliferation, and was found to also inhibit cellular TrxR activity. Hemin and the ferrochelatase inhibitor NMPP also inhibited TrxR1 and showed cytotoxicity, but less potently compared to PpIX. We conclude that rottlerin-induced cellular effects may involve targeting of TrxR1. The unexpected finding of PpIX as a TrxR1 inhibitor suggests that such inhibition may contribute to symptoms associated with conditions of abnormally high PpIX levels, such as reduced ferrochelatase activity seen in erythropoietic protoporphyria. Finally, additional inhibitors of TrxR1 may be discovered and further characterized based upon the new high-throughput TrxR1 assay presented here. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Prast-Nielsen, Stefanie; Stafford, William C.; Cheng, Qing; Xu, Jianqiang; Arner, Elias S. J.] Karolinska Inst, Dept Med Biochem & Biophys, Div Biochem, SE-17177 Stockholm, Sweden.
[Dexheimer, Thomas S.; Schultz, Lena; Jadhav, Ajit; Simeonov, Anton] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
RP Arner, ESJ (reprint author), Karolinska Inst, Dept Med Biochem & Biophys, Div Biochem, SE-17177 Stockholm, Sweden.
EM elias.arner@ki.se; asimeono@mail.nih.gov
RI Arner, Elias/J-5832-2012;
OI Arner, Elias/0000-0002-4807-6114; Prast-Nielsen,
Stefanie/0000-0001-5877-7988
FU Molecular Libraries Initiative of the NIH Road map for Medical Research
[R03MH090846]; National Human Genome Research Institute, NIH; Swedish
Research Council; Swedish Cancer Society; Wallenberg Foundations;
Karolinska Institutet
FX This research was supported in part by the Molecular Libraries
Initiative of the NIH Road map for Medical Research (Award R03MH090846)
and the Intramural Research Program of the National Human Genome
Research Institute, NIH. The content is solely the responsibility of the
authors and does not necessarily represent the official views of the
NIH. Additional support to E.S.J.A. from the Swedish Research Council,
the Swedish Cancer Society, The Wallenberg Foundations, and the
Karolinska Institutet is also acknowledged.
NR 48
TC 11
Z9 11
U1 2
U2 10
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 MAY 1
PY 2011
VL 50
IS 9
BP 1114
EP 1123
DI 10.1016/j.freeradbiomed.2011.01.020
PG 10
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 752CA
UT WOS:000289664500011
PM 21262347
ER
PT J
AU Nierenberg, K
Hollenbeck, J
Fleming, LE
Stephan, W
Reich, A
Backer, LC
Currier, R
Kirkpatrick, B
AF Nierenberg, Kate
Hollenbeck, Julie
Fleming, Lora E.
Stephan, Wendy
Reich, Andrew
Backer, Lorraine C.
Currier, Robert
Kirkpatrick, Barbara
TI Frontiers in outreach and education: The Florida red tide experience
SO HARMFUL ALGAE
LA English
DT Article
DE Communication tools; Evaluation of outreach and education; Florida red
tide; Harmful algal blooms and public knowledge; Karenia brevis;
Outreach and education
AB To enhance information sharing and garner increased support from the public for scientific research, funding agencies now typically require that research groups receiving support convey their work to stakeholders. The National Institute of Environmental Health Sciences (NIEHS) funded Aerosolized Florida Red Tide P01 research group (Florida Red Tide Research Group) has employed a variety of outreach strategies to meet this requirement. Messages developed from this project began a decade ago and have evolved from basic print material (fliers and posters) to an interactive website, to the use of video and social networking technologies, such as Facebook and Twitter. The group was able to track dissemination of these information products; however, evaluation of their effectiveness presented much larger challenges. The primary lesson learned by the Florida Red Tide Research Group is that the best ways to reach specific stakeholders are to develop unique products or services to address specific stakeholders' needs, such as the Beach Conditions Reporting System. Based on the experience of the Group, the most productive messaging products result when scientific community engages potential stakeholders and outreach experts during the very initial phases of a project. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Nierenberg, Kate] Mote Marine Lab, Environm Hlth Program, Sarasota, FL 34236 USA.
[Hollenbeck, Julie; Fleming, Lora E.; Stephan, Wendy] Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NSF, Miami, FL 33149 USA.
[Hollenbeck, Julie; Fleming, Lora E.; Stephan, Wendy] Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS Oceans & Human Hlth Ctr, Miami, FL 33149 USA.
[Hollenbeck, Julie; Fleming, Lora E.; Stephan, Wendy] Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA.
[Reich, Andrew] Florida Dept Hlth, Tallahassee, FL 32399 USA.
[Backer, Lorraine C.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30329 USA.
[Kirkpatrick, Barbara] Miller Sch Med, Miami, FL 33149 USA.
RP Nierenberg, K (reprint author), Mote Marine Lab, Environm Hlth Program, 1600 Ken Thompson Pkwy, Sarasota, FL 34236 USA.
EM knierenberg@mote.org
FU DHHS NIH of the National Institute of Environmental Health Sciences [P01
ES 10594]; National Institute of Environmental Health Sciences (NIEHS)
Oceans and Human Health Center at the University of Miami Rosenstiel
School [NSF OCE0432368, NSF OCE0911373, NIEHS 1 P50 ES12736]; National
Science Foundation (NSF) [GEO-1009063]; National Institute of
Environmental Health Sciences (NIEHS) [1R21ES017413-01A2]; Centers for
Disease Control and Prevention and the Florida Department of Health
[U50/CCU423360-02]
FX This research was supported by the P01 ES 10594, DHHS NIH of the
National Institute of Environmental Health Sciences. Additional support
was received from the National Institute of Environmental Health
Sciences (NIEHS) Oceans and Human Health Center at the University of
Miami Rosenstiel School (NSF OCE0432368, NSF OCE0911373 and NIEHS 1 P50
ES12736), the National Science Foundation (NSF GEO-1009063), the
National Institute of Environmental Health Sciences (NIEHS
1R21ES017413-01A2) as well as by the Centers for Disease Control and
Prevention and the Florida Department of Health (Cooperative Agreement:
U50/CCU423360-02).[SS]
NR 12
TC 6
Z9 6
U1 5
U2 19
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-9883
J9 HARMFUL ALGAE
JI Harmful Algae
PD MAY
PY 2011
VL 10
IS 4
BP 374
EP 380
DI 10.1016/j.hal.2011.01.004
PG 7
WC Marine & Freshwater Biology
SC Marine & Freshwater Biology
GA 753WB
UT WOS:000289809600004
PM 21532966
ER
PT J
AU Johnson, AD
Newton-Cheh, C
Chasman, DI
Ehret, GB
Johnson, T
Rose, L
Rice, K
Verwoert, GC
Launer, LJ
Gudnason, V
Larson, MG
Chakravarti, A
Psaty, BM
Caulfield, M
van Duijn, CM
Ridker, PM
Munroe, PB
Levy, D
AF Johnson, Andrew D.
Newton-Cheh, Christopher
Chasman, Daniel I.
Ehret, Georg B.
Johnson, Toby
Rose, Lynda
Rice, Kenneth
Verwoert, Germaine C.
Launer, Lenore J.
Gudnason, Vilmundur
Larson, Martin G.
Chakravarti, Aravinda
Psaty, Bruce M.
Caulfield, Mark
van Duijn, Cornelia M.
Ridker, Paul M.
Munroe, Patricia B.
Levy, Daniel
CA Cohorts Heart Aging Res Genom
Global BPgen Consortium
Women's Genome Hlth Study
TI Association of Hypertension Drug Target Genes With Blood Pressure and
Hypertension in 86 588 Individuals
SO HYPERTENSION
LA English
DT Article
DE drug target; genome-wide; SNP; hypertension; blood pressure
ID GENOME-WIDE ASSOCIATION; BETA(1)-ADRENERGIC RECEPTOR POLYMORPHISMS;
CALCIUM-CHANNEL BLOCKERS; ANGIOTENSINOGEN GENE; ADRENERGIC-RECEPTOR;
WHITE SUBJECTS; SUBUNIT GENES; HEART-RATE; RISK; POPULATION
AB We previously conducted genome-wide association meta-analysis of systolic blood pressure, diastolic blood pressure, and hypertension in 29 136 people from 6 cohort studies in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Here we examine associations of these traits with 30 gene regions encoding known antihypertensive drug targets. We find nominal evidence of association of ADRB1, ADRB2, AGT, CACNA1A, CACNA1C, and SLC12A3 polymorphisms with 1 or more BP traits in the Cohorts for Heart and Aging Research in Genomic Epidemiology genome-wide association meta-analysis. We attempted replication of the top meta-analysis single nucleotide polymorphisms for these genes in the Global BPgen Consortium (n = 34 433) and the Women's Genome Health Study (n = 23 019) and found significant results for rs1801253 in ADRB1 (Arg389Gly), with the Gly allele associated with a lower mean systolic blood pressure (beta : 0.57 mm Hg; SE: 0.09 mm Hg; meta-analysis: P = 4.7 x 10(-10)), diastolic blood pressure (beta : 0.36 mm Hg; SE: 0.06 mm Hg; meta-analysis: P = 9.5 x 10(-10)), and prevalence of hypertension (beta : 0.06 mm Hg; SE: 0.02 mm Hg; meta-analysis: P = 3.3 x 10(-4)). Variation in AGT (rs2004776) was associated with systolic blood pressure (beta : 0.42 mm Hg; SE: 0.09 mm Hg; meta-analysis: P = 3.8 x 10(-6)), as well as diastolic blood pressure (P = 5.0 x 10(-8)) and hypertension (P = 3.7 x 10(-7)). A polymorphism in ACE (rs4305) showed modest replication of association with increased hypertension (beta : 0.06 mm Hg; SE: 0.01 mm Hg; meta-analysis: P = 3.0 x 10(-5)). Two loci, ADRB1 and AGT, contain single nucleotide polymorphisms that reached a genome-wide significance threshold in meta-analysis for the first time. Our findings suggest that these genes warrant further studies of their genetic effects on blood pressure, including pharmacogenetic interactions. (Hypertension. 2011;57:903-910.) . Online Data Supplement
C1 [Johnson, Andrew D.; Larson, Martin G.; Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Johnson, Andrew D.; Levy, Daniel] NHLBI, Ctr Populat Studies, Framingham, MA 01702 USA.
[Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA.
[Newton-Cheh, Christopher] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[Newton-Cheh, Christopher] MIT, Cambridge, MA 02139 USA.
[Chasman, Daniel I.; Rose, Lynda; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Chasman, Daniel I.; Rose, Lynda; Ridker, Paul M.] Harvard Univ, Sch Med, Boston, MA USA.
[Ehret, Georg B.; Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD USA.
[Ehret, Georg B.] CHU Vaudois, Inst Social & Prevent Med IUMSP, Lausanne, Switzerland.
[Ehret, Georg B.] Univ Lausanne, Lausanne, Switzerland.
[Ehret, Georg B.] Univ Hosp Geneva, Dept Med, Ctr Cardiol, Geneva, Switzerland.
[Johnson, Toby; Caulfield, Mark; Munroe, Patricia B.] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Clin Pharmacol & Genome Ctr, London, England.
[Rice, Kenneth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Verwoert, Germaine C.; van Duijn, Cornelia M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Verwoert, Germaine C.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Verwoert, Germaine C.] Leiden Univ, Med Ctr, Netherlands Ctr Healthy Aging, Dept Mol Epidemiol, Leiden, Netherlands.
[Launer, Lenore J.] NIA, Lab Epidemiol, NIH, Bethesda, MD 20892 USA.
[Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Larson, Martin G.] Boston Univ, Dept Math, Boston, MA 02215 USA.
[Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[van Duijn, Cornelia M.] Erasmus MC, Ctr Med Syst Biol, Rotterdam, Netherlands.
[Ridker, Paul M.] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA.
RP Levy, D (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM levyd@nhlbi.nih.gov
RI EHRET, Georg/A-9532-2009; Rice, Kenneth/A-4150-2013; Johnson,
Andrew/G-6520-2013; Gudnason, Vilmundur/K-6885-2015;
OI EHRET, Georg/0000-0002-5730-0675; Rice, Kenneth/0000-0001-5779-4495;
Gudnason, Vilmundur/0000-0001-5696-0084; Larson,
Martin/0000-0002-9631-1254; Johnson, Toby/0000-0002-5998-3270
FU National Heart, Lung, and Blood Institute [N01-HC-85079, N01-HC-85086,
N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133,
U01 HL080295, R01 HL087652]; National Institute of Neurological
Disorders and Stroke; National Center for Research Resources
[M01-RR00425]; National Institute of Diabetes and Digestive and Kidney
Diseases [DK063491]; National Heart, Lung, and Blood Institute's
Framingham Heart Study [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278];
Robert Dawson Evans Endowment of the Boston University School of
Medicine Department of Medicine; Boston Medical Center; Erasmus Medical
Center and Erasmus University Rotterdam; Netherlands Organization for
Scientific Research; Netherlands Organization for Health Research and
Development (ZonMw); Research Institute for Diseases in the Elderly;
Netherlands Heart Foundation; Ministry of Education, Culture, and
Science; the Ministry of Health, Welfare, and Sports; European
Commission; Municipality of Rotterdam; Netherlands Organization for
Scientific Research (NWO Groot) [175.010.2005.011, 911.03.012]; Research
Institute for Diseases in the Elderly [014.93.015, RIDE2]; Netherlands
Genomics Initiative/Netherlands Organization for Scientific Research
[050-060-810]; National Genomics Initiative Centre for Medical Systems
Biology; Netherlands Centre for Healthy Aging; Doris Duke Charitable
Foundation; Burroughs Wellcome Fund; National Institutes of Health
[N01-AG-12100, HHSN268200625226C]; National Institute on Aging
Intramural Research, Hjartavernd; National Human Genome Research
Institute [U01HG004402]; National Institute for Health Research
Biomedical Research Unit; National Heart, Lung, and Blood Institute.
[N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020,
N01-HC55021, N01-HC-55022, R01HL087641, R01HL59367, R37HL051021,
R01HL086694, U10HL054512]; [UL1RR025005]
FX The Cardiovascular Health Study research reported in this article was
supported by contract numbers N01-HC-85079 through N01-HC-85086,
N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133,
U01 HL080295, and R01 HL087652 from the National Heart, Lung, and Blood
Institute, with additional contribution from the National Institute of
Neurological Disorders and Stroke. DNA handling and genotyping were
supported in part by National Center for Research Resources grant
M01-RR00425 to the Cedars-Sinai General Clinical Research Center
Genotyping core and National Institute of Diabetes and Digestive and
Kidney Diseases grant DK063491 to the Southern California Diabetes
Endocrinology Research Center.; The National Heart, Lung, and Blood
Institute's Framingham Heart Study is a joint project of the National
Institutes of Health and Boston University School of Medicine and was
supported by the National Heart, Lung, and Blood Institute's Framingham
Heart Study (contract N01-HC-25195) and its contract with Affymetrix,
Inc, for genotyping services (contract No. N02-HL-6-4278). A portion of
this research was conducted using the Linux Cluster for Genetic Analysis
(LinGA-II) funded by the Robert Dawson Evans Endowment of the Boston
University School of Medicine Department of Medicine and Boston Medical
Center.; The Rotterdam Study is supported by the Erasmus Medical Center
and Erasmus University Rotterdam; the Netherlands Organization for
Scientific Research; the Netherlands Organization for Health Research
and Development (ZonMw); the Research Institute for Diseases in the
Elderly; the Netherlands Heart Foundation; the Ministry of Education,
Culture, and Science; the Ministry of Health, Welfare, and Sports; the
European Commission; and the Municipality of Rotterdam. Support for
genotyping was provided by the Netherlands Organization for Scientific
Research (NWO Groot 175.010.2005.011 and 911.03.012) and Research
Institute for Diseases in the Elderly (014.93.015; RIDE2). This study
was supported by the Netherlands Genomics Initiative/Netherlands
Organization for Scientific Research project 050-060-810 and the
National Genomics Initiative Centre for Medical Systems Biology and
Netherlands Centre for Healthy Aging.; C. N.-C. is supported by the
Doris Duke Charitable Foundation, the Burroughs Wellcome Fund, and the
National Institutes of Health. The Age, Gene/Environment Susceptibility
Reykjavik Study is funded by National Institutes of Health contract
N01-AG-12100, the National Institute on Aging Intramural Research
Program, Hjartavernd (the Icelandic Heart Association), and the Althingi
(the Icelandic Parliament). The Atherosclerosis Risk in Communities
Study is carried out as a collaborative study supported by National
Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016,
N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC55021, and N01-HC-55022,
and grants R01HL087641, R01HL59367, R37HL051021, R01HL086694, and
U10HL054512; National Human Genome Research Institute contract
U01HG004402; and National Institutes of Health contract
HHSN268200625226C. Infrastructure was partly supported by grant
UL1RR025005, a component of the National Institutes of Health and
National Institutes of Health Roadmap for Medical Research.; M. C. and
P. M. are funded by the National Institute for Health Research
Biomedical Research Unit.
NR 54
TC 83
Z9 86
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD MAY
PY 2011
VL 57
IS 5
BP 903
EP U99
DI 10.1161/HYPERTENSIONAHA.110.158667
PG 24
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 752YA
UT WOS:000289730200016
PM 21444836
ER
PT J
AU Jones, JM
Bhattacharyya, A
Simkus, C
Vallieres, B
Veenstra, TD
Zhou, M
AF Jones, Jessica M.
Bhattacharyya, Anamika
Simkus, Carrie
Vallieres, Brice
Veenstra, Timothy D.
Zhou, Ming
TI The RAG1 V(D)J recombinase/ubiquitin ligase promotes ubiquitylation of
acetylated, phosphorylated histone 3.3
SO IMMUNOLOGY LETTERS
LA English
DT Article
DE RAG1; Ubiquitin ligase; Histone H3.3; V(D)J recombination; DNA repair
ID UBIQUITIN LIGASE; VARIANT H3.3; ACTIVE CHROMATIN; RECOMBINATION;
COMPLEX; METHYLATION; PROTEINS; DOMAIN; ENDS; DNA
AB Histone variant H3.3 is associated with transcriptionally active chromatin and accumulates at loci undergoing preparation for V(D)J recombination, a DNA rearrangement required for the assembly of antigen receptors and development of B and T lymphocytes. Here we demonstrate that the RAG1 V(D)J recombinase protein promotes ubiquitylation of H3.3 that has been heavily acetylated and phosphorylated on serine 31 (acetyl-H3.3 S31 p). A fragment of RAG1 promoted formation of a mono-ubiquitylated H3 product that was identified using mass spectrometry as ubiquitylated acetyl-H3.3 S31p. H3 was ubiquitylated at multiple lysine residues, and correspondingly, di-, tri- and higher-order ubiquitylated products were detected at low levels. Ubiquitylation was dependent on an intact RAG1 RING finger/ubiquitin ligase domain and required additional regions of the RAG1 amino terminus that are likely to interact with H3. Acetylated residues within the H3 amino terminal tail were also required. Purified, recombinant H3.1 and H3.3 were not good substrates, suggesting that post-translational modifications enhance recognition by RAG1. A complex including damage-DNA binding protein has also been shown to ubiquitylate H3 in response to UV treatment, suggesting the H3 ubiquitylation may be a common step in multiple DNA repair pathways. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Jones, Jessica M.; Bhattacharyya, Anamika; Simkus, Carrie; Vallieres, Brice] Georgetown Univ, Dept Biochem Mol & Cell Biol, Washington, DC 20057 USA.
[Veenstra, Timothy D.; Zhou, Ming] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Jones, JM (reprint author), Georgetown Univ, Dept Biochem Mol & Cell Biol, 3900 Reservoir Rd NW,Basic Sci Bldg,Room 329, Washington, DC 20057 USA.
EM jonesj5@georgetown.edu
FU National Cancer Institute, National Institutes of Health [N01-CO-12400,
P30CA051008]; National Institutes of Health [AI062854-01]
FX The authors wish to thank Hsin Chih Liu and Chelsey Pearson for critical
reading of this manuscript and assistance in general laboratory
maintenance, and Dr. Garnett Kelsoe (Duke University Medical Center,
Durham, NC, USA) for the gift of 103/Bcl2/4 cells. FACS analysis was
performed by Dr. Karen Creswell, Director, Lombardi Comprehensive Cancer
Center Flow Cytometry Shared Resource. This project has been funded in
whole or in part with federal funds from the National Cancer Institute,
National Institutes of Health, under Contract [N01-CO-12400] and award
number [P30CA051008]. 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 United States
Government. This project was supported in part by a grant to J.M.J. from
the National Institutes of Health [AI062854-01]. The content is solely
the responsibility of the authors.
NR 28
TC 21
Z9 22
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-2478
J9 IMMUNOL LETT
JI Immunol. Lett.
PD MAY
PY 2011
VL 136
IS 2
BP 156
EP 162
DI 10.1016/j.imlet.2011.01.005
PG 7
WC Immunology
SC Immunology
GA 753ZO
UT WOS:000289820200006
PM 21256161
ER
PT J
AU Yang, SX
Steinberg, SM
Nguyen, D
Swain, SM
AF Yang, Sherry X.
Steinberg, Seth M.
Nguyen, Dat
Swain, Sandra M.
TI p53, HER2 and tumor cell apoptosis correlate with clinical outcome after
neoadjuvant bevacizumab plus chemotherapy in breast cancer
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE apoptosis; bevacizumab; breast cancer; HER2; Ki67; p53
ID ANGIOGENESIS; EXPRESSION; PROTEIN; BIOMARKERS; DOCETAXEL; PROGNOSIS;
ERLOTINIB; C-ERBB-2; THERAPY; PROFILE
AB Bevacizumab, an antibody to vascular endothelial growth factor (VEGF), has been incorporated into chemotherapy regimens in the treatment of several cancer types including breast cancer. The aim of this study was to identify tumor and angiogenic factors that potentially associate with outcome. In a pilot trial, 21 patients with inflammatory breast cancer and locally advanced breast cancer received bevacizumab plus doxorubicin-docetaxel chemotherapy before surgery. Baseline p53, HER2, tumor apoptosis, Ki67, estrogen receptor (ER), VEGF-A, serum VEGF (sVEGF), VEGFR2-Y951 and microvessel density (MVD) were prospectively designed and determined by immunohistochemistry and enzyme-linked immunosorbent assay. Hazard ratios (HR) and 95% confidence intervals for survival and progression-free survival (PFS) were estimated using Cox proportional hazards analyses. With a median follow-up of 65.9 months, patients with low apoptosis or p53-negative tumors had significantly longer survival than those with high apoptosis or p53-positive tumors (median 61.5 vs. 20.2 months; HR 0.22; p=0.011 for apoptosis and median 59.6 vs. 24.2 months; HR 0.27; p=0.01.6 for p53). Low Ki67 versus high Ki67 exhibited a trend towards association with survival (median 57.1 vs. 17.3 months, HR 0.34, p=0.07). Patients with HER2-negative tumors had significantly longer PFS than those with HER2-positive tumors (median 31.2 vs. 9.4 months; HR 0.23; p=0.03). ER, VEGF-A, sVEGF, VEGFR2-Y951 and MVD were not significantly associated with outcome. Our data suggest that baseline p53, apoptosis and HER2 are each significantly associated with outcome in patients who received bevacizumab plus chemotherapy.
C1 [Yang, Sherry X.] NCI, Natl Clin Target Validat Lab, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
[Swain, Sandra M.] Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA.
RP Yang, SX (reprint author), NCI, Natl Clin Target Validat Lab, Div Canc Treatment & Diag, NIH, Bldg 37 Rm 1048, Bethesda, MD 20892 USA.
EM xy32rn@nih.gov
FU Division of Cancer Treatment and Diagnosis; Center for Cancer Research,
National Cancer Institute, National Institutes of Health
FX This study was supported in part by the Division of Cancer Treatment and
Diagnosis, and Center for Cancer Research, National Cancer Institute,
National Institutes of Health. We thank Arlene Berman, Medical Oncology
Branch, Center for Cancer Research, National Cancer Institute for
patient follow-up. Dr S. Swain received research grants from Genentech
and Bristol Myers Squibb, and travel supports from Genentech and
Sanofi-Aventis to attend investigator meetings. She has been an
uncompensated consultant for Genentech, Roche, and Sanofi-Aventis. The
others have no potential conflict of interest.
NR 36
TC 9
Z9 10
U1 0
U2 0
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1019-6439
J9 INT J ONCOL
JI Int. J. Oncol.
PD MAY
PY 2011
VL 38
IS 5
BP 1445
EP 1452
PG 8
WC Oncology
SC Oncology
GA 753YE
UT WOS:000289815800028
PM 21399868
ER
PT J
AU Long, EO
AF Long, Eric O.
TI ICAM-1: Getting a Grip on Leukocyte Adhesion
SO JOURNAL OF IMMUNOLOGY
LA English
DT Editorial Material
ID FUNCTION-ASSOCIATED ANTIGEN-1; CELL-ADHESION; MOLECULE-1 ICAM-1;
T-CELLS; LFA-1; RECEPTOR; LIGAND; SURFACE; DISTINCT; ARREST
C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Long, EO (reprint author), NIAID, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA.
EM elong@nih.gov
RI Long, Eric/G-5475-2011
OI Long, Eric/0000-0002-7793-3728
FU Intramural NIH HHS [ZIA AI001118-04]
NR 32
TC 57
Z9 58
U1 0
U2 8
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAY 1
PY 2011
VL 186
IS 9
BP 5021
EP 5023
DI 10.4049/jimmunol.1100646
PG 3
WC Immunology
SC Immunology
GA 752GN
UT WOS:000289679600003
PM 21505213
ER
PT J
AU Pobezinskaya, YL
Choksi, S
Morgan, MJ
Cao, XM
Liu, ZG
AF Pobezinskaya, Yelena L.
Choksi, Swati
Morgan, Michael J.
Cao, Xiumei
Liu, Zheng-gang
TI The Adaptor Protein TRADD Is Essential for TNF-Like Ligand 1A/Death
Receptor 3 Signaling
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; DOMAIN-CONTAINING RECEPTOR; TOLL-LIKE-RECEPTORS;
KAPPA-B ACTIVATION; CELL-DEATH; T-CELL; APOPTOSIS; DR3; TL1A; PATHWAY
AB TNFR-associated death domain protein (TRADD) is a key effector protein of TNFR1 signaling. However, the role of TRADD in other death receptor (DR) signaling pathways, including DR3, has not been completely characterized. Previous studies using overexpression systems suggested that TRADD is recruited to the DR3 complex in response to the DR3 ligand, TNF-like ligand 1A (TL1A), indicating a possible role in DR3 signaling. Using T cells from TRADD knockout mice, we demonstrate in this study that the response of both CD4(+) and CD8(+) T cells to TL1A is dependent upon the presence of TRADD. TRADD knockout T cells therefore lack the appropriate proliferative response to TL1A. Moreover, in the absence of TRADD, both the stimulation of MAPK signaling and activation of NF-kappa B in response to TL1A are dramatically reduced. Unsurprisingly, TRADD is required for recruitment of receptor interacting protein 1 and TNFR-associated factor 2 to the DR3 signaling complex and for the ubiquitination of receptor interacting protein 1. Thus, our findings definitively establish an essential role of TRADD in DR3 signaling. The Journal of Immunology, 2011, 186: 5212-5216.
C1 [Pobezinskaya, Yelena L.; Choksi, Swati; Morgan, Michael J.; Cao, Xiumei; Liu, Zheng-gang] NCI, Cell & Canc Biol Branch, NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Liu, ZG (reprint author), NCI, Cell & Canc Biol Branch, NIH, Ctr Canc Res, Bldg 37,Room 1130,37 Convent Dr, Bethesda, MD 20892 USA.
EM zgliu@helix.nih.gov
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, National Institutes of
Health.
NR 29
TC 22
Z9 23
U1 1
U2 9
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAY 1
PY 2011
VL 186
IS 9
BP 5212
EP 5216
DI 10.4049/jimmunol.1002374
PG 5
WC Immunology
SC Immunology
GA 752GN
UT WOS:000289679600023
PM 21421854
ER
PT J
AU Simard, N
Konforte, D
Tran, AH
Esufali, J
Leonard, WJ
Paige, CJ
AF Simard, Nathalie
Konforte, Danijela
Tran, Anne H.
Esufali, Jessica
Leonard, Warren J.
Paige, Christopher J.
TI Analysis of the Role of IL-21 in Development of Murine B Cell
Progenitors in the Bone Marrow
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CD4(+) T-CELLS; CYTIDINE DEAMINASE EXPRESSION; CLASS-SWITCH
RECOMBINATION; FOLLICULAR-HELPER-CELLS; ANTIBODY-PRODUCTION; HUMAN
NAIVE; DIFFERENTIATION; ACTIVATION; RECEPTOR; APOPTOSIS
AB IL-21 plays a key role in the late stage of B cell development, where it has been shown to induce growth and differentiation of mature B cells into Ig-secreting plasma cells. Because IL-21R has also been reported on bone marrow (BM) B cell progenitors, we investigated whether IL-21R influenced earlier stages of B cell development. IL-21R is functional as early as the pro-B cell stage, and the strength of receptor-mediated signaling increases as cells mature. The addition of IL-21 to B cell progenitors in cell culture resulted in the accelerated appearance of mature B cell markers and was associated with the induction of Aid, Blimp1, and germline transcripts. We also found that stimulation of both IL-21R and CD40 was sufficient to induce the maturation of early B cell progenitors into IgM- and IgG-secreting cells. Consistent with a role for IL-21 in promoting B cell differentiation, the number of B220(+)CD43(+)IgM(-) pro-B cells was increased, and the number of mature IgM(hi)IgD(hi) cells was decreased in BM of IL-21R-deficient mice. We also report in this paper that IL-21 is expressed by BM CD4(+) T cells. These results provide evidence that IL-21R is functional in B cell progenitors and indicate that IL-21 regulates B cell development. The Journal of Immunology, 2011, 186: 5244-5253.
C1 [Simard, Nathalie; Konforte, Danijela; Tran, Anne H.; Esufali, Jessica; Paige, Christopher J.] Princess Margaret Hosp, Univ Hlth Network, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada.
[Simard, Nathalie; Paige, Christopher J.] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada.
[Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Paige, Christopher J.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, Canada.
RP Simard, N (reprint author), Princess Margaret Hosp, Univ Hlth Network, Ontario Canc Inst, 610 Univ Ave,8 105, Toronto, ON M5G 2M9, Canada.
EM n.simard@utoronto.ca
FU Canadian Institutes of Health and Research [9862]; Terry Fox Foundation
FX This work was supported by Grant 9862 from the Canadian Institutes of
Health and Research and by the Terry Fox Foundation. N.S. received a
doctoral award from the Canadian Institutes of Health and Research.
NR 52
TC 8
Z9 8
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 MAY 1
PY 2011
VL 186
IS 9
BP 5244
EP 5253
DI 10.4049/jimmunol.1004040
PG 10
WC Immunology
SC Immunology
GA 752GN
UT WOS:000289679600027
PM 21430229
ER
PT J
AU Huang, JP
Wang, QJ
Yang, SC
Li, YF
El-Gamil, M
Rosenberg, SA
Robbins, PF
AF Huang, Jianping
Wang, Qiong J.
Yang, Shicheng
Li, Yong F.
El-Gamil, Mona
Rosenberg, Steven A.
Robbins, Paul F.
TI Irradiation Enhances Human T-cell Function by Upregulating CD70
Expression on Antigen-presenting Cells In Vitro
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE radiation; total body irradiation; CD70; CD27; mature human dendritic
cells; costimulation; human T cells; adoptive cell transfer; cancer
immunotherapy
ID DENDRITIC CELLS; LIGAND CD70; IFN-GAMMA; RESPONSES; VIVO; STIMULATION;
CD27; COSTIMULATION; TOLERANCE; RADIATION
AB In addition to the direct killing of tumor cells, radiation therapy can alter the balance of immune cells in vivo due to the differential radiosensitivity of different cell types. The addition of adjuvant radiation therapy before adoptive cell transfer therapy has been shown to enhance antitumor responses in both mouse models and clinical trials. This study examines the effects of in vitro irradiation on the phenotype and function of human antigen-presenting cells. The results indicated that irradiation upregulated CD70 expression on both B cells and mature dendritic cells (DCs). Expression of CD70 on mature DCs was enhanced in a dose-dependent manner, whereas under the same conditions, no significant upregulation of CD80, CD86, or CD40 was observed. The levels of expression of CD70 induced on mature DC by irradiation correlated highly with the ability of those cells to stimulate T-cell proliferation and interferon-gamma production. Furthermore, significant reductions in T-cell proliferation and interferon-gamma production were seen when CD70 expression on DCs was partially reduced using shRNA, as well as when DCs were incubated with a blocking anti-CD70 antibody. Radiation therapy may therefore enhance T-cell activation in vivo through the CD27 pathway by virtue of its ability to upregulate the expression of CD70 on antigen-presenting cells.
C1 [Huang, Jianping] NCI, Tumor Immunol & Biol Lab, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Huang, JP (reprint author), NCI, Tumor Immunol & Biol Lab, Surg Branch, NIH, Bldg 10,Room 8B01,10 Ctr Dr, Bethesda, MD 20892 USA.
EM jianping_huang@-nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX Supported by the Intramural Research Program of the National Institutes
of Health, National Cancer Institute, Center for Cancer Research.
NR 27
TC 13
Z9 13
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD MAY
PY 2011
VL 34
IS 4
BP 327
EP 335
DI 10.1097/CJI.0b013e318216983d
PG 9
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 752SE
UT WOS:000289713200001
PM 21499130
ER
PT J
AU Sundin, M
D'Arcy, P
Johansson, CC
Barrett, AJ
Lonnies, H
Sundberg, B
Nava, S
Kiessling, R
Mougiakakos, D
Le Blanc, K
AF Sundin, Mikael
D'Arcy, Padraig
Johansson, C. Christian
Barrett, A. John
Loennies, Helena
Sundberg, Berit
Nava, Silvia
Kiessling, Rolf
Mougiakakos, Dimitrios
Le Blanc, Katarina
TI Multipotent Mesenchymal Stromal Cells Express FoxP3: A Marker for the
Immunosuppressive Capacity?
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE transplantation; forkhead box 3; mesenchymal stem cells
ID REGULATORY T-CELLS; VERSUS-HOST-DISEASE; STEM-CELLS; INTESTINAL
INFLAMMATION; IMMUNE SUPPRESSION; TRANSPLANTATION; INHIBIT; MECHANISMS;
TRANSCRIPTION; LYMPHOCYTES
AB Multipotent mesenchymal stromal cells (MSCs) have immunosuppressive capacity but the exact mechanism by which they suppress proliferation of T lymphocytes is not fully understood. Recently, the characteristics and function of regulatory T lymphocytes (Tregs) have become better defined. Tregs and MSCs have immunosuppressive features in common. Here, we looked for a common basis for immunosuppression in these distinct cell types. Forkhead box P3 (FoxP3) and CD39 expression in MSCs was measured by flow cytometry and real-time quantitative polymerase chain reaction. The importance of FoxP3 in MSC-mediated immunosuppression was investigated by siRNA technology and mixed lymphocyte culture (MLC). The effect of 5-azacytidine and other immunosuppressive drugs on FoxP3 expression and immunosuppression by MSCs was explored by flow cytometry, MLC, and real-time quantitative polymerase chain reaction. MSCs express FoxP3 at variable levels, but they do not express CD39. FoxP3(high) MSCs suppress MLC to a greater extent than cells with lower FoxP3 expression. However, FoxP3-decreased MSCs were found to retain their immunosuppressive properties. 5-azacytitine had no effect on FoxP3 expression or MLC suppression by MSCs. However, immunosuppressive drugs led to increased FoxP3 levels and MLC inhibition in FoxP3(low) MSCs. This is the first demonstration of FoxP3 expression by MSCs. Although MSCs share several features with Tregs, and FoxP3(high) MSCs tend to be more immunosuppressive, MSCs do not require functional FoxP3 for their immunosuppressive activity. The increased MSC-mediated suppression of immune responses by immunosuppressive drugs deserves further investigation.
C1 [Sundin, Mikael] Karolinska Inst, Div Pediat, Dept Clin Sci Intervent & Technol, Huddinge, Sweden.
[D'Arcy, Padraig; Johansson, C. Christian; Kiessling, Rolf; Mougiakakos, Dimitrios] Karolinska Inst, Canc Ctr Karolinska, Dept Oncol Pathol, Huddinge, Sweden.
[Loennies, Helena; Sundberg, Berit; Nava, Silvia; Le Blanc, Katarina] Karolinska Inst, Div Clin Immunol, Dept Lab Med, Huddinge, Sweden.
[Sundin, Mikael] Astrid Lindgren Childrens Hosp, Huddinge, Sweden.
[Le Blanc, Katarina] Karolinska Univ Hosp, Hematol Ctr, Huddinge, Sweden.
[Barrett, A. John] NIH, Allogenet Stem Cell Transplant Sect, Hematol Branch, Bethesda, MD 20892 USA.
RP Sundin, M (reprint author), B57 Karolinska Univ Hosp Huddinge, Div Pediat, SE-14186 Stockholm, Sweden.
EM mikael.sundin@ki.se
RI Sundin, Mikael/E-5942-2013;
OI D'Arcy, Padraig/0000-0001-6671-7600; Sundin, Mikael/0000-0002-9871-0961;
Nava, Silvia/0000-0002-1890-6041
FU Signe and Olof Wallenius Foundation; Stiftelsen Byggmastare Olle
Engkvist; Swedish Cancer Society; Children's Cancer Foundation; Swedish
Research Council; Tobias Foundation; Cancer Society in Stockholm;
Swedish Society of Medicine; Ebba-Christina Hagbergs Foundation;
Stockholm County Council; Karolinska Institutet
FX Supported by unrestricted grants from the Signe and Olof Wallenius
Foundation (M.S.), the Stiftelsen Byggmastare Olle Engkvist (M.S.), the
Swedish Cancer Society (K.L.B.), the Children's Cancer Foundation
(K.L.B.), the Swedish Research Council, the Tobias Foundation (K.L.B.),
the Cancer Society in Stockholm (K.L.B.), the Swedish Society of
Medicine (K.L.B.), the Ebba-Christina Hagbergs Foundation (K.L.B.), the
Stockholm County Council (M.S. and K.L.B.), and Karolinska Institutet
(M.S. and K.L.B.).
NR 42
TC 15
Z9 15
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD MAY
PY 2011
VL 34
IS 4
BP 336
EP 342
DI 10.1097/CJI.0b013e318217007c
PG 7
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 752SE
UT WOS:000289713200002
PM 21499129
ER
PT J
AU Kerkar, SP
Sanchez-Perez, L
Yang, SC
Borman, ZA
Muranski, P
Ji, Y
Chinnasamy, D
Kaiser, ADM
Hinrichs, CS
Klebanoff, CA
Scott, CD
Gattinoni, L
Morgan, RA
Rosenberg, SA
Restifo, NP
AF Kerkar, Sid P.
Sanchez-Perez, Luis
Yang, Shicheng
Borman, Zachary A.
Muranski, Pawel
Ji, Yun
Chinnasamy, Dhanalakshmi
Kaiser, Andrew D. M.
Hinrichs, Christian S.
Klebanoff, Christopher A.
Scott, Christopher D.
Gattinoni, Luca
Morgan, Richard A.
Rosenberg, Steven A.
Restifo, Nicholas P.
TI Genetic Engineering of Murine CD8(+) and CD4(+) T Cells for Preclinical
Adoptive Immunotherapy Studies
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE gene therapy; immunotherapy; adoptive transfer; lentivirus; retrovirus;
HIV; melanoma; cancer
ID PERIPHERAL-BLOOD LYMPHOCYTES; LENTIVIRAL VECTOR; HEMATOPOIETIC-CELLS;
CANCER REGRESSION; OVARIAN-CANCER; THERAPY; EXPRESSION; TCR;
TRANSDUCTION; INFECTION
AB T-cell receptor (TCR) gene therapy enables for the rapid creation of antigen-specific T cells from mice of any strain and represents a valuable tool for preclinical immunotherapy studies. Here, we describe the superiority of gamma-retroviral vectors compared with lentiviral vectors for transduction of murine T cells and surprisingly illustrate robust gene-transfer into phenotypically naive/memory-stem cell like (TN/TSCM; CD62L(hi)/CD44(low)) and central memory (TCM; CD62L(hi)/CD44(hi)) CD8(+) T cells using murine stem cell-based g-retroviral vectors (MSGV1). We created MSGV1 vectors for a major histocompatibility complex-class I-restricted TCR specific for the melanocyte-differentiation antigen, glycoprotein 100 (MSGV1-pmel-1), and a major histocompatibility complex-class II-restricted TCR specific for tyrosinase-related protein-1 (MSGV1-TRP-1), and found that robust gene expression required codon optimization of TCR sequences for the pmel-1 TCR. To test for functionality, we adoptively transferred TCR-engineered T cells into mice bearing B16 melanomas and observed delayed growth of established tumors with pmel-1 TCR engineered CD8(+) T cells and significant tumor regression with TRP-1 TCR transduced CD4(+) T cells. We simultaneously created lentiviral vectors encoding the pmel-1 TCR, but found that these vectors mediated low TCR expression in murine T cells, but robust gene expression in other murine and human cell lines. These results indicate that preclinical murine models of adoptive immunotherapies are more practical using gamma-retroviral rather than lentiviral vectors.
C1 [Kerkar, Sid P.; Sanchez-Perez, Luis; Yang, Shicheng; Borman, Zachary A.; Muranski, Pawel; Ji, Yun; Chinnasamy, Dhanalakshmi; Kaiser, Andrew D. M.; Hinrichs, Christian S.; Klebanoff, Christopher A.; Scott, Christopher D.; Gattinoni, Luca; Morgan, Richard A.; Rosenberg, Steven A.; Restifo, Nicholas P.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Restifo, NP (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM restifon@nih.gov
RI Gattinoni, Luca/A-2281-2008; Klebanoff, Christopher/D-9581-2011; Kaiser,
Andrew/C-2617-2012; Ji, Yun/B-7245-2009; Restifo, Nicholas/A-5713-2008;
OI Gattinoni, Luca/0000-0003-2239-3282; Ji, Yun/0000-0001-6340-7009;
Restifo, Nicholas P./0000-0003-4229-4580
FU NIH, National Cancer Institute, Center for Cancer Research
FX Supported by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research. The authors have no conflicting
financial interests.
NR 51
TC 33
Z9 35
U1 0
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD MAY
PY 2011
VL 34
IS 4
BP 343
EP 352
DI 10.1097/CJI.0b013e3182187600
PG 10
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 752SE
UT WOS:000289713200003
PM 21499127
ER
PT J
AU Langan, RC
Prieto, PA
Sherry, RM
Zlott, D
Wunderlich, J
Csako, G
Costello, R
White, DE
Rosenberg, SA
Yang, JC
AF Langan, Russell C.
Prieto, Peter A.
Sherry, Richard M.
Zlott, Daniel
Wunderlich, John
Csako, Gyorgy
Costello, Rene
White, Donald E.
Rosenberg, Steven A.
Yang, James C.
TI Assessment of Ovarian Function After Preparative Chemotherapy and Total
Body Radiation for Adoptive Cell Therapy
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE ovarian toxicity; follicle stimulating hormone; ovarian recovery;
premature ovarian failure; cyclophosphamide
ID BONE-MARROW-TRANSPLANTATION; METASTATIC MELANOMA; CYCLOPHOSPHAMIDE;
FAILURE; CANCER; PRESERVATION; HORMONE
AB The aim of the study is to analyze treatment-induced gonadal damage and premature ovarian failure after adoptive cell therapy (ACT) after a cytotoxic lymphodepleting preparative regimen. Records of 66 consecutive females who received ACT at the Surgery Branch, National Cancer Institute, NIH (Bethesda, MD) were reviewed. Patients received a conditioning regimen of high-dose cyclophosphamide (60 mg/kg x 2 doses) and fludarabine (25 mg/m(2) x 5 doses). Some patients also received total body radiation at 200 or 600 cGy. Assessment of ovarian function was determined by analysis of monthly follicle stimulating hormone (FSH) levels, menstrual history, and symptoms. Among patients with serum available and normal pretreatment ovarian function, 21 had a preparative regimen with chemotherapy alone and 5 patients had received chemotherapy with total body radiation. Nine (43%) patients in the chemotherapy cohort and all 5 patients in the chemotherapy plus total body radiation cohort had persistently elevated FSH levels and were given the diagnosis of premature ovarian failure. Twelve (57%) patients had normal FSH levels at 6 months posttreatment. Median age of all patients at treatment was 34 years. Median age of women retaining normal ovarian function was 30 (range, 19-45) vs. 41 years (range, 30-49) for those who did not regain function. The conditioning regimen of 2 doses of cyclophosphamide (60 mg/kg) and 5 doses of fludarabine (25 mg/m(2)) may induce gonadal damage and premature ovarian failure. Younger age at treatment was associated with a higher frequency of normal ovarian function posttreatment, whereas adding total body radiation was associated with a high risk of ovarian failure.
C1 [Langan, Russell C.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Csako, Gyorgy; Costello, Rene] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Langan, RC (reprint author), NCI, Surg Branch, NIH, Bldg 10 Hatfield CRC,Room 3-3940,10 Ctr Dr, Bethesda, MD 20892 USA.
EM LanganRC@mail.nih.gov
FU National Cancer Institute, NIH
FX National Cancer Institute, NIH.
NR 16
TC 4
Z9 4
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD MAY
PY 2011
VL 34
IS 4
BP 397
EP 402
DI 10.1097/CJI.0b013e3182187508
PG 6
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 752SE
UT WOS:000289713200009
PM 21499128
ER
PT J
AU Duplantis, BN
Bosio, CM
Nano, FE
AF Duplantis, Barry N.
Bosio, Catherine M.
Nano, Francis E.
TI Temperature-sensitive bacterial pathogens generated by the substitution
of essential genes from cold-loving bacteria: potential use as live
vaccines
SO JOURNAL OF MOLECULAR MEDICINE-JMM
LA English
DT Review
DE Essential gene; Psychrophile; Live vaccine; Temperature sensitivity;
Francisella; Cold-adapted
ID TRANSPOSON MUTANT LIBRARY; MYCOBACTERIUM-BOVIS BCG; INFLUENZA-VIRUS
VACCINE; PSYCHROPHILIC ENZYMES; SALMONELLA-TYPHI; TY 21A;
IDENTIFICATION; TUBERCULOSIS; MUTAGENESIS; PROTECTION
AB Temperature-sensitive (TS) viruses have been used for decades as vaccines capable of limited replication in their hosts. Although attenuated bacteria, such as the Bacille Calmette-Gu,rin anti-tuberculosis vaccine, have been used for almost a century, it is only recently that there has been progress in using TS bacterial strains as live vaccines. Decades of work on essential bacterial genes and the recent explosion in the number of available bacterial genomic sequences set the groundwork for the identification of essential genes from diverse bacteria. This knowledge has allowed for the substitution of essential genes from cold-loving bacteria into the chromosomes of pathogenic bacteria. Many of these gene substitutions generated TS pathogenic bacterial strains, and some were demonstrated to provide protective immunity in mice. This work opens the possibility of engineering many pathogenic bacteria to create TS strains that can be used as vaccines.
C1 [Duplantis, Barry N.; Nano, Francis E.] Univ Victoria, Dept Biochem & Microbiol, Victoria, BC V8W 3P6, Canada.
[Bosio, Catherine M.] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
RP Nano, FE (reprint author), Univ Victoria, Dept Biochem & Microbiol, POB 3055,STN CSC, Victoria, BC V8W 3P6, Canada.
EM fnano@uvic.ca
RI Bosio, Catharine/D-7456-2015
FU Bill and Melinda Gates Foundation; Natural Sciences and Engineering
Council of Canada
FX This work was supported by the Bill and Melinda Gates Foundation and by
the Natural Sciences and Engineering Council of Canada.
NR 50
TC 1
Z9 1
U1 0
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0946-2716
J9 J MOL MED
JI J. Mol. Med.
PD MAY
PY 2011
VL 89
IS 5
BP 437
EP 444
DI 10.1007/s00109-010-0721-3
PG 8
WC Genetics & Heredity; Medicine, Research & Experimental
SC Genetics & Heredity; Research & Experimental Medicine
GA 752JY
UT WOS:000289688700003
PM 21229224
ER
PT J
AU Nunez, J
Cristofalo, E
McGinley, B
Katz, R
Glen, DR
Gauda, E
AF Nunez, Jeanne
Cristofalo, Elizabeth
McGinley, Brian
Katz, Richard
Glen, Daniel R.
Gauda, Estelle
TI Temporal Association of Polysomnographic Cardiorespiratory Events With
GER Detected by MII-pH Probe in the Premature Infant at Term
SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
LA English
DT Article
DE cardiorespiratory events; gastroesophageal reflux; multichannel
intraluminal impedance; obstructive sleep apnea; pH probe;
polysomnography; premature infants
ID MULTICHANNEL INTRALUMINAL IMPEDANCE; OBSTRUCTIVE SLEEP-APNEA; ACID
GASTROESOPHAGEAL-REFLUX; LARYNGEAL SENSATION; PRETERM INFANTS; AIRWAY;
CHILDREN; REFLEXES
AB Objectives: The aim of the study was to examine temporal association (TA) between polysomnographic cardiorespiratory (CR) events and gastroesophageal reflux (GER) in premature infants with persistent CR events at >39 weeks postmenstrual age and determine whether the use of multichannel intraluminal impedance (MII)-pH probe improves sensitivity of the TA compared with pH probe alone.
Patients and Methods: Seven infants born between 24 and 29 weeks' gestational age with persistent CR events at 39 to 48 weeks' postmenstrual age underwent a polysomnography with MII-pH probe. Symptom index (SI) and symptom-associated probability were calculated for diverse types of reflux and CR events. SI and a Fisher exact test with variable association windows were calculated for obstructive apnea (OA). Odds ratios for an OA given a reflux event and for a reflux event given an OA were determined.
Results: With a Fisher exact test, a subject-specific association between MII events and OA was found in the 3 patients who required a fundoplication or had the worse clinical GER. Some level of TA was found with SI and symptom-associated probability in 6 of 7 infants. Association was found for pH >4 and pH <= 4 reflux events. pH-only events with no change of MII had only a limited role in generating CR events.
Conclusions: TA between CR events and GER was found in a single-subject-level analysis in some infants with persistent CR events at term. This TA suggests a causal relation between CR and reflux events that was further strengthened by the clinical outcomes of each infant.
C1 [Nunez, Jeanne; Cristofalo, Elizabeth; Gauda, Estelle] Johns Hopkins Univ Hosp, Dept Pediat, Baltimore, MD 21287 USA.
[Nunez, Jeanne; Cristofalo, Elizabeth; Gauda, Estelle] Sch Med, Baltimore, MD USA.
[McGinley, Brian] Johns Hopkins Univ Hosp, Dept Pediat Pulmonol & Sleep Med, Baltimore, MD 21287 USA.
[Katz, Richard] Johns Hopkins Univ, Div Pediat Gastroenterol, Baltimore, MD USA.
[Katz, Richard] Mt Washington Pediat Hosp, Baltimore, MD USA.
[Glen, Daniel R.] NIMH, Intramural Res Program, Bethesda, MD 20892 USA.
[Glen, Daniel R.] NIMH, NIH, Bethesda, MD 20892 USA.
RP Nunez, J (reprint author), Johns Hopkins Bayview Med Ctr Neonatal Intens Car, AA2 Bldg,4940 Eastern Ave, Baltimore, MD 21224 USA.
EM jnunez4@jhmi.edu
FU Thomas Wilson grant
FX This work was supported by a Thomas Wilson grant.
NR 33
TC 12
Z9 13
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0277-2116
J9 J PEDIATR GASTR NUTR
JI J. Pediatr. Gastroenterol. Nutr.
PD MAY
PY 2011
VL 52
IS 5
BP 523
EP 531
DI 10.1097/MPG.0b013e3181fa06d7
PG 9
WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics
SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics
GA 752EI
UT WOS:000289671900005
PM 21502823
ER
PT J
AU Bercovitch, L
Martin, L
Chassaing, N
Hefferon, TW
Bessis, D
Vanakker, O
Terry, SF
AF Bercovitch, Lionel
Martin, Ludovic
Chassaing, Nicolas
Hefferon, Timothy W.
Bessis, Didier
Vanakker, Olivier
Terry, Sharon F.
TI Acquired pseudoxanthoma elasticum presenting after liver transplantation
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Article
DE ABCC6; liver transplantation; pseudoxanthoma elasticum
ID DEFICIENCY; ABCC6; MUTATIONS; TISSUES; GENE
AB Background: Pseudoxanthoma elasticum (PXE) is thought to be a metabolic disorder resulting from mutations in the gene encoding the cellular transporter, ABCC6, which is primarily expressed in liver and kidney. We encountered 3 patients who developed clinical and histopathological evidence of PXE after liver transplantation, suggesting that PXE could have been acquired from the transplanted organ.
Objective: We sought to delineate the clinical features and screen each patient and samples of donor liver for mutations in the ABCC6 gene.
Methods: Each patient underwent full clinical examination, skin biopsy, and ophthalmologic examination, and whole genome sequencing using standard techniques. Fixed samples of donor liver tissue were available for mutation analysis in two patients and of donor kidney tissue in one.
Results: All 3 patients had unequivocal clinical and histopathologic evidence of PXE. No patient (or family member available for screening) had evidence of mutations in ABCC6. Neither liver specimen nor the single available kidney specimen showed evidence of mutations in ABCC6.
Limitations: Liver tissue was not available from one patient and DNA was of poor quality in another, resulting in limited screening. Genetic testing does not detect ABCC6 mutations in 10% of patients with confirmed PXE.
Conclusion: Although we were unable to demonstrate A.BCC6 mutations in limited screening of fixed donor livers, the absence of any PXE mutations in the affected patients, the timing of onset of PXE, and the known acquisition of other metabolic disorders and coagulopathies from donor livers suggest that PXE was likely acquired via liver transplantation. (J Am Acad Dermatol 2011;64:873-8.)
C1 [Bercovitch, Lionel] Rhode Isl Hosp, Dept Dermatol, Providence, RI 02903 USA.
[Bercovitch, Lionel] Brown Univ, Warren Alpert Med Sch, Providence, RI 02903 USA.
[Martin, Ludovic] Angers Univ Hosp, Dept Dermatol, Angers, France.
[Martin, Ludovic] Univ Angers, Angers, France.
[Chassaing, Nicolas] Univ Toulouse, Dept Genet, Toulouse Univ Hosp, Toulouse, France.
[Hefferon, Timothy W.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA.
[Bessis, Didier] Univ Montpellier, Montpellier Univ Hosp, Dept Dermatol, F-34059 Montpellier, France.
[Vanakker, Olivier] Univ Ghent, State Univ Ghent Hosp, Ctr Med Genet, B-9000 Ghent, Belgium.
[Bercovitch, Lionel; Terry, Sharon F.] PXE Int Inc, Washington, DC USA.
RP Bercovitch, L (reprint author), Rhode Isl Hosp, Dept Dermatol, 593 Eddy St, Providence, RI 02903 USA.
EM Lionel_Bercovitch@brown.edu
RI Martin, Ludovic/K-2674-2015
FU PXE International Inc
FX PXE International Inc provided funding for genetic testing related to
case 3. DNA sequencing of the liver explant sample in case 3 was
performed at the National Human Genome Research Institute.
NR 19
TC 4
Z9 5
U1 0
U2 6
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD MAY
PY 2011
VL 64
IS 5
BP 873
EP 878
DI 10.1016/j.jaad.2010.03.030
PG 6
WC Dermatology
SC Dermatology
GA 754PW
UT WOS:000289869800009
PM 21397982
ER
PT J
AU Malykhina, O
Yednak, MA
Collins, PL
Olivo, PD
Peeples, ME
AF Malykhina, Olga
Yednak, Mark A.
Collins, Peter L.
Olivo, Paul D.
Peeples, Mark E.
TI A Respiratory Syncytial Virus Replicon That Is Noncytotoxic and Capable
of Long-Term Foreign Gene Expression
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID VESICULAR STOMATITIS-VIRUS; BACULOVIRUS GP64 PROTEIN; ENVELOPE-RELATED
GENES; SENDAI-VIRUS; PERSISTENT INFECTION; IN-VIVO; AIRWAY EPITHELIUM;
RNA REPLICATION; MEASLES VIRUSES; CELL-CULTURE
AB Respiratory syncytial virus (RSV) infection of most cultured cell lines causes cell-cell fusion and death. Cell fusion is caused by the fusion (F) glycoprotein and is clearly cytopathic, but other aspects of RSV infection may also contribute to cytopathology. To investigate this possibility, we generated an RSV replicon that lacks all three of its glycoprotein genes and so cannot cause cell-cell fusion or virus spread. This replicon includes a green fluorescent protein gene and an antibiotic resistance gene to enable detection and selection of replicon-containing cells. Adaptive mutations in the RSV replicon were not required for replicon maintenance. Cells containing the replicon could be cloned and passaged many times in the absence of antibiotic selection, with 99% or more of the cells retaining the replicon after each cell division. Transient expression of the F and G (attachment) glycoproteins supported the production of virions that could transfer the replicon into most cell lines tested. Since the RSV replicon is not toxic to these cultured cells and does not affect their rate of cell division, none of the 8 internal viral proteins, the viral RNA transcripts, or the host response to these molecules or their activities is cytopathic. However, the level of replicon genome and gene expression is controlled in some manner well below that of complete virus and, as such, might avoid cytotoxicity. RSV replicons could be useful for cytoplasmic gene expression in vitro and in vivo and for screening for compounds active against the viral polymerase.
C1 [Malykhina, Olga; Yednak, Mark A.; Peeples, Mark E.] Nationwide Childrens Hosp, Res Inst, Ctr Vaccines & Immun, Columbus, OH 43205 USA.
[Peeples, Mark E.] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43210 USA.
[Malykhina, Olga; Peeples, Mark E.] Ohio State Univ, Coll Med, Integrated Biomed Sci Grad Program, Columbus, OH 43210 USA.
[Collins, Peter L.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Olivo, Paul D.] Apath LLC, St Louis, MO 63141 USA.
RP Peeples, ME (reprint author), Nationwide Childrens Hosp, Res Inst, Ctr Vaccines & Immun, 700 Childrens Dr, Columbus, OH 43205 USA.
EM Mark.Peeples@nationwidechildrens.org
FU Apath, LLC; National Institutes of Health [AI047213, HL051818]; NIAID,
NIH
FX This work was supported by Apath, LLC, and by grants AI047213 and
HL051818 from the National Institutes of Health. P.L.C. was supported by
the NIAID, NIH, Intramural Research Program.
NR 58
TC 16
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 MAY
PY 2011
VL 85
IS 10
BP 4792
EP 4801
DI 10.1128/JVI.02399-10
PG 10
WC Virology
SC Virology
GA 753NZ
UT WOS:000289787300016
PM 21389127
ER
PT J
AU Chaipan, C
Dilley, KA
Paprotka, T
Delviks-Frankenberry, KA
Venkatachari, NJ
Hu, WS
Pathak, VK
AF Chaipan, Chawaree
Dilley, Kari A.
Paprotka, Tobias
Delviks-Frankenberry, Krista A.
Venkatachari, Narasimhan J.
Hu, Wei-Shau
Pathak, Vinay K.
TI Severe Restriction of Xenotropic Murine Leukemia Virus-Related Virus
Replication and Spread in Cultured Human Peripheral Blood Mononuclear
Cells
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROSTATE CARCINOMA-CELLS;
CHRONIC-FATIGUE-SYNDROME; HUMAN RETROVIRUS XMRV; STRAND DNA TRANSFER;
HIV-1 DNA; INFECTIOUS RETROVIRUS; CYTIDINE DEAMINATION; APOBEC PROTEINS;
VIF PROTEIN
AB Xenotropic murine leukemia virus-related virus (XMRV) is a gammaretrovirus recently isolated from human prostate cancer and peripheral blood mononuclear cells (PBMCs) of patients with chronic fatigue syndrome (CFS). We and others have shown that host restriction factors APOBEC3G (A3G) and APOBEC3F (A3F), which are expressed in human PBMCs, inhibit XMRV in transient-transfection assays involving a single cycle of viral replication. However, the recovery of infectious XMRV from human PBMCs suggested that XMRV can replicate in these cells despite the expression of APOBEC3 proteins. To determine whether XMRV can replicate and spread in cultured PBMCs even though it can be inhibited by A3G/A3F, we infected phytohemagglutinin-activated human PBMCs and A3G/A3F-positive and -negative cell lines (CEM and CEM-SS, respectively) with different amounts of XMRV and monitored virus production by using quantitative real-time PCR. We found that XMRV efficiently replicated in CEM-SS cells and viral production increased by >4,000-fold, but there was only a modest increase in viral production from CEM cells (<14-fold) and a decrease in activated PBMCs, indicating little or no replication and spread of XMRV. However, infectious XMRV could be recovered from the infected PBMCs by cocultivation with a canine indicator cell line, and we observed hypermutation of XMRV genomes in PBMCs. Thus, PBMCs can potentially act as a source of infectious XMRV for spread to cells that express low levels of host restriction factors. Overall, these results suggest that hypermutation of XMRV in human PBMCs constitutes one of the blocks to replication and spread of XMRV. Furthermore, hypermutation of XMRV proviruses at GG dinucleotides may be a useful and reliable indicator of human PBMC infection.
C1 [Chaipan, Chawaree; Paprotka, Tobias; Delviks-Frankenberry, Krista A.; Venkatachari, Narasimhan J.; Pathak, Vinay K.] NCI, HIV Drug Resistance Program, Viral Mutat Sect, Frederick, MD 21702 USA.
[Dilley, Kari A.; Hu, Wei-Shau] NCI, HIV Drug Resistance Program, Viral Recombinat Sect, Frederick, MD 21702 USA.
RP Pathak, VK (reprint author), NCI, HIV Drug Resistance Program, Viral Mutat Sect, POB B,Bldg 535,Room 334, Frederick, MD 21702 USA.
EM vinay.pathak@nih.gov
RI Delviks-Frankenberry, Krista/M-4822-2013
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research.
NR 61
TC 17
Z9 18
U1 1
U2 3
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 MAY
PY 2011
VL 85
IS 10
BP 4888
EP 4897
DI 10.1128/JVI.00046-11
PG 10
WC Virology
SC Virology
GA 753NZ
UT WOS:000289787300025
PM 21325415
ER
PT J
AU Goff, AJ
Chapman, J
Foster, C
Wlazlowski, C
Shamblin, J
Lin, K
Kreiselmeier, N
Mucker, E
Paragas, J
Lawler, J
Hensley, L
AF Goff, Arthur J.
Chapman, Jennifer
Foster, Chad
Wlazlowski, Carly
Shamblin, Joshua
Lin, Kenny
Kreiselmeier, Norman
Mucker, Eric
Paragas, Jason
Lawler, James
Hensley, Lisa
TI A Novel Respiratory Model of Infection with Monkeypox Virus in
Cynomolgus Macaques
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID SMALLPOX; CONGO; PATHOLOGY; ST-246
AB Variola, the causative agent of smallpox, and the related monkeypox virus are both select agents that, if purposefully released, would cause public panic and social disruption. For this reason research continues in the areas of animal model and therapeutic development. Orthopoxviruses show a widely varying degree of host specificity, making development of accurate animal models difficult. In this paper, we demonstrate a novel respiratory infection technique that resulted in "classic" orthopox disease in nonhuman primates and takes the field of research one step closer to a better animal model.
C1 [Goff, Arthur J.; Chapman, Jennifer; Wlazlowski, Carly; Shamblin, Joshua; Lin, Kenny; Mucker, Eric; Hensley, Lisa] USA, Med Res Inst Infect Dis, Frederick, MD USA.
[Foster, Chad] USA, Med Dept Ctr & Sch, Ft Sam Houston, TX USA.
[Kreiselmeier, Norman] Tripler Army Med Ctr, Honolulu, HI 96859 USA.
[Paragas, Jason; Lawler, James] NIAID, Integrated Res Facil, NIH, Frederick, MD USA.
RP Goff, AJ (reprint author), USA, Med Res Inst Infect Dis, Div Virol, Viral Therapeut Branch, 1425 Porter St,903Q, Ft Detrick, MD 21702 USA.
EM Arthur.Goff@amedd.army.mil
FU Department of Homeland Security/National Biodefense and Countermeasures
Center [RSRD-05-00378]
FX This work was supported by Department of Homeland Security/National
Biodefense and Countermeasures Center, Contract number RSRD-05-00378.
NR 18
TC 32
Z9 33
U1 0
U2 3
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 MAY
PY 2011
VL 85
IS 10
BP 4898
EP 4909
DI 10.1128/JVI.02525-10
PG 12
WC Virology
SC Virology
GA 753NZ
UT WOS:000289787300026
PM 21389129
ER
PT J
AU Vaine, M
Duenas-Decamp, M
Peters, P
Liu, Q
Arthos, J
Wang, SX
Clapham, P
Lu, S
AF Vaine, Michael
Duenas-Decamp, Maria
Peters, Paul
Liu, Qin
Arthos, James
Wang, Shixia
Clapham, Paul
Lu, Shan
TI Two Closely Related Env Antigens from the Same Patient Elicited
Different Spectra of Neutralizing Antibodies against Heterologous HIV-1
Isolates
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; RECOMBINANT GLYCOPROTEIN-120 VACCINE; CD4
BINDING LOOP; R5 ENVELOPES; MACROPHAGE TROPISM; GP120 PROTEIN;
SUBTYPE-B; DNA; INFECTION; RESPONSES
AB Identification of immunogens capable of eliciting broadly neutralizing antibody (NAb) responses against HIV-1 is a major goal toward the development of an AIDS vaccine. Despite significant progress in understanding the structural features of the HIV-1 envelope glycoprotein (Env) and the discovery of multiple broadly neutralizing monoclonal antibodies with defined antigenic structures, the design of optimal Env immunogens to elicit broad NAbs remains a major challenge. As the structural determinants of Env immunogenicity remain unclear, we assessed two closely related Env antigens isolated from the same HIV-1-infected patient with different phenotypic features to identify what may result in a favorable immunogenic profile. One Env, B33, isolated from brain, was highly macrophage tropic with a high CD4 affinity, while the other, LN40, isolated from the lymph nodes, was poorly macrophage tropic with a low CD4 affinity. Using a DNA prime-protein boost approach, rabbits primed with LN40 Env antigen had a NAb response against heterologous primary isolates, while B33 Env antigens were capable of eliciting NAbs against only homologous and sensitive viral isolates. Further analysis revealed that the specificity of NAbs elicited by the LN40 antigen mapped to limited residues within or flanking the CD4 binding site. Certain key structural determinants were identified that could differentiate primary Env immunogens based on their potential to elicit broader NAbs. This progress will facilitate the rational design of effective HIV-1 vaccine formulations with optimal Env antigens.
C1 [Lu, Shan] Univ Massachusetts, Sch Med, Dept Med, LRB, Worcester, MA 01605 USA.
[Duenas-Decamp, Maria; Peters, Paul; Clapham, Paul] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA.
[Arthos, James] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Lu, S (reprint author), Univ Massachusetts, Sch Med, Dept Med, LRB, Room 304,364 Plantat St,Lazare Res Bldg, Worcester, MA 01605 USA.
EM shan.lu@umassmed.edu
FU NIH [R01AI065250, P01AI082274, U19AI082676, R01MH064408]
FX This study was funded in part by NIH grants R01AI065250, P01AI082274,
U19AI082676, and R01MH064408.
NR 33
TC 8
Z9 8
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 MAY
PY 2011
VL 85
IS 10
BP 4927
EP 4936
DI 10.1128/JVI.00081-11
PG 10
WC Virology
SC Virology
GA 753NZ
UT WOS:000289787300028
PM 21411542
ER
PT J
AU Anderson, JA
Archin, NM
Ince, W
Parker, D
Wiegand, A
Coffin, JM
Kuruc, J
Eron, J
Swanstrom, R
Margolis, DM
AF Anderson, Jeffrey A.
Archin, Nancie M.
Ince, William
Parker, Daniel
Wiegand, Ann
Coffin, John M.
Kuruc, Joann
Eron, Joseph
Swanstrom, Ronald
Margolis, David M.
TI Clonal Sequences Recovered from Plasma from Patients with Residual HIV-1
Viremia and on Intensified Antiretroviral Therapy Are Identical to
Replicating Viral RNAs Recovered from Circulating Resting CD4(+) T Cells
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID NEIGHBOR-JOINING METHOD; VIRUS TYPE-1 VIREMIA; PROGENITOR CELLS;
INFECTION; RESERVOIRS; SENSITIVITY; CHALLENGE; MULTIPLE; PROVIRUS;
REVEALS
AB Despite successful antiretroviral therapy (ART), low-level viremia (LLV) may be intermittently detected in most HIV-infected patients. Longitudinal blood plasma and resting CD4(+) T cells were obtained from two patients on suppressive ART to investigate the source of LLV. Single-genome sequencing of HIV-1 env from LLV plasma was performed, and the sequences were compared to sequences recovered from limiting-dilution outgrowth assays of resting CD4(+) T cells. The circulating LLV virus clone was identical to virus recovered from outgrowth assays from pools of millions of resting CD4(+) T cells. Understanding the sources of LLV requires evaluation of all possible reservoirs of persistent HIV infection.
C1 [Anderson, Jeffrey A.; Archin, Nancie M.; Ince, William; Parker, Daniel; Kuruc, Joann; Eron, Joseph; Swanstrom, Ronald; Margolis, David M.] Univ N Carolina, Chapel Hill, NC 27599 USA.
[Wiegand, Ann; Coffin, John M.] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA.
RP Margolis, DM (reprint author), Univ N Carolina, 2060 Genet Med Bldg,CB 7042, Chapel Hill, NC 27599 USA.
EM dmargo@med.unc.edu
OI Margolis, David/0000-0001-5714-0002
FU National Institutes of Health [AI45297, AI064074, AI44667, RR025747
CTSA, AI50410]; Merck; GlaxoSmithKline
FX Funding for the study was provided by National Institutes of Health
grants AI45297 and AI064074 to D. M. M., AI44667 to R. S., RR025747 CTSA
to the UNC CTRC, and AI50410 to the UNC CFAR.; J.E. is a consultant for
Abbott, GlaxoSmithKline, Merck, and Bristol-Myers Squibb, has received
grants from Merck and GlaxoSmithKline, and has been an invited speaker
for Bristol-Myers Squibb and Gilead. All remaining authors declare no
conflicts of interest.
NR 32
TC 50
Z9 50
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 MAY
PY 2011
VL 85
IS 10
BP 5220
EP 5223
DI 10.1128/JVI.00284-11
PG 4
WC Virology
SC Virology
GA 753NZ
UT WOS:000289787300057
PM 21367910
ER
PT J
AU Anderson, LA
Moore, SC
Gridley, G
Stone, BJ
Landgren, O
AF Anderson, Lesley A.
Moore, Steven C.
Gridley, Gloria
Stone, B. J.
Landgren, Ola
TI Concomitant and antecedent deep venous thrombosis and cancer survival in
male US veterans
SO LEUKEMIA & LYMPHOMA
LA English
DT Article
ID PULMONARY-EMBOLISM; LUNG-CANCER; THROMBOEMBOLISM; RISK; EPIDEMIOLOGY;
DIAGNOSIS; AFFAIRS; CARE
AB Survival is reportedly worse in patients with cancer concurrently diagnosed with deep venous thrombosis. However, information on specific malignancies is limited. From a cohort study of male US veterans we identified incident cancer cases (n aEuroS== aEuroS412 008) and compared survival patterns among those with versus without a history of deep venous thrombosis. Using Cox proportional hazard models, we estimated hazard ratios (HRs) and 95%% confidence intervals as measures of the relative risk of dying. Individuals with (versus without) a concomitant deep venous thrombosis and cancer diagnosis had a higher risk of dying (HR aEuroS== aEuroS1.38; 1.28--1.49). The most prominent excess mortality (HR aEuroS== aEuroS1.29--2.55) was observed among patients diagnosed with deep venous thrombosis at the time of diagnosis of lung, gastric, prostate, bladder, or kidney cancer. Increased risk of dying was also found among cancer patients diagnosed with deep venous thrombosis 1 year (HR aEuroS== aEuroS1.14; 1.07--1.22), 1--5 years (HR aEuroS== aEuroS1.14; 1.10--1.19), and > 5 years (HR aEuroS== aEuroS1.27; 1.23--1.31) before cancer; this was true for most cancer sites (HR aEuroS== aEuroS1.17--1.64). In summary, antecedent deep venous thrombosis confers a worse prognosis upon cancer patients. Advanced stage at diagnosis, treatment effects, lifestyle factors, and comorbidity could explain differences by cancer site and time frame between a prior deep venous thrombosis diagnosis and cancer outcome.-/-
mice; F. Brombacher (University of Cape Town) for Il4r-/-
mice; C. Wilson (Washington University) for Cd4-Cre mice; R. Abe (Tokyo
University of Science) for the PV-1 mAb to CD28; T. Kitamura (Tokyo
University) for Platinum-E packaging cells; H. Fujimoto, Y. Suzuki, K.
Ikari and E. Hayashi for technical assistance; and P. Burrows for
comments on the manuscript. Supported by RIKEN (Y. Motomura), the
Ministry of Education, Culture, Sports, Science and Technology of Japan,
and the Program for Promotion of Fundamental Studies in Health Sciences
of the National Institute of Biomedical Innovation.
NR 50
TC 67
Z9 70
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD MAY
PY 2011
VL 12
IS 5
BP 450
EP U111
DI 10.1038/ni.2020
PG 11
WC Immunology
SC Immunology
GA 752CT
UT WOS:000289666600016
PM 21460847
ER
PT J
AU Steeg, PS
Camphausen, KA
Smith, QR
AF Steeg, Patricia S.
Camphausen, Kevin A.
Smith, Quentin R.
TI Brain metastases as preventive and therapeutic targets
SO NATURE REVIEWS CANCER
LA English
DT Review
ID CENTRAL-NERVOUS-SYSTEM; CELL LUNG-CANCER; PROPHYLACTIC CRANIAL
IRRADIATION; HER2-POSITIVE BREAST-CANCER; CLINICAL-PRACTICE GUIDELINE;
IN-VIVO RADIOSENSITIZATION; RADIATION-INDUCED CHANGES; PHASE-II TRIAL;
NUDE-MICE; LEPTOMENINGEAL METASTASES
AB The incidence of metastasis to the brain is apparently rising in cancer patients and threatens to limit the gains that have been made by new systemic treatments. The brain is considered a 'sanctuary site' as the blood-tumour barrier limits the ability of drugs to enter and kill tumour cells. Translational research examining metastasis to the brain needs to be multi-disciplinary, marrying advanced chemistry, blood-brain barrier pharmacokinetics, neurocognitive testing and radiation biology with metastasis biology, to develop and implement new clinical trial designs. Advances in the chemoprevention of brain metastases, the validation of tumour radiation sensitizers and the amelioration of cognitive deficits caused by whole-brain radiation therapy are discussed.
C1 [Steeg, Patricia S.] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Camphausen, Kevin A.] NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Smith, Quentin R.] Texas Tech Univ Hlth Sci Ctr, Dept Pharmaceut Sci, Amarillo, TX 79106 USA.
RP Steeg, PS (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
EM steegp@mail.nih.gov
FU Center for Cancer Research, US National Cancer Institute; Center of
Excellence from the US Department of Defense [W81XWH-062-0033]
FX This work was supported by the Intramural Program, Center for Cancer
Research, US National Cancer Institute, and from the Center of
Excellence grant W81XWH-062-0033 from the US Department of Defense
Breast Cancer Research Program. The authors regret that space
restrictions did not permit all citations to be included.
NR 142
TC 131
Z9 138
U1 4
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-175X
EI 1474-1768
J9 NAT REV CANCER
JI Nat. Rev. Cancer
PD MAY
PY 2011
VL 11
IS 5
BP 352
EP 363
DI 10.1038/nrc3053
PG 12
WC Oncology
SC Oncology
GA 753MN
UT WOS:000289779800012
PM 21472002
ER
PT J
AU McGavern, DB
Kang, SS
AF McGavern, Dorian B.
Kang, Silvia S.
TI Illuminating viral infections in the nervous system
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Review
ID HERPES-SIMPLEX-VIRUS; SIMIAN IMMUNODEFICIENCY VIRUS; PROGRESSIVE
MULTIFOCAL LEUKOENCEPHALOPATHY; BLOOD-BRAIN-BARRIER; CD8(+) T-CELLS;
HUMAN TRIGEMINAL GANGLIA; SENSORY NEURONS; IN-VIVO; MICROGLIAL CELLS;
IMMUNE-RESPONSE
AB Viral infections are a major cause of human disease. Although most viruses replicate in peripheral tissues, some have developed unique strategies to move into the nervous system, where they establish acute or persistent infections. Viral infections in the central nervous system (CNS) can alter homeostasis, induce neurological dysfunction and result in serious, potentially life-threatening inflammatory diseases. This Review focuses on the strategies used by neurotropic viruses to cross the barrier systems of the CNS and on how the immune system detects and responds to viral infections in the CNS. A special emphasis is placed on immune surveillance of persistent and latent viral infections and on recent insights gained from imaging both protective and pathogenic antiviral immune responses.
C1 [McGavern, Dorian B.; Kang, Silvia S.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
RP McGavern, DB (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
EM mcgavernd@mail.nih.gov
OI McGavern, Dorian/0000-0001-9568-545X
FU National Institutes of Health (NIH) [NS061447-01]
FX This work was supported by the National Institutes of Health (NIH)
intramural program. S. S. K. is presently supported by a NIH National
Research Service Award (NS061447-01). We would like to thank J. Kim and
M. Dustin at New York University for insightful discussions and a very
supportive collaboration focused on imaging CNS antiviral immunity.
NR 120
TC 76
Z9 76
U1 0
U2 18
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1733
J9 NAT REV IMMUNOL
JI Nat. Rev. Immunol.
PD MAY
PY 2011
VL 11
IS 5
BP 318
EP 329
DI 10.1038/nri2971
PG 12
WC Immunology
SC Immunology
GA 753LH
UT WOS:000289774700012
PM 21508982
ER
PT J
AU Mackall, CL
Fry, TJ
Gress, RE
AF Mackall, Crystal L.
Fry, Terry J.
Gress, Ronald E.
TI Harnessing the biology of IL-7 for therapeutic application
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Review
ID TISSUE-INDUCER CELLS; INTERLEUKIN-7 RECEPTOR-ALPHA;
BONE-MARROW-TRANSPLANTATION; CD8(+) T-CELLS; ROR-GAMMA-T; KERATINOCYTE
GROWTH-FACTOR; RECENT THYMIC EMIGRANTS; VERSUS-HOST-DISEASE;
NATURAL-KILLER-CELL; LYMPHOID-TISSUE
AB Interleukin-7 (IL-7) is required for T cell development and for maintaining and restoring homeostasis of mature T cells. IL-7 is a limiting resource under normal conditions, but it accumulates during lymphopaenia, leading to increased T cell proliferation. The administration of recombinant human IL-7 to normal or lymphopenic mice, non-human primates and humans results in widespread T cell proliferation, increased T cell numbers, modulation of peripheral T cell subsets and increased T cell receptor repertoire diversity. These effects raise the prospect that IL-7 could mediate therapeutic benefits in several clinical settings. This Review summarizes the biology of IL-7 and the results of its clinical use that are available so far to provide a perspective on the opportunities for clinical application of this cytokine.
C1 [Mackall, Crystal L.] NCI, Immunol Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Fry, Terry J.] NCI, Blood & Marrow Transplant Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Gress, Ronald E.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Mackall, CL (reprint author), NCI, Immunol Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA.
EM cm35c@nih.gov
FU National Institutes of Health, USA
FX We would like to thank S. Durum for his critical review of the
manuscript and his helpful discussions. This work was supported by the
Intramural Research Program of the National Institutes of Health, USA.
NR 132
TC 178
Z9 183
U1 1
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1733
J9 NAT REV IMMUNOL
JI Nat. Rev. Immunol.
PD MAY
PY 2011
VL 11
IS 5
BP 330
EP 342
DI 10.1038/nri2970
PG 13
WC Immunology
SC Immunology
GA 753LH
UT WOS:000289774700013
PM 21508983
ER
PT J
AU Amara, SG
Grillner, S
Insel, T
Nutt, D
Tsumoto, T
AF Amara, Susan G.
Grillner, Sten
Insel, Tom
Nutt, David
Tsumoto, Tadaharu
TI Neuroscience in recession?
SO NATURE REVIEWS NEUROSCIENCE
LA English
DT Editorial Material
AB As the global financial downturn continues, its impact on neuroscientists - both on an individual level and at the level of their research institute - becomes increasingly apparent. How is the economic crisis affecting neuroscience funding, career prospects, international collaborations and scientists' morale in different parts of the world? Nature Reviews Neuroscience gauged the opinions of a number of leading neuroscientists: the President of the Society for Neuroscience, the President Elect of the British Neuroscience Association, the former President of the Japan Neuroscience Society, the President of the Federation of European Neuroscience Societies and the Director of the US National Institute of Mental Health. Their responses provide interesting and important insights into the regional impact of the global financial downturn, with some causes for optimism for the future of neuroscience research.
C1 [Amara, Susan G.] Univ Pittsburgh, Dept Neurobiol, Sch Med, Pittsburgh, PA 15260 USA.
[Amara, Susan G.] Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA 15260 USA.
[Grillner, Sten] Karolinska Inst, Dept Neurosci, Nobel Inst Neurophysiol, SE-17177 Stockholm, Sweden.
[Insel, Tom] NIMH, NIH, Bethesda, MD 20892 USA.
[Nutt, David] Univ London Imperial Coll Sci Technol & Med, Neuropsychopharmacol Unit, Div Expt Med, Hammersmith Hosp, London W12 0NN, England.
[Tsumoto, Tadaharu] RIKEN, Lab Cort Circuit Plast, Brain Sci Inst, Wako, Saitama 3510198, Japan.
RP Amara, SG (reprint author), Univ Pittsburgh, Dept Neurobiol, Sch Med, Biomed Sci Tower 3,6th Floor,Room 6057,3501 5th A, Pittsburgh, PA 15260 USA.
EM amaras@pitt.edu; sten.grillner@ki.se; tinsel@mail.nih.gov;
d.nutt@imperial.ac.uk; tsumoto@brain.riken.jp
OI nutt, david/0000-0002-1286-1401
NR 0
TC 6
Z9 6
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-003X
J9 NAT REV NEUROSCI
JI Nat. Rev. Neurosci.
PD MAY
PY 2011
VL 12
IS 5
BP 297
EP +
DI 10.1038/nrn3023
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 752VS
UT WOS:000289724200011
PM 21505517
ER
PT J
AU Ravasi, L
Shimoji, K
Soto-Montenegro, ML
Esaki, T
Seidel, J
Sokoloff, L
Schmidt, K
AF Ravasi, Laura
Shimoji, Kazuaki
Soto-Montenegro, Marisa L.
Esaki, Takanori
Seidel, Jurgen
Sokoloff, Louis
Schmidt, Kathleen
TI Use of [F-18]fluorodeoxyglucose and the ATLAS small animal PET scanner
to examine cerebral functional activation by whisker stimulation in
unanesthetized rats
SO NUCLEAR MEDICINE COMMUNICATIONS
LA English
DT Article
DE [C-14]deoxyglucose; 2-[F-18]fluoro-2-deoxyglucose; PET; small animal
imaging; whisker stimulation
ID POSITRON-EMISSION-TOMOGRAPHY; BLOOD INPUT FUNCTION; NEURONAL ACTIVATION;
GLUCOSE-UTILIZATION; RESOLUTION; BRAIN; MICROPET; AUTORADIOGRAPHY;
DEOXYGLUCOSE; SENSITIVITY
AB Purpose Stroking the whiskers of a rat is known to increase cerebral blood flow and glucose utilization in the somatosensory cortex. We sought to determine whether this activation could be detected with small animal PET and 2-[F-18]fluoro-2-deoxyglucose ([F-18]FDG).
Methods Awake rats were coinjected with [F-18]FDG and [C-14]deoxyglucose ([C-14]IDG), and during the uptake of the tracers, five, 10, or 15 whiskers on one side of the face were continuously stimulated. At the end of uptake, the animal was killed and imaged with the Advanced Technology Laboratory Animal Scanner small animal PET scanner. Carbon-14 autoradiography was then performed on brain sections obtained from each animal, and increases in tracer uptake in the somatosensory cortex were compared with those determined with PET.
Results Both methods showed increases in [F-18]FDG and [C-14]DG uptake in the somatosensory cortex in response to the stimulation of as few as five whiskers. However, the magnitude of activation determined from the PET images was less than that from autoradiography due to the lower spatial resolution of the PET scanner.
Conclusion Advanced Technology Laboratory Animal Scanner small animal PET imaging with [F-18]FDG can be used to assess neuronal functional activity in vivo. Nucl Med Commun 32:336-342 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Schmidt, Kathleen] NIMH, Sect Neuroadaptat & Prot Metab, NIH, Bethesda, MD 20892 USA.
[Ravasi, Laura; Shimoji, Kazuaki; Soto-Montenegro, Marisa L.] NIMH, Dept Positron Emiss Tomog, NIH, Bethesda, MD 20892 USA.
[Seidel, Jurgen] NIMH, Dept Nucl Med, Ctr Clin, NIH, Bethesda, MD 20892 USA.
[Esaki, Takanori; Sokoloff, Louis; Schmidt, Kathleen] NIMH, Cerebral Metab Lab, NIH, Bethesda, MD 20892 USA.
RP Schmidt, K (reprint author), NIMH, Sect Neuroadaptat & Prot Metab, NIH, Bldg 10,Room 2D56,10 Ctr Dr, Bethesda, MD 20892 USA.
EM kschmidt@mail.nih.gov
FU National Institute of Mental Health
FX This research was supported in part by the Intramural Research Program
of the National Institute of Mental Health. Conflict of interest: the
authors declare that they have no conflict of interest.
NR 19
TC 7
Z9 7
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0143-3636
J9 NUCL MED COMMUN
JI Nucl. Med. Commun.
PD MAY
PY 2011
VL 32
IS 5
BP 336
EP 342
DI 10.1097/MNM.0b013e3283447292
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 753GY
UT WOS:000289761500002
PM 21326123
ER
PT J
AU Levy, DT
Mabry, PL
Wang, YC
Gortmaker, S
Huang, TTK
Marsh, T
Moodie, M
Swinburn, B
AF Levy, D. T.
Mabry, P. L.
Wang, Y. C.
Gortmaker, S.
Huang, T. T. -K.
Marsh, T.
Moodie, M.
Swinburn, B.
TI Simulation models of obesity: a review of the literature and
implications for research and policy
SO OBESITY REVIEWS
LA English
DT Review
DE Obesity; policy; simulation models
ID CORONARY-HEART-DISEASE; ASSESSING COST-EFFECTIVENESS; FULL-TIME
EMPLOYEES; FOOD-ENERGY INTAKE; BODY-MASS INDEX; UNITED-STATES;
WEIGHT-GAIN; SOCIAL NETWORKS; PUBLIC-HEALTH; ADOLESCENT OVERWEIGHT
AB P>Simulation models (SMs) combine information from a variety of sources to provide a useful tool for examining how the effects of obesity unfold over time and impact population health. SMs can aid in the understanding of the complex interaction of the drivers of diet and activity and their relation to health outcomes. As emphasized in a recently released report of the Institute or Medicine, SMs can be especially useful for considering the potential impact of an array of policies that will be required to tackle the obesity problem. The purpose of this paper is to present an overview of existing SMs for obesity. First, a background section introduces the different types of models, explains how models are constructed, shows the utility of SMs and discusses their strengths and weaknesses. Using these typologies, we then briefly review extant obesity SMs. We categorize these models according to their focus: health and economic outcomes, trends in obesity as a function of past trends, physiologically based behavioural models, environmental contributors to obesity and policy interventions. Finally, we suggest directions for future research.
C1 [Levy, D. T.] Univ Baltimore, Pacific Inst Res & Evaluat, Baltimore, MD 21201 USA.
[Levy, D. T.] Univ Baltimore, Dept Econ, Baltimore, MD 21201 USA.
[Mabry, P. L.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
[Wang, Y. C.] Columbia Mailman Sch Publ Hlth, Dept Hlth Policy & Management, New York, NY USA.
[Gortmaker, S.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA.
[Huang, T. T. -K.] Univ Nebraska Med Ctr, Dept Hlth Promot & Social & Behav Hlth, Omaha, NE USA.
[Marsh, T.] Natl Heart Forum, London, England.
[Moodie, M.] Deakin Univ, Hlth Econ Unit, Melbourne, Vic, Australia.
[Swinburn, B.] Deakin Univ, WHO, Collaborating Ctr Obes Prevent, Melbourne, Vic, Australia.
RP Levy, DT (reprint author), Pacific Inst, 11720 Beltsville Dr,Suite 900, Calverton, MD 20705 USA.
EM levy@pire.org
FU Healthy Eatiing Research group of the Robert Wood Johnson Foundation
(RWJF) [63048]; NIH Office of Behavioral and Social Sciences Research
(OBSSR) [HHSN200700356P]; RWJF
FX David Levy gratefully acknowledges support from the Healthy Eatiing
Research group of the Robert Wood Johnson Foundation (RWJF; contract
#63048). In addition the authors gratefully acknowledge support from the
NIH Office of Behavioral and Social Sciences Research (OBSSR; contract #
HHSN200700356P) and RWJF which together supported a series of meetings
of the Collaborative Obesity Modeling Network (COMNet) where this work
was conceived and developed. While not all COMNet members are authors on
this article, the authors acknowledge the contributions of the entire
COMNet group in stimulating and refining this article. In particular,
the authors would like to thank Diane Finegood, Bill Flanagan and Kevin
Hall for their very useful comments on earlier drafts of this work.
NR 134
TC 35
Z9 35
U1 4
U2 37
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1467-7881
EI 1467-789X
J9 OBES REV
JI Obes. Rev.
PD MAY
PY 2011
VL 12
IS 5
BP 378
EP 394
DI 10.1111/j.1467-789X.2010.00804.x
PG 17
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 751TZ
UT WOS:000289641800007
PM 20973910
ER
PT J
AU Klebanoff, MA
Harper, M
Lai, YL
Thorp, J
Sorokin, Y
Varner, MW
Wapner, RJ
Caritis, SN
Iams, JD
Carpenter, MW
Peaceman, AM
Mercer, BM
Sciscione, A
Rouse, DJ
Ramin, SM
Anderson, GD
AF Klebanoff, Mark A.
Harper, Margaret
Lai, Yinglei
Thorp, John, Jr.
Sorokin, Yoram
Varner, Michael W.
Wapner, Ronald J.
Caritis, Steve N.
Iams, Jay D.
Carpenter, Marshall W.
Peaceman, Alan M.
Mercer, Brian M.
Sciscione, Anthony
Rouse, Dwight J.
Ramin, Susan M.
Anderson, Garland D.
CA Eunice Kennedy Shriver Natl Inst
TI Fish Consumption, Erythrocyte Fatty Acids, and Preterm Birth
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID RANDOMIZED-CONTROLLED-TRIAL; PROSPECTIVE COHORT; SEAFOOD INTAKE;
PREGNANCY; WEIGHT; RISK; WOMEN; AGE; SUPPLEMENTATION; CONTAMINANTS
AB OBJECTIVE: To estimate the association between fish consumption and erythrocyte omega-3 long-chain polyunsaturated fatty acids and preterm birth in a high-risk cohort.
METHODS: This was an ancillary study to a randomized trial of omega-3 supplementation to prevent preterm birth in women with at least one previous spontaneous preterm delivery. Dietary fish intake was assessed by questionnaire and erythrocyte fatty acids were measured at enrollment (16-21 completed weeks of gestation). The association between fish consumption and preterm delivery was modeled with linear and quadratic terms.
RESULTS: The probability of preterm birth was 48.6% among women eating fish less than once a month and 35.9% among women eating fish more often (P<.001). The adjusted odds ratio for preterm birth among women reporting moderately frequent fish consumption (three servings per week) was 0.60 (95% confidence interval 0.38-0.95), with no further reduction in preterm birth among women who consumed more than three servings of fish per week. Erythrocyte omega-3 levels correlated weakly but significantly with frequency of fish intake (Spearman r=0.22, P<.001); women in the lowest quartile of erythrocyte omega-3 levels were more likely to report consuming less than one fish meal per month (40.3%) than were women in the highest three quartiles (26.3%, P<.001).
CONCLUSION: Moderate fish intake (up to three meals per week) before 22 weeks of gestation was associated with a reduction in repeat preterm birth. More than moderate consumption did not confer additional benefit. These results support the recommendations of the U. S. Food and Drug Administration and the American Congress of Obstetricians and Gynecologists for fish consumption during pregnancy.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00135902. (Obstet Gynecol 2011; 117: 1071-7) DOI: 10.1097/AOG.0b013e31821645dc
C1 [Klebanoff, Mark A.] Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
Wake Forest Univ Hlth Sci, Dept Obstet, Winston Salem, NC USA.
Wake Forest Univ Hlth Sci, Dept Gynecol, Winston Salem, NC USA.
George Washington Univ, Ctr Biostat, Washington, DC USA.
Univ N Carolina, Chapel Hill, NC USA.
Wayne State Univ, Detroit, MI USA.
Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA.
Columbia Univ, New York, NY USA.
Brown Univ, Women & Infants Hosp, Providence, RI USA.
Univ Pittsburgh, Pittsburgh, PA USA.
Ohio State Univ, Columbus, OH 43210 USA.
Northwestern Univ, Chicago, IL 60611 USA.
Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA.
Drexel Univ, Coll Med, Philadelphia, PA 19104 USA.
Univ Alabama, Birmingham, AL USA.
Univ Texas Houston, Houston, TX USA.
Univ Texas Med Branch, Galveston, TX USA.
RP Klebanoff, MA (reprint author), Nationwide Childrens Hosp, Res Inst, Room W285,700 Childrens Dr, Columbus, OH 43205 USA.
EM Mark.Klebanoff@nationwidechildrens.org
RI Varner, Michael/K-9890-2013
OI caritis, steve/0000-0002-2169-0712; Peaceman, Alan/0000-0002-4515-4850;
Varner, Michael/0000-0001-9455-3973
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [HD27860, HD27917, HD40560, HD34208, HD40485, HD21410,
HD27915, HD40500, HD40512, HD40544, MO1-RR-000080, HD34136, HD27869,
HD40545, HD36801, HD19897]
FX Supported by grants from the Eunice Kennedy Shriver National Institute
of Child Health and Human Development (HD27860, HD27917, HD40560,
HD34208, HD40485, HD21410, HD27915, HD40500, HD40512, HD40544,
MO1-RR-000080, HD34136, HD27869, HD40545, HD36801, and HD19897) and does
not necessarily represent the official views of the NICHD or the
National Institutes of Health.
NR 28
TC 15
Z9 17
U1 1
U2 13
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 MAY
PY 2011
VL 117
IS 5
BP 1071
EP 1077
DI 10.1097/AOG.0b013e31821645dc
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 753KF
UT WOS:000289771000007
PM 21508745
ER
PT J
AU Manuck, TA
Lai, YL
Meis, PJ
Sibai, B
Spong, CY
Rouse, DJ
Iams, JD
Caritis, SN
O'Sullivan, MJ
Wapner, RJ
Mercer, B
Ramin, SM
Peaceman, AM
AF Manuck, Tracy A.
Lai, Yinglei
Meis, Paul J.
Sibai, Baha
Spong, Catherine Y.
Rouse, Dwight J.
Iams, Jay D.
Caritis, Steve N.
O'Sullivan, Mary J.
Wapner, Ronald J.
Mercer, Brian
Ramin, Susan M.
Peaceman, Alan M.
CA Eunice Kennedy Shriver Natl Inst
TI Admixture Mapping to Identify Spontaneous Preterm Birth Susceptibility
Loci in African Americans
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID GENE DISCOVERY; DISEASE GENES; DELIVERY; RISK; TRAITS; WOMEN; SNP
AB OBJECTIVE: Preterm birth is 1.5 times more common in African American (17.8%) than European American women (11.5%), even after controlling for confounding variables. We hypothesize that genetic factors may account for this disparity and can be identified by admixture mapping.
METHODS: This is a secondary analysis of women with at least one prior spontaneous preterm birth enrolled in a multicenter prospective study. DNA was extracted and whole-genome amplified from stored saliva samples. Self-identified African American patients were geno-typed with a 1,509 single nucleotide polymorphism (SNP) commercially available admixture panel. A logarithm of odds locus-genome score of 1.5 or higher was considered suggestive and 2 or higher was considered significant for a disease locus.
RESULTS: One hundred seventy-seven African American women with one or more prior spontaneous preterm births were studied. One thousand four hundred fifty SNPs were in Hardy-Weinberg equilibrium and passed quality filters. Individuals had a mean of 78.3% to 87.9% African American ancestry for each SNP. A locus on chromosome 7q21-22 was suggestive of an association with spontaneous preterm birth before 37 weeks of gestation (three SNPs with logarithm of odds scores 1.50-1.99). This signal strengthened when women with at least one preterm birth before 35.0 (eight SNPs with logarithm of odds scores greater than 1.50) and before 32.0 weeks of gestation were considered (15 SNPs with logarithm of odds scores greater than 1.50). No other areas of the genome had logarithm of odds scores higher than 1.5.
CONCLUSION: Spontaneous preterm birth in African American women may be genetically mediated by a susceptibility locus on chromosome 7. This region contains multiple potential candidate genes, including collagen type 1-alpha-2 gene and genes involved with calcium regulation. (Obstet Gynecol 2011; 117: 1078-84) DOI: 10.1097/AOG.0b013e318214e67f
C1 Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA.
Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
Univ Tennessee, Memphis, TN USA.
Univ Alabama, Birmingham, AL USA.
Ohio State Univ, Columbus, OH 43210 USA.
Univ Pittsburgh, Pittsburgh, PA USA.
Univ Miami, Miami, FL USA.
Drexel Univ, Philadelphia, PA 19104 USA.
Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA.
Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
Northwestern Univ, Chicago, IL 60611 USA.
George Washington Univ, Ctr Biostat, Washington, DC USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Manuck, TA (reprint author), 30 North,1900 East,Room 2B200, Salt Lake City, UT 84132 USA.
EM tracy.manuck@hsc.utah.edu
OI caritis, steve/0000-0002-2169-0712; Peaceman, Alan/0000-0002-4515-4850
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [HD27860, HD36801, HD27917, HD21414, HD27861,
HD27869, HD27905, HD34208, HD34116, HD21410, HD27915, HD34136, HD34210,
HD34122, HD40500, HD40544, HD40560, HD40512]
FX Supported by grants from the Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD) (HD27860, HD36801,
HD27917, HD21414, HD27861, HD27869, HD27905, HD34208, HD34116, HD21410,
HD27915, HD34136, HD34210, HD34122, HD40500, HD40544, HD34116, HD40560,
HD40512) and does not necessarily represent the official views of the
NICHD or the National Institutes of Health.
NR 30
TC 10
Z9 11
U1 0
U2 1
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 MAY
PY 2011
VL 117
IS 5
BP 1078
EP 1084
DI 10.1097/AOG.0b013e318214e67f
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 753KF
UT WOS:000289771000008
PM 21508746
ER
PT J
AU Hoye, BJ
Munster, VJ
Nishiura, H
Fouchier, RAM
Madsen, J
Klaassen, M
AF Hoye, Bethany J.
Munster, Vincent J.
Nishiura, Hiroshi
Fouchier, Ron A. M.
Madsen, Jesper
Klaassen, Marcel
TI Reconstructing an annual cycle of interaction: natural infection and
antibody dynamics to avian influenza along a migratory flyway
SO OIKOS
LA English
DT Article
ID A VIRUSES; NORTH-AMERICA; AQUATIC BIRDS; LONG-TERM; WEST-NILE;
WATERFOWL; SURVEILLANCE; PREVALENCE; GEESE; PARAMYXOVIRUSES
AB Migratory animals may play an important role in connecting disparate ecosystems, including the introduction of various pathogens. The incidence of these pathogens may vary over time and space, such that events along the entire migratory flyway are likely to be important in the interaction between pathogens and their migratory hosts. On this premise, the annual cycle of a naturally occurring host-pathogen system was reconstructed by examining infection with and antibodies to avian influenza virus along the flyway of a long-distance Arctic migrant, the Svalbard-breeding pink-footed goose Anser brachyrhynchus. A highly-localized transmission period was identified in winter, in contrast to the north-south decline expected from dabbling ducks, indicating the dynamics of infection may differ among host species. In spring, 63% (95% CI: 57.1, 68.9) of adults had detectable antibodies to the nucleoprotein of avian influenza virus, compared to just 15% (95% CI: 8.7, 23.4) of juveniles, suggesting inter-annual antibody maintenance. Nevertheless, adult seroprevalence declined by approximately 30% from spring to late summer, indicating significant seroreversion in the population. Integrating these findings in an epidemiological model, detectable antibodies to nucleoprotein were estimated to persist for just 343 days (95% CI: 221, 607); considerably shorter than for other wildlife diseases in long-lived bird species. The investigation of wildlife diseases in migratory populations is an inherently complex task, yet, by integrating disease incidence and seroprevalence along a migratory flyway, our findings suggest that the ecological interactions and life history of the host, as well as the life-history of the pathogen, can influence the dynamics of infection and host immune response.
C1 [Hoye, Bethany J.] Netherlands Inst Ecol NIOO KNAW, Dept Anim Ecol, NL-3631 AC Nieuwersluis, Netherlands.
[Klaassen, Marcel] Deakin Univ, Ctr Integrat Ecol, Sch Life & Environm Sci, Geelong, Vic 3217, Australia.
[Munster, Vincent J.; Fouchier, Ron A. M.] Erasmus MC, Dept Virol, NL-3000 CA Rotterdam, Netherlands.
[Munster, Vincent J.] NIAID, Virol Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Nishiura, Hiroshi] Univ Utrecht, NL-3584 CL Utrecht, Netherlands.
[Nishiura, Hiroshi] Japan Sci & Technol Agcy, PRESTO, Saitama, Japan.
[Madsen, Jesper] Aarhus Univ, Dept Arctic Environm, Natl Environm Res Inst, DK-4000 Roskilde, Denmark.
RP Hoye, BJ (reprint author), Netherlands Inst Ecol NIOO KNAW, Dept Anim Ecol, Rijksstr Weg 6, NL-3631 AC Nieuwersluis, Netherlands.
EM b.hoye@nioo.knaw.nl
RI Klaassen, Marcel/B-4325-2008; Hoye, Bethany/A-4486-2010; Madsen,
Jesper/J-7853-2013; Fouchier, Ron/A-1911-2014;
OI Munster, Vincent/0000-0002-2288-3196; Klaassen,
Marcel/0000-0003-3907-9599; Hoye, Bethany/0000-0001-9502-5582; Madsen,
Jesper/0000-0003-3246-0215; Fouchier, Ron/0000-0001-8095-2869; Nishiura,
Hiroshi/0000-0003-0941-8537
FU Netherlands Organisation for Scientific Research (NWO) [851.40.073,
851.40.074]; EU [044490]; NIAIDNIH [HHSN266200700010C]; JST PRESTO;
Danish Forest and Nature Agency
FX We would like to thank Pascal Lexmond and Chantal Baas for excellent
laboratory assistance; Eckhart Kuijken, Christine Verscheure, Fred
Cottaar and Per Ivar Nicolaisen for invaluable local knowledge of the
goose stopover sites; and Silke Bauer for valuable comments on an
earlier version of this manuscript. This study was supported through the
Bird Health programme within the International Polar Year by the
Netherlands Organisation for Scientific Research (NWO; grant 851.40.073
and 851.40.074), EU Framework six program NewFluBird (044490), contract
NIAIDNIH HHSN266200700010C, JST PRESTO program, and the Danish Forest
and Nature Agency. The Governor of Svalbard kindly gave permission to
catch geese in Svalbard. This is publication 4875 of the Netherlands
Institute of Ecology (NIOO-KNAW).
NR 52
TC 39
Z9 39
U1 4
U2 39
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0030-1299
J9 OIKOS
JI Oikos
PD MAY
PY 2011
VL 120
IS 5
BP 748
EP 755
DI 10.1111/j.1600-0706.2010.18961.x
PG 8
WC Ecology
SC Environmental Sciences & Ecology
GA 753BW
UT WOS:000289740200012
ER
PT J
AU Lubet, RA
Lu, Y
Bode, AM
You, M
Verney, ZM
Steele, VE
Townsend, R
Juliana, MM
Grubbs, CJ
AF Lubet, Ronald A.
Lu, Yan
Bode, Ann M.
You, Ming
Verney, Zoe M.
Steele, Vernon E.
Townsend, Reid
Juliana, M. Margaret
Grubbs, Clinton J.
TI Efficacy of the EGFr inhibitor Iressa on development of
chemically-induced urinary bladder cancers: Dose dependency and
modulation of biomarkers
SO ONCOLOGY REPORTS
LA English
DT Article
DE hydroxybutyl(butyl)nitrosamine; epidermal growth factor receptor
inhibitors; urinary bladder cancer
ID DIFFERENCE GEL-ELECTROPHORESIS; TRANSITIONAL-CELL CARCINOMA; EXPRESSION
PROFILES; MAMMARY CANCERS; PHOSPHORYLATION; RECEPTORS; TUMORS
AB The effects of the EGFr inhibitor Iressa on development of urinary bladder cancers induced by hydroxybutyl(butyl) nitrosamine (OH-BBN) in rats were examined. Iressa treatment (4.5 or 1.5 mg/kg BW/day) beginning one week after the last dose of OH-BBN decreased the occurrence of large (>200 mg) bladder cancers at termination of the study by 75 and 52%, respectively. Treatment with Iressa (10 mg/kg BW/day) beginning one week or three months (delayed initiation) after the last dose of OH-BBN also significantly increased tumor latency and decreased the incidence of palpable bladder cancers. In the delayed initiation study, microscopic cancers already existed when treatment was initiated; implying that the effects of Iressa occur late in tumor progression. Potential pharmacodynamics and/or efficacy biomarkers modulated by short-term exposure (5 day) to Iressa (10 mg/kg BW/day) were determined in palpable bladder lesions by using three different approaches: i) direct immunohistochemical examination of EGFr related proteins; which showed that phosphorylated EGFr, AKT and ERK were significantly decreased; ii) measurement of protein expression by two dimensional gel electrophoresis and tandem mass spectrometry. This showed that the Annex in A2, MAP kinase kinase and nucleolin (all proteins associated with the VEGF pathway) were decreased in treated tumors; and iii) measurement of gene expression determined in gene microarrays demonstrated that numerous pathways were markedly altered by Iressa treatment. In particular, cell cycle genes related to the anaphase protein complex (APC) pathway, including CDC 20, cyclin B1, BUB1 and both of the Aurora kinases, were significantly decreased.
C1 [Lubet, Ronald A.; Steele, Vernon E.] NCI, Canc Prevent Div, Rockville, MD 20852 USA.
[Lu, Yan; You, Ming] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA.
[Bode, Ann M.; Townsend, Reid] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA.
[Verney, Zoe M.] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA.
[Juliana, M. Margaret] Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35294 USA.
[Grubbs, Clinton J.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA.
RP Lubet, RA (reprint author), NCI, Canc Prevent Div, Execut Plaza N,Suite 2110,6130 Execut Blvd, Rockville, MD 20852 USA.
EM lubetr@mail.nih.gov
NR 23
TC 6
Z9 6
U1 0
U2 0
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1021-335X
EI 1791-2431
J9 ONCOL REP
JI Oncol. Rep.
PD MAY
PY 2011
VL 25
IS 5
BP 1389
EP 1397
DI 10.3892/or.2011.1200
PG 9
WC Oncology
SC Oncology
GA 753YS
UT WOS:000289817300024
PM 21369704
ER
PT J
AU Oh, KS
Imoto, K
Emmert, S
Tamura, D
DiGiovanna, JJ
Kraemer, KH
AF Oh, Kyu-Seon
Imoto, Kyoko
Emmert, Steffen
Tamura, Deborah
DiGiovanna, John J.
Kraemer, Kenneth H.
TI Nucleotide Excision Repair Proteins Rapidly Accumulate but Fail to
Persist in Human XP-E (DDB2 Mutant) Cells
SO PHOTOCHEMISTRY AND PHOTOBIOLOGY
LA English
DT Article
ID PIGMENTOSUM GROUP-E; DNA-BINDING-PROTEIN; UV-DAMAGED DNA; CYCLOBUTANE
PYRIMIDINE DIMERS; UBIQUITIN LIGASE COMPLEX; XERODERMA-PIGMENTOSUM; 6-4
PHOTOPRODUCTS; INDUCED UBIQUITYLATION; IN-VIVO; RECOGNITION
AB The xeroderma pigmentosum (XP-E) DNA damage binding protein (DDB2) is involved in early recognition of global genome DNA damage during DNA nucleotide excision repair (NER). We found that skin fibroblasts from four newly reported XP-E patients with numerous skin cancers and DDB2 mutations had slow repair of 6-4 photoproducts (6-4PP) and markedly reduced repair of cyclobutane pyrimidine dimers (CPD). NER proteins (XPC, XPB, XPG, XPA and XPF) colocalized to CPD and 6-4PP positive regions immediately (<0.1 h) after localized UV irradiation in cells from the XP-E patients and normal controls. While these proteins persist in normal cells, surprisingly, within 0.5 h these repair proteins were no longer detectable at the sites of DNA damage in XP-E cells. Our results indicate that DDB2 is not required for the rapid recruitment of NER proteins to sites of UV photoproducts or for partial repair of 6-4PP but is essential for normal persistence of these proteins for CPD photoproduct removal.
C1 [Oh, Kyu-Seon; Imoto, Kyoko; Tamura, Deborah; DiGiovanna, John J.; Kraemer, Kenneth H.] NCI, DNA Repair Sect, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Emmert, Steffen] Univ Gottingen, Dept Dermatol Venerol & Allergol, Gottingen, Germany.
RP Kraemer, KH (reprint author), NCI, DNA Repair Sect, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM kraemerk@nih.gov
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health; Deutsche Krebshilfe; Deutsche
Forschungsgemeinschaft
FX This research was supported in part by the Intramural Research Program
of the Center for Cancer Research, National Cancer Institute, National
Institutes of Health. This research was supported in part by the
Deutsche Krebshilfe and the Deutsche Forschungsgemeinschaft (to S. E.).
We thank Drs. Kiyoji Tanaka, Osaka University and Leon Mullenders,
Leiden University for insightful comments. We thank the patients for
their participation.
NR 33
TC 5
Z9 5
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 MAY-JUN
PY 2011
VL 87
IS 3
BP 729
EP 733
DI 10.1111/j.1751-1097.2011.00909.x
PG 5
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 753LD
UT WOS:000289774200031
PM 21388382
ER
PT J
AU Gozzi, M
Cherubini, P
Papagno, C
Bricolo, E
AF Gozzi, Marta
Cherubini, Paolo
Papagno, Costanza
Bricolo, Emanuela
TI Recruitment of intuitive versus analytic thinking strategies affects the
role of working memory in a gambling task
SO PSYCHOLOGICAL RESEARCH-PSYCHOLOGISCHE FORSCHUNG
LA English
DT Article
ID SOMATIC MARKER HYPOTHESIS; SYLLOGISTIC-REASONING TASKS; DECISION-MAKING;
PREFRONTAL CORTEX; 2 SYSTEMS; PERFORMANCE; CHOICE; DAMAGE; CONSEQUENCES;
RATIONALITY
AB Previous studies found mixed results concerning the role of working memory (WM) in the gambling task (GT). Here, we aimed at reconciling inconsistencies by showing that the standard version of the task can be solved using intuitive strategies operating automatically, while more complex versions require analytic strategies drawing on executive functions. In Study 1, where good performance on the GT could be achieved using intuitive strategies, participants performed well both with and without a concurrent WM load. In Study 2, where analytical strategies were required to solve a more complex version of the GT, participants without WM load performed well, while participants with WM load performed poorly. In Study 3, where the complexity of the GT was further increased, participants in both conditions performed poorly. In addition to the standard performance measure, we used participants' subjective expected utility, showing that it differs from the standard measure in some important aspects.
C1 [Gozzi, Marta] NIMH, Pediat & Dev Neurosci Branch, NIH, Bethesda, MD 20892 USA.
[Gozzi, Marta; Cherubini, Paolo; Papagno, Costanza; Bricolo, Emanuela] Univ Milano Bicocca, Dipartimento Psicol, Milan, Italy.
RP Gozzi, M (reprint author), NIMH, Pediat & Dev Neurosci Branch, NIH, 10 Ctr Dr,MSC 1255,Bldg 10,Room 4N208, Bethesda, MD 20892 USA.
EM gozzim@mail.nih.gov
RI papagno, costanza/K-8460-2012
OI papagno, costanza/0000-0002-3659-6294
NR 52
TC 3
Z9 3
U1 1
U2 5
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-0727
J9 PSYCHOL RES-PSYCH FO
JI Psychol. Res.-Psychol. Forsch.
PD MAY
PY 2011
VL 75
IS 3
BP 188
EP 201
DI 10.1007/s00426-010-0296-1
PG 14
WC Psychology, Experimental
SC Psychology
GA 749QV
UT WOS:000289484800003
PM 20697767
ER
PT J
AU Scichilone, N
Callari, A
Augugliaro, G
Marchese, M
Togias, A
Bellia, V
AF Scichilone, Nicola
Callari, Adriana
Augugliaro, Giuseppe
Marchese, Margherita
Togias, Alkis
Bellia, Vincenzo
TI The impact of age on prevalence of positive skin prick tests and
specific IgE tests
SO RESPIRATORY MEDICINE
LA English
DT Review
DE Immunoglobulin E; Skin testing; Asthma; Allergen; Aging
ID QUALITY-OF-LIFE; TOTAL SERUM IGE; COMMUNITY POPULATION-SAMPLE; TEST
REACTIVITY; AIRWAY HYPERRESPONSIVENESS; IMMUNOGLOBULIN-E; ASTHMA
SEVERITY; IMMUNE-SYSTEM; OLDER-ADULTS; RHINITIS
AB Aging is associated with modifications of the immune system, defined as immunosenescence. This could contribute to a reduced prevalence of allergic disease in the elderly population. In this regard, atopy has rarely been considered in the clinical assessment of the geriatric respiratory patient. This article is a review of the available literature assessing the impact of age on atopy. In the majority of papers, we found a lower prevalence of atopy in the most advanced ages, both in healthy subjects and in individuals affected by allergic respiratory diseases. Unfortunately, no large, longitudinal studies performed in the general population have been conducted to further explore this observation. Although available data seem to favor the decline of allergen sensitization with age, the prevalence of allergic sensitizations in the elderly population with respiratory symptoms is substantial enough to warrant evaluation of the atopic condition. From a clinical perspective, allergic reactions in older adults can have the same or even worse manifestations compared to young people. For this reasons, the evaluation of the atopic condition also in the geriatric patient is recommended. Thus, the role of atopy as it pertains to the diagnosis, therapy (adoption of preventive measure such as removal of environmental allergen or immunotherapy), and prognosis (influence on morbidity and mortality) of chronic respiratory illnesses in the elderly is addressed. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Scichilone, Nicola; Callari, Adriana; Augugliaro, Giuseppe; Marchese, Margherita; Bellia, Vincenzo] Univ Palermo, Dipartimento Biomed Med Interna & Specialist DIBI, Sez Pneumol, Villa Sofia Cervello Hosp, I-90146 Palermo, Italy.
[Togias, Alkis] NIAD, NIH, Bethesda, MD USA.
RP Scichilone, N (reprint author), Univ Palermo, Div Pulmonol DIBIMIS, Dept Internal Med, Villa Sofia Cervello Hosp, Via Trabucco 180, I-90146 Palermo, Italy.
EM n.scichilone@libero.it
OI Scichilone, Nicola/0000-0001-6400-6573
NR 58
TC 31
Z9 34
U1 0
U2 3
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0954-6111
J9 RESP MED
JI Respir. Med.
PD MAY
PY 2011
VL 105
IS 5
BP 651
EP 658
DI 10.1016/j.rmed.2010.12.014
PG 8
WC Cardiac & Cardiovascular Systems; Respiratory System
SC Cardiovascular System & Cardiology; Respiratory System
GA 753XN
UT WOS:000289814000001
PM 21220195
ER
PT J
AU Roberson, R
Kuddo, T
Benassou, I
Abebe, D
Spong, C
AF Roberson, Robin
Kuddo, Thea
Benassou, Ines
Abebe, Daniel
Spong, Catherine
TI Neuroprotective fractalkine in fetal alcohol syndrome
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE fetal alcohol syndrome; fractalkine; NAPVSIPQ; SALLRSIPA
ID MOUSE MODEL; PREVENTION; CYTOKINE; RECEPTOR
AB OBJECTIVE: Neuroprotective peptides (SALLRSIPA [SAL] and NAPV-SIPQ [NAP]) can prevent some alcohol-induced damage in fetal alcohol syndrome (FAS). Fractalkine, a chemokine constitutively expressed in the central nervous system reduces neuronal death from activated microglia. Using a model of FAS, we evaluated whether fractalkine is altered and whether NAP + SAL work through fractalkine.
STUDY DESIGN: With an FAS model, C57BL6/J-mice were treated on gestational day 8 with alcohol (0.03 mL/g), placebo, or alcohol + peptides. Embryos were harvested after 6 hours and 10 days later. Fractalkine was measured in the protein lysate. Statistical analysis included the Kruskal-Wallis test.
RESULTS: Fractalkine was significantly elevated at 6 hours (median, 341pg/mL; range, 263-424 pg/mL) vs controls (median, 228 pg/mL; range, 146 -332 pg/mL; P < .001). NAP + SAL prevented the alcohol-induced increase (median, 137 pg/mL; range, 97-255 pg/mL; P < .001). Ten days later, fractalkine levels were similar in all groups (P = .7).
CONCLUSION: Prenatal alcohol exposure acutely elevates fractalkine, perhaps in an effort to counter the alcohol toxicity. Pretreatment with NAP + SAL prevents the acute increase in fractalkine.
C1 [Roberson, Robin; Kuddo, Thea; Benassou, Ines; Abebe, Daniel; Spong, Catherine] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Perinatal & Dev Neurobiol, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
RP Roberson, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Perinatal & Dev Neurobiol, Div Intramural Res, NIH, Bldg 9 1W125 & 1W116, Bethesda, MD 20892 USA.
EM robersor@mail.nih.gov
FU Intramural NIH HHS [Z99 HD999999]
NR 16
TC 1
Z9 1
U1 0
U2 5
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 MAY
PY 2011
VL 204
IS 5
AR 400.e1
DI 10.1016/j.ajog.2011.03.034
PG 3
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 758YZ
UT WOS:000290206200023
PM 21572545
ER
PT J
AU Gautam, P
Zhao, LP
Patel, P
AF Gautam, Pawan
Zhao, Linping
Patel, Pravin
TI Determining the osteotomy pattern in surgically assisted rapid maxillary
expansion in a unilateral palatal cleft A finite element model approach
SO ANGLE ORTHODONTIST
LA English
DT Article
DE Surgically assisted rapid maxillary expansion; Finite element analysis
ID TRANSPALATAL DISTRACTION; SURGERY; MANAGEMENT; DEFICIENCY
AB Objectives: To evaluate the stress pattern in the craniofacial skeleton in a patient with unilateral cleft deformity of the secondary palate and alveolus in response to various techniques of surgically assisted rapid maxillary expansion (SARME).
Materials and Methods: Three patient-specific composite skull models were developed for finite element model analysis. The details of the modeling procedure have been described in Part I of this series. The finite element analysis was performed on each model with a specified SARME technique in combination with RME using Abaqus (6.7).
Results: The ideal form of surgery in SARME for patients with unilateral cleft deformity of the secondary palate and alveolus would be complete unilateral Le Fort I with pterygoid dysjunction in combination with midpalatal split, followed by isolated midpalatal split and zygomatic buttress osteotomies.
Conclusions: A more invasive SARME technique can significantly reduce the resultant stresses. However, this benefit should be weighed against the risk of increasing complications associated with more extensive surgeries. When a more conservative surgical technique is selected, it would be preferable to perform a midpalatal split rather than zygomatic buttress osteotomies, as indicated by the stress-strain distribution and displacement pattern associated with different SARME techniques. (Angle Orthod. 2011;81:410-419.)
C1 [Gautam, Pawan; Zhao, Linping; Patel, Pravin] Univ Illinois, Craniofacial Ctr, Chicago, IL 60612 USA.
[Gautam, Pawan] NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
RP Gautam, P (reprint author), Univ Illinois, Craniofacial Ctr, MC 588,811 S Paulina St, Chicago, IL 60612 USA.
NR 20
TC 2
Z9 2
U1 2
U2 7
PU E H ANGLE EDUCATION RESEARCH FOUNDATION, INC
PI NEWTON N
PA 1615 BEACON ST, NEWTON N, MA 02468-1507 USA
SN 0003-3219
J9 ANGLE ORTHOD
JI Angle Orthod.
PD MAY
PY 2011
VL 81
IS 3
BP 410
EP 419
DI 10.2319/070110-369.1
PG 10
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 753HB
UT WOS:000289761800008
PM 21299391
ER
PT J
AU Kaplan, BB
AF Kaplan, Barry B.
TI MicroRNA-Mediated Regulation of Translation of Axonal Nuclear-Encoded
mRNAs and the Modulation of Local Mitochondrial Activity and Axonal
Growth
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Kaplan, Barry B.] NIMH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 14
BP 5S
EP 5S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800015
ER
PT J
AU Barr, CS
AF Barr, Christina S.
TI Across-Species Genetic Variation and Epigenetic Regulation of
SLC6A4-Relevance to Genetic Selection and GxE Interactions
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Barr, Christina S.] NIAAA, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 31
BP 10S
EP 10S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800032
ER
PT J
AU Dudek, SM
AF Dudek, Serena M.
TI Synaptic Plasticity, and the Lack Thereof, in Hippocampal CA2
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Dudek, Serena M.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 70
BP 19S
EP 19S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800063
ER
PT J
AU Pine, DS
AF Pine, Daniel S.
TI Ventral-Prefrontal-Amygdala Circuitry Function in Pediatric Anxiety
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Pine, Daniel S.] NIMH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
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 MAY 1
PY 2011
VL 69
IS 9
SU S
MA 68
BP 19S
EP 19S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800061
ER
PT J
AU Kar, AN
Gioio, AE
Natera-Naranjo, O
Kaplan, BB
AF Kar, Amar N.
Gioio, Anthony E.
Natera-Naranjo, Orlangie
Kaplan, Barry B.
TI Local Synthesis of Eukaryotic Translation Initiation Factors (EIF)
EIF2B2 and EIF4G2 Regulates Axonal Growth and Elongation in Rat
Sympathetic Neurons
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Kar, Amar N.; Gioio, Anthony E.; Natera-Naranjo, Orlangie; Kaplan, Barry B.] NIMH, Mol Biol Lab, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 117
BP 32S
EP 32S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800102
ER
PT J
AU Shamir, A
Karavanov, I
Vullhorst, D
Buonanno, A
AF Shamir, Alon
Karavanov, Irina
Vullhorst, Detlef
Buonanno, Andres
TI Behavioral Characterization of Mice Harboring a Complete or Targeted
Mutation of ErbB4 Receptor
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Shamir, Alon; Karavanov, Irina; Vullhorst, Detlef; Buonanno, Andres] NICHD, Mol Neurobiol Sect, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 199
BP 57S
EP 57S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800184
ER
PT J
AU Muse, J
Mattay, VS
Das, S
Burdick, M
Kolachana, B
Callicott, JH
Weinberger, DR
AF Muse, John
Mattay, Venkata S.
Das, Saumitra
Burdick, Madeline
Kolachana, Bhaskar
Callicott, Joseph H.
Weinberger, Daniel R.
TI Functional Polymorphisms in Catechol-O-methyltransferase and KCNH2 Genes
Modulate Age-Related Changes in Working Memory Function
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Muse, John; Mattay, Venkata S.; Das, Saumitra; Burdick, Madeline; Kolachana, Bhaskar; Callicott, Joseph H.; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 MAY 1
PY 2011
VL 69
IS 9
SU S
MA 233
BP 67S
EP 67S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800218
ER
PT J
AU Killgore, WD
Rosso, IM
Britton, JC
Schwab, ZJ
Weiner, MR
Rauch, SL
AF Killgore, William D.
Rosso, Isabelle M.
Britton, Jennifer C.
Schwab, Zachary J.
Weiner, Melissa R.
Rauch, Scott L.
TI Cortico-Limbic Activation Differentiates Among Anxiety Disorders with
and without a Generalized Threat Response
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Killgore, William D.; Rosso, Isabelle M.; Schwab, Zachary J.; Weiner, Melissa R.; Rauch, Scott L.] McLean Hosp, Belmont, MA 02178 USA.
[Britton, Jennifer C.] NIMH, Bethesda, MD 20892 USA.
RI Britton, Jennifer/J-4501-2013
NR 0
TC 0
Z9 0
U1 0
U2 2
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 MAY 1
PY 2011
VL 69
IS 9
SU S
MA 254
BP 74S
EP 74S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800239
ER
PT J
AU Robinson, OJ
Charney, D
Overstreet, C
Vytal, K
Grillon, C
AF Robinson, Oliver J.
Charney, Danielle
Overstreet, Cassie
Vytal, Katherine
Grillon, Christian
TI The Neural Basis of Negative Affective Biases under Anxiety
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Robinson, Oliver J.; Charney, Danielle; Overstreet, Cassie; Vytal, Katherine; Grillon, Christian] NIMH, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 263
BP 77S
EP 77S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800248
ER
PT J
AU Cheon, YW
Modi, HR
Park, JY
Kim, HW
Chang, LS
Rao, JS
Rapoport, SI
AF Cheon, Yewon
Modi, Hiren R.
Park, Jee-Young
Kim, Hyung-Wook
Chang, Lisa
Rao, Jagadeesh S.
Rapoport, Stanley I.
TI Olanzapine Decreases Brain Arachidonic Acid (AA) Metabolism in Rats by
Reducing Plasma Availability of AA
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Cheon, Yewon; Modi, Hiren R.; Park, Jee-Young; Kim, Hyung-Wook; Chang, Lisa; Rao, Jagadeesh S.; Rapoport, Stanley I.] NIA, BPMS, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 327
BP 97S
EP 97S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800312
ER
PT J
AU Leibenluft, E
AF Leibenluft, Ellen
TI Clinical, Pathophysiological, and Genetic Associations Between
Non-episodic Irritability in Youth and Unipolar Depression in Adulthood
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Leibenluft, Ellen] NIMH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 MAY 1
PY 2011
VL 69
IS 9
SU S
MA 335
BP 100S
EP 101S
PG 2
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800320
ER
PT J
AU Cadet, JL
AF Cadet, Jean Lud
TI The Potential Primacy of Cognitive Disturbances in Substance Abuse
Disorders and Co-morbid States: Relevance to Treatment
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Cadet, Jean Lud] NIDA, Intramural Res Program, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 346
BP 104S
EP 104S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800331
ER
PT J
AU Du, J
AF Du, Jing
TI Glutamatergic Synaptic Plasticity: A Window into Mood Disorders
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Du, Jing] NIMH, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 391
BP 116S
EP 116S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800368
ER
PT J
AU Laje, G
AF Laje, Gonzalo
TI Can Genetic Variation Predict Response to Ketamine Treatment?
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Laje, Gonzalo] NIMH, Human Genet Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 392
BP 116S
EP 116S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800369
ER
PT J
AU Taha, AY
Kim, HW
Hamadani, A
Tragon, T
Ramadan, E
Chen, G
Rapoport, SI
Rao, JS
AF Taha, Ameer Y.
Kim, Hyung-Wook
Hamadani, Anahita
Tragon, Tyson
Ramadan, Epolia
Chen, Guang
Rapoport, Stanley I.
Rao, Jagadeesh S.
TI Chronic N-methyl D-aspartate Administration Induces "Bipolar-like"
Behavioral Changes in Rats
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Taha, Ameer Y.; Kim, Hyung-Wook; Ramadan, Epolia; Rapoport, Stanley I.; Rao, Jagadeesh S.] NIA, NIH, Bethesda, MD 20892 USA.
[Hamadani, Anahita; Tragon, Tyson; Chen, Guang] NIMH, NIH, Bethesda, MD 20892 USA.
RI Chen, Guang/A-2570-2017
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 432
BP 128S
EP 129S
PG 2
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800409
ER
PT J
AU Thomas, LA
Rosen, BH
Bones, BL
Pine, DS
Leibenluft, E
AF Thomas, Laura A.
Rosen, Brooke H.
Bones, Brian L.
Pine, Daniel S.
Leibenluft, Ellen
TI Parametric Modulation of Amygdala Activity by Emotion in Youth with
Bipolar Disorder, Severe Mood Dysregulation, and Controls
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Thomas, Laura A.; Rosen, Brooke H.; Bones, Brian L.; Pine, Daniel S.; Leibenluft, Ellen] NIMH, Emot & Dev Branch, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 476
BP 142S
EP 142S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800453
ER
PT J
AU Kattan, GC
Cui, LH
Merikangas, KR
AF Kattan, Gabriela C.
Cui, Lihong
Merikangas, Kathleen R.
TI Service Patterns for Youth with Bipolar Disorder: Results from the
National Comorbidity Survey - Adolescent Supplement (NCS-A)
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Kattan, Gabriela C.; Cui, Lihong; Merikangas, Kathleen R.] NIMH, Sect Dev Genet Epidemiol, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 MAY 1
PY 2011
VL 69
IS 9
SU S
MA 496
BP 148S
EP 148S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800472
ER
PT J
AU Raila, H
Jabbi, M
Kohn, P
Nash, T
Cropp, B
Mattay, R
Zhang, J
Kippenhan, JS
Berman, KF
AF Raila, Hannah
Jabbi, Mbemba
Kohn, Philip
Nash, Tiffany
Cropp, Brett
Mattay, Raghav
Zhang, James
Kippenhan, J. Shane
Berman, Karen F.
TI Behavioral Activation and Inhibition Tendencies Predict Differential
BOLD Response to Reward and Loss
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Raila, Hannah; Jabbi, Mbemba; Kohn, Philip; Nash, Tiffany; Cropp, Brett; Mattay, Raghav; Zhang, James; Kippenhan, J. Shane; Berman, Karen F.] NIMH, Sect Integrat Neuroimaging, Clin Brain Disorders Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 535
BP 160S
EP 160S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800511
ER
PT J
AU Ramadan, E
Basselin, M
Taha, A
Cheon, Y
Rapoport, SI
AF Ramadan, Epolia
Basselin, Mireille
Taha, Ameer
Cheon, Yewon
Rapoport, Stanley I.
TI Chronic Valproate Blocks D2-like Receptor-Mediated Brain Signaling via
Arachidonic Acid in Unanesthetized Rats
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Ramadan, Epolia; Basselin, Mireille; Taha, Ameer; Cheon, Yewon; Rapoport, Stanley I.] NIA, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 573
BP 172S
EP 172S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800549
ER
PT J
AU Schmitz, A
Duncko, R
Grillon, C
Merikangas, KR
AF Schmitz, Anja
Duncko, Roman
Grillon, Christian
Merikangas, Kathleen R.
TI The Nociceptive Eyeblink Reflex is Altered in Migraine with Aura, but
not in Major Depression
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Schmitz, Anja; Duncko, Roman; Grillon, Christian; Merikangas, Kathleen R.] NIMH, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 627
BP 190S
EP 190S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800603
ER
PT J
AU Goldman, D
AF Goldman, David
TI A Common, Population Specific Stop Codon in the Human HTR2B Gene Found
by Resequencing
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Goldman, David] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 664
BP 201S
EP 201S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800640
ER
PT J
AU Bevilacqua, L
AF Bevilacqua, Laura
TI Common and Rare Genetic Variation at the HTR2B Gene Influence Impulsive
Behavior
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Bevilacqua, Laura] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 666
BP 202S
EP 202S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800642
ER
PT J
AU Lee, MR
AF Lee, Mary R.
TI Nicotine and COMT Val158Met Genotype Regulate Activation in a
Cortico-Striatal Network during Reward Processing
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Lee, Mary R.] Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 704
BP 212S
EP 212S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800673
ER
PT J
AU Modi, HR
Cheon, Y
Chang, LS
Kim, HW
Rao, J
Rapoport, SI
AF Modi, Hiren R.
Cheon, Yewon
Chang, Lisa
Kim, Hyung-Wook
Rao, Jagadeesh
Rapoport, Stanley I.
TI Chronic Effects of Clozapine on Arachidonic Acid (AA) Cascade in Rat
Brain
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Modi, Hiren R.; Cheon, Yewon; Chang, Lisa; Kim, Hyung-Wook; Rao, Jagadeesh; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 740
BP 221S
EP 221S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800701
ER
PT J
AU Reese, EA
AF Reese, Edmund A.
TI Altered Expression of G-protein Receptor Kinases in Alzheimer's Disease
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Reese, Edmund A.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 750
BP 224S
EP 224S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800711
ER
PT J
AU Bongaarts, A
Hyde, TM
Dalley, R
Henry, A
Hawrylycz, M
Hohmann, J
Jones, A
Kuan, L
Royall, J
Shen, E
Swanson, B
Wininger, M
Zeng, HK
Kleinman, JE
AF Bongaarts, Angela
Hyde, Thomas M.
Dalley, Rachel
Henry, Alex
Hawrylycz, Mike
Hohmann, John
Jones, Allan
Kuan, Leonard
Royall, Josh
Shen, Elaine
Swanson, Beryl
Wininger, Mike
Zeng, Hongkui
Kleinman, Joel E.
TI Gene Expression Patterns in the DLPFC of Patients with Schizophrenia and
Controls
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Bongaarts, Angela; Dalley, Rachel; Henry, Alex; Hawrylycz, Mike; Hohmann, John; Jones, Allan; Kuan, Leonard; Royall, Josh; Shen, Elaine; Swanson, Beryl; Zeng, Hongkui] Allen Inst Brain Sci, Seattle, WA USA.
[Hyde, Thomas M.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intermural Res Program,NIH, Bethesda, MD 20892 USA.
[Wininger, Mike] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intarmural Res Program,NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 753
BP 225S
EP 225S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800714
ER
PT J
AU Davis, KN
AF Davis, Kasey N.
TI Alternative Transcripts in Fetal and Adult Human Brain for GAD1 and GAD2
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Davis, Kasey N.] NIMH, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 755
BP 225S
EP 226S
PG 2
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800716
ER
PT J
AU Ye, TZ
Lipska, B
Tao, R
Hyde, T
Wang, LQ
Kleinman, J
Weinberger, D
AF Ye, Tianzhang
Lipska, Barbara
Tao, Ran
Hyde, Tom
Wang, Liqin
Kleinman, Joel
Weinberger, Daniel
TI CNV Analysis of Brain DNA in Schizophrenia and Other Psychiatric
Disorders
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Ye, Tianzhang; Lipska, Barbara; Tao, Ran; Hyde, Tom; Wang, Liqin; Kleinman, Joel; Weinberger, Daniel] NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 759
BP 227S
EP 227S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800720
ER
PT J
AU Mattai, A
Miller, R
Weisinger, B
Greenstein, D
Bakalar, J
Tossell, J
Wassermann, E
Rapoport, J
Gogtay, N
AF Mattai, Anand
Miller, Rachel
Weisinger, Brian
Greenstein, Deanna
Bakalar, Jennifer
Tossell, Julia
Wassermann, Eric
Rapoport, Judith
Gogtay, Nitin
TI Safety of Transcranial Direct Current Stimulation in Childhood-Onset
Schizophrenia
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Mattai, Anand; Miller, Rachel; Weisinger, Brian; Greenstein, Deanna; Bakalar, Jennifer; Tossell, Julia; Rapoport, Judith; Gogtay, Nitin] NIMH, Rockville, MD 20857 USA.
[Wassermann, Eric] NINDS, Brain Stimulat Unit, Rockville, MD USA.
RI Gogtay, Nitin/A-3035-2008
NR 0
TC 0
Z9 0
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 765
BP 228S
EP 229S
PG 2
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800726
ER
PT J
AU David, CN
Greenstein, D
Clasen, L
Gochman, P
Miller, R
Tossell, JW
Mattai, AA
Gogtay, N
Rapoport, JL
AF David, Christopher N.
Greenstein, Deanna
Clasen, Liv
Gochman, Peter
Miller, Rachel
Tossell, Julia W.
Mattai, Anand A.
Gogtay, Nitin
Rapoport, Judith L.
TI Childhood Onset Schizophrenia: High Rate of Visual Hallucinations
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [David, Christopher N.; Greenstein, Deanna; Clasen, Liv; Gochman, Peter; Miller, Rachel; Tossell, Julia W.; Mattai, Anand A.; Gogtay, Nitin; Rapoport, Judith L.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
RI Gogtay, Nitin/A-3035-2008
NR 0
TC 0
Z9 0
U1 0
U2 2
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 MAY 1
PY 2011
VL 69
IS 9
SU S
MA 771
BP 230S
EP 230S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800732
ER
PT J
AU Todarello, G
Feng, NP
Li, C
Weinberger, DR
Straub, RE
AF Todarello, Giovanna
Feng, Ningping
Li, Chao
Weinberger, Daniel R.
Straub, Richard E.
TI NRXN1 Deletions in Schizophrenia Patients and Their Family Members But
Not in Normal Controls
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Todarello, Giovanna; Feng, Ningping; Li, Chao; Weinberger, Daniel R.; Straub, Richard E.] NIMH, CBDB, GCAP, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 831
BP 250S
EP 250S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800792
ER
PT J
AU Trampush, JW
Straub, RE
Feng, NP
Li, C
Weinberger, DR
Dickinson, D
AF Trampush, Joey W.
Straub, Richard E.
Feng, Ningping
Li, Chao
Weinberger, Daniel R.
Dickinson, Dwight
TI A Genome-Wide Association Analysis of Personality Dimensions in
Individuals with and without Schizophrenia
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 832
BP 250S
EP 250S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800793
ER
PT J
AU Stidd, R
Mattai, A
Weisinger, B
Greenstein, D
Clasen, L
Gogtay, N
AF Stidd, Reva
Mattai, Andy
Weisinger, Brian
Greenstein, Dede
Clasen, Liv
Gogtay, Nitin
TI Fusiform Gyrus Volume Differences between Childhood-Onset Schizophrenia
Patients and their Nonpsychotic Siblings
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Stidd, Reva; Mattai, Andy; Weisinger, Brian; Greenstein, Dede; Clasen, Liv; Gogtay, Nitin] NIMH, Bethesda, MD 20892 USA.
RI Gogtay, Nitin/A-3035-2008
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 882
BP 267S
EP 267S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800843
ER
PT J
AU Thurin, K
Rasetti, R
Sambataro, F
Safrin, M
Callicott, J
Mattay, VS
Weinberger, DR
AF Thurin, Kristina
Rasetti, Roberta
Sambataro, Fabio
Safrin, Martin
Callicott, Joseph
Mattay, Venkata S.
Weinberger, Daniel R.
TI Effect of ZNF804A Gene, A Genome-wide Supported Psychosis Risk Variant,
on Neural Activation During Cognitive Control
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Thurin, Kristina; Rasetti, Roberta; Sambataro, Fabio; Safrin, Martin; Callicott, Joseph; Mattay, Venkata S.; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA.
[Sambataro, Fabio] Italian Inst Technol, Brain Ctr Motor & Social Cognit, Parma, Italy.
RI Sambataro, Fabio/E-3426-2010
OI Sambataro, Fabio/0000-0003-2102-416X
NR 0
TC 0
Z9 0
U1 1
U2 3
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 MAY 1
PY 2011
VL 69
IS 9
SU S
MA 885
BP 268S
EP 268S
PG 1
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800846
ER
PT J
AU Vyas, NS
Mattai, AK
Carter, FW
Rubinstein, DW
Stidd, R
Weisinger, BM
Miller, R
Coppola, R
Rapoport, JL
Gogtay, N
AF Vyas, Nora S.
Mattai, Anand K.
Carter, Frederick W.
Rubinstein, Daniel W.
Stidd, Reva
Weisinger, Brian M.
Miller, Rachel
Coppola, Richard
Rapoport, Judith L.
Gogtay, Nitin
TI Altered Oscillatory Patterns During Resting-state in Childhood-onset
Schizophrenia: A Magnetoencephalographic Study
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Vyas, Nora S.; Mattai, Anand K.; Stidd, Reva; Weisinger, Brian M.; Miller, Rachel; Rapoport, Judith L.; Gogtay, Nitin] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
[Carter, Frederick W.; Rubinstein, Daniel W.; Coppola, Richard] NIH, MEG Core Facil, Bethesda, MD 20892 USA.
RI Gogtay, Nitin/A-3035-2008
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 886
BP 268S
EP 269S
PG 2
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800847
ER
PT J
AU Weisinger, B
Greenstein, D
Mattai, A
Clasen, L
Lalonde, F
Feldman, S
Stidd, R
Rapoport, J
Gogtay, N
AF Weisinger, Brian
Greenstein, Deanna
Mattai, Anand
Clasen, Liv
Lalonde, Francois
Feldman, Sarah
Stidd, Reva
Rapoport, Judith
Gogtay, Nitin
TI The Lack of Differential Sex Effects on Cortical and Subcortical
Structures in Childhood-Onset Schizophrenia
SO BIOLOGICAL PSYCHIATRY
LA English
DT Meeting Abstract
CT 66th Annual Meeting of the Society-of-Biological-Psychiatry
CY MAY 12-14, 2011
CL San Francisco, CA
SP Soc Biol Psychiat
C1 [Weisinger, Brian; Greenstein, Deanna; Mattai, Anand; Clasen, Liv; Lalonde, Francois; Feldman, Sarah; Stidd, Reva; Rapoport, Judith; Gogtay, Nitin] NIMH, NIH, Bethesda, MD 20892 USA.
RI Gogtay, Nitin/A-3035-2008
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD MAY 1
PY 2011
VL 69
IS 9
SU S
MA 944
BP 287S
EP 288S
PG 2
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 764OR
UT WOS:000290641800905
ER
PT J
AU Berger, K
Klein, HG
Seitz, R
Schramm, W
Spieser, JM
AF Berger, Karin
Klein, Harvey G.
Seitz, Rainer
Schramm, Wolfgang
Spieser, Jean-Marc
TI The Wildbad Kreuth initiative: European current practices and
recommendations for optimal use of blood components
SO BIOLOGICALS
LA English
DT Article
DE Blood; Blood products; Optimal use
ID ELECTIVE SURGERY
AB With the aging population in Europe it is anticipated that the growing demand for blood products will not be met by the estimated supply. Therefore up-to-date recommendations for optimal administration of blood products in hemotherapy are needed. Ten years after the first meeting on optimal use of blood products at Wildbad Kreuth, Germany, a second symposium was organized to convene leading experts from the clinical, regulatory and economic perspective. The aim was to re-evaluate the existing state of hemotherapy, identify areas where further studies are needed, and to provide up-dated recommendations. A preparatory survey by questionnaire concerning guidelines, quality management in clinical use of blood products, provision of products in the individual countries and re-evaluation of the 1999 Wildbad Kreuth recommendations was completed in advance. The second Kreuth Meeting in April 2009 was attended by 110 experts in transfusion medicine, regulators and regulatory authorities from 38 countries. By consensus, 20 new recommendations were adopted. Most of the 1999 recommendations were found to still be valid 10 years later. But their realization and implementation on the levels of clinical practice, regulatory authorities and health policy decision makers is still lagging behind leaving an important task to accomplish. The Kreuth initiative toward optimal use of blood products should continue.
C1 [Berger, Karin; Schramm, Wolfgang] Univ Hosp Munich, Dept Transfus Med & Hemostasis, D-81377 Munich, Germany.
[Klein, Harvey G.] NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA.
[Seitz, Rainer] Paul Ehrlich Inst, Div Hematol Transfus Med, D-6070 Langen, Germany.
[Spieser, Jean-Marc] Council Europe, European Directorate Qual Med & HealthCare EDQM, Dept Biol Standardizat, OMCL Network & HealthCare DBO, Strasbourg, France.
RP Berger, K (reprint author), Univ Hosp Munich, Dept Transfus Med & Hemostasis, Marchioninistr 15, D-81377 Munich, Germany.
EM Karin.Berger@med.uni-muenchen.de
NR 13
TC 2
Z9 2
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1045-1056
J9 BIOLOGICALS
JI Biologicals
PD MAY
PY 2011
VL 39
IS 3
BP 189
EP 193
DI 10.1016/j.biologicals.2011.03.002
PG 5
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Pharmacology & Pharmacy
GA 785IT
UT WOS:000292223400009
PM 21524591
ER
PT J
AU Sampson, JN
AF Sampson, Joshua Neil
TI What Are the Consequences if I Postpone Treatment of My PSA-Detected
Prostate Cancer?
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID MORTALITY
C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
RP Sampson, JN (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,8038, Rockville, MD 20852 USA.
EM joshua.sampson@nih.gov
NR 3
TC 0
Z9 0
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD MAY
PY 2011
VL 20
IS 5
BP 727
EP 728
DI 10.1158/1055-9965.EPI-11-0057
PG 2
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 759MU
UT WOS:000290251000002
PM 21546364
ER
PT J
AU Sourbier, C
AF Sourbier, Carole
TI Met and the microenvironment New insights for ovarian cancer metastasis
SO CELL ADHESION & MIGRATION
LA English
DT Article
DE Met; independent-ligand activation; ovarian cancer metastasis; integrin;
fibronectin; FAK
ID EXPRESSION; INHIBITOR; KINASE
AB Ovarian cancer often has few symptoms, which makes it difficult to detect at an early stage. Therefore, most of the women will already have metastasis at the time of diagnosis. In their search of undercovering the mechanisms underlying ovarian cancer invasion, Mitra and collaborators demonstrate that the fibronectin receptor (alpha(5)beta(1)-integrin) can directly activate the receptor tyrosine kinase Met, independently of its ligand. By linking the extracellular matrix with Met activation, and the invasion of ovarian cancer cells, Mitra et al. confirm the crucial role played by Met in ovarian cancer and open new perspectives in the development of ovarian cancer targeted therapies.
C1 NCI, NIH, Bethesda, MD 20892 USA.
RP Sourbier, C (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM sourbierc@mail.nih.gov
NR 10
TC 1
Z9 1
U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1933-6918
J9 CELL ADHES MIGR
JI Celll Adhes. Migr.
PD MAY-JUN
PY 2011
VL 5
IS 3
BP 209
EP 210
DI 10.4161/cam.5.3.15258
PG 2
WC Cell Biology
SC Cell Biology
GA 898CM
UT WOS:000300713000001
PM 21436615
ER
PT J
AU Rosenberg, HF
AF Rosenberg, H. F.
TI Eosinophilic inflammation: life, death and apoptosis
SO CLINICAL AND EXPERIMENTAL ALLERGY
LA English
DT Editorial Material
ID AIRWAY INFLAMMATION; TISSUE EOSINOPHILS; STEROID TREATMENT; CELL
APOPTOSIS; R-ROSCOVITINE; RESOLUTION; ASTHMA; CLEARANCE; INHIBITOR;
EXPRESSION
AB Cite this as: H. F. Rosenberg, Clinical & Experimental Allergy, 2011 (41) 612-614.
C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM hrosenberg@niaid.nih.gov
NR 28
TC 3
Z9 3
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0954-7894
J9 CLIN EXP ALLERGY
JI Clin. Exp. Allergy
PD MAY
PY 2011
VL 41
IS 5
BP 612
EP 614
DI 10.1111/j.1365-2222.2011.03727.x
PG 3
WC Allergy; Immunology
SC Allergy; Immunology
GA 749QE
UT WOS:000289482900004
PM 21488994
ER
PT J
AU Sacks, DB
AF Sacks, D. B.
TI HBA1C IN THE DIAGNOSIS OF DIABETES: OPPORTUNITIES AND PROBLEMS
SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE
LA English
DT Meeting Abstract
C1 [Sacks, D. B.] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
EM dbs1999@verizon.net
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WALTER DE GRUYTER & CO
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 1434-6621
J9 CLIN CHEM LAB MED
JI Clin. Chem. Lab. Med.
PD MAY
PY 2011
VL 49
SU 1
BP S37
EP S37
PG 1
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 755XR
UT WOS:000289974200037
ER
PT J
AU Geiger, B
Yamada, KM
AF Geiger, Benjamin
Yamada, Kenneth M.
TI Molecular Architecture and Function of Matrix Adhesions
SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
LA English
DT Article
ID ACTIN STRESS FIBERS; FOCAL ADHESIONS; EXTRACELLULAR-MATRIX;
CELL-MIGRATION; CULTURED FIBROBLASTS; INTEGRIN FUNCTION; TYROSINE
PHOSPHORYLATION; ALPHA(5)BETA(1) FUNCTION; SIGNAL-TRANSDUCTION; TUMOR
PROGRESSION
AB Cell adhesions mediate important bidirectional interactions between cells and the extracellular matrix. They provide an interactive interface between the extracellular chemical and physical environment and the cellular scaffolding and signaling machinery. This dynamic, reciprocal regulation of intracellular processes and the matrix is mediated by membrane receptors such as the integrins, as well as many other components that comprise the adhesome. Adhesome constituents assemble themselves into different types of cell adhesion structures that vary in molecular complexity and change over time. These cell adhesions play crucial roles in cell migration, proliferation, and determination of cell fate.
C1 [Geiger, Benjamin] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.
[Yamada, Kenneth M.] Natl Inst Craniofacial & Dent Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Geiger, B (reprint author), Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.
EM benny.geiger@weizmann.ac.il; kenneth.yamada@nih.gov
OI Yamada, Kenneth/0000-0003-1512-6805
FU National Institute of General Medical Sciences (NIH) [U54GM64346];
Nanotechnology Center for Mechanics in Regenerative Medicine [PN2
EY016586]; Mario Negri Institute for Pharmacological Research - Weizmann
Institute of Science; Israel Science Foundation; National Institute of
Dental and Craniofacial Research; National Institutes of Health
FX BG is the incumbent of the Erwin Neter Professorial Chair in Cell and
Tumor Biology. Studies addressing the adhesome network and
mechanosensitivity were supported by the National Institute of General
Medical Sciences grant for the Cell Migration Consortium (NIH grant no.
U54GM64346); the Nanotechnology Center for Mechanics in Regenerative
Medicine (part of the NIH Nanomedicine Development Center Network; NIH
grant no. PN2 EY016586), the Mario Negri Institute for Pharmacological
Research - Weizmann Institute of Science Exchange Program, and the
Israel Science Foundation. KMY is supported by the Intramural Research
Program of the National Institute of Dental and Craniofacial Research,
National Institutes of Health. The authors would like to express their
gratitude to Chen Luxenburg, Tova Volberg, Ronen Zaidel-Bar, and Baruch
Zimerman for providing data presented in this article. The authors also
wish to thank Barbara Morgenstern for excellent editorial assistance.
NR 144
TC 112
Z9 112
U1 2
U2 22
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1943-0264
J9 CSH PERSPECT BIOL
JI Cold Spring Harbor Perspect. Biol.
PD MAY
PY 2011
VL 3
IS 5
AR a005033
DI 10.1101/cshperspect.a005033
PG 21
WC Cell Biology
SC Cell Biology
GA 810JU
UT WOS:000294122400008
ER
PT J
AU Gea-Banacloche, J
AF Gea-Banacloche, Juan
TI Biomarkers in fever and neutropenia: A solution in search of a problem?
SO CRITICAL CARE MEDICINE
LA English
DT Editorial Material
DE febrile neutropenia; fever; granulocytopenia; sTREM-1; interleukin 8;
procalcitonin; biomarkers
ID C-REACTIVE PROTEIN; CANCER; PROCALCITONIN; INFECTION; FEASIBILITY;
DIAGNOSIS; THERAPY; SEPSIS; TREM-1; RISK
C1 NIH, Bethesda, MD 20892 USA.
RP Gea-Banacloche, J (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 18
TC 2
Z9 2
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD MAY
PY 2011
VL 39
IS 5
BP 1205
EP 1206
DI 10.1097/CCM.0b013e31820f6d6d
PG 2
WC Critical Care Medicine
SC General & Internal Medicine
GA 752CX
UT WOS:000289667000042
PM 21610578
ER
PT J
AU Cecchi, F
Rabe, DC
Bottaro, DP
AF Cecchi, Fabiola
Rabe, Daniel C.
Bottaro, Donald P.
TI The Hepatocyte Growth Factor Receptor: Structure, Function and
Pharmacological Targeting in Cancer
SO CURRENT SIGNAL TRANSDUCTION THERAPY
LA English
DT Review
DE Hepatocyte growth factor; Met
ID CELL LUNG-CANCER; TYROSINE KINASE INHIBITOR; MET SIGNALING PATHWAY;
C-MET; SCATTER FACTOR; THERAPEUTIC INHIBITION; FACTOR/SCATTER FACTOR;
LIVER-REGENERATION; TPR-MET; BIOLOGICAL-ACTIVITY
AB Under normal conditions, hepatocyte growth factor (HGF)-induced activation of its cell surface receptor, the Met tyrosine kinase (TK), is tightly regulated by paracrine ligand delivery, ligand activation at the target cell surface, and ligand activated receptor internalization and degradation. Despite these controls, HGF/Met signaling contributes to oncogenesis and tumor progression in several cancers and promotes aggressive cellular invasiveness that is strongly linked to tumor metastasis. The prevalence of HGF/Met pathway activation in human malignancies has driven rapid growth in cancer drug development programs. Pathway inhibitors can be divided broadly into biologicals and low molecular weight synthetic TK inhibitors; of these, the latter now outnumber all other inhibitor types. We review here Met structure and function, the basic properties of HGF/Met pathway antagonists now in preclinical and clinical development, as well as the latest clinical trial results. The main challenges facing the effective use of HGF/Met-targeted antagonists for cancer treatment include optimal patient selection, diagnostic and pharmacodynamic biomarker development, and the identification and testing of optimal therapy combinations. The wealth of basic information, analytical reagents and model systems available concerning HGF/Met oncogenic signaling will continue to be invaluable in meeting these challenges and moving expeditiously toward more effective disease control.
C1 [Cecchi, Fabiola; Rabe, Daniel C.; Bottaro, Donald P.] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Cecchi, F (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bldg 10,CRC Rm 1W-5832,10 Ctr Dr,MSC 1107, Bethesda, MD 20892 USA.
EM cecchif@mail.nih.gov
RI Bottaro, Donald/F-8550-2010
OI Bottaro, Donald/0000-0002-5057-5334
FU NIH, National Cancer Institute, Center for Cancer Research
FX Web site addresses are provided as an informational resource, not as an
endorsement of any product or manufacturer. This work was supported by
the Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research.
NR 90
TC 4
Z9 4
U1 0
U2 6
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1574-3624
EI 2212-389X
J9 CURR SIGNAL TRANSD T
JI Curr. Signal Transduct. Ther.
PD MAY
PY 2011
VL 6
IS 2
BP 146
EP 151
PG 6
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 940BX
UT WOS:000303866100003
PM 25197268
ER
PT J
AU Simone, CB
Simone, CB
AF Simone, Charles B., II
Simone, Charles B.
TI Re: Firas Abdollah, Maxine Sun, Rodolphe Thuret, et al. A
Competing-Risks Analysis of Survival After Alternative Treatment
Modalities for Prostate Cancer Patients: 1988-2006. Eur Urol
2011;59:88-95
SO EUROPEAN UROLOGY
LA English
DT Letter
ID MEN; DEATH
C1 [Simone, Charles B., II; Simone, Charles B.] Simone Protect Canc Ctr, Lawrenceville, NJ 08648 USA.
[Simone, Charles B., II] NCI, NIH, Radiat Oncol Branch, Bethesda, MD 20892 USA.
RP Simone, CB (reprint author), Simone Protect Canc Ctr, 123 Franklin Corner Rd,Suite 108, Lawrenceville, NJ 08648 USA.
EM csimone@alumni.upenn.edu; csimone@alumni.upenn.edu
NR 6
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
J9 EUR UROL
JI Eur. Urol.
PD MAY
PY 2011
VL 59
IS 5
BP E29
EP E30
DI 10.1016/j.eururo.2011.01.042
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 743BT
UT WOS:000288991500003
PM 21296483
ER
PT J
AU Cooper, AR
Baker, VL
Sterling, EW
Ryan, ME
Woodruff, TK
Nelson, LM
AF Cooper, Amber R.
Baker, Valerie L.
Sterling, Evelina W.
Ryan, Mary E.
Woodruff, Teresa K.
Nelson, Lawrence M.
TI The time is now for a new approach to primary ovarian insufficiency
SO FERTILITY AND STERILITY
LA English
DT Article
DE Primary ovarian insufficiency (POI); premature ovarian failure (POF);
premature menopause; diminished ovarian reserve; sex steroid deficiency;
infertility; menstrual cycle; patient registry; research consortia;
participatory research; integrative medicine
ID CHILDHOOD-CANCER SURVIVOR; PARTICIPATORY RESEARCH; AUTOIMMUNE
OOPHORITIS; YOUNG-WOMEN; FAILURE; DYSFUNCTION; PHYSICIANS; FERTILITY;
NEEDS; CARE
AB Objective: To articulate the need for a new approach to primary ovarian insufficiency. The condition, also known as premature menopause or premature ovarian failure, is defined by the presence of menopausal-level serum gonadotropins in association with irregular menses in adolescent girls or women younger than 40 years. It can be iatrogenic as related to cancer therapy or may arise spontaneously, either alone or as part of a host of ultrarare syndromes. In a large percentage of spontaneous cases no pathogenic mechanism can be identified.
Design: Literature review and consensus building at a multidisciplinary scientific workshop.
Conclusion(s): There are major gaps in knowledge regarding the etiologic mechanisms, psychosocial effects, natural history, and medical and psychosocial management of primary ovarian insufficiency. An international research consortium and disease registry formed under the guidance of an umbrella organization would provide a pathway to comprehensively increase basic and clinical knowledge about the condition. Such a consortium and patient registry also would provide clinical samples and clinical data with a goal toward defining the specific pathogenic mechanisms. An international collaborative approach that combines the structure of a patient registry with the principles of integrative care and community-based participatory research is needed to advance the field of primary ovarian insufficiency. (Fertil Steril (R) 2011; 95: 1890-7. (C)2011 by American Society for Reproductive Medicine.)
C1 [Nelson, Lawrence M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Integrat Reprod Med Unit, Intramural Res Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Cooper, Amber R.] Washington Univ, Sch Med, Div Reprod Endocrinol & Infertil, St Louis, MO USA.
[Baker, Valerie L.] Stanford Univ, Med Ctr, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Palo Alto, CA 94304 USA.
[Sterling, Evelina W.] Rachels Well Inc, Atlanta, GA USA.
[Ryan, Mary E.] Natl Inst Hlth Lib, Bethesda, MD USA.
[Woodruff, Teresa K.] Northwestern Univ, Dept Obstet & Gynecol, Feinberg Sch Med, Chicago, IL 60611 USA.
RP Nelson, LM (reprint author), NICHD, Integrat Reprod Med Unit, Intramural Res Program Reprod & Adult Endocrinol, CRC, Rm 1-3140,10 Ctr Dr,MSC-1109, Bethesda, MD 20892 USA.
EM lawrence_nelson@nih.gov
FU Rachel's Well, Inc.; American Society for Reproductive Medicine (ASRM);
National Institutes of Health (NIH); Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD); NIH Office of
Research on Women's Health (OWRH); NIH Office of Rare Diseases (ORD);
Department of Health and Human Services Office on Women's Health; NIH
Roadmap Interdisciplinary Consortium [NIH UL1 DE019587]; NICHD SCCPIR
[NIH U54-HD41857]; Institut Biochimique SA (IBSA)
FX The work shop was sponsored in part by Rachel's Well, Inc., American
Society for Reproductive Medicine (ASRM), the National Institutes of
Health (NIH), the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(NICHD), the NIH Office of Research on Women's Health (OWRH), the NIH
Office of Rare Diseases (ORD), and the Department of Health and Human
Services Office on Women's Health. L.M.N. is a commissioned officer in
the United States Public Health Service. The Oncofertility Consortium is
supported by an NIH Roadmap Interdisciplinary Consortium grant
mechanism: NIH UL1 DE019587 (to T.K.W.) and was initially fostered
through the NICHD SCCPIR program NIH U54-HD41857 (T.K.W.). V.L.B.
received research support from Institut Biochimique SA (IBSA).
NR 34
TC 25
Z9 26
U1 1
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD MAY
PY 2011
VL 95
IS 6
BP 1890
EP 1897
DI 10.1016/j.fertnstert.2010.01.016
PG 8
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 751MA
UT WOS:000289620900007
PM 20188353
ER
PT J
AU Nelson, LM
AF Nelson, Lawrence M.
TI Synchronizing the world of women's health: young Turks and
transformational leaders report for duty
SO FERTILITY AND STERILITY
LA English
DT Article
AB Health care and research together in one system is a grand paradigm shift. Partnering with patients via social media can make it real. (Fertil Steril (R) 2011; 95: 1902. (C)2011 by American Society for Reproductive Medicine.)
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Integrat Reprod Med Grp, Intramural Res Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
RP Nelson, LM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Integrat Reprod Med Grp, Intramural Res Program Reprod & Adult Endocrinol, NIH, 10 Ctr Dr,Bldg 10,CRC,Room 1-3140, Bethesda, MD 20892 USA.
EM nelsonl@cc1.nichd.nih.gov
FU Intramural NIH HHS [ZIA HD000633-20]
NR 3
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD MAY
PY 2011
VL 95
IS 6
BP 1902
EP 1902
DI 10.1016/j.fertnstert.2011.03.009
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 751MA
UT WOS:000289620900011
PM 21841843
ER
PT J
AU Henderson, DK
AF Henderson, David K.
TI Does a Little Bit Really Go a Long Way? Infection Prevention in
Ambulatory Healthcare Facilities
SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY
LA English
DT Editorial Material
ID UNSAFE INJECTION PRACTICES; C VIRUS-INFECTIONS; NEVADA
C1 [Henderson, David K.] NIH, Hosp Epidemiol Serv, Bethesda, MD 20892 USA.
[Henderson, David K.] NIH, Off Deputy Director Clin Care, Bethesda, MD 20892 USA.
RP Henderson, DK (reprint author), Bldg 10,Room 6-1480,10 Ctr Dr, Bethesda, MD 20892 USA.
EM dkh@nih.gov
NR 8
TC 1
Z9 1
U1 0
U2 0
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0899-823X
J9 INFECT CONT HOSP EP
JI Infect. Control Hosp. Epidemiol.
PD MAY
PY 2011
VL 32
IS 5
BP 425
EP 427
DI 10.1086/659402
PG 3
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 791GE
UT WOS:000292652100002
PM 21515971
ER
PT J
AU Auer, R
Bauer, DC
Marques-Vidal, P
Butler, J
Kim, L
Cornuz, J
Satterfield, S
Newman, A
Rodondi, N
AF Auer, Reto
Bauer, Douglas C.
Marques-Vidal, Pedro
Butler, Javed
Kim, Lauren
Cornuz, Jacques
Satterfield, Suzanne
Newman, Anne
Rodondi, Nicolas
TI THE ASSOCIATION BETWEEN MINOR AND MAJOR ECG CHANGES AND INCIDENCE OF
CORONARY HEART DISEASE EVENTS
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Meeting Abstract
C1 [Auer, Reto; Marques-Vidal, Pedro; Cornuz, Jacques; Rodondi, Nicolas] Univ Lausanne, Lausanne, Switzerland.
[Bauer, Douglas C.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Butler, Javed] Emory Univ, Atlanta, GA 30322 USA.
[Kim, Lauren] NIA, NIH, Bethesda, MD 20892 USA.
[Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
[Newman, Anne] Univ Pittsburgh, Pittsburgh, PA 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 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD MAY
PY 2011
VL 26
SU 1
BP S48
EP S49
PG 2
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA V30JQ
UT WOS:000208812700082
ER
PT J
AU Bracey, JE
Phillips, KA
Stewart, R
AF Bracey, Jennifer E.
Phillips, Karran A.
Stewart, Rosalyn
TI INCARCERATION MEDICINE AND RE-ENTRY: A CURRICULUM FOR URBAN HEALTH
LEARNERS
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Meeting Abstract
C1 [Bracey, Jennifer E.; Stewart, Rosalyn] Johns Hopkins Univ Sch Med, Baltimore, MD USA.
[Phillips, Karran A.] NIDA, NIH, Beltsville, MD USA.
[Phillips, Karran A.] Johns Hopkins Univ Sch Med, Beltsville, 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 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD MAY
PY 2011
VL 26
SU 1
BP S603
EP S604
PG 2
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA V30JQ
UT WOS:000208812703328
ER
PT J
AU Clair, C
Rigotti, NA
Shrader, P
Caroline
Pencina, MSF
Meigs, J
AF Clair, Carole
Rigotti, Nancy A.
Shrader, Peter
Caroline
Pencina, Michael S. Fox
Meigs, James
TI EFFECTS OF SMOKING CESSATION AND WEIGHT CHANGE ON CARDIOVASCULAR DISEASE
AMONG PEOPLE WITH AND WITHOUT DIABETES
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Meeting Abstract
C1 [Clair, Carole; Shrader, Peter; Caroline] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Rigotti, Nancy A.] Harvard Univ, Sch Med, Boston, MA USA.
[Pencina, Michael S. Fox] Boston Univ, NHLBI, Framingham Heart Study, Framingham, MA USA.
[Meigs, James] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
RI Clair, Carole/D-9786-2014
OI Clair, Carole/0000-0001-5281-0943
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 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD MAY
PY 2011
VL 26
SU 1
BP S12
EP S14
PG 3
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA V30JQ
UT WOS:000208812700023
ER
PT J
AU Clayman, ML
Makoul, G
Webb, J
Bylund, C
Chewning, B
Arora, NK
AF Clayman, Marla L.
Makoul, Gregory
Webb, Jennifer
Bylund, Carma
Chewning, Betty
Arora, Neeraj K.
TI THE EFFECT OF PATIENT PARTICIPATION IN HEALTH DECISIONS: AN
EVIDENCE-BASED REVIEW
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Meeting Abstract
C1 [Clayman, Marla L.; Webb, Jennifer] Northwestern Univ, Chicago, IL 60611 USA.
[Makoul, Gregory] St Francis Hosp Syst, Hartford, CT USA.
[Bylund, Carma] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Chewning, Betty] Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA.
[Arora, Neeraj K.] NCI, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD MAY
PY 2011
VL 26
SU 1
BP S230
EP S231
PG 2
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA V30JQ
UT WOS:000208812701192
ER
PT J
AU Lopez, L
Cook, N
Grant, R
Pabon-Nau, L
Hicks, L
AF Lopez, Lenny
Cook, Nakela
Grant, Richard
Pabon-Nau, Lina
Hicks, Leroi
TI HIGHER CARDIOLOGY CONSULTATION RATES FOR CARDIOVASCULAR DISEASE FOR
HISPANICS SEEN IN HIGH PROPORTION HISPANIC VS. LOW PROPORTION HISPANIC
CLINICS IN A LARGE INTEGRATED ACADEMIC HEALTHCARE SYSTEM
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Meeting Abstract
C1 [Lopez, Lenny; Grant, Richard; Pabon-Nau, Lina] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Cook, Nakela] NHLBI, Bethesda, MD 20892 USA.
[Hicks, Leroi] Brigham & Womens Hosp, Boston, MA 02115 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 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD MAY
PY 2011
VL 26
SU 1
BP S305
EP S305
PG 1
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA V30JQ
UT WOS:000208812702033
ER
PT J
AU Odulana, AA
Kim, M
Taylor, Y
Green, M
Goldmon, M
Godley, P
Meade, SA
Boyd, C
Howard, D
Corbie-Smith, G
AF Odulana, Adebowale Ayoola
Kim, Mimi
Taylor, Yhenneko
Green, Melissa
Goldmon, Moses
Godley, Paul
Meade, Shelly-Ann
Boyd, Carlton
Howard, Daniel
Corbie-Smith, Giselle
TI ASSESSING AFRICAN AMERICAN CONGREGATION MEMBERS' READINESS TO
PARTICIPATE IN RESEARCH
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Meeting Abstract
C1 [Odulana, Adebowale Ayoola] Univ North Carolina Chapel Hill, Cecil G Sheps Ctr Hlth Serv Res, Raleigh, NC USA.
[Kim, Mimi; Green, Melissa; Godley, Paul; Corbie-Smith, Giselle] Univ N Carolina, Cecil G Sheps Ctr Hlth Res, Chapel Hill, NC USA.
[Taylor, Yhenneko] Univ N Carolina, Coll Hlth & Human Serv, Charlotte, NC 28223 USA.
[Goldmon, Moses] Shaw Univ, Raleigh, NC USA.
[Meade, Shelly-Ann] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Boyd, Carlton] NIEHS, Durham, NC USA.
[Howard, Daniel] Robert Wood Johnson Fdn, Meharry Med Coll, Ctr Heatlh Policy, Nashville, TN 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 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD MAY
PY 2011
VL 26
SU 1
BP S186
EP S187
PG 2
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA V30JQ
UT WOS:000208812701110
ER
PT J
AU Odim, J
AF Odim, Jonah
TI Proteins caught in the proteome of the unloaded remodeling pump
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Editorial Material
ID VENTRICULAR ASSIST DEVICE
C1 [Odim, Jonah] NIAID, Bethesda, MD 20892 USA.
RP Odim, J (reprint author), 6610 Rockledge Dr,Rm 6227, Bethesda, MD 20892 USA.
EM odimj@niaid.nih.gov
NR 6
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD MAY
PY 2011
VL 30
IS 5
BP 494
EP 496
DI 10.1016/j.healun.2011.01.724
PG 3
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA 753EN
UT WOS:000289748800002
PM 21388831
ER
PT J
AU Vasaitis, TS
Bruno, RD
Njar, VCO
AF Vasaitis, Tadas S.
Bruno, Robert D.
Njar, Vincent C. O.
TI CYP17 inhibitors for prostate cancer therapy
SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Review
DE Prostate cancer (PC); PC treatment; Inhibition of androgen synthesis;
CYP17; Inhibitors of CYP17; Ketoconazole; Abiraterone acetate; VN/124-1
(TOK-001); TAK-700
ID LOW-DOSE KETOCONAZOLE; HEPATIC MICROSOMAL CYTOCHROME; ANDROGEN
DEPRIVATION THERAPY; REMAINS HORMONE DRIVEN; I CLINICAL-TRIAL;
ABIRATERONE ACETATE; ANTITUMOR-ACTIVITY; ANTIANDROGEN WITHDRAWAL; DRUG
INTERACTION; PHASE-I
AB Prostate cancer (PC) is now the second most prevalent cause of death in men in the USA and Europe. At present, the major treatment options include surgical or medical castration. These strategies cause ablation of the production of testosterone (T), dihydrotestosterone (DHT) and related androgens by the testes. However, because these procedures do not affect adrenal, prostate and other tissues' androgen production, they are often combined with androgen receptor antagonists to block their action. Indeed, recent studies have unequivocally established that in castration-resistant prostate cancer (CRPC) many androgen-regulated genes become re-expressed and tissue androgen levels increase despite low serum levels.
Clearly, inhibition of the key enzyme which catalyzes the biosynthesis of androgens from pregnane precursors, 17 alpha-hydroxy/17,20-lyase (hereafter referred to as CYP17) could prevent androgen production from all sources. Thus, total ablation of androgen production by potent CYP17 inhibitors may provide effective treatment of prostate cancer patients. This review highlights the role of androgen biosynthesis in the progression of prostate cancer and the impact of CYP17 inhibitors, such as ketoconazole, abiraterone acetate, VN/124-1 (TOK-001) and TAK-700 in the clinic and in clinical development.
Article from the special issue on Targeted Inhibitors. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Njar, Vincent C. O.] Thomas Jefferson Univ, Jefferson Sch Pharm, Dept Pharmaceut Sci, Philadelphia, PA 19107 USA.
[Njar, Vincent C. O.] Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA.
[Vasaitis, Tadas S.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Vasaitis, Tadas S.] Univ Maryland Eastern Shore, Dept Pharmaceut Sci, Princess Anne, MD USA.
[Bruno, Robert D.] NCI, Mammary Stem Cell Biol Sect, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Njar, VCO (reprint author), Thomas Jefferson Univ, Jefferson Sch Pharm, Dept Pharmaceut Sci, 130 S 9th St,Edison Bldg,Suite 1510 F, Philadelphia, PA 19107 USA.
EM Vincent.Njar@jefferson.edu
OI Bruno, Robert/0000-0003-3329-9478
FU NIH [R21 CA11799-01]; Thomas Jefferson University; US National
Institutes of Health [T32 AG000219]
FX Part of this work was supported by NIH grant R21 CA11799-01 and start-up
funds from Thomas Jefferson University (Njar, VCO). Vasaitis, TS was
supported in part by US National Institutes of Health training grant T32
AG000219.
NR 90
TC 64
Z9 65
U1 2
U2 14
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-0760
J9 J STEROID BIOCHEM
JI J. Steroid Biochem. Mol. Biol.
PD MAY
PY 2011
VL 125
IS 1-2
SI SI
BP 23
EP 31
DI 10.1016/j.jsbmb.2010.11.005
PG 9
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 784QX
UT WOS:000292174400004
PM 21092758
ER
PT J
AU Dawson, DA
Grant, BF
AF Dawson, Deborah A.
Grant, Bridget F.
TI The "Gray Area" of Consumption Between Moderate and Risk Drinking
SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS
LA English
DT Article
ID ALCOHOL-CONSUMPTION; MORTALITY; DISEASE; IV
AB Objective: The objective of this study was to see whether levels of alcohol consumption newly included as "moderate" in proposed changes to the 2010 Dietary Guidelines for Americans are associated with significant levels of alcohol-related harm. Method: Using longitudinal data from a nationally representative sample of U.S. adults (N = 26,438; 51.8% female), we compared relative risks and population attributable fractions for nine measures of concurrent and eight measures of prospective alcohol-related harm among three groups of drinkers: those whose consumption lay within the old 2005 Dietary Guidelines for Americans guidelines for moderate drinking, those in the "gray area" of consumption between the 2005 and proposed 2010 Dietary Guidelines for Americans, and those who exceeded the proposed 2010 Dietary Guidelines for Americans. Results: The gray area of consumption was associated with small but significantly increased risks of prevalent and incident alcohol dependence, incident alcohol-related interpersonal problems, and prevalent job loss. There were no associations with medical conditions or mental disorders. Although the harms associated with this level of consumption reflected low absolute and/or relative risks of harm, their impact was not negligible because of the large proportion of drinkers in the gray area of consumption (29.1%). The overwhelming majority of incident harm among baseline gray area drinkers was associated with consumption that had increased over the follow-up interval to exceed the proposed 2010 Dietary Guidelines for Americans. Conclusions: We recommend two alternative approaches to rewording the proposed changes to the 2010 Dietary Guidelines for Americans that would avoid suggesting that there are benefits associated with the gray area of alcohol consumption. (.1 Stud. Alcohol Drugs, 72, 453-458, 2011)
C1 [Dawson, Deborah A.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, NIH, Bethesda, MD 20892 USA.
RP Dawson, DA (reprint author), NIAAA, Lab Epidemiol & Biometry, NIH, 5635 Fishers Lane,MSC 9304,Room 3093, Bethesda, MD 20892 USA.
EM ddawson@mail.nih.gov
FU National Institute on Alcohol Abuse and Alcoholism (NIAAA), National
Institutes of Health, U.S. Department of Health and Human Services;
National Institutes of Health, NIAAA
FX The study on which this article is based, the National Epidemiologic
Survey on Alcohol and Related Conditions (NESARC), is sponsored by the
National Institute on Alcohol Abuse and Alcoholism (NIAAA), National
Institutes of Health, U.S. Department of Health and Human Services, with
supplemental support from the National Institute on Drug Abuse. This
research was supported, in part, by the Intramural Program of the
National Institutes of Health, NIAAA. The views and opinions expressed
in this article are those of the authors and should not be construed to
represent the views of any of the sponsoring organizations, agencies, or
the U.S. government.
NR 14
TC 9
Z9 9
U1 0
U2 5
PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV
PI PISCATAWAY
PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA
SN 1937-1888
J9 J STUD ALCOHOL DRUGS
JI J. Stud. Alcohol Drugs
PD MAY
PY 2011
VL 72
IS 3
BP 453
EP 458
PG 6
WC Substance Abuse; Psychology
SC Substance Abuse; Psychology
GA 762FM
UT WOS:000290460200012
PM 21513682
ER
PT J
AU Shuch, B
Pacak, K
Linehan, WM
Bratslavsky, G
AF Shuch, Brian
Pacak, Karel
Linehan, W. Marston
Bratslavsky, Gennady
TI Predictive Factors for Malignant Pheochromocytoma: Analysis of 136
Patients EDITORIAL COMMENT
SO JOURNAL OF UROLOGY
LA English
DT Editorial Material
ID SCALED SCORE PASS
C1 [Shuch, Brian; Pacak, Karel; Linehan, W. Marston; Bratslavsky, Gennady] NCI, NIH, Bethesda, MD 20892 USA.
RP Shuch, B (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [Z01 HD008735-08]
NR 5
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
EI 1527-3792
J9 J UROLOGY
JI J. Urol.
PD MAY
PY 2011
VL 185
IS 5
BP 1589
EP 1590
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA 746WQ
UT WOS:000289279600011
PM 21419442
ER
PT J
AU Jun, SB
Carlson, VC
Ikeda, S
Lovinger, D
AF Jun, Sang Beom
Carlson, Verginia Cuzon
Ikeda, Stephen
Lovinger, David
TI Vibrodissociation of Neurons from Rodent Brain Slices to Study Synaptic
Transmission and Image Presynaptic Terminals
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Neuroscience; Issue 51; neuronal dissociation; synaptic transmission;
GABA; calcium imaging; electrophysiology; hippocampus; striatum
AB Mechanical dissociation of neurons from the central nervous system has the advantage that presynaptic boutons remain attached to the isolated neuron of interest. This allows for examination of synaptic transmission under conditions where the extracellular and postsynaptic intracellular environments can be well controlled. A vibration-based technique without the use of proteases, known as vibrodissociation, is the most popular technique for mechanical isolation. A micropipette, with the tip fire-polished to the shape of a small ball, is placed into a brain slice made from a P1-P21 rodent. The micropipette is vibrated parallel to the slice surface and lowered through the slice thickness resulting in the liberation of isolated neurons. The isolated neurons are ready for study within a few minutes of vibrodissociation. This technique has advantages over the use of primary neuronal cultures, brain slices and enzymatically isolated neurons including: rapid production of viable, relatively mature neurons suitable for electrophysiological and imaging studies; superior control of the extracellular environment free from the influence of neighboring cells; suitability for well-controlled pharmacological experiments using rapid drug application and total cell superfusion; and improved space-clamp in whole-cell recordings relative to neurons in slice or cell culture preparations. This preparation can be used to examine synaptic physiology, pharmacology, modulation and plasticity. Real-time imaging of both pre- and postsynaptic elements in the living cells and boutons is also possible using vibrodissociated neurons. Characterization of the molecular constituents of pre- and postsynaptic elements can also be achieved with immunological and imaging-based approaches.
C1 [Jun, Sang Beom; Carlson, Verginia Cuzon; Lovinger, David] NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, NIH, Bethesda, MD USA.
[Jun, Sang Beom] Ewha Womans Univ, Dept Elect Engn, Seodaemun, South Korea.
[Ikeda, Stephen] NIAAA, Sect Transmitter Signaling, Lab Mol Physiol, NIH, Bethesda, MD USA.
RP Lovinger, D (reprint author), NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, NIH, Bethesda, MD USA.
EM lovindav@mail.nih.gov
FU Division of Intramural Clinical and Biomedical Research of NIAAA
FX We would like to acknowledge Drs. Ping Jun Zhu and Susumu Koyama for
their assistance during the initial set up of the technique, and Dr.
Veronica Alvarez for assistance in formatting the written manuscript.
This study was funded by the Division of Intramural Clinical and
Biomedical Research of NIAAA.
NR 13
TC 1
Z9 1
U1 0
U2 1
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD MAY
PY 2011
IS 51
AR e2752
DI 10.3791/2752
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36MA
UT WOS:000209214800042
ER
PT J
AU Kuriki, Y
Liu, YN
Xia, DS
Gjerde, EM
Khalili, S
Mui, B
Zheng, CY
Tran, SD
AF Kuriki, Yusuke
Liu, Younan
Xia, Dengsheng
Gjerde, Eva M.
Khalili, Saeed
Mui, Brennan
Zheng, Changyu
Tran, Simon D.
TI Cannulation of the Mouse Submandibular Salivary Gland via the Wharton's
Duct
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Medicine; Issue 51; Mouse; Salivary Gland; Wharton's Duct; dental
disease; progenitor; stem cells
AB Severe salivary gland hypofunction is frequently found in patients with Sjogren's syndrome and those who receiving therapeutic irradiation in their head and neck regions for cancer treatment. Both groups of patients experience symptoms such as xerostomia (dry mouth), dysphagia (impaired chewing and swallowing), severe dental caries, altered taste, oro-pharyngeal infections (candidiasis), mucositis, pain and discomfort.
One innovative approach of regenerative medicine for the treatment of salivary gland hypo-function is speculated in RS Redman, E Mezey et al. 2009: stem cells can be directly deposited by cannulation into the gland as a potent method in reviving the functions of the impaired organ. Presumably, the migrated foreign stem cells will differentiate into glandular cells to function as part of the host salivary gland. Also, this cannulation technique is an expedient and effective delivery method for clinical gene transfer application.
Here we illustrate the steps involved in performing the cannulation procedure on the mouse submandibular salivary gland via the Wharton's duct (Fig 1). C3H mice (Charles River, Montreal, QC, Canada) are used for this experiment, which have been kept under clean conventional conditions at the McGill University animal resource center. All experiments have been approved by the University Animal Care Committee and were in accordance with the guidelines of the Canadian Council on Animal Care.
For this experiment, a trypan blue solution is infused into the gland through the opening of the Wharton's duct using a insulin syringe with a 29-gauge needle encased inside a polyethylene tube. Subsequently, the mouse is dissected to show that the infusions migrated into the gland successfully.
C1 [Kuriki, Yusuke; Liu, Younan; Xia, Dengsheng; Gjerde, Eva M.; Khalili, Saeed; Mui, Brennan; Tran, Simon D.] McGill Univ, Fac Dent, Montreal, PQ H3A 2T5, Canada.
[Zheng, Changyu] NIH, Bethesda, MD 20892 USA.
RP Kuriki, Y (reprint author), McGill Univ, Fac Dent, Montreal, PQ H3A 2T5, Canada.
FU Canadian Institutes for Health Research
FX The authors are grateful to Dr. Ana Cotrim for technical consultation
and to Dr. Monzur Murshed for equipment. This work was in part funded by
the Canadian Institutes for Health Research.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD MAY
PY 2011
IS 51
AR UNSP e3074
DI 10.3791/3074
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36MA
UT WOS:000209214800053
ER
PT J
AU Li, WL
Mukouyama, YS
AF Li, Wenling
Mukouyama, Yoh-suke
TI Whole-mount Immunohistochemical Analysis for Embryonic Limb Skin
Vasculature: a Model System to Study Vascular Branching Morphogenesis in
Embryo
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Developmental Biology; Issue 51; Confocal microscopy; whole-mount
immunohistochemistry; mouse embryo; blood vessel; lymphatic vessel;
vascular patterning; arterial differentiation
AB Whole-mount immunohistochemical analysis for imaging the entire vasculature is pivotal for understanding the cellular mechanisms of branching morphogenesis. We have developed the limb skin vasculature model to study vascular development in which a pre-existing primitive capillary plexus is reorganized into a hierarchically branched vascular network. Whole-mount confocal microscopy with multiple labelling allows for robust imaging of intact blood vessels as well as their cellular components including endothelial cells, pericytes and smooth muscle cells, using specific fluorescent markers. Advances in this limb skin vasculature model with genetic studies have improved understanding molecular mechanisms of vascular development and patterning. The limb skin vasculature model has been used to study how peripheral nerves provide a spatial template for the differentiation and patterning of arteries. This video article describes a simple and robust protocol to stain intact blood vessels with vascular specific antibodies and fluorescent secondary antibodies, which is applicable for vascularized embryonic organs where we are able to follow the process of vascular development.
C1 [Li, Wenling; Mukouyama, Yoh-suke] NHLBI, Lab Stem Cell & Neurovasc Biol, Genet & Dev Biol Ctr, NIH, Tucson, AZ USA.
RP Mukouyama, YS (reprint author), NHLBI, Lab Stem Cell & Neurovasc Biol, Genet & Dev Biol Ctr, NIH, Tucson, AZ USA.
EM mukoyamay@nhlbi.nih.gov
FU Intramural Research Program of Naitonal Institutes of Health
FX We thank K. Gill for assistance with mouse breeding and care and for
laboratory management. Thanks also to Mukoyama lab members for technical
help. Funding was provided by Intramural Research Program of Naitonal
Institutes of Health.
NR 4
TC 0
Z9 0
U1 3
U2 3
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD MAY
PY 2011
IS 51
AR e2620
DI 10.3791/2620
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA V36MA
UT WOS:000209214800012
ER
PT J
AU Maric, I
Calvo, KR
AF Maric, Irina
Calvo, Katherine R.
TI Mastocytosis: the new differential diagnosis of CD30-positive neoplasms
SO LEUKEMIA & LYMPHOMA
LA English
DT Editorial Material
ID MAST-CELL DISEASE
C1 [Maric, Irina; Calvo, Katherine R.] NIH, Hematol Sect, DLM, CC, Bethesda, MD 20892 USA.
RP Maric, I (reprint author), NIH, Hematol Sect, DLM, CC, Bldg 10-2C390,10 Ctr Dr, Bethesda, MD 20892 USA.
EM marici@cc.nih.gov
RI Calvo, Katherine/A-8109-2009;
OI Calvo, Katherine/0000-0002-0771-4191
NR 8
TC 3
Z9 3
U1 0
U2 0
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1042-8194
J9 LEUKEMIA LYMPHOMA
JI Leuk. Lymphoma
PD MAY
PY 2011
VL 52
IS 5
BP 732
EP 733
DI 10.3109/10428194.2011.561389
PG 2
WC Oncology; Hematology
SC Oncology; Hematology
GA 752JD
UT WOS:000289686500002
PM 21463113
ER
PT J
AU Glynn, NW
Santanasto, AJ
Newman, MA
Mackey, DC
Simonsick, EM
Newman, AB
Goodpaster, BH
AF Glynn, Nancy W.
Santanasto, Adam J.
Newman, Mark A.
Mackey, Dawn C.
Simonsick, Eleanor M.
Newman, Anne B.
Goodpaster, Bret H.
TI Determinants Of Peak Oxygen Consumption In Older Adults: Function Or
Fatigue?
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
C1 [Glynn, Nancy W.; Santanasto, Adam J.; Newman, Mark A.; Newman, Anne B.; Goodpaster, Bret H.] Univ Pittsburgh, Pittsburgh, PA USA.
[Mackey, Dawn C.] Calif Pacific Med Ctr, San Francisco, CA USA.
[Simonsick, Eleanor M.] NIA, Baltimore, MD 21224 USA.
EM glynnn@edc.pitt.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2011
VL 43
IS 5
SU 1
MA 547
BP 4
EP 4
PG 1
WC Sport Sciences
SC Sport Sciences
GA V34IG
UT WOS:000209079500011
ER
PT J
AU Matthews, CE
George, SM
Moore, SC
Bowles, HR
Park, Y
Blair, A
Troiano, RP
Hollenbeck, A
Schatzkin, A
AF Matthews, Charles E.
George, Stephanie M.
Moore, Steven C.
Bowles, Heather R.
Park, Yikyung
Blair, Aaron
Troiano, Richard P.
Hollenbeck, Albert
Schatzkin, Arthur
TI Amount Of Time Spent In Sedentary Behaviors And Cause-specific Mortality
In Us Adults
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
C1 [Matthews, Charles E.; George, Stephanie M.; Moore, Steven C.; Bowles, Heather R.; Park, Yikyung; Blair, Aaron; Troiano, Richard P.; Schatzkin, Arthur] NCI, Rockville, MD USA.
[Hollenbeck, Albert] AARP, Washington, DC USA.
EM charles.matthews2@nih.gov
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 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2011
VL 43
IS 5
SU 1
MA 623
BP 28
EP 28
PG 1
WC Sport Sciences
SC Sport Sciences
GA V34IG
UT WOS:000209079500076
ER
PT J
AU Moore, SC
Patel, A
Matthews, CE
de Gonzalez, AB
Park, Y
Schatzkin, A
Linet, MS
Weiderpass, E
Visvanathan, K
Thun, M
Hartge, P
Lee, IM
AF Moore, Steven C.
Patel, Alpa
Matthews, Charles E.
de Gonzalez, Amy Berrington
Park, Yikyung
Schatzkin, Arthur
Linet, Martha S.
Weiderpass, Elisabete
Visvanathan, Kala
Thun, Michael
Hartge, Patricia
Lee, I-Min
TI Physical Activity, Body Mass Index, And Mortality: a Pooled Analysis Of
650,000 Adults
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
C1 [Moore, Steven C.; Matthews, Charles E.; de Gonzalez, Amy Berrington; Park, Yikyung; Schatzkin, Arthur; Linet, Martha S.; Hartge, Patricia] NCI, Rockville, MD USA.
[Patel, Alpa; Thun, Michael] Amer Canc Soc, Atlanta, GA 30329 USA.
[Weiderpass, Elisabete] Karolinska Inst, Stockholm, Sweden.
[Visvanathan, Kala] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Lee, I-Min] Harvard Univ, Sch Med, Boston, MA USA.
RI Weiderpass, Elisabete/M-4029-2016
OI Weiderpass, Elisabete/0000-0003-2237-0128
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2011
VL 43
IS 5
SU 1
MA 622
BP 28
EP 28
PG 1
WC Sport Sciences
SC Sport Sciences
GA V34IG
UT WOS:000209079500075
ER
PT J
AU Parascandola, M
AF Parascandola, Mark
TI The Smokeless Tobacco Industry's Use Of Sports Medicine In Marketing And
Promotion
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
C1 [Parascandola, Mark] NCI, Rockville, MD USA.
EM markparascandola@yahoo.com
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2011
VL 43
IS 5
SU 1
MA 1359
BP 276
EP 276
PG 1
WC Sport Sciences
SC Sport Sciences
GA V34IG
UT WOS:000209079501116
ER
PT J
AU Brown, JC
Huedo-Medina, TB
Johnson, BT
Pescatello, SM
Ryan, SM
Ferrer, RA
Pescatello, LS
AF Brown, Justin C.
Huedo-Medina, Tania B.
Johnson, Blair T.
Pescatello, Shannon M.
Ryan, Stacey M.
Ferrer, Rebecca A.
Pescatello, Linda S.
TI The Efficacy Of Exercise Interventions On Depression Among
Cancer-Survivors: A Meta-Analysis
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
C1 [Brown, Justin C.; Huedo-Medina, Tania B.; Johnson, Blair T.; Pescatello, Linda S.] Univ Connecticut, Storrs, CT USA.
[Pescatello, Shannon M.] Western New England Coll, Springfield, MA USA.
[Ryan, Stacey M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Ferrer, Rebecca A.] NCI, Rockville, MD 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 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2011
VL 43
IS 5
SU 1
MA 1362
BP 277
EP 278
PG 2
WC Sport Sciences
SC Sport Sciences
GA V34IG
UT WOS:000209079501119
ER
PT J
AU DellaValle, DM
Haas, JD
AF DellaValle, Diane M.
Haas, Jere D.
TI What Is The Impact Of Iron Supplementation On Training Quality In
Non-anemic Female Rowers?
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
C1 [DellaValle, Diane M.] NIH, Bethesda, MD 20892 USA.
[Haas, Jere D.] Cornell Univ, Ithaca, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2011
VL 43
IS 5
SU 1
MA 2004
BP 510
EP 510
PG 1
WC Sport Sciences
SC Sport Sciences
GA V34IG
UT WOS:000209079502116
ER
PT J
AU Caserotti, P
Rasmussen, C
Lysdahlgaard, M
Puggaard, L
Harris, T
Aagaard, P
AF Caserotti, Paolo
Rasmussen, Cuno
Lysdahlgaard, Morten
Puggaard, Lis
Harris, Tamara
Aagaard, Per
TI Effects of Heavy-resistance Power Training on Force Steadiness in Old
and Very Old Women
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
C1 [Caserotti, Paolo; Harris, Tamara] NIH, Maryland, WA USA.
[Rasmussen, Cuno] Univ Aarhus, Aarhus, Denmark.
[Lysdahlgaard, Morten; Puggaard, Lis; Aagaard, Per] Univ Southern Denmark, Odense, Denmark.
EM paagaard@health.sdu.dk
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2011
VL 43
IS 5
SU 1
MA 2014
BP 513
EP 513
PG 1
WC Sport Sciences
SC Sport Sciences
GA V34IG
UT WOS:000209079502126
ER
PT J
AU Volshoj, E
Thorlund, JB
Andrijauskaite, Z
Caserotti, P
Aagaard, P
AF Volshoj, Esben
Thorlund, Jonas B.
Andrijauskaite, Zita
Caserotti, Paolo
Aagaard, Per
TI Transitional Postural Stability Differs Between Male and Female Team
Handball Players: Potential Implications for ACL Injury
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
C1 [Volshoj, Esben; Thorlund, Jonas B.; Aagaard, Per] Univ Southern Denmark, Odense, Denmark.
[Andrijauskaite, Zita] Lithuanian Acad Phys Educ, Kaunas, Lithuania.
[Caserotti, Paolo] NIH, Maryland, WA USA.
EM paagaard@health.sdu.dk
NR 0
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2011
VL 43
IS 5
SU 1
MA 2062
BP 530
EP 531
PG 3
WC Sport Sciences
SC Sport Sciences
GA V34IG
UT WOS:000209079502174
ER
PT J
AU Aagaard, P
Eie, R
Harris, T
Caserotti, P
AF Aagaard, Per
Eie, Rune
Harris, Tamara
Caserotti, Paolo
TI Explosive-type Heavy-resistance Strength Training Leads To Improved
Postural Stability in 60 And 80-yr Old Women
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
C1 [Aagaard, Per; Eie, Rune] Inst Sports Sci & Clin Biomech, Odense, Denmark.
[Harris, Tamara; Caserotti, Paolo] NIH, Bethesda, MD USA.
EM paagaard@health.sdu.dk
NR 0
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2011
VL 43
IS 5
SU 1
MA 2063
BP 531
EP 531
PG 1
WC Sport Sciences
SC Sport Sciences
GA V34IG
UT WOS:000209079502175
ER
PT J
AU Gabriel, KKP
McClain, JJ
Schmid, KK
High, RR
Whitfield, GP
Ainsworth, BE
AF Gabriel, Kelley K. Pettee
McClain, James J.
Schmid, Kendra K.
High, Robin R.
Whitfield, Geoffrey P.
Ainsworth, Barbara E.
TI Descriptive Study Of Accelerometer-derived Measures Of Sedentary
Behavior In Middle-aged Women
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
C1 [Gabriel, Kelley K. Pettee; Whitfield, Geoffrey P.] Univ Texas Austin, Sch Publ Hlth, Austin, TX 78712 USA.
[McClain, James J.] Canc Prevent Fellowship Program, Bethesda, MD USA.
[McClain, James J.] NCI, Bethesda, MD 20892 USA.
[Schmid, Kendra K.; High, Robin R.] Univ Nebraska Med Ctr, Omaha, NE USA.
[Ainsworth, Barbara E.] Arizona State Univ, Mesa, AZ USA.
EM Kelley.P.Gabriel@uth.tmc.edu
NR 0
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2011
VL 43
IS 5
SU 1
MA 2084
BP 538
EP 538
PG 1
WC Sport Sciences
SC Sport Sciences
GA V34IG
UT WOS:000209079502196
ER
PT J
AU McClain, JJ
Troiano, RP
Berrigan, D
Brychta, RJ
Koster, A
AF McClain, James J.
Troiano, Richard P.
Berrigan, David
Brychta, Robert J.
Koster, Annemarie
TI Principal Component Analysis of Accelerometer-Assessed Daily Physical
Activity and Inactivity Among Adults
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
C1 [McClain, James J.; Troiano, Richard P.; Berrigan, David] NCI, Bethesda, MD 20892 USA.
[Brychta, Robert J.] NIDDK, Bethesda, MD USA.
[Koster, Annemarie] NIA, Bethesda, MD 20892 USA.
EM james.mcclain@nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2011
VL 43
IS 5
SU 1
MA 2087
BP 539
EP 539
PG 1
WC Sport Sciences
SC Sport Sciences
GA V34IG
UT WOS:000209079502199
ER
PT J
AU Hoehner, CM
Handy, SL
Yan, Y
Blair, SN
Berrigan, D
AF Hoehner, Christine M.
Handy, Susan L.
Yan, Yan
Blair, Steven N.
Berrigan, David
TI Association Between Neighborhood Walkability, Cardiorespiratory Fitness,
And Body-Mass Index
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
C1 [Hoehner, Christine M.; Yan, Yan] Washington Univ, St Louis, MO USA.
[Handy, Susan L.] Univ Calif Davis, Davis, CA 95616 USA.
[Blair, Steven N.] Univ S Carolina, Columbia, SC 29208 USA.
[Berrigan, David] NCI, Bethesda, MD 20892 USA.
EM hoehnerc@wustl.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2011
VL 43
IS 5
SU 1
MA 2169
BP 569
EP 570
PG 3
WC Sport Sciences
SC Sport Sciences
GA V34IG
UT WOS:000209079502281
ER
PT J
AU Smith, K
Shizukuda, Y
Tripodi, D
Arena, R
Bolan, CD
Yau, YY
Leitman, SF
Rosing, DR
AF Smith, Kevin
Shizukuda, Yukitaka
Tripodi, Dorothy
Arena, Ross
Bolan, Charles D.
Yau, Yu Ying
Leitman, Susan F.
Rosing, Douglas R.
TI Changes in Exercise Capacity of Asymptomatic Hereditary Hemochromatosis
Subjects Over 5-year Follow Up
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
C1 [Smith, Kevin; Tripodi, Dorothy; Bolan, Charles D.; Yau, Yu Ying; Leitman, Susan F.; Rosing, Douglas R.] NIH, Bethesda, MD 20892 USA.
[Shizukuda, Yukitaka] VA Med Ctr, Cincinnati, OH USA.
[Arena, Ross] Virginia Commonwealth Univ, Richmond, VA USA.
EM smithkp@nhlbi.nih.gov
RI Arena, Ross/A-3141-2008
OI Arena, Ross/0000-0002-6675-1996
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2011
VL 43
IS 5
SU 1
MA 2715
BP 758
EP 758
PG 1
WC Sport Sciences
SC Sport Sciences
GA V34IG
UT WOS:000209079503184
ER
PT J
AU Unick, J
Beavers, D
Jakicic, JM
Kitabchi, AE
Knowler, WC
Wing, RR
AF Unick, Jessica
Beavers, Daniel
Jakicic, John M.
Kitabchi, Abbas E.
Knowler, William C.
Wing, Rena R.
TI Changes in Fitness following a Behavioral Weight Loss Program in
Severely Obese Individuals
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Meeting Abstract
C1 [Unick, Jessica; Wing, Rena R.] Miriam Hosp, Providence, RI 02906 USA.
[Unick, Jessica; Wing, Rena R.] Brown Med Sch, Providence, RI USA.
[Beavers, Daniel] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Jakicic, John M.] Univ Pittsburgh, Pittsburgh, PA USA.
[Kitabchi, Abbas E.] Univ Tennessee, Memphis, TN USA.
[Knowler, William C.] NIDDK, Phoenix, AZ USA.
EM junick@lifespan.org
RI Beavers, Daniel/G-5338-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2011
VL 43
IS 5
SU 1
MA 3056
BP 877
EP 878
PG 2
WC Sport Sciences
SC Sport Sciences
GA V34IG
UT WOS:000209079503523
ER
PT J
AU Leiva-Salinas, C
Hom, J
Warach, S
Wintermark, M
AF Leiva-Salinas, Carlos
Hom, Jason
Warach, Steven
Wintermark, Max
TI Stroke Imaging Research Road Map
SO NEUROIMAGING CLINICS OF NORTH AMERICA
LA English
DT Article
DE Stroke; MR imaging; CT; DWI; Perfusion; Thrombolysis
ID ACUTE ISCHEMIC-STROKE; DIFFUSION; MRI; HETEROGENEITY; DESMOTEPLASE;
THROMBOLYSIS; ALTEPLASE; FUTURE; TRIALS
AB Although acute stroke imaging has made significant progress in the last few years, several improvements and validation steps are needed to make stroke-imaging techniques fully operational and appropriate in daily clinical practice. This review outlines the needs in the stroke-imaging field and describes a consortium that was founded to provide them.
C1 [Leiva-Salinas, Carlos; Wintermark, Max] Univ Virginia, Neuroradiol Div, Dept Radiol, Charlottesville, VA 22908 USA.
[Leiva-Salinas, Carlos] Univ Autonoma Barcelona, Dept Med, Cerdanola Del Valles 08290, Spain.
[Hom, Jason] Univ Calif San Francisco, Neuroradiol Sect, Dept Radiol, San Francisco, CA 94143 USA.
[Warach, Steven] NINDS, Sect Stroke Diagnost & Therapeut, NIH, Bethesda, MD 20892 USA.
RP Wintermark, M (reprint author), Univ Virginia, Neuroradiol Div, Dept Radiol, 1215 Lee St New Hosp,POB 800170, Charlottesville, VA 22908 USA.
EM Max.Wintermark@virginia.edu
OI Wintermark, Max/0000-0002-6726-3951
FU NINDS NIH HHS [R13 NS061371-01, R13 NS061371]
NR 16
TC 6
Z9 6
U1 1
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1052-5149
J9 NEUROIMAG CLIN N AM
JI Neuroimaging Clin. N. Am.
PD MAY
PY 2011
VL 21
IS 2
BP 239
EP +
DI 10.1016/j.nic.2011.01.009
PG 8
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 782KP
UT WOS:000292007900005
PM 21640297
ER
PT J
AU Kubben, N
Voncken, JW
Konings, G
van Weeghel, M
van den Hoogenhof, MMG
Gijbels, M
van Erk, A
Schoonderwoerd, K
van den Bosch, B
Dahlmans, V
Calis, C
Houten, SM
Misteli, T
Pinto, YM
AF Kubben, Nard
Voncken, Jan Willem
Konings, Gonda
van Weeghel, Michel
van den Hoogenhof, Maarten M. G.
Gijbels, Marion
van Erk, Arie
Schoonderwoerd, Kees
van den Bosch, Bianca
Dahlmans, Vivian
Calis, Chantal
Houten, Sander M.
Misteli, Tom
Pinto, Yigal M.
TI Post-natal myogenic and adipogenic developmental Defects and metabolic
impairment upon loss of A-type lamins
SO NUCLEUS-AUSTIN
LA English
DT Article
DE laminopathies; lamin A; LMNA; knock-out mouse; cardiac hypertrophy;
muscular dystrophy; differentiation
AB A-type lamins are a major component of the nuclear lamina. Mutations in the LMNA gene, which encodes the A-type lamins A and C, cause a set of phenotypically diverse diseases collectively called laminopathies. While adult LMNA null mice show various symptoms typically associated with laminopathies, the effect of loss of lamin A/C on early postnatal development is poorly understood. Here we developed a novel LMNA null mouse (LMNA(GT-/-)) based on genetrap technology and analyzed its early post-natal development. We detect LMNA transcripts in heart, the outflow tract, dorsal aorta, liver and somites during early embryonic development. Loss of A-type lamins results in severe growth retardation and developmental defects of the heart, including impaired myocyte hypertrophy, skeletal muscle hypotrophy, decreased amounts of subcutaneous adipose tissue and impaired ex vivo adipogenic differentiation. These defects cause death at 2 to 3 weeks post partum associated with muscle weakness and metabolic complications, but without the occurrence of dilated cardiomyopathy or an obvious progeroid phenotype. Our results indicate that defective early postnatal development critically contributes to the disease phenotypes in adult laminopathies.
C1 [Kubben, Nard] Maastricht Univ, Med Ctr, Heart Failure Res Ctr, Maastricht, Netherlands.
[Kubben, Nard] Maastricht Univ, Med Ctr, Dept Cardiol, Maastricht, Netherlands.
[Gijbels, Marion] Maastricht Univ, Med Ctr, Cardiovasc Res Inst Maastricht, Dept Mol Genet, Maastricht, Netherlands.
[Voncken, Jan Willem; Dahlmans, Vivian] Maastricht Univ, Med Ctr, Dept Mol Genet, Maastricht, Netherlands.
[van den Bosch, Bianca; Calis, Chantal] Maastricht Univ, Med Ctr, Sch Oncol & Dev Biol, Dept Clin Genom,Transgenesis & Target Unit, Maastricht, Netherlands.
[Konings, Gonda] Maastricht Univ, Med Ctr, Dept Resp Med, NUTRIM Sch Nutr Toxicol & Metab, Maastricht, Netherlands.
[van Erk, Arie] Maastricht Univ, Med Ctr, BiGCaT Bioinformat, Maastricht, Netherlands.
[van den Bosch, Bianca; Calis, Chantal] Maastricht Univ, Med Ctr, Dept Clin Genet, Maastricht, Netherlands.
[Kubben, Nard; Misteli, Tom] NCI, Genome Cell Biol Grp, NIH, Bethesda, MD 20892 USA.
[van Weeghel, Michel; Houten, Sander M.] Univ Amsterdam, Acad Med Ctr, Dept Paediat, Emma Childrens Hosp,Lab Genet Metab Dis,AZ, NL-1105 AZ Amsterdam, Netherlands.
[van Weeghel, Michel; Houten, Sander M.] Univ Amsterdam, Acad Med Ctr, Dept Clin Chem, Emma Childrens Hosp,Lab Genet Metab Dis,AZ, NL-1105 AZ Amsterdam, Netherlands.
[van den Hoogenhof, Maarten M. G.; Pinto, Yigal M.] Univ Amsterdam, Acad Med Ctr, Heart Failure Res Ctr, AZ, NL-1105 AZ Amsterdam, Netherlands.
[Schoonderwoerd, Kees] ErasmusMC Univ, Med Ctr, Dept Clin Genet, GE, Rotterdam, Netherlands.
RP Pinto, YM (reprint author), Univ Amsterdam, Acad Med Ctr, Heart Failure Res Ctr, AZ, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
EM Y.Pinto@uva.amc.nl
RI van Weeghel, Michel/A-2766-2010;
OI Houten, Sander/0000-0002-6167-9147
FU Intramural Research Program of the National Institutes of Health (NIH),
NCI, Center for Cancer Research; Dutch Heart Foundation; ZonMW; EU-KP7
grant 'Inheritance'
FX We thank S. Frints, M. W. Schellings, C. van het Hoofd and A. Voets for
technical expertise and help. J.P. Cleutjens is thanked for help with
quantification of myocyte cross-sectional areas, H. Duimel for electron
microscopy imaging, and P. Scaffidi and S. G. Rane for adipogenic
differentiation assays. Fast and reliable assistance in arranging animal
experiments by members of the central animal facilities was instrumental
for phenotypic analyses. This research was supported in part by the
Intramural Research Program of the National Institutes of Health (NIH),
NCI, Center for Cancer Research, grants from the Dutch Heart Foundation,
ZonMW and the EU-KP7 grant 'Inheritance'.
NR 32
TC 38
Z9 39
U1 0
U2 7
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1949-1034
J9 NUCLEUS-AUSTIN
JI Nucleus-Austin
PD MAY-JUN
PY 2011
VL 2
IS 3
BP 195
EP 207
DI 10.4161/nucl.2.3.15731
PG 13
WC Cell Biology
SC Cell Biology
GA V28GJ
UT WOS:000208669000011
PM 21818413
ER
PT J
AU Landon, MB
Mele, L
Spong, CY
AF Landon, Mark B.
Mele, Lisa
Spong, Catherine Y.
TI The Relationship Between Maternal Glycemia and Perinatal Outcome Reply
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Letter
C1 [Landon, Mark B.; Mele, Lisa; Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units MFMU Network, Bethesda, MD USA.
RP Landon, MB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units MFMU Network, Bethesda, MD USA.
NR 3
TC 1
Z9 1
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 MAY
PY 2011
VL 117
IS 5
BP 1230
EP 1231
DI 10.1097/AOG.0b013e31821769ff
PG 5
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 753KF
UT WOS:000289771000041
ER
PT J
AU Huppi, K
Pitt, J
Wahlberg, B
Caplen, NJ
AF Huppi, Konrad
Pitt, Jason
Wahlberg, Brady
Caplen, Natasha J.
TI Genomic instability and mouse microRNAs
SO TOXICOLOGY MECHANISMS AND METHODS
LA English
DT Review
DE MicroRNA; retrovirus; genomic instability
ID B-CELL LYMPHOMAS; GLIOBLASTOMA CELLS; LUNG-CANCER; LEUKEMIA;
MUTAGENESIS; TARGETS; CLUSTER; MICE; TRANSLOCATIONS; IDENTIFICATION
AB Tumor progression is the continual selection of variant subpopulations of malignant cells that have acquired increasing levels of genetic instability (Nowell Science 1976, 194, 23-28). This instability is manifested as chromosomal aneuploidy or translocations, viral integration or somatic mutations that typically affect the expression of a gene (oncogene) that is especially damaging to the proper function of a cell. With the recent discovery of non-coding RNAs such as microRNAs (miRNAs), the concept that a target of genetic instability must be a protein-encoding gene is no longer tenable. Over the years, we have conducted several studies comparing the location of miRNA genes to positions of genetic instability, principally retroviral integration sites and chromosomal translocations in the mouse as a means of identifying miRNAs of importance in carcinogenesis. In this current study, we have used the most recent annotation of the mouse miRome (miRBase, release 16.0), and several datasets reporting the sites of integration of different retroviral vectors in a variety of mouse strains and mouse models of cancer, including for the first time a model that shows a propensity to form solid tumors, as a means to further identify or define, candidate oncogenic miRNAs. Several miRNA genes and miRNA gene clusters stand out as interesting new candidate oncogenes due to their close proximity to common retroviral integration sites including miR-29a/b/c and miR106a similar to 363. We also discussed some recently identified miRNAs including miR-1965, miR-1900, miR-1945, miR-1931, miR-1894, and miR-1936 that are close to common retroviral integration sites and are therefore likely to have some role in cell homeostasis.
C1 [Huppi, Konrad; Pitt, Jason; Wahlberg, Brady; Caplen, Natasha J.] NCI, Gene Silencing Sect, Genet Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Huppi, K (reprint author), NCI, Gene Silencing Sect, Genet Branch, Ctr Canc Res,NIH, Bldg 37,Room 6128, Bethesda, MD 20892 USA.
EM huppi@helix.nih.gov
RI Caplen, Natasha/H-2768-2016
OI Caplen, Natasha/0000-0002-0001-9460
FU (Center for Cancer Research, NCI) of the NIH
FX We wish to acknowledge support of the intramural research program
(Center for Cancer Research, NCI) of the NIH.
NR 33
TC 7
Z9 8
U1 0
U2 2
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1537-6516
EI 1537-6524
J9 TOXICOL MECH METHOD
JI Toxicol. Mech. Methods
PD MAY
PY 2011
VL 21
IS 4
SI SI
BP 325
EP 333
DI 10.3109/15376516.2011.562759
PG 9
WC Toxicology
SC Toxicology
GA 751PL
UT WOS:000289629900007
PM 21495870
ER
PT J
AU Reedy, J
Kirkpatrick, SI
AF Reedy, Jill
Kirkpatrick, Sharon I.
TI The Use of Proprietary Nutrient Profiling Tools in Nutrition Science and
Policy A Commentary
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Editorial Material
ID INDEX; FOODS
C1 [Reedy, Jill; Kirkpatrick, Sharon I.] NCI, Div Canc Control & Populat Sci, Appl Res Program, Risk Factor Monitoring & Methods Branch, Bethesda, MD 20892 USA.
RP Reedy, J (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, Risk Factor Monitoring & Methods Branch, 6130 Execut Blvd,EPN 4005,MSC 7344, Bethesda, MD 20892 USA.
EM reedyj@mail.nih.gov
OI Kirkpatrick, Sharon/0000-0001-9896-5975
NR 4
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 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD MAY
PY 2011
VL 40
IS 5
BP 581
EP 582
DI 10.1016/j.amepre.2011.02.010
PG 2
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 749YC
UT WOS:000289506900018
PM 21496762
ER
PT J
AU Song, JY
Eberle, FC
Xi, LQ
Raffeld, M
Rahma, O
Wilson, WH
Dunleavy, K
Pittaluga, S
Jaffe, ES
AF Song, Joo Y.
Eberle, Franziska C.
Xi, Liqiang
Raffeld, Mark
Rahma, Osama
Wilson, Wyndham H.
Dunleavy, Kieron
Pittaluga, Stefania
Jaffe, Elaine S.
TI Coexisting and Clonally Identical Classic Hodgkin Lymphoma and Nodular
Lymphocyte Predominant Hodgkin Lymphoma
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE nodular lymphocyte predominant Hodgkin lymphoma; classic Hodgkin
lymphoma; LP cell; Reed-Sternberg cell; familial lymphoma
ID REED-STERNBERG CELLS; IMMUNOGLOBULIN GENE REARRANGEMENTS; B-CELL;
DISEASE; ORIGIN; POPULATIONS; PROGRESSION; COMPOSITE; REPRESENT;
EXPANSION
AB We report a case of concurrent nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and classic Hodgkin lymphoma (cHL), of nodular sclerosis subtype, in an otherwise healthy 24-year-old man with a strong family history of cHL. The patient was found to have a parotid mass, which was diagnosed as NLPHL, and a thymic mass diagnosed as cHL, of nodular sclerosis subtype concurrently. The lesion in the parotid showed features typical of NLPHL by morphology and immunophenotype. The LP cells were positive for PAX5, CD20, Oct2, weakly positive for CD30, and negative for CD15. The thymic lesion, diagnosed as cHL, of nodular sclerosis subtype, showed prominent bands of fibrosis and Hodgkin/Reed-Sternberg and lacunar cells positive for CD30 and CD15. These cells were variably positive for CD20 and negative for Oct2. PAX5 was weakly positive. Immunoglobulin gene rearrangement studies by polymerase chain reaction were carried out on microdissected Hodgkin/Reed-Sternberg and LP cells, which were shown to have identically sized peaks. NLPHL and cHL are 2 distinct diseases and are almost never seen concurrently. We present a case in which polymerase chain reaction analysis indicated that the tumor cells of these 2 distinct entities were clonally identical.
C1 [Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Rahma, Osama] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Wilson, Wyndham H.; Dunleavy, Kieron] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bldg 10,Room 2B 42,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA.
EM elainejaffe@nih.gov
RI Song, Joo/E-5356-2016;
OI Song, Joo/0000-0003-3497-2513; Jaffe, Elaine/0000-0003-4632-0301
FU Center for Cancer Research, National Cancer Institute, NIH
FX Supported by funding from the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, NIH.
NR 30
TC 7
Z9 7
U1 0
U2 2
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 MAY
PY 2011
VL 35
IS 5
BP 767
EP 772
DI 10.1097/PAS.0b013e3182147f91
PG 6
WC Pathology; Surgery
SC Pathology; Surgery
GA 749XZ
UT WOS:000289506600019
PM 21490448
ER
PT J
AU Schug, TT
Li, XL
AF Schug, Thaddeus T.
Li, Xiaoling
TI Sirtuin 1 in lipid metabolism and obesity
SO ANNALS OF MEDICINE
LA English
DT Article
DE Metabolic syndrome; metabolism; SIRT1
ID INDUCED INSULIN-RESISTANCE; SMALL-MOLECULE ACTIVATORS; WHITE
ADIPOSE-TISSUE; CALORIE RESTRICTION; DEACETYLASE SIRT1; PPAR-GAMMA;
LIFE-SPAN; SACCHAROMYCES-CEREVISIAE; ALTERNATIVE ACTIVATION; MACROPHAGE
ACTIVATION
AB Sirtuin 1 (SIRT1), the mammalian ortholog of yeast Sir2, is a highly conserved NADReasons for performing study:
To improve the understanding of exercise related sudden death in Thoroughbred racehorses.
Objectives:
To describe the post mortem findings in cases of sudden death associated with exercise in 268 Thoroughbred racehorses.
Methods:
Gross and histological post mortem findings of 268 cases of sudden death were collated and reviewed. Cases originated from 6 racing jurisdictions around the world. Sudden death was defined as acute collapse and death in a closely observed and previously apparently healthy Thoroughbred racehorse, during, or within one hour after, exercise. Cause of death as determined by the attending pathologist was categorised as definitive, presumptive or unexplained and compared between the different populations. Cardiopulmonary lesions recorded at post mortem examination were compared between different populations.
Results:
Pathologists recorded a definitive cause of death in 53% (143/268) of cases. Major definitive causes of sudden death included cardiac failure, apparent pulmonary failure, pulmonary haemorrhage, haemorrhage associated with pelvic fractures or with idiopathic blood vessel rupture, and spinal cord injury. A presumptive cause of death was made in 25% (67/268) of cases and death remained unexplained in 22% (58/268) of cases. There were several statistically significant inter-population differences in the cause of death and in reporting of cardiopulmonary lesions.
Conclusions:
Sudden death can be attributed to a variety of causes. Causes of sudden death and the lesions found in cases of exercise-related sudden death are similar in different racing jurisdictions. However, the lesions are often not specific for the cause of death and determination of the cause of death is therefore affected by interpretation by the individual pathologist.
C1 [Lyle, C. H.; McGorum, B. C.; Blissitt, K. J.] Univ Edinburgh, Royal Dick Sch Vet Studies, Easter Bush Vet Ctr, Edinburgh EH8 9YL, Midlothian, Scotland.
[Uzal, F. A.] Univ Calif Davis, Calif Anim Hlth & Food Safety Lab Syst, Davis, CA 95616 USA.
[Aida, H.] Equine Res Inst, Utsunomiya, Tochigi, Japan.
[Kusano, K.] Racehorse Hosp, Miho Training Ctr, Inashiki, Ibaraki, Japan.
[Case, J. T.] NIH, Natl Lib Med, US Dept Hlth & Human Serv, Bethesda, MD USA.
[Charles, J. T.; Slocombe, R. F.] Univ Melbourne, Ctr Vet Clin, Melbourne, Vic 3010, Australia.
[Horadagoda, N.] Univ Sydney, Univ Vet Teaching Hosp Camden, Sydney, NSW 2006, Australia.
[Lam, K.; Stewart, B. D.] Hong Kong Jockey Club, Dept Vet Regulat & Int Liaison, Sha Tin Racecourse, Hong Kong, Peoples R China.
[Pack, J. D.] Penn Natl Racetrack & Penn Anim Diagnost Lab, Grantville, PA USA.
[Parkin, T. D.; Boden, L. A.] Univ Glasgow, Coll Med Vet & Life Sci, Glasgow G12 8QQ, Lanark, Scotland.
RP Lyle, CH (reprint author), Univ Edinburgh, Royal Dick Sch Vet Studies, Easter Bush Vet Ctr, Edinburgh EH8 9YL, Midlothian, Scotland.
EM catriona.lyle@ed.ac.uk
OI Boden, Lisa/0000-0002-9317-4741; Parkin, Tim/0000-0003-3566-9030
FU Horserace Betting Levy Board
FX The Horserace Betting Levy Board who fund C.L.'s Senior Clinical
Training Scholarship at the University of Edinburgh; the contributing
centres (the California Horseracing Board, the California Animal Health
and Food Safety Laboratory System, University California Davis, Penn
National Race Track, the Pennsylvania Animal Diagnostic Laboratory
Harrisburg, Racing Victoria Ltd, the University of Melbourne, Racing New
South Wales, the University of Sydney, Department of Veterinary Clinical
Services Hong Kong Jockey Club and the Japan Racing Association); the
contributing pathologists (Adaska, J., Anderson, M., Barr, B.,
Blanchard, P., Corson, B., Daft, B., Diab, S., Farman, C., Ghoddus, M.,
Johnson, B., Kinde, H., La Roche, D., Loretti, A., Moore, J., Mysore,
J., Odani, J., Pesaven, P., Read, D., Shahriar, M., Stleger, J., Woods,
L.); the racecourse veterinarians and the Dorothy Havemeyer Foundation.
NR 24
TC 21
Z9 21
U1 2
U2 30
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0425-1644
J9 EQUINE VET J
JI Equine Vet. J.
PD MAY
PY 2011
VL 43
IS 3
BP 324
EP 331
DI 10.1111/j.2042-3306.2010.00164.x
PG 8
WC Veterinary Sciences
SC Veterinary Sciences
GA 750DB
UT WOS:000289523600012
PM 21492210
ER
PT J
AU Cao, J
de Lecea, L
Ikemoto, S
AF Cao, Junran
de Lecea, Luis
Ikemoto, Satoshi
TI Intraventricular administration of neuropeptide S has reward-like
effects
SO EUROPEAN JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE Self-administration; Place conditioning; Locomotion; Neuropeptide S; SB
334867; SCH 23390
ID HYPOTHALAMIC HYPOCRETIN SYSTEM; OLFACTORY TUBERCLE; LOCOMOTOR-ACTIVITY;
SENSITIZES RATS; COCAINE-SEEKING; DOPAMINE; AMPHETAMINE; AROUSAL; BRAIN;
MICE
AB Neuropeptide S (NPS) is an endogenous brain peptide produced by neurons located in the lower brainstem, and functional studies suggest that NPS has arousing effects. Because its receptors are found in reward-associated regions throughout the brain, we evaluated whether intraventricular NPS injections elicit reward-related effects in rats. Rats increased lever presses that led to intraventricular administration of NPS (0.34-34 pmol per infusion) in a dose dependent manner, with a cue-assisted procedure. Cue-assisted self-administration of NPS was decreased by systemic administration of the dopamine receptor antagonist SCH 23390 (0.025 mg/kg, i.p.) or the hypocretin-1 (orexin-1) receptor antagonist SB 334867 (20 mg/kg, i.p.). In addition, intraventricular NPS injections (1000 pmol) induced conditioned place preference, whereas a lower dose (100 pmol) of NPS induced conditioned place aversion. Finally, NPS injections (100-1000 pmol) acutely facilitated locomotor activity, whereas repeated NPS injections did not lead to locomotor sensitization. Our data suggest that intraventricular NPS injections have reward-like effects in that NPS weakly facilitates seeking and induces positive reinforcement. These effects may depend on intact dopamine and hypocretin systems. Published by Elsevier B.V.
C1 [Cao, Junran; Ikemoto, Satoshi] NIDA, Behav Neurosci Res Branch, NIH, US Dept HHS, Baltimore, MD 21224 USA.
[de Lecea, Luis] Stanford Univ, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA.
RP Ikemoto, S (reprint author), NIDA, Behav Neurosci Res Branch, NIH, US Dept HHS, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM satoshi.ikemoto@nih.gov
RI Cao, Junran/E-7354-2013;
OI Ikemoto, Satoshi/0000-0002-0732-7386
FU National Institute on Drug Abuse, National Institutes of Health;
[R01DA021880]
FX The present research was supported by the Intramural Research Program of
the National Institute on Drug Abuse, National Institutes of Health and
the extramural research grant R01DA021880 (to LdL).
NR 29
TC 11
Z9 11
U1 0
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-2999
EI 1879-0712
J9 EUR J PHARMACOL
JI Eur. J. Pharmacol.
PD MAY 1
PY 2011
VL 658
IS 1
BP 16
EP 21
DI 10.1016/j.ejphar.2011.02.009
PG 6
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 748MM
UT WOS:000289394700003
PM 21349268
ER
PT J
AU Lu, SJ
Crawford, GL
Dore, J
Anderson, SA
DesPres, D
Horowits, R
AF Lu, Shajia
Crawford, Garland L.
Dore, Justin
Anderson, Stasia A.
DesPres, Daryl
Horowits, Robert
TI Cardiac-specific NRAP overexpression causes right ventricular
dysfunction in mice
SO EXPERIMENTAL CELL RESEARCH
LA English
DT Article
DE NRAP; Cardiomyopathy; Heart; Intercalated disk; Transgenic;
Tetracycline-controlled transactivator
ID NEBULIN-RELATED PROTEIN; MUSCLE LIM PROTEIN; N-RAP; DILATED
CARDIOMYOPATHY; HEART-FAILURE; ALPHA-ACTININ; INTERCALATED DISC;
GENE-EXPRESSION; TRANSGENIC MICE; STRIATED-MUSCLE
AB The muscle-specific protein NRAP is concentrated at cardiac intercalated disks, plays a role in myofibril assembly, and is upregulated early in mouse models of dilated cardiomyopathy. Using a tet-off system, we developed novel transgenic lines exhibiting cardiac-specific NRAP overexpression similar to 2.5 times greater than normal. At 40-50 weeks, NRAP overexpression resulted in dilation and decreased ejection fraction in the right ventricle, with little effect on the left ventricle. Expression of transcripts encoding brain natriuretic peptide and skeletal alpha-actin was increased by cardiac-specific NRAP overexpression, indicative of a cardiomyopathic response. NRAP overexpression did not alter the levels or organization of N-cadherin and connexin-43. The results show that chronic NRAP overexpression in the mouse leads to right ventricular cardiomyopathy by 10 months, but that the early NRAP upregulation previously observed in some mouse models of dilated cardiomyopathy is unlikely to account for the remodeling of intercalated disks and left ventricular dysfunction observed in those cases. Published by Elsevier Inc.
C1 [Lu, Shajia; Crawford, Garland L.; Dore, Justin; Horowits, Robert] NIAMSD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Anderson, Stasia A.] NHLBI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[DesPres, Daryl] NINDS, Bethesda, MD 20892 USA.
[DesPres, Daryl] NIH, Mouse Imaging Facil, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Horowits, R (reprint author), NIAMSD, NIH, Dept Hlth & Human Serv, Bldg 50,Room 1154,MSC 8024, Bethesda, MD 20892 USA.
EM horowits@helix.nih.gov
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of
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 of
the National Institutes of Health. We thank Dr. Lionel Feigenbaum
(Laboratory Animal Sciences Program of the National Cancer Institute,
Frederick, MD) for producing the transgenic myc-NRAP founder mice, and
Dr. Kimberly Makar (NIAMS) for assistance with the design of the
myc-NRAP transgene. We are grateful to Dr. Brenda Klaunberg (NIH Mouse
Imaging Facility) for facilitating this work, and to Dr. Klaunberg and
Dr. Bob Adelstein (NHLBI) for helpful comments on the manuscript.
NR 38
TC 2
Z9 3
U1 1
U2 5
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4827
EI 1090-2422
J9 EXP CELL RES
JI Exp. Cell Res.
PD MAY 1
PY 2011
VL 317
IS 8
BP 1226
EP 1237
DI 10.1016/j.yexcr.2011.01.020
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 747RI
UT WOS:000289336700013
PM 21276443
ER
PT J
AU Hayashi, T
Tsai, SY
Mori, T
Fujimoto, M
Su, TP
AF Hayashi, Teruo
Tsai, Shang-Yi
Mori, Tomohisa
Fujimoto, Michiko
Su, Tsung-Ping
TI Targeting ligand-operated chaperone sigma-1 receptors in the treatment
of neuropsychiatric disorders
SO EXPERT OPINION ON THERAPEUTIC TARGETS
LA English
DT Review
ID ENDOPLASMIC-RETICULUM STRESS; OPEN CLINICAL-TRIAL; IMPROVED COGNITIVE
IMPAIRMENTS; POSITRON-EMISSION-TOMOGRAPHY; IMPROVES NEGATIVE SYMPTOMS;
UNFOLDED PROTEIN RESPONSE; UNIPOLAR MAJOR DEPRESSION; EMD 57445
PANAMESINE; ALZHEIMERS-DISEASE; MOLECULAR-MECHANISMS
AB Areas covered: Recent evidence that has shed light on sigma-1 receptor ligands, which may serve as a new class of antidepressants or neuroprotective agents. Sigma-1 receptors are novel ligand-operated molecular chaperones regulating signal transduction, ER stress, cellular redox, cellular survival and synaptogenesis. Selective sigma-1 receptor ligands exert rapid antidepressant-like, anxiolytic, antinociceptive and robust neuroprotective actions in preclinical studies. Recent studies that suggest that reactive oxygen species might play a role as signal integrators downstream of Sig-1Rs are also covered.
Expert opinion: The advances in sigma receptor research in the last decade have begun to elucidate the intracellular signal cascades upstream and downstream of sigma-1 receptors. The novel ligand-operated properties of the sigma-1 receptor chaperone may enable interventions by which stress-related cellular systems can be pharmacologically controlled.
C1 [Hayashi, Teruo; Fujimoto, Michiko] Natl Inst Drug Abuse, NIH, Cellular Stress Signaling Unit, Integrat Neurosci Branch, Baltimore, MD 21224 USA.
[Tsai, Shang-Yi; Mori, Tomohisa; Su, Tsung-Ping] Natl Inst Drug Abuse, NIH, Cellular Pathobiol Sect, Integral Neurosci Branch, Baltimore, MD 21224 USA.
RP Hayashi, T (reprint author), Natl Inst Drug Abuse, NIH, Cellular Stress Signaling Unit, Integrat Neurosci Branch, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM Thayashi@intra.nida.nih.gov
FU NIDA, NIH, DHHS; Japan Society for the Promotion of Sciences (JSPS)
FX All authors declare no conflict of interest. All authors are supported
by the Intramural Research Program, NIDA, NIH, DHHS. M Fujimoto is also
supported by a Japan Society for the Promotion of Sciences (JSPS)
Fellowship for Japanese Biochemical and Behavioral Researchers at NIH.
NR 141
TC 87
Z9 89
U1 3
U2 8
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1472-8222
J9 EXPERT OPIN THER TAR
JI Expert Opin. Ther. Targets
PD MAY
PY 2011
VL 15
IS 5
BP 557
EP 577
DI 10.1517/14728222.2011.560837
PG 21
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 748BQ
UT WOS:000289365400003
PM 21375464
ER
PT J
AU Boretsky, YR
Pynyaha, YV
Boretsky, VY
Fedorovych, DV
Fayura, LR
Protchenko, O
Philpott, CC
Sibirny, AA
AF Boretsky, Yuriy R.
Pynyaha, Yuriy V.
Boretsky, Volodymyr Y.
Fedorovych, Dariya V.
Fayura, Lyubov R.
Protchenko, Olha
Philpott, Caroline C.
Sibirny, Andriy A.
TI Identification of the genes affecting the regulation of riboflavin
synthesis in the flavinogenic yeast Pichia guilliermondii using
insertion mutagenesis
SO FEMS YEAST RESEARCH
LA English
DT Article
DE riboflavin biosynthesis; iron acquisition; VMA1; FES1; FRA1; oxidative
stress
ID NUCLEOTIDE EXCHANGE FACTOR; TRANSFORMATION SYSTEM; IRON ASSIMILATION;
CANDIDA-FAMATA; DEBARYOMYCES-HANSENII; OXIDATIVE STRESS
AB Pichia guilliermondii is a representative of a group of so-called flavinogenic yeast species that overproduce riboflavin (vitamin B(2)) in response to iron limitation. Using insertion mutagenesis, we isolated P. guilliermondii mutants overproducing riboflavin. Analysis of nucleotide sequence of recombination sites revealed that insertion cassettes integrated into the genome disrupting P. guilliermondii genes similar to the VMA1 gene of Ashbya gossypii and Saccharomyces cerevisiae and FES1 and FRA1 genes of S. cerevisiae. The constructed P. guilliermondii delta vma1-17 mutant possessed five- to sevenfold elevated riboflavin production and twofold decreased iron cell content as compared with the parental strain. Pichia guilliermondii delta fra1-45 mutant accumulated 1.8-2.2-fold more iron in the cells and produced five- to sevenfold more riboflavin as compared with the parental strain. Both delta vma1-17 and delta fes1-77 knockout strains could not grow at 37 degrees C in contrast to the wild-type strain and the delta fra1-45 mutant. Increased riboflavin production by the wild-type strain was observed at 37 degrees C. Although the delta fes1-77 mutant did not overproduce riboflavin, it showed partial complementation when crossed with previously isolated P. guilliermondii riboflavin-overproducing mutant rib80-22. Complementation analysis revealed that delta vma1-17 and delta fra1-45 mutants are distinct from previously reported riboflavin-producing mutants hit1-1, rib80-22 and rib81-31 of this yeast.
C1 [Boretsky, Yuriy R.; Pynyaha, Yuriy V.; Boretsky, Volodymyr Y.; Fedorovych, Dariya V.; Fayura, Lyubov R.; Sibirny, Andriy A.] Natl Acad Sci Ukraine, Dept Mol Genet & Biotechnol, Inst Cell Biol, UA-79005 Lvov, Ukraine.
[Protchenko, Olha; Philpott, Caroline C.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA.
[Sibirny, Andriy A.] Rzeszow Univ, Dept Biotechnol & Microbiol, Rzeszow, Poland.
RP Sibirny, AA (reprint author), Natl Acad Sci Ukraine, Dept Mol Genet & Biotechnol, Inst Cell Biol, Drahomanov St 14-16, UA-79005 Lvov, Ukraine.
EM sibirny@cellbiol.lviv.ua
OI Boretsky, Yuriy/0000-0001-7892-8915
FU Intramural NIH HHS [ZIA DK054507-13]
NR 32
TC 7
Z9 7
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1567-1356
J9 FEMS YEAST RES
JI FEMS Yeast Res.
PD MAY
PY 2011
VL 11
IS 3
BP 307
EP 314
DI 10.1111/j.1567-1364.2011.00720.x
PG 8
WC Biotechnology & Applied Microbiology; Microbiology; Mycology
SC Biotechnology & Applied Microbiology; Microbiology; Mycology
GA 748BG
UT WOS:000289364400008
PM 21261808
ER
PT J
AU Bookman, EB
McAllister, K
Gillanders, E
Wanke, K
Balshaw, D
Rutter, J
Reedy, J
Shaughnessy, D
Agurs-Collins, T
Paltoo, D
Atienza, A
Bierut, L
Kraft, P
Fallin, MD
Perera, F
Turkheimer, E
Boardman, J
Marazita, ML
Rappaport, SM
Boerwinkle, E
Suomi, SJ
Caporaso, NE
Hertz-Picciotto, I
Jacobson, KC
Lowe, WL
Goldman, LR
Duggal, P
Gunnar, MR
Manolio, TA
Green, ED
Olster, DH
Birnbaum, LS
AF Bookman, Ebony B.
McAllister, Kimberly
Gillanders, Elizabeth
Wanke, Kay
Balshaw, David
Rutter, Joni
Reedy, Jill
Shaughnessy, Daniel
Agurs-Collins, Tanya
Paltoo, Dina
Atienza, Audie
Bierut, Laura
Kraft, Peter
Fallin, M. Daniele
Perera, Frederica
Turkheimer, Eric
Boardman, Jason
Marazita, Mary L.
Rappaport, Stephen M.
Boerwinkle, Eric
Suomi, Stephen J.
Caporaso, Neil E.
Hertz-Picciotto, Irva
Jacobson, Kristen C.
Lowe, William L.
Goldman, Lynn R.
Duggal, Priya
Gunnar, Megan R.
Manolio, Teri A.
Green, Eric D.
Olster, Deborah H.
Birnbaum, Linda S.
CA NIH G E Interplay Workshop Partici
TI Gene-Environment Interplay in Common Complex Diseases: Forging an
Integrative Model-Recommendations From an NIH Workshop
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE gene-environment interaction; epidemiology; study design; genetics;
environment
ID GENOME-WIDE ASSOCIATION; CHILDRENS; GENOTYPE; HEALTH; RISK; MAOA
AB Although it is recognized that many common complex diseases are a result of multiple genetic and environmental risk factors, studies of gene-environment interaction remain a challenge and have had limited success to date. Given the current state-of-the-science, NIH sought input on ways to accelerate investigations of gene-environment interplay in health and disease by inviting experts from a variety of disciplines to give advice about the future direction of gene-environment interaction studies. Participants of the NIH Gene-Environment Interplay Workshop agreed that there is a need for continued emphasis on studies of the interplay between genetic and environmental factors in disease and that studies need to be designed around a multifaceted approach to reflect differences in diseases, exposure attributes, and pertinent stages of human development. The participants indicated that both targeted and agnostic approaches have strengths and weaknesses for evaluating main effects of genetic and environmental factors and their interactions. The unique perspectives represented at the workshop allowed the exploration of diverse study designs and analytical strategies, and conveyed the need for an interdisciplinary approach including data sharing, and data harmonization to fully explore gene-environment interactions. Further, participants also emphasized the continued need for high-quality measures of environmental exposures and new genomic technologies in ongoing and new studies. Genet. Epidemiol. 35: 217-225, 2011. (c) 2011 Wiley-Liss, Inc.
C1 [Bookman, Ebony B.; Manolio, Teri A.; Green, Eric D.] NHGRI, NIH, Bethesda, MD 20892 USA.
[McAllister, Kimberly; Balshaw, David; Shaughnessy, Daniel; Birnbaum, Linda S.] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA.
[Gillanders, Elizabeth; Reedy, Jill; Agurs-Collins, Tanya; Atienza, Audie] NCI, NIH, Bethesda, MD 20892 USA.
[Wanke, Kay; Olster, Deborah H.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
[Rutter, Joni] Natl Inst Drug Abuse, NIH, Bethesda, MD USA.
[Paltoo, Dina] NHLBI, NIH, Bethesda, MD 20892 USA.
[Bierut, Laura] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Fallin, M. Daniele; Goldman, Lynn R.; Duggal, Priya] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Perera, Frederica] Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY USA.
[Turkheimer, Eric] Univ Virginia, Dept Psychol, Charlottesville, VA 22903 USA.
[Boardman, Jason] Univ Colorado, Dept Sociol, Boulder, CO 80309 USA.
[Boardman, Jason] Univ Colorado, Inst Behav Sci, Boulder, CO 80309 USA.
[Marazita, Mary L.] Univ Pittsburgh, Sch Dent Med, Ctr Craniofacial & Dent Genet, Dept Oral Biol, Pittsburgh, PA USA.
[Rappaport, Stephen M.] Univ Calif Berkeley, Sch Publ Hlth, Dept Environm Hlth Sci, Berkeley, CA 94720 USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Sch Publ Hlth, Houston, TX USA.
[Suomi, Stephen J.] NICHHD, Comparat Ethol Lab, NIH, Bethesda, MD 20892 USA.
[Caporaso, Neil E.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Hertz-Picciotto, Irva] Univ Calif Davis, Dept Publ Hlth Sci, Davis, CA 95616 USA.
[Jacobson, Kristen C.] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA.
[Lowe, William L.] Northwestern Univ, Dept Med, Div Endocrinol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Gunnar, Megan R.] Univ Minnesota, Inst Child Dev, Minneapolis, MN 55455 USA.
RP Bookman, EB (reprint author), NHGRI, Off Populat Genom, 530 Davis Dr Room 3130 MSC K3-02, Morrisville, NC 27560 USA.
EM ebony.bookman@nih.gov
RI Jacobson, Kristen/D-2064-2009; Goldman, Lynn/D-5372-2012;
OI Rutter, Joni/0000-0002-6502-2361
FU Intramural NIH HHS [Z99 ES999999]; NCI NIH HHS [P01 CA089392-09, P01
CA089392]; NHGRI NIH HHS [U01 HG004422, U01 HG004422-02]; NICHD NIH HHS
[R21 HD051146, R21 HD051146-05]; NIDA NIH HHS [R01 DA013423, R01
DA013423-05, R01 DA019963, R01 DA019963-03]
NR 38
TC 39
Z9 41
U1 1
U2 18
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD MAY
PY 2011
VL 35
IS 4
BP 217
EP 225
DI 10.1002/gepi.20571
PG 9
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 748FM
UT WOS:000289375400002
PM 21308768
ER
PT J
AU Sampson, J
Jacobs, K
Yeager, M
Chanock, S
Chatterjee, N
AF Sampson, Joshua
Jacobs, Kevin
Yeager, Meredith
Chanock, Stephen
Chatterjee, Nilanjan
TI Efficient Study Design for Next Generation Sequencing
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE next generation sequencing; sequencing depth; study design; rare
variants
ID HUMAN GENOME; SNP DISCOVERY; ASSOCIATION
AB Next Generation Sequencing represents a powerful tool for detecting genetic variation associated with human disease. Because of the high cost of this technology, it is critical that we develop efficient study designs that consider the trade-off between the number of subjects (n) and the coverage depth (m). How we divide our resources between the two can greatly impact study success, particularly in pilot studies. We propose a strategy for selecting the optimal combination of n and m for studies aimed at detecting rare variants and for studies aimed at detecting associations between rare or uncommon variants and disease. For detecting rare variants, we find the optimal coverage depth to be between 2 and 8 reads when using the likelihood ratio test. For association studies, we find the strategy of sequencing all available subjects to be preferable. In deriving these combinations, we provide a detailed analysis describing the distribution of depth across a genome and the depth needed to identify a minor allele in an individual. The optimal coverage depth depends on the aims of the study, and the chosen depth can have a large impact on study success. Genet. Epidemiol. 35: 269-277, 2011. (c) 2011 Wiley-Liss, Inc.
C1 [Sampson, Joshua; Chatterjee, Nilanjan] NCI, Biostat Branch, DCEG, Rockville, MD 20852 USA.
[Jacobs, Kevin; Yeager, Meredith; Chanock, Stephen] NCI, Core Genotyping Facil, DCEG, Gaithersburg, MD USA.
RP Sampson, J (reprint author), NCI, Biostat Branch, DCEG, 6120 Execut Blvd,8038, Rockville, MD 20852 USA.
EM joshua.sampson@nih.gov
RI Sincan, Murat /A-3794-2010
FU Intramural NIH HHS [Z01 CP010181-06]
NR 27
TC 22
Z9 22
U1 2
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD MAY
PY 2011
VL 35
IS 4
BP 269
EP 277
DI 10.1002/gepi.20575
PG 9
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 748FM
UT WOS:000289375400007
PM 21370254
ER
PT J
AU Murphy, G
Fan, JH
Mark, SD
Dawsey, SM
Selhub, J
Wang, JB
Taylor, PR
Qiao, YL
Abnet, CC
AF Murphy, Gwen
Fan, Jin-Hu
Mark, Steven D.
Dawsey, Sanford M.
Selhub, Jacob
Wang, Jianbing
Taylor, Philip R.
Qiao, You-Lin
Abnet, Christian C.
TI Prospective study of serum cysteine levels and oesophageal and gastric
cancers in China
SO GUT
LA English
DT Article
ID NUTRITION INTERVENTION TRIAL; GENERAL-POPULATION; N-ACETYLCYSTEINE;
CASE-COHORT; LINXIAN; GLUTATHIONE; PLASMA; RISK; HOMOCYSTEINE;
EXPRESSION
AB Background Cancers of the upper gastrointestinal tract remain a significant cause of morbidity and mortality. Cysteine, known to be involved in a myriad of immunomodulatory, anti-oxidant, and anti-carcinogenic pathways, has not been investigated in the aetiology of oesophageal or gastric cancers. To examine the relationship between serum cysteine concentration and risk of these cancers we conducted a nested caseecohort study within the General Population Nutrition Intervention Trial in Linxian, China.
Methods 498 oesophageal squamous cell carcinomas (OSCCs) and 255 gastric cardia adenocarcinomas (GCAs) were matched by age and sex to 947 individuals from the wider cohort. We calculated HRs and 95% CIs using the caseecohort estimator for the Cox proportional hazards models, stratified on age and sex, with adjustment for potential confounders.
Results Higher concentrations of serum cysteine were significantly associated with a lower risk of both OSCC and GCA. For those in the highest quartile of serum cysteine, compared to those in the lowest, the multivariate HRs were 0.70 for OSCC (95% CI 0.51 to 0.98) and 0.59 for GCA (95% CI 0.38 to 0.91). These associations were dose dependent (p for trend = 0.006 and 0.008, respectively). These inverse associations were not significantly modified by other risk factors, with the exception of age, where a stronger association was noted among persons in the older age strata.
Conclusion Higher serum concentrations of cysteine were associated with a significantly reduced risk of OSCC and GCA. Cysteine should be further investigated for its potential as a chemopreventive agent for upper gastrointestinal cancers.
C1 [Murphy, Gwen] NCI, Nutr Epidemiol Branch, DCEG, NIH, Bethesda, MD 20892 USA.
[Fan, Jin-Hu; Wang, Jianbing; Qiao, You-Lin] Chinese Acad Med Sci, Inst Canc, Dept Epidemiol, Beijing 100021, Peoples R China.
[Mark, Steven D.] Univ Colorado, Denver, CO 80202 USA.
[Selhub, Jacob] Tufts Univ, Jean Mayer US Dept Agr Human Nutr Res Ctr Ageing, Boston, MA 02111 USA.
RP Murphy, G (reprint author), NCI, Nutr Epidemiol Branch, DCEG, NIH, 6120 Execut Blvd,EPS 3034, Bethesda, MD 20892 USA.
EM murphygw@mail.nih.gov; qiaoy@cicams.ac.cn
RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015
OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843
FU Division of Cancer Epidemiology and Genetics, the National Cancer
Institute, at the National Institutes of Health, Department of Health
and Human Services
FX This work was supported by the Intramural Research Program, Division of
Cancer Epidemiology and Genetics, the National Cancer Institute, at the
National Institutes of Health, Department of Health and Human Services.
NR 34
TC 14
Z9 14
U1 1
U2 8
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0017-5749
J9 GUT
JI Gut
PD MAY
PY 2011
VL 60
IS 5
BP 618
EP 623
DI 10.1136/gut.2010.225854
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 744EG
UT WOS:000289076700006
PM 21242262
ER
PT J
AU You, XZ
Adjouadi, M
Guillen, MR
Ayala, M
Barreto, A
Rishe, N
Sullivan, J
Dlugos, D
VanMeter, J
Morris, D
Donner, E
Bjornson, B
Smith, ML
Bernal, B
Berl, M
Gaillard, WD
AF You, Xiaozhen
Adjouadi, Malek
Guillen, Magno R.
Ayala, Melvin
Barreto, Armando
Rishe, Naphtali
Sullivan, Joseph
Dlugos, Dennis
VanMeter, John
Morris, Drew
Donner, Elizabeth
Bjornson, Bruce
Smith, Mary Lou
Bernal, Byron
Berl, Madison
Gaillard, William D.
TI Sub-Patterns of Language Network Reorganization in Pediatric
Localization Related Epilepsy: A Multisite Study
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE brain activation pattern; data-driven clustering; fMRI; epilepsy;
language; PCA-based decisional space
ID TEMPORAL-LOBE EPILEPSY; INTRACAROTID AMOBARBITAL PROCEDURE;
RIGHT-HEMISPHERIC ORGANIZATION; PRINCIPAL COMPONENT ANALYSIS; COMPLEX
PARTIAL EPILEPSY; FUNCTIONAL MRI; WADA TEST; CEREBRAL LATERALIZATION;
STATISTICAL-ANALYSIS; ATYPICAL LANGUAGE
AB To study the neural networks reorganization in pediatric epilepsy, a consortium of imaging centers was established to collect functional imaging data. Common paradigms and similar acquisition parameters were used. We studied 122 children (64 control and 58 LRE patients) across five sites using EPI BOLD fMRI and an auditory description decision task. After normalization to the MNI atlas, activation maps generated by FSL were separated into three sub-groups using a distance method in the principal component analysis (PCA)-based decisional space. Three activation patterns were identified: (1) the typical distributed network expected for task in left inferior frontal gyrus (Broca's) and along left superior temporal gyrus (Wernicke's) (60 controls, 35 patients); (2) a variant left dominant pattern with greater activation in IFG, mesial left frontal lobe, and right cerebellum (three controls, 15 patients); and (3) activation in the right counterparts of the first pattern in Broca's area (one control, eight patients). Patients were over represented in Groups 2 and 3 (P < 0.0004). There were no scanner (P = 0.4) or site effects (P = 0.6). Our data-driven method for fMRI activation pattern separation is independent of a priori notions and bias inherent in region of interest and visual analyses. In addition to the anticipated atypical right dominant activation pattern, a sub-pattern was identified that involved intensity and extent differences of activation within the distributed left hemisphere language processing network. These findings suggest a different, perhaps less efficient, cognitive strategy for LRE group to perform the task. Hum Brain Mapp 32: 784-799, 2011. (C) 2010 Wiley-Liss, Inc.
C1 [You, Xiaozhen; Adjouadi, Malek; Guillen, Magno R.; Ayala, Melvin; Barreto, Armando; Rishe, Naphtali] Florida Int Univ, Coll Engn & Comp, Miami, FL 33174 USA.
[Sullivan, Joseph; Dlugos, Dennis] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[VanMeter, John; Gaillard, William D.] Georgetown Univ, Dept Neurol, Washington, DC USA.
[Morris, Drew; Donner, Elizabeth; Smith, Mary Lou] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Bjornson, Bruce] BC Childrens Hosp, Vancouver, BC, Canada.
[Smith, Mary Lou] Univ Toronto, Dept Psychol, Toronto, ON M5S 1A1, Canada.
[Bernal, Byron] Miami Childrens Hosp, Miami, FL USA.
[Berl, Madison; Gaillard, William D.] George Washington Univ, Childrens Natl Med Ctr, Dept Neurosci, Washington, DC USA.
[Gaillard, William D.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA.
RP Adjouadi, M (reprint author), Florida Int Univ, Coll Engn & Comp, 10555 W Flagler St,EC 2672, Miami, FL 33174 USA.
EM adjouadi@fiu.edu
RI Bjornson, Bruce/A-8616-2010;
OI Bjornson, Bruce/0000-0002-1465-6196; Guilen, Magno/0000-0001-9649-8429
FU American Epilepsy Society [NINDS R01 NS44280]; Children's Research
Institute, Intellectual and Developmental Disabilities Research Center
at Children's National Medical Center [NIH IDDRC P30HD40677]; General
Clinic Research Center [NIH GCRC M01-RR13297]; National Science
Foundation [HRD-0833093, CNS-0426125, CNS-0520811, CNS-0540592]; Ware
Foundation; Joint Neuro-Engineering Program; Miami Children's Hospital;
FIU Graduate School
FX Contract grant sponsor: American Epilepsy Society (Impetus and
Infrastructure); Contract grant number: NINDS R01 NS44280; Contract
grant sponsor: Children's Research Institute Avery Award, Intellectual
and Developmental Disabilities Research Center at Children's National
Medical Center; Contract grant number: NIH IDDRC P30HD40677; Contract
grant sponsor: General Clinic Research Center; Contract grant number:
NIH GCRC M01-RR13297; Contract grant sponsor: National Science
Foundation; Contract grant numbers: HRD-0833093, CNS-0426125,
CNS-0520811, CNS-0540592; Contract grant sponsors: Ware Foundation and
the Joint Neuro-Engineering Program with Miami Children's Hospital
(Clinical support), FIU Graduate School Dissertation Year Fellowship
(Financial support).
NR 69
TC 20
Z9 21
U1 4
U2 12
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1065-9471
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD MAY
PY 2011
VL 32
IS 5
BP 784
EP 799
DI 10.1002/hbm.21066
PG 16
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 748WK
UT WOS:000289423400010
PM 21484949
ER
PT J
AU Liu, CY
Ackerman, HH
Carulli, JP
AF Liu, Chunyu
Ackerman, H. Hoxie
Carulli, John P.
TI A genome-wide screen of gene-gene interactions for rheumatoid arthritis
susceptibility
SO HUMAN GENETICS
LA English
DT Article
ID SINGLE-NUCLEOTIDE POLYMORPHISM; SYSTEMIC-LUPUS-ERYTHEMATOSUS;
SAMPLE-SIZE REQUIREMENTS; CITRULLINATED PROTEINS; DISEASE ASSOCIATION;
SHARED EPITOPE; RISK LOCUS; PTPN22; POPULATION; HAPLOTYPES
AB The objective of the study was to identify interacting genes contributing to rheumatoid arthritis (RA) susceptibility and identify SNPs that discriminate between RA patients who were anti-cyclic citrullinated protein positive and healthy controls. We analyzed two independent cohorts from the North American Rheumatoid Arthritis Consortium. A cohort of 908 RA cases and 1,260 controls was used to discover pairwise interactions among SNPs and to identify a set of single nucleotide polymorphisms (SNPs) that predict RA status, and a second cohort of 952 cases and 1,760 controls was used to validate the findings. After adjusting for HLA-shared epitope alleles, we identified and replicated seven SNP pairs within the HLA class II locus with significant interaction effects. We failed to replicate significant pairwise interactions among non-HLA SNPs. The machine learning approach "random forest" applied to a set of SNPs selected from single-SNP and pairwise interaction tests identified 93 SNPs that distinguish RA cases from controls with 70% accuracy. HLA SNPs provide the most classification information, and inclusion of non-HLA SNPs improved classification. While specific gene-gene interactions are difficult to validate using genome-wide SNP data, a stepwise approach combining association and classification methods identifies candidate interacting SNPs that distinguish RA cases from healthy controls.
C1 [Liu, Chunyu] NHLBI, Ctr Populat Studies, Framingham, MA 01702 USA.
[Liu, Chunyu] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Ackerman, H. Hoxie] Univ Calif Berkeley, Dept Stat, PhD Program, Berkeley, CA 94720 USA.
[Carulli, John P.] Biogen Idec Inc, Genet & Genom Dept, Cambridge, MA USA.
RP Liu, CY (reprint author), NHLBI, Ctr Populat Studies, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM liuchunyu2002@yahoo.com; hoxie@stat.berkeley.edu;
john.carulli@biogenidec.com
NR 54
TC 18
Z9 19
U1 1
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD MAY
PY 2011
VL 129
IS 5
BP 473
EP 485
DI 10.1007/s00439-010-0943-z
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 750FT
UT WOS:000289531700002
PM 21210282
ER
PT J
AU Stratton, P
Berkley, KJ
AF Stratton, Pamela
Berkley, Karen J.
TI Chronic pelvic pain and endometriosis: translational evidence of the
relationship and implications
SO HUMAN REPRODUCTION UPDATE
LA English
DT Article
DE endometriosis; chronic pelvic pain; central nervous system
sensitization; pathophysiology; neurovascular
ID RANDOMIZED CONTROLLED-TRIAL; RECTOVAGINAL SEPTUM ENDOMETRIOSIS; DEEP
INFILTRATING ENDOMETRIOSIS; PITUITARY-ADRENAL AXIS; NERVE GROWTH-FACTOR;
ADD-BACK THERAPY; TERM-FOLLOW-UP; ADMINISTERED PROGESTOGEN
LEVONORGESTREL; UNRUPTURED FOLLICLE SYNDROME; PLACEBO-CONTROLLED TRIAL
AB BACKGROUND: Many clinicians and patients believe that endometriosis-associated pain is due to the lesions. Yet causality remains an enigma, because pain symptoms attributed to endometriosis occur in women without endometriosis and because pain symptoms and severity correlate poorly with lesion characteristics. Most research and reviews focus on the lesions, not the pain. This review starts with the recognition that the experience of pain is determined by the central nervous system (CNS) and focuses on the pain symptoms.
METHODS: Comprehensive searches of Pubmed, Medline and Embase were conducted for current basic and clinical research on chronic pelvic pain and endometriosis. The information was mutually interpreted by a basic scientist and a clinical researcher, both in the field of endometriosis. The goal was to develop new ways to conceptualize how endometriosis contributes to pain symptoms in the context of current treatments and the reproductive tract.
RESULTS: Endometriotic lesions can develop their own nerve supply, thereby creating a direct and two-way interaction between lesions and the CNS. This engagement provides a mechanism by which the dynamic and hormonally responsive nervous system is brought directly into play to produce a variety of individual differences in pain that can, in some women, become independent of the disease itself.
CONCLUSIONS: Major advances in improving understanding and alleviating pain in endometriosis will likely occur if the focus changes from lesions to pain. In turn, how endometriosis affects the CNS would be best examined in the context of mechanisms underlying other chronic pain conditions.
C1 [Stratton, Pamela] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Berkley, Karen J.] Florida State Univ, Program Neurosci, Tallahassee, FL 32306 USA.
RP Stratton, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Program Reprod & Adult Endocrinol, NIH, Bldg 10,CRC,RM 1 3140,10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA.
EM strattop@mail.nih.gov
FU Eunice Kennedy Shriver National Institutes of Health; NIH [RO1 NS11892]
FX Supported by the Intramural Program, Program in Reproductive and Adult
Endocrinology, Eunice Kennedy Shriver National Institutes of Health
(P.S.) and NIH grant RO1 NS11892 (K.J.B.)
NR 296
TC 92
Z9 102
U1 6
U2 22
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1355-4786
J9 HUM REPROD UPDATE
JI Hum. Reprod. Update
PD MAY-JUN
PY 2011
VL 17
IS 3
BP 327
EP 346
DI 10.1093/humupd/dmq050
PG 20
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 747IA
UT WOS:000289312300004
PM 21106492
ER
PT J
AU Cheung, GYC
Wang, R
Khan, BA
Sturdevant, DE
Otto, M
AF Cheung, Gordon Y. C.
Wang, Rong
Khan, Burhan A.
Sturdevant, Daniel E.
Otto, Michael
TI Role of the Accessory Gene Regulator agr in Community-Associated
Methicillin-Resistant Staphylococcus aureus Pathogenesis
SO INFECTION AND IMMUNITY
LA English
DT Article
ID PANTON-VALENTINE LEUKOCIDIN; PEPTIDE-SENSING SYSTEM; VIRULENCE
DETERMINANTS; GLOBAL REGULATION; ALPHA-HEMOLYSIN; USA300 CLONE;
INFECTIONS; EXPRESSION; PNEUMONIA; EVOLUTION
AB The molecular basis underlying the pathogenic success of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is not completely understood, but differential gene expression has been suggested to account at least in part for the high virulence of CA-MRSA strains. Here, we show that the agr gene regulatory system has a crucial role in the development of skin infections in the most prevalent CA-MRSA strain USA300. Importantly, our data indicate that this is due to discrepancies between the agr regulon of CA-MRSA and those of hospital-associated MRSA and laboratory strains. In particular, agr regulation in strain USA300 led to exceptionally strong expression of toxins and exoenzymes, upregulation of fibrinogen-binding proteins, increased capacity to bind fibrinogen, and increased expression of methicillin resistance genes. Our findings demonstrate that agr functionality is critical for CA-MRSA disease and indicate that an adaptation of the agr regulon contributed to the evolution of highly pathogenic CA-MRSA.
C1 [Cheung, Gordon Y. C.; Wang, Rong; Khan, Burhan A.; Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA.
[Sturdevant, Daniel E.] NIAID, Res Technol Branch, Genom Unit, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
RP Otto, M (reprint author), NIAID, Lab Human Bacterial Pathogenesis, NIH, Bldg 33,1W10,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM motto@niaid.nih.gov
RI Cheung, Yiu Chong /K-3565-2012;
OI Otto, Michael/0000-0002-2222-4115
FU National Institute of Allergy and Infectious Diseases (NIAID), The
National Institutes of Health (NIH)
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases (NIAID), The
National Institutes of Health (NIH).
NR 49
TC 91
Z9 92
U1 1
U2 12
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD MAY
PY 2011
VL 79
IS 5
BP 1927
EP 1935
DI 10.1128/IAI.00046-11
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 752EP
UT WOS:000289672700015
PM 21402769
ER
PT J
AU Goodman, AL
Epp, C
Moss, D
Holder, AA
Wilson, JM
Gao, GP
Long, CA
Remarque, EJ
Thomas, AW
Ammendola, V
Colloca, S
Dicks, MDJ
Biswas, S
Seibel, D
van Duivenvoorde, LM
Gilbert, SC
Hill, AVS
Draper, SJ
AF Goodman, Anna L.
Epp, C.
Moss, D.
Holder, A. A.
Wilson, J. M.
Gao, G. P.
Long, C. A.
Remarque, E. J.
Thomas, A. W.
Ammendola, V.
Colloca, S.
Dicks, M. D. J.
Biswas, S.
Seibel, D.
van Duivenvoorde, L. M.
Gilbert, S. C.
Hill, A. V. S.
Draper, S. J.
TI New Candidate Vaccines against Blood-Stage Plasmodium falciparum
Malaria: Prime-Boost Immunization Regimens Incorporating Human and
Simian Adenoviral Vectors and Poxviral Vectors Expressing an Optimized
Antigen Based on Merozoite Surface Protein 1, (vol 78, pg 4610, 2010)
SO INFECTION AND IMMUNITY
LA English
DT Correction
C1 [Goodman, Anna L.] Univ Oxford, Jenner Inst, Oxford OX3 7DQ, England.
Univ Klinikum Heidelberg, Inst Hyg, Abt Parasitol, D-69120 Heidelberg, Germany.
Natl Inst Med Res, MRC, Div Parasitol, London NW7 1AA, England.
Univ Penn, Dept Pathol & Lab Med, Div Transfus Med, Gene Therapy Program, Philadelphia, PA 19104 USA.
Biomed Primate Res Ctr, NL-2288 GJ Rijswijk, Netherlands.
NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
Okairos AG, I-00040 Pomezia, Rome, Italy.
RP Goodman, AL (reprint author), Univ Oxford, Jenner Inst, Old Rd Campus Res Bldg, Oxford OX3 7DQ, England.
RI Holder, Anthony/A-7554-2013; Wilson, James/F-9220-2011
OI Holder, Anthony/0000-0002-8490-6058; Wilson, James/0000-0002-9630-3131
NR 1
TC 0
Z9 0
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD MAY
PY 2011
VL 79
IS 5
BP 2132
EP 2132
DI 10.1128/IAI.00187-11
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 752EP
UT WOS:000289672700036
ER
PT J
AU Easterbrook, JD
Kash, JC
Sheng, ZM
Qi, L
Gao, J
Kilbourne, ED
Eichelberger, MC
Taubenberger, JK
AF Easterbrook, Judith D.
Kash, John C.
Sheng, Zong-Mei
Qi, Li
Gao, Jin
Kilbourne, Edwin D.
Eichelberger, Maryna C.
Taubenberger, Jeffery K.
TI Immunization with 1976 swine H1N1-or 2009 pandemic H1N1-inactivated
vaccines protects mice from a lethal 1918 influenza infection
SO INFLUENZA AND OTHER RESPIRATORY VIRUSES
LA English
DT Article
DE 1918 influenza; 1976 influenza; 2009 pandemic H1N1; cross-protection;
microneutralization
ID NEURAMINIDASE ANTIBODY; VIRUS; ORIGIN; IMMUNITY; GENES; PATHOGENICITY;
HEMAGGLUTININ; RECOMBINANT; PERSPECTIVE; VACCINATION
AB Background
Zoonotic infections with H1N1 influenza viruses that evolved initially from the 1918 virus (1918) and adapted to swine threatened a pandemic in 1976 (1976 swH1N1) and a novel reassortant H1N1 virus caused a pandemic in 2009-2010 (2009 pH1N1). Epidemiological and laboratory animal studies show that protection from severe 2009 pH1N1 infection is conferred by vaccination or prior infection with 1976 swH1N1 or 1918.
Objectives
Our aim was to demonstrate cross-protection by immunization with 2009 pH1N1 or 1976 swH1N1 vaccines following a lethal challenge with 1918. Further, the mechanisms of cross-protective antibody responses were evaluated.
Methods
Mice were immunized with 1976 swH1N1, 2009 pH1N1, 2009 seasonal trivalent, or 1918 vaccines and challenged with 1918. Cross-reactive antibody responses were assessed and protection monitored by survival, weight loss, and pathology in mice.
Results and Conclusions
Vaccination with the 1976 swH1N1 or 2009 pH1N1 vaccines protected mice from a lethal challenge with 1918, and these mice lost no weight and had significantly reduced viral load and pathology in the lungs. Protection was likely due to cross-reactive antibodies detected by microneutralization assay. Our data suggest that the general population may be protected from a future 1918-like pandemic because of prior infection or immunization with 1976 swH1N1 or 2009 pH1N1. Also, influenza protection studies generally focus on cross-reactive hemagglutination-inhibiting antibodies; while hemagglutinin is the primary surface antigen, this fails to account for other influenza viral antigens. Neutralizing antibody may be a better correlate of human protection against pathogenic influenza strains and should be considered for vaccine efficacy.
C1 [Easterbrook, Judith D.; Kash, John C.; Sheng, Zong-Mei; Qi, Li; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Gao, Jin; Eichelberger, Maryna C.] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD USA.
[Kilbourne, Edwin D.] New York Med Coll, Valhalla, NY 10595 USA.
RP Taubenberger, JK (reprint author), NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, 33 North Dr,MSC 3203, Bethesda, MD 20892 USA.
EM taubenbergerj@niaid.nih.gov
FU NIH; NIAID
FX We thank the Comparative Medicine Branch (NIH/NIAID) for their
assistance with animal studies. This work was supported by the
Intramural Research Program of the NIH and the NIAID.
NR 40
TC 11
Z9 11
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1750-2640
J9 INFLUENZA OTHER RESP
JI Influenza Other Respir. Viruses
PD MAY
PY 2011
VL 5
IS 3
BP 198
EP 205
DI 10.1111/j.1750-2659.2010.00191.x
PG 8
WC Infectious Diseases; Virology
SC Infectious Diseases; Virology
GA 747BT
UT WOS:000289296000009
PM 21477139
ER
PT J
AU Mueller, SC
Merke, DP
Leschek, EW
Fromm, S
VanRyzin, C
Ernst, M
AF Mueller, Sven C.
Merke, Deborah P.
Leschek, Ellen W.
Fromm, Steven
VanRyzin, Carol
Ernst, Monique
TI Increased medial temporal lobe and striatal grey-matter volume in a rare
disorder of androgen excess: a voxel-based morphometry (VBM) study
SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE ADHD; brain development; FMPP; precocious puberty; sex steroid
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; CONGENITAL
ADRENAL-HYPERPLASIA; MALE PRECOCIOUS PUBERTY; LUTEINIZING-HORMONE
RECEPTOR; LONG-TERM TREATMENT; FUSIFORM FACE AREA; STEROID-HORMONES;
SEX-DIFFERENCES; MALE-RATS; DEVELOPMENTAL TRAJECTORIES
AB Major questions remain about how sex hormones influence human brain development and cognition. Studies in humans and animals suggest a strong impact of androgen on the structure and function of the medial temporal lobe (MTL) and striatum. Using voxel-based morphometry (DARTEL), we compared MTL and striatal structures in 13 [ mean age (+/- S.D.) 12.7 +/- 3.2 yr, mean bone age 14.8 +/- 3.2 yr] boys with familial male precocious puberty (FMPP), characterized by early excess androgen secretion, and 39 healthy age-matched boys (mean age 14.3 +/- 2.5 yr). The FMPP group showed significantly larger grey-matter volume (GMV) in parahippocampal and fusiform gyri as well as putamen relative to controls. By comparison, larger GMV for controls relative to patients was only apparent in the precentral gyrus. Exploratory regression analyses that examined the impact of age on the current findings revealed a significant increase of GMV in the putamen with age in patients suffering from excess androgen but not in controls. Finally, current levels of free testosterone were obtained in the patient group. Analyses revealed a significant negative association indicating that FMPP boys with low levels of bioavailable testosterone exhibited high GMV in the bilateral striatum. The findings suggest a critical influence of androgen on human brain development and are discussed in relation to male-dominant psychiatric childhood disorders.
C1 [Mueller, Sven C.; Fromm, Steven; Ernst, Monique] NIMH, SDAN, NIH, Bethesda, MD 20892 USA.
[Merke, Deborah P.; VanRyzin, Carol] NICHD, Ctr Clin, NIH, Bethesda, MD USA.
[Merke, Deborah P.; VanRyzin, Carol] NICHD, PDEGEN, NIH, Bethesda, MD USA.
[Leschek, Ellen W.] NIDDK, NIH, Bethesda, MD USA.
RP Mueller, SC (reprint author), 15K North Dr, Bethesda, MD 20892 USA.
EM msven@mail.nih.gov
FU National Institute of Mental Health; Eunice Kennedy Shriver National
Institute of Child Health and Human Development; National Institutes of
Health Clinical Center; Phoqus Pharmaceuticals
FX This research was supported by the Intramural Research Programs of the
National Institute of Mental Health, the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, and the National
Institutes of Health Clinical Center.; D.P.M. received research funds
from Phoqus Pharmaceuticals during 2007-2008.
NR 82
TC 19
Z9 19
U1 3
U2 8
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1461-1457
EI 1469-5111
J9 INT J NEUROPSYCHOPH
JI Int. J. Neuropsychopharmacol.
PD MAY
PY 2011
VL 14
IS 4
BP 445
EP 457
DI 10.1017/S1461145710001136
PG 13
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 748FD
UT WOS:000289374500002
PM 20860880
ER
PT J
AU Mah, L
Zarate, CA
Nugent, AC
Singh, JB
Manji, HK
Drevets, WC
AF Mah, Linda
Zarate, Carlos A., Jr.
Nugent, Allison C.
Singh, Jaskaran B.
Manji, Husseini K.
Drevets, Wayne C.
TI Neural mechanisms of antidepressant efficacy of the dopamine receptor
agonist pramipexole in treatment of bipolar depression
SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE Bipolar disorder; glucose metabolism; major depression; orbitofrontal
cortex; positron emission tomography (PET)
ID POSITRON-EMISSION-TOMOGRAPHY; MAJOR DEPRESSION; GLUCOSE-METABOLISM; II
DEPRESSION; DISORDER; DEPLETION; MOOD
AB The D2/D3 receptor agonist pramipexole has clinical efficacy as an antidepressant, but its neural mechanisms are unknown. We used 18FDG-PET to investigate the cerebral metabolic effects of pramipexole augmentation of mood stabilizers in bipolar II depression. Fifteen bipolar II depressed patients on mood stabilizers were imaged at baseline and following 6 wk of pramipexole (n = 7) or placebo (n = 8) augmentation. Relative to placebo, pramipexole treatment was associated with reductions in normalized metabolism in bilateral orbitofrontal cortex, left ventrolateral prefrontal cortex (PFC), and right anteromedial PFC. Voxel-wise analyses additionally showed decreased normalized metabolism in the left inferior parietal cortex and medial frontopolar cortical (BA 10P) area of the anteromedial PFC following pramipexole treatment. These pramipexole-induced effects on regional metabolism suggest a mechanism of antidepressant action distinct from that previously reported under serotonin reuptake inhibitor treatment and appear compatible with evidence that the central dopaminergic system plays a role in the pathophysiology of bipolar depression.
C1 [Mah, Linda] Univ Toronto, Kunin Lunenfeld Appl Res Unit, Rotman Res Inst, Toronto, ON, Canada.
[Mah, Linda; Nugent, Allison C.; Drevets, Wayne C.] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Mol Imaging Branch, Mood & Anxiety Program,NIH, Bethesda, MD 20892 USA.
[Zarate, Carlos A., Jr.; Singh, Jaskaran B.; Manji, Husseini K.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
RP Mah, L (reprint author), Brain Hlth Complex,7th Floor,3560 Bathurst St, Toronto, ON M6A 2E1, Canada.
EM lmah@klaru-baycrest.on.ca
OI Nugent, Allison/0000-0003-2569-2480
FU National Institute of Mental Health; National Institutes of Health;
Department of Health Human Services; Geoffrey H. Wood Foundation;
Scottish Rite Charitable Foundation; University of Toronto
FX The study was supported by the Intramural Research Program at the
National Institute of Mental Health, the National Institutes of Health,
and the Department of Health & Human Services.; Dr Mah receives research
support from the Geoffrey H. Wood Foundation, the Scottish Rite
Charitable Foundation, and the University of Toronto. Dr Manji and Dr
Singh are currently at Johnson & Johnson Pharmaceutical Research and
Development L.L.C. Dr Drevets served as a consultant to Pfizer on
imaging biomarkers in 2009.
NR 26
TC 14
Z9 15
U1 0
U2 0
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1461-1457
J9 INT J NEUROPSYCHOPH
JI Int. J. Neuropsychopharmacol.
PD MAY
PY 2011
VL 14
IS 4
BP 545
EP 551
DI 10.1017/S1461145710001203
PG 7
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 748FD
UT WOS:000289374500009
PM 21029512
ER
PT J
AU Cohen, MM
Amiott, EA
Day, AR
Leboucher, GP
Pryce, EN
Glickman, MH
McCaffery, JM
Shaw, JM
Weissman, AM
AF Cohen, Mickael M.
Amiott, Elizabeth A.
Day, Adam R.
Leboucher, Guillaume P.
Pryce, Erin N.
Glickman, Michael H.
McCaffery, J. Michael
Shaw, Janet M.
Weissman, Allan M.
TI Sequential requirements for the GTPase domain of the mitofusin Fzo1 and
the ubiquitin ligase SCFMdm30 in mitochondrial outer membrane fusion
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Oxidative phosphorylation; Fzo1p; Mdm30p; Membrane fusion; SCF; F-box
ID DYNAMIN-LIKE PROTEIN; SACCHAROMYCES-CEREVISIAE; YEAST; MDM30;
DEGRADATION; MAINTENANCE; MORPHOLOGY; TURNOVER; FISSION; SYSTEM
AB The ability of cells to respire requires that mitochondria undergo fusion and fission of their outer and inner membranes. The means by which levels of fusion 'machinery' components are regulated and the molecular details of how fusion occurs are largely unknown. In Saccharomyces cerevisiae, a central component of the mitochondrial outer membrane (MOM) fusion machinery is the mitofusin Fzo1, a dynamin-like GTPase. We demonstrate that an early step in fusion, mitochondrial tethering, is dependent on the Fzo1 GTPase domain. Furthermore, the ubiquitin ligase SCFMdm30 (a SKP1-cullin-1-F-box complex that contains Mdm30 as the F-box protein), which targets Fzo1 for ubiquitylation and proteasomal degradation, is recruited to Fzo1 as a consequence of a GTPase-domain-dependent alteration in the mitofusin. Moreover, evidence is provided that neither Mdm30 nor proteasome activity are necessary for tethering of mitochondria. However, both Mdm30 and proteasomes are critical for MOM fusion. To better understand the requirement for the ubiquitin-proteasome system in mitochondrial fusion, we used the N-end rule system of degrons and determined that ongoing degradation of Fzo1 is important for mitochondrial morphology and respiration. These findings suggest a sequence of events in early mitochondrial fusion where Fzo1 GTPase-domain-dependent tethering leads to recruitment of SCFMdm30 and ubiquitin-mediated degradation of Fzo1, which facilitates mitochondrial fusion.
C1 [Cohen, Mickael M.; Day, Adam R.; Leboucher, Guillaume P.; Weissman, Allan M.] NCI Frederick, Lab Prot Dynam & Signaling, Ctr Canc Res, Ft Detrick, MD 21702 USA.
[Amiott, Elizabeth A.; Shaw, Janet M.] Univ Utah, Sch Med, Dept Biochem, Salt Lake City, UT 84112 USA.
[Leboucher, Guillaume P.; Glickman, Michael H.] Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel.
[Pryce, Erin N.; McCaffery, J. Michael] Johns Hopkins Univ, Dept Biol, Integrated Imaging Ctr, Baltimore, MD 21218 USA.
RP Cohen, MM (reprint author), CNRS, FRE3354, IBPC, Lab Membrane Dynam, 13 Rue Pierre & Marie Curie, F-75005 Paris, France.
EM cohen@ibpc.fr; amw@nih.gov
RI Cohen, Mickael/F-4122-2011
FU United Mitochondrial Disease Foundation (UMDF) [08-064]; NIH [5 T32
HD07576-22, GM53466]; National Institutes of Health, National Cancer
Institute, Center for Cancer Research; Michael J. Fox Foundation for
Parkinson's Research; USA-Israel Bi-National Science Foundation (BSF);
NCRR [1 S10 RR023454-01]
FX We thank Greg J. Hermann (University of Utah) for generating anti-Fzo1
antisera and David C. Chan (California Institute of Technology),
Benjamin S. Glick (University of Chicago), Agnes Delahodde (Institut de
Genetique et Microbiologie) and Eric E. Griffin (California Institute of
Technology) for generously providing reagents critical to this study and
Y.C. Tsai for assistance with assessment of proteasome inhibition. We
thank T. J. Turbyville and members of the Weissman and Shaw laboratories
for discussions and N. Belgareh-Touze, Z. Kostova, M. B. Metzger and M.
Nejati for review of this manuscript. E.A.A. was supported by grants
from the United Mitochondrial Disease Foundation (UMDF# 08-064
Mitochondrial Fusion Defects in Neurological Disease) and NIH (T32
Institutional Training Grant # 5 T32 HD07576-22). Research in the Shaw
laboratory and Weissman laboratories is supported by NIH GM53466 and the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research, respectively. This work was also supported by a grant
to A.M.W. from the Michael J. Fox Foundation for Parkinson's Research; a
grant to A. M. W. and M.H.G. from the USA-Israel Bi-National Science
Foundation (BSF); and a NIH grant to J.M.M. (NCRR grant 1 S10
RR023454-01). Deposited in PMC for release after 12 months.
NR 31
TC 27
Z9 29
U1 2
U2 6
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
J9 J CELL SCI
JI J. Cell Sci.
PD MAY 1
PY 2011
VL 124
IS 9
BP 1403
EP 1410
DI 10.1242/jcs.079293
PG 8
WC Cell Biology
SC Cell Biology
GA 751MD
UT WOS:000289621300006
PM 21502136
ER
PT J
AU Alter, A
Huong, NT
Singh, M
Orlova, M
Thuc, NV
Katoch, K
Gao, XJ
Thai, VH
Ba, NN
Carrington, M
Abel, L
Mehra, N
Alcais, A
Schurr, E
AF Alter, Andrea
Nguyen Thu Huong
Singh, Meenakshi
Orlova, Marianna
Nguyen Van Thuc
Katoch, Kiran
Gao, Xiaojiang
Vu Hong Thai
Nguyen Ngoc Ba
Carrington, Mary
Abel, Laurent
Mehra, Narinder
Alcais, Alexandre
Schurr, Erwin
TI Human Leukocyte Antigen Class I Region Single-Nucleotide Polymorphisms
are Associated with Leprosy Susceptibility in Vietnam and India
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID HLA-C; QUANTITATIVE TRAITS; TUBERCULOID LEPROSY; GENETIC DISSECTION;
DISEASE; POPULATION; EXPRESSION; RESISTANCE; SEQUENCE; IMMUNITY
AB Experimental evidence suggested the existence of unidentified leprosy susceptibility loci in the human leukocyte antigen (HLA) complex. To identify such genetic risk factors, a high-density association scan of a 1.9-mega-base (Mb) region in the HLA complex was performed. Among 682 single-nucleotide polymorphisms (SNPs), 59 were associated with leprosy (P <.01) in 198 Vietnamese single-case leprosy families. Genotyping of these SNPs in an independent sample of 292 Vietnamese single-case leprosy families replicated the association of 12 SNPs (P <.01). Multivariate analysis of these 12 SNPs showed that the association information could be captured by 2 intergenic HLA class I region SNPs (P = 9.4 x 10(-9))-rs2394885 and rs2922997 (marginal multivariate P = 2.1 x 10(-7) and P = .0016, respectively). SNP rs2394885 tagged the HLA-C*15:05 allele in the Vietnamese population. The identical associations were validated in a third sample of 364 patients with leprosy and 371 control subjects from North India. These results implicated class I alleles in leprosy pathogenesis.
C1 [Alter, Andrea; Orlova, Marianna; Schurr, Erwin] McGill Univ, McGill Ctr Study Host Resistance, Dept Med, Res Inst,Hlth Ctr, Montreal, PQ, Canada.
[Nguyen Thu Huong; Nguyen Van Thuc; Vu Hong Thai; Nguyen Ngoc Ba] Hosp Dermatovenereol, Ho Chi Minh City, Vietnam.
[Singh, Meenakshi; Mehra, Narinder] All India Inst Med Sci, Dept Transplant Immunol & Immunogenet, New Delhi, India.
[Katoch, Kiran] Cent JALMA Inst Leprosy & Other Infect Dis, Agra, Uttar Pradesh, India.
[Gao, Xiaojiang; Carrington, Mary] NCI Frederick, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD USA.
[Carrington, Mary] MGH MIT & Harvard Univ, Ragon Inst, Boston, MA USA.
[Abel, Laurent; Alcais, Alexandre] Univ Paris 05, Fac Med Necker, Paris, France.
[Abel, Laurent] Rockefeller Univ, Rockefeller Branch, Lab Human Genet Infect Dis, New York, NY 10021 USA.
[Alter, Andrea; Orlova, Marianna; Schurr, Erwin] McGill Univ, McGill Ctr Study Host Resistance, Dept Human Genet, Res Inst,Hlth Ctr, Montreal, PQ, Canada.
[Abel, Laurent; Alcais, Alexandre] INSERM, U550, Lab Genet Malad Infect, F-75654 Paris 13, France.
RP Schurr, E (reprint author), Montreal Gen Hosp, Res Inst, 1650 Cedar Ave,Room L11-521, Montreal, PQ H3G 1A4, Canada.
EM erwin.schurr@mcgill.ca
FU Canadian Institutes of Health Research; MAGRALEPRE from l'Ordre de
Malte; Rockefeller University Center for Clinical and Translational
Science [5UL1RR024143-03]; Rockefeller University; Natural Science and
Engineering Research Council of Canada; Assistance Publique-Hopitaux de
Paris; Programme de Recherche Fondamentale en Microbiologie Maladies
Infectieuses et Parasitaires; Agence Nationale de la Recherche of the
Ministere Francxais de l'Education Nationale de la Recherche et de la
Technologie
FX This work was supported by the Canadian Institutes of Health Research
(to ES) and MAGRALEPRE from l'Ordre de Malte (to AlA). The Laboratory of
Human Genetics of Infectious Diseases is supported by grants from The
Rockefeller University Center for Clinical and Translational Science
grant number 5UL1RR024143-03 and The Rockefeller University. AnA holds a
graduate studentship from the Natural Science and Engineering Research
Council of Canada. AlA and LA are supported by the Assistance
Publique-Hopitaux de Paris, Programme de Recherche Fondamentale en
Microbiologie Maladies Infectieuses et Parasitaires, and the Agence
Nationale de la Recherche of the Ministere Francxais de l'Education
Nationale de la Recherche et de la Technologie. ES is a Chercheur
National du Fonds de la Recherche en Sante du Quebec and an
International Research Scholar of the Howard Hughes Medical Institute.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 50
TC 24
Z9 24
U1 1
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAY 1
PY 2011
VL 203
IS 9
BP 1274
EP 1281
DI 10.1093/infdis/jir024
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 747FQ
UT WOS:000289306100011
PM 21459816
ER
PT J
AU Di Renzo, GC
Roura, LC
Facchinetti, F
Antsaklis, A
Breborowicz, G
Gratacos, E
Husslein, P
Lamont, R
Mikhailov, A
Montenegro, N
Radunovic, N
Robson, M
Robson, SC
Sen, C
Shennan, A
Stamatian, F
Ville, Y
AF Di Renzo, Gian Carlo
Cabero Roura, Lluis
Facchinetti, Fabio
Antsaklis, Aris
Breborowicz, Gregor
Gratacos, Eduard
Husslein, Peter
Lamont, Ronnie
Mikhailov, Anton
Montenegro, Nuno
Radunovic, Nebojsa
Robson, Mike
Robson, Stephen C.
Sen, Cihat
Shennan, Andrew
Stamatian, Florin
Ville, Yves
CA European Assoc Perinatal Medicine
TI Guidelines for the management of spontaneous preterm labor:
identification of spontaneous preterm labor, diagnosis of preterm
premature rupture of membranes, and preventive tools for preterm birth
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Preterm labor; premature rupture or membranes; preventive tools
ID FACTOR BINDING PROTEIN-1; RANDOMIZED CONTROLLED-TRIAL;
PLACEBO-CONTROLLED TRIAL; SHORT CERVIX; 17-ALPHA-HYDROXYPROGESTERONE
CAPROATE; FETAL MEMBRANES; AMNIOTIC-FLUID; DOUBLE-BLIND; PLACENTAL
ALPHA-MICROGLOBULIN-1; INTACT MEMBRANES
C1 [Di Renzo, Gian Carlo] Univ Perugia, Dept Obstet & Gynecol, I-06100 Perugia, Italy.
[Cabero Roura, Lluis] Hosp Valle De Hebron, Dept Obstet & Gynecol, Barcelona, Spain.
[Facchinetti, Fabio] Univ Modena & Reggio Emilia, Sch Midwifery, Mother Infant Dept, Reggio Emilia, Italy.
[Antsaklis, Aris] Univ Athens, Dept Obstet & Gynecol, GR-10679 Athens, Greece.
[Breborowicz, Gregor] Poznan Univ Med Sci, Dept Perinatol & Gynecol, Poznan, Poland.
[Gratacos, Eduard] Univ Barcelona, Hosp Clin IDIBAPS, Barcelona, Spain.
[Gratacos, Eduard] CIBER ER, Barcelona, Spain.
[Husslein, Peter] Univ Vienna, Dept Obstet & Gynecol, A-1010 Vienna, Austria.
[Lamont, Ronnie] Wayne State Univ, Dept Obstet & Gynecol, Div Maternal Fetal Med, Perinatol Res Branch NICHD NIH DHHS, Detroit, MI USA.
[Lamont, Ronnie] Northwick Pk Inst Med Res, Div Surg, London, England.
[Mikhailov, Anton] St Petersburg State Univ, Dept Obstet & Gynecol, Matern Hosp 1, St Petersburg, Russia.
[Montenegro, Nuno] Univ Hosp S Joao, Dept Obstet & Gynecol, Oporto, Portugal.
[Radunovic, Nebojsa] Univ Belgrade, Inst Obstet & Gynecol, Belgrade 11001, Serbia.
[Robson, Stephen C.] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Robson, Mike] Natl Matern Hosp, Dublin 2, Ireland.
[Sen, Cihat] Istanbul Univ, Dept Perinatal Med, Istanbul, Turkey.
[Shennan, Andrew] Kings Coll London, St Thomas Hosp, London, England.
[Stamatian, Florin] Univ Cluj Napoca, Dept Obstet & Gynecol, Cluj Napoca, Romania.
[Ville, Yves] Univ Paris 05, Dept Obstet & Gynecol, Paris, France.
RP Di Renzo, GC (reprint author), Univ Hosp, Dept Obstet & Gynecol, Ctr Perinatal & Reprod Med, I-06132 Perugia, Italy.
EM direnzo@unipg.it
RI Facchinetti, Fabio/K-9929-2014
OI Cabero, Luis/0000-0002-1905-5680; Montenegro, Nuno/0000-0002-3733-3613;
Gratacos, Eduard/0000-0002-7405-7224; Facchinetti,
Fabio/0000-0003-4694-9564
NR 117
TC 57
Z9 64
U1 3
U2 14
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1476-7058
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD MAY
PY 2011
VL 24
IS 5
BP 659
EP 667
DI 10.3109/14767058.2011.553694
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 747EM
UT WOS:000289303100001
PM 21366393
ER
PT J
AU Hauser, DN
Cookson, MR
AF Hauser, David N.
Cookson, Mark R.
TI Astrocytes in Parkinson's disease and DJ-1
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Editorial Material
C1 [Hauser, David N.; Cookson, Mark R.] NIA, NIH, Cell Biol & Gene Express Unit, Neurogenet Lab, Bethesda, MD USA.
[Hauser, David N.] Brown Univ, NIH, Dept Neurosci, Grad Partnership Program, Providence, RI 02912 USA.
RP Cookson, MR (reprint author), NIA, Gene Express Unit, Neurogenet Lab, 35 Convent Dr, Bethesda, MD 20892 USA.
EM cookson@mail.nih.gov
RI Hauser, David/I-4933-2012
OI Hauser, David/0000-0002-9500-5255
FU Intramural NIH HHS [ZIA AG000953-09]
NR 8
TC 9
Z9 9
U1 1
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD MAY
PY 2011
VL 117
IS 3
BP 357
EP 358
DI 10.1111/j.1471-4159.2011.07217.x
PG 2
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 749KJ
UT WOS:000289464500001
PM 21413989
ER
PT J
AU Sambamurti, K
Greig, NH
Utsuki, T
Barnwell, EL
Sharma, E
Mazell, C
Bhat, NR
Kindy, MS
Lahiri, DK
Pappolla, MA
AF Sambamurti, Kumar
Greig, Nigel H.
Utsuki, Tadanobu
Barnwell, Eliza L.
Sharma, Ekta
Mazell, Cheryl
Bhat, Narayan R.
Kindy, Mark S.
Lahiri, Debomoy K.
Pappolla, Miguel A.
TI Targets for AD treatment: conflicting messages from gamma-secretase
inhibitors
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Review
DE Alzheimer; amyloid; degeneration; gamma-secretase
ID AMYLOID PRECURSOR PROTEIN; MICROTUBULE-ASSOCIATED PROTEIN; FAMILIAL
ALZHEIMERS-DISEASE; PAIRED HELICAL FILAMENTS; TRANSGENIC MOUSE MODEL;
SHARE ANTIGENIC DETERMINANTS; BETA-SECRETASE; TRANSMEMBRANE DOMAIN;
IN-VIVO; OXIDATIVE STRESS
AB P>Current evidence suggests that Alzheimer's disease (AD) is a multi-factorial disease that starts with accumulation of multiple proteins. We have previously proposed that inhibition of gamma-secretase may impair membrane recycling causing neurodegeneration starting at synapses (Sambamurti K., Suram A., Venugopal C., Prakasam A., Zhou Y., Lahiri D. K. and Greig N. H. A partial failure of membrane protein turnover may cause Alzheimer's disease: a new hypothesis. Curr. Alzheimer Res., 3, 2006, 81). We also proposed familal AD mutations increase A beta 42 by inhibiting gamma-secretase. Herein, we discuss the failure of Eli Lilly's gamma-secretase inhibitor, semagacestat, in clinical trials in the light of our hypothesis, which extends the problem beyond toxicity of A beta aggregates. We elaborate that gamma-secretase inhibitors lead to accumulation of amyloid precursor protein C-terminal fragments that can later be processed by gamma-secretase to yields bursts of A beta to facilitate aggregation. Although we do not exclude a role for toxic A beta aggregates, inhibition of gamma-secretase can affect numerous substrates other than amyloid precursor protein to affect multiple pathways and the combined accumulation of multiple peptides in the membrane may impair its function and turnover. Taken together, protein processing and turnover pathways play an important role in maintaining cellular homeostasis and unless we clearly see consistent disease-related increase in their levels or activity, we need to focus on preserving their function rather than inhibiting them for treatment of AD and similar diseases.
C1 [Sambamurti, Kumar; Utsuki, Tadanobu; Barnwell, Eliza L.; Sharma, Ekta; Mazell, Cheryl; Bhat, Narayan R.; Kindy, Mark S.; Pappolla, Miguel A.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
[Greig, Nigel H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Baltimore, MD 21224 USA.
[Lahiri, Debomoy K.] Indiana Univ Sch Med, Inst Psychiat Res, Dept Psychiat, Indianapolis, IN USA.
RP Sambamurti, K (reprint author), Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
FU NIH [AG023055, AG022103, AG18379, AG18884]; Alzheimer's Association
[IIRG-10-173180]
FX The authors thank the funding from NIH intramural and extramural
(AG023055, AG022103, AG18379 and AG18884) and Alzheimer's Association
IIRG-10-173180. The authors thank Dr Jennifer Schnellmann of the MUSC
library science and informatics center for reading and editing the
document. This research does not represent a conflict of interest for
the authors.
NR 171
TC 47
Z9 50
U1 3
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD MAY
PY 2011
VL 117
IS 3
BP 359
EP 374
DI 10.1111/j.1471-4159.2011.07213.x
PG 16
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 749KJ
UT WOS:000289464500002
PM 21320126
ER
PT J
AU Ryott, M
Marklund, L
Wangsa, D
Elmberger, G
Munck-Wikland, E
AF Ryott, Michael
Marklund, Linda
Wangsa, Darawalee
Elmberger, Goran
Munck-Wikland, Eva
TI Cyclooxygenase-2 expression in oral tongue squamous cell carcinoma
SO JOURNAL OF ORAL PATHOLOGY & MEDICINE
LA English
DT Article
DE cyclooxygenase-2; head and neck cancer; immunohistochemistry; squamous
cell carcinoma
ID VEGF EXPRESSION; NECK-CANCER; HEAD; COX-2; OVEREXPRESSION; PATHWAY;
ANGIOGENESIS; INHIBITORS; APOPTOSIS; SURVIVAL
AB Background:
Cyclooxygenase-2 expression is associated with unfavorable outcome in various cancers, and evidence is accumulating that carcinogenesis possibly evolves from intracellular changes in response to induction of this enzyme. Today selective cyclooxygenase-2 inhibitors are being studied and used as complement in cancer treatment. This study examined the prognostic value of cyclooxygenase-2 expression in oral tongue squamous cell carcinoma (OTSCC).
Methods:
Expression of cyclooxygenase-2 was determined in biopsies from 76 stage matched patients with OTSCC by immunohistochemistry between January 2000 and December 2004 in Stockholm, Sweden. Additionally, twelve samples taken after pre-operative radiotherapy were investigated.
Results:
All OTSCC specimen expressed cyclooxygenase-2 by immunostaining. The cyclooxygenase-2 staining intensity increased significantly with more advanced stage (P = 0.020). Fifty percent of the surgical specimen showed a decrease in immunostaining post-radiation (P = 0.031). No association was found with survival.
Conclusion:
Cyclooxygenase-2 expression has limited prognostic value in OTSCC.
C1 [Ryott, Michael; Marklund, Linda; Munck-Wikland, Eva] Karolinska Univ Hosp, Dept Clin Sci Intervent & Technol, Karolinska Inst, S-17176 Stockholm, Sweden.
[Ryott, Michael; Marklund, Linda; Munck-Wikland, Eva] Karolinska Univ Hosp, Dept Otorhinolaryngol Head & Neck Surg, S-17176 Stockholm, Sweden.
[Wangsa, Darawalee] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Elmberger, Goran] Karolinska Univ Hosp, Dept Oncol Pathol, Karolinska Inst, S-17176 Stockholm, Sweden.
RP Ryott, M (reprint author), Karolinska Univ Hosp, Dept Clin Sci Intervent & Technol, Karolinska Inst, S-17176 Stockholm, Sweden.
EM michael.ryott@karolinska.se
RI Marklunf, Linda/L-1913-2015
NR 31
TC 5
Z9 6
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0904-2512
J9 J ORAL PATHOL MED
JI J. Oral Pathol. Med.
PD MAY
PY 2011
VL 40
IS 5
BP 385
EP 389
DI 10.1111/j.1600-0714.2010.00992.x
PG 5
WC Dentistry, Oral Surgery & Medicine; Pathology
SC Dentistry, Oral Surgery & Medicine; Pathology
GA 749KO
UT WOS:000289465200004
PM 21481000
ER
PT J
AU Pappas, A
Shankaran, S
Laptook, AR
Langer, JC
Bara, R
Ehrenkranz, RA
Goldberg, RN
Das, A
Higgins, RD
Tyson, JE
Walsh, MC
AF Pappas, Athina
Shankaran, Seetha
Laptook, Abbot R.
Langer, John C.
Bara, Rebecca
Ehrenkranz, Richard A.
Goldberg, Ronald N.
Das, Abhik
Higgins, Rosemary D.
Tyson, Jon E.
Walsh, Michele C.
CA Eunice Kennedy Shriver Natl Inst
TI Hypocarbia and Adverse Outcome in Neonatal Hypoxic-Ischemic
Encephalopathy
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID HYPOTHERMIC CARDIOPULMONARY BYPASS; BIRTH-WEIGHT INFANTS;
CEREBRAL-BLOOD-FLOW; PH-STAT STRATEGIES; KINASE-IV ACTIVITY; NEWBORN
PIGLETS; ALPHA-STAT; DNA FRAGMENTATION; CARBON-DIOXIDE; PERIVENTRICULAR
LEUKOMALACIA
AB Objective To evaluate the association between early hypocarbia and 18- to 22-month outcome among neonates with hypoxic-ischemic encephalopathy.
Study design Data from the National Institute of Child Health and Human Development Neonatal Research Network randomized, controlled trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy were used for this secondary observational study. Infants (n = 204) had multiple blood gases recorded from birth to 12 hours of study intervention (hypothermia versus intensive care alone). The relationship between hypocarbia and outcome (death/disability at 18 to 22 months) was evaluated by unadjusted and adjusted analyses examining minimum PCO(2) and cumulative exposure to PCO(2) <35 mm Hg. The relationship between cumulative PCO(2) <35 mm Hg (calculated as the difference between 35 mm Hg and the sampled PCO(2) multiplied by the duration of time spent <35 mm Hg) and outcome was evaluated by level of exposure (none-high) using a multiple logistic regression analysis with adjustments for pH, level of encephalopathy, treatment group (+/- hypothermia), and time to spontaneous respiration and ventilator days; results were expressed as odds ratios and 95% confidence intervals. Alternative models of CO(2) concentration were explored to account for fluctuations in CO(2).
Results Both minimum PCO(2) and cumulative PCO(2) <35 mm Hg were associated with poor outcome (P < .05). Moreover, death/disability increased with greater cumulative exposure to PCO(2) < 35 mm Hg.
Conclusions Hypocarbia is associated with poor outcome after hypoxic-ischemic encephalopathy. (J Pediatr 2011; 158: 752-8).
C1 [Pappas, Athina; Shankaran, Seetha; Bara, Rebecca] 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.
[Langer, John C.; Das, Abhik] RTI Int, Stat & Epidemiol, Res Triangle Pk, NC USA.
[Ehrenkranz, Richard A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Goldberg, Ronald N.] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA.
[Tyson, Jon E.] Univ Texas Med Sch Houston, Dept Pediat, Houston, TX USA.
[Walsh, Michele C.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
RP Pappas, A (reprint author), Wayne State Univ, Sch Med, Childrens Hosp Michigan, 3901 Beaubien Blvd, Detroit, MI 48201 USA.
EM apappas@med.wayne.edu
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD)
FX Supported by the National Institutes of Health and the Eunice Kennedy
Shriver National Institute of Child Health and Human Development (NICHD)
for the NICHD Neonatal Research Network's Whole Body Cooling for Hypoxic
Ischemic Encephalopathy Study.
NR 30
TC 35
Z9 35
U1 2
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
J9 J PEDIATR-US
JI J. Pediatr.
PD MAY
PY 2011
VL 158
IS 5
BP 752
EP U82
DI 10.1016/j.jpeds.2010.10.019
PG 8
WC Pediatrics
SC Pediatrics
GA 746YH
UT WOS:000289286100014
PM 21146184
ER
PT J
AU Rabiee, A
Magruder, JT
Salas-Carrillo, R
Carlson, O
Egan, JM
Askin, FB
Elahi, D
Andersen, DK
AF Rabiee, Atoosa
Magruder, J. Trent
Salas-Carrillo, Rocio
Carlson, Olga
Egan, Josephine M.
Askin, Frederic B.
Elahi, Dariush
Andersen, Dana K.
TI Hyperinsulinemic Hypoglycemia After Roux-en-Y Gastric Bypass: Unraveling
the Role of Gut Hormonal and Pancreatic Endocrine Dysfunction
SO JOURNAL OF SURGICAL RESEARCH
LA English
DT Article
DE hyperinsulinemia; Roux-en-Y; GLP-1; glucagons; hypoglycemia; bariatric
surgery
ID DIFFUSE NESIDIOBLASTOSIS; ISLET HYPERPLASIA; SURGERY; MECHANISMS;
REMISSION; ADULTS
AB Background. Profound hypoglycemia occurs rarely as a late complication after Roux-en-Y gastric bypass (RYGB). We investigated the role of glucagon-like-peptide-1 (GLP-1) in four subjects who developed recurrent neuro-glycopenia 2 to 3 y after RYGB.
Methods. A standardized test meal (STM) was administered to all four subjects. A 2 h hyperglycemic clamp with GLP-1 infusion during the second hour was performed in one subject, before, during a 4 wk trial of octreotide (Oc), and after 85% distal pancreatectomy. After cessation of both glucose and GLP-1 infusion at the end of the 2 h clamp, blood glucose levels were monitored for 30 min. Responses were compared with a control group (five subjects 12 mo status post-RYGB without hypoglycemic symptoms).
Results. During STM, both GLP-1 and insulin levels were elevated 3- to 4-fold in all subjects, and plasma glucose-dependent insulinotropic peptide (GIP) levels were elevated 2-fold. Insulin responses to hyperglycemia +/- GLP-1 infusion in one subject were comparable to controls, but after cessation of glucose infusion, glucose levels fell to 40 mg/dL. During Oc, the GLP-1 and insulin responses to STM were reduced (>50%). During the clamp, insulin response to hyperglycemia alone was reduced, but remained unchanged during GLP-1. Glucagon levels during hyperglycemia alone were suppressed and further suppressed after the addition of GLP-1. With the substantial drop in glucose during the 30 min follow-up, glucagon levels failed to rise. Due to persistent symptoms, one subject underwent 85% distal pancreatectomy; postoperatively, the subject remained asymptomatic (blood glucose: 119-220 mg/dL), but a repeat STM showed persistence of elevated levels of GLP-1. Histologically enlarged islets, and beta-cell clusters scattered throughout the acinar parenchyma were seen, as well as beta-cells present within pancreatic duct epithelium. An increase in pancreatic and duodenal homeobox-1 protein (PDX-1) expression was observed in the subject compared with control pancreatic tissue.
Conclusions. A persistent exaggerated hypersecretion of GLP-1, which has been shown to be insulinotropic, insulinomimetic, and glucagonostatic, is the likely cause of post-RYGB hypoglycemia. The hypertrophy and ectopic location of beta-cells is likely due to overexpression of the islet cell transcription factor, PDX-1, caused by prolonged hypersecretion of GLP-1. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Rabiee, Atoosa; Magruder, J. Trent; Salas-Carrillo, Rocio; Elahi, Dariush; Andersen, Dana K.] Johns Hopkins Univ, Sch Med, Johns Hopkins Bayview Med Ctr, Dept Surg, Baltimore, MD 21218 USA.
[Rabiee, Atoosa; Elahi, Dariush] Johns Hopkins Univ, Sch Med, Johns Hopkins Bayview Med Ctr, Dept Med, Baltimore, MD 21218 USA.
[Askin, Frederic B.] Johns Hopkins Univ, Sch Med, Johns Hopkins Bayview Med Ctr, Dept Pathol, Baltimore, MD 21218 USA.
[Carlson, Olga; Egan, Josephine M.] NIA, Clin Physiol Branch, NIH, Baltimore, MD 21224 USA.
RP Elahi, D (reprint author), Univ Penn, Dept Med, Sch Med, Penn Presbyterian Hosp, Mutch 108,51 N 39th St, Philadelphia, PA 19104 USA.
EM dariush.elahi@uphs.upenn.edu
FU Intramural NIH HHS [Z99 AG999999]
NR 23
TC 36
Z9 39
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 0022-4804
EI 1095-8673
J9 J SURG RES
JI J. Surg. Res.
PD MAY
PY 2011
VL 167
IS 2
BP 199
EP 205
DI 10.1016/j.jss.2010.09.047
PG 7
WC Surgery
SC Surgery
GA 748RG
UT WOS:000289407800046
PM 21414635
ER
PT J
AU Heinze, B
Frey, S
Mordstein, M
Schmitt-Graeff, A
Ehl, S
Buchholz, UJ
Collins, PL
Staeheli, P
Krempl, CD
AF Heinze, Britta
Frey, Stefanie
Mordstein, Markus
Schmitt-Graeff, Anette
Ehl, Stephan
Buchholz, Ursula J.
Collins, Peter L.
Staeheli, Peter
Krempl, Christine D.
TI Both Nonstructural Proteins NS1 and NS2 of Pneumonia Virus of Mice are
Inhibitors of the Interferon Type I and Type III Responses In Vivo
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RESPIRATORY SYNCYTIAL VIRUS; NF-KAPPA-B; IFN-LAMBDA; ANTIVIRAL
RESPONSES; REGULATORY FACTOR-3; SIGNAL-TRANSDUCTION; INFECTION; ALPHA;
CELLS; REPLICATION
AB Infection of mice with pneumonia virus of mice (PVM) provides a convenient experimental pathogenesis model in a natural host for a human respiratory syncytial virus-related virus. Extending our previous work showing that the PVM nonstructural (NS) proteins were pathogenicity factors in mice, we identify both the NS1 and NS2 proteins as antagonists of alpha/beta interferon (IFN-alpha/beta) and IFN-lambda by use of recombinant PVM (rPVM) with single and combined deletions of the NS proteins (Delta NS1, Delta NS2, and Delta NS1 Delta NS2). Wild-type and NS deletion PVMs were evaluated for growth and pathogenesis by infecting knockout mice that lack functional receptors to IFN-alpha/beta, IFN-lambda, or both. The absence of the receptor to IFN-alpha/beta (IFNAR) or IFN-lambda (interleukin-28 receptor alpha chain [IL-28R alpha]) individually did not reverse the attenuated virulence of the NS deletion viruses although loss of IFNAR partially restored replication efficiency. When both receptors were deleted, replication and virulence were largely rescued for rPVM Delta NS1 and were significantly but not completely rescued for rPVM Delta NS2. As for rPVM Delta NS1 Delta NS2, the effect was mostly limited to partial enhancement of replication. This indicates that both IFN-alpha/beta and IFN-lambda contributed to restricting the NS deletion viruses, with the former playing the greater role. Interestingly, the replication and virulence of wild-type PVM were completely unaffected by the presence or absence of functional receptors to IFN-alpha/beta and IFN-lambda, indicating that both systems are strongly suppressed during infection. However, pretreatment of mice with IFN-alpha/beta was protective against lethal rPVM challenge, whereas pretreatment with IFN-lambda delayed but did not prevent disease and, in some cases, reduced mortality. The fact that virulence of rPVM lacking NS2 was not recovered completely when both interferon receptors were deleted suggests that NS2 may have further functions outside the IFN system.
C1 [Heinze, Britta; Krempl, Christine D.] Univ Wurzburg, Inst Virol & Immunobiol, D-97078 Wurzburg, Germany.
[Frey, Stefanie; Ehl, Stephan] Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, Freiburg, Germany.
[Frey, Stefanie] Univ Freiburg, Fac Biol, Freiburg, Germany.
[Mordstein, Markus; Staeheli, Peter] Univ Freiburg, Inst Med Microbiol & Hyg, Dept Virol, Freiburg, Germany.
[Schmitt-Graeff, Anette] Univ Freiburg, Inst Pathol, D-7800 Freiburg, Germany.
[Buchholz, Ursula J.; Collins, Peter L.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Krempl, CD (reprint author), Univ Wurzburg, Inst Virol & Immunobiol, Versbacher Str 7, D-97078 Wurzburg, Germany.
EM ckrempl@vim.uni-wuerzburg.de
RI Krempl, Christine/O-2081-2015
FU German Research Foundation [KR2964/1-2, EH145/4-2]; NIAID
FX This work has been supported by grants KR2964/1-2 and EH145/4-2 from the
German Research Foundation to C. D. K. and S. E. P. L. C. and U.J.B.
were supported by the NIAID Intramural Program.
NR 39
TC 14
Z9 14
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD MAY
PY 2011
VL 85
IS 9
BP 4071
EP 4084
DI 10.1128/JVI.01365-10
PG 14
WC Virology
SC Virology
GA 751LG
UT WOS:000289618600003
PM 21307191
ER
PT J
AU Datta, SAK
Temeselew, LG
Crist, RM
Soheilian, F
Kamata, A
Mirro, J
Harvin, D
Nagashima, K
Cachau, RE
Rein, A
AF Datta, Siddhartha A. K.
Temeselew, Lakew G.
Crist, Rachael M.
Soheilian, Ferri
Kamata, Anne
Mirro, Jane
Harvin, Demetria
Nagashima, Kunio
Cachau, Raul E.
Rein, Alan
TI On the Role of the SP1 Domain in HIV-1 Particle Assembly: a Molecular
Switch?
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ROUS-SARCOMA-VIRUS; PROTEIN SECONDARY
STRUCTURE; CIRCULAR-DICHROISM SPECTRA; MATURATION INHIBITOR PA-457;
ALPHA-HELICAL STRUCTURE; TYPE-1 MATRIX PROTEIN; IN-VITRO; GAG PROTEIN;
CAPSID PROTEIN
AB Expression of a retroviral protein, Gag, in mammalian cells is sufficient for assembly of immature virus-like particles (VLPs). VLP assembly is mediated largely by interactions between the capsid (CA) domains of Gag molecules but is facilitated by binding of the nucleocapsid (NC) domain to nucleic acid. We have investigated the role of SP1, a spacer between CA and NC in HIV-1 Gag, in VLP assembly. Mutational analysis showed that even subtle changes in the first 4 residues of SP1 destroy the ability of Gag to assemble correctly, frequently leading to formation of tubes or other misassembled structures rather than proper VLPs. We also studied the conformation of the CA-SP1 junction region in solution, using both molecular dynamics simulations and circular dichroism. Consonant with nuclear magnetic resonance (NMR) studies from other laboratories, we found that SP1 is nearly unstructured in aqueous solution but undergoes a concerted change to an alpha-helical conformation when the polarity of the environment is reduced by addition of dimethyl sulfoxide (DMSO), trifluoroethanol, or ethanol. Remarkably, such a coil-to-helix transition is also recapitulated in an aqueous medium at high peptide concentrations. The exquisite sensitivity of SP1 to mutational changes and its ability to undergo a concentration-dependent structural transition raise the possibility that SP1 could act as a molecular switch to prime HIV-1 Gag for VLP assembly. We suggest that changes in the local environment of SP1 when Gag oligomerizes on nucleic acid might trigger this switch.
C1 [Datta, Siddhartha A. K.; Temeselew, Lakew G.; Crist, Rachael M.; Mirro, Jane; Harvin, Demetria; Rein, Alan] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[Soheilian, Ferri; Kamata, Anne; Nagashima, Kunio] SAIC Frederick Inc, Electron Microscope Lab, Frederick, MD 21702 USA.
[Cachau, Raul E.] SAIC Frederick Inc, Informat Syst Program, Frederick, MD 21702 USA.
RP Datta, SAK (reprint author), NCI, HIV Drug Resistance Program, POB B, Frederick, MD 21702 USA.
EM dattasi@mail.nih.gov; reina@mail.nih.gov
RI Crist, Rachael/K-7603-2012;
OI Datta, Siddhartha/0000-0002-4098-7490
FU NIH, National Cancer Institute, Center for Cancer Research; National
Cancer Institute, National Institutes of Health [HHSN26120080001E]
FX This work 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 HHSN26120080001E.
NR 74
TC 47
Z9 47
U1 0
U2 17
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD MAY
PY 2011
VL 85
IS 9
BP 4111
EP 4121
DI 10.1128/JVI.00006-11
PG 11
WC Virology
SC Virology
GA 751LG
UT WOS:000289618600006
PM 21325421
ER
PT J
AU Geisbert, TW
Bailey, M
Hensley, L
Asiedu, C
Geisbert, J
Stanley, D
Honko, A
Johnson, J
Mulangu, S
Pau, MG
Custers, J
Vellinga, J
Hendriks, J
Jahrling, P
Roederer, M
Goudsmit, J
Koup, R
Sullivan, NJ
AF Geisbert, Thomas W.
Bailey, Michael
Hensley, Lisa
Asiedu, Clement
Geisbert, Joan
Stanley, Daphne
Honko, Anna
Johnson, Joshua
Mulangu, Sabue
Pau, Maria Grazia
Custers, Jerome
Vellinga, Jort
Hendriks, Jenny
Jahrling, Peter
Roederer, Mario
Goudsmit, Jaap
Koup, Richard
Sullivan, Nancy J.
TI Recombinant Adenovirus Serotype 26 (Ad26) and Ad35 Vaccine Vectors
Bypass Immunity to Ad5 and Protect Nonhuman Primates against Ebolavirus
Challenge
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID PRIME-BOOST REGIMENS; T-CELL RESPONSES; DENDRITIC CELLS; RHESUS-MONKEYS;
NEUTRALIZING ANTIBODIES; PREEXISTING IMMUNITY; ANTI-AD5 IMMUNITY;
HEALTHY-ADULTS; IMMUNOGENICITY; VIRUS
AB The use of adenoviruses (Ad) as vaccine vectors against a variety of pathogens has demonstrated their capacity to elicit strong antibody and cell-mediated immune responses. Adenovirus serotype C vectors, such as Ad serotype 5 (Ad5), expressing Ebolavirus (EBOV) glycoprotein (GP), protect completely after a single inoculation at a dose of 10(10) viral particles. However, the clinical application of a vaccine based on Ad5 vectors may be hampered, since impairment of Ad5 vaccine efficacy has been demonstrated for humans and nonhuman primates with high levels of preexisting immunity to the vector. Ad26 and Ad35 segregate genetically from Ad5 and exhibit lower seroprevalence in humans, making them attractive vaccine vector alternatives. In the series of studies presented, we show that Ad26 and Ad35 vectors generate robust antigen-specific cell-mediated and humoral immune responses against EBOV GP and that Ad5 immune status does not affect the generation of GP-specific immune responses by these vaccines. We demonstrate partial protection against EBOV by a single-shot Ad26 vaccine and complete protection when this vaccine is boosted by Ad35 1 month later. Increases in efficacy are paralleled by substantial increases in T-and B-cell responses to EBOV GP. These results suggest that Ad26 and Ad35 vectors warrant further development as candidate vaccines for EBOV.
C1 [Bailey, Michael; Asiedu, Clement; Stanley, Daphne; Mulangu, Sabue; Sullivan, Nancy J.] NIAID, Biodefense Res Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Geisbert, Thomas W.; Hensley, Lisa; Geisbert, Joan; Honko, Anna; Johnson, Joshua] USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA.
[Roederer, Mario; Koup, Richard] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Jahrling, Peter] NIAID, Integrated Res Facil, NIH, Bethesda, MD 20817 USA.
[Pau, Maria Grazia; Custers, Jerome; Vellinga, Jort; Hendriks, Jenny; Goudsmit, Jaap] Crucell, NL-2333 CN Leiden, Netherlands.
RP Sullivan, NJ (reprint author), NIAID, Biodefense Res Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM nsullivan@nih.gov
OI Johnson, Joshua/0000-0002-5677-3841; Honko, Anna/0000-0001-9165-148X
NR 50
TC 61
Z9 68
U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD MAY
PY 2011
VL 85
IS 9
BP 4222
EP 4233
DI 10.1128/JVI.02407-10
PG 12
WC Virology
SC Virology
GA 751LG
UT WOS:000289618600016
PM 21325402
ER
PT J
AU Teterina, NL
Pinto, Y
Weaver, JD
Jensen, KS
Ehrenfeld, E
AF Teterina, Natalya L.
Pinto, Yuval
Weaver, Joseph D.
Jensen, Kenneth S.
Ehrenfeld, Ellie
TI Analysis of Poliovirus Protein 3A Interactions with Viral and Cellular
Proteins in Infected Cells
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID EXCHANGE FACTOR GBF1; RNA REPLICATION; NONSTRUCTURAL PROTEINS; MEMBRANE
ASSOCIATION; POLYMERASE 3D(POL); HYDROPHOBIC DOMAIN; SECRETORY PATHWAY;
LINKAGE MAP; BREFELDIN-A; INHIBITION
AB Poliovirus proteins 3A and 3AB are small, membrane-binding proteins that play multiple roles in viral RNA replication complex formation and function. In the infected cell, these proteins associate with other viral and cellular proteins as part of a supramolecular complex whose structure and composition are unknown. We isolated viable viruses with three different epitope tags (FLAG, hemagglutinin [HA], and c-myc) inserted into the N-terminal region of protein 3A. These viruses exhibited growth properties and characteristics very similar to those of the wild-type, untagged virus. Extracts prepared from the infected cells were subjected to immunoaffinity purification of the tagged proteins by adsorption to commercial antibody-linked beads and examined after elution for cellular and other viral proteins that remained bound to 3A sequences during purification. Viral proteins 2C, 2BC, 3D, and 3CD were detected in all three immunopurified 3A samples. Among the cellular proteins previously reported to interact with 3A either directly or indirectly, neither LIS1 nor phosphoinositol-4 kinase (PI4K) were detected in any of the purified tagged 3A samples. However, the guanine nucleotide exchange factor GBF1, which is a key regulator of membrane trafficking in the cellular protein secretory pathway and which has been shown previously to bind enteroviral protein 3A and to be required for viral RNA replication, was readily recovered along with immunoaffinity-purified 3A-FLAG. Surprisingly, we failed to cocapture GBF1 with 3A-HA or 3A-myc proteins. A model for variable binding of these 3A mutant proteins to GBF1 based on amino acid sequence motifs and the resulting practical and functional consequences thereof are discussed.
C1 [Teterina, Natalya L.; Pinto, Yuval; Weaver, Joseph D.; Jensen, Kenneth S.; Ehrenfeld, Ellie] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Teterina, NL (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 33,Room 3W10A2,33 North Dr,MSC 3203, Bethesda, MD 20892 USA.
EM nteterina@niaid.nih.gov
FU NIAID, NIH
FX This research was supported by the Intramural Research Program of NIAID,
NIH.
NR 41
TC 26
Z9 29
U1 1
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD MAY
PY 2011
VL 85
IS 9
BP 4284
EP 4296
DI 10.1128/JVI.02398-10
PG 13
WC Virology
SC Virology
GA 751LG
UT WOS:000289618600021
PM 21345960
ER
PT J
AU Chen, ZC
Chumakov, K
Dragunsky, E
Kouiavskaia, D
Makiya, M
Neverov, A
Rezapkin, G
Sebrell, A
Purcell, R
AF Chen, Zhaochun
Chumakov, Konstantin
Dragunsky, Eugenia
Kouiavskaia, Diana
Makiya, Michelle
Neverov, Alexander
Rezapkin, Gennady
Sebrell, Andrew
Purcell, Robert
TI Chimpanzee-Human Monoclonal Antibodies for Treatment of Chronic
Poliovirus Excretors and Emergency Postexposure Prophylaxis
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID VACCINE-DERIVED POLIOVIRUS; POTENT NEUTRALIZATION; POLIOMYELITIS;
IMMUNIZATION; ERADICATION; RECEPTOR; TYPE-1; VIRUS; ELISA; MUTANTS
AB Six poliovirus-neutralizing Fabs were recovered from a combinatorial Fab phage display library constructed from bone marrow-derived lymphocytes of immunized chimpanzees. The chimeric chimpanzee-human full-length IgGs (hereinafter called monoclonal antibodies [MAbs]) were generated by combining a chimpanzee IgG light chain and a variable domain of heavy chain with a human constant Fc region. The six MAbs neutralized vaccine strains and virulent strains of poliovirus. Five MAbs were serotype specific, while one MAb cross-neutralized serotypes 1 and 2. Epitope mapping performed by selecting and sequencing antibody-resistant viral variants indicated that the cross-neutralizing MAb bound between antigenic sites 1 and 2, thereby covering the canyon region containing the receptor-binding site. Another serotype 1-specific MAb recognized a region located between antigenic sites 2 and 3 that included parts of capsid proteins VP1 and VP3. Both serotype 2-specific antibodies recognized antigenic site 1. No escape mutants to serotype 3-specific MAbs could be generated. The administration of a serotype 1-specific MAb to transgenic mice susceptible to poliovirus at a dose of 5 mu g/mouse completely protected them from paralysis after challenge with a lethal dose of wild-type poliovirus. Moreover, MAb injection 6 or 12 h after virus infection provided significant protection. The MAbs described here could be tested in clinical trials to determine whether they might be useful for treatment of immunocompromised chronic virus excretors and for emergency protection of contacts of a paralytic poliomyelitis case.
C1 [Chumakov, Konstantin; Dragunsky, Eugenia; Kouiavskaia, Diana; Neverov, Alexander; Rezapkin, Gennady] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA.
[Chen, Zhaochun; Makiya, Michelle; Sebrell, Andrew; Purcell, Robert] NIAID, NIH, Bethesda, MD 20892 USA.
RP Chumakov, K (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-470, Rockville, MD 20852 USA.
EM konstantin.chumakov@fda.hhs.gov
FU NIAID/NIH; CBER/FDA
FX The work was supported by intramural research funding from NIAID/NIH and
CBER/FDA.
NR 43
TC 18
Z9 18
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAY
PY 2011
VL 85
IS 9
BP 4354
EP 4362
DI 10.1128/JVI.02553-10
PG 9
WC Virology
SC Virology
GA 751LG
UT WOS:000289618600027
PM 21345966
ER
PT J
AU Wu, XL
Changela, A
O'Dell, S
Schmidt, SD
Pancera, M
Yang, YP
Zhang, BS
Gorny, MK
Phogat, S
Robinson, JE
Stamatatos, L
Zolla-Pazner, S
Kwong, PD
Mascola, JR
AF Wu, Xueling
Changela, Anita
O'Dell, Sijy
Schmidt, Stephen D.
Pancera, Marie
Yang, Yongping
Zhang, Baoshan
Gorny, Miroslaw K.
Phogat, Sanjay
Robinson, James E.
Stamatatos, Leonidas
Zolla-Pazner, Susan
Kwong, Peter D.
Mascola, John R.
TI Immunotypes of a Quaternary Site of HIV-1 Vulnerability and Their
Recognition by Antibodies
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; NEUTRALIZING
ANTIBODIES; POTENT NEUTRALIZATION; ENVELOPE VARIANTS; EARLY SUBTYPE; ENV
CLONES; EPITOPE; GP120; BROAD
AB HIV-1 is neutralized by a class of antibodies that preferentially recognize a site formed on the assembled viral spike. Such quaternary structure-specific antibodies have diverse neutralization breadths, with antibodies PG16 and PG9 able to neutralize 70 to 80% of circulating HIV-1 isolates while antibody 2909 is specific for strain SF162. We show that alteration between a rare lysine and a common N-linked glycan at position 160 of HIV-1 gp120 is primarily responsible for toggling between 2909 and PG16/PG9 neutralization sensitivity. Quaternary structure-specific antibodies appear to target antigenic variants of the same epitope, with neutralization breadth determined by the prevalence of recognized variants among circulating isolates.
C1 [Wu, Xueling; Changela, Anita; O'Dell, Sijy; Schmidt, Stephen D.; Pancera, Marie; Yang, Yongping; Zhang, Baoshan; Kwong, Peter D.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Gorny, Miroslaw K.; Zolla-Pazner, Susan] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
[Phogat, Sanjay] Int AIDS Vaccine Initiat, AIDS Vaccine Design & Dev Lab, New York, NY 11226 USA.
[Robinson, James E.] Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70012 USA.
[Stamatatos, Leonidas] Univ Washington, Dept Global Hlth, Seattle, WA 98109 USA.
[Stamatatos, Leonidas] Seattle BioMed, Seattle, WA 98109 USA.
[Zolla-Pazner, Susan] New York Vet Affairs Med Ctr, New York, NY 10010 USA.
RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA.
EM jmascola@nih.gov
RI Schmidt, Stephen/B-5398-2012;
OI Gorny, Miroslaw/0000-0002-2714-8780
FU Vaccine Research Center, NIAID, NIH; International AIDS Vaccine
Initiative; NIH [AI36085, HL59725, AI27742]; Department of Veterans
Affairs
FX Support for this work was provided by the Intramural Research Program of
the Vaccine Research Center, NIAID, NIH, by the International AIDS
Vaccine Initiative, by grants from the NIH (AI36085, HL59725, and
AI27742), and by research funds from the Department of Veterans Affairs.
NR 33
TC 32
Z9 32
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD MAY
PY 2011
VL 85
IS 9
BP 4578
EP 4585
DI 10.1128/JVI.02585-10
PG 8
WC Virology
SC Virology
GA 751LG
UT WOS:000289618600050
PM 21325411
ER
PT J
AU Schwartz, JA
Buonocore, L
Suguitan, A
Hunter, M
Marx, PA
Subbarao, K
Rose, JK
AF Schwartz, Jennifer A.
Buonocore, Linda
Suguitan, Amorsolo, Jr.
Hunter, Meredith
Marx, Preston A.
Subbarao, Kanta
Rose, John K.
TI Vesicular Stomatitis Virus-Based H5N1 Avian Influenza Vaccines Induce
Potent Cross-Clade Neutralizing Antibodies in Rhesus Macaques
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID LONG-TERM PROTECTION; REPLICATION-COMPETENT; VECTORS; TRANSCRIPTION;
IMMUNIZATION; CHALLENGE; MICE; LIVE
AB We analyzed the ability of a vaccine vector based on vesicular stomatitis virus (VSV) to induce a neutralizing antibody (NAb) response to avian influenza viruses (AIVs) in rhesus macaques. Animals vaccinated with vectors expressing either strain A/Hong Kong/156/1997 or strain A/Vietnam/1203/2004 H5 hemagglutinin (HA) were able to generate robust NAb responses. The ability of the vectors to induce NAbs against homologous and heterologous AIVs after a single dose was dependent upon the HA antigen incorporated into the VSV vaccine. The vectors expressing strain A/Vietnam/1203/2004 H5 HA were superior to those expressing strain A/Hong Kong/156/1997 HA at inducing cross-clade NAbs.
C1 [Schwartz, Jennifer A.; Buonocore, Linda; Rose, John K.] Yale Univ, Dept Pathol, Sch Med, New Haven, CT 06520 USA.
[Suguitan, Amorsolo, Jr.; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Hunter, Meredith; Marx, Preston A.] Tulane Univ, Tulane Natl Primate Res Ctr, Covington, LA 70433 USA.
RP Rose, JK (reprint author), Yale Univ, Dept Pathol, Sch Med, 310 Cedar St,LH 315, New Haven, CT 06520 USA.
EM john.rose@yale.edu
OI Schwartz, Jennifer/0000-0001-8239-8857
FU NIH [RO1AI080781, RO1AI45510, U54 AI057158]; TNPRC [RR000164]; National
Institute of Allergy and Infectious Diseases (NIAID), NIH
FX This research was supported in part by NIH grants RO1AI080781,
RO1AI45510, and U54 AI057158, TNPRC base grant RR000164, and the
Intramural Research Program of the National Institute of Allergy and
Infectious Diseases (NIAID), NIH.
NR 19
TC 21
Z9 22
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD MAY
PY 2011
VL 85
IS 9
BP 4602
EP 4605
DI 10.1128/JVI.02491-10
PG 4
WC Virology
SC Virology
GA 751LG
UT WOS:000289618600054
PM 21325423
ER
PT J
AU Shuh, M
Morse, BA
Heidecker, G
Derse, D
AF Shuh, Maureen
Morse, Barry A.
Heidecker, Gisela
Derse, David
TI Association of Src-Related Kinase Lyn with the Interleukin-2 Receptor
and Its Role in Maintaining Constitutive Phosphorylation of JAK/STAT in
Human T-Cell Leukemia Virus Type 1-Transformed T Cells
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID COLONY-STIMULATING FACTOR; PROTEIN-TYROSINE KINASE; HTLV-I;
SIGNAL-TRANSDUCTION; PHOSPHATIDYLINOSITOL 3-KINASE; HEMATOPOIETIC-CELLS;
HUMAN NEUTROPHILS; IL-2 RECEPTOR; TAX GENE; ACTIVATION
AB Human T-cell leukemia virus type 1 (HTLV-1) infection and transformation are associated with an incremental switch in the expression of the Src-related protein tyrosine kinases Lck and Lyn. We examined the physical and functional interactions of Lyn with receptors and signal transduction proteins in HTLV-1-infected T cells. Lyn coimmunoprecipitates with the interleukin-2 beta receptor (IL-2R beta) and JAK3 proteins; however, the association of Lyn with the IL-2R beta and Lyn kinase activity was independent of IL-2 stimulation. Phosphorylation of Janus kinase 3 (JAK3) and signal transducers and activator of transcription 5 (STAT5) proteins was reduced by treatment of cells with the Src kinase inhibitor PP2 or by ectopic expression of a dominant negative Lyn kinase protein.
C1 [Shuh, Maureen] Xavier Univ, Div Basic Pharmaceut Sci, Coll Pharm, New Orleans, LA 70125 USA.
[Morse, Barry A.] Centocor Ortho Biotech Inc, Horsham, PA 19044 USA.
[Heidecker, Gisela; Derse, David] NCI, HIV Drug Resistance Program, Retrovirus Gene Regulat Sect, Frederick, MD 21702 USA.
RP Shuh, M (reprint author), Xavier Univ, Div Basic Pharmaceut Sci, Coll Pharm, 1 Drexel Dr, New Orleans, LA 70125 USA.
EM mshuh@xula.edu
FU Louisiana Cancer Research Consortium; Louisiana Board of Regents
[RC/EEP-12]
FX M. Shuh is grateful to the Louisiana Cancer Research Consortium and the
Louisiana Board of Regents (RC/EEP-12) for funding and to Steven W. Rick
for his unwavering support.
NR 49
TC 6
Z9 7
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD MAY
PY 2011
VL 85
IS 9
BP 4623
EP 4627
DI 10.1128/JVI.00839-10
PG 5
WC Virology
SC Virology
GA 751LG
UT WOS:000289618600058
PM 21345943
ER
PT J
AU Sugiyama, N
Tsukiyama, T
Yamaguchi, TP
Yokoyama, T
AF Sugiyama, Noriyuki
Tsukiyama, Tadasuke
Yamaguchi, Terry P.
Yokoyama, Takahiko
TI The canonical Wnt signaling pathway is not involved in renal cyst
development in the kidneys of inv mutant mice
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE ERK; inversin; inv; planar cell polarity; renal cyst; Wnt
ID PLANAR CELL POLARITY; BETA-CATENIN; PRIMARY CILIA; EPITHELIAL-CELLS;
DISEASE; GENE; PROLIFERATION; INACTIVATION; CYSTOGENESIS; INVERSIN
AB Recent studies have identified several genes whose defects cause hereditary renal cystic diseases with most of the gene products located in the primary cilia. It has been suggested that primary cilia are involved in signaling pathways, defects of which result in abnormal cell proliferation and randomization of oriented cell division in the kidney leading to cyst formation. Mice with a mutation in the inv gene are a model for human nephronophthisis type 2 and develop multiple renal cysts. Inv protein (also called inversin) is located in the base of primary cilia and acts as a switch from canonical to non-canonical Wnt signaling. Here, we studied the orientation of cell division and proliferation in the kidneys of inv mutant mice, as its loss is thought to maintain activation of the canonical Wnt signaling. To establish if canonical signaling was involved in this process, we mated inv mutant with BATlacZ mice to measure canonical Wnt activity. Based on these reporter mice, nuclear localization and phosphorylation of beta-catenin, and responsiveness to Wnt ligands in inv mutant cells, we found that random oriented cell division is an initial event for renal tubule expansion and precedes cell proliferation. Thus, our results do not support the hypothesis that canonical Wnt signaling causes renal cyst development in these mice. Kidney International (2011) 79, 957-965; doi:10.1038/ki.2010.534; published online 19 January 2011
C1 [Yokoyama, Takahiko] Kyoto Prefectural Univ Med, Dept Anat & Dev Biol, Grad Sch Med Sci, Kamigyo Ku, Kyoto 6028566, Japan.
[Tsukiyama, Tadasuke] Hokkaido Univ, Dept Biochem, Grad Sch Med, Sapporo, Hokkaido 060, Japan.
[Yamaguchi, Terry P.] NCI, Canc & Dev Biol Lab, NIH, Frederick, MD 21701 USA.
RP Yokoyama, T (reprint author), Kyoto Prefectural Univ Med, Dept Anat & Dev Biol, Grad Sch Med Sci, Kamigyo Ku, Kyoto 6028566, Japan.
EM tyoko@koto.kpu-m.ac.jp
RI Tsukiyama, Tadasuke/D-7589-2012
FU Ministry of Education, Science, Sports, and Culture [19790587, 21790818]
FX We thank Kunitada Shimotohno for the pTcf7wt-BP-Luc and pTcf7mut-BP-Luc
reporter plasmids, and Shinji Takada for Wnt-3a- and Wnt-5a-producing L
cells and pGKWnt-3a and pGKWnt-5a plasmids. This work was supported by
Grants-in-Aid for Young Scientists from the Ministry of Education,
Science, Sports, and Culture (19790587 and 21790818) to NS.
NR 29
TC 23
Z9 23
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD MAY
PY 2011
VL 79
IS 9
BP 957
EP 965
DI 10.1038/ki.2010.534
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 750AD
UT WOS:000289514400005
PM 21248711
ER
PT J
AU Rudra, CB
Wactawski-Wende, J
Hovey, KM
Browne, RW
Zhang, CL
Hediger, ML
Schisterman, EF
AF Rudra, Carole B.
Wactawski-Wende, Jean
Hovey, Kathleen M.
Browne, Richard W.
Zhang, Cuilin
Hediger, Mary L.
Schisterman, Enrique F.
TI Energy Expenditure and Plasma F-2-Isoprostanes across the Menstrual
Cycle
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
DE PHYSICAL ACTIVITY; MENSES; EXERCISE; OXIDATIVE STRESS; PREMENOPAUSAL;
WOMEN
ID PHYSICAL-ACTIVITY QUESTIONNAIRE; TYPE-2 DIABETES-MELLITUS; INDUCED
OXIDATIVE STRESS; LIPID-PEROXIDATION; ACTIVITY PROGRAM; WEIGHT-LOSS;
EXERCISE; ESTROGENS; ADULTS; LIPOPROTEINS
AB RUDRA, C. B., J. WACTAWSKI-WENDE, K. M. HOVEY, R. W. BROWNE, C. ZHANG, M. L. HEDIGER, and E. F. SCHISTERMAN. Energy Expenditure and Plasma F-2-Isoprostanes across the Menstrual Cycle. Med. Sci. Sports Exerc., Vol. 43, No. 5, pp. 785-792, 2011. Introduction: Habitual energy expenditure seems to favorably alter oxidant/antioxidant balance. Sparse evidence suggests that hormones that fluctuate during the menstrual cycle, particularly estrogens, may influence concentrations of oxidative biomarkers and their relation to energy expenditure. Methods: We investigated the relation between energy expenditure and plasma free F-2-isoprostane concentrations in 259 healthy, regularly menstruating 18- to 44-yr-old participants of the BioCycle Study. Habitual energy expenditure was measured using a baseline International Physical Activity Questionnaire and categorized as low, moderate, or high. Women were followed for one or two subsequent menstrual cycles. Past-week and past-day physical activity were measured during follow-up using questionnaires and diaries, respectively. F-2-isoprostane concentrations were measured in blood samples collected at both menses (approximate cycle day 2; low serum estradiol concentration) and the late follicular phase (approximate cycle day 12; peak estradiol concentration). Generalized estimating equations were used to model the energy expenditure/isoprostane association, adjusting for confounders. Results: Habitual energy expenditure was positively associated with F-2-isoprostane concentration (adjusted difference in median F-2-isoprostane, high versus low energy expenditure: 17.4%; 95% confidence interval (CI) = 3.3%-31.4%). This association was not modified by cycle phase (interaction, P = 0.61) or differences in peak estradiol concentration across women (interaction, P = 0.20). Past-week and past-day physical activity measures were not associated with F-2-isoprostane concentration (category trend, P = 0.50 and P = 0.18, respectively). Conclusions: These results suggest that higher habitual energy expenditure may be associated with higher concentration of F-2-isoprostanes in healthy, reproductive-aged women. Estradiol concentration changes during the menstrual cycle do not seem to influence this relationship.
C1 [Rudra, Carole B.; Wactawski-Wende, Jean; Hovey, Kathleen M.] SUNY Buffalo, Dept Social & Prevent Med, Sch Publ Hlth & Hlth Profess, Buffalo, NY 14214 USA.
[Rudra, Carole B.; Wactawski-Wende, Jean] SUNY Buffalo, Dept Obstet Gynecol, Sch Med & Biomed Sci, Buffalo, NY 14214 USA.
[Browne, Richard W.] SUNY Buffalo, Dept Clin Lab Sci, Sch Med & Biomed Sci, Buffalo, NY 14214 USA.
[Zhang, Cuilin; Hediger, Mary L.; Schisterman, Enrique F.] NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA.
RP Rudra, CB (reprint author), SUNY Buffalo, Dept Social & Prevent Med, Sch Publ Hlth & Hlth Profess, 270 Farber Hall, Buffalo, NY 14214 USA.
EM cbrudra@buffalo.edu
OI Schisterman, Enrique/0000-0003-3757-641X
FU National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development [HHSN275200403394C]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development contract No. HHSN275200403394C.
NR 35
TC 2
Z9 2
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2011
VL 43
IS 5
BP 785
EP 792
DI 10.1249/MSS.0b013e3181fc5eab
PG 8
WC Sport Sciences
SC Sport Sciences
GA 750OF
UT WOS:000289557100007
PM 20881883
ER
PT J
AU Atienza, AA
Moser, RP
Perna, F
Dodd, K
Ballard-Barbash, R
Troiano, RP
Berrigan, D
AF Atienza, Audie A.
Moser, Richard P.
Perna, Frank
Dodd, Kevin
Ballard-Barbash, Rachel
Troiano, Richard P.
Berrigan, David
TI Self-Reported and Objectively Measured Activity Related to Biomarkers
Using NHANES
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
DE PHYSICAL ACTIVITY; ACCELEROMETRY; MEASUREMENT; NATIONAL SURVEY
ID PHYSICAL-ACTIVITY; BODY-COMPOSITION; RISK-FACTORS; MUSCULAR STRENGTH;
HEALTH; MORTALITY; FITNESS; ACCELEROMETER; PREDICTORS; ADIPOSITY
AB ATIENZA, A. A., R. P. MOSER, F. PERNA, K. DODD, R. BALLARD-BARBASH, R. P. TROIANO, and D. BERRIGAN. Self-Reported and Objectively Measured Activity Related to Biomarkers Using NHANES. Med. Sci. Sports Exerc., Vol. 43, No. 5, pp. 815-821, 2011. Purpose: The purpose of this study was to examine the independent associations of self-reported and objectively measured (using accelerometers) moderate to vigorous physical activity (MVPA) with physiological and anthropometric biomarkers in a nationally representative sample of U.S. adults. Methods: Data from the cross-sectional National Health and Nutrition Examination Survey 2003-2006 data were analyzed. Adults 20 yr and older (N = 5797) with self-reported PA and 4 d or more of accelerometer data were included in the analyses. Pregnant or lactating women were excluded. Outcomes were blood pressure, body mass index, waist circumference, triceps and subscapular skinfolds, cholesterol, triglyceride, C-reactive protein, homocysteine, and insulin resistance and hyperinsulinemia indices. Results: Objectively measured MVPA displayed stronger independent associations with the biomarkers than did self-reported MVPA, even after adjusting for sociodemographic and health factors (adjusted Wald F values = 3.9-85.6, P < 0.05-0.0001). Self-reported and objectively measured MVPA were independently associated with skinfold measures, HDL, and C-reactive protein when both were included in the model. Conclusions: Objectively measured MVPA displayed stronger associations with physiological and anthropometric biomarkers than self-reported MVPA. However, self-reported and objectively measured MVPA appear to capture distinct aspects of PA that are independently associated with certain biomarkers. Further understanding of the distinct contributions of self-reported and objectively measured PA to health outcomes could help to better identify optimal activity level and pattern.
C1 [Atienza, Audie A.] NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Dodd, Kevin] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Atienza, AA (reprint author), NCI, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4082, Bethesda, MD 20892 USA.
EM atienzaa@mail.nih.gov
OI Troiano, Richard/0000-0002-6807-989X
FU U.S. National Cancer Institute
FX This study was not supported by external funding. The U.S. National
Cancer Institute provided funds for the data collection.
NR 33
TC 65
Z9 65
U1 6
U2 25
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2011
VL 43
IS 5
BP 815
EP 821
DI 10.1249/MSS.0b013e3181fdfc32
PG 7
WC Sport Sciences
SC Sport Sciences
GA 750OF
UT WOS:000289557100011
PM 20962693
ER
PT J
AU Clark, BK
Healy, GN
Winkler, EAH
Gardiner, PA
Sugiyama, T
Dunstan, DW
Matthews, CE
Owen, N
AF Clark, Bronwyn K.
Healy, Genevieve N.
Winkler, Elisabeth A. H.
Gardiner, Paul A.
Sugiyama, Takemi
Dunstan, David W.
Matthews, Charles E.
Owen, Neville
TI Relationship of Television Time with Accelerometer-Derived Sedentary
Time: NHANES
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
DE SEDENTARY BEHAVIOR; MEASUREMENT; GENDER; AGE; RACE/ETHNICITY; WORK
STATUS
ID PHYSICAL-ACTIVITY QUESTIONNAIRE; TYPE-2 DIABETES-MELLITUS; TEST-RETEST
RELIABILITY; VIEWING TIME; METABOLIC SYNDROME; AUSTRALIAN ADULTS;
UNITED-STATES; LIFE-STYLE; RISK; BEHAVIOR
AB CLARK, B. K., G. N. HEALY, E. A. H. WINKLER, P. A. GARDINER, T. SUGIYAMA, D. W. DUNSTAN, C. E. MATTHEWS, and N. OWEN. Relationship of Television Time with Accelerometer-Derived Sedentary Time: NHANES. Med. Sci. Sports Exerc., Vol. 43, No. 5, pp. 822-828, 2011. Purpose: To examine the relationship of self-reported television (TV) viewing time with accelerometer-derived total sedentary time and to determine whether it differs by subgroup. Methods: Using data for adults (>= 20 yr) from the 2003-2004 and 2005-2006 nationally representative US National Health and Nutrition Examination Surveys (NHANES; n = 5738), linear regression models examined the associations of categories of self-reported TV viewing time (< 1, 1, 2, 3, 4, and 95 h.d(-1)) with accelerometer-derived sedentary time (< 100 counts per minute; h.d(-1)). Spearman rho assessed the correlation between participants' rankings on the two measures. Analyses were stratified by gender, age, race/ethnicity, and, in the 2003-2004 NHANES cycle, by work status among working-aged adults (20-65 yr, n = 2069). Results: TV viewing time was significantly associated with sedentary time, with positive associations for all gender, age, race/ethnicity groups, and for those not working or working part-time, but not for those in full-time work. However, correlations between rankings of the measures were only "fair" overall (rho = 0.22) and were similar for all gender and racial/ethnic groups and for those of mid- and older age but not for those of younger age (20-39 yr, rho = 0.05). In the working-aged subgroup, there was also a fair correlation between the measures for those not working (rho = 0.22) but no significant correlation for those in part-time (rho = 0.14) or full-time work (rho = 0.03). Conclusions: Associations of TV viewing time with accelerometer-derived total sedentary time were statistically significant, but correlations were of only fair magnitude, and the strength of the relationship was not consistent across all population subgroups. These findings suggest that TV viewing time has an influence on overall sedentary time at a population level; however, measurement of sedentary time in other domains is also important.
C1 [Clark, Bronwyn K.; Healy, Genevieve N.; Winkler, Elisabeth A. H.; Gardiner, Paul A.; Sugiyama, Takemi; Dunstan, David W.; Owen, Neville] Univ Queensland, Sch Populat Hlth, Canc Prevent Res Ctr, Brisbane, Qld, Australia.
[Healy, Genevieve N.; Dunstan, David W.; Owen, Neville] Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia.
[Dunstan, David W.] Deakin Univ, Sch Exercise & Nutr Sci, Melbourne, Vic, Australia.
[Dunstan, David W.] Edith Cowan Univ, Vario Hlth Inst, Perth, WA, Australia.
[Dunstan, David W.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia.
[Matthews, Charles E.] NCI, Bethesda, MD 20892 USA.
RP Clark, BK (reprint author), Univ Queensland, Sch Populat Hlth, Canc Prevent Res Ctr, Herston Rd, Herston, Qld 4006, Australia.
EM b.clark3@uq.edu.au
RI Gardiner, Paul/F-2751-2010; Healy, Genevieve/A-7408-2008; Clark,
Bronwyn/F-8028-2010; Owen, Neville/K-5986-2012; matthews,
Charles/E-8073-2015; Dunstan, David/E-8473-2010;
OI Owen, Neville/0000-0003-2784-4820; Gardiner, Paul/0000-0002-8072-2673;
Healy, Genevieve/0000-0001-7093-7892; Clark,
Bronwyn/0000-0001-7527-4311; matthews, Charles/0000-0001-8037-3103;
Dunstan, David/0000-0003-2629-9568; Sugiyama, Takemi/0000-0002-8859-5269
FU Queensland Health; National Health and Medical Research Council of
Australia; Australian Post Graduate Award; NHMRC [569861, 301200];
National Heart Foundation of Australia [PH 08B 3905, PP 06B 2889];
Victorian Health Promotion Foundation
FX This study was supported by funding from Queensland Health and the
National Health and Medical Research Council of Australia (#301200).;
Clark is supported by an Australian Post Graduate Award Scholarship and
Queensland Health funding. Healy is supported by a NHMRC (#569861) /
National Heart Foundation of Australia (PH 08B 3905) Postdoctoral
Fellowship. Dunstan is supported by a Victorian Health Promotion
Foundation Public Health Research Fellowship. Winkler, Sugiyama, and
Owen are supported by a Queensland Health Core Research Infrastructure
grant and by NHMRC Program Grant funding (#301200). Gardiner is
supported by a National Heart Foundation of Australia (#PP 06B 2889)
Postgraduate Scholarship. The authors have no conflict of interest to
declare.
NR 43
TC 51
Z9 51
U1 2
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2011
VL 43
IS 5
BP 822
EP 828
DI 10.1249/MSS.0b013e3182019510
PG 7
WC Sport Sciences
SC Sport Sciences
GA 750OF
UT WOS:000289557100012
PM 20980928
ER
PT J
AU Colbert, LH
Matthews, CE
Havighurst, TC
Kim, K
Schoeller, DA
AF Colbert, Lisa H.
Matthews, Charles E.
Havighurst, Thomas C.
Kim, Kyungmann
Schoeller, Dale A.
TI Comparative Validity of Physical Activity Measures in Older Adults
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
DE ACCELEROMETER; PEDOMETER; QUESTIONNAIRE; DOUBLY LABELED WATER
ID DOUBLY LABELED WATER; TOTAL-ENERGY-EXPENDITURE; ACTIVITY SCALE; ELDERLY
PASE; ACTIVITY QUESTIONNAIRES; UNITED-STATES; VALIDATION; ACCELEROMETER;
HUMANS; COST
AB COLBERT, L. H., C. E. MATTHEWS, T. C. HAVIGHURST, K. KIM, and D. A. SCHOELLER. Comparative Validity of Physical Activity Measures in Older Adults. Med. Sci. Sports Exerc., Vol. 43, No. 5, pp. 867-876, 2011. Purpose: To compare the validity of various physical activity measures with doubly labeled water (DLW)-measured physical activity energy expenditure (PAEE) in free-living older adults. Methods: Fifty-six adults aged >= 65 yr wore three activity monitors (New Lifestyles pedometer, ActiGraph accelerometer, and a SenseWear (SW) armband) during a 10-d free-living period and completed three different surveys (Yale Physical Activity Survey (YPAS), Community Health Activities Model Program for Seniors (CHAMPS), and a modified Physical Activity Scale for the Elderly (modPASE)). Total energy expenditure was measured using DLW, resting metabolic rate was measured with indirect calorimetry, the thermic effect of food was estimated, and from these, estimates of PAEE were calculated. The degree of linear association between the various measures and PAEE was assessed, as were differences in group PAEE, when estimable by a given measure. Results: All three monitors were significantly correlated with PAEE (r = 0.48-0.60, P < 0.001). Of the questionnaires, only CHAMPS was significantly correlated with PAEE (r = 0.28, P = 0.04). Statistical comparison of the correlations suggested that the monitors were superior to YPAS and modPASE. Mean squared errors for all correlations were high, and the median PAEE from the different tools was significantly different from DLW for all but the YPAS and regression-estimated PAEE from the ActiGraph. Conclusions: Objective devices more appropriately rank PAEE than self-reported instruments in older adults, but absolute estimates of PAEE are not accurate. Given the cost differential and ease of use, pedometers seem most useful in this population when ranking by physical activity level is adequate.
C1 [Colbert, Lisa H.] Univ Wisconsin, Dept Kinesiol, Madison, WI 53706 USA.
[Colbert, Lisa H.; Havighurst, Thomas C.; Kim, Kyungmann] Univ Wisconsin, Carbone Comprehens Canc Ctr, Madison, WI 53706 USA.
[Havighurst, Thomas C.; Kim, Kyungmann] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53706 USA.
[Schoeller, Dale A.] Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA.
[Matthews, Charles E.] NCI, Nutr Epidemiol Branch, NIH, Bethesda, MD 20892 USA.
RP Colbert, LH (reprint author), Univ Wisconsin, Dept Kinesiol, 2000 Observ Dr, Madison, WI 53706 USA.
EM lhcolbert@education.wisc.edu
RI matthews, Charles/E-8073-2015
OI matthews, Charles/0000-0001-8037-3103
FU National Institutes of Health [R21AG025839]; National Cancer Institute,
National Institutes of Health [P30 CA14520]; National Center for
Research Resources, National Institutes of Health [1UL1RR025011];
Graduate School, University of Wisconsin-Madison
FX This study was supported by R21AG025839 from the National Institutes of
Health; P30 CA14520 from the National Cancer Institute, National
Institutes of Health; 1UL1RR025011 from the Clinical and Translational
Science Award program of the National Center for Research Resources,
National Institutes of Health; and from the Graduate School, University
of Wisconsin-Madison.
NR 40
TC 70
Z9 73
U1 1
U2 30
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2011
VL 43
IS 5
BP 867
EP 876
DI 10.1249/MSS.0b013e3181fc7162
PG 10
WC Sport Sciences
SC Sport Sciences
GA 750OF
UT WOS:000289557100018
PM 20881882
ER
PT J
AU Van Domelen, DR
Koster, A
Harris, TB
AF Van Domelen, Dane R.
Koster, Annemarie
Harris, Tamara B.
TI ACCELEROMETER NONWEAR ALGORITHMS: OPTIMIZING PARAMETERS FOR BOTH WEAR
STATES
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Letter
C1 [Van Domelen, Dane R.; Koster, Annemarie; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Koster, Annemarie] Maastricht Univ, Dept Internal Med, Sch Publ Hlth & Primary Care, Med Ctr, Maastricht, Netherlands.
RP Van Domelen, DR (reprint author), NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RI Koster, Annemarie/E-7438-2010;
OI Van Domelen, Dane/0000-0003-0051-7790
NR 2
TC 4
Z9 4
U1 2
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2011
VL 43
IS 5
BP 932
EP 932
DI 10.1249/MSS.0b013e318212b002
PG 1
WC Sport Sciences
SC Sport Sciences
GA 750OF
UT WOS:000289557100028
PM 21499057
ER
PT J
AU Choi, L
Liu, ZW
Matthews, CE
Buchowski, MS
AF Choi, Leena
Liu, Zhouwen
Matthews, Charles E.
Buchowski, Maciej S.
TI ACCELEROMETER NONWEAR ALGORITHMS: OPTIMIZING PARAMETERS FOR BOTH WEAR
STATES RESPONSE
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Letter
ID UNITED-STATES
C1 [Choi, Leena; Liu, Zhouwen] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA.
[Matthews, Charles E.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Buchowski, Maciej S.] Vanderbilt Univ, Med Ctr, Dept Med, Energy Balance Lab, Nashville, TN USA.
RP Choi, L (reprint author), Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA.
RI Buchowski, Maciej/A-2683-2008; matthews, Charles/E-8073-2015
OI Buchowski, Maciej/0000-0002-0566-1743; matthews,
Charles/0000-0001-8037-3103
NR 5
TC 0
Z9 0
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD MAY
PY 2011
VL 43
IS 5
BP 933
EP 933
DI 10.1249/MSS.0b013e318212b017
PG 1
WC Sport Sciences
SC Sport Sciences
GA 750OF
UT WOS:000289557100029
ER
PT J
AU Cooper, AM
Mayer-Barber, KD
Sher, A
AF Cooper, A. M.
Mayer-Barber, K. D.
Sher, A.
TI Role of innate cytokines in mycobacterial infection
SO MUCOSAL IMMUNOLOGY
LA English
DT Review
ID TUMOR-NECROSIS-FACTOR; BACILLUS-CALMETTE-GUERIN; TUBERCULOSIS INFECTION;
IMMUNE-RESPONSE; HOST-DEFENSE; IFN-GAMMA; PULMONARY TUBERCULOSIS;
LYMPHOTOXIN-ALPHA; T-CELLS; LISTERIA-MONOCYTOGENES
AB Cells of the innate immune system produce cytokines and lipid mediators that strongly influence the outcome of mycobacterial infection. In the case of Mycobacterium tuberculosis, the lung is a critical site for this interaction. Here, we review current information on the role of the major innate cytokine pathways both in controlling initial infection as well as in promoting and maintaining adaptive T-cell responses that mediate host resistance or immunopathology. Understanding this important feature of the host-pathogen interaction can provide major insights into the mechanisms of virulence and can lead to new approaches for immunological intervention in tuberculosis and other mycobacterial diseases.
C1 [Cooper, A. M.] Trudeau Inst Inc, Saranac Lake, NY 12983 USA.
[Mayer-Barber, K. D.; Sher, A.] NIAID, Parasit Dis Lab, Immunobiol Sect, NIH, Bethesda, MD 20892 USA.
RP Cooper, AM (reprint author), Trudeau Inst Inc, POB 59, Saranac Lake, NY 12983 USA.
EM acooper@trudeauinstitute.org; asher@niaid.nih.gov
OI Cooper, Andrea/0000-0001-6050-3863
FU NIAID; Trudeau Institute NIH [AI67723, AI69121, AI46530]; American Lung
Association
FX We thank Dan Barber, Carl Feng, Bruno Andrade, Alena Srinivasan, David
Kugler, Bernadette Saunders, and Alexei Tumanov for helpful discussion.
AS and KMB are supported by the intramural research program of the
NIAID. AMC is supported by the Trudeau Institute NIH grants AI67723,
AI69121, and AI46530 and an American Lung Association De Souza award.
NR 102
TC 98
Z9 101
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD MAY
PY 2011
VL 4
IS 3
BP 252
EP 260
DI 10.1038/mi.2011.13
PG 9
WC Immunology
SC Immunology
GA 751KQ
UT WOS:000289616800002
PM 21430655
ER
PT J
AU Chen, A
Weimer, L
Brannagan, T
Andrews, J
Mitsumoto, H
Kaufmann, P
AF Chen, Amy
Weimer, Louis
Brannagan, Thomas, III
Andrews, Jinsy
Mitsumoto, Hiroshi
Kaufmann, Petra
TI AWAJI ISLAND MODIFIED CRITERIA FOR ALS-INCREASED SENSITIVITY WITHOUT
CHANGE IN SPECIFICITY: ARE THEY REALLY TWO SIDES OF THE SAME COIN? REPLY
SO MUSCLE & NERVE
LA English
DT Letter
ID AMYOTROPHIC-LATERAL-SCLEROSIS
C1 [Chen, Amy] Univ Rochester, Dept Neurol, Rochester, NY 14627 USA.
[Weimer, Louis; Brannagan, Thomas, III; Mitsumoto, Hiroshi; Kaufmann, Petra] Columbia Univ, Dept Neurol, New York, NY USA.
[Andrews, Jinsy] Univ Connecticut, Hosp Special Care, New Britain, CT USA.
[Kaufmann, Petra] NINDS, NIH, Bethesda, MD 20892 USA.
RP Chen, A (reprint author), Univ Rochester, Dept Neurol, Rochester, NY 14627 USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0148-639X
EI 1097-4598
J9 MUSCLE NERVE
JI Muscle Nerve
PD MAY
PY 2011
VL 43
IS 5
BP 769
EP 769
DI 10.1002/mus.22026
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 748VI
UT WOS:000289420500027
ER
PT J
AU Xiong, W
Cheng, KJ
Cui, TX
Godlewski, G
Rice, KC
Xu, Y
Zhang, L
AF Xiong, Wei
Cheng, KeJun
Cui, Tanxing
Godlewski, Grzegorz
Rice, Kenner C.
Xu, Yan
Zhang, Li
TI Cannabinoid potentiation of glycine receptors contributes to
cannabis-induced analgesia
SO NATURE CHEMICAL BIOLOGY
LA English
DT Article
ID PAIN SENSITIZATION; KNOCKOUT MICE; MODULATION; SUBUNIT; CHANNEL;
HYPEREKPLEXIA; DYNAMICS; MODEL; ENDOCANNABINOIDS; INHIBITION
AB Cannabinoids enhance the function of glycine receptors (GlyRs). However, little is known about the mechanisms and behavioral implication of cannabinoid-GlyR interaction. Using mutagenesis and NMR analysis, we have identified a serine at 296 in the GlyR protein critical for the potentiation of I(Gly) by Delta(9)-tetrahydrocannabinol (THC), a major psychoactive component of marijuana. The polarity of the amino acid residue at 296 and the hydroxyl groups of THC are critical for THC potentiation. Removal of the hydroxyl groups of THC results in a compound that does not affect I(Gly) when applied alone but selectively antagonizes cannabinoid-induced potentiating effect on I(Gly) and analgesic effect in a tail-flick test in mice. The cannabinoid-induced analgesia is absent in mice lacking alpha 3GlyRs but not in those lacking CB1 and CB2 receptors. These findings reveal a new mechanism underlying cannabinoid potentiation of GlyRs, which could contribute to some of the cannabis-induced analgesic and therapeutic effects.
C1 [Xiong, Wei; Zhang, Li] US Natl Inst Alcohol Abuse & Alcoholism, Lab Integrat Neurosci, US Natl Inst Hlth, Bethesda, MD USA.
[Cheng, KeJun; Rice, Kenner C.] US Natl Inst Drug Abuse, Chem Biol Res Branch, US Natl Inst Hlth, Bethesda, MD USA.
[Cui, Tanxing; Xu, Yan] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15261 USA.
[Cui, Tanxing; Xu, Yan] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15261 USA.
[Cui, Tanxing; Xu, Yan] Univ Pittsburgh, Sch Med, Dept Biol Struct, Pittsburgh, PA 15261 USA.
[Godlewski, Grzegorz] US Natl Inst Alcohol Abuse & Alcoholism, Lab Physiol Studies, US Natl Inst Hlth, Bethesda, MD USA.
RP Zhang, L (reprint author), US Natl Inst Alcohol Abuse & Alcoholism, Lab Integrat Neurosci, US Natl Inst Hlth, Bethesda, MD USA.
EM lzhang@mail.nih.gov
RI Xiong, Wei/F-8251-2011;
OI Xu, Yan/0000-0003-2773-8024
FU US National Institute on Alcohol Abuse and Alcoholism; US National
Institute of General Medical Sciences of the US National Institutes of
Health [R37GM049202]
FX We thank C. L. Cepko for providing alpha 2-/- Glra mice. We
especially thank D. M. Lovinger for critical comments on the manuscript.
This work was supported by funds from the intramural program of the US
National Institute on Alcohol Abuse and Alcoholism. We acknowledge the
grant support (R37GM049202 to Y.X.) from the US National Institute of
General Medical Sciences of the US National Institutes of Health.
NR 44
TC 40
Z9 42
U1 5
U2 18
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1552-4450
J9 NAT CHEM BIOL
JI Nat. Chem. Biol.
PD MAY
PY 2011
VL 7
IS 5
BP 296
EP 303
DI 10.1038/nchembio.552
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 751KZ
UT WOS:000289617800013
PM 21460829
ER
PT J
AU Ghuman, AS
McDaniel, JR
Martin, A
AF Ghuman, Avniel Singh
McDaniel, Jonathan R.
Martin, Alex
TI A wavelet-based method for measuring the oscillatory dynamics of
resting-state functional connectivity in MEG
SO NEUROIMAGE
LA English
DT Article
DE Resting-state; Magnetoencephalography; Functional connectivity;
Phase-locking; Neural oscillations; Oscillatory dynamics
ID HUMAN AUDITORY-CORTEX; HUMAN BRAIN; COMPONENT ANALYSIS; 10-HZ RHYTHM;
FLUCTUATIONS; SYNCHRONY; HUMANS; MEMORY; ALPHA; EEG
AB Determining the dynamics of functional connectivity is critical for understanding the brain. Recent functional magnetic resonance imaging (fMRI) studies demonstrate that measuring correlations between brain regions in resting-state activity can be used to reveal intrinsic neural networks. To study the oscillatory dynamics that underlie intrinsic functional connectivity between regions requires high temporal resolution measures of electrophysiological brain activity, such as magnetoencephalography (MEG). However, there is a lack of consensus as to the best method for examining connectivity in resting-state MEG data. Here we adapted a wavelet-based method for measuring phase-locking with respect to Me frequency of neural oscillations. This method employs anatomical MRI information combined with MEG data using the minimum norm estimate inverse solution to produce functional connectivity maps from a "seed" region to all other locations on the cortical surface at any and all frequencies of interest. We test this method by simulating phase-locked oscillations at various points on the cortical surface, which illustrates a substantial artifact that results from imperfections in the inverse solution. We demonstrate that normalizing resting-state MEG data using phase-locking values computed on empty room data reduces much of the effects of this artifact. We then use this method with eight subjects to reveal intrinsic interhemispheric connectivity in the auditory network in the alpha frequency band in a silent environment. This spectral resting-state functional connectivity imaging method may allow us to better understand the oscillatory dynamics underlying intrinsic functional connectivity in the human brain. Published by Elsevier Inc.
C1 [Ghuman, Avniel Singh; McDaniel, Jonathan R.; Martin, Alex] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA.
RP Ghuman, AS (reprint author), NIMH, Lab Brain & Cognit, 10 Ctr Dr,Room 4C116,MSC 1366, Bethesda, MD 20892 USA.
EM ghumana@mail.nih.gov
RI martin, alex/B-6176-2009;
OI Ghuman, Avniel/0000-0003-1746-4656
FU NIMH-DIRP
FX We thank Rebecca van den Honert for assistance with data collection and
analysis, Steve Gotts, Richard Coppola, and for insightful comments, Tom
Holroyd and the staff NIMH MEG core for assistance with data collection,
Gang Chen for assistance with statistics, Zhongming Liu for assistance
with the cardiac artifact removal procedure, and Ziad Saad for
assistance with MRI processing. This work was supported by NIMH-DIRP.
NR 41
TC 23
Z9 23
U1 0
U2 10
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD MAY 1
PY 2011
VL 56
IS 1
BP 69
EP 77
DI 10.1016/j.neuroimage.2011.01.046
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 749HK
UT WOS:000289454900009
PM 21256967
ER
PT J
AU Liu, HS
Shen, H
Harvey, BK
Castillo, P
Lu, HB
Yang, YH
Wang, Y
AF Liu, Hua-Shan
Shen, Hui
Harvey, Brandon K.
Castillo, Priscila
Lu, Hanbing
Yang, Yihong
Wang, Yun
TI Post-treatment with amphetamine enhances reinnervation of the
ipsilateral side cortex in stroke rats
SO NEUROIMAGE
LA English
DT Article
ID MIDDLE CEREBRAL-ARTERY; BONE MORPHOGENETIC PROTEIN-7; ISCHEMIC
BRAIN-INJURY; NEUROTROPHIC FACTOR; MATRIX-METALLOPROTEINASE; AXONAL
PLASTICITY; DENDRITIC GROWTH; EMBOLIC STROKE; MOTOR RECOVERY;
MESSENGER-RNA
AB Amphetamine (AM) treatment has been shown to alter behavioral recovery after ischemia caused by embolism, permanent unilateral occlusion of the common carotid and middle cerebral arteries, or unilateral sensorimotor cortex ablation in rats. However, the behavioral results are inconsistent possibly due to difficulty controlling the size of the lesion before treatment. There is also evidence that AM promotes neuroregeneration in the cortex contralateral to the infarction; however, the effects of AM in the ipsilateral cortex remain unclear. The purpose of this study was to employ T2-weighted imaging (T2WI) to establish controlled criteria for AM treatment and to examine neuroregenerative effects in both cortices after stroke. Adult rats were anesthetized, and the right middle cerebral artery was ligated for 90 min to generate lesions in the ipsilateral cortex. Animals were separated into two equal treatment groups (AM or saline) according to the size of infarction, measured by T2WI at 2 days after stroke. AM or saline was administered to stroke rats every third day starting on day 3 for 4 weeks. AM treatment significantly reduced neurological deficits, as measured by body asymmetry and Bederson's score. T2WI and diffusion tensor imaging (DTI) were used to examine the size of infarction and axonal reinnervation, respectively, before and following treatment on days 2, 10 and 25 after stroke. AM treatment reduced the volume of tissue loss on days 10 and 25. A significant increase in fractional anisotropy ratio was found in the ipsilateral cortex after repeated AM administration, suggesting a possible increase in axonal outgrowth in the lesioned side cortex. Western analysis indicated that AM significantly increased the expression of synaptophysin ipsilaterally and neurofilament bilaterally. AM also enhanced matrix metalloproteinase (MMP) enzymatic activity, determined by MMP zymography in the lesioned side cortex. qRT-PCR was used to examine the expression of trophic factors after the 1st and 2nd doses of AM or saline injection. The expression of BDNF, but not BMP7 or CART, was significantly enhanced by AM in the lesioned side cortex. In conclusion, post-stroke treatment with AM facilitates behavioral recovery, which is associated with an increase in fractional anisotropy activity, enhanced fiber growth in tractography, synaptogenesis, upregulation of BDNF, and MMP activity mainly in the lesioned cortex. Our data suggest that the ipsilateral cortex may be the major target of action in stroke brain after AM treatment. Published by Elsevier Inc.
C1 [Wang, Yun] Natl Inst Drug Abuse, Neural Protect & Regenerat Sect, Intramural Res Program, Baltimore, MD 21224 USA.
[Liu, Hua-Shan; Lu, Hanbing; Yang, Yihong] Natl Inst Drug Abuse, Magnet Resonance Imaging & Spect Sect, Baltimore, MD 21224 USA.
RP Wang, Y (reprint author), Natl Inst Drug Abuse, Neural Protect & Regenerat Sect, Intramural Res Program, Baltimore, MD 21224 USA.
EM ywang@intra.nida.nih.gov
FU National Institute on Drug Abuse
FX This study was supported by National Institute on Drug Abuse, Intramural
Research Program.
NR 54
TC 19
Z9 21
U1 3
U2 11
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD MAY 1
PY 2011
VL 56
IS 1
BP 280
EP 289
DI 10.1016/j.neuroimage.2011.02.049
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 749HK
UT WOS:000289454900028
PM 21349337
ER
PT J
AU Copeland, WE
Sun, H
Costello, EJ
Angold, A
Heilig, MA
Barr, CS
AF Copeland, William E.
Sun, Hui
Costello, E. Jane
Angold, Adrian
Heilig, Markus A.
Barr, Christina S.
TI Child mu-Opioid Receptor Gene Variant Influences Parent-Child Relations
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE genetics; OPRM1; parent-child relations; separation anxiety; childhood
ID SINGLE-NUCLEOTIDE POLYMORPHISM; PSYCHIATRIC-ASSESSMENT CAPA; SEPARATION
DISTRESS; ATTACHMENT BEHAVIOR; A118G POLYMORPHISM; INFANT PRIMATES;
ASSOCIATION; SENSITIVITY; BINDING; OPRM1
AB Variation in the mu-opioid receptor gene has been associated with early social behavior in mice and rhesus macaques. The current study tested whether the functional OPRM1 A118G predicted various indices of social relations in children. The sample included 226 subjects of self-reported European ancestry (44% female; mean age 13.6, SD = 2.2) who were part of a larger representative study of children aged 9-17 years in rural North Carolina. Multiple aspects of recent (past 3 months) parent-child relationship were assessed using the Child and Adolescent Psychiatric Assessment. Parent problems were coded based upon a lifetime history of mental health problems, substance abuse, or criminality. Child genotype interacted with parent behavior such that there were no genotype differences for those with low levels of parent problems; however, when a history of parent problems was reported, the G allele carriers had more enjoyment of parent-child interactions (mean ratio (MR) = 3.5, 95% CI = 1.6, 8.0) and fewer arguments (MR = 3.1, 95% CI = 1.1, 8.9). These findings suggest a role for the OPRM1 gene in the genetic architecture of social relations in humans. In summary, a variant in the mu-opioid receptor gene (118G) was associated with improved parent-child relations, but only in the context of a significant disruption in parental functioning. Neuropsychopharmacology (2011) 36, 1165-1170; doi: 10.1038/npp.2010.251; published online 16 February 2011
C1 [Copeland, William E.; Costello, E. Jane; Angold, Adrian] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Dev Epidemiol Program, Durham, NC 27710 USA.
[Sun, Hui; Heilig, Markus A.; Barr, Christina S.] NIAAA, Sect Comparat Behav Genom, NIH, LNG, Bethesda, MD USA.
RP Copeland, WE (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Dev Epidemiol Program, Box 3454, Durham, NC 27710 USA.
EM william.copeland@duke.edu
RI copeland, william/N-5413-2014;
OI Heilig, Markus/0000-0003-2706-2482
FU National Institute on Alcohol Abuse and Alcoholism Intramural Research
Program; National Institute of Drug Abuse [DA024413]; National Institute
for Mental Health [MH080230]
FX The work was supported by the National Institute on Alcohol Abuse and
Alcoholism Intramural Research Program, the National Institute of Drug
Abuse (DA024413 to EJC), and the National Institute for Mental Health
(MH080230 to WEC).
NR 37
TC 18
Z9 18
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD MAY
PY 2011
VL 36
IS 6
BP 1165
EP 1170
DI 10.1038/npp.2010.251
PG 6
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 749ZJ
UT WOS:000289511800004
PM 21326192
ER
PT J
AU Umhau, JC
Schwandt, ML
Usala, J
Geyer, C
Singley, E
George, DT
Heilig, M
AF Umhau, John C.
Schwandt, Melanie L.
Usala, Julie
Geyer, Christopher
Singley, Erick
George, David T.
Heilig, Markus
TI Pharmacologically induced alcohol craving in treatment seeking
alcoholics correlates with alcoholism severity, but is insensitive to
acamprosate
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE alcoholism; craving; yohimbine; meta-chlorophenylpiperazine; acamprosate
ID CORTICOTROPIN-RELEASING-FACTOR; COMPULSIVE DRINKING SCALE; DEPENDENT
PATIENTS; CUE REACTIVITY; PREVENTING RELAPSE; CONTROLLED-TRIAL;
DOUBLE-BLIND; STRESS; MECHANISMS; RATS
AB Modulation of alcohol craving induced by challenge stimuli may predict the efficacy of new pharmacotherapies for alcoholism. We evaluated two pharmacological challenges, the alpha(2)-adrenergic antagonist yohimbine, which reinstates alcohol seeking in rats, and the serotonergic compound meta-chlorophenylpiperazine (mCPP), previously reported to increase alcohol craving in alcoholics. To assess the predictive validity of this approach, the approved alcoholism medication acamprosate was evaluated for its ability to modulate challenge-induced cravings. A total of 35 treatment seeking alcohol dependent inpatients in early abstinence were randomized to placebo or acamprosate (2997 mg daily). Following two weeks of medication, subjects underwent three challenge sessions with yohimbine, mCPP or saline infusion under double blind conditions, carried out in counterbalanced order, and separated by at least 5 days. Ratings of cravings and anxiety, as well as biochemical measures were obtained. In all, 25 subjects completed all three sessions and were included in the analysis. Cravings were modestly, but significantly higher following both yohimbine and mCPP challenge compared with saline infusion. The mCPP, but not yohimbine significantly increased anxiety ratings. Both challenges produced robust ACTH, cortisol and prolactin responses. There was a significant correlation between craving and the degree of alcoholism severity. Acamprosate administration did not influence craving. Both yohimbine and mCPP challenges lead to elevated alcohol craving in a clinical population of alcoholics, and these cravings correlate with alcoholism severity. Under the experimental conditions used, alcohol cravings induced by these two stimuli are not sensitive to acamprosate at clinically used doses. Neuropsychopharmacology (2011) 36, 1178-1186; doi: 10.1038/npp.2010.253; published online 2 February 2011
C1 [Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
RP Heilig, M (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM markus.heilig@mail.nih.gov
RI Schwandt, Melanie/L-9866-2016;
OI Heilig, Markus/0000-0003-2706-2482
FU NIAAA
FX The authors thank MJ Phillips, BS for technical assistance, LE Kwako,
PhD for providing comments on the article, and the NIH Clinical Center
Pharmaceutical Development Services for formulating drug and placebo.
This research was supported by NIAAA intramural research funding.
NR 54
TC 27
Z9 27
U1 2
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD MAY
PY 2011
VL 36
IS 6
BP 1178
EP 1186
DI 10.1038/npp.2010.253
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 749ZJ
UT WOS:000289511800006
PM 21289601
ER
PT J
AU Sabino, V
Cottone, P
Blasio, A
Iyer, MR
Steardo, L
Rice, KC
Conti, B
Koob, GF
Zorrilla, EP
AF Sabino, Valentina
Cottone, Pietro
Blasio, Angelo
Iyer, Malliga R.
Steardo, Luca
Rice, Kenner C.
Conti, Bruno
Koob, George F.
Zorrilla, Eric P.
TI Activation of sigma-Receptors Induces Binge-like Drinking in Sardinian
Alcohol-Preferring Rats
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE alcohol & alcoholism; addiction & substance abuse; alcohol OR ethanol;
dependence; self-administration; binge-like OR binge
ID VENTRAL TEGMENTAL AREA; CONDITIONED PLACE PREFERENCE; CROSS-FOSTERING
ANALYSIS; CENTRAL-NERVOUS-SYSTEM; H-3 DOPAMINE RELEASE; FREELY MOVING
RATS; MU-OPIOID AGONIST; GUINEA-PIG BRAIN; NUCLEUS-ACCUMBENS;
BINDING-SITES
AB Sigma (sigma) receptors have been implicated in the behavioral and motivational effects of alcohol and psychostimulants. Sigma receptor antagonists reduce the reinforcing effects of alcohol and excessive alcohol intake in both genetic (alcohol-preferring rats) and environmental (chronic alcohol-induced) models of alcoholism. The present study tested the hypothesis that pharmacological activation of sigma-receptors facilitates ethanol reinforcement and induces excessive, binge-like ethanol intake. The effects of repeated subcutaneous treatment with the selective sigma-receptor agonist 1,3-di-(2-tolyl) guanidine (DTG; 15 mg/kg, twice a day for 7 days) on operant ethanol (10%) self-administration were studied in Sardinian alcohol-preferring (sP) rats. To confirm that the effect of DTG was mediated by sigma-receptors, the effects of pretreatment with the selective sigma-receptor antagonist BD-1063 (7 mg/kg, subcutaneously) were determined. To assess the specificity of action, the effects of DTG on the self-administration of equally reinforcing solutions of saccharin or sucrose were also determined. Finally, gene expression of opioid receptors in brain areas implicated in ethanol reinforcement was analyzed in ethanol-naive sP rats treated acutely or repeatedly with DTG, because of the well-established role of the opioid system in alcohol reinforcement and addiction. Repeatedly administered DTG progressively and dramatically increased ethanol self-administration in sP rats and increased blood alcohol levels, which reached mean values close to 100 mg% in 1 h drinking sessions. Repeated DTG treatment also increased the rats' motivation to work for alcohol under a progressive-ratio schedule of reinforcement. BD-1063 prevented the effects of DTG, confirming that sigma-receptors mediate the effects of DTG. Repeated DTG treatment also increased the self-administration of the non-drug reinforcers saccharin and sucrose. Naive sP rats repeatedly treated with DTG showed increased mRNA expression of m-and delta-opioid receptors in the ventral tegmental area. These results suggest a key facilitatory role for sigma-receptors in the reinforcing effects of alcohol and identify a potential mechanism that contributes to binge-like and excessive drinking. Neuropsychopharmacology (2011) 36, 1207-1218; doi: 10.1038/npp.2011.5; published online 23 February 2011
C1 [Sabino, Valentina; Cottone, Pietro; Blasio, Angelo] Boston Univ, Sch Med, Lab Addict Disorders, Dept Pharmacol & Expt Therapeut, Boston, MA 02118 USA.
[Sabino, Valentina; Cottone, Pietro; Koob, George F.; Zorrilla, Eric P.] Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA 92037 USA.
[Iyer, Malliga R.; Rice, Kenner C.] NIDA, Chem Biol Res Branch, Bethesda, MD 20892 USA.
[Iyer, Malliga R.; Rice, Kenner C.] NIAAA, Bethesda, MD USA.
[Blasio, Angelo; Steardo, Luca] Univ Roma La Sapienza, Dept Human Physiol & Pharmacol, Rome, Italy.
[Conti, Bruno] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA.
RP Sabino, V (reprint author), Boston Univ, Sch Med, Lab Addict Disorders, Dept Pharmacol & Expt Therapeut, 72 Concord St,R612, Boston, MA 02118 USA.
EM vsabino@bu.edu; ezorrilla@scripps.edu
RI Cottone, Pietro/F-5291-2012; Sabino, Valentina/F-5290-2012; koob,
george/P-8791-2016
OI Cottone, Pietro/0000-0003-1320-1672; Sabino,
Valentina/0000-0002-6680-1279;
FU National Institute on Alcohol Abuse and Alcoholism [AA016731, AA006420,
AA12602]; Peter McManus Trust; Pearson Center for Alcoholism and
Addiction Research; NIH, NIDA
FX We thank Jeanette Helfers, Stephanie Dela Cruz, Bob Lintz and Molly
Brennan for excellent technical assistance and Mike Arends and Jina Kwak
for editorial assistance. This publication was made possible by grant
numbers AA016731, AA006420, and AA12602 from the National Institute on
Alcohol Abuse and Alcoholism, by the Peter McManus Trust, and the
Pearson Center for Alcoholism and Addiction Research. The research of
the Drug Design and Synthesis Section, Chemical Biology Research Branch,
National Institute on Drug Abuse (NIDA), and National Institute on
Alcohol Abuse and Alcoholism (NIAAA), was supported by the NIH
Intramural Research Programs of the NIDA and NIAAA. The contents of this
publication are solely the responsibility of the authors and do not
necessarily represent the official views of the National Institutes of
Health. This is manuscript number 20891 from The Scripps Research
Institute.
NR 104
TC 22
Z9 22
U1 2
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD MAY
PY 2011
VL 36
IS 6
BP 1207
EP 1218
DI 10.1038/npp.2011.5
PG 12
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 749ZJ
UT WOS:000289511800009
PM 21346735
ER
PT J
AU Brinkley, TE
Hsu, FC
Carr, JJ
Hundley, WG
Bluemke, DA
Polak, JF
Ding, J
AF Brinkley, T. E.
Hsu, F. -C.
Carr, J. J.
Hundley, W. G.
Bluemke, D. A.
Polak, J. F.
Ding, J.
TI Pericardial fat is associated with carotid stiffness in the Multi-Ethnic
Study of Atherosclerosis
SO NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
LA English
DT Article
DE Pericardial fat; Arterial stiffness; Distensibility; Carotid artery
ID EPICARDIAL ADIPOSE-TISSUE; CARDIOVASCULAR RISK-FACTORS;
CORONARY-ARTERY-DISEASE; COMPUTED-TOMOGRAPHY; OBESITY; QUANTIFICATION;
CALCIFICATION; PATHOGENESIS; CALCIUM; PLAQUE
AB Background and aims: Arterial stiffness is a prominent feature of vascular aging and a risk factor for cardiovascular disease (CVD). Fat around the heart and blood vessels (i.e. pericardial fat, Pfat) may contribute to arterial stiffness via a local paracrine effect of adipose tissue on the surrounding vasculature. Thus, we determined the association between Pfat and carotid stiffness in 5770 participants (mean age 62 years, 53% female, 25% African American, 24% Hispanic, and 13% Chinese) from the Multi-Ethnic Study of Atherosclerosis.
Methods and results: Pfat was measured by computed tomography, and ultrasonography of the common carotid artery was used to calculate the distensibility coefficient (DC) and Young's modulus (YM). Lower DC and higher YM values indicate stiffer arteries. Pfat quartile was highly associated with demographic, behavioral, anthropometric, hemodynamic, metabolic, and disease variables in both men and women. After adjusting for height, clinical site, CVD risk factors, and medications, a 1 standard deviation (41.91 cm(3)) increment in Pfat was associated with a 0.00007 +/- 0.00002 1/mmHg lower DC (p = 0.0002) in men and a 48.1 +/- 15.1 mmHg/mm higher YM in women (p = 0.002). Additional adjustment for C-reactive protein, coronary artery calcification, and carotid intima-media thickness had only modest effects. More importantly, adjusting for body mass index and waist circumference did not significantly change the overall results.
Conclusion: Higher Pfat is associated with higher carotid stiffness, independent of traditional CVD risk factors and obesity. (C) 2009 Elsevier B. V. All rights reserved.
C1 [Brinkley, T. E.] Wake Forest Univ, Bowman Gray Sch Med, Sect Gerontol & Geriatr Med, Dept Internal Med,J Paul Stitcht Ctr Aging, Winston Salem, NC 27157 USA.
[Hsu, F. -C.] Wake Forest Univ, Bowman Gray Sch Med, Div Publ Hlth Sci, Dept Biostat Sci, Winston Salem, NC 27157 USA.
[Carr, J. J.] Wake Forest Univ, Bowman Gray Sch Med, Div Radiol Sci, Dept Radiol, Winston Salem, NC 27157 USA.
[Hundley, W. G.] Wake Forest Univ, Bowman Gray Sch Med, Cardiol Sect, Dept Internal Med, Winston Salem, NC 27157 USA.
[Bluemke, D. A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Polak, J. F.] Tufts Med Ctr, Dept Radiol, Boston, MA USA.
RP Brinkley, TE (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Sect Gerontol & Geriatr Med, Dept Internal Med,J Paul Stitcht Ctr Aging, 300 S Hawthorne Rd, Winston Salem, NC 27157 USA.
EM tbrinkle@wfubmc.edu
RI Carr, John/A-1938-2012;
OI Carr, John/0000-0002-4398-8237; Bluemke, David/0000-0002-8323-8086
FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95169]
FX This work was supported by contracts N01-HC-95159 through N01-HC-95169
from the National Heart, Lung, and Blood Institute. The authors thank
the other investigators, the staff, and the participants of the MESA
study for their valuable contributions. A full list of participating
MESA investigators and institutions can be found at
http://www.mesa-nhlbi.org. The authors have no disclosures to report.
NR 23
TC 15
Z9 15
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0939-4753
J9 NUTR METAB CARDIOVAS
JI Nutr. Metab. Carbiovasc. Dis.
PD MAY
PY 2011
VL 21
IS 5
BP 332
EP 338
DI 10.1016/j.numecd.2009.10.010
PG 7
WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism; Nutrition
& Dietetics
SC Cardiovascular System & Cardiology; Endocrinology & Metabolism;
Nutrition & Dietetics
GA 750OZ
UT WOS:000289559100003
PM 20153618
ER
PT J
AU Olin, JT
Burns, K
Carson, JL
Metjian, H
Atkinson, JJ
Davis, SD
Dell, SD
Ferkol, TW
Milla, CE
Olivier, KN
Rosenfeld, M
Baker, B
Leigh, MW
Knowles, MR
Sagel, SD
AF Olin, J. Tod
Burns, Kim
Carson, Johnny L.
Metjian, Hilda
Atkinson, Jeffrey J.
Davis, Stephanie D.
Dell, Sharon D.
Ferkol, Thomas W.
Milla, Carlos E.
Olivier, Kenneth N.
Rosenfeld, Margaret
Baker, Brock
Leigh, Margaret W.
Knowles, Michael R.
Sagel, Scott D.
CA Genetic Disorders Mucociliary
TI Diagnostic Yield of Nasal Scrape Biopsies in Primary Ciliary Dyskinesia:
A Multicenter Experience
SO PEDIATRIC PULMONOLOGY
LA English
DT Article
DE cilia; nasal biopsy; primary ciliary dyskinesia
ID ELECTRON-MICROSCOPY; MUTATIONS; CHILDREN; DEFECTS
AB Examination of ciliary ultrastructure remains the cornerstone diagnostic test for primary ciliary dyskinesia (PCD), a disease of abnormal ciliary structure and/or function. Obtaining a biopsy with sufficient interpretable cilia and producing quality transmission electron micrographs (TEM) is challenging. Methods for processing tissues for optimal preservation of axonemal structures are not standardized. This study describes our experience using a standard operating procedure (SOP) for collecting nasal scrape biopsies and processing TEMs in a centralized laboratory. We enrolled patients with suspected PCD at research sites of the Genetic Disorders of Mucociliary Clearance Consortium. Biopsies were performed according to a SOP whereby curettes were used to scrape the inferior surface of the inferior turbinate, with samples placed in fixative. Specimens were shipped to a central laboratory where TEMs were prepared and blindly reviewed. Four hundred forty-eight specimens were obtained from 107 young children (0-5 years), 189 older children (5-18 years), and 152 adults (> 18 years), and 88% were adequate for formal interpretation. The proportion of adequate specimens was higher in adults than in children. Fifty percent of the adequate TEMs showed normal ciliary ultrastructure, 39% showed hallmark ultrastructural changes of PCD, and 11% had indeterminate findings. Among specimens without clearly normal ultrastructure, 72% had defects of the outer and/or inner dynein arms (IDA), while 7% had central apparatus defects with or without IDA defects. In summary, nasal scrape biopsies can be performed in the outpatient setting and yield interpretable samples, when performed by individuals with adequate training and experience according to an SOP. Pediatr Pulmonol. 2011; 46: 483-488. (c) 2011 Wiley-Liss, Inc.
C1 [Olin, J. Tod; Sagel, Scott D.] Childrens Hosp, Dept Pediat, Aurora, CO 80045 USA.
[Olin, J. Tod; Sagel, Scott D.] Univ Colorado, Sch Med, Aurora, CO USA.
[Burns, Kim; Carson, Johnny L.; Metjian, Hilda; Baker, Brock; Knowles, Michael R.] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
[Atkinson, Jeffrey J.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
[Davis, Stephanie D.; Leigh, Margaret W.] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA.
[Dell, Sharon D.] Univ Toronto, Dept Pediat, Toronto, ON, Canada.
[Ferkol, Thomas W.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
[Milla, Carlos E.] Stanford Univ, Dept Pediat, Palo Alto, CA 94304 USA.
[Olivier, Kenneth N.] NIAID, Bethesda, MD 20892 USA.
[Rosenfeld, Margaret] Seattle Childrens Hosp, Dept Pediat, Seattle, WA USA.
[Rosenfeld, Margaret] Univ Washington, Seattle, WA 98195 USA.
RP Olin, JT (reprint author), Childrens Hosp, Dept Pediat, 13123 E 16th Ave,Box B-395, Aurora, CO 80045 USA.
EM olin.tod@tchden.org
OI Milla, Carlos/0000-0001-5515-3053
FU National Institutes of Health [U54 RR019480-05, U54 HL096458-06, R01
HL071798]; Division of Intramural Research (NIAID), Cystic Fibrosis
Foundation [OLIN08B0]; NIH/NCRR [UL1 RR025780, UL1RR025014,
5UL1RR025744]
FX National Institutes of Health, Numbers U54 RR019480-05, U54 HL096458-06,
R01 HL071798; Division of Intramural Research (NIAID), Cystic Fibrosis
Foundation, Numbers OLIN08B0; Clinical and Translational Science Awards
Program, NIH/NCRR, Numbers UL1 RR025780, UL1RR025014, 5UL1RR025744.
NR 21
TC 20
Z9 20
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 8755-6863
J9 PEDIATR PULM
JI Pediatr. Pulmonol.
PD MAY
PY 2011
VL 46
IS 5
BP 483
EP 488
DI 10.1002/ppul.21402
PG 6
WC Pediatrics; Respiratory System
SC Pediatrics; Respiratory System
GA 749ZC
UT WOS:000289510500010
PM 21284095
ER
PT J
AU Nguyen, RHN
Umbach, DM
Parad, RB
Stroehla, B
Rogan, WJ
Estroff, JA
AF Nguyen, Ruby H. N.
Umbach, David M.
Parad, Richard B.
Stroehla, Berrit
Rogan, Walter J.
Estroff, Judy A.
TI US assessment of estrogen-responsive organ growth among healthy term
infants: piloting methods for assessing estrogenic activity
SO PEDIATRIC RADIOLOGY
LA English
DT Article
DE US; Infant; Organ growth; Soy formula
ID EXPERT PANEL REPORT; THYMUS SIZE; SOY FORMULA; DEVELOPMENTAL TOXICITY;
ULTRASOUND EVALUATION; KIDNEY GROWTH; HUMAN-MILK; BIRTH; LIFE; CHILDREN
AB A mother's circulating estrogen increases over the third trimester, producing physiological effects on her newborn that wane postnatally. Estrogenization might be prolonged in newborns exposed to exogenous estrogens, such as isoflavones in soy formula.
We evaluated ultrasonography for monitoring growth of multiple estrogen-responsive organs in healthy infants and developed organ-growth trajectories.
We studied 38 boys (61 visits) from birth to age 6 months and 41 girls (96 visits) from birth to age 1 year using a partly cross-sectional, partly longitudinal design. We measured uterus and ovaries in girls, testes and prostate in boys, and kidneys, breasts, thymus, and thyroid in all children. We imaged all organs from the body surface in one session of < 1 h.
Uterine volume decreased from birth (P < 0.0001), whereas ovarian volume increased sharply until age 2 months and then decreased (P < 0.001). Testicular volume increased with age (P < 0.0001), but prostatic volume showed minimal age trend. Breast bud diameter showed no age trend in girls but declined from birth in boys (P = 0.03).
US examination of multiple estrogen-responsive organs in infants in a single session is feasible and yields volume estimates useful for assessing potential endocrine disruptor effects on organ growth.
C1 [Umbach, David M.] Natl Inst Environm Hlth Sci, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Nguyen, Ruby H. N.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Nguyen, Ruby H. N.; Rogan, Walter J.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Parad, Richard B.] Harvard Univ, Brigham & Womens Hosp, Dept Newborn Med, Sch Med, Boston, MA 02115 USA.
[Parad, Richard B.] Harvard Univ, Sch Med, Div Newborn Med, Childrens Hosp Boston, Boston, MA USA.
[Stroehla, Berrit] Social & Sci Syst Inc, Durham, NC USA.
[Estroff, Judy A.] Harvard Univ, Sch Med, Dept Radiol, Childrens Hosp Boston, Boston, MA 02115 USA.
RP Umbach, DM (reprint author), Natl Inst Environm Hlth Sci, Biostat Branch, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM umbach@niehs.nih.gov
RI Parad, Richard/E-8559-2010; Rogan, Walter/I-6034-2012
OI Rogan, Walter/0000-0002-9302-0160
FU NIH, National Institute of Environmental Health Sciences (NIEHS)
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences (NIEHS). RHNN
was an NIEHS Intramural Post-doctoral Fellow at the time of this work.
The authors appreciate study coordination and analysis assistance of
Janet Archer and Holly Schmidt-Davis; clinical contributions of Jane
Share, Kathy Howard, Julie Hart, and Deirdre Ellard; recruitment
assistance by Drs. Joanne Cox and Lise Johnson; imaging supervision at
BWH by Dr. Carol Benson, and imaging by all participating sonologists at
BWH and Children's Hospital Boston.
NR 31
TC 6
Z9 6
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0301-0449
EI 1432-1998
J9 PEDIATR RADIOL
JI Pediatr. Radiol.
PD MAY
PY 2011
VL 41
IS 5
BP 633
EP 642
DI 10.1007/s00247-010-1895-0
PG 10
WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging
SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging
GA 750EN
UT WOS:000289527900014
PM 21104239
ER
PT J
AU Marciante, KD
Durda, JP
Heckbert, SR
Lumley, T
Rice, K
McKnight, B
Totah, RA
Tamraz, B
Kroetz, DL
Fukushima, H
Kaspera, R
Bis, JC
Glazer, NL
Li, G
Austin, TR
Taylor, KD
Rotter, JI
Jaquish, CE
Kwok, PY
Tracy, RP
Psaty, BM
AF Marciante, Kristin D.
Durda, Jon P.
Heckbert, Susan R.
Lumley, Thomas
Rice, Ken
McKnight, Barbara
Totah, Rheem A.
Tamraz, Bani
Kroetz, Deanna L.
Fukushima, Hisayo
Kaspera, Ruediger
Bis, Joshua C.
Glazer, Nicole L.
Li, Guo
Austin, Thomas R.
Taylor, Kent D.
Rotter, Jerome I.
Jaquish, Cashell E.
Kwok, Pui-Yan
Tracy, Russell P.
Psaty, Bruce M.
TI Cerivastatin, genetic variants, and the risk of rhabdomyolysis
SO PHARMACOGENETICS AND GENOMICS
LA English
DT Article
DE drugs; epidemiology; genetics; rhabdomyolysis
ID ADVERSE DRUG-REACTIONS; SINGLE-NUCLEOTIDE POLYMORPHISMS; RYANODINE
RECEPTOR; SARCOPLASMIC-RETICULUM; MALIGNANT HYPERTHERMIA;
PLASMA-CONCENTRATIONS; RELEASE CHANNEL; MUSCLE-FIBERS; PHARMACOKINETICS;
ASSOCIATION
AB Objective The withdrawal of cerivastatin involved an uncommon but serious adverse reaction, rhabdomyolysis. The bimodal response, rhabdomyolysis in a small proportion of users, points to genetic factors as a potential cause. We conducted a case-control study to evaluate genetic markers for cerivastatin-associated rhabdomyolysis.
Methods This study had two components: a candidate gene study to evaluate variants in CYP2C8, UGT1A1, UGT1A3, and SLCO1B1; and a genome-wide association study to identify risk factors in other regions of the genome. A total of 185 rhabdomyolysis cases were frequency matched to statin-using controls from the Cardiovascular Health Study (n = 374) and the Heart and Vascular Health Study (n = 358). Validation relied on functional studies.
Results Permutation test results suggested an association between cerivastatin-associated rhabdomyolysis and variants in SLCO1B1 (P = 0.002), but not variants in CYP2C8 (P = 0.073) or UGTs (P = 0.523). An additional copy of the minor allele of SLCO1B1 rs4149056 (p.Val174Ala) was associated with the risk of rhabdomyolysis (odds ratio: 1.89; 95% confidence interval: 1.40-2.56). In transfected cells, this variant reduced cerivastatin transport by 40% compared with the reference transporter (P < 0.001). The genome-wide association study identified an intronic variant (rs2819742) in the ryanodine receptor 2 gene (RYR2) as significant (P = 1.74E-07). An additional copy of the minor allele of the RYR2 variant was associated with a reduced risk of rhabdomyolysis (odds ratio: 0.48; 95% confidence interval: 0.36-0.63).
Conclusion We identified modest genetic risk factors for an extreme response to cerivastatin. Disabling genetic variants in the candidate genes were not responsible for the bimodal response to cerivastatin. Pharmacogenetics and Genomics 21:280-288 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.
C1 [Marciante, Kristin D.; Heckbert, Susan R.; Lumley, Thomas; Rice, Ken; McKnight, Barbara; Bis, Joshua C.; Glazer, Nicole L.; Li, Guo; Austin, Thomas R.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
[Marciante, Kristin D.; Bis, Joshua C.; Glazer, Nicole L.; Li, Guo; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA 98101 USA.
[Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA.
[Lumley, Thomas; Rice, Ken; McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98101 USA.
[Totah, Rheem A.; Kaspera, Ruediger] Univ Washington, Dept Med Chem, Seattle, WA 98101 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA.
[Heckbert, Susan R.; Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Austin, Thomas R.] Whitman Coll, Walla Walla, WA 99362 USA.
[Durda, Jon P.; Tracy, Russell P.] Univ Vermont, Dept Pathol, Colchester, VT USA.
[Tracy, Russell P.] Univ Vermont, Dept Biochem, Colchester, VT USA.
[Kwok, Pui-Yan] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA.
[Tamraz, Bani; Kwok, Pui-Yan] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA.
[Kroetz, Deanna L.; Fukushima, Hisayo] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.
[Taylor, Kent D.; Rotter, Jerome I.] Cedars Sinai Med Ctr, Med Genet Res Inst, Los Angeles, CA 90048 USA.
[Jaquish, Cashell E.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
RP Marciante, KD (reprint author), Univ Washington, Cardiovasc Hlth Res Unit, 1730 Minor Ave,Suite 1360, Seattle, WA 98101 USA.
EM marciant@uw.edu
RI Li, Guo/E-5613-2012; Rice, Kenneth/A-4150-2013; Kwok,
Pui-Yan/F-7725-2014
OI Rice, Kenneth/0000-0001-5779-4495; Kwok, Pui-Yan/0000-0002-5087-3059
FU National Heart, Lung, and Blood Institute [HL078888, HL085251, HL074745,
HL43201, HL068639, HL068986, HL73410, N01-HC-85079, N01-HC-85086,
N01HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC45133, U01
HL080295, R01HL087652]; National Institute of Neurological Disorders and
Stroke; National Center for Research Resources [M01-RR00425]; National
Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; NIH
[GM61390]; Amgen Research Fellowship
FX For their excellent work, the authors thank the attorneys and their
staff. We also thank the dedicated staff members at the Cardiovascular
Health Research Unit, and thank the rhabdomyolysis case participants,
the participants at Group Health, and the participants from the
Cardiovascular Health Study. Funding sources: the rhabdomyolysis case
recruitment and the genotyping was supported in part by the grants
HL078888 and HL085251 from the National Heart, Lung, and Blood
Institute. The HVH research reported in this article was supported in
part by the grants HL074745, HL43201, HL068639, HL068986, and HL73410
from the National Heart, Lung and Blood Institute. The CHS research
reported in this work was supported in part by contract numbers
N01-HC-85079 through N01-HC-85086, N01HC- 35129, N01-HC-15103,
N01-HC-55222, N01-HC-75150, N01-HC45133, and grant numbers U01 HL080295
and R01HL087652 from the National Heart, Lung, and Blood Institute, with
additional contribution from the National Institute of Neurological
Disorders and Stroke. A full list of principal CHS investigators and
institutions can be found at http://www.chs-nhlbi.org/pi.htm. The CHS
DNA handling and genotyping was supported in part by National Center for
Research Resources grant M01-RR00425 to the Cedars-Sinai General
Clinical Research Center Genotyping core and National Institute of
Diabetes and Digestive and Kidney Diseases grant DK063491 to the
Southern California Diabetes Endocrinology Research Center. The SLCO1B1
functional work was supported in part by NIH grant GM61390 and Amgen
Research Fellowship. Financial disclosures: one author, Bruce M. Psaty,
worked for plaintiffs' attorneys between 2002 and 2003. A complete
statement of disclosure is available in Ref. [ 6]. No other author
reported having financial disclosures.
NR 45
TC 50
Z9 50
U1 0
U2 5
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 MAY
PY 2011
VL 21
IS 5
BP 280
EP 288
DI 10.1097/FPC.0b013e328343dd7d
PG 9
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology
& Pharmacy
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology
& Pharmacy
GA 749JD
UT WOS:000289460200005
PM 21386754
ER
PT J
AU Matei, E
Louis, JM
Jee, J
Gronenborn, AM
AF Matei, Elena
Louis, John M.
Jee, JunGoo
Gronenborn, Angela M.
TI NMR solution structure of a cyanovirin homolog from wheat head blight
fungus
SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
LA English
DT Article
DE NMR solution structure; CVNH; lectin; antiviral protein; HIV
ID HIV-INACTIVATING PROTEIN; TORSION ANGLE DYNAMICS; CRYSTAL-STRUCTURE;
BINDING; DOMAIN; MUTANT; GP120; SPECTROSCOPY; LECTINS; SYSTEM
AB Members of the cyanovirin-N homolog (CVNH) lectin family are found in bacteria, fungi and plants. As part of our ongoing work on CVNH structure-function studies, we determined the high-resolution NMR solution structure of the homolog from the wheat head blight disease causing ascomycetous fungus Gibberella zeae (or Fusarium graminearum), hereafter called GzCVNH. Like cyanovirin-N (CV-N), GzCVNH comprises two tandem sequence repeats and the protein sequence exhibits 30% identity with CV-N. The overall structure is similar to those of other members of the CVNH family, with the conserved pseudo-symmetric halves of the structure, domains A and B, closely resembling recently determined structures of Tuber borchii, Neurospora crassa, and Ceratopteris richardii CVNH proteins. Although GzCVNH exhibits a similar glycan recognition profile to CV-N and specifically binds to Man alpha(1-2) Man alpha, its weak carbohydrate binding affinity to only one binding site is insufficient for conferring anti-HIV activity. Proteins 2011; 79: 1538-1549. (C) 2011 Wiley-Liss, Inc.
C1 [Matei, Elena; Jee, JunGoo; Gronenborn, Angela M.] Univ Pittsburgh, Sch Med, Dept Biol Struct, Pittsburgh, PA 15260 USA.
[Louis, John M.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Gronenborn, AM (reprint author), Univ Pittsburgh, Sch Med, Dept Biol Struct, Biomed Sci Tower 3,3501 5th Ave, Pittsburgh, PA 15260 USA.
EM amg100@pitt.edu
OI Gronenborn, Angela M/0000-0001-9072-3525
FU National Institutes of Health [GM080642]; NIH [GM62116]
FX Grant sponsor: National Institutes of Health; Grant number: GM080642.;
We thank Annie Aniana for useful discussions, In-Ja Byeon for expert
help with NMR experiments and Chris Aiken and Jeremy Rose for carrying
out HIV activity assays. The Protein-Glycan Interaction Core (Core H) of
the Consortium for Functional Glycomics (supported by NIH grant GM62116)
is gratefully acknowledged for glycan array analyses.
NR 42
TC 7
Z9 7
U1 1
U2 9
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0887-3585
J9 PROTEINS
JI Proteins
PD MAY
PY 2011
VL 79
IS 5
BP 1538
EP 1549
DI 10.1002/prot.22981
PG 12
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 750EU
UT WOS:000289528700014
PM 21365681
ER
PT J
AU Fleischhauer, K
Wang, T
Spellman, SR
Crivello, P
Haagenson, M
Battiwalla, M
Baxter-Lowe, LA
Dehn, JW
Gajewski, JL
Hale, GA
Heemskerk, MB
Lee, SJ
McCarthy, PL
Miklos, DB
Oudshoorn, M
Pollack, MS
Marino, S
Reddy, V
Senitzer, D
Shaw, B
Waller, EK
Fernandez-Vina, M
AF Fleischhauer, K.
Wang, T.
Spellman, S. R.
Crivello, P.
Haagenson, M.
Battiwalla, M.
Baxter-Lowe, L. A.
Dehn, J. W.
Gajewski, J. L.
Hale, G. A.
Heemskerk, M. B.
Lee, S. J.
McCarthy, P. L.
Miklos, D. B.
Oudshoorn, M.
Pollack, M. S.
Marino, S.
Reddy, V.
Senitzer, D.
Shaw, B.
Waller, E. K.
Fernandez-Vina, M.
TI No apparent contribution of HLA-DPA1 to the significantly increased risk
for non-relapse mortality associated with non-permissive donor-recipient
HLA-DPB1 T cell epitope disparities in unrelated stem cell transplants
facilitated through the National Marrow Donor Program
SO TISSUE ANTIGENS
LA English
DT Meeting Abstract
CT 25th Conference on European Immunogenetics and Histocompatibility
CY MAY 04-07, 2011
CL Prague, CZECH REPUBLIC
C1 [Fleischhauer, K.; Crivello, P.] Ist Sci San Raffaele, Unit Mol & Funct Immunogenet, I-20132 Milan, Italy.
[Wang, T.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Spellman, S. R.; Haagenson, M.] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA.
[Battiwalla, M.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Baxter-Lowe, L. A.] Univ Calif San Francisco, Med Ctr, San Francisco, CA 94143 USA.
[Dehn, J. W.] Natl Marrow Donor Program, Minneapolis, MN USA.
[Gajewski, J. L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Hale, G. A.] Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA.
[Heemskerk, M. B.] Dutch Transplant Fdn, Leiden, Netherlands.
[Lee, S. J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[McCarthy, P. L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Miklos, D. B.] Stanford Hosp & Clin, Stanford, CA USA.
[Oudshoorn, M.] Europdonor Fdn, Leiden, Netherlands.
[Pollack, M. S.] UTHSC Vet Hlth Care Syst, San Antonio, TX USA.
[Marino, S.] Univ Chicago, Chicago, IL 60637 USA.
[Reddy, V.] Florida Ctr Cellular Therapy, Orlando, FL USA.
[Senitzer, D.] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
[Shaw, B.] Anthony Nolan Res Inst, London, England.
[Waller, E. K.] Emory Univ Hosp, Atlanta, GA 30322 USA.
[Fernandez-Vina, M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
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 0001-2815
J9 TISSUE ANTIGENS
JI Tissue Antigens
PD MAY
PY 2011
VL 77
IS 5
BP 397
EP 398
PG 2
WC Cell Biology; Immunology; Pathology
SC Cell Biology; Immunology; Pathology
GA 746LT
UT WOS:000289249000068
ER
PT J
AU Pincerati, MR
Guerreiro, J
Santos, EJ
Martin, MP
Carrington, M
Meyer, D
AF Pincerati, M. R.
Guerreiro, J.
Santos, E. J.
Martin, M. P.
Carrington, M.
Meyer, D.
TI Diversity of KIR2DL4 gene in Amerindian populations
SO TISSUE ANTIGENS
LA English
DT Meeting Abstract
CT 25th Conference on European Immunogenetics and Histocompatibility
CY MAY 04-07, 2011
CL Prague, CZECH REPUBLIC
C1 [Pincerati, M. R.; Meyer, D.] Biociencias, Sao Paulo, Brazil.
[Guerreiro, J.; Santos, E. J.] Inst Ciencias Biol, Belem, Para, Brazil.
[Martin, M. P.; Carrington, M.] NCI, Frederick, MD 21701 USA.
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 0001-2815
J9 TISSUE ANTIGENS
JI Tissue Antigens
PD MAY
PY 2011
VL 77
IS 5
BP 429
EP 430
PG 2
WC Cell Biology; Immunology; Pathology
SC Cell Biology; Immunology; Pathology
GA 746LT
UT WOS:000289249000150
ER
PT J
AU Strauss, RG
Klein, HG
Leitman, SF
Price, TH
Lichtiger, B
Martinez, F
Reesink, HW
Panzer, S
AF Strauss, R. G.
Klein, H. G.
Leitman, S. F.
Price, T. H.
Lichtiger, B.
Martinez, F.
Reesink, H. W.
Panzer, S.
TI Preparation of granulocyte concentrates by apheresis: collection
modalities in the USA
SO VOX SANGUINIS
LA English
DT Letter
C1 [Strauss, R. G.] Univ Iowa, Coll Med, Iowa City, IA 52242 USA.
[Panzer, S.] Univ Vienna, Dept Blood Grp Serol & Transfus Med, A-1090 Vienna, Austria.
[Reesink, H. W.] Acad Med Ctr, Dept Gastroenterol & Hepatol Amsterdam, Amsterdam, Netherlands.
[Lichtiger, B.; Martinez, F.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Klein, H. G.; Leitman, S. F.] NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA.
[Price, T. H.] Univ Washington, Puget Sound Blood Ctr, Seattle, WA 98195 USA.
RP Strauss, RG (reprint author), Univ Iowa, Coll Med, 200 Hawkins Dr,C250 GH, Iowa City, IA 52242 USA.
EM ronald-strauss@uiowa.edu; hklein@dtm.cc.nih.gov; sleitman@cc.nih.gov;
thprice@psbc.org; blichtig@mdanderson.org; h.w.reesink@amc.nl;
simon.panzer@meduniwien.ac.at
FU Intramural NIH HHS [Z99 CL999999, ZIA CL002124-01]
NR 0
TC 6
Z9 7
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0042-9007
EI 1423-0410
J9 VOX SANG
JI Vox Sang.
PD MAY
PY 2011
VL 100
IS 4
BP 426
EP 433
DI 10.1111/j.1423-0410.2010.01417.x
PG 8
WC Hematology
SC Hematology
GA 750EX
UT WOS:000289529000012
PM 21320130
ER
PT J
AU Flores-Santana, W
Salmon, DJ
Donzelli, S
Switzer, CH
Basudhar, D
Ridnour, L
Cheng, R
Glynn, SA
Paolocci, N
Fukuto, JM
Miranda, KM
Wink, DA
AF Flores-Santana, Wilmarie
Salmon, Debra J.
Donzelli, Sonia
Switzer, Christopher H.
Basudhar, Debashree
Ridnour, Lisa
Cheng, Robert
Glynn, Sharon A.
Paolocci, Nazareno
Fukuto, Jon M.
Miranda, Katrina M.
Wink, David A.
TI The Specificity of Nitroxyl Chemistry Is Unique Among Nitrogen Oxides in
Biological Systems
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Review
ID HYDROXY-L-ARGININE; NO-CENTER-DOT; CARDIAC SARCOPLASMIC-RETICULUM;
SOLUBLE GUANYLATE-CYCLASE; DETERRENT AGENT CYANAMIDE; NEUTRAL
AQUEOUS-SOLUTION; PROTEIN S-NITROSOTHIOLS; CYSTEINE SULFINIC ACID; FREE
NITRIC-OXIDE; ANGELIS SALT
AB The importance of nitric oxide in mammalian physiology has been known for nearly 30 years. Similar attention for other nitrogen oxides such as nitroxyl (HNO) has been more recent. While there has been speculation as to the biosynthesis of HNO, its pharmacological benefits have been demonstrated in several pathophysiological settings such as cardiovascular disorders, cancer, and alcoholism. The chemical biology of HNO has been identified as related to, but unique from, that of its redox congener nitric oxide. A summary of these findings as well as a discussion of possible endogenous sources of HNO is presented in this review. Antioxid. Redox Signal. 14, 1659-1674.
C1 [Flores-Santana, Wilmarie; Switzer, Christopher H.; Basudhar, Debashree; Ridnour, Lisa; Cheng, Robert; Glynn, Sharon A.; Wink, David A.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA.
[Salmon, Debra J.; Basudhar, Debashree; Miranda, Katrina M.] Univ Arizona, Dept Chem & Biochem, Tucson, AZ USA.
[Donzelli, Sonia] Univ Med Ctr Hamburg Eppendorf, Dept Neurol, Hamburg, Germany.
[Donzelli, Sonia] Univ Med Ctr Hamburg Eppendorf, Dept Expt & Clin Pharmacol, Hamburg, Germany.
[Donzelli, Sonia] Univ Med Ctr Hamburg Eppendorf, Cardiovasc Res Ctr, Hamburg, Germany.
[Paolocci, Nazareno] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
[Paolocci, Nazareno] Univ Perugia, Sect Gen Pathol, Dept Clin Med, I-06100 Perugia, Italy.
[Fukuto, Jon M.] Sonoma State Univ, Dept Chem, Rohnert Pk, CA 94928 USA.
RP Wink, DA (reprint author), NCI, Radiat Biol Branch, NIH, Bldg 10,Room B3-B35, Bethesda, MD 20892 USA.
EM wink@mail.nih.gov
RI Miranda, Katrina/B-7823-2009; Glynn, Sharon/D-7136-2013; Switzer,
Christopher/D-9203-2013;
OI Glynn, Sharon/0000-0003-1459-2580; Cheng, Robert/0000-0003-0287-6439;
Paolocci, Nazareno/0000-0001-7011-997X
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research; NIH [R01-GM076247]; NIH, NIAAA [1F31AA018069-01A1];
National Science Foundation [CHE-0645818]; European Community
[PIEF-GA-2008-221666]; Forschungsforderungsfonds [NWF-08/04]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research (to D. A. W.), by NIH grants (R01-GM076247 to K. M. M.;
NIAAA 1F31AA018069-01A1 to D.J.S.), by the National Science Foundation
(CHE-0645818 to K. M. M.), by a Marie Curie Intra European Fellowship
within the 7th European Community Framework Programme
(PIEF-GA-2008-221666 to S.D.), and by the Forschungsforderungsfonds
NWF-08/04 (S.D.)
NR 178
TC 47
Z9 48
U1 0
U2 12
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1523-0864
J9 ANTIOXID REDOX SIGN
JI Antioxid. Redox Signal.
PD MAY
PY 2011
VL 14
IS 9
BP 1659
EP 1674
DI 10.1089/ars.2010.3841
PG 16
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 746WL
UT WOS:000289278900008
PM 21235346
ER
PT J
AU Tocchetti, CG
Stanley, BA
Murray, CI
Sivakumaran, V
Donzelli, S
Mancardi, D
Pagliaro, P
Gao, WD
van Eyk, J
Kass, DA
Wink, DA
Paolocci, N
AF Tocchetti, Carlo G.
Stanley, Brian A.
Murray, Christopher I.
Sivakumaran, Vidhya
Donzelli, Sonia
Mancardi, Daniele
Pagliaro, Pasquale
Gao, Wei Dong
van Eyk, Jennifer
Kass, David A.
Wink, David A.
Paolocci, Nazareno
TI Playing with Cardiac "Redox Switches'': The "HNO Way'' to Modulate
Cardiac Function
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Review
ID NITRIC-OXIDE SYNTHASE; GENE-RELATED PEPTIDE; HYDROXY-L-ARGININE;
NO-CENTER-DOT; NITROXYL HNO; HEART-FAILURE; SARCOPLASMIC-RETICULUM;
RYANODINE RECEPTOR; IN-VIVO; CONTRACTILE-FORCE
AB The nitric oxide (NO center dot) sibling, nitroxyl or nitrosyl hydride (HNO), is emerging as a molecule whose pharmacological properties include providing functional support to failing hearts. HNO also preconditions myocardial tissue, protecting it against ischemia-reperfusion injury while exerting vascular antiproliferative actions. In this review, HNO's peculiar cardiovascular assets are discussed in light of its unique chemistry that distinguish HNO from NO center dot as well as from reactive oxygen and nitrogen species such as the hydroxyl radical and peroxynitrite. Included here is a discussion of the possible routes of HNO formation in the myocardium and its chemical targets in the heart. HNO has been shown to have positive inotropic/lusitropic effects under normal and congestive heart failure conditions in animal models. The mechanistic intricacies of the beneficial cardiac effects of HNO are examined in cellular models. In contrast to beta-receptor/cyclic adenosine monophosphate/protein kinase A-dependent enhancers of myocardial performance, HNO uses its "thiophylic'' nature as a vehicle to interact with redox switches such as cysteines, which are located in key components of the cardiac electromechanical machinery ruling myocardial function. Here, we will briefly review new features of HNO's cardiovascular effects that when combined with its positive inotropic/lusitropic action may render HNO donors an attractive addition to the current therapeutic armamentarium for treating patients with acutely decompensated congestive heart failure. Antioxid. Redox Signal. 14, 1687-1698.
C1 [Tocchetti, Carlo G.; Stanley, Brian A.; Murray, Christopher I.; Sivakumaran, Vidhya; van Eyk, Jennifer; Kass, David A.; Paolocci, Nazareno] Johns Hopkins Med Inst, Div Cardiol, Baltimore, MD 21205 USA.
[Tocchetti, Carlo G.] G Pascale Fdn, Natl Canc Inst, Div Cardiol, Naples, Italy.
[Donzelli, Sonia] Univ Hosp Hamburg Eppendorf, Dept Neurol Clin Pharmacol & Toxicol, Cardiovasc Res Ctr, Hamburg, Germany.
[Mancardi, Daniele; Pagliaro, Pasquale] Univ Turin, Dept Clin & Biol Sci, Turin, Italy.
[Gao, Wei Dong] Johns Hopkins Med Inst, Dept Anesthesiol, Baltimore, MD 21205 USA.
[Wink, David A.] NIH, Natl Canc Inst, Radiat Biol Branch, Bethesda, MD 20892 USA.
[Paolocci, Nazareno] Univ Perugia, Dept Clin Med, Gen Pathol Sect, I-06100 Perugia, Italy.
RP Paolocci, N (reprint author), Johns Hopkins Sch Med, Div Cardiol, Traylor 911,720 Rutland Ave, Baltimore, MD 21205 USA.
EM npaoloc1@jhmi.edu
RI Pagliaro, Pasquale/E-5239-2010;
OI MANCARDI, Daniele/0000-0003-3809-6047; tocchetti, carlo
gabriele/0000-0001-5983-688X; Paolocci, Nazareno/0000-0001-7011-997X
FU ISHR-ES/Servier; European Community [PIEF-GA-2008-221666]; American
Heart Association [10POST414001, 0815145E, 0815217E]; NIH [P01-HL081427,
PO1-HL077180, HL-077180, HL075265, HL091923]
FX This work is dedicated to the memory of Dr. Jeffrey P. Froehlich
(1943-2009), who pioneered studies on HNO effects on SERCA2a/PLN
interaction. This work was supported by the ISHR-ES/Servier to C. G. T.,
the Marie Curie Intra European Fellowship within the 7th European
Community Framework Programme (PIEF-GA-2008-221666 to S. D.), the
American Heart Association (GIA to N.P., 10POST414001 to B. A. S.,
Pre-Doctoral Grant to 0815145E and 0815217E to V. S.); the NIH grants
P01-HL081427 and PO1-HL077180 to J.V.E., HL-077180 to D. A. K., and
HL075265 and HL091923 to N.P.
NR 79
TC 54
Z9 54
U1 2
U2 8
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1523-0864
J9 ANTIOXID REDOX SIGN
JI Antioxid. Redox Signal.
PD MAY
PY 2011
VL 14
IS 9
BP 1687
EP 1698
DI 10.1089/ars.2010.3859
PG 12
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 746WL
UT WOS:000289278900010
PM 21235349
ER
PT J
AU Buehler, PW
Karnaukhova, E
Gelderman, MP
Alayash, AI
AF Buehler, Paul W.
Karnaukhova, Elena
Gelderman, Monique P.
Alayash, Abdu I.
TI Blood Aging, Safety, and Transfusion: Capturing the "Radical'' Menace
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Review
ID HUMAN-SERUM-ALBUMIN; HAPTOGLOBIN-HEMOGLOBIN COMPLEX; CELL-FREE
HEMOGLOBIN; ALPHA-HEMOGLOBIN; NITRIC-OXIDE; HEME-DEGRADATION; LIPOCALIN
ALPHA(1)-MICROGLOBULIN; LIPOPROTEIN OXIDATION; STABILIZING PROTEIN;
SCAVENGER RECEPTOR
AB Throughout their life span, circulating red blood cells (RBCs) transport oxygen (O-2) primarily from the lungs to tissues and return with carbon dioxide (CO2) from respiring tissues for final elimination by lungs. This simplistic view of RBCs as O-2 transporter has changed in recent years as other gases, for example, nitric oxide (NO), and small molecules, such as adenosine triphosphate (ATP), have been shown to either be produced and/or carried by RBCs to perform other signaling and O-2 sensing functions. In spite of the numerous biochemical and metabolic changes occurring within RBCs during storage, prior to, and after transfusion, perturbations of RBC membrane are likely to affect blood flow in the microcirculation. Subsequent hemolysis due to storage conditions and/or hemolytic disorders may have some pathophysiological consequences as a result of the release of Hb. In this review, we show that evolution has provided a multitude of protection and intervention strategies against free Hb from "cradle'' to "death''; from early biosynthesis to its final degradation and a lot more in between. Furthermore, some of the same naturally occurring protective mechanisms can potentially be employed to oxidatively inactivate this redox active protein and control its damaging side reactions when released outside of the RBC. Antioxid. Redox Signal. 14, 1713-1728.
C1 [Buehler, Paul W.; Karnaukhova, Elena; Gelderman, Monique P.; Alayash, Abdu I.] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA.
RP Alayash, AI (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, NIH Bldg 29,Rm 112 8800 Rockville Pike, Bethesda, MD 20892 USA.
EM abdu.alayash@fda.hhs.gov
NR 117
TC 18
Z9 19
U1 2
U2 10
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1523-0864
J9 ANTIOXID REDOX SIGN
JI Antioxid. Redox Signal.
PD MAY
PY 2011
VL 14
IS 9
BP 1713
EP 1728
DI 10.1089/ars.2010.3447
PG 16
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 746WL
UT WOS:000289278900012
PM 20954814
ER
PT J
AU Dolan, BP
Bennink, JR
Yewdell, JW
AF Dolan, Brian P.
Bennink, Jack R.
Yewdell, Jonathan W.
TI Translating DRiPs: progress in understanding viral and cellular sources
of MHC class I peptide ligands
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Review
DE Antigen processing; MHC class I; Proteasome; Translation; Virus
ID DEFECTIVE RIBOSOMAL PRODUCTS; VIRUS NUCLEAR ANTIGEN-1; NEWLY SYNTHESIZED
PROTEINS; TOXIC LYMPHOCYTES-T; MESSENGER-RNA TRANSLATION;
NONSENSE-MEDIATED DECAY; ENDOPLASMIC-RETICULUM; MAMMALIAN-CELLS;
PROCESSING PATHWAY; CROSS-PRESENTATION
AB It has been 15 years since we proposed the defective ribosomal product (DRiP) hypothesis to explain the rapid presentation of viral peptides by MHC class I molecules on the surface of infected cells. Here, we review the evidence for the contribution of DRiPs to antigen processing, pointing to the uncertainties regarding the physical nature of DRiPs, and emphasizing recent findings suggesting that peptide generation is a specialized process involving compartmentalized translation.
C1 [Dolan, Brian P.; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
EM jyewdell@nih.gov
RI yewdell, jyewdell@nih.gov/A-1702-2012
FU Division of Intramural Research, NIAID, Bethesda, MD
FX This work was generously supported by the Division of Intramural
Research, NIAID, Bethesda, MD
NR 96
TC 35
Z9 36
U1 1
U2 6
PU BIRKHAUSER VERLAG AG
PI BASEL
PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND
SN 1420-682X
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD MAY
PY 2011
VL 68
IS 9
BP 1481
EP 1489
DI 10.1007/s00018-011-0656-z
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 746LC
UT WOS:000289247300003
PM 21416150
ER
PT J
AU Pham, TTH
Moon, DO
Kim, SO
Kim, KE
Jeong, SJ
Lee, KW
Lee, KS
Jang, JH
Erikson, RL
Ahn, JS
Kim, BY
AF Pham Thi Thu Huong
Moon, Dong-Oh
Kim, Sun Ok
Kim, Kyoon Eon
Jeong, Sook Jung
Lee, Ki Won
Lee, Kyung Sang
Jang, Jae Hyuk
Erikson, Raymond Leo
Ahn, Jong Seog
Kim, Bo Yeon
TI Proteasome inhibitor-I enhances tunicamycin-induced chemosensitization
of prostate cancer cells through regulation of NF-kappa B and CHOP
expression
SO CELLULAR SIGNALLING
LA English
DT Article
DE Proteasome inhibitor-1; Tunicamycin; ER-stress; NF-kappa B; CHOP
ID ENDOPLASMIC-RETICULUM STRESS; APOPTOSIS; DEATH; THERAPY; PATHWAY;
PHOSPHORYLATION; STIMULATION; CASPASE-12; RESISTANCE; ALPHA
AB Although endoplasmic reticulum (ER) stress induction by some anticancer drugs can lead to apoptotic death of cancer cells, combination therapy with other chemicals would be much more efficient. It has been reported that proteasome inhibitors could induce cancer cell death through ER-stress. Our study, however, showed a differential mechanism of proteasome inhibitor-I (Pro-I)-induced cell death. Pro-I significantly enhanced apoptotic death of PO prostate cancer cells pretreated with tunicamycin (TM) while other signaling inhibitors against p38. mitogen activated kinase (MEK) and phosphatidyl-inositol 3-kinase (PI3K) did not, as evidenced by cell proliferation and cell cycle analyses. NF-kappa B inhibition by Pro-I, without direct effect on ER-stress, was found to be responsible for the TM-induced chemosensitization of PC3 cells. Moreover, TM-induced/enhancer-binding protein (C/EBP) homologous protein (CHOP) expression was enhanced by Pro-I without change in GRP78 expression. CHOP knockdown by siRNA also showed a significant decrease in Pro-I chemosensitization. All these data suggest that although TM could induce both NF-kappa B activation and CHOP expression through ER-stress, both NF-kappa B inhibition and increased CHOP level by Pro-I are required for enhanced chemosensitization of PC3 prostate cancer cells. Thus. our study might contribute to the identification of anticancer targets against prostate cancer cells. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Pham Thi Thu Huong; Moon, Dong-Oh; Kim, Sun Ok; Jeong, Sook Jung; Jang, Jae Hyuk; Ahn, Jong Seog; Kim, Bo Yeon] KRIBB, Chem Biol Res Ctr, Ochangeup 363883, Cheongwongun, South Korea.
[Pham Thi Thu Huong; Kim, Kyoon Eon] Chungnam Natl Univ, Coll Nat Sci, Dept Biochem, Taejon 305764, South Korea.
[Lee, Ki Won] Seoul Natl Univ, Ctr Agr Biomat, Dept Agr Biotechnol, Seoul 151921, South Korea.
[Lee, Kyung Sang] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
[Erikson, Raymond Leo] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA.
RP Ahn, JS (reprint author), KRIBB, Chem Biol Res Ctr, 685-1 Yangcheonri, Ochangeup 363883, Cheongwongun, South Korea.
EM jsahn@kribb.re.kr; bykim@kribb.re.kr
FU National Research Foundation of Korea (NRF) [2009-0073109]; Korea
Foundation for International Cooperation of Science and Technology
[M60602000001-06E0200-00100]; Ministry of Education, Science and
Technology (MEST); Ministry of Health Welfare, Korea [0820260]
FX This work was supported by the World Class Institute (WCI) Program,
Nuclear Research Program (2009-0073109) of the National Research
Foundation of Korea (NRF), Global Partnership Program of Korea
Foundation for International Cooperation of Science and Technology
(M60602000001-06E0200-00100), KRIBB Research Initiative Program, all
grants from the Ministry of Education, Science and Technology (MEST),
National R&D Program for Cancer Control (0820260) from the Ministry of
Health & Welfare, Korea.
NR 29
TC 0
Z9 0
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0898-6568
J9 CELL SIGNAL
JI Cell. Signal.
PD MAY
PY 2011
VL 23
IS 5
BP 857
EP 865
DI 10.1016/j.cellsig.2011.01.010
PG 9
WC Cell Biology
SC Cell Biology
GA 742XA
UT WOS:000288977400013
ER
PT J
AU O'Grady, NP
Alexander, M
Burns, LA
Dellinger, EP
Garland, J
Heard, SO
Lipsett, PA
Masur, H
Mermel, LA
Pearson, ML
Raad, II
Randolph, AG
Rupp, ME
Saint, S
AF O'Grady, Naomi P.
Alexander, Mary
Burns, Lillian A.
Dellinger, E. Patchen
Garland, Jeffrey
Heard, Stephen O.
Lipsett, Pamela A.
Masur, Henry
Mermel, Leonard A.
Pearson, Michele L.
Raad, Issam I.
Randolph, Adrienne G.
Rupp, Mark E.
Saint, Sanjay
CA HICPAC
TI Summary of Recommendations: Guidelines for the Prevention of
Intravascular Catheter-related Infections
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Editorial Material
ID CENTRAL VENOUS CATHETERS; BLOOD-STREAM INFECTIONS; INTENSIVE-CARE-UNIT;
RANDOMIZED CONTROLLED-TRIAL; PULMONARY-ARTERY CATHETERS; CRITICALLY-ILL
PATIENTS; DOUBLE-BLIND TRIAL; PERIPHERAL INTRAVENOUS CATHETERS;
SERRATIA-MARCESCENS BACTEREMIA; STERILE BARRIER PRECAUTIONS
C1 [O'Grady, Naomi P.; Masur, Henry] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Alexander, Mary] Infus Nurses Soc, Norwood, MA USA.
[Burns, Lillian A.] Staten Isl Univ Hosp, Staten Isl, NY USA.
[Dellinger, E. Patchen] Univ Washington, Dept Surg, Seattle, WA 98195 USA.
[Garland, Jeffrey] Wheaton Franciscan Healthcare St Joseph, Dept Pediat, Milwaukee, WI USA.
[Heard, Stephen O.] Univ Massachusetts, Sch Med, Dept Anesthesiol, Worcester, MA USA.
[Lipsett, Pamela A.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA.
[Mermel, Leonard A.] Brown Univ, Warren Alpert Med Sch, Div Infect Dis, Providence, RI 02912 USA.
[Mermel, Leonard A.] Rhode Isl Hosp, Providence, RI USA.
[Pearson, Michele L.] CDC, Off Infect Dis, Atlanta, GA 30333 USA.
[Raad, Issam I.] Univ Texas MD Anderson Canc Ctr, Dept Infect Dis, Houston, TX 77030 USA.
[Randolph, Adrienne G.] Childrens Hosp, Dept Anesthesiol, Boston, MA 02115 USA.
[Rupp, Mark E.] Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE USA.
[Saint, Sanjay] Ann Arbor VA Med Ctr, Dept Internal Med, Ann Arbor, MI USA.
[Saint, Sanjay] Univ Michigan, Ann Arbor, MI 48109 USA.
RP O'Grady, NP (reprint author), NIH, Dept Crit Care Med, Bldg 10,Room 2C145,Ctr Dr,MSC 1662, Bethesda, MD 20892 USA.
EM nogrady@mail.cc.nih.gov
OI Randolph, Adrienne/0000-0002-3084-3071
NR 205
TC 105
Z9 114
U1 2
U2 22
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD MAY 1
PY 2011
VL 52
IS 9
BP 1087
EP 1099
DI 10.1093/cid/cir138
PG 13
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 747DR
UT WOS:000289301000003
PM 21467014
ER
PT J
AU O'Grady, NP
Alexander, M
Burns, LA
Dellinger, EP
Garland, J
Heard, SO
Lipsett, PA
Masur, H
Mermel, LA
Pearson, ML
Raad, II
Randolph, AG
Rupp, ME
Saint, S
AF O'Grady, Naomi P.
Alexander, Mary
Burns, Lillian A.
Dellinger, E. Patchen
Garland, Jeffrey
Heard, Stephen O.
Lipsett, Pamela A.
Masur, Henry
Mermel, Leonard A.
Pearson, Michele L.
Raad, Issam I.
Randolph, Adrienne G.
Rupp, Mark E.
Saint, Sanjay
CA HICPAC
TI Guidelines for the Prevention of Intravascular Catheter-related
Infections
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Editorial Material
ID CENTRAL VENOUS CATHETERS; BLOOD-STREAM INFECTION; INTENSIVE-CARE-UNIT;
RANDOMIZED CONTROLLED-TRIAL; PULMONARY-ARTERY CATHETERS; CRITICALLY-ILL
PATIENTS; TOTAL PARENTERAL-NUTRITION; COAGULASE-NEGATIVE STAPHYLOCOCCI;
PERIPHERAL INTRAVENOUS CATHETERS; CUFFED HEMODIALYSIS CATHETERS
C1 [O'Grady, Naomi P.; Masur, Henry] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Alexander, Mary] Infus Nurses Soc, Norwood, MA USA.
[Burns, Lillian A.] Staten Isl Univ Hosp, Staten Isl, NY USA.
[Dellinger, E. Patchen] Univ Washington, Dept Surg, Seattle, WA 98195 USA.
[Garland, Jeffrey] Wheaton Franciscan Healthcare St Joseph, Dept Pediat, Milwaukee, WI USA.
[Heard, Stephen O.] Univ Massachusetts, Sch Med, Dept Anesthesiol, Worcester, MA USA.
[Lipsett, Pamela A.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA.
[Mermel, Leonard A.] Brown Univ, Warren Alpert Med Sch, Div Infect Dis, Providence, RI 02912 USA.
[Mermel, Leonard A.] Rhode Isl Hosp, Providence, RI USA.
[Pearson, Michele L.] CDC, Off Infect Dis, Atlanta, GA 30333 USA.
[Raad, Issam I.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Infect Dis, Houston, TX 77030 USA.
[Randolph, Adrienne G.] Childrens Hosp, Dept Anesthesiol, Boston, MA 02115 USA.
[Rupp, Mark E.] Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE USA.
[Saint, Sanjay] Ann Arbor VA Med Ctr, Dept Internal Med, Ann Arbor, MI USA.
[Saint, Sanjay] Univ Michigan, Ann Arbor, MI 48109 USA.
RP O'Grady, NP (reprint author), NIH, Dept Crit Care Med, Bldg 10,Room 2C145,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA.
EM nogrady@mail.cc.nih.gov
OI Randolph, Adrienne/0000-0002-3084-3071
NR 371
TC 389
Z9 413
U1 3
U2 35
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD MAY 1
PY 2011
VL 52
IS 9
BP E162
EP E193
DI 10.1093/cid/cir257
PG 32
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 747DR
UT WOS:000289301000001
PM 21460264
ER
PT J
AU Liu, YH
Zhang, J
Li, Z
AF Liu, Yinghui
Zhang, Jun
Li, Zhu
TI Perinatal outcomes in native Chinese and Chinese-American women
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE pregnancy outcome; birthweight; preterm birth; stillbirth; migration
ID BIRTH CERTIFICATE DATA; PREGNANCY OUTCOMES; GESTATIONAL-AGE; US-BORN;
UNITED-STATES; WEIGHT; HEALTH; RISK; ACCULTURATION; VALIDATION
AB P>Liu Y, Zhang J, Li Z. Perinatal outcomes in native Chinese and Chinese-American women. Paediatric and Perinatal Epidemiology 2011; 25: 202-209.
This study aimed to compare perinatal outcomes in native Chinese, foreign-born and US-born Chinese-American women by analysing a cohort of 950 624 singleton pregnancies in south-east China and 293 849 singleton births from the US live and stillbirth certificates from 1995 to 2004. Only births at 28 weeks or later were included. Compared with US-born Chinese-American women, native Chinese and foreign-born Chinese-American women had substantially lower risks of having a small-for-gestational age (SGA) infant (adjusted relative risk [aRR] ranging from 0.46 to 0.66) or preterm birth (aRR ranging from 0.53 to 0.82). While having a White or Black father had a reduced risk of SGA (aRR = 0.45 and 0.62, respectively), it has an increased risk for preterm birth (aRR = 1.13 and 1.57, respectively). Infants with Chinese father and foreign-born mother were heavier than those with Chinese father and US-born mothers. All findings were statistically significant. Our findings demonstrated the protective role of foreign-born status on low birthweight and preterm delivery. The paternal contribution to fetal size is substantial.
C1 [Zhang, Jun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA.
[Liu, Yinghui] Peking Univ, Hosp 1, Dept Obstet & Gynecol, Womens & Childrens Hlth Ctr, Beijing, Peoples R China.
[Li, Zhu] Peking Univ, Hlth Sci Ctr, Natl Ctr Maternal & Child Hlth, Beijing 100871, Peoples R China.
RP Zhang, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA.
EM zhangj@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health
FX J Zhang is supported by the Intramural Program of Eunice Kennedy Shriver
National Institute of Child Health and Human Development, National
Institutes of Health.
NR 38
TC 3
Z9 3
U1 0
U2 2
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 MAY
PY 2011
VL 25
IS 3
BP 202
EP 209
DI 10.1111/j.1365-3016.2010.01185.x
PG 8
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 746LE
UT WOS:000289247500001
PM 21470259
ER
PT J
AU Lim, SM
Kim, TH
Jiang, HH
Park, CW
Lee, S
Chen, X
Lee, KC
AF Lim, Sung Mook
Kim, Tae Hyung
Jiang, Hai Hua
Park, Chan Woong
Lee, Seulki
Chen, Xiaoyuan
Lee, Kang Choon
TI Improved biological half-life and anti-tumor activity of TNF-related
apoptosis-inducing ligand (TRAIL) using PEG-exposed nanoparticles
SO BIOMATERIALS
LA English
DT Article
DE Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL);
Polyethylene glycol (PEG); Nanoparticle protein/peptide drug delivery
ID GROWTH-FACTOR; IN-VIVO; CANCER-THERAPY; GENE DELIVERY; STABILITY;
APO2L/TRAIL; RELEASE; DRUG; PHARMACOKINETICS; PEGYLATION
AB TRAIL has received considerable attention as a potential anti-cancer agent due to its specific ability to target tumors. However, recombinant TRAIL has several limitations, such as, its short biological half-life, its inherent instability, and its potential hepatotoxicity. In this study, we developed a sustained release nanoparticle formulation of TRAIL and investigated its therapeutic effects in tumor-bearing mice. TRAIL-loaded nanoparticles (NPs) were prepared by mixing PEGylated heparin (PEG-HE), poly-L-lysine (PLL). and TRAIL NPs prepared by the ionic interaction between polymer and TRAIL showed uniform spherical structures of diameter 213.3 +/- 9.7 nm and a surface charge of 5.33 +/- 1.2 mV. An in vitro study of the bioactivity of TRAIL in NPs showed that TRAIL-loaded PEG-HE/PL. NPs (TRAIL-PEG-NPs) were slightly less cytotoxic than TRAIL in vitro. To investigate pharmacokinetic parameters, TRAIL and TRAIL-PEG-NPs were intravenously injected into SD rats. The PEG-NP-based formulation demonstrated a 28.3 fold greater half-life than TRAIL alone. To evaluate the anti-tumor effect, TRAIL TRAIL-loaded HE/PLL NPs (TRAIL-NPs), and TRAIL-PEG-NPs were intravenously injected into HCT-116 tumor-bearing BALB/c athymic mice. The TRAIL-PEG-NP formulation efficiently suppressed tumor growth (>70%), and histological findings confirmed that NPs induced significant tumor cell apoptosis without inducing liver toxicity. The PEG-exposed NP fabrication method applied in this study could be widely applied to protein and peptide delivery systems. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Lim, Sung Mook; Kim, Tae Hyung; Jiang, Hai Hua; Park, Chan Woong; Lee, Kang Choon] Sungkyunkwan Univ, Coll Pharm, Suwon 440746, South Korea.
[Lee, Seulki; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
RP Lee, KC (reprint author), Sungkyunkwan Univ, Coll Pharm, 300 Cheoncheon Dong, Suwon 440746, South Korea.
EM kclee@skku.edu
FU Korean Ministry of Education, Science, and Technology [2010K001256]
FX This work was supported by a grant from the Korean Ministry of
Education, Science, and Technology (Grant No. 2010K001256).
NR 38
TC 30
Z9 31
U1 4
U2 40
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0142-9612
J9 BIOMATERIALS
JI Biomaterials
PD MAY
PY 2011
VL 32
IS 13
BP 3538
EP 3546
DI 10.1016/j.biomaterials.2011.01.054
PG 9
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 741SM
UT WOS:000288884800019
PM 21306770
ER
PT J
AU Basso, O
Wilcox, AJ
AF Basso, Olga
Wilcox, Allen J.
TI Might Rare Factors Account for Most of the Mortality of Preterm Babies?
SO EPIDEMIOLOGY
LA English
DT Article
ID COLLIDER-STRATIFICATION BIAS; BIRTH-WEIGHT; GESTATIONAL-AGE; PARTURITION
SYNDROME; INFANT-MORTALITY; PREGNANCY; CURVES; RISK; HYPERTENSION;
MATURATION
AB Background: Preterm delivery has a variety of causes, with each of these presumably carrying its own mortality risk. To the extent that they add to the risk of mortality, the various pathologic factors triggering preterm delivery will confound the causal contribution of gestational age to mortality, inflating the observed rates of gestational-age-specific mortality. We have previously estimated that about half of the mortality of US preterm singletons may be due to unmeasured pathologies that increase mortality risk and also cause preterm birth. In this paper, we examine the impact that rare factors may have, at least in theory, on preterm mortality.
Methods: We constructed a simple model of gestational-age-specific mortality, in which we arbitrarily selected a function to represent the mortality due to immaturity alone ("baseline" risk). We then added "unmeasured" confounding factors that cause mortality and also cause preterm birth. This construct allowed us to calculate, in simple scenarios, the proportion of preterm mortality that could be caused by unmeasured confounding.
Results: We found that rare pathologies with moderate-to-strong effects can substantially contribute to preterm mortality. The presence of such rare factors can also produce an intersection of gestational-age-specific mortality curves when stratifying by known risk factors.
Conclusions: It is possible that a few relatively rare factors may account for a large fraction of preterm mortality. The search for such factors should be a primary focus of future research on preterm delivery.
C1 [Basso, Olga] McGill Univ, Royal Victoria Hosp, Dept Obstet & Gynecol, Montreal, PQ H3A 1A1, Canada.
[Basso, Olga] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 1A1, Canada.
[Basso, Olga; Wilcox, Allen J.] NIEHS, Epidemiol Branch, Durham, NC USA.
RP Basso, O (reprint author), McGill Univ, Royal Victoria Hosp, Dept Obstet & Gynecol, 687 Pine Ave W,Room F9-05, Montreal, PQ H3A 1A1, Canada.
EM olga.basso@mcgill.ca
RI Basso, Olga/E-5384-2010;
OI Basso, Olga/0000-0001-9298-4921; Wilcox, Allen/0000-0002-3376-1311
FU NIH, National Institute of Environmental Health Sciences [Z01 ES044003]
FX Supported in part by the Intramural program of the NIH, National
Institute of Environmental Health Sciences (Z01 ES044003).
NR 32
TC 16
Z9 16
U1 1
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD MAY
PY 2011
VL 22
IS 3
BP 320
EP 327
DI 10.1097/EDE.0b013e31821266c5
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 745DG
UT WOS:000289144600009
PM 21372718
ER
PT J
AU Shi, M
Umbach, DM
Weinberg, CR
AF Shi, Min
Umbach, David M.
Weinberg, Clarice R.
TI Family-based Gene-by-environment Interaction Studies Revelations and
Remedies
SO EPIDEMIOLOGY
LA English
DT Article
ID CASE-PARENT TRIADS; LINKAGE DISEQUILIBRIUM; ASSOCIATION; TESTS;
GENOTYPE; JOINT; INDEPENDENCE; EXPOSURES; DESIGN; POWER
AB Bias can arise in case-control studies of genotype effects if the underlying population is structured (genetically stratified or admixed). Nuclear-family-based studies enjoy robustness against such bias, provided that inference conditions properly on the parents. Investigators have extended family-based methods to study gene-by-environment interactions, regarding such extensions as retaining robustness. We demonstrate via simulations that, if population structure involves the exposure, nuclear-family-based analyses of gene-by-exposure interaction remain vulnerable to inflated Type I error rates through subtle dependencies that investigators have failed to appreciate. Motivated by the Two Sister Study, an ongoing study of families affected by young-onset breast cancer, we consider a design that supplements the case-parents design with a sibling who is not genotyped but provides exposure data. If, in the population at large, inheritance is Mendelian and genotypes do not influence propensity for exposure, then this 4-person (or tetrad) structure permits the study of genetic effects, exposure effects, and genotype-by-exposure interactions. We show for a dichotomous exposure that, when exposure of an unaffected sibling is available, a modification to the analysis of case-sib or tetrad data re-establishes robustness for tests of multiplicative gene-by-environment interaction. We also use simulations to assess the power for detecting interaction across a range of scenarios, designs, and analytic methods.
C1 [Shi, Min; Umbach, David M.; Weinberg, Clarice R.] NIEHS, Biostat Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Weinberg, CR (reprint author), NIEHS, Biostat Branch, NIH, DHHS, Mail Drop A3-03 101-A315, Res Triangle Pk, NC 27709 USA.
EM weinber2@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences [Z01-ES040007,
Z01-ES45002]
FX Supported by the Intramural Research Program of the NIH, National
Institute of Environmental Health Sciences (Z01-ES040007; Z01-ES45002).
NR 31
TC 10
Z9 10
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD MAY
PY 2011
VL 22
IS 3
BP 400
EP 407
DI 10.1097/EDE.0b013e318212fec6
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 745DG
UT WOS:000289144600021
PM 21490534
ER
PT J
AU Hallett, M
AF Hallett, Mark
TI Neurophysiology of dystonia: The role of inhibition
SO NEUROBIOLOGY OF DISEASE
LA English
DT Review
DE Dystonia; Physiology; Inhibition; Motor control; GABA; Surround
inhibition; Sensory function; Sensorimotor integration; Basal ganglia;
Transcranial magnetic stimulation
ID FOCAL HAND DYSTONIA; HUMAN MOTOR CORTEX; TRANSCRANIAL MAGNETIC
STIMULATION; PRIMARY SOMATOSENSORY CORTEX; CONTINGENT
NEGATIVE-VARIATION; LATENCY AFFERENT INHIBITION; HIGH-FREQUENCY
OSCILLATIONS; PALSY-INDUCED BLEPHAROSPASM; TONIC VIBRATION REFLEX;
TASK-SPECIFIC DYSTONIA
AB The pathophysiology of dystonia has been best studied in patients with focal hand dystonia. A loss of inhibitory function has been demonstrated at spinal, brainstem and cortical levels. Many cortical circuits seem to be involved. One consequence of the loss of inhibition is a failure of surround inhibition. and this appears to directly lead to overflow and unwanted muscle spasms. There are mild sensory abnormalities and deficits in sensorimotor integration; these also might be explained by a loss of inhibition. Increasing inhibition may be therapeutic. A possible hypothesis is that there is a genetic loss of inhibitory interneurons in dystonia and that this deficit is a substrate on which other factors can act to produce dystonia. This article is part of a Special Issue entitled "Advances in dystonia". Published by Elsevier Inc.
C1 Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
RP Hallett, M (reprint author), Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, Bldg 10,Room 7D37,10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA.
EM hallettm@ninds.nih.gov
FU Intramural NIH HHS [ZIA NS003031-03]
NR 114
TC 95
Z9 97
U1 0
U2 15
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0969-9961
EI 1095-953X
J9 NEUROBIOL DIS
JI Neurobiol. Dis.
PD MAY
PY 2011
VL 42
IS 2
SI SI
BP 177
EP 184
DI 10.1016/j.nbd.2010.08.025
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 743LE
UT WOS:000289019000008
PM 20817092
ER
PT J
AU Jouhanneau, JS
Ball, SM
Molnar, E
Isaac, JTR
AF Jouhanneau, Jean-Sebastien
Ball, Simon M.
Molnar, Elek
Isaac, John T. R.
TI Mechanisms of bi-directional modulation of thalamocortical transmission
in barrel cortex by presynaptic kainate receptors
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Synaptic transmission; Presynaptic mechanisms; Kainate receptors; Barrel
cortex
ID MOSSY-FIBER SYNAPSES; LONG-TERM POTENTIATION; SYNAPTIC-TRANSMISSION;
GLUTAMATE-RECEPTOR; ION CHANNELS; RAT-BRAIN; DEVELOPMENTAL-CHANGES;
SOMATOSENSORY CORTEX; DEPENDENT REGULATION; GABAERGIC SYNAPSES
AB Presynaptic kainate receptors play an important role in synaptic transmission and short-term plasticity to profoundly regulate network activity in many parts of the mammalian brain. In primary sensory neocortex, where short-term synaptic plasticity is important for receptive field structure and information processing, kainate receptors are highly expressed and regulate thalamocortical inputs, particularly during development. However, the mechanisms of the kainate receptor-dependent presynaptic regulation of thalamocortical transmission are unclear. We therefore investigated this issue using electrophysiology in neonatal thalamocortical slices of barrel cortex combined with pharmacology and biochemical analyses. We show that presynaptic kainate receptors can both facilitate or depress synaptic transmission depending on the extent of their activation. This bi-directional regulation is mediated in part by kainate receptors that directly influence thalamocortical axonal excitability, but also likely involves receptors acting at thalamocortical terminals to regulate transmitter release. The efficacy of kainate in regulating thalamocortical transmission is low compared to that reported for other inputs. Consistent with this low efficacy, our biochemical analyses indicate that the presynaptic kainate receptors regulating neonatal thalamocortical inputs likely lack the high kainate affinity GluK4 and 5 subunits. Thus thalamocortical transmission can be bi-directionally regulated by low affinity kainate receptors through two mechanisms. Such presynaptic regulation provides a potentially powerful mechanism to influence sensory processing during development of barrel cortex. (C) 2010 Published by Elsevier Ltd.
C1 [Jouhanneau, Jean-Sebastien; Isaac, John T. R.] NINDS, Dev Synapt Plast Sect, NIH, Bethesda, MD 20892 USA.
[Ball, Simon M.; Molnar, Elek] Univ Bristol, MRC Ctr Synapt Plast, Sch Physiol & Pharmacol, Bristol BS8 1TD, Avon, England.
RP Isaac, JTR (reprint author), Eli Lilly & Co, Erl Wood Manor, Windlesham GU20 6PH, Surrey, England.
EM isaacjo@lilly.com
FU MRC [G0601509]; Wellcome Trust; NINDS
FX We are very grateful to Dr. Christophe Mulle for advice on the study and
comments on the manuscript. This work supported by the MRC (G0601509,
E.M.), Wellcome Trust (J.T.R.I., E.M.) and NINDS Intramural Program
(J.T.R.I.). SMB was an MRC funded PhD student.
NR 61
TC 6
Z9 6
U1 0
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD MAY
PY 2011
VL 60
IS 6
BP 832
EP 841
DI 10.1016/j.neuropharm.2010.12.023
PG 10
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 744ZH
UT WOS:000289133200002
PM 21187105
ER
PT J
AU Moaddel, R
Rosenberg, A
Spelman, K
Frazier, J
Frazier, C
Nocerino, S
Brizzi, A
Mugnaini, C
Wainer, IW
AF Moaddel, R.
Rosenberg, A.
Spelman, K.
Frazier, J.
Frazier, C.
Nocerino, S.
Brizzi, A.
Mugnaini, C.
Wainer, I. W.
TI Development and characterization of immobilized cannabinoid receptor
(CB1/CB2) open tubular column for on-line screening
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Article
DE Biochromatography; Basophils; Zanthoxylum; Cannabinoids; KU-812
ID P-GLYCOPROTEIN; CB2 RECEPTORS; IN-VIVO; AFFINITY; CHROMATOGRAPHY;
BINDING; IDENTIFICATION; PHARMACOLOGY; ALKYLAMIDES; EXPRESSION
AB Cannabinoid receptors, CB1 and CB2, are therapeutic targets in the treatment of anxiety, obesity, movement disorders, glaucoma, and pain. We have developed an on-line screening method for CB1 and CB2 ligands, where cellular membrane fragments of a chronic myelogenous leukemia cell line, KU-812, were immobilized onto the surface of an open tubular (OT) capillary to create a CB1/CB2-OT column. The binding activities of the immobilized CB1/CB2 receptors were established using frontal affinity chromatographic techniques. This is the first report that confirms the presence of functional CB1 and CB2 receptors on KU-812 cells. The data from this study confirm that the CB1/CB2-OT column can be used to determine the binding affinities (K(i) values) for a single compound and to screen individual compounds or a mixture of multiple compounds. The CB1/CB2-OT column was also used to screen a botanical matrix, Zanthoxylum clava-herculis, where preliminary results suggest the presence of a high-affinity phytocannabinoid. Published by Elsevier Inc.
C1 [Moaddel, R.; Rosenberg, A.; Spelman, K.; Frazier, J.; Frazier, C.; Wainer, I. W.] NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA.
[Nocerino, S.; Brizzi, A.; Mugnaini, C.] Univ Siena, Dipartimento Farm Chim Tecnol, I-53100 Siena, Italy.
RP Moaddel, R (reprint author), NIA, Gerontol Res Ctr, NIH, 4940 Eastern Ave, Baltimore, MD 21224 USA.
EM moaddelru@grc.nia.nih.gov
FU National Institute on Aging/National Institutes of Health
FX This research was supported in part by the Intramural Research Program
of the National Institute on Aging/National Institutes of Health.
NR 31
TC 22
Z9 22
U1 0
U2 27
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 MAY 1
PY 2011
VL 412
IS 1
BP 85
EP 91
DI 10.1016/j.ab.2010.12.034
PG 7
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 737SY
UT WOS:000288589700012
PM 21215722
ER
PT J
AU Robinson, GW
Hennighausen, L
AF Robinson, Gertraud W.
Hennighausen, Lothar
TI MMTV-Cre transgenes can adversely affect lactation: Considerations for
conditional gene deletion in mammary tissue
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Article
DE Mouse mammary tumor virus; Long terminal repeat; CRE recombinase;
Mammary gland; Lactation; Transgenic mice
ID GLAND; EXPRESSION; EPITHELIUM; PREGNANCY; SURVIVAL; CELLS; LEADS; MICE
AB CRE-loxP-mediated inactivation and activation of genes in mouse mammary epithelium have been widely used to study genetic pathways in normal development and neoplastic transformation in vivo. In 1997, we generated three distinct mouse lines carrying an identical MMTV-Cre transgene (lines A, D, and F). Because the presence of CRE recombinase can adversely affect the physiology of nonmammary cells, we explored whether transgenic females display lactational defects. Whereas dams from line D nurse their pups and display overtly normal mammary development, line A shows some impairment during lactation and females from line F completely fail to nurse their litters. The ability to nurse a litter correlates with the extent of alveolar development and differentiation. This study demonstrates the importance of including appropriate "Cre-only" controls and provides guidelines to avoid problems in data interpretation. Published by Elsevier Inc.
C1 [Robinson, Gertraud W.; Hennighausen, Lothar] NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA.
RP Robinson, GW (reprint author), NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA.
EM traudl@nih.gov
RI Robinson, Gertraud/I-2136-2012
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX Oksana Gavrilova is gratefully acknowledged for help with statistical
analyses. This work was supported by the Intramural Research Program of
the National Institute of Diabetes and Digestive and Kidney Diseases.
NR 19
TC 13
Z9 13
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 0003-2697
J9 ANAL BIOCHEM
JI Anal. Biochem.
PD MAY 1
PY 2011
VL 412
IS 1
BP 92
EP 95
DI 10.1016/j.ab.2011.01.020
PG 4
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 737SY
UT WOS:000288589700013
PM 21255551
ER
PT J
AU Stabinski, L
Reynolds, SJ
Ocama, P
Laeyendecker, O
Serwadda, D
Gray, RH
Wawer, M
Thomas, DL
Quinn, TC
Kirk, GD
AF Stabinski, Lara
Reynolds, Steven J.
Ocama, Ponsiano
Laeyendecker, Oliver
Serwadda, David
Gray, Ron H.
Wawer, Maria
Thomas, David L.
Quinn, Thomas C.
Kirk, Gregory D.
TI Hepatitis B Virus and Sexual Behavior in Rakai, Uganda
SO JOURNAL OF MEDICAL VIROLOGY
LA English
DT Article
DE hepatitis B virus (HBV); HIV; sexual transmission; Uganda; Africa
ID RISK-FACTORS; TRANSMISSION PATTERNS; VIRAL-HEPATITIS; C VIRUSES;
INFECTION; EPIDEMIOLOGY; TANZANIA; SYPHILIS; AFRICA; SEROPREVALENCE
AB HIV and hepatitis B virus (HBV) co-infection poses important public health considerations in resource-limited settings. Demographic data and sera from adult participants of the Rakai Health Sciences Program Cohort in Southwestern Uganda were examined to determine HBV seroprevalence patterns in this area of high HIV endemicity prior to the introduction of anti-retroviral therapy. Commercially available EIAs were used to detect prevalent HBV infection (positive for HBV core antibody [anti-HBc] and/or positive HBV surface antigen [HBsAg]), and chronic infection (positive for HBsAg). Of 438 participants, 181 (41%) had prevalent HBV infection while 21 (5%) were infected chronically. Fourteen percent of participants were infected with HIV. Fifty three percent showed evidence of prevalent HBV infection compared to 40% among participants infected with HIV (P = 0.067). Seven percent of participants infected with HIV were HBsAg positive compared to 4% among participants not infected with HIV (P = 0.403). The prevalence of prevalent HBV infection was 55% in adults aged > 50 years old, and 11% in persons under 20 years. In multivariable analysis, older age, HIV status, and serologic syphilis were significantly associated with prevalent HBV infection. Transfusion status and receipt of injections were not significantly associated with HBV infection. Contrary to expectations that HBV exposure in Uganda occurred chiefly during childhood, prevalent HBV infection was found to increase with age and was associated sexually transmitted diseases (HIV and syphilis.) Therefore vaccination against HBV, particularly susceptible adults with HIV or at risk of HIV/STDs should be a priority. J. Med. Virol. 83:796-800, 2011. (C) 2011 Wiley-Liss, Inc.
C1 [Stabinski, Lara; Reynolds, Steven J.; Laeyendecker, Oliver; Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Reynolds, Steven J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Johns Hopkins Ctr Global Hlth, Baltimore, MD USA.
[Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda.
[Serwadda, David; Gray, Ron H.; Wawer, Maria] Rakai Hlth Sci Program, Entebbe, Uganda.
[Gray, Ron H.; Wawer, Maria] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, Baltimore, MD USA.
[Thomas, David L.; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Kirk, Gregory D.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
RP Stabinski, L (reprint author), Rangos Bldg,Room 530,855 N,Wolfe St, Baltimore, MD USA.
EM stabinskil@niaid.nih.gov
RI Laeyendecker, Oliver/B-9331-2009;
OI Laeyendecker, Oliver/0000-0002-6429-4760
FU NIH, National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Bethesda, Maryland
FX Grant sponsor: The Intramural Research Program of the NIH, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, Bethesda, Maryland.
NR 30
TC 6
Z9 6
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0146-6615
J9 J MED VIROL
JI J. Med. Virol.
PD MAY
PY 2011
VL 83
IS 5
BP 796
EP 800
DI 10.1002/jmv.22051
PG 5
WC Virology
SC Virology
GA 736BL
UT WOS:000288464400007
PM 21412787
ER
PT J
AU Laassri, M
Bidzhieva, B
Speicher, J
Pletnev, AG
Chumakov, K
AF Laassri, Majid
Bidzhieva, Bella
Speicher, James
Pletnev, Alexander G.
Chumakov, Konstantin
TI Microarray Hybridization for Assessment of the Genetic Stability of
Chimeric West Nile/Dengue 4 Virus
SO JOURNAL OF MEDICAL VIROLOGY
LA English
DT Article
DE flavivirus vaccine; mutants screening; mutants quantitation; molecular
consistency; quality control
ID BORNE ENCEPHALITIS-VIRUS; YELLOW-FEVER VIRUS; DENGUE VIRUS; NILE-VIRUS;
OLIGONUCLEOTIDE MICROARRAY; POLIOVIRUS VACCINE; ATTENUATED VACCINE;
NONHUMAN-PRIMATES; RHESUS-MONKEYS; LIVE
AB Genetic stability is an important characteristic of live viral vaccines because an accumulation of mutants can cause reversion to a virulent phenotype as well as a loss of immunogenic properties. This study was aimed at evaluating the genetic stability of a live attenuated West Nile (WN) virus vaccine candidate that was generated by replacing the pre-membrane and envelope protein genes of dengue 4 virus with those from WN. Chimeric virus was serially propagated in Vero, SH-SY5Y human neuroblastoma and HeLa cells and screened for point mutations using hybridization with microarrays of overlapping oligonucleotide probes covering the entire genome. The analysis revealed several spontaneous mutations that led to amino acid changes, most of which were located inthe envelope (E) and non-structural NS4A, NS4B, and NS5 proteins. Viruses passaged in Vero and SH-SY5Y cells shared two common mutations: G(2337)C (Met(457)Ile) in the E gene and A(6751)G (Lys(125)Arg) in the NS4A gene. Quantitative assessment of the contents of these mutants in viral stocks indicated that they accumulated independently with different kinetics during propagation in cell cultures. Mutant viruses grew better in Vero cells compared to the parental virus, suggesting that they have a higher fitness. When tested in newborn mice, the cell culture-passaged viruses did not exhibit increased neurovirulence. The approach described in this article could be useful for monitoring the molecular consistency and quality control of vaccine strains. J. Med. Virol. 83:910-920, 2011. (C) 2011 Wiley-Liss, Inc.
C1 [Laassri, Majid; Bidzhieva, Bella; Chumakov, Konstantin] US FDA, Lab Method Dev, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA.
[Speicher, James; Pletnev, Alexander G.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Chumakov, K (reprint author), US FDA, Lab Method Dev, Ctr Biol Evaluat & Res, 1401 Rockville Pike HFM-470, Rockville, MD 20852 USA.
EM apletnev@niaid.nih.gov; konstantin.chumakov@fda.hhs.gov
FU National Institute of Allergy and Infectious Diseases, Division of
Microbiology and Infectious Diseases [224-06-1322/Y1-AI-6153-01]
FX Grant sponsor: National Institute of Allergy and Infectious Diseases,
Division of Microbiology and Infectious Diseases; Grant number:
Interagency agreement number between FDA and NIH,
224-06-1322/Y1-AI-6153-01.
NR 32
TC 8
Z9 9
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0146-6615
J9 J MED VIROL
JI J. Med. Virol.
PD MAY
PY 2011
VL 83
IS 5
BP 910
EP 920
DI 10.1002/jmv.22033
PG 11
WC Virology
SC Virology
GA 736BL
UT WOS:000288464400025
PM 21360544
ER
PT J
AU Ho, M
Feng, MQ
Fisher, RJ
Rader, C
Pastan, I
AF Ho, Mitchell
Feng, Mingqian
Fisher, Robert J.
Rader, Christoph
Pastan, Ira
TI A novel high-affinity human monoclonal antibody to mesothelin
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE human monoclonal antibody; mesothelin; CA125/MUC16; mesothelioma;
ovarian cancer
ID OVARIAN-CANCER ANTIGEN; IN-VITRO; EXTRACELLULAR SUPERSTRUCTURE;
ANTITUMOR-ACTIVITY; MOLECULAR-CLONING; PHAGE DISPLAY; CELL-ADHESION;
TUMOR-CELLS; CA-125 GENE; IMMUNOTOXIN
AB Mesothelin is a glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed on the cell surface of mesothelioma, ovarian cancer and other malignant tumors. The interaction between mesothelin and CA125 (also called MUC16) may facilitate the implantation and metastasis of tumors in the peritoneal cavity. A desirable therapeutic agent involves finding a fully human monoclonal antibody (mAb) that binds to mesothelin or CA125 and inhibits their interaction. Here, we report the identification of a novel human mAb to mesothelin. HN1, a human single-chain Fv specific for mesothelin, was isolated from a naive human single-chain variable fragment (scFv) phage display library. To investigate HN1 as a potential therapeutic, we generated a fully human IgG with the gamma 1 heavy chain and the kappa light chain and an immuntoxin by fusing the HN1 scFv to a truncated Pseudomonas exotoxin A. The HN1 IgG kills cancer cells with very strong antibody-dependent cell-mediated cytotoxicity. HN1 binds a conformation-sensitive epitope in human mesothelin with high affinity (K-D = 3 nM). The HN1 epitope is different from that of SS1, a mouse Fv used to develop therapeutic antibodies that are currently in clinical trials. HN1 binds to cell surface-associated mesothelin on human mesothelioma, ovarian cancer, lung adenocarcinoma and pancreatic cancer cells. In addition, HN1 can functionally block the interaction of mesothelin and CA125 on cancer cells. Most importantly, because the HN1 immuntoxin kills mesothelin-expressing cancer cells with high cytotoxic activity, we believe that it has significant potential for mesothelin-expressing cancer treatment and diagnosis. Published 2010 UICC. This article is a US Government work and, as such, is in the public domain of the United States of America.
C1 [Ho, Mitchell; Feng, Mingqian; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Fisher, Robert J.] SAIC Frederick Natl Canc Inst, Prot Chem Lab, Frederick, MD USA.
[Rader, Christoph] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Ho, M (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5002C, Bethesda, MD 20892 USA.
EM homi@mail.nih.gov
RI Ho, Mitchell/F-5059-2015
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer
Research; Ovarian Cancer Research Fund Individual Investigator Award;
Mesothelioma Applied Research Foundation
FX Grant sponsor: National Cancer Institute, National Institutes of Health;
Grant number: HHSN261200800001E; Grant sponsors: Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research, Ovarian Cancer Research Fund Individual Investigator Award,
Mesothelioma Applied Research Foundation Grant in Honor of Craig Kozicki
NR 36
TC 30
Z9 30
U1 1
U2 14
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD MAY 1
PY 2011
VL 128
IS 9
BP 2020
EP 2030
DI 10.1002/ijc.25557
PG 11
WC Oncology
SC Oncology
GA 732HW
UT WOS:000288176600003
PM 20635390
ER
PT J
AU Decrausaz, L
Goncalves, AR
Domingos-Pereira, S
Pythoud, C
Stehle, JC
Schiller, J
Jichlinski, P
Nardelli-Haefliger, D
AF Decrausaz, Loane
Goncalves, Ana-Rita
Domingos-Pereira, Sonia
Pythoud, Christelle
Stehle, Jean-Christophe
Schiller, John
Jichlinski, Patrice
Nardelli-Haefliger, Denise
TI A novel mucosal orthotopic murine model of human
papillomavirus-associated genital cancers
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE human papillomavirus; cervical cancer; genital tumor model; therapeutic
vaccination
ID REGULATORY T-CELLS; CERVICAL-CANCER; MOUSE MODEL; INFECTION; RESPONSES;
TRANSMISSION; MICROBICIDES; INFLAMMATION; VACCINATION; PROGRESSION
AB Cervical cancer results from infection with high-risk type human papillomaviruses (HPV). Therapeutic vaccines aiming at controlling existing genital HPV infections and associated lesions are usually tested in mice with HPV-expressing tumor cells subcutaneously implanted into their flank. However, effective vaccine-induced regression of these ectopic tumors strongly contrasts with the poor clinical results of these vaccines produced in patients with HPV-associated genital neoplasia. To assess HPV therapeutic vaccines in a more relevant setting, we have, here, established an orthotopic mouse model where tumors in the genital mucosa (GM) develop after an intravaginal instillation of HPV16 E6/E7-expressing tumor cells transduced with a luciferase-encoding lentiviral vector for in vivo imaging of tumor growth. Tumor take was 80-90% after nonoxynol-9 induced damage of the epithelium. Tumors remained localized in the genital tract, and histological analysis showed that most tumors grew within the squamous epithelium of the vaginal wall. Those tumors induced (i) E7-specific CD8 T cells restricted to the GM and draining lymph nodes, in agreement with their mucosal location and (ii) high Foxp3+ CD4+ infiltrates, similarly to those found in natural non-regressing HPV lesions. This novel genital HPV-tumor model by requiring GM homing of vaccine-induced immune responses able to overcome local immuno-suppression may be more representative of the situation occurring in patients upon therapeutic vaccination.
C1 [Nardelli-Haefliger, Denise] CHUV, IMUL, Dept Urol, CH-1011 Lausanne, Switzerland.
[Decrausaz, Loane; Goncalves, Ana-Rita; Domingos-Pereira, Sonia; Pythoud, Christelle; Stehle, Jean-Christophe; Jichlinski, Patrice; Nardelli-Haefliger, Denise] Univ Lausanne, Lausanne, Switzerland.
[Stehle, Jean-Christophe] CHUV, Inst Pathol, CH-1011 Lausanne, Switzerland.
[Schiller, John] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
RP Nardelli-Haefliger, D (reprint author), CHUV, IMUL, Dept Urol, Bugnon 48, CH-1011 Lausanne, Switzerland.
EM dnardell@hospvd.ch
OI nardelli-haefliger, denise/0000-0003-1812-9905
FU Swiss National Science Foundation [310000-112406]; Oncosuisse
[02304-082008]
FX Grant sponsor: Swiss National Science Foundation; Grant number:
310000-112406; Grant sponsor: Oncosuisse; Grant number: 02304-082008
NR 27
TC 14
Z9 15
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD MAY 1
PY 2011
VL 128
IS 9
BP 2105
EP 2113
DI 10.1002/ijc.25561
PG 9
WC Oncology
SC Oncology
GA 732HW
UT WOS:000288176600011
PM 20635385
ER
PT J
AU Feng, MQ
Kim, H
Phung, Y
Ho, M
AF Feng, Mingqian
Kim, Heungnam
Phung, Yen
Ho, Mitchell
TI Recombinant soluble glypican 3 protein inhibits the growth of
hepatocellular carcinoma in vitro
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Letter
C1 [Feng, Mingqian; Kim, Heungnam; Phung, Yen; Ho, Mitchell] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Ho, M (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5002C, Bethesda, MD 20892 USA.
EM homi@mail.nih.gov
RI Ho, Mitchell/F-5059-2015
FU Intramural NIH HHS [Z01 BC010891-01, Z99 CA999999, ZIA BC010891-02]
NR 5
TC 15
Z9 19
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD MAY 1
PY 2011
VL 128
IS 9
BP 2246
EP 2247
DI 10.1002/ijc.25549
PG 2
WC Oncology
SC Oncology
GA 732HW
UT WOS:000288176600028
PM 20617511
ER
PT J
AU Lewis, DR
AF Lewis, D. Riedel
TI OVERVIEW OF HODGKIN LYMPHOMA FROM THE SURVEILLANCE EPIDEMIOLOGY AND END
RESULTS (SEER) REGISTRIES
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Lewis, D. Riedel] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD MAY
PY 2011
VL 56
IS 5
MA II-2
BP 877
EP 877
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 731TK
UT WOS:000288132100044
ER
PT J
AU Austin, BP
Tozser, J
Bagossi, P
Tropea, JE
Waugh, DS
AF Austin, Brian P.
Toezser, Jozsef
Bagossi, Peter
Tropea, Joseph E.
Waugh, David S.
TI The substrate specificity of Metarhizium anisopliae and Bos taurus
carboxypeptidases A: Insights into their use as tools for the removal of
affinity tags
SO PROTEIN EXPRESSION AND PURIFICATION
LA English
DT Article
DE Carboxypeptidase; Affinity tag; Polyhistidine tag; His-tag; Protease
ID YERSINIA-PESTIS; 3-DIMENSIONAL STRUCTURE; PROCARBOXYPEPTIDASE A2;
PROTEINASES; CLONING; SENSITIVITY; SEQUENCE; ZYMOGEN; BINDING; FAMILY
AB Carboxypeptidases may serve as tools for removal of C-terminal affinity tags. In the present study, we describe the expression and purification of an A-type carboxypeptidase from the fungal pathogen Metarhizium anisopliae (MeCPA) that has been genetically engineered to facilitate the removal of polyhistidine tags from the C-termini of recombinant proteins. A complete, systematic analysis of the specificity of MeCPA in comparison with that of bovine carboxypeptidase A (BoCPA) was carried out. Our results indicate that the specificity of the two enzymes is similar but not identical. Histidine residues are removed more efficiently by MeCPA. The very inefficient digestion of peptides with C-terminal lysine or arginine residues, along with the complete inability of the enzyme to remove a C-terminal proline, suggests a strategy for designing C-terminal affinity tags that can be trimmed by MeCPA (or BoCPA) to produce a digestion product with a homogeneous endpoint. Published by Elsevier Inc.
C1 [Austin, Brian P.; Tropea, Joseph E.; Waugh, David S.] NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Toezser, Jozsef; Bagossi, Peter] Univ Debrecen, Fac Med, Dept Biochem & Mol Biol, H-4012 Debrecen, Hungary.
RP Waugh, DS (reprint author), NCI, Macromol Crystallog Lab, Ctr Canc Res, POB B, Frederick, MD 21702 USA.
EM waughd@mail.nih.gov
RI Tozser, Jozsef/A-7840-2008;
OI Tozser, Jozsef/0000-0003-0274-0056; Tozser, Jozsef/0000-0001-5076-8729
FU NIH; National Cancer Institute; Center for Cancer Research
FX This research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research.
Electrospray mass spectrometry experiments were conducted on the LC/ESMS
instrument maintained by the Biophysics Resource in the Structural
Biophysics Laboratory, Center for Cancer Research, National Cancer
Institute at Frederick. We thank the staff of the SAIC-Frederick Protein
Expression Laboratory for assistance with the construction of a
recombinant baculovirus for the production of MeCPA.
NR 27
TC 6
Z9 6
U1 0
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-5928
EI 1096-0279
J9 PROTEIN EXPRES PURIF
JI Protein Expr. Purif.
PD MAY
PY 2011
VL 77
IS 1
BP 53
EP 61
DI 10.1016/j.pep.2010.11.005
PG 9
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA 733SW
UT WOS:000288284200007
PM 21073956
ER
PT J
AU Yothers, G
Sampson, AR
AF Yothers, Greg
Sampson, Allan R.
TI Simultaneous confidence band for the difference of segmented linear
models (vol 141, pg 1059, 2011)
SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE
LA English
DT Correction
C1 [Yothers, Greg] Univ Pittsburgh, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15260 USA.
Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15260 USA.
RP Yothers, G (reprint author), Univ Pittsburgh, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15260 USA.
EM yothers@nsabp.pitt.edu
OI Yothers, Greg/0000-0002-7965-7333
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-3758
J9 J STAT PLAN INFER
JI J. Stat. Plan. Infer.
PD MAY
PY 2011
VL 141
IS 5
BP 2004
EP 2005
DI 10.1016/j.jspi.2010.11.042
PG 2
WC Statistics & Probability
SC Mathematics
GA 721EU
UT WOS:000287337200037
ER
PT J
AU Feng, YA
He, XZ
Yang, YL
Chen, JS
Yin, KS
Xia, Y
AF Feng, Yuan
He, Xiaozhou
Yang, Yilin
Chen, Jingshan
Yin, Kaisheng
Xia, Ying
TI Effect of Delta-Opioid Receptor Over-Expression on Cortical Expression
of GABA(A) Receptor alpha 1-Subunit in Hypoxia
SO CHINESE JOURNAL OF PHYSIOLOGY
LA English
DT Article
DE GABA receptor; delta-opioid receptor; cortex; hypoxia
ID RAT MODEL; FOREBRAIN ISCHEMIA; NEUROPROTECTION; SURVIVAL; IMMATURE;
AGONIST; NEURONS; INJURY; CORTEX; BRAIN
AB Recent studies show that both delta-opioid receptors (DOR) and GABA receptors play a neuroprotective role in the mature cortex. Since we have observed that DOR over-expression renders the cortex more tolerant to hypoxic stress, we asked whether DOR over-expression affects GABA receptors expression in the cortex under hypoxia. As the first step, we investigated the expression of GABA(A) receptor alpha 1-subunit (GABA(A) R alpha 1, the most abundant alpha-subunit of GABA receptors in the adult brain) in the mouse cortex with transgenic DOR over-expression after hypoxia. The results showed that GABA(A) R alpha 1 expression was lower in the transgenic than wild-type cortex, suggesting that DOR overexpression induces an inhibitory effect on GABA(A) receptor expression. Hypoxia for 1-3 days significantly increased GABA(A) R alpha 1 expression in the wild-type cortex, which may be an adaptive strategy for protecting the cortex against hypoxic stress. interestingly, such increase was not found in the transgenic cortex with DOR over-expression. This may represent an interactive regulation in the transgenic cortex to efficiently balance energy production and consumption for better adaptation to hypoxic environment. Since DOR over-expression increases cortical tolerance to hypoxia, an increase in GABA receptors expression (an energy-costing process) may not be necessary in the cortex with DOR over-expression.
C1 [Xia, Ying] Univ Texas Med Sch, Vivian L Smith Dept Neurosurg, Houston, TX 77030 USA.
[Chen, Jingshan] NIMH, NIH, Bethesda, MD 20892 USA.
[He, Xiaozhou; Yang, Yilin] Soochow Univ, Clin Coll 3, Changzhou, Jiangsu, Peoples R China.
[Feng, Yuan; Xia, Ying] Yale Univ, Sch Med, New Haven, CT USA.
[Feng, Yuan; Yin, Kaisheng] Nanjing Med Univ, Affiliated Hosp 1, Nanjing, Jiangsu, Peoples R China.
RP Xia, Y (reprint author), Univ Texas Med Sch, Vivian L Smith Dept Neurosurg, Houston, TX 77030 USA.
EM ying.xia@uth.tmc.edu
FU NIH [HD-34852, AT-004422]; American Heart Association, USA
[AHA-0755993T]
FX This work was supported by NIH (HD-34852, AT-004422) and American Heart
Association (AHA-0755993T), USA.
NR 25
TC 9
Z9 9
U1 0
U2 3
PU CHINESE PHYSIOLOGICAL SOC
PI TAIPEI
PA NATL YANG-MING UNIV, TAIPEI, TAIWAN
SN 0304-4920
J9 CHINESE J PHYSIOL
JI Chin. J. Physiol.
PD APR 30
PY 2011
VL 54
IS 2
BP 118
EP 123
DI 10.4077/CJP.2011.AMM047
PG 6
WC Physiology
SC Physiology
GA 751GP
UT WOS:000289605800007
PM 21789893
ER
PT J
AU Elvevag, B
Wynn, R
Covington, MA
AF Elvevag, Brita
Wynn, Rolf
Covington, Michael A.
TI Meaningful confusions and confusing meanings in communication in
schizophrenia
SO PSYCHIATRY RESEARCH
LA English
DT Article
DE Semantics; Semiotics; Schizophrenia
ID SEMIOTIC DISORDER; SPEECH
AB Unconventional discourse in schizophrenia has been speculated to be attributable to the mixing up of symbols and signs. We illustrate how a series of scientific images, cartoons, and prose are used by a patient to weave disparate-and objectively unrelated-concepts. The resulting prose is incoherent science. Published by Elsevier Ireland Ltd.
C1 [Elvevag, Brita] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
[Wynn, Rolf] Univ Tromso, Inst Clin Med, Tromso, Norway.
[Covington, Michael A.] Univ Georgia, Inst Artificial Intelligence, Athens, GA 30602 USA.
RP Elvevag, B (reprint author), NIMH, Clin Brain Disorders Branch, NIH, 10 Ctr Dr,3C104,MSC 1379, Bethesda, MD 20892 USA.
EM brita@elvevaag.net
FU National Institute of Mental Health
FX The authors are grateful to the patient for allowing us to discuss these
findings. We are thankful to Denise Niner LICSW and Krista Wisner B.S.
for their assistance, and also for the useful suggestions of an
anonymous reviewer. This research was supported by the Intramural
Research Program of the National Institute of Mental Health.
NR 10
TC 3
Z9 3
U1 0
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0165-1781
J9 PSYCHIAT RES
JI Psychiatry Res.
PD APR 30
PY 2011
VL 186
IS 2-3
BP 461
EP 464
DI 10.1016/j.psychres.2010.08.015
PG 4
WC Psychiatry
SC Psychiatry
GA 744YS
UT WOS:000289131700055
PM 20843559
ER
PT J
AU Amarnath, S
Chen, H
Foley, JE
Costanzo, CM
Sennesh, JD
Solomon, MA
Fowler, DH
AF Amarnath, Shoba
Chen, Hao
Foley, Jason E.
Costanzo, Carliann M.
Sennesh, Joel D.
Solomon, Michael A.
Fowler, Daniel H.
TI Host-Based Th2 Cell Therapy for Prolongation of Cardiac Allograft
Viability
SO PLOS ONE
LA English
DT Article
ID REGULATORY T-CELLS; IN-VIVO; TRANSPLANTATION TOLERANCE; INFECTIOUS
TOLERANCE; BLOOD-TRANSFUSIONS; GRAFT-REJECTION; RAPAMYCIN; CYCLOSPORINE;
RECIPIENTS; SURVIVAL
AB Donor T cell transfusion, which is a long-standing approach to prevent allograft rejection, operates indirectly by alteration of host T cell immunity. We therefore hypothesized that adoptive transfer of immune regulatory host Th2 cells would represent a novel intervention to enhance cardiac allograft survival. Using a well-described rat cardiac transplant model, we first developed a method for ex vivo manufacture of rat host-type Th2 cells in rapamycin, with subsequent injection of such Th2. R cells prior to class I and class II disparate cardiac allografting. Second, we determined whether Th2. R cell transfer polarized host immunity towards a Th2 phenotype. And third, we evaluated whether Th2. R cell therapy prolonged allograft viability when used alone or in combination with a short-course of cyclosporine (CSA) therapy. We found that host-type Th2. R cell therapy prior to cardiac allografting: (1) reduced the frequency of activated T cells in secondary lymphoid organs; (2) shifted post-transplant cytokines towards a Th2 phenotype; and (3) prolonged allograft viability when used in combination with short-course CSA therapy. These results provide further support for the rationale to use "direct" host T cell therapy for prolongation of allograft viability as an alternative to "indirect" therapy mediated by donor T cell infusion.
C1 [Amarnath, Shoba; Foley, Jason E.; Costanzo, Carliann M.; Fowler, Daniel H.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Chen, Hao; Solomon, Michael A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Chen, Hao] Fudan Univ, Huadong Hosp, Dept Cardiac Surg, Shanghai 200433, Peoples R China.
[Sennesh, Joel D.] Inova Fairfax Hosp, Dept Pathol, Fairfax, VA USA.
[Solomon, Michael A.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
RP Amarnath, S (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
EM samarnath@mail.nih.gov
FU Center for Cancer Research; National Cancer Institute; Critical Care
Medicine Department
FX This work was supported by the Center for Cancer Research, National
Cancer Institute, and Critical Care Medicine Department, Clinical Center
Intramural Research Program. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 46
TC 3
Z9 3
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 APR 29
PY 2011
VL 6
IS 4
AR e18885
DI 10.1371/journal.pone.0018885
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 756OZ
UT WOS:000290024700031
PM 21559526
ER
PT J
AU He, L
Li, H
Chen, L
Miao, JY
Jiang, YL
Zhang, Y
Xiao, ZX
Hanley, G
Li, Y
Zhang, XM
LeSage, G
Peng, Y
Yin, DL
AF He, Lei
Li, Hui
Chen, Lin
Miao, Junying
Jiang, Yulin
Zhang, Yi
Xiao, Zuoxiang
Hanley, Gregory
Li, Yi
Zhang, Xiumei
LeSage, Gene
Peng, Ying
Yin, Deling
TI Toll-Like Receptor 9 Is Required for Opioid-Induced Microglia Apoptosis
SO PLOS ONE
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; MORPHINE PROMOTES APOPTOSIS; BETA-ARRESTIN 2;
INNATE IMMUNITY; MAP KINASES; CELL-DEATH; P38 MAPK; B-CELLS; RESPONSES;
PATHWAY
AB Opioids have been widely applied in clinics as one of the most potent pain relievers for centuries, but their abuse has deleterious physiological effects beyond addiction. However, the underlying mechanism by which microglia in response to opioids remains largely unknown. Here we show that morphine induces the expression of Toll-like receptor 9 (TLR9), a key mediator of innate immunity and inflammation. Interestingly, TLR9 deficiency significantly inhibited morphine-induced apoptosis in microglia. Similar results were obtained when endogenous TLR9 expression was suppressed by the TLR9 inhibitor CpGODN. Inhibition of p38 MAPK by its specific inhibitor SB203580 attenuated morphine-induced microglia apoptosis in wild type microglia. Morphine caused a dramatic decrease in Bcl-2 level but increase in Bax level in wild type microglia, but not in TLR9 deficient microglia. In addition, morphine treatment failed to induce an increased levels of phosphorylated p38 MAPK and MAP kinase kinase 3/6 (MKK3/6), the upstream MAPK kinase of p38 MAPK, in either TLR9 deficient or mu-opioid receptor (mu OR) deficient primary microglia, suggesting an involvement of MAPK and mu OR in morphine-mediated TLR9 signaling. Moreover, morphine-induced TLR9 expression and microglia apoptosis appears to require mu OR. Collectively, these results reveal that opioids prime microglia to undergo apoptosis through TLR9 and mu OR as well. Taken together, our data suggest that inhibition of TLR9 and/or blockage of mu OR is capable of preventing opioid-induced brain damage.
C1 [He, Lei; Li, Yi; Peng, Ying] Sun Yat Sen Univ, Dept Neurol, Sun Yat Sen Mem Hosp, Guangzhou 510275, Guangdong, Peoples R China.
[He, Lei; Li, Hui; Chen, Lin; Zhang, Yi; LeSage, Gene; Yin, Deling] E Tennessee State Univ, Coll Med, Dept Internal Med, Johnson City, TN 37614 USA.
[Chen, Lin; Zhang, Xiumei] Shandong Univ, Sch Med, Dept Pharmacol, Jinan 250100, Peoples R China.
[Miao, Junying] Shandong Univ, Sch Life Sci, Inst Dev Biol, Jinan 250100, Peoples R China.
[Jiang, Yulin] E Tennessee State Univ, Dept Chem, Johnson City, TN 37614 USA.
[Xiao, Zuoxiang] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
[Hanley, Gregory] E Tennessee State Univ, Coll Med, Div Lab Anim Resources, Johnson City, TN 37614 USA.
RP He, L (reprint author), Sun Yat Sen Univ, Dept Neurol, Sun Yat Sen Mem Hosp, Guangzhou 510275, Guangdong, Peoples R China.
EM lesage@etsu.edu; docpengy@yahoo.com.cn; yin@etsu.edu
RI LI, HUI/G-1227-2011
FU National Institutes of Health [DA020120-03A1]; East Tennessee State
University Research Development Committee
FX This work was supported by National Institutes of Health grant
DA020120-03A1 and East Tennessee State University Research Development
Committee grant to D. Yin. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 48
TC 14
Z9 15
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 APR 29
PY 2011
VL 6
IS 4
AR e18190
DI 10.1371/journal.pone.0018190
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 756OZ
UT WOS:000290024700008
PM 21559519
ER
PT J
AU Poleg-Polsky, A
Diamond, JS
AF Poleg-Polsky, Alon
Diamond, Jeffrey S.
TI Imperfect Space Clamp Permits Electrotonic Interactions between
Inhibitory and Excitatory Synaptic Conductances, Distorting Voltage
Clamp Recordings
SO PLOS ONE
LA English
DT Article
ID RETINAL GANGLION-CELLS; PRIMARY VISUAL-CORTEX; DIRECTION SELECTIVITY;
NMDA-RECEPTOR; IN-VIVO; AUDITORY-CORTEX; RABBIT RETINA; MOUSE RETINA;
NEURONS; SIMULATIONS
AB The voltage clamp technique is frequently used to examine the strength and composition of synaptic input to neurons. Even accounting for imperfect voltage control of the entire cell membrane ("space clamp"), it is often assumed that currents measured at the soma are a proportional indicator of the postsynaptic conductance. Here, using NEURON simulation software to model somatic recordings from morphologically realistic neurons, we show that excitatory conductances recorded in voltage clamp mode are distorted significantly by neighboring inhibitory conductances, even when the postsynaptic membrane potential starts at the reversal potential of the inhibitory conductance. Analogous effects are observed when inhibitory postsynaptic currents are recorded at the reversal potential of the excitatory conductance. Escape potentials in poorly clamped dendrites reduce the amplitude of excitatory or inhibitory postsynaptic currents recorded at the reversal potential of the other conductance. In addition, unclamped postsynaptic inhibitory conductances linearize the recorded current-voltage relationship of excitatory inputs comprising AMPAR and NMDAR-mediated components, leading to significant underestimation of the relative contribution by NMDARs, which are particularly sensitive to small perturbations in membrane potential. Voltage clamp accuracy varies substantially between neurons and dendritic arbors of different morphology; as expected, more reliable recordings are obtained from dendrites near the soma, but up to 80% of the synaptic signal on thin, distant dendrites may be lost when postsynaptic interactions are present. These limitations of the voltage clamp technique may explain how postsynaptic effects on synaptic transmission could, in some cases, be attributed incorrectly to presynaptic mechanisms.
C1 [Poleg-Polsky, Alon; Diamond, Jeffrey S.] Natl Inst Neurol Disorders & Stroke, Synapt Physiol Sect, NIH, Bethesda, MD 20824 USA.
RP Poleg-Polsky, A (reprint author), Natl Inst Neurol Disorders & Stroke, Synapt Physiol Sect, NIH, Bethesda, MD 20824 USA.
EM polegpolskya@mail.nih.gov
RI Diamond, Jeffrey/C-1835-2015;
OI Diamond, Jeffrey/0000-0002-1770-2629; Poleg-Polsky,
Alon/0000-0003-1327-5129
FU NINDS; Rothschild Foundation
FX This work was supported by the NINDS Intramural Program and by the
Rothschild Foundation. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 41
TC 30
Z9 30
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 APR 29
PY 2011
VL 6
IS 4
AR e19463
DI 10.1371/journal.pone.0019463
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 756OZ
UT WOS:000290024700185
PM 21559357
ER
PT J
AU Steel, C
Nutman, TB
AF Steel, Cathy
Nutman, Thomas B.
TI Altered T Cell Memory and Effector Cell Development in Chronic Lymphatic
Filarial Infection That Is Independent of Persistent Parasite Antigen
SO PLOS ONE
LA English
DT Article
ID CHRONIC VIRAL-INFECTION; CHRONIC CHAGAS-DISEASE; C HIV-1 INFECTION;
LEISHMANIA-MAJOR; BANCROFTIAN FILARIASIS; HUMAN IMMUNOSENESCENCE;
RECEPTOR EXPRESSION; ENDEMIC FILARIASIS; CYTOKINE CONTROL; PACIFIC
ISLAND
AB Chronic lymphatic filarial (LF) infection is associated with suppression of parasite-specific T cell responses that persist even following elimination of infection. While several mechanisms have been implicated in mediating this T cell specific downregulation, a role for alterations in the homeostasis of T effector and memory cell populations has not been explored. Using multiparameter flow cytometry, we investigated the role of persistent filarial infection on the maintenance of T cell memory in patients from the filarial-endemic Cook Islands. Compared to filarial-uninfected endemic normals (EN), microfilaria (mf) positive infected patients (Inf) had a reduced CD4 central memory (T(CM)) compartment. In addition, Inf patients tended to have more effector memory cells (T(EM)) and fewer effector cells (T(EFF)) than did ENs giving significantly smaller T(EFF) : T(EM) ratios. These contracted T(CM) and T(EFF) populations were still evident in patients previously mf+ who had cleared their infection (CLInf). Moreover, the density of IL-7R alpha, necessary for T memory cell maintenance (but decreased in T effector cells), was significantly higher on memory cells of Inf and CLInf patients, although there was no evidence for decreased IL-7 or increased soluble IL7-R alpha, both possible mechanisms for signaling defects in memory cells. However, effector cells that were present in Inf and CLInf patients had lower percentages of HLA-DR suggesting impaired function. These changes in T cell populations appear to reflect chronicity of infection, as filarial-infected children, despite the presence of active infection, did not show alterations in the frequencies of these T cell phenotypes. These data indicate that filarial-infected patients have contracted T(CM) compartments and a defect in effector cell development, defects that persist even following clearance of infection. The fact that these global changes in memory and effector cell compartments do not yet occur in infected children makes early treatment of LF even more crucial.
C1 [Steel, Cathy; Nutman, Thomas B.] NIH, Parasit Dis Lab, Bethesda, MD 20892 USA.
RP Steel, C (reprint author), NIH, Parasit Dis Lab, Bethesda, MD 20892 USA.
EM csteel@niaid.nih.gov
FU NIH/NIAID
FX This research was supported by the Intramural Research Program of the
NIH/NIAID. The funder had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 75
TC 9
Z9 9
U1 0
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 APR 29
PY 2011
VL 6
IS 4
AR e19197
DI 10.1371/journal.pone.0019197
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 756OZ
UT WOS:000290024700098
PM 21559422
ER
PT J
AU Sun, YC
Koumoutsi, A
Jarrett, C
Lawrence, K
Gherardini, FC
Darby, C
Hinnebusch, BJ
AF Sun, Yi-Cheng
Koumoutsi, Alexandra
Jarrett, Clayton
Lawrence, Kevin
Gherardini, Frank C.
Darby, Creg
Hinnebusch, B. Joseph
TI Differential Control of Yersinia pestis Biofilm Formation In Vitro and
in the Flea Vector by Two c-di-GMP Diguanylate Cyclases
SO PLOS ONE
LA English
DT Article
ID EARLY-PHASE TRANSMISSION; STORAGE HMS(+) PHENOTYPE; ESCHERICHIA-COLI;
PIGMENTATION PHENOTYPE; CAENORHABDITIS-ELEGANS; CYCLIC DIGUANYLATE;
PROTEIN DOMAIN; PLAGUE; PSEUDOTUBERCULOSIS; MECHANISM
AB Yersinia pestis forms a biofilm in the foregut of its flea vector that promotes transmission by flea bite. As in many bacteria, biofilm formation in Y. pestis is controlled by intracellular levels of the bacterial second messenger c-di-GMP. Two Y. pestis diguanylate cyclase (DGC) enzymes, encoded by hmsT and y3730, and one phosphodiesterase (PDE), encoded by hmsP, have been shown to control biofilm production in vitro via their opposing c-di-GMP synthesis and degradation activities, respectively. In this study, we provide further evidence that hmsT, hmsP, and y3730 are the only three genes involved in c-di-GMP metabolism in Y. pestis and evaluated the two DGCs for their comparative roles in biofilm formation in vitro and in the flea vector. As with HmsT, the DGC activity of Y3730 depended on a catalytic GGDEF domain, but the relative contribution of the two enzymes to the biofilm phenotype was influenced strongly by the environmental niche. Deletion of y3730 had a very minor effect on in vitro biofilm formation, but resulted in greatly reduced biofilm formation in the flea. In contrast, the predominant effect of hmsT was on in vitro biofilm formation. DGC activity was also required for the Hms-independent autoaggregation phenotype of Y. pestis, but was not required for virulence in a mouse model of bubonic plague. Our results confirm that only one PDE (HmsP) and two DGCs (HmsT and Y3730) control c-di-GMP levels in Y. pestis, indicate that hmsT and y3730 are regulated post-transcriptionally to differentially control biofilm formation in vitro and in the flea vector, and identify a second c-di-GMP-regulated phenotype in Y. pestis.
C1 [Sun, Yi-Cheng; Jarrett, Clayton; Lawrence, Kevin; Gherardini, Frank C.; Hinnebusch, B. Joseph] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Koumoutsi, Alexandra; Darby, Creg] Univ Calif San Francisco, Dept Cell & Tissue Biol, Program Microbial Pathogenesis, San Francisco, CA 94143 USA.
RP Sun, YC (reprint author), Chinese Acad Med Sci, Inst Pathogen Biol, Beijing 100037, Peoples R China.
EM sunyc@ipbcams.ac.cn
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases (NIAID), National Institutes of Health (NIH); NIH
[AI057512]
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases (NIAID), National
Institutes of Health (NIH); and NIH Grant AI057512 (to C.D.). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 47
TC 37
Z9 40
U1 1
U2 10
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 APR 29
PY 2011
VL 6
IS 4
AR e19267
DI 10.1371/journal.pone.0019267
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 756OZ
UT WOS:000290024700118
PM 21559445
ER
PT J
AU Adams, DK
McGillicuddy, DJ
Zamudio, L
Thurnherr, AM
Liang, XF
Rouxel, O
German, CR
Mullineaux, LS
AF Adams, Diane K.
McGillicuddy, Dennis J., Jr.
Zamudio, Luis
Thurnherr, Andreas M.
Liang, Xinfeng
Rouxel, Olivier
German, Christopher R.
Mullineaux, Lauren S.
TI Surface-Generated Mesoscale Eddies Transport Deep-Sea Products from
Hydrothermal Vents
SO SCIENCE
LA English
DT Article
ID EAST PACIFIC RISE; TROPICAL PACIFIC; LARVAE; RIDGE; REPRODUCTION;
TEHUANTEPEC; PATTERNS; FIELDS; PLUME; IRON
AB Atmospheric forcing, which is known to have a strong influence on surface ocean dynamics and production, is typically not considered in studies of the deep sea. Our observations and models demonstrate an unexpected influence of surface-generated mesoscale eddies in the transport of hydrothermal vent efflux and of vent larvae away from the northern East Pacific Rise. Transport by these deep-reaching eddies provides a mechanism for spreading the hydrothermal chemical and heat flux into the deep-ocean interior and for dispersing propagules hundreds of kilometers between isolated and ephemeral communities. Because the eddies interacting with the East Pacific Rise are formed seasonally and are sensitive to phenomena such as El Nino, they have the potential to introduce seasonal to interannual atmospheric variations into the deep sea.
C1 [Adams, Diane K.; McGillicuddy, Dennis J., Jr.; Rouxel, Olivier; German, Christopher R.; Mullineaux, Lauren S.] Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA.
[Zamudio, Luis] Florida State Univ, Ctr Ocean Atmospher Predict Studies, Tallahassee, FL 32306 USA.
[Thurnherr, Andreas M.; Liang, Xinfeng] Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
[Rouxel, Olivier] Univ Brest, Univ Europeenne Bretagne, UMR 6538, Inst Francais Rech Exploitat Mer IFREMER,IUEM, F-29280 Plouzane, France.
RP Adams, DK (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
EM dadams@whoi.edu
RI Liang, Xinfeng/D-6366-2011; Liang, Xinfeng/B-4716-2014; Rouxel,
Olivier/F-3954-2014; Adams, Diane/E-7831-2015
OI Liang, Xinfeng/0000-0002-5628-4896; Adams, Diane/0000-0001-6638-5781
FU NSF [OCE-0424953, OCE-0425361, OCE-0647948]; Deep Ocean Exploration
Institute; Ocean Venture Fund; National Defense Science and Engineering;
WHOI Jannasch Chair for Excellence in Oceanography
FX We are grateful for help at sea from S. Beaulieu, K. Buckman, D.
Fornari, A. Fusaro, I. Garcia Berdeal, B. Govenar, B. Hogue, R. Jackson,
S. Mills, C. Strasser, T. Shank, S. Worrilow, and to the Captains and
crew, Alvin group, and Chief Scientists (M. Lilley and C. Vetriani)
during Atlantis cruises AT11-20, 11-26, 15-12, and 15-26. Altimeter
products were produced and distributed by AVISO
(www.aviso.oceanobs.com/) as part of the Ssalto ground processing
segment. V. Kosnyrev assisted in the analysis of altimetric data. M.
Auro and S. Birdwhistell assisted with geochemical analysis. The LADDER
group provided input during numerous discussions. HYCOM simulations were
performed as part of the Office of Naval Research project Eddy Resolving
Global Ocean Prediction Including Tides using challenge and nonchallenge
time from the U. S. Department of Defense (DOD) High Performance
Computing Modernization Office on Cray XT5 and IBM P6 computers at the
Navy DOD Supercomputing Resource Center, Stennis Space Center. Support
was provided by NSF grants OCE-0424953, OCE-0425361, and OCE-0647948;
Woods Hole Oceanographic Institution (WHOI) grants from the Deep Ocean
Exploration Institute and the Ocean Venture Fund; a National Defense
Science and Engineering Graduate Fellowship to D.K.A.; and the WHOI
Jannasch Chair for Excellence in Oceanography to L.S.M. Larval fluxes,
chemical fluxes, and current records from 2004-2005 have been deposited
in the Marine Geoscience Data System: RIDGE 2000 Data Portal. The
authors declare no competing financial interests.
NR 30
TC 40
Z9 45
U1 4
U2 42
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 APR 29
PY 2011
VL 332
IS 6029
BP 580
EP 583
DI 10.1126/science.1201066
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 756DE
UT WOS:000289991100046
PM 21527710
ER
PT J
AU Kaur, S
Kuznetsova, SA
Pendrak, ML
Sipes, JM
Romeo, MJ
Li, ZQ
Zhang, LJ
Roberts, DD
AF Kaur, Sukhbir
Kuznetsova, Svetlana A.
Pendrak, Michael L.
Sipes, John M.
Romeo, Martin J.
Li, Zhuqing
Zhang, Lijuan
Roberts, David D.
TI Heparan Sulfate Modification of the Transmembrane Receptor CD47 Is
Necessary for Inhibition of T Cell Receptor Signaling by
Thrombospondin-1
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID INTEGRIN-ASSOCIATED PROTEIN; PRECURSOR-LIKE PROTEIN-2; HAMSTER OVARY
CELL; C-TERMINAL DOMAIN; CHONDROITIN SULFATE; CYCLOPHILIN-B;
NITRIC-OXIDE; EXTRACELLULAR-MATRIX; MEDIATED ADHESION; MELANOMA-CELLS
AB Cell surface proteoglycans on T cells contribute to retroviral infection, binding of chemokines and other proteins, and are necessary for some T cell responses to the matricellular glycoprotein thrombospondin-1. The major cell surface proteoglycans expressed by primary T cells and Jurkat T cells have an apparent M(r) > 200,000 and are modified with chondroitin sulfate and heparan sulfate chains. Thrombospondin-1 bound in a heparin-inhibitable manner to this proteoglycan and to a soluble form released into the medium. Based on mass spectrometry, knockdown, and immunochemical analyses, the proteoglycan contains two major core proteins as follows: amyloid precursor-like protein-2 (APLP2, apparent M(r) 230,000) and CD47 (apparent M(r) > 250,000). CD47 is a known thrombospondin-1 receptor but was not previously reported to be a proteoglycan. This proteoglycan isoform of CD47 is widely expressed on vascular cells. Mutagenesis identified glycosaminoglycan modification of CD47 at Ser(64) and Ser(79). Inhibition of T cell receptor signaling by thrombospondin-1 was lost in CD47-deficient T cells that express the proteoglycan isoform of APLP2, indicating that binding to APLP2 is not sufficient. Inhibition of CD69 induction was restored in CD47-deficient cells by re-expressing CD47 or an S79A mutant but not by the S64A mutant. Therefore, inhibition of T cell receptor signaling by thrombospondin-1 is mediated by CD47 and requires its modification at Ser(64).
C1 [Kaur, Sukhbir; Kuznetsova, Svetlana A.; Pendrak, Michael L.; Sipes, John M.; Romeo, Martin J.; Li, Zhuqing; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20982 USA.
[Zhang, Lijuan] Ocean Univ China, Sch Med & Pharm, Qingdao 266003, Peoples R China.
RP Roberts, DD (reprint author), NIH, Bldg 10,Rm 2A33,10 Ctr Dr, Bethesda, MD 20892 USA.
EM droberts@helix.nih.gov
RI Roberts, David/A-9699-2008
OI Roberts, David/0000-0002-2481-2981
FU NCI
FX This work was supported, in whole or in part, by National Institutes of
Health Intramural Research Program of the NCI.
NR 79
TC 23
Z9 23
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 APR 29
PY 2011
VL 286
IS 17
BP 14991
EP 15002
DI 10.1074/jbc.M110.179663
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 753OI
UT WOS:000289788300029
PM 21343308
ER
PT J
AU McNulty, DE
Li, ZG
White, CD
Sacks, DB
Annan, RS
AF McNulty, Dean E.
Li, Zhigang
White, Colin D.
Sacks, David B.
Annan, Roland S.
TI MAPK Scaffold IQGAP1 Binds the EGF Receptor and Modulates Its Activation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; PROTEIN-KINASE-C; PHOSPHORYLATION-DEPENDENT
MANNER; ACTIN-BINDING; INTEGRATES CA2+/CALMODULIN; CELL-PROLIFERATION;
SMALL GTPASES; B-RAF; CALMODULIN; CDC42
AB Cellular responses produced by EGF are mediated through the receptor (EGFR) and by various enzymes and scaffolds. Recent studies document IQGAP1 as a scaffold for the MAPK cascade, binding directly to B-Raf, MEK, and ERK and regulating their activation in response to EGF. We previously showed that EGF is unable to activate B-Raf in cells lacking IQGAP1. However, the mechanism by which IQGAP1 links B-Raf to EGFR was unknown. Here we report that endogenous EGFR and IQGAP1 co-localize and co-immunoprecipitate in cells. EGF has no effect on the association, but Ca(2+) attenuates binding. In vitro analysis demonstrated a direct association mediated through the IQ and kinase domains of IQGAP1 and EGFR, respectively. Calmodulin disrupts this interaction. Using a mass spectrometry-based assay, we show that EGF induces phosphorylation of IQGAP1 Ser(1443), a residue known to be phosphorylated by PKC. This phosphorylation is eliminated by pharmacological inhibition of either EGFR or PKC and transfection with small interfering RNA directed against the PKC alpha isoform. In IQGAP1-null cells, EGF-stimulated tyrosine phosphorylation of EGFR is severely attenuated. Normal levels of autophosphorylation are restored by reconstituting wild type IQGAP1 and enhanced by an IQGAP1 S1443D mutant. Collectively, these data demonstrate a functional interaction between IQGAP1 and EGFR and suggest that IQGAP1 modulates EGFR activation.
C1 [McNulty, Dean E.; Annan, Roland S.] GlaxoSmithKline Inc, Prote & Biol Mass Spectrometry Lab, Collegeville, PA 19426 USA.
[McNulty, Dean E.] UMDNJ Grad Sch Biomed Sci, Stratford, NJ 08084 USA.
[Li, Zhigang; White, Colin D.; Sacks, David B.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Li, Zhigang; White, Colin D.; Sacks, David B.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Sacks, DB (reprint author), NIH, DLM, 10 Ctr Dr,Bldg 10,Rm 2C427, Bethesda, MD 20892 USA.
EM sacksdb@mail.nih.gov; roland.s.annan@gsk.com
OI Sacks, David/0000-0003-3100-0735
FU National Institutes of Health [RO1-CA93645]; Department of Defense
[BC087504 (FY08)]
FX This work was supported, in whole or in part, by a grant from the
National Institutes of Health Grant RO1-CA93645 (to D.B.S.). This work
was also supported by the Department of Defense Breast Cancer Research
Program Grant BC087504 (FY08) (to C.D.W.).
NR 61
TC 30
Z9 31
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 APR 29
PY 2011
VL 286
IS 17
BP 15010
EP 15021
DI 10.1074/jbc.M111.227694
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 753OI
UT WOS:000289788300031
PM 21349850
ER
PT J
AU Davies, JS
Klein, DC
Carter, DA
AF Davies, Jeff S.
Klein, David C.
Carter, David A.
TI Selective Genomic Targeting by FRA-2/FOSL2 Transcription Factor
REGULATION OF THE Rgs4 GENE IS MEDIATED BY A VARIANT ACTIVATOR PROTEIN 1
(AP-1) PROMOTER SEQUENCE/CREB-BINDING PROTEIN (CBP) MECHANISM
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CAMP-RESPONSE-ELEMENT; ARYLALKYLAMINE N-ACETYLTRANSFERASE; RAT
PINEAL-GLAND; CIRCADIAN EXPRESSION; C-JUN; GENE-EXPRESSION; PC12 CELLS;
RGS4 POLYMORPHISMS; DYNAMIC EXPRESSION; ANTIGEN-2 FRA-2
AB FRA-2/FOSL2 is a basic region-leucine zipper motif transcription factor that is widely expressed in mammalian tissues. The functional repertoire of this factor is unclear, partly due to a lack of knowledge of genomic sequences that are targeted. Here, we identified novel, functional FRA-2 targets across the genome through expression profile analysis in a knockdown transgenic rat. In this model, a nocturnal rhythm of pineal gland FRA-2 is suppressed by a genetically encoded, dominant negative mutant protein. Bioinformatic analysis of validated sets of FRA-2-regulated and -nonregulated genes revealed that the FRA-2 regulon is limited by genomic target selection rules that, in general, transcend core cis-sequence identity. However, one variant AP-1related (AP-1R) sequence was common to a subset of regulated genes. The functional activity and protein binding partners of a candidate AP-1R sequence were determined for a novel FRA-2-repressed gene, Rgs4. FRA-2 protein preferentially associated with a proximal Rgs4 AP-1R sequence as demonstrated by ex vivo ChIP and in vitro EMSA analysis; moreover, transcriptional repression was blocked by mutation of the AP-1R sequence, where as mutation of an upstream consensus AP-1 family sequence did not affect Rgs4 expression. Nocturnal changes in protein complexes at the Rgs4 AP-1R sequence are associated with FRA-2-dependent dismissal of the co-activator, CBP; this provides a mechanistic basis for Rgs4 gene repression. These studies have also provided functional insight into selective genomic targeting by FRA-2, highlighting discordance between predicted and actual targets. Future studies should address FRA-2-Rgs4 interactions in other systems, including the brain, where FRA-2 function is poorly understood.
C1 [Davies, Jeff S.; Carter, David A.] Cardiff Univ, Sch Biosci, Cardiff CF10 3AX, S Glam, Wales.
[Klein, David C.] NICHD, Sect Neuroendocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
RP Carter, DA (reprint author), Cardiff Univ, Sch Biosci, Museum Ave, Cardiff CF10 3AX, S Glam, Wales.
EM carterda@cardiff.ac.uk
RI Carter, David/A-4479-2010
OI Carter, David/0000-0002-8419-3975
FU National Institutes of Health; Wellcome Trust
FX This work was supported, in whole or in part, by National Institutes of
Health Intramural Research Program (to D. C. K.). This work was also
supported by the Wellcome Trust (to J. D. and D. A. C.).
NR 77
TC 5
Z9 5
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 APR 29
PY 2011
VL 286
IS 17
BP 15227
EP 15239
DI 10.1074/jbc.M110.201996
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 753OI
UT WOS:000289788300054
PM 21367864
ER
PT J
AU Wu, CWH
Vasalatiy, O
Liu, N
Wu, HT
Cheal, S
Chen, DY
Koretsky, AP
Griffiths, GL
Tootell, RBH
Ungerleider, LG
AF Wu, Carolyn W-H
Vasalatiy, Olga
Liu, Ning
Wu, Haitao
Cheal, Sarah
Chen, Der-Yow
Koretsky, Alan P.
Griffiths, Gary L.
Tootell, Roger B. H.
Ungerleider, Leslie G.
TI Development of a MR-Visible Compound for Tracing Neuroanatomical
Connections In Vivo
SO NEURON
LA English
DT Article
ID PRIMARY SOMATOSENSORY CORTEX; TOXIN SUBUNIT-B; MANGANESE-ENHANCED MRI;
WHITE-MATTER MICROSTRUCTURE; CENTRAL-NERVOUS-SYSTEM; SLOW
AXONAL-TRANSPORT; STANDING LIMB LOSS; RAT MOTOR CORTEX; CHOLERA-TOXIN;
DIFFUSION TENSOR
AB Traditional studies of neuroanatomical connections require injection of tracer compounds into living brains, then histology of the postmortem tissue. Here, we describe and validate a compound that reveals neuronal connections in vivo, using MRI. The classic anatomical tracer CTB (cholera-toxin subunit-B) was conjugated with a gadolinium-chelate to form GdDOTA-CTB. GdDOTA-CTB was injected into the primary somatosensory cortex (Si) or the olfactory pathway of rats. High-resolution MR images were collected at a range of time points at 11.71 and 7T. The transported GdDOTA-CTB was visible for at least 1 month post-injection, clearing within 2 months. Control injections of non-conjugated GdDOTA into Si were not transported and cleared within 1-2 days. Control injections of Gd-Albumin were not transported either, clearing within 7 days. These MR results were verified by classic immunohistochemical staining for CTB, in the same animals. The GdDOTA-CTB neuronal transport was target specific, monosynaptic, stable for several weeks, and reproducible.
C1 [Wu, Carolyn W-H; Chen, Der-Yow; Koretsky, Alan P.] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20814 USA.
[Vasalatiy, Olga; Wu, Haitao; Cheal, Sarah; Griffiths, Gary L.] NHLBI, Imaging Probe Dev Ctr, NIH, Bethesda, MD 20814 USA.
[Liu, Ning; Tootell, Roger B. H.; Ungerleider, Leslie G.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20814 USA.
[Wu, Carolyn W-H] CEA Saclay, Lab Integrated Biol, Unit Brain Plast, NeuroSpin I2BM, F-91191 Gif Sur Yvette, Ile de France, France.
[Tootell, Roger B. H.] Massachusetts Gen Hosp Charlestown, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
RP Wu, CWH (reprint author), NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20814 USA.
EM carolyn.wu@cea.fr
RI Koretsky, Alan/C-7940-2015
OI Koretsky, Alan/0000-0002-8085-4756
FU NIMH; NINDS IRP; NeuroSpin/CEA; Martinos Center for Biomedical Imaging;
NCRR; MIND Institute; NIH [R01 EY017081]; French L'Agence Nationale de
la Recherche [ANR-09-BLAN-0061-CSD8]
FX We are grateful to Steve Dodd for pulse sequence optimization, David Yu
for brain slicing, and Kathy Sharer for animal ordering and care. This
work was supported in part by the NIMH and NINDS IRP, NeuroSpin/CEA, the
Martinos Center for Biomedical Imaging, the NCRR, the MIND Institute,
NIH grant R01 EY017081 to R.B.H.T., and the French L'Agence Nationale de
la Recherche grant ANR-09-BLAN-0061-CSD8 to C.W.-H.W.
NR 97
TC 12
Z9 12
U1 0
U2 9
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD APR 28
PY 2011
VL 70
IS 2
BP 229
EP 243
DI 10.1016/j.neuron.2011.03.010
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA 770FZ
UT WOS:000291073700006
PM 21521610
ER
PT J
AU Matta, JA
Ashby, MC
Sanz-Clemente, A
Roche, KW
Isaac, JTR
AF Matta, Jose A.
Ashby, Michael C.
Sanz-Clemente, Antonio
Roche, Katherine W.
Isaac, John T. R.
TI mGluR5 and NMDA Receptors Drive the Experience- and Activity-Dependent
NMDA Receptor NR2B to NR2A Subunit Switch
SO NEURON
LA English
DT Article
ID LONG-TERM POTENTIATION; EXCITATORY SYNAPTIC-TRANSMISSION; MOSSY FIBER
SYNAPSES; D-ASPARTATE RECEPTOR; VISUAL-CORTEX; MICE LACKING; IN-VIVO;
FUNCTIONAL-PROPERTIES; HIPPOCAMPAL-NEURONS; HUNTINGTONS-DISEASE
AB In cerebral cortex there is a developmental switch from NR2B- to NR2A-containing NMDA receptors (NMDARs) driven by activity and sensory experience. This subunit switch alters NMDAR function, influences synaptic plasticity, and its dysregulation is associated with neurological disorders. However, the mechanisms driving the subunit switch are not known. Here, we show in hippocampal CA1 pyramidal neurons that the NR2B to NR2A switch driven acutely by activity requires activation of NMDARs and mGluR5, involves PLC, Ca2+ release from IP3R-dependent stores, and PKC activity. In mGluR5 knockout mice the developmental NR2B-NR2A switch in CA1 is deficient. Moreover, in visual cortex of mGluR5 knockout mice, the NR2B-NR2A switch evoked in vivo by visual experience is absent. Thus, we establish that mGluR5 and NMDARs are required for the activity-dependent NR2B-NR2A switch and play a critical role in experience-dependent regulation of NMDAR subunit composition in vivo.
C1 [Matta, Jose A.; Ashby, Michael C.; Isaac, John T. R.] Natl Inst Neurol Disorders & Stroke, Dev Synapt Plast Sect, NIH, Bethesda, MD 20892 USA.
[Sanz-Clemente, Antonio; Roche, Katherine W.] Natl Inst Neurol Disorders & Stroke, Receptor Biol Sect, NIH, Bethesda, MD 20892 USA.
RP Matta, JA (reprint author), Natl Inst Neurol Disorders & Stroke, Dev Synapt Plast Sect, NIH, Bethesda, MD 20892 USA.
EM mattaja@mail.nih.gov; isaacjo@lilly.com
OI Roche, Katherine/0000-0001-7282-6539
FU National Institute of Neurological Disorders and Stroke; NIGMS
FX This work was supported by the National Institute of Neurological
Disorders and Stroke Intramural Program. J.A.M. is supported on a
Pharmacology Research Associate fellowship from NIGMS. We are grateful
to Chris McBain and members cif the McBain and Isaac labs for
discussions on this study. We thank Hey Kyoung Lee and Emily Petrus for
advice on the visual cortex experiments.
NR 68
TC 68
Z9 70
U1 0
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 APR 28
PY 2011
VL 70
IS 2
BP 339
EP 351
DI 10.1016/j.neuron.2011.02.045
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 770FZ
UT WOS:000291073700014
PM 21521618
ER
PT J
AU Rader, C
AF Rader, Christoph
TI DARTs take aim at BiTEs
SO BLOOD
LA English
DT Editorial Material
ID CANCER-THERAPY; ANTIBODY; RECRUITMENT
C1 NCI, Bethesda, MD 20892 USA.
RP Rader, C (reprint author), NCI, Bethesda, MD 20892 USA.
NR 11
TC 15
Z9 15
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 APR 28
PY 2011
VL 117
IS 17
BP 4403
EP 4404
PG 2
WC Hematology
SC Hematology
GA 756AV
UT WOS:000289984800001
PM 21527536
ER
PT J
AU Pidala, J
Kurland, B
Chai, XY
Majhail, N
Weisdorf, DJ
Pavletic, S
Cutler, C
Jacobsohn, D
Palmer, J
Arai, S
Jagasia, M
Lee, SJ
AF Pidala, Joseph
Kurland, Brenda
Chai, Xiaoyu
Majhail, Navneet
Weisdorf, Daniel J.
Pavletic, Steven
Cutler, Corey
Jacobsohn, David
Palmer, Jeanne
Arai, Sally
Jagasia, Madan
Lee, Stephanie J.
TI Patient-reported quality of life is associated with severity of chronic
graft-versus-host disease as measured by NIH criteria: report on
baseline data from the Chronic GVHD Consortium
SO BLOOD
LA English
DT Article
ID CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT;
BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; CLINICAL-TRIALS;
SYSTEMIC-SCLEROSIS; HEALTH; PREDICTORS; DIAGNOSIS; SURVIVORS
AB Quality of life (QOL) after hematopoietic cell transplantation (HCT) is compromised by chronic GVHD. In a prospectively assembled multicenter cohort of adults with chronic GVHD (n = 298), we examined the relationship between chronic GVHD severity defined by National Institutes of Health (NIH) criteria and QOL as measured by the SF-36 and FACT-BMT instruments at time of enrollment. Chronic GVHD severity was independently associated with QOL, adjusting for age. Compared with population normative data, SF-36 scores were more than a SD (10 points) lower on average for the summary physical component score (PCS) and role-physical subscale, and significantly lower (with magnitude 4-10 points) for several other subscales. Patients with moderate and severe cGVHD had PCS scores comparable with scores reported for systemic sclerosis, systemic lupus erythematosus, and multiple sclerosis, and greater impairment compared with common chronic conditions including diabetes, hypertension, and chronic lung disease. Moderate to severe cGVHD as defined by NIH criteria is associated with significant compromise in multiple QOL domains, with PCS scores in the range of other systemic autoimmune diseases. Compromised QOL provides a functional assessment of the effects of chronic GVHD, and may be measured in cGVHD clinical studies using either the SF-36 or the FACT-BMT. (Blood. 2011;117(17):4651-4657)
C1 [Pidala, Joseph] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
[Kurland, Brenda; Chai, Xiaoyu; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Majhail, Navneet; Weisdorf, Daniel J.] Univ Minnesota, Minneapolis, MN USA.
[Pavletic, Steven] NCI, Bethesda, MD 20892 USA.
[Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Jacobsohn, David] Childrens Mem Hosp, Chicago, IL 60614 USA.
[Palmer, Jeanne] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Arai, Sally] Stanford Univ, Stanford, CA 94305 USA.
[Jagasia, Madan] Vanderbilt Univ, Nashville, TN USA.
RP Pidala, J (reprint author), H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr,FOB 3308, Tampa, FL 33612 USA.
EM joseph.pidala@moffitt.org
OI Kurland, Brenda/0000-0002-5669-0595
FU National Institutes of Health/National Cancer Institute [CA 118953-03]
FX This work was supported by National Institutes of Health/National Cancer
Institute grant CA 118953-03 (PI: S.J.L.).
NR 34
TC 103
Z9 106
U1 1
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 APR 28
PY 2011
VL 117
IS 17
BP 4651
EP 4657
DI 10.1182/blood-2010-11-319509
PG 7
WC Hematology
SC Hematology
GA 756AV
UT WOS:000289984800031
PM 21355084
ER
PT J
AU Jetten, AM
AF Jetten, Anton M.
TI IMMUNOLOGY A helping hand against autoimmunity
SO NATURE
LA English
DT Editorial Material
ID ROR-GAMMA; DIFFERENTIATION; CELLS
C1 Natl Inst Environm Hlth Sci, Cell Biol Sect, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
RP Jetten, AM (reprint author), Natl Inst Environm Hlth Sci, Cell Biol Sect, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
EM jetten@niehs.nih.gov
OI Jetten, Anton/0000-0003-0954-4445
FU Intramural NIH HHS [Z01 ES101586-06]
NR 7
TC 6
Z9 7
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD APR 28
PY 2011
VL 472
IS 7344
BP 421
EP 422
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 755QC
UT WOS:000289949600020
PM 21525918
ER
PT J
AU Kulkarni, S
Savan, R
Qi, Y
Gao, XJ
Yuki, Y
Bass, SE
Martin, MP
Hunt, P
Deeks, SG
Telenti, A
Pereyra, F
Goldstein, D
Wolinsky, S
Walker, B
Young, HA
Carrington, M
AF Kulkarni, Smita
Savan, Ram
Qi, Ying
Gao, Xiaojiang
Yuki, Yuko
Bass, Sara E.
Martin, Maureen P.
Hunt, Peter
Deeks, Steven G.
Telenti, Amalio
Pereyra, Florencia
Goldstein, David
Wolinsky, Steven
Walker, Bruce
Young, Howard A.
Carrington, Mary
TI Differential microRNA regulation of HLA-C expression and its association
with HIV control
SO NATURE
LA English
DT Article
ID HUMAN CELL-LINE; SURFACE EXPRESSION; MESSENGER-RNAS; GENES;
DEADENYLATION; ANTIGENS; GENOME
AB The HLA-C locus is distinct relative to the other classical HLA class I loci in that it has relatively limited polymorphism(1), lower expression on the cell surface(2,3), and more extensive ligand-receptor interactions with killer-cell immunoglobulin-like receptors(4). A single nucleotide polymorphism (SNP) 35 kb upstream of HLA-C (rs9264942; termed -35) associates with control of HIV(5-7), and with levels of HLA-C messenger RNA transcripts(8) and cell-surface expression(7), but the mechanism underlying its varied expression is unknown. We proposed that the -35 SNP is not the causal variant for differential HLA-C expression, but rather is marking another polymorphism that directly affects levels of HLA-C(7). Here we show that variation within the 3' untranslated region (UTR) of HLA-C regulates binding of the microRNA hsa-miR-148 to its target site, resulting in relatively low surface expression of alleles that bind this microRNA and high expression of HLA-C alleles that escape post-transcriptional regulation. The 3' UTR variant associates strongly with control of HIV, potentially adding to the effects of genetic variation encoding the peptide-binding region of the HLA class I loci. Variation in HLA-C expression adds another layer of diversity to this highly polymorphic locus that must be considered when deciphering the function of these molecules in health and disease.
C1 [Kulkarni, Smita; Qi, Ying; Gao, Xiaojiang; Yuki, Yuko; Bass, Sara E.; Martin, Maureen P.; Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Kulkarni, Smita; Qi, Ying; Gao, Xiaojiang; Yuki, Yuko; Martin, Maureen P.; Pereyra, Florencia; Walker, Bruce; Carrington, Mary] Harvard Univ, Boston, MA 02114 USA.
[Kulkarni, Smita; Qi, Ying; Gao, Xiaojiang; Yuki, Yuko; Martin, Maureen P.; Pereyra, Florencia; Walker, Bruce; Carrington, Mary] MIT, Ragon Inst, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hunt, Peter; Deeks, Steven G.] Univ Calif San Francisco, San Francisco Gen Hosp, Div Aids, San Francisco, CA 94110 USA.
[Telenti, Amalio] Univ Lausanne, Inst Microbiol, CH-1011 Lausanne, Switzerland.
[Goldstein, David] Duke Univ, Inst Genome Sci & Policy, Ctr Human Genome Variat, Durham, NC 27708 USA.
[Wolinsky, Steven] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA.
RP Carrington, M (reprint author), NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA.
EM carringm@mail.nih.gov
RI Wolinsky, Steven/B-2893-2012; SHCS, int. coll. A/G-4083-2011; SHCS,
all/G-4072-2011;
OI Wolinsky, Steven/0000-0002-9625-6697; Young, Howard/0000-0002-3118-5111
FU National Cancer Institute, National Institutes of Health (NIH)
[HHSN261200800001E, N02-CP-55504, R01-DA04334, R01-DA12568]; NIH,
National Cancer Institute, Center for Cancer Research; Cancer
Inflammation Program Project Award; Bill & Melinda Gates Foundation;
Mark and Lisa Schwartz Foundation; National Institute of Allergy and
Infectious Diseases; National Cancer Institute; National Heart, Lung and
Blood Institute [UO1-AI-35042, 5-MO1-RR-00722, UO1-AI-35043,
UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041];
Swiss HIV Cohort Study; Swiss National Science Foundation
[33CSC0-108787]; [UL1 RR024131]; [P30 AI27763]
FX This project has been funded in part with federal funds from the
National Cancer Institute, National Institutes of Health (NIH), under
contracts HHSN261200800001E, N02-CP-55504, R01-DA04334 and R01-DA12568.
The content of this publication does not necessarily reflect the views
or policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the US Government. This research was supported in part by
the Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research and the Cancer Inflammation Program Project
Award for the year 2009, a grant from the Bill & Melinda Gates
Foundation as part of the Collaboration for AIDS Vaccine Discovery, and
the Mark and Lisa Schwartz Foundation. We would also like to thank the
patients and investigators involved in the Multicenter AIDS Cohort Study
(the MACS is funded by the National Institute of Allergy and Infectious
Diseases, with supplemental funding from the National Cancer Institute
and the National Heart, Lung and Blood Institute (grants UO1-AI-35042,
5-MO1-RR-00722 (GCRC), UO1-AI-35043, UO1-AI-37984, UO1-AI-35039,
UO1-AI-35040, UO1-AI-37613 and UO1-AI-35041), the Swiss HIV Cohort Study
(see Supplementary Note 4 for the list of members), supported by the
Swiss National Science Foundation grant number 33CSC0-108787, and the
SCOPE study, which was funded by the UL1 RR024131 (Clinical and
Translational Sciences Award) and P30 AI27763 (Center for AIDS Research)
grants. We thank S. Anderson, G. O'Connor and R. Thomas for advice, A.
Kronfli and K. Ramakrishnan for assistance in plasmid and genomic DNA
preparations, A. McFarland for western blots, V. Braud for the DT9
antibody, R. Johnson and G. Nelson for statistical advice and T. Covell
for administrative assistance.
NR 27
TC 148
Z9 158
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD APR 28
PY 2011
VL 472
IS 7344
BP 495
EP U548
DI 10.1038/nature09914
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 755QC
UT WOS:000289949600039
PM 21499264
ER
PT J
AU Ding, PR
Tiwari, AK
Ohnuma, S
Lee, JWKK
An, X
Dai, CL
Lu, QS
Singh, S
Yang, DH
Talele, TT
Ambudkar, SV
Chen, ZS
AF Ding, Pei-Rong
Tiwari, Amit K.
Ohnuma, Shinobu
Lee, Jeferson W. K. K.
An, Xin
Dai, Chun-Ling
Lu, Qi-Si
Singh, Satyakam
Yang, Dong-Hua
Talele, Tanaji T.
Ambudkar, Suresh V.
Chen, Zhe-Sheng
TI The Phosphodiesterase-5 Inhibitor Vardenafil Is a Potent Inhibitor of
ABCB1/P-Glycoprotein Transporter
SO PLOS ONE
LA English
DT Article
ID REVERSES MULTIDRUG-RESISTANCE; SUBFAMILY-B MEMBER-1; HUMAN
P-GLYCOPROTEIN; MOLECULAR-BASIS; MRP1 ABCC1; BINDING; CANCER; CELLS;
MODULATION; CHEMOTHERAPY
AB One of the major causes of chemotherapy failure in cancer treatment is multidrug resistance (MDR) which is mediated by the ABCB1/P-glycoprotein. Previously, through the use of an extensive screening process, we found that vardenafil, a phosphodiesterase 5 (PDE-5) inhibitor significantly reverses MDR in ABCB1 overexpressing cancer cells, and its efficacy was greater than that of tadalafil, another PDE-5 inhibitor. The present study was designed to determine the reversal mechanisms of vardenafil and tadalafil on ABC transporters-mediated MDR. Vardenafil or tadalafil alone, at concentrations up to 20 mu M, had no significant toxic effects on any of the cell lines used in this study, regardless of their membrane transporter status. However, vardenafil when used in combination with anticancer substrates of ABCB1, significantly potentiated their cytotoxicity in ABCB1 overexpressing cells in a concentration-dependent manner, and this effect was greater than that of tadalafil. The sensitivity of the parenteral cell lines to cytotoxic anticancer drugs was not significantly altered by vardenafil. The differential effects of vardenafil and tadalafil appear to be specific for the ABCB1 transporter as both vardenafil and tadalafil had no significant effect on the reversal of drug resistance conferred by ABCC1 (MRP1) and ABCG2 (BCRP) transporters. Vardenafil significantly increased the intracellular accumulation of [(3)H]-paclitaxel in the ABCB1 overexpressing KB-C2 cells. In addition, vardenafil significantly stimulated the ATPase activity of ABCB1 and inhibited the photolabeling of ABCB1 with [(125)I]-IAAP. Furthermore, Western blot analysis indicated the incubation of cells with either vardenafil or tadalafil for 72 h did not alter ABCB1 protein expression. Overall, our results suggest that vardenafil reverses ABCB1-mediated MDR by directly blocking the drug efflux function of ABCB1.
C1 [Ding, Pei-Rong; Tiwari, Amit K.; Lee, Jeferson W. K. K.; An, Xin; Dai, Chun-Ling; Lu, Qi-Si; Singh, Satyakam; Talele, Tanaji T.; Chen, Zhe-Sheng] St Johns Univ, Coll Pharm & Allied Hlth Profess, Dept Pharmaceut Sci, Jamaica, NY 11439 USA.
[Ding, Pei-Rong; An, Xin] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol S China, Guangzhou 510275, Guangdong, Peoples R China.
[Ding, Pei-Rong] Sun Yat Sen Univ, Ctr Canc, Dept Colorectal Surg, Guangzhou 510275, Guangdong, Peoples R China.
[Ohnuma, Shinobu; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[An, Xin] Sun Yat Sen Univ, Ctr Canc, Dept Med Oncol, Guangzhou 510275, Guangdong, Peoples R China.
[Yang, Dong-Hua] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
RP Ding, PR (reprint author), St Johns Univ, Coll Pharm & Allied Hlth Profess, Dept Pharmaceut Sci, Jamaica, NY 11439 USA.
EM Chenz@stjohns.edu
RI Tiwari, Amit/A-3667-2012;
OI Tiwari, Amit/0000-0002-7427-7155; Singh, Satyakam/0000-0001-9115-3296
FU St. John's University [579-1110]; National Institutes of Health (NIH),
National Cancer Institute, Center for Cancer Research
FX This work was supported by funds from St. John's University Seed Grant
No. 579-1110, (Z.S.C.) and S.O. and S.V.A. were supported by the
Intramural Research Program of the National Institutes of Health (NIH),
National Cancer Institute, Center for Cancer Research. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 42
TC 35
Z9 38
U1 0
U2 10
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 APR 28
PY 2011
VL 6
IS 4
AR e19329
DI 10.1371/journal.pone.0019329
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 756NX
UT WOS:000290020700048
PM 21552528
ER
PT J
AU Pike, VW
Rash, KS
Chen, ZG
Pedregal, C
Statnick, MA
Kimura, Y
Hong, J
Zoghbi, SS
Fujita, M
Toledo, MA
Diaz, N
Gackenheimer, SL
Tauscher, JT
Barth, VN
Innis, RB
AF Pike, Victor W.
Rash, Karen S.
Chen, Zhaogen
Pedregal, Concepcion
Statnick, Michael A.
Kimura, Yasuyuki
Hong, Jinsoo
Zoghbi, Sami S.
Fujita, Masahiro
Toledo, Miguel A.
Diaz, Nuria
Gackenheimer, Susan L.
Tauscher, Johannes T.
Barth, Vanessa N.
Innis, Robert B.
TI Synthesis and Evaluation of Radioligands for Imaging Brain
Nociceptin/Orphanin FQ Peptide (NOP) Receptors with Positron Emission
Tomography
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID IN-VIVO; OPIOID RECEPTOR; PHARMACOLOGICAL CHARACTERIZATION;
AUTORADIOGRAPHIC LOCALIZATION; ANTAGONIST SB-612111; DRUG DEVELOPMENT;
BINDING-SITES; FREE-FRACTION; DOPAMINE D2; ORPHANIN-FQ
AB Positron emission tomography (PET) coupled to an effective radioligand could provide an important tool for understanding possible links between neuropsychiatric disorders and brain NOP (nociceptin/orphanin FQ peptide) receptors. We sought to develop such a PET radioligand. High-affinity NOP ligands were synthesized based on a 3-(2'-fluoro-4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran]-1-yl)-2(2-halobenzyl)-N-alkylpropanamide scaffold and from experimental screens in rats, with ex vivo LC-MS/MS measures, three ligands were identified for labeling with carbon-11 and evaluation with PET in monkey. Each ligand was labeled by C-11-methylation of an N-desmethyl precursor and studied in monkey under baseline and NOP receptor-preblock conditions. The three radioligands, [C-11] (S) 10a-c, gave similar results. Baseline scans showed high entry of radioactivity into the brain to give a distribution reflecting that expected for NOP receptors. Preblock experiments showed high early peak levels of brain radioactivity, which rapidly declined to a Much lower level than seen in baseline scans, thereby indicating a high level of receptor-specific binding in baseline experiments. Overall, [C-11](S)-10c showed the most favorable receptor-specific signal and kinetics and is now selected for evaluation in human subjects.
C1 [Pike, Victor W.; Kimura, Yasuyuki; Hong, Jinsoo; Zoghbi, Sami S.; Fujita, Masahiro; Innis, Robert B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Rash, Karen S.; Chen, Zhaogen; Statnick, Michael A.; Gackenheimer, Susan L.; Tauscher, Johannes T.; Barth, Vanessa N.] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA.
[Pedregal, Concepcion; Toledo, Miguel A.; Diaz, Nuria] Lilly SA, Madrid 28108, Spain.
RP Pike, VW (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 10,Room B3 C346A,10 Ctr Dr, Bethesda, MD 20892 USA.
EM pikev@mail.nih.gov
RI Kimura, Yasuyuki/D-4459-2016; Tauscher, Johannes/M-5976-2016
OI Kimura, Yasuyuki/0000-0002-7927-9483;
FU National Institute of Mental Health (NIMH), National Institutes of
Health (NIH)
FX This study was supported by the Intramural Research Program of the
National Institutes of Health (NIH), specifically the National Institute
of Mental Health (NIMH). We thank the NIH PET Department for
radioisotope production, Dr. Talakad G. Lohith, Dr. Harushige Ozaki,
Leah Dickstein, and Robert L. Gladding for assistance with PET imaging,
Dr. Fabrice G. Simeon, and Cheryl L. Morse for contribution to
radiochemistry, and Dr. H. Umesha Shetty for LC-MS measurements.
NR 38
TC 32
Z9 32
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 APR 28
PY 2011
VL 54
IS 8
BP 2687
EP 2700
DI 10.1021/jm101487v
PG 14
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 752ND
UT WOS:000289697800010
PM 21438532
ER
PT J
AU Bahta, M
Lountos, GT
Dyas, B
Kim, SE
Ulrich, RG
Waugh, DS
Burke, TR
AF Bahta, Medhanit
Lountos, George T.
Dyas, Beverly
Kim, Sung-Eun
Ulrich, Robert G.
Waugh, David S.
Burke, Terrence R., Jr.
TI Utilization of Nitrophenylphosphates and Oxime-Based Ligation for the
Development of Nanomolar Affinity Inhibitors of the Yersinia pestis
Outer Protein H (YopH) Phosphatase
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID TYROSINE-PHOSPHATASE; PROMISCUOUS INHIBITORS; NONPEPTIDIC INHIBITORS;
RAPID IDENTIFICATION; INORGANIC-PHOSPHATE; POTENT INHIBITORS; MECHANISM;
LIBRARY; 1B; SPECIFICITY
AB Our current study reports the first K(M) optimization of a library of nitrophenylphosphate-containing substrates for generating an inhibitor lead against the Yersinia pestis outer protein phosphatase (YopH). A high activity substrate identified by this method (K(M) = 80 mu M) was converted from a subs trate into an inhibitor by replacement of its phosphate group with difluoromethylphosphonic acid, and by attachment of an aminooxy handle for further structural optimization by mime ligation. A cocrystal structure of this aminooxy-containing platform in complex with YopH allowed the identification of a conserved water molecule proximal to the aminooxy group that was subsequenly employed for the design of furanyl-based oxime derivatives. By this process, a potent (IC(50) = 190 nM) and nonpromiscuous inhibitor was developed with good YopH selectivity relative to a panel of phosphatases. The inhibitor showed significant inhibition Of intracellular Y pestis replication at a noncytotoxic concentration. The current work presents general approaches to PTP inhibitor development that may be useful beyond YopH.
C1 [Bahta, Medhanit; Kim, Sung-Eun; Burke, Terrence R., Jr.] NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
[Lountos, George T.; Waugh, David S.] NCI, Macromol Crystallog Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Dyas, Beverly; Ulrich, Robert G.] USA, Lab Mol Immunol, Med Res Inst Infect Dis, Frederick, MD 21702 USA.
RP Burke, TR (reprint author), NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
EM tburke@helix.nih.gov
RI Burke, Terrence/N-2601-2014; Lountos, George/B-3983-2015
FU U.S. Department of Energy, Office of Science, Office of Basic Energy
Sciences [W-31-109-Eng-38]; NIH, Center for Cancer Research;
NCI-Frederick; National Cancer Institute, National Institutes of Health;
Joint Science and Technology Office of the Department of Defense
FX Appreciation is expressed to Afroz Sultana (LMI) far technical support
and to Joseph Tropea and Scott Cherry (MCL) for assistance with the
production of phosphatases. Electrospray mass spectrometry experiments
were conducted on the LC/ESMS instrument maintained by the Biophysics
Resource in the Structural Biophysics Laboratory, Center for Cancer
Research, National Cancer Institute at Frederick. X-ray diffraction data
were collected at the Southeast Regional Collaborative Access Team
(SER-CAT) beamline 22-ID at the Advanced Photon Source, Argonne National
Laboratory. Supporting institutions may be found at
http://www.ser-cat.org/members.html. 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 No. W-31-109-Eng-38.
This work was supported in part by the Intramural Research Program of
the NIH, Center for Cancer Research, NCI-Frederick and the National
Cancer Institute, National Institutes of Health, and the Joint Science
and Technology Office of the Department of Defense. 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 80
TC 29
Z9 29
U1 1
U2 4
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 APR 28
PY 2011
VL 54
IS 8
BP 2933
EP 2943
DI 10.1021/jm200022g
PG 11
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 752ND
UT WOS:000289697800028
PM 21443195
ER
PT J
AU Donohue, SR
Dannals, RF
Halldin, C
Pike, VW
AF Donohue, Sean R.
Dannals, Robert F.
Halldin, Christer
Pike, Victor W.
TI N-(4-Cyanotetrahydro-2H-pyran-4-yl) and N-(1-Cyanocyclohexyl)
Derivatives of 1,5-Diarylpyrazole-3-carboxamides Showing High Affinity
for 18 kDa Translocator Protein and/or Cannabinoid Receptors
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; PERIPHERAL BENZODIAZEPINE-RECEPTOR;
IN-VIVO; HUMAN BRAIN; CB1; LIGANDS; RADIOLIGANDS; POTENT; SCHIZOPHRENIA;
ANTAGONISTS
AB In order to develop improved radioligands for imaging brain CB(1) receptors with positron emission tomography (PET) based on rimonabant (5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide, 1), we synthesized compounds 9a-s in which the N-piperidinyl ring was replaced with a 4-(4-cyanotetrahydro-2H-pyranyl) or 1-cyanocyclohexyl ring. Such changes were expected to be almost isosteric with 1, confer greater metabolic resistance, and in the case of the 4-(4-cyanotetrahydro-2H-pyranyl) compounds, substantially reduce lipophilicity. One derivative, 1-(2-bromophenyl)-N-(1-cyanocyclohexyl)-5-(4-methoxyphenyl)-4-methylpyrazole-3-carboxamide (9n), showed high affinity (K(i) = 15.7 nM) and selectivity for binding to CB(1) receptors. The corresponding 4-(4-cyanotetrahydro-2H-pyranyl) derivative (9m) also showed quite high affinity for CB(1) receptors (K(i) = 62 nM) but was found to have even higher affinity (K(i) = 29 nM) for the structurally unrelated 18 kDa translocator protein (TSPO). Some other minor structural changes among 9a-s were also found to switch binding selectivity from CB(1) receptors to TSPO or vice versa. These unexpected findings and their implications for the development of selective ligands or PET radioligands for CB(1) receptors or TSPO are discussed in relation to current pharmacophore models of CB(1) receptor and TSPO binding sites.
C1 [Donohue, Sean R.; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Donohue, Sean R.; Halldin, Christer] Karolinska Inst, Karolinska Hosp, Psychiat Sect, Dept Clin Neurosci, S-17176 Stockholm, Sweden.
[Donohue, Sean R.; Dannals, Robert F.] Johns Hopkins PET Ctr, Div Nucl Med, Baltimore, MD 21287 USA.
RP Pike, VW (reprint author), NIMH, Mol Imaging Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM pikev@mail.nih.gov
FU NIH (NIMH) [Z01-MH-002795]; National Institute of Mental Health (NIMH)
under the NIH-Karolinska Institutet Graduate Partnership in
Neuroscience; Hoffmann-La Roche; Johns Hopkins PET Center; University of
North Carolina at Chapel Hill [NO1MH32004]
FX V.W.P. and S.R.D. were supported by the Intramural Research Program of
NIH (NIMH) (Project No. Z01-MH-002795); specifically S.R.D. was
initially supported by the National Institute of Mental Health (NIMH)
through a studentship to S.R. D. under the NIH-Karolinska Institutet
Graduate Partnership in Neuroscience. S.R.D. was subsequently supported
by Hoffmann-La Roche and The Johns Hopkins PET Center through a
postdoctoral fellowship. We are grateful to the NIMH Psychoactive Drug
Screening Program (PDSP) for pharmacological assays and screens. The
PDSP is directed by Bryan L. Roth, Ph.D., with project officer Jamie
Driscol (NIMH), at the University of North Carolina at Chapel Hill
(Contract No. NO1MH32004).
NR 39
TC 23
Z9 23
U1 0
U2 7
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 APR 28
PY 2011
VL 54
IS 8
BP 2961
EP 2970
DI 10.1021/jm2000536
PG 10
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 752ND
UT WOS:000289697800031
PM 21428406
ER
PT J
AU Chung, HS
Gopich, IV
McHale, K
Cellmer, T
Louis, JM
Eaton, WA
AF Chung, Hoi Sung
Gopich, Irina V.
McHale, Kevin
Cellmer, Troy
Louis, John M.
Eaton, William A.
TI Extracting Rate Coefficients from Single-Molecule Photon Trajectories
and FRET Efficiency Histograms for a Fast-Folding Protein
SO JOURNAL OF PHYSICAL CHEMISTRY A
LA English
DT Article
ID RESONANCE ENERGY-TRANSFER; 3-HELIX BUNDLE PROTEIN; HIDDEN MARKOV-MODELS;
CONFORMATIONAL DYNAMICS; FLUORESCENCE; SPECTROSCOPY; TIME; KINETICS;
STATES
AB Recently developed statistical methods by Gopich and Szabo were used to extract folding and unfolding rate coefficients from single-molecule Forster resonance energy transfer (FRET) data for proteins with kinetics too fast to measure waiting time distributions. Two types of experiments an two different analyses were performed. In one experiment bursts of photons were collected from donor and acceptor fluorophores attached to a 73-residue protein, alpha(3)D, freely diffusing through the illuminated volume of a con focal microscope system. In the second the protein was immobilized by linkage to a surface, and photons were collected until one of the fluorophores bleached. Folding and unfolding rate coefficients and mean FRET efficiencies for the folded and unfolded subpopulations were obtained from a photon by photon analysis of the trajectories using a maximum likelihood method. The ability of the method to describe the data in terms of a two-state model was checked by recoloring the photon trajectories with the extracted parameters and comparing the calculated FRET efficiency histograms with the measured histograms. The sum of the rate coefficients for the two-state model agreed to within 30% with the relaxation rate obtained from the decay of the donor acceptor cross-correlation function, confirming the high accuracy of the method. Interestingly, apparently reliable rate coefficients could be;extracted using the maximum likelihood method, even at low (< 10%) population of the minor component where the cross-correlation function was too noisy to obtain any useful information. The rate coefficients and mean FRET efficiencies were also obtained in an approximate procedure by simply fitting the FRET efficiency histograms, calculated by binning the donor and acceptor photons,;with a sum of three-Gaussian functions. The kinetics are exposed in these histograms by the growth of a FRET efficiency peak at values intermediate between the folded and unfolded peaks as the bin size increases, a phenomenon with similarities to NMR exchange broadening. When comparable populations of folded and unfolded molecules are I, present, this method yields rate coefficients in very good agreement with those obtained with the maximum likelihood method. As a first step toward characterizing transition paths, the Viterbi algorithm was used to locate the most probable transition points in the photon trajectories.
C1 [Chung, Hoi Sung; Gopich, Irina V.; McHale, Kevin; Cellmer, Troy; Louis, John M.; Eaton, William A.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Chung, HS (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM chunghoi@niddk.nih.gov; eaton@helix.nih.gov
RI Chung, Hoi Sung/C-2624-2009
FU NIDDK, NIH
FX We thank Attila Szabo for numerous helpful discussions, and Annie Aniana
for technical assistance. This work was supported by the Intramural
Research Program of the NIDDK, NIH.
NR 36
TC 47
Z9 48
U1 4
U2 40
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 APR 28
PY 2011
VL 115
IS 16
BP 3642
EP 3656
DI 10.1021/jp1009669
PG 15
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 752NB
UT WOS:000289697500003
PM 20509636
ER
PT J
AU Damjanovic, A
Brooks, BR
Garcia-Moreno, EB
AF Damjanovic, Ana
Brooks, Bernard R.
Garcia-Moreno, Bertrand E.
TI Conformational Relaxation and Water Penetration Coupled to Ionization of
Internal Groups in Proteins
SO JOURNAL OF PHYSICAL CHEMISTRY A
LA English
DT Article
ID PH MOLECULAR-DYNAMICS; PHOTOACTIVE YELLOW PROTEIN; CONSTANT-PH;
STAPHYLOCOCCAL NUCLEASE; STRUCTURAL-CHANGES; PK(A) VALUES; HYDROPHOBIC
INTERIOR; IMPLICIT SOLVENT; ATP SYNTHASE; SUBUNIT-C
AB Molecular dynamics simulations were used to examine the effects of ionization of internal groups on the structures of eighteen variants of staphylococcal nuclease (SNase) with internal Lys, Asp, or Glu. In most cases the RMSD values of internal ionizable side chains were larger when the ionizable moieties were charged than when they were neutral. Calculations of solvent-accessible surface area showed that the internal ionizable side chains were buried in the protein interior when they were neutral and moved toward crevices and toward the protein-water interface when they were charged. The only exceptions are Lys-36, Lys-62, and Lys-103 which remained buried even after charging. With the exception of Lys-38, the number of internal water molecules surrounding the ionizable group increased upon charging: the average number of water oxygen atoms within the first hydration shell increased by 1.7 for Lys residues, by 5.2 for Asp residues, and by 3.2 for Glu residues. The polarity of the microenvironment of the ionizable group also increased when the groups were charged: the average number of polar atoms of any kind within the first hydration shell increased by 2.7 for Lys residues, by 4.8 for Asp residues, and by 4.0 for Glu residues. An unexpected correlation was observed between the absolute value of the shifts in pK(a) values measured experimentally, and several parameters of structural relaxation: the net difference in the polarity of the microenvironment of the charged and neutral forms of the ionizable groups, the net difference in hydration of the charged and neutral forms of the ionizable groups, and the difference in RMSD values of the charged and neutral forms of the ionizable groups. The effects of ionization of internal groups on the conformation of the backbone were noticeable but mostly small and localized to the area immediately next to the internal ionizable moiety. Some variants did exhibit local unfolding.
C1 [Damjanovic, Ana; Garcia-Moreno, Bertrand E.] Johns Hopkins Univ, Dept Biophys, Baltimore, MD 21218 USA.
[Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
RP Damjanovic, A (reprint author), Johns Hopkins Univ, Dept Biophys, Baltimore, MD 21218 USA.
EM ad@jhu.edu
FU NIH [R01 GM-073838]; NIH, NHLBI
FX This work was supported by the NIH grant (R01 GM-073838) to B.G.M.E. The
research was also supported by the Intramural research Program of the
NIH, NHLBI. Molecular dynamics runs were partly performed at the NIH
Biowulf cluster. We thank Petar Maksimovic for help with the program
ROOT.59
NR 61
TC 18
Z9 18
U1 1
U2 15
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 APR 28
PY 2011
VL 115
IS 16
BP 4042
EP 4053
DI 10.1021/jp110373f
PG 12
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 752NB
UT WOS:000289697500041
PM 21428436
ER
PT J
AU McCormack, FX
Inoue, Y
Moss, J
Singer, LG
Strange, C
Nakata, K
Barker, AF
Chapman, JT
Brantly, ML
Stocks, JM
Brown, KK
Lynch, JP
Goldberg, HJ
Young, LR
Kinder, BW
Downey, GP
Sullivan, EJ
Colby, TV
Mckay, RT
Cohen, MM
Korbee, L
Taveira-DaSilva, AM
Lee, HS
Krischer, JP
Trapnell, BC
AF McCormack, Francis X.
Inoue, Yoshikazu
Moss, Joel
Singer, Lianne G.
Strange, Charlie
Nakata, Koh
Barker, Alan F.
Chapman, Jeffrey T.
Brantly, Mark L.
Stocks, James M.
Brown, Kevin K.
Lynch, Joseph P., III
Goldberg, Hilary J.
Young, Lisa R.
Kinder, Brent W.
Downey, Gregory P.
Sullivan, Eugene J.
Colby, Thomas V.
Mckay, Roy T.
Cohen, Marsha M.
Korbee, Leslie
Taveira-DaSilva, Angelo M.
Lee, Hye-Seung
Krischer, Jeffrey P.
Trapnell, Bruce C.
CA Natl Inst Hlth Rare Lung Dis Conso
MILES Trial Grp
TI Efficacy and Safety of Sirolimus in Lymphangioleiomyomatosis
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID TUBEROUS SCLEROSIS COMPLEX; PULMONARY LYMPHANGIOLEIOMYOMATOSIS;
LUNG-FUNCTION; CELLS; LYMPHANGIOGENESIS; TRANSPLANTATION; PROGESTERONE;
PROGRESSION; MECHANISM; DECLINE
AB BACKGROUND
Lymphangioleiomyomatosis (LAM) is a progressive, cystic lung disease in women; it is associated with inappropriate activation of mammalian target of rapamycin (mTOR) signaling, which regulates cellular growth and lymphangiogenesis. Sirolimus (also called rapamycin) inhibits mTOR and has shown promise in phase 1-2 trials involving patients with LAM.
METHODS
We conducted a two-stage trial of sirolimus involving 89 patients with LAM who had moderate lung impairment - a 12-month randomized, double-blind comparison of sirolimus with placebo, followed by a 12-month observation period. The primary end point was the difference between the groups in the rate of change (slope) in forced expiratory volume in 1 second (FEV(1)).
RESULTS
During the treatment period, the FEV(1) slope was -12 +/- 2 ml per month in the placebo group (43 patients) and 1 +/- 2 ml per month in the sirolimus group (46 patients) (P<0.001). The absolute between-group difference in the mean change in FEV(1) during the treatment period was 153 ml, or approximately 11% of the mean FEV(1) at enrollment. As compared with the placebo group, the sirolimus group had improvement from baseline to 12 months in measures of forced vital capacity, functional residual capacity, serum vascular endothelial growth factor D (VEGF-D), and quality of life and functional performance. There was no significant between-group difference in this interval in the change in 6-minute walk distance or diffusing capacity of the lung for carbon monoxide. After discontinuation of sirolimus, the decline in lung function resumed in the sirolimus group and paralleled that in the placebo group. Adverse events were more common with sirolimus, but the frequency of serious adverse events did not differ significantly between the groups.
CONCLUSIONS
In patients with LAM, sirolimus stabilized lung function, reduced serum VEGF-D levels, and was associated with a reduction in symptoms and improvement in quality of life. Therapy with sirolimus may be useful in selected patients with LAM.
C1 [McCormack, Francis X.; Young, Lisa R.; Kinder, Brent W.; Mckay, Roy T.; Trapnell, Bruce C.] Univ Cincinnati, Cincinnati, OH USA.
[Young, Lisa R.; Korbee, Leslie; Trapnell, Bruce C.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
[Inoue, Yoshikazu] Natl Hosp Org, Kinki Chuo Chest Med Ctr, Osaka, Japan.
[Nakata, Koh] Niigata Univ, Med & Dent Hosp, Niigata, Japan.
[Moss, Joel; Taveira-DaSilva, Angelo M.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Sullivan, Eugene J.] United Therapeut, Silver Spring, MD USA.
[Singer, Lianne G.; Downey, Gregory P.; Cohen, Marsha M.] Univ Toronto, Toronto, ON, Canada.
[Strange, Charlie] Med Univ S Carolina, Charleston, SC 29425 USA.
[Barker, Alan F.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Chapman, Jeffrey T.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Brantly, Mark L.] Univ Florida, Gainesville, FL USA.
[Stocks, James M.] Univ Texas Hlth Sci Ctr Tyler, Tyler, TX USA.
[Brown, Kevin K.; Downey, Gregory P.] Natl Jewish Hlth, Denver, CO USA.
[Lynch, Joseph P., III] Univ Calif Los Angeles, Los Angeles, CA USA.
[Goldberg, Hilary J.] Harvard Univ, Sch Med, Boston, MA USA.
[Colby, Thomas V.] Mayo Clin, Scottsdale, AZ USA.
[Lee, Hye-Seung; Krischer, Jeffrey P.] Univ S Florida, Tampa, FL USA.
RP McCormack, FX (reprint author), MSB 6114,231 Albert Sabin Way, Cincinnati, OH 45267 USA.
EM frank.mccormack@uc.edu
OI McCormack, Francis/0000-0001-7168-9464; Strange,
Charlie/0000-0002-8109-8067; Downey, Gregory/0000-0003-3253-5862;
Singer, Lianne/0000-0002-2693-8676
FU NIH Office of Rare Disease Research [RR019498, RR019259]; Food and Drug
Administration [FD003362]; Canadian Institutes of Health Research;
Pfizer (formerly Wyeth) Pharmaceuticals; Japanese Ministry of Health,
Labor, and Welfare [H-19-Rinshoshiken-008]; Tuberous Sclerosis Alliance;
Cincinnati Children's Hospital Medical Center [1UL1RR026314-01]; Vi and
John Adler; Adler Foundation; Division of Intramural Research, National
Heart, Lung, and Blood Institute; Pfizer
FX Supported by grants from the NIH Office of Rare Disease Research,
administered by the National Center for Research Resources (RR019498, to
Drs. Trapnell and McCormack; and RR019259, to Drs. Lee and Krischer),
the Food and Drug Administration (FD003362, to Dr. McCormack), Canadian
Institutes of Health Research (to Drs. Downey, Cohen, and Singer),
Pfizer (formerly Wyeth) Pharmaceuticals (to Dr. McCormack), the Japanese
Ministry of Health, Labor, and Welfare (H-19-Rinshoshiken-008, to Drs.
Nakata and Inoue), the LAM Foundation (to Dr. McCormack), the Tuberous
Sclerosis Alliance (Rothberg Courage Award, to Dr. McCormack),
Cincinnati Children's Hospital Medical Center (Institutional Clinical
and Translational Science Award 1UL1RR026314-01, to Drs. Young and
McCormack, and Translational Research Initiative Award, to Drs.
McCormack and Trapnell), Vi and John Adler, and the Adler Foundation.
Drs. Moss and Taveira-DaSilva were supported by the Division of
Intramural Research, National Heart, Lung, and Blood Institute. Pfizer
provided the study drug and money for study visit costs.
NR 27
TC 329
Z9 341
U1 2
U2 21
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 APR 28
PY 2011
VL 364
IS 17
BP 1595
EP 1606
DI 10.1056/NEJMoa1100391
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 755NW
UT WOS:000289940400006
PM 21410393
ER
PT J
AU Velazquez, EJ
Lee, KL
Deja, MA
Jain, A
Sopko, G
Marchenko, A
Ali, IS
Pohost, G
Gradinac, S
Abraham, WT
Yii, M
Prabhakaran, D
Szwed, H
Ferrazzi, P
Petrie, MC
O'Connor, CM
Panchavinnin, P
She, LL
Bonow, RO
Rankin, GR
Jones, RH
Rouleau, JL
AF Velazquez, Eric J.
Lee, Kerry L.
Deja, Marek A.
Jain, Anil
Sopko, George
Marchenko, Andrey
Ali, Imtiaz S.
Pohost, Gerald
Gradinac, Sinisa
Abraham, William T.
Yii, Michael
Prabhakaran, Dorairaj
Szwed, Hanna
Ferrazzi, Paolo
Petrie, Mark C.
O'Connor, Christopher M.
Panchavinnin, Pradit
She, Lilin
Bonow, Robert O.
Rankin, Gena Roush
Jones, Robert H.
Rouleau, Jean-Lucien
CA STICH Investigators
TI Coronary-Artery Bypass Surgery in Patients with Left Ventricular
Dysfunction
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID HEART-FAILURE; RANDOMIZED TRIAL; SURGICAL-TREATMENT; CLINICAL-TRIALS;
STABLE ANGINA; SURVIVAL-DATA; DISEASE; REVASCULARIZATION; GUIDELINES;
ASSOCIATION
AB BACKGROUND
The role of coronary-artery bypass grafting (CABG) in the treatment of patients with coronary artery disease and heart failure has not been clearly established.
METHODS
Between July 2002 and May 2007, a total of 1212 patients with an ejection fraction of 35% or less and coronary artery disease amenable to CABG were randomly assigned to medical therapy alone (602 patients) or medical therapy plus CABG (610 patients). The primary outcome was the rate of death from any cause. Major secondary outcomes included the rates of death from cardiovascular causes and of death from any cause or hospitalization for cardiovascular causes.
RESULTS
The primary outcome occurred in 244 patients (41%) in the medical-therapy group and 218 (36%) in the CABG group (hazard ratio with CABG, 0.86; 95% confidence interval [CI], 0.72 to 1.04; P = 0.12). A total of 201 patients (33%) in the medical-therapy group and 168 (28%) in the CABG group died from an adjudicated cardiovascular cause (hazard ratio with CABG, 0.81; 95% CI, 0.66 to 1.00; P = 0.05). Death from any cause or hospitalization for cardiovascular causes occurred in 411 patients (68%) in the medical-therapy group and 351 (58%) in the CABG group (hazard ratio with CABG, 0.74; 95% CI, 0.64 to 0.85; P<0.001). By the end of the follow-up period (median, 56 months), 100 patients in the medical-therapy group (17%) underwent CABG, and 555 patients in the CABG group (91%) underwent CABG.
CONCLUSIONS
In this randomized trial, there was no significant difference between medical therapy alone and medical therapy plus CABG with respect to the primary end point of death from any cause. Patients assigned to CABG, as compared with those assigned to medical therapy alone, had lower rates of death from cardiovascular causes and of death from any cause or hospitalization for cardiovascular causes.
C1 [Velazquez, Eric J.; She, Lilin; Rankin, Gena Roush] Duke Univ, Duke Clin Res Inst, Med Ctr, Durham, NC 27705 USA.
[Velazquez, Eric J.; O'Connor, Christopher M.] Duke Univ, Div Cardiovasc Med, Med Ctr, Durham, NC 27705 USA.
[Lee, Kerry L.] Duke Univ, Dept Biostat, Med Ctr, Durham, NC 27705 USA.
[Lee, Kerry L.] Duke Univ, Dept Bioinformat, Med Ctr, Durham, NC 27705 USA.
[Jones, Robert H.] Duke Univ, Dept Surg, Med Ctr, Durham, NC 27705 USA.
[Deja, Marek A.] Med Univ Silesia, Dept Cardiac Surg 2, Katowice, Poland.
[Szwed, Hanna] Natl Inst Cardiol, Warsaw, Poland.
[Jain, Anil] SAL Hosp & Med Inst, Ahmadabad, Gujarat, India.
[Prabhakaran, Dorairaj] Ctr Chron Dis Control, New Delhi, India.
[Sopko, George] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Marchenko, Andrey] Res Inst Circulat Pathol, Novosibirsk, Russia.
[Ali, Imtiaz S.] Dalhousie Univ, Div Cardiac Surg, Halifax, NS, Canada.
[Ali, Imtiaz S.] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada.
[Pohost, Gerald] Univ So Calif, Keck Sch Med, Viterbi Sch Engn, Los Angeles, CA 90033 USA.
[Gradinac, Sinisa] Univ Belgrade, Dedinje Cardiovasc Inst, Sch Med, Belgrade, Serbia.
[Abraham, William T.] Ohio State Univ, Div Cardiovasc Med, Columbus, OH 43210 USA.
[Yii, Michael] Univ Melbourne, St Vincents Hosp, Dept Cardiothorac Surg, Melbourne, Vic, Australia.
[Yii, Michael] Univ Melbourne, St Vincents Hosp, Dept Surg, Melbourne, Vic, Australia.
[Ferrazzi, Paolo] Osped Riuniti Bergamo, Dipartimento Cardiovasc Clin & Ric, I-24100 Bergamo, Italy.
[Petrie, Mark C.] Golden Jubilee Natl Hosp, Scottish Natl Adv Heart Failure Serv, Glasgow, Lanark, Scotland.
[Panchavinnin, Pradit] Mahidol Univ, Siriraj Hosp, Bangkok 10700, Thailand.
[Bonow, Robert O.] Northwestern Univ, Div Cardiol, Chicago, IL 60611 USA.
[Rouleau, Jean-Lucien] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.
RP Velazquez, EJ (reprint author), Duke Univ, Duke Clin Res Inst, Med Ctr, Rm 0311 Terrace Level,2400 Pratt St, Durham, NC 27705 USA.
EM eric.velazquez@duke.edu
RI Crestanello, Juan/E-2930-2011;
OI Prabhakaran, Dorairaj/0000-0002-3172-834X
FU National Heart, Lung, and Blood Institute [U01HL69015, U01HL69013];
Abbott Laboratories; Novartis; Gilead; Boehringer Ingelheim
Pharmaceuticals; Medtronic; St. Jude Medical; Biotronik; CardioMEMS
FX Supported by grants (U01HL69015 and U01HL69013) from the National Heart,
Lung, and Blood Institute and by Abbott Laboratories.; Dr. Velazquez
reports receiving consulting fees from Novartis, Gilead, and Boehringer
Ingelheim Pharmaceuticals; Dr. Abraham, consulting fees from Medtronic,
St. Jude Medical, Biotronik, and CardioMEMS; and Dr. Rouleau, consulting
fees and grant support from Novartis. No other potential conflict of
interest relevant to this article was reported.
NR 28
TC 355
Z9 374
U1 11
U2 44
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 APR 28
PY 2011
VL 364
IS 17
BP 1607
EP 1616
DI 10.1056/NEJMoa1100356
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 755NW
UT WOS:000289940400007
PM 21463150
ER
PT J
AU Bonow, RO
Maurer, G
Lee, KL
Holly, TA
Binkley, PF
Desvigne-Nickens, P
Drozdz, J
Farsky, PS
Feldman, AM
Doenst, T
Michler, RE
Berman, DS
Nicolau, JC
Pellikka, PA
Wrobel, K
Alotti, N
Asch, FM
Favaloro, LE
She, LL
Velazquez, EJ
Jones, RH
Panza, JA
AF Bonow, Robert O.
Maurer, Gerald
Lee, Kerry L.
Holly, Thomas A.
Binkley, Philip F.
Desvigne-Nickens, Patrice
Drozdz, Jaroslaw
Farsky, Pedro S.
Feldman, Arthur M.
Doenst, Torsten
Michler, Robert E.
Berman, Daniel S.
Nicolau, Jose C.
Pellikka, Patricia A.
Wrobel, Krzysztof
Alotti, Nasri
Asch, Federico M.
Favaloro, Liliana E.
She, Lilin
Velazquez, Eric J.
Jones, Robert H.
Panza, Julio A.
CA STICH Trial Investigators
TI Myocardial Viability and Survival in Ischemic Left Ventricular
Dysfunction
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID CORONARY-ARTERY-DISEASE; DOSE DOBUTAMINE ECHOCARDIOGRAPHY;
POSITRON-EMISSION-TOMOGRAPHY; BETA-BLOCKER THERAPY; LONG-TERM SURVIVAL;
PROGNOSTIC VALUE; HEART-FAILURE; HIBERNATING MYOCARDIUM; CONTRACTILE
RESERVE; SURGICAL-TREATMENT
AB BACKGROUND
The assessment of myocardial viability has been used to identify patients with coronary artery disease and left ventricular dysfunction in whom coronary-artery bypass grafting (CABG) will provide a survival benefit. However, the efficacy of this approach is uncertain.
METHODS
In a substudy of patients with coronary artery disease and left ventricular dysfunction who were enrolled in a randomized trial of medical therapy with or without CABG, we used single-photon-emission computed tomography (SPECT), dobutamine echocardiography, or both to assess myocardial viability on the basis of pre-specified thresholds.
RESULTS
Among the 1212 patients enrolled in the randomized trial, 601 underwent assessment of myocardial viability. Of these patients, we randomly assigned 298 to receive medical therapy plus CABG and 303 to receive medical therapy alone. A total of 178 of 487 patients with viable myocardium (37%) and 58 of 114 patients without viable myocardium (51%) died (hazard ratio for death among patients with viable myocardium, 0.64; 95% confidence interval [CI], 0.48 to 0.86; P = 0.003). However, after adjustment for other baseline variables, this association with mortality was not significant (P = 0.21). There was no significant interaction between viability status and treatment assignment with respect to mortality (P = 0.53).
CONCLUSIONS
The presence of viable myocardium was associated with a greater likelihood of survival in patients with coronary artery disease and left ventricular dysfunction, but this relationship was not significant after adjustment for other baseline variables. The assessment of myocardial viability did not identify patients with a differential survival benefit from CABG, as compared with medical therapy alone.
C1 [Bonow, Robert O.] Northwestern Univ, Ctr Cardiovasc Innovat, Feinberg Sch Med, Chicago, IL 60611 USA.
[Maurer, Gerald] Med Univ Vienna, Vienna, Austria.
[Lee, Kerry L.; She, Lilin; Velazquez, Eric J.; Jones, Robert H.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
[Binkley, Philip F.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA.
[Desvigne-Nickens, Patrice] NHLBI, Bethesda, MD 20892 USA.
[Drozdz, Jaroslaw] Med Univ Lodz, Lodz, Poland.
[Wrobel, Krzysztof] John Paul 2 Hosp, Krakow, Poland.
[Farsky, Pedro S.] Univ Sao Paulo, Inst Dante Pazzanese Cardiol, Sao Paulo, Brazil.
[Nicolau, Jose C.] Univ Sao Paulo, Hosp Clin, Fac Med, Inst Coracao, Sao Paulo, Brazil.
[Feldman, Arthur M.] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA.
[Doenst, Torsten] Univ Leipzig, Ctr Heart, Leipzig, Germany.
[Michler, Robert E.] Albert Einstein Coll Med, Montefiore Med Ctr, New York, NY USA.
[Berman, Daniel S.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Pellikka, Patricia A.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA.
[Alotti, Nasri] Zala Cty Hosp, Zalaegerszeg, Hungary.
[Asch, Federico M.; Panza, Julio A.] Washington Hosp Ctr, Washington, DC 20010 USA.
[Favaloro, Liliana E.] Univ Hosp, Favaloro Fdn, Buenos Aires, DF, Argentina.
RP Bonow, RO (reprint author), Northwestern Univ, Ctr Cardiovasc Innovat, Feinberg Sch Med, 645 N Michigan Ave,Suite 1006, Chicago, IL 60611 USA.
EM r-bonow@northwestern.edu
RI Binkley, Philip/E-2759-2011; Nicolau, Jose/E-1487-2012; Crestanello,
Juan/E-2930-2011
FU National Heart, Lung, and Blood Institute [U01-HL-069009, HL-069010,
HL-069011, HL-069012, HL-069012-03, HL-069013, HL-069015, HL-070011,
HL-072683]; Sorin; Astellas Healthcare; Bracco; Lantheus Medical
Imaging; Mitralign; RegeneRx; Novartis; Gilead; Boehringer Ingelheim
Pharmaceuticals
FX Supported by cooperative agreements (U01-HL-069009, HL-069010,
HL-069011, HL-069012, HL-069012-03, HL-069013, HL-069015, HL-070011, and
HL-072683) with the National Heart, Lung, and Blood Institute.; Dr.
Feldman reports having an equity interest in Cardiokine; Dr. Michler,
receiving grant support from Sorin; Dr. Berman, receiving consulting
fees from Astellas Healthcare, Bracco, and Lantheus Medical Imaging and
grant support from Lantheus Medical Imaging and Astellas Healthcare and
having an equity interest in Spectrum Dynamics; Dr. Asch, being an
investigator in studies for which his institution received grant support
from Sorin, Mitralign, and RegeneRx; and Dr. Velazquez, receiving
consulting fees from Novartis, Gilead, and Boehringer Ingelheim
Pharmaceuticals. No other potential conflict of interest relevant to
this article was reported.
NR 45
TC 286
Z9 296
U1 3
U2 30
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 APR 28
PY 2011
VL 364
IS 17
BP 1617
EP 1625
DI 10.1056/NEJMoa1100358
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 755NW
UT WOS:000289940400008
PM 21463153
ER
PT J
AU Bungay, PM
Sumbria, RK
Bickel, U
AF Bungay, Peter M.
Sumbria, Rachita K.
Bickel, Ulrich
TI Unifying the mathematical modeling of in vivo and in vitro microdialysis
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE Microdialysis; Mathematical model; Extraction efficiency; Diffusion
ID DUAL-PROBE MICRODIALYSIS; QUANTITATIVE MICRODIALYSIS; DIFFUSION; BRAIN
AB A unifying approach is presented for developing mathematical models of microdialysis that are applicable to both in vitro and in vivo situations. Previous models for cylindrical probes have been limited by accommodating analyte diffusion through the surrounding medium in the radial direction only, i.e., perpendicular to the probe axis, or by incomplete incorporation of diffusion in the axial direction. Both radial and axial diffusion are included in the present work by employing two-dimensional finite element analysis. As in previous models, the nondimensional clearance modulus (Theta) represents the degree to which analyte clearance from the external medium influences diffusion through the medium for systems exhibiting analyte concentration linearity. Incorporating axial diffusion introduces a second dimensionless group, which is the length-to-radius aspect ratio of the membrane. These two parameter groups uniquely determine the external medium permeability, which is time dependent under transient conditions. At steady-state, the dependence of this permeability on the two groups can be approximated by an algebraic formula for much of the parameter ranges. Explicit steady-state expressions derived for the membrane and fluid permeabilities provide good approximations under transient conditions (quasi-steady-state assumption). The predictive ability of the unifying approach is illustrated for microdialysis of sucrose in vivo (brain) and inert media in vitro, under both well-stirred and quiescent conditions. Published by Elsevier B.V.
C1 [Bungay, Peter M.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
[Sumbria, Rachita K.; Bickel, Ulrich] Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Dept Pharmaceut Sci, Amarillo, TX 79106 USA.
[Sumbria, Rachita K.; Bickel, Ulrich] Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Ctr Vasc Drug Res, Amarillo, TX 79106 USA.
RP Bungay, PM (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, Bldg 13-3N17, Bethesda, MD 20892 USA.
EM bungayp@mail.nih.gov
FU NIH, National Institute of Biomedical Imaging and Bioengineering
FX This research was supported [in part] by the Intramural Research
Programs of the NIH, including the National Institute of Biomedical
Imaging and Bioengineering. The authors are grateful to Paul F. Morrison
for his critical review of the manuscript and suggestions for revision.
NR 16
TC 8
Z9 8
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0731-7085
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD APR 28
PY 2011
VL 55
IS 1
BP 54
EP 63
DI 10.1016/j.jpba.2011.01.005
PG 10
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 734UT
UT WOS:000288365900006
PM 21310575
ER
PT J
AU Huang, RL
Southall, N
Wang, YH
Yasgar, A
Shinn, P
Jadhav, A
Nguyen, DT
Austin, CP
AF Huang, Ruili
Southall, Noel
Wang, Yuhong
Yasgar, Adam
Shinn, Paul
Jadhav, Ajit
Dac-Trung Nguyen
Austin, Christopher P.
TI The NCGC Pharmaceutical Collection: A Comprehensive Resource of
Clinically Approved Drugs Enabling Repurposing and Chemical Genomics
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID IDENTIFICATION; PREGABALIN; LIBRARIES; FIBROMYALGIA; WITHDRAWALS;
SAFETY; AGENT; PHASE; TRIAL
AB Small-molecule compounds approved for use as drugs may be "repurposed" for new indications and studied to determine the mechanisms of their beneficial and adverse effects. A comprehensive collection of all small-molecule drugs approved for human use would be invaluable for systematic repurposing across human diseases, particularly for rare and neglected diseases, for which the cost and time required for development of a new chemical entity are often prohibitive. Previous efforts to build such a comprehensive collection have been limited by the complexities, redundancies, and semantic inconsistencies of drug naming within and among regulatory agencies worldwide; a lack of clear conceptualization of what constitutes a drug; and a lack of access to physical samples. We report here the creation of a definitive, complete, and nonredundant list of all approved molecular entities as a freely available electronic resource and a physical collection of small molecules amenable to high-throughput screening.
C1 [Huang, Ruili; Southall, Noel; Wang, Yuhong; Yasgar, Adam; Shinn, Paul; Jadhav, Ajit; Dac-Trung Nguyen; Austin, Christopher P.] NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
RP Austin, CP (reprint author), NIH, Chem Genom Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM austinc@mail.nih.gov
RI Southall, Noel/H-8991-2012
OI Southall, Noel/0000-0003-4500-880X
FU National Human Genome Research Institute, NIH
FX This work was supported by the Intramural Program of the National Human
Genome Research Institute, NIH.
NR 63
TC 111
Z9 111
U1 3
U2 17
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD APR 27
PY 2011
VL 3
IS 80
AR 80ps16
DI 10.1126/scitranslmed.3001862
PG 12
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 795MC
UT WOS:000292977300002
PM 21525397
ER
PT J
AU Ryabov, Y
Schwieters, CD
Clore, GM
AF Ryabov, Yaroslav
Schwieters, Charles D.
Clore, G. Marius
TI Impact of N-15 R-2/R-1 Relaxation Restraints on Molecular Size, Shape,
and Bond Vector Orientation for NMR Protein Structure Determination with
Sparse Distance Restraints
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID RESIDUAL DIPOLAR COUPLINGS; ROTATIONAL DIFFUSION ANISOTROPY; LONG-RANGE
ORDER; MULTIDIMENSIONAL NMR; CHEMICAL-SHIFTS; PHOSPHOTRANSFERASE SYSTEM;
3-DIMENSIONAL STRUCTURES; GLOBULAR-PROTEINS; TERMINAL DOMAIN; GLOBAL
FOLDS
AB N-15 R-2/R-1 relaxation data contain information on molecular shape and size as well as on bond vector orientations relative to the diffusion tensor. Since the diffusion tensor can be directly calculated from the molecular coordinates, direct inclusion of N-15 R-2/R-1 restraints in NMR structure calculations without any a priori assumptions is possible. Here we show that N-15 R-2/R-1 restraints are particularly valuable when only sparse distance restraints are available. Using three examples of proteins of varying size, namely, GB3 (56 residues), ubiquitin (76 residues), and the N-terminal domain of enzyme I (EIN, 249 residues), we show that incorporation of N-15 R-2/R-1 restraints results in large and significant increases in coordinate accuracy that can make the difference between being able or unable to determine an approximate global fold. For GB3 and ubiquitin, good coordinate accuracy was obtained using only backbone hydrogen-bond restraints supplemented by N-15 R-2/R-1 relaxation restraints. For EIN, the global fold could be determined using sparse nuclear Overhauser enhancement (NOE) distance restraints involving only NH and methyl groups in conjunction with N-15 R-2/R-1 restraints. These results are of practical significance in the study of larger and more complex systems, where the increasing spectral complexity and number of chemical shift degeneracies reduce the number of unambiguous NOE asssignments that can be readily obtained, resulting in progressively reduced NOE coverage as the size of the protein increases.
C1 [Ryabov, Yaroslav; Schwieters, Charles D.] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Clore, G. Marius] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Schwieters, CD (reprint author), NIH, Div Computat Biosci, Ctr Informat Technol, Bldg 12A, Bethesda, MD 20892 USA.
EM charles.schwieters@nih.gov; mariusc@mail.nih.gov
RI Clore, G. Marius/A-3511-2008
OI Clore, G. Marius/0000-0003-3809-1027
FU NIH; NIDDK; Office of the Director of the NIH
FX This work was supported by the NIH Intramural Research Programs of CIT
(C.D.S.) and NIDDK (G.M.C.) and by the AIDS Targeted Antiviral Program
of the Office of the Director of the NIH (G.M.C.)
NR 38
TC 5
Z9 5
U1 1
U2 7
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 APR 27
PY 2011
VL 133
IS 16
BP 6154
EP 6157
DI 10.1021/ja201020c
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA 792BM
UT WOS:000292715500015
PM 21462982
ER
PT J
AU Sgourakis, NG
Lange, OF
DiMaio, F
Andre, I
Fitzkee, NC
Rossi, P
Montelione, GT
Bax, A
Baker, D
AF Sgourakis, Nikolaos G.
Lange, Oliver F.
DiMaio, Frank
Andre, Ingemar
Fitzkee, Nicholas C.
Rossi, Paolo
Montelione, Gaetano T.
Bax, Ad
Baker, David
TI Determination of the Structures of Symmetric Protein Oligomers from NMR
Chemical Shifts and Residual Dipolar Couplings
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID HIV-1 CAPSID PROTEIN; X-RAY-SCATTERING; HIGH-RESOLUTION;
CRYSTAL-STRUCTURE; TUMOR-SUPPRESSOR; CORE DOMAIN; DOCKING; COMPLEXES;
ALIGNMENT; DYNAMICS
AB Symmetric protein dimers, trimers, and higher-order cyclic oligomers play key roles in many biological processes. However, structural studies of oligomeric systems by solution NMR can be difficult due to slow tumbling of the system and the difficulty in identifying NOE interactions across protein interfaces. Here, we present an automated method (RosettaOligomers) for determining the solution structures of oligomeric systems using only chemical shifts, sparse NOEs, and domain orientation restraints from residual dipolar couplings (RDCs) without a need for a previously determined structure of the monomeric subunit. The method integrates previously developed Rosetta protocols for solving the structures of monomeric proteins using sparse NMR data and for predicting the structures of both nonintertwined and intertwined symmetric oligomers. We illustrated the performance of the method using a benchmark set of nine protein dimers, one trimer, and one tetramer with available experimental data and various interface topologies. The final converged structures are found to be in good agreement with both experimental data and previously published high-resolution structures. The new approach is more readily applicable to large oligomeric systems than conventional structure-determination protocols, which often require a large number of NOEs, and will likely become increasingly relevant as more high-molecular weight systems are studied by NMR
C1 [Sgourakis, Nikolaos G.; Lange, Oliver F.; DiMaio, Frank; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
[Baker, David] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA.
[Andre, Ingemar] Lund Univ, Ctr Chem, Ctr Mol Prot Sci, Dept Biochem & Struct Biol, SE-22100 Lund, Sweden.
[Fitzkee, Nicholas C.; Bax, Ad] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Rossi, Paolo; Montelione, Gaetano T.] Rutgers State Univ, Dept Mol Biol & Biochem, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA.
[Rossi, Paolo; Montelione, Gaetano T.] Rutgers State Univ, NE Struct Genom Consortium, Piscataway, NJ 08854 USA.
RP Baker, D (reprint author), Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
EM dabaker@u.washington.edu
RI Lange, Oliver/K-5749-2012; Andre, Ingemar/O-4777-2014; Baker,
David/K-8941-2012
OI Lange, Oliver/0000-0002-4018-7020; Andre, Ingemar/0000-0002-4753-8233;
Baker, David/0000-0001-7896-6217
FU NIH [5R01GM092802 - 02]; HHMI; NIDDK, NIH; Office of the Director, NIH;
Knut and Alice Wallenberg foundation; Human Frontiers of Science Program
FX This work was supported by NIH (grant 5R01GM092802 - 02) and HHMI (to
D.B.), the Intramural Research Program of the NIDDK, NIH, by the
Intramural AIDS-Targeted Antiviral Program of the Office of the
Director, NIH (to A.B.), and by an NIH Intramural AIDS Research
Postdoctoral Fellowship (to N.C.F.). A fellowship by Knut and Alice
Wallenberg foundation (to I.A.) and the Human Frontiers of Science
Program (to O.F.L.).
NR 59
TC 38
Z9 38
U1 0
U2 20
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 APR 27
PY 2011
VL 133
IS 16
BP 6288
EP 6298
DI 10.1021/ja111318m
PG 11
WC Chemistry, Multidisciplinary
SC Chemistry
GA 792BM
UT WOS:000292715500032
PM 21466200
ER
PT J
AU Hu, VW
Addington, A
Hyman, A
AF Hu, Valerie W.
Addington, Anjene
Hyman, Alexander
TI Novel Autism Subtype-Dependent Genetic Variants Are Revealed by
Quantitative Trait and Subphenotype Association Analyses of Published
GWAS Data
SO PLOS ONE
LA English
DT Article
ID SPECTRUM DISORDERS; TUBEROUS-SCLEROSIS; GTP CYCLOHYDROLASE; LOCUS
ANALYSIS; LINKAGE; COMMON; SCAN; HAPLOTYPE; FAMILIES; 5P14.1
AB The heterogeneity of symptoms associated with autism spectrum disorders (ASDs) has presented a significant challenge to genetic analyses. Even when associations with genetic variants have been identified, it has been difficult to associate them with a specific trait or characteristic of autism. Here, we report that quantitative trait analyses of ASD symptoms combined with case-control association analyses using distinct ASD subphenotypes identified on the basis of symptomatic profiles result in the identification of highly significant associations with 18 novel single nucleotide polymorphisms (SNPs). The symptom categories included deficits in language usage, non-verbal communication, social development, and play skills, as well as insistence on sameness or ritualistic behaviors. Ten of the trait-associated SNPs, or quantitative trait loci (QTL), were associated with more than one subtype, providing partial replication of the identified QTL. Notably, none of the novel SNPs is located within an exonic region, suggesting that these hereditary components of ASDs are more likely related to gene regulatory processes (or gene expression) than to structural or functional changes in gene products. Seven of the QTL reside within intergenic chromosomal regions associated with rare copy number variants that have been previously reported in autistic samples. Pathway analyses of the genes associated with the QTL identified in this study implicate neurological functions and disorders associated with autism pathophysiology. This study underscores the advantage of incorporating both quantitative traits as well as subphenotypes into large-scale genome-wide analyses of complex disorders.
C1 [Hu, Valerie W.; Hyman, Alexander] George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA.
[Addington, Anjene] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA.
RP Hu, VW (reprint author), George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA.
EM bcmvwh@gwumc.edu
OI Hu, Valerie/0000-0002-3357-0777
NR 36
TC 29
Z9 29
U1 1
U2 6
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 APR 27
PY 2011
VL 6
IS 4
AR e19067
DI 10.1371/journal.pone.0019067
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 756NO
UT WOS:000290019400027
PM 21556359
ER
PT J
AU Pomeroy, J
Brage, S
Curtis, JM
Swan, PD
Knowler, WC
Franks, PW
AF Pomeroy, Jeremy
Brage, Soren
Curtis, Jeffrey M.
Swan, Pamela D.
Knowler, William C.
Franks, Paul W.
TI Between-Monitor Differences in Step Counts Are Related to Body Size:
Implications for Objective Physical Activity Measurement
SO PLOS ONE
LA English
DT Article
ID AMBULATORY ACTIVITY; PEDOMETER ACCURACY; ENERGY-EXPENDITURE;
BLOOD-PRESSURE; LIFE-STYLE; WALKING; ADULTS; OVERWEIGHT; PREVENTION;
SEDENTARY
AB Background: The quantification of the relationships between walking and health requires that walking is measured accurately. We correlated different measures of step accumulation to body size, overall physical activity level, and glucose regulation.
Methods: Participants were 25 men and 25 women American Indians without diabetes (Age: 20-34 years) in Phoenix, Arizona, USA. We assessed steps/day during 7 days of free living, simultaneously with three different monitors (Accusplit-AX120, MTI-ActiGraph, and Dynastream-AMP). We assessed total physical activity during free-living with doubly labeled water combined with resting metabolic rate measured by expired gas indirect calorimetry. Glucose tolerance was determined during an oral glucose tolerance test.
Findings: Based on observed counts in the laboratory, the AMP was the most accurate device, followed by the MTI and the AX120, respectively. The estimated energy cost of 1000 steps per day was lower in the AX120 than the MTI or AMP. The correlation between AX120-assessed steps/day and waist circumference was significantly higher than the correlation between AMP steps and waist circumference. The difference in steps per day between the AX120 and both the AMP and the MTI were significantly related to waist circumference.
Interpretation: Between-monitor differences in step counts influence the observed relationship between walking and obesity-related traits.
C1 [Pomeroy, Jeremy; Brage, Soren; Curtis, Jeffrey M.; Knowler, William C.; Franks, Paul W.] NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA.
[Pomeroy, Jeremy; Swan, Pamela D.] Arizona State Univ, Coll Nursing & Hlth Innovat, Hlth Lifestyle Res Ctr, Phoenix, AZ USA.
[Franks, Paul W.] Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden.
[Brage, Soren] MRC Epidemiol Unit, Cambridge, England.
RP Pomeroy, J (reprint author), NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA.
EM jeremy.pomeroy@nih.gov
RI Brage, Soren/C-6415-2013;
OI Brage, Soren/0000-0002-1265-7355; Franks, Paul/0000-0002-0520-7604
FU NIDDK; National Cancer Institute; Visare Norr Foundation
FX This research was supported by the NIDDK intramural research program and
the National Cancer Institute. PWF was also supported in part by a grant
from the Visare Norr Foundation. Dynastream Inc, Cochrane, Alberta,
Canada loaned the AMP-331 activity monitors. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript. No additional external funding received
for this study.
NR 31
TC 6
Z9 6
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 APR 27
PY 2011
VL 6
IS 4
AR e18942
DI 10.1371/journal.pone.0018942
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 756NO
UT WOS:000290019400020
PM 21556140
ER
PT J
AU Joullie, MM
Berritt, S
Hamel, E
AF Joullie, Madeleine M.
Berritt, Simon
Hamel, Ernest
TI Structure-activity relationships of ustiloxin analogues
SO TETRAHEDRON LETTERS
LA English
DT Article
DE Ustiloxin; Tubulin polymerization; Aziridine ring opening;
Structure-activity relationships
ID FALSE SMUT BALLS; NATURAL-PRODUCTS; RICE PANICLES; DERIVATIVES; TUBULIN
AB Four novel ustiloxin D analogues were synthesized focusing on the size of the macrocyclic core, the stereochemistry at the bridgehead ether, and the enantiomer of ustiloxin D. All four were subjected to biological evaluation testing the inhibition of tubulin polymerization. Only 2,2-dimethyl-ustiloxin D retained any activity. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Joullie, Madeleine M.; Berritt, Simon] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA.
[Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA.
RP Joullie, MM (reprint author), Univ Penn, Dept Chem, 231 S 34th St, Philadelphia, PA 19104 USA.
EM mjoullie@sas.upenn.edu
OI Berritt, Simon/0000-0001-5572-6771
FU NIH [CA-40081, 1S10RR23444-1]; NSF [CHE-0951394]
FX We thank NIH (CA-40081) and NSF (CHE-0951394) for support of this work.
Financial support for the departmental instrumentation was provided by
NIH (1S10RR23444-1). We also thank Dr. George Furst and Dr. Rakesh Kohli
for NMR and MS assistance, respectively.
NR 14
TC 9
Z9 9
U1 1
U2 14
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0040-4039
J9 TETRAHEDRON LETT
JI Tetrahedron Lett.
PD APR 27
PY 2011
VL 52
IS 17
SI SI
BP 2136
EP 2139
DI 10.1016/j.tetlet.2010.11.165
PG 4
WC Chemistry, Organic
SC Chemistry
GA 758RT
UT WOS:000290184700031
PM 21607116
ER
PT J
AU Chen, XB
Nelson, CD
Li, X
Winters, CA
Azzam, R
Sousa, AA
Leapman, RD
Gainer, H
Sheng, M
Reese, TS
AF Chen, Xiaobing
Nelson, Christopher D.
Li, Xiang
Winters, Christine A.
Azzam, Rita
Sousa, Alioscka A.
Leapman, Richard D.
Gainer, Harold
Sheng, Morgan
Reese, Thomas S.
TI PSD-95 Is Required to Sustain the Molecular Organization of the
Postsynaptic Density
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID MAGUK SCAFFOLDING PROTEINS; NMDA RECEPTOR SUBUNITS; AMPA RECEPTORS;
SYNAPTIC FUNCTION; GLUTAMATE RECEPTORS; EXCITATORY SYNAPSES; GUANYLATE
KINASES; DOMAIN; TRAFFICKING; EXPRESSION
AB PSD-95, a membrane-associated guanylate kinase, is the major scaffolding protein in the excitatory postsynaptic density (PSD) and a potent regulator of synaptic strength. Here we show that PSD-95 is in an extended configuration and positioned into regular arrays of vertical filaments that contact both glutamate receptors and orthogonal horizontal elements layered deep inside the PSD in rat hippocampal spine synapses. RNA interference knockdown of PSD-95 leads to loss of entire patches of PSD material, and electron microscopy tomography shows that the patchy loss correlates with loss of PSD-95-containing vertical filaments, horizontal elements associated with the vertical filaments, and putative AMPA receptor-type, but not NMDA receptor-type, structures. These observations show that the orthogonal molecular scaffold constructed from PSD-95-containing vertical filaments and their associated horizontal elements is essential for sustaining the three-dimensional molecular organization of the PSD. Our findings provide a structural basis for understanding the functional role of PSD-95 at the PSD.
C1 [Chen, Xiaobing; Winters, Christine A.; Azzam, Rita; Reese, Thomas S.] Natl Inst Neurol Disorders & Stroke, Neurobiol Lab, NIH, Bethesda, MD 20892 USA.
[Gainer, Harold] Natl Inst Neurol Disorders & Stroke, Neurochem Lab, NIH, Bethesda, MD 20892 USA.
[Nelson, Christopher D.; Sheng, Morgan] MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA.
[Nelson, Christopher D.; Sheng, Morgan] Genentech Inc, Dept Neurosci, San Francisco, CA 94080 USA.
[Li, Xiang] Columbia Univ, Neurosci Program, New York, NY 10027 USA.
[Sousa, Alioscka A.; Leapman, Richard D.] Natl Inst Biomed Imaging & Bioengn, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA.
RP Reese, TS (reprint author), Natl Inst Neurol Disorders & Stroke, Neurobiol Lab, NIH, Bldg 49 3A60, Bethesda, MD 20892 USA.
EM treese@mbl.edu
FU National Institute of Neurological Disorders and Stroke (NINDS);
National Institute of Biomedical Imaging and Bioengineering
FX The work was supported by National Institute of Neurological Disorders
and Stroke (NINDS) and National Institute of Biomedical Imaging and
Bioengineering intramural research programs and Morgan Sheng was an
investigator of Howard Hughes Medical Institute. We thank Dr. Susan
Cheng and Virginia Crocker of NINDS Electron Microscopy Facility for
their help on immunogold labeling; Dr. Carolyn Smith and Dr. Paul
Gallant of NINDS Light Imaging Facility for their guidance on
immunofluorescence microscopy and laser confocal light microscopy; Dr.
Ayse Dosemeci for PSD-95 antibody; Drs. Carolyn Smith, Brian Andrews,
and Ronald Petralia for critical reading of the manuscript; and John
Chludzinski, Sam Carton, and Austin Hou for help on data analysis.
NR 51
TC 68
Z9 70
U1 3
U2 16
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD APR 27
PY 2011
VL 31
IS 17
BP 6329
EP 6338
DI 10.1523/JNEUROSCI.5968-10.2011
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 755MB
UT WOS:000289934600009
PM 21525273
ER
PT J
AU Wang, H
Ge, GN
Uchida, Y
Luu, B
Ahn, S
AF Wang, Hui
Ge, Guannan
Uchida, Yutaka
Luu, Brian
Ahn, Sohyun
TI Gli3 Is Required for Maintenance and Fate Specification of Cortical
Progenitors
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID NEURAL STEM-CELLS; SONIC HEDGEHOG; DEVELOPING NEOCORTEX; DORSAL
TELENCEPHALON; CEREBRAL-CORTEX; MULTIPLE ROLES; NERVOUS-SYSTEM; RADIAL
GLIA; GENE; EXPRESSION
AB Gli3, one of three vertebrate Gli transcription factors in Hedgehog (Hh) pathway, is processed into a repressor form (Gli3R) in the absence of Hh signal and acts as the major negative transducer of the pathway. Although the role of Gli3 in embryonic patterning has been extensively studied, its role in cortical neurogenesis, especially in the regulation of neural progenitors in proliferation and cell fate specification, is largely unknown. To bypass the patterning defects caused by loss of Gli3, we conditionally deleted Gli3 after patterning was complete in mouse. Our results from birthdating and in utero electroporation experiments demonstrate that the Gli3, specifically Gli3R, is critical for specifying the fate of cortical neurons that are generated following a stereotypical temporal order. Moreover, Gli3 is required for maintaining the cortical progenitors in active cell cycle, suggesting that cells may acquire differentiated status as they turn off Gli3 expression during neurogenesis.
C1 [Wang, Hui; Ge, Guannan; Luu, Brian; Ahn, Sohyun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Dev Neurogenet, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[Uchida, Yutaka] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Ahn, S (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Dev Neurogenet, Program Genom Differentiat, NIH, 9000 Rockville Pike 6B-2B220, Bethesda, MD 20892 USA.
EM ahnsohyun@mail.nih.gov
FU National Institutes of Health
FX This work was supported by Intramural Research Program of National
Institutes of Health. We thank Y. Zhao and members of Ahn laboratory for
critical comments on the manuscript; A. Joyner, T. Haydar, B. Wang, and
A. McMahon for providing mice and reagents; National Institute of Child
Health and Human Development Microscopy and Imaging Core for the use of
a confocal microscope; and T. Haydar for advice on in utero
electroporation. We are especially grateful to M. Zervas, J. Li, and Y.
Mukoyama for their comments and discussions during various stages of
this work.
NR 34
TC 24
Z9 25
U1 0
U2 4
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 APR 27
PY 2011
VL 31
IS 17
BP 6440
EP 6448
DI 10.1523/JNEUROSCI.4892-10.2011
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 755MB
UT WOS:000289934600021
PM 21525285
ER
PT J
AU Lavine, JE
Schwimmer, JB
Van Natta, ML
Molleston, JP
Murray, KF
Rosenthal, P
Abrams, SH
Scheimann, AO
Sanyal, AJ
Chalasani, N
Tonascia, J
Unalp, A
Clark, JM
Brunt, EM
Kleiner, DE
Hoofnagle, JH
Robuck, PR
AF Lavine, Joel E.
Schwimmer, Jeffrey B.
Van Natta, Mark L.
Molleston, Jean P.
Murray, Karen F.
Rosenthal, Philip
Abrams, Stephanie H.
Scheimann, Ann O.
Sanyal, Arun J.
Chalasani, Naga
Tonascia, James
Uenalp, Aynur
Clark, Jeanne M.
Brunt, Elizabeth M.
Kleiner, David E.
Hoofnagle, Jay H.
Robuck, Patricia R.
CA Nonalcoholic Steatohepatitis Clini
TI Effect of Vitamin E or Metformin for Treatment of Nonalcoholic Fatty
Liver Disease in Children and Adolescents The TONIC Randomized
Controlled Trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID STEATOHEPATITIS; HISTOPATHOLOGY; THERAPY
AB Context Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in US children and adolescents and can present with advanced fibrosis or nonalcoholic steatohepatitis (NASH). No treatment has been established.
Objective To determine whether children with NAFLD would improve from therapeutic intervention with vitamin E or metformin.
Design, Setting, and Patients Randomized, double-blind, double-dummy, placebo-controlled clinical trial conducted at 10 university clinical research centers in 173 patients (aged 8-17 years) with biopsy-confirmed NAFLD conducted between September 2005 and March 2010.
Interventions Daily dosing of 800 IU of vitamin E (58 patients), 1000 mg of metformin (57 patients), or placebo (58 patients) for 96 weeks.
Main Outcome Measures The primary outcome was sustained reduction in alanine aminotransferase (ALT) defined as 50% or less of the baseline level or 40 U/L or less at visits every 12 weeks from 48 to 96 weeks of treatment. Improvements in histological features of NAFLD and resolution of NASH were secondary outcome measures.
Results Sustained reduction in ALT level was similar to placebo (10/58; 17%; 95% CI, 9% to 29%) in both the vitamin E (15/58; 26%; 95% CI, 15% to 39%; P=.26) and metformin treatment groups (9/57; 16%; 95% CI, 7% to 28%; P=.83). The mean change in ALT level from baseline to 96 weeks was -35.2 U/L (95% CI, -56.9 to -13.5) with placebo vs -48.3 U/L (95% CI, -66.8 to -29.8) with vitamin E (P=.07) and -41.7 U/L (95% CI, -62.9 to -20.5) with metformin (P=.40). The mean change at 96 weeks in hepatocellular ballooning scores was 0.1 with placebo (95% CI, -0.2 to 0.3) vs -0.5 with vitamin E (95% CI, -0.8 to -0.3; P=.006) and -0.3 with metformin (95% CI, -0.6 to -0.0; P=.04); and in NAFLD activity score, -0.7 with placebo (95% CI, -1.3 to -0.2) vs -1.8 with vitamin E (95% CI, -2.4 to -1.2; P=.02) and -1.1 with metformin (95% CI, -1.7 to -0.5; P=.25). Among children with NASH, the proportion who resolved at 96 weeks was 28% with placebo (95% CI, 15% to 45%; 11/39) vs 58% with vitamin E (95% CI, 42% to 73%; 25/43; P=.006) and 41% with metformin (95% CI, 26% to 58%; 16/39; P=.23). Compared with placebo, neither therapy demonstrated significant improvements in other histological features.
Conclusion Neither vitamin E nor metformin was superior to placebo in attaining the primary outcome of sustained reduction in ALT level in patients with pediatric NAFLD.
C1 [Lavine, Joel E.] Columbia Univ, Med Ctr, Dept Pediat, Div Pediat Gastroenterol Hepatol & Nutr, New York, NY 10032 USA.
[Schwimmer, Jeffrey B.] Univ Calif San Diego, Dept Pediat, Div Gastroenterol Hepatol & Nutr, San Diego, CA 92103 USA.
[Van Natta, Mark L.; Uenalp, Aynur] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Clark, Jeanne M.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Scheimann, Ann O.] Johns Hopkins Univ, Dept Pediat, Div Gastroenterol & Nutr, Baltimore, MD 21218 USA.
[Tonascia, James] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA.
[Molleston, Jean P.] Indiana Univ, James Whitcomb Riley Hosp Children, Dept Pediat, Sect Pediat Gastroenterol, Indianapolis, IN USA.
[Murray, Karen F.] Univ Washington, Sch Med, Dept Pediat, Seattle Childrens Hosp, Seattle, WA 98195 USA.
[Rosenthal, Philip] Univ Calif San Francisco, Dept Pediat, Div Gastroenterol Hepatol & Nutr, San Francisco, CA 94143 USA.
[Abrams, Stephanie H.] Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Sect Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA.
[Sanyal, Arun J.] Virginia Commonwealth Univ, Dept Med, Virginia Commonwealth Med Ctr, Div Pediat Gastroenterol Hepatol & Nutr, Richmond, VA 23298 USA.
[Chalasani, Naga] Indiana Univ, Dept Med, Div Gastroenterol Hepatol, Indianapolis, IN USA.
[Brunt, Elizabeth M.] Washington Univ, Dept Pathol & Immunol, St Louis, MO USA.
[Kleiner, David E.] NCI, Dept Labs, NIH, Bethesda, MD 20892 USA.
[Hoofnagle, Jay H.; Robuck, Patricia R.] NIDDK, NIH, Bethesda, MD USA.
RP Lavine, JE (reprint author), Columbia Univ, Med Ctr, Dept Pediat, Div Pediat Gastroenterol Hepatol & Nutr, 3959 Broadway,CHN 7-702, New York, NY 10032 USA.
EM jl3553@columbia.edu
RI Vaughn, Ivana/B-6138-2016;
OI Vaughn, Ivana/0000-0002-7201-0289; Kleiner, David/0000-0003-3442-4453
FU Schering; Roche; Bristol-Myers Squibb; GlaxoSmithKline; Takeda; Salix;
Gore; Astellas; Exalenz; Norgine; Gore Associates; Gilead Sciences;
Mochida; Karo Bio; Johnson Johnson; Gilead; Abbott; Medpace;
Astra-Zeneca; Teva; Amylin; Phenomix; Lilly; National Institute of
Diabetes and Digestive and Kidney Diseases [U01DK061718, U01DK061728,
U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738,
U01DK061730, U01DK061713]; National Cancer Institute; Eunice Kennedy
Shriver National Institute of Child Health and Human Development;
National Institutes of Health General Clinical Research Centers
[UL1RR024989, UL1RR024128, M01RR000750, UL1RR024131, M01RR000827,
UL1RR02501401, M01RR000065, M01RR00188, M01RR020359]
FX All authors have completed and submitted the ICMJE Form for Disclosure
of Potential Conflicts of Interest. Dr Molleston reported receiving
grant support from Schering and Roche. Dr Rosenthal reported receiving
consulting fees from Roche, grant support from Bristol-Myers Squibb and
Roche, and speaking fees from GlaxoSmithKline. Dr Sanyal reported
receiving consulting fees from Takeda, Salix, Gore, Astellas, Exalenz,
and Norgine; grant support from Salix, Gore & Associates, Gilead
Sciences, Exalenz, Roche, and Mochida; royalties from UptoDate; and
travel and meeting expenses from Salix and Astellas. Dr Chalasani
reported receiving consulting fees from Merck, Karo Bio, Johnson &
Johnson, Gilead, Abbott, Medpace, Astra-Zeneca, Teva, Salix, Amylin, and
Phenomix and grant support from Amylin and Lilly. Dr Brunt reported
receiving consulting fees from Amylin and Pfizer. The other authors
reported no conflicts of interest.; The Nonalcoholic Steatohepatitis
Clinical Research Network (NASH CRN) is supported by the National
Institute of Diabetes and Digestive and Kidney Diseases grants
U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734,
U01DK061737, U01DK061738, U01DK061730, and U01DK061713. This study was
supported in part by the Intramural Research Program of the National
Cancer Institute and the Eunice Kennedy Shriver National Institute of
Child Health and Human Development. Other grant support included the
following National Institutes of Health General Clinical Research
Centers or Clinical and Translational Science Awards: UL1RR024989,
UL1RR024128, M01RR000750, UL1RR024131, M01RR000827, UL1RR02501401,
M01RR000065, M01RR00188, and M01RR020359. The vitamin E soft gels and
matching placebo were provided by Pharmavite through a Clinical Trial
Agreement with the National Institutes of Health.
NR 20
TC 284
Z9 297
U1 3
U2 24
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 APR 27
PY 2011
VL 305
IS 16
BP 1659
EP 1668
DI 10.1001/jama.2011.520
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 754XG
UT WOS:000289890500019
PM 21521847
ER
PT J
AU Yoon, SC
Hurst, FP
Jindal, RM
George, SA
Neff, RT
Agodoa, LY
Kimmel, PL
Abbott, KC
AF Yoon, Sylvia C.
Hurst, Frank P.
Jindal, Rahul M.
George, Susan A.
Neff, Robert T.
Agodoa, Lawrence Y.
Kimmel, Paul L.
Abbott, Kevin C.
TI Trends in Renal Transplantation in Patients With Human Immunodeficiency
Virus Infection: An Analysis of the United States Renal Data System
SO TRANSPLANTATION
LA English
DT Article
DE HIV nephropathy; Transplant outcomes; Transplantation; AIDS
ID ACTIVE ANTIRETROVIRAL THERAPY; SOLID-ORGAN TRANSPLANTATION;
HIV-INFECTION; KIDNEY; SURVIVAL; NEPHROPATHY; DISEASES; SAFETY
AB Background. We examined the United States Renal Data System registry to analyze trends in renal transplantation in patients with human immunodeficiency virus (HIV) infection.
Methods. A retrospective cohort study was performed using the United States Renal Data System, analyzing patients receiving renal transplants from January 1, 1995, to September 29, 2006. Factors independently associated with transplantation in HIV-infected patients with end-stage renal disease were identified.
Results. There was a significant increase in renal transplant recipients who were HIV seropositive who received renal transplants from 2001 to 2006 (n = 208, 0.26%) versus 1995 to 2000 era (n = 43, 0.06%, P < 0.001). Before 2001, only 18 states performed renal transplants in HIV-infected patients, whereas most states transplanted HIV-infected patients in the second era. There were more African American recipients with HIV infection from 2001 to 2006 compared with the earlier cohort (n = 118 vs. 8, P < 0.001). Patients with HIV infection were more likely to have received induction therapy (n = 121 vs. 37, P < 0.001) and tacrolimus maintenance suppression (n = 105 vs. 13, P < 0.001) in the latter era. There were also more deceased donor transplants from 2001 to 2006 (n = 143 vs. 25, P < 0.001). In logistic regression analysis, when adjusted for multiple factors including recipient and donor age, race, gender, and donor type, patients with HIV infection were more likely to have been transplanted after 2001 (adjusted odds ratio, 2.21; 95% confidence interval = 1.49-3.28). In analysis adjusted for multiple factors including hepatitis C virus coinfection, HIV infection was not significantly associated with all-cause graft loss.
Conclusions. There has been a dramatic increase in the number of transplants among HIV-infected patients. These findings suggest improved access to transplant wait listing and better management of immunosuppression, especially among African American patients.
C1 [Yoon, Sylvia C.; Hurst, Frank P.; Jindal, Rahul M.; George, Susan A.; Neff, Robert T.; Abbott, Kevin C.] Walter Reed Army Med Ctr, Dept Med, Washington, DC 20307 USA.
[Yoon, Sylvia C.; Hurst, Frank P.; Jindal, Rahul M.; George, Susan A.; Neff, Robert T.; Abbott, Kevin C.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Jindal, Rahul M.] Walter Reed Army Med Ctr, Dept Surg, Washington, DC USA.
[Jindal, Rahul M.; Kimmel, Paul L.] George Washington Univ, Dept Med, Washington, DC USA.
[Agodoa, Lawrence Y.; Kimmel, Paul L.] NIDDK, NIH, Bethesda, MD USA.
RP Jindal, RM (reprint author), Walter Reed Army Med Ctr, Dept Organ Transplant, 6630 Georgia Ave, Washington, DC 20307 USA.
EM jindalr@msn.com
OI Abbott, Kevin/0000-0003-2111-7112
NR 21
TC 14
Z9 14
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD APR 27
PY 2011
VL 91
IS 8
BP 864
EP 868
DI 10.1097/TP.0b013e31820f081f
PG 5
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 746VX
UT WOS:000289277000011
PM 21301399
ER
PT J
AU Zaremba, A
Schmuecker, U
Esche, H
AF Zaremba, Angelika
Schmuecker, Ursula
Esche, Helmut
TI Sprouty is a cytoplasmic target of adenoviral E1A oncoproteins to
regulate the receptor tyrosine kinase signalling pathway
SO VIROLOGY JOURNAL
LA English
DT Article
ID RETINOBLASTOMA GENE-PRODUCT; PROTEIN-KINASE; CELL; EXPRESSION;
INHIBITOR; GROWTH; PHOSPHORYLATION; CANCER; TRANSLOCATION; ASSOCIATION
AB Background: Oncoproteins encoded by the early region of adenoviruses have been shown to be powerful tools to study gene regulatory mechanisms, which affect major cellular events such as proliferation, differentiation, apoptosis and oncogenic transformation. They are possesing a key role to favor viral replication via their interaction with multiple cellular proteins. In a yeast two-hybrid screen we have identified Sprouty1 (Spry1) as a target of adenoviral E1A Oncoproteins. Spry proteins are central and complex regulators of the receptor tyrosine kinase (RTK) signalling pathway. The deregulation of Spry family members is often associated with alterations of the RTK signalling and its downstream effectors, leading to the ERK pathway.
Results: Here, we confirm our yeast two-hybrid data, showing the interaction between Spry1 and E1A in GST pull-down and immunoprecipitation assays. We also demonstrated the interaction of E1A with two further Spry isoforms. Using deletion mutants we identified the N-terminus and the CR conserved region (CR) 3 of E1A- and the C-terminal half of Spry1, which contains the highly conserved Spry domain, as the essential sites for direct interaction between Spry and E1A. Immunofluorescent microscopy data revealed a co-localization of E1A(13S) with Spry1 in the cytoplasm. SRE and TRE reporter assays demonstrated that co-expression of Spry1 with E1A(13S) abolishes the inhibitory function of Spry1 in RTK signalling, which is consequently accompanied with a decrease of E1A(13S)-induced gene expression.
Conclusions: These results establish Spry1 as a cytoplasmic localized cellular target for E1A oncoproteins to regulate the RTK signalling pathway, and consequently cellular events downstream of RTK that are essential for viral replication and transformation.
C1 [Zaremba, Angelika] NIEHS, Lab Signal Transduct, Durham, NC 27709 USA.
[Schmuecker, Ursula; Esche, Helmut] Univ Essen Gesamthsch, Inst Mol Biol Canc Res, Sch Med, D-45122 Essen, Germany.
RP Zaremba, A (reprint author), NIEHS, Lab Signal Transduct, POB 12233, Durham, NC 27709 USA.
EM zarembaa@niehs.nih.gov
NR 50
TC 4
Z9 4
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1743-422X
J9 VIROL J
JI Virol. J.
PD APR 26
PY 2011
VL 8
AR 192
DI 10.1186/1743-422X-8-192
PG 12
WC Virology
SC Virology
GA 775HU
UT WOS:000291450400001
PM 21518456
ER
PT J
AU Abnet, CC
Zheng, W
Ye, W
Kamangar, F
Ji, BT
Persson, C
Yang, G
Li, HL
Rothman, N
Shu, XO
Gao, YT
Chow, WH
AF Abnet, C. C.
Zheng, W.
Ye, W.
Kamangar, F.
Ji, B-T
Persson, C.
Yang, G.
Li, H-L
Rothman, N.
Shu, X-O
Gao, Y-T
Chow, W-H
TI Plasma pepsinogens, antibodies against Helicobacter pylori, and risk of
gastric cancer in the Shanghai Women's Health Study Cohort
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE gastric cancer; pepsinogens; Helicobacter pylori; cohort; China
ID CHRONIC ATROPHIC GASTRITIS; SERUM PEPSINOGENS; INFECTION;
ADENOCARCINOMA; POPULATION; EPIDEMIOLOGY; PREVALENCE; PREVENTION;
ESOPHAGEAL; CARCINOMA
AB BACKGROUND: Circulating pepsinogens can indicate atrophic gastritis, a precursor of gastric cancer. We tested the association between gastric cancer and plasma pepsinogens and antibodies against Helicobacter pylori in a case-control study nested in a prospective cohort.
METHODS: We selected 141 gastric cancer cases and 282 incidence-density sampled controls. Plasma concentrations of pepsinogens 1 and 2 were measured using ELISA kits, and anti-H. pylori antibodies were measured using a kit specific to Chinese strains. Associations were estimated using conditional logistic regression models adjusted for potential confounders.
RESULTS: Gastric cancer subjects were more likely to be anti-H. pylori positive than controls, 97 vs 92%. A plasma pepsinogen 1 (PG1) concentration <50 ng ml(-1) (15% of cases) was associated with a significantly increased risk of gastric cancer (OR 4.23; (95% CI: 1.86-9.63), whereas a plasma pepsinogen 2 (PG2) concentration >6.6 ng ml(-1) (75% of cases) was also associated with a significantly increased risk of gastric cancer (OR 3.62; (95% CI: 1.85-7.09). We also found that the PG1: 2 ratio had a nearly linear association with gastric cancer risk.
CONCLUSION: Lower plasma PG1 : 2 ratios are associated with a higher risk of gastric cancer. Furthermore, it appears that circulating pepsinogens 1 and 2 may be independently associated with the risk of gastric cancer. British Journal of Cancer (2011) 104, 1511-1516. doi:10.1038/bjc.2011.77 www.bjcancer.com Published online 15 March 2011 (C) 2011 Cancer Research UK
C1 [Abnet, C. C.; Ji, B-T; Persson, C.; Rothman, N.; Chow, W-H] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Zheng, W.; Yang, G.; Shu, X-O] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr,Dept Med,Div Epidemiol, Nashville, TN 37212 USA.
[Zheng, W.; Shu, X-O] Vanderbilt Univ, Ctr Hlth Serv Res, Dept Med, Nashville, TN USA.
[Ye, W.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Kamangar, F.] Morgan State Univ, Sch Community Hlth & Policy, Dept Publ Hlth Anal, Baltimore, MD 21239 USA.
[Li, H-L; Gao, Y-T] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
RP Abnet, CC (reprint author), NCI, Div Canc Epidemiol & Genet, Execut Plaza S,Room 320,6120 Execut Blvd,MSC 7232, Rockville, MD 20852 USA.
EM abnetc@mail.nih.gov
RI Abnet, Christian/C-4111-2015
OI Abnet, Christian/0000-0002-3008-7843
FU NIH [R37 CA070867]; NCI [NO2-CP-11010-66]; National Institutes of
Health, National Cancer Institute
FX This research was supported by the NIH Grant R37 CA070867, NCI contract
(NO2-CP-11010-66), and by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute.
NR 34
TC 10
Z9 12
U1 0
U2 2
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 APR 26
PY 2011
VL 104
IS 9
BP 1511
EP 1516
DI 10.1038/bjc.2011.77
PG 6
WC Oncology
SC Oncology
GA 755ME
UT WOS:000289934900021
PM 21407214
ER
PT J
AU Yan, RT
Bluemke, D
Gomes, A
Burke, G
Shea, S
Liu, K
Bahrami, H
Sinha, S
Wu, C
Fernandes, V
McClelland, R
Lima, JAC
AF Yan, Raymond T.
Bluemke, David
Gomes, Antoinette
Burke, Gregory
Shea, Steve
Liu, Kiang
Bahrami, Hossein
Sinha, Shantanu
Wu, Colin
Fernandes, Veronica
McClelland, Robyn
Lima, Joao A. C.
TI Regional Left Ventricular Myocardial Dysfunction as a Predictor of
Incident Cardiovascular Events MESA (Multi-Ethnic Study of
Atherosclerosis)
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE epidemiology; heart failure; magnetic resonance imaging; myocardial
dysfunction; prognosis
ID CONGESTIVE-HEART-FAILURE; WALL-MOTION ABNORMALITIES; ASYMPTOMATIC
INDIVIDUALS; CLINICAL CARDIOLOGY; MAGNETIC-RESONANCE; LOW-RISK;
COMMITTEE; DISEASE; ECHOCARDIOGRAPHY; ASSOCIATION
AB Objectives We sought to examine the prognostic value of subclinical left ventricular (LV) regional myocardial dysfunction (RMD) measured by magnetic resonance imaging (MRI) among asymptomatic individuals.
Background LV RMD, defined as segmental impairment in systolic wall thickening, predicts adverse events in patients with established cardiovascular disease. MRI is highly accurate for detecting subtle RMD, of which the prognostic significance in a large multiethnic asymptomatic population is not known.
Methods We used MRI to evaluate baseline regional LV myocardial function and prospectively followed a multiethnic (African American, Caucasian, Chinese, and Hispanic) population-based sample of 4,510 men and women without cardiovascular disease for a mean of 4.6 years. Regional myocardial dysfunction was defined as the presence of impaired systolic wall thickening (<10th percentile of segment-specific population distribution) in >2 contiguous LV segments within any given coronary artery territory.
Results Baseline prevalence of RMD was 25.6%. Heart failure developed in 34 (1.0%) and 30 (2.6%) participants without and with RMD, respectively (p < 0.001). After adjustment for demographics and traditional risk factors, RMD remained independently associated with incident heart failure (hazard ratio [HR]: 2.62; 95% confidence interval [CI]: 1.56 to 4.39; p < 0.001). The relationship persisted after further adjustment for biomarkers of reported association with cardiovascular disease and indexes of global LV systolic dysfunction and hypertrophy (HR: 1.80; 95% CI: 1.02 to 3.20; p = 0.044). Similarly, RMD independently conferred an increased risk for hard coronary events (myocardial infarction or death from coronary heart disease; HR: 1.75; 95% CI: 1.06 to 2.89; p = 0.029), the composite of hard coronary events and stroke (HR: 1.72; 95% CI: 1.16 to 2.56; p = 0.005), and all atherosclerotic cardiovascular events (HR: 1.50; 95% CI: 1.09 to 2.07; p = 0.012).
Conclusions Among an asymptomatic multiethnic American cohort, RMD is an independent predictor beyond traditional risk factors and global LV assessment for incident heart failure and atherosclerotic cardiovascular events. The clinical utility of early recognition of this subclinical phenotype deserves further investigation. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487) (J Am Coll Cardiol 2011;57:1735-44) (C) 2011 by the American College of Cardiology Foundation
C1 [Yan, Raymond T.; Bahrami, Hossein; Fernandes, Veronica; Lima, Joao A. C.] Johns Hopkins Univ, Dept Med, Div Cardiol, Baltimore, MD USA.
[Bluemke, David] NIH, Bethesda, MD 20892 USA.
[Gomes, Antoinette] Univ Calif Los Angeles, Sch Med, Dept Radiol, Los Angeles, CA 90024 USA.
[Burke, Gregory] Wake Forest Univ Hlth Sci, Dept Publ Hlth Sci, Winston Salem, NC USA.
[Shea, Steve] Columbia Univ, New York, NY USA.
[Liu, Kiang] Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL USA.
[Sinha, Shantanu] Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA.
[Wu, Colin] NHLBI, Dept Biostat, Bethesda, MD 20892 USA.
[McClelland, Robyn] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[McClelland, Robyn] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA.
RP Lima, JAC (reprint author), Johns Hopkins Univ Hosp, Div Cardiol, Blalock 524,600 N Wolfe St, Baltimore, MD 21287 USA.
EM jlima@jhmi.edu
OI Bluemke, David/0000-0002-8323-8086
FU National, Heart, Lung and Blood Institute [RO1-HL66075-01]; MESA
[NO1-HC-95159, NO1-HC-95168]; Canadian Institutes of Health Research;
Royal College of Physicians and Surgeons of Canada
FX Department of Biostatistics, National Heart, Lung and Blood Institute,
Bethesda, Maryland; and the dagger dagger Department of Biostatistics
and Collaborative Health Studies Coordinating Center, University of
Washington, Seattle, Washington. This study was supported in part by
National, Heart, Lung and Blood Institute grants RO1-HL66075-01 and MESA
study contracts NO1-HC-95159 through NO1-HC-95168. Dr. Yan was supported
by Fellowship Awards from the Canadian Institutes of Health Research and
the Detweiler Travelling Fellowship Award from the Royal College of
Physicians and Surgeons of Canada. The authors have reported that they
have no relationships to disclose. Kim Allan Williams, Sr, MD, served as
Guest Editor for this paper.
NR 37
TC 15
Z9 17
U1 0
U2 4
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 APR 26
PY 2011
VL 57
IS 17
BP 1735
EP 1744
DI 10.1016/j.jacc.2010.10.060
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 752SY
UT WOS:000289715600003
PM 21511109
ER
PT J
AU Deininger, KNW
Horikawa, A
Kitko, RD
Tatsumi, R
Rosner, JL
Wachi, M
Slonczewski, JL
AF Deininger, Kari N. W.
Horikawa, Akina
Kitko, Ryan D.
Tatsumi, Ryoko
Rosner, Judah L.
Wachi, Masaaki
Slonczewski, Joan L.
TI A Requirement of TolC and MDR Efflux Pumps for Acid Adaptation and GadAB
Induction in Escherichia coli
SO PLOS ONE
LA English
DT Article
ID MULTIDRUG-RESISTANCE; OUTER-MEMBRANE; PH; BACTERIA; SYSTEM; EXPRESSION;
REGULATOR; GENES; K-12; TYPHIMURIUM
AB Background: The TolC outer membrane channel is a key component of several multidrug resistance (MDR) efflux pumps driven by H+ transport in Escherichia coli. While tolC expression is under the regulation of the EvgA-Gad acid resistance regulon, the role of TolC in growth at low pH and extreme-acid survival is unknown.
Methods and Principal Findings: TolC was required for extreme-acid survival (pH 2) of strain W3110 grown aerobically to stationary phase. A tolC deletion decreased extreme-acid survival (acid resistance) of aerated pH 7.0-grown cells by 10(5)-fold and of pH 5.5-grown cells by 10-fold. The requirement was specific for acid resistance since a tolC defect had no effect on aerobic survival in extreme base (pH 10). TolC was required for expression of glutamate decarboxylase (GadA, GadB), a key component of glutamate-dependent acid resistance (Gad). TolC was also required for maximal exponential growth of E. coli K-12 W3110, in LBK medium buffered at pH 4.5-6.0, but not at pH 6.5-8.5. The TolC growth requirement in moderate acid was independent of Gad. TolC-associated pump components EmrB and MdtB contributed to survival in extreme acid (pH 2), but were not required for growth at pH 5. A mutant lacking the known TolC-associated efflux pumps (acrB, acrD, emrB, emrY, macB, mdtC, mdtF, acrEF) showed no growth defect at acidic pH and a relatively small decrease in extreme-acid survival when pre-grown at pH 5.5.
Conclusions: TolC and proton-driven MDR efflux pump components EmrB and MdtB contribute to E. coli survival in extreme acid and TolC is required for maximal growth rates below pH 6.5. The TolC enhancement of extreme-acid survival includes Gad induction, but TolC-dependent growth rates below pH 6.5 do not involve Gad. That MDR resistance can enhance growth and survival in acid is an important consideration for enteric organisms passing through the acidic stomach.
C1 [Deininger, Kari N. W.; Kitko, Ryan D.; Slonczewski, Joan L.] Kenyon Coll, Dept Biol, Gambier, OH 43022 USA.
[Horikawa, Akina; Tatsumi, Ryoko; Wachi, Masaaki] Tokyo Inst Technol, Dept Bioengn, Yokohama, Kanagawa 227, Japan.
[Rosner, Judah L.] NIDDK, NIH, Bethesda, MD USA.
RP Deininger, KNW (reprint author), Kenyon Coll, Dept Biol, Gambier, OH 43022 USA.
EM slonczewski@kenyon.edu
RI Wachi, Masaaki/D-1220-2015
OI Wachi, Masaaki/0000-0002-3655-4035
FU National Science Foundation [MCB-1050080]
FX This work was supported by grant MCB-1050080 to JLS from the National
Science Foundation. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 44
TC 16
Z9 17
U1 2
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 26
PY 2011
VL 6
IS 4
AR e18960
DI 10.1371/journal.pone.0018960
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 756NE
UT WOS:000290018400019
PM 21541325
ER
PT J
AU Leitzmann, MF
Moore, SC
Koster, A
Harris, TB
Park, Y
Hollenbeck, A
Schatzkin, A
AF Leitzmann, Michael F.
Moore, Steven C.
Koster, Annemarie
Harris, Tamara B.
Park, Yikyung
Hollenbeck, Albert
Schatzkin, Arthur
TI Waist Circumference as Compared with Body-Mass Index in Predicting
Mortality from Specific Causes
SO PLOS ONE
LA English
DT Article
ID VISCERAL FAT; ABDOMINAL ADIPOSITY; LUNG-CANCER; US ADULTS; RISK;
SMOKING; HEALTH; SEX; ASSOCIATION; FATNESS
AB Background: Whether waist circumference provides clinically meaningful information not delivered by body-mass index regarding prediction of cause-specific death is uncertain.
Methods: We prospectively examined waist circumference (WC) and body-mass index (BMI) in relation to cause-specific death in 225,712 U. S. women and men. Cox regression was used to estimate relative risks and 95% confidence intervals (CI). Statistical analyses were conducted using SAS version 9.1.
Results: During follow-up from 1996 through 2005, we documented 20,977 deaths. Increased WC consistently predicted risk of death due to any cause as well as major causes of death, including deaths from cancer, cardiovascular disease, and noncancer/non-cardiovascular diseases, independent of BMI, age, sex, race/ethnicity, smoking status, and alcohol intake. When WC and BMI were mutually adjusted in a model, WC was related to 1.37 fold increased risk of death from any cancer and 1.82 fold increase risk of death from cardiovascular disease, comparing the highest versus lowest WC categories. Importantly, WC, but not BMI showed statistically significant positive associations with deaths from lung cancer and chronic respiratory disease. Participants in the highest versus lowest WC category had a relative risk of death from lung cancer of 1.77 (95% CI, 1.41 to 2.23) and of death from chronic respiratory disease of 2.77 (95% CI, 1.95 to 3.95). In contrast, subjects in the highest versus lowest BMI category had a relative risk of death from lung cancer of 0.94 (95% CI, 0.75 to 1.17) and of death from chronic respiratory disease of 1.18 (95% CI, 0.89 to 1.56).
Conclusions: Increased abdominal fat measured by WC was related to a higher risk of deaths from major specific causes, including deaths from lung cancer and chronic respiratory disease, independent of BMI.
C1 [Leitzmann, Michael F.; Moore, Steven C.; Park, Yikyung; Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Leitzmann, Michael F.] Univ Regensburg, Med Ctr, Dept Epidemiol & Prevent Med, Regensburg, Germany.
[Koster, Annemarie; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Koster, Annemarie] Maastricht Univ, Dept Internal Med, Sch Publ Hlth & Primary Care CAPHRI, Maastricht, Netherlands.
[Hollenbeck, Albert] AARP, Washington, DC USA.
RP Leitzmann, MF (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM michael.leitzmann@klinik.uni-regensburg.de
RI Koster, Annemarie/E-7438-2010; Moore, Steven/D-8760-2016;
OI Moore, Steven/0000-0002-8169-1661; Park, Yikyung/0000-0002-6281-489X
FU National Institutes of Health (NIH), National Cancer Institute; NCI
(National Cancer Institute)
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Cancer Institute. AARP has
not provided direct funds to the NIH-AARP Diet and Health Study. The
AARP contribution has consisted of help in drawing the study sample and
sponsoring Dr. Yikyung Park as a research fellow for two years. That
funding went to the NCI (National Cancer Institute) but not to the
NIH-AARP Diet and Health Study itself. AARP has also provided funds for
the development of an online physical activity assessment tool, but that
project is not part of the current study. In addition, AARP had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript. The term 'AARP' is not an acronym, but
has been the legal name of the organization for the past 15 years. AARP
was formerly known as the American Association of Retired Persons.
NR 28
TC 43
Z9 44
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 APR 26
PY 2011
VL 6
IS 4
AR e18582
DI 10.1371/journal.pone.0018582
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 756NE
UT WOS:000290018400005
PM 21541313
ER
PT J
AU Frankowski, KJ
Setola, V
Evans, JM
Neuenswander, B
Roth, BL
Aube, J
AF Frankowski, Kevin J.
Setola, Vincent
Evans, Jon M.
Neuenswander, Ben
Roth, Bryan L.
Aube, Jeffrey
TI Synthesis and receptor profiling of Stemona alkaloid analogues reveal a
potent class of sigma ligands
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE diversity-oriented synthesis; probe discovery
ID ANTITUSSIVE ACTIVITY; NATURAL-PRODUCT; ORIENTED SYNTHESIS; SCHMIDT
REACTION; (+/-)-STENINE; TUBEROSA; TUBEROSTEMONINE; (-)-STENINE;
(+/-)-NEOSTENINE; DISCOVERY
AB Reported biological activities of Stemona natural products, such as antitussive activity, inspired the development of synthetic methods to access several alkaloids within this family and in so doing develop a general route to the core skeleta shared by the class of natural products. The chemistry was subsequently adapted to afford a series of analogue sets bearing simplified, diverse Stemona-inspired skeleta. Over 100 of these analogues were subjected to general G protein-coupled receptor profiling along with the known antitussive compound, neostenine; this led to the identification of hit compounds targeting several receptor types. The particularly rich hit subset for sigma receptors was expanded with two focused library sets, which resulted in the discovery of a fully synthetic, potent chemotype of sigma ligands. This collaborative effort combined the development of synthetic methods with extensive, flexible screening resources and exemplifies the role of natural products in bioactivity mining.
C1 [Frankowski, Kevin J.; Neuenswander, Ben; Aube, Jeffrey] Univ Kansas, Delbert M Shankel Struct Biol Ctr, Dept Med Chem, Lawrence, KS 66047 USA.
[Setola, Vincent; Evans, Jon M.; Roth, Bryan L.] Univ N Carolina, Dept Pharmacol, Sch Med, Chapel Hill, NC 27514 USA.
[Setola, Vincent; Evans, Jon M.; Roth, Bryan L.] Univ N Carolina, Natl Inst Mental Hlth, Psychoact Drug Screening Program CB 7365, Chapel Hill, NC 27514 USA.
RP Aube, J (reprint author), Univ Kansas, Delbert M Shankel Struct Biol Ctr, Dept Med Chem, 2121 Simons Dr, Lawrence, KS 66047 USA.
EM jaube@ku.edu
RI Roth, Bryan/F-3928-2010
FU National Institute of General Medical Sciences [GM-49093,
P050-GM069663]; National Institute of Mental Health
[HHSN-271-2008-000025-C (NIMH-PDSP)]; National Institutes of Health
[R01DA017204]
FX We are grateful to Victor Day for X-ray crystallography services. We
thank the National Institute of General Medical Sciences (GM-49093 and
P050-GM069663), the National Institute of Mental Health's Psychoactive
Drug Screening Program [Contract HHSN-271-2008-000025-C (NIMH-PDSP)] and
the National Institutes of Health (R01DA017204) for financial support.
NR 46
TC 11
Z9 11
U1 1
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 APR 26
PY 2011
VL 108
IS 17
BP 6727
EP 6732
DI 10.1073/pnas.1016558108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 754WM
UT WOS:000289888500013
PM 21368188
ER
PT J
AU Brown, LE
Cheng, KCC
Wei, WG
Yuan, PW
Dai, P
Trilles, R
Ni, F
Yuan, J
MacArthur, R
Guha, R
Johnson, RL
Su, XZ
Dominguez, MM
Snyder, JK
Beeler, AB
Schaus, SE
Inglese, J
Porco, JA
AF Brown, Lauren E.
Cheng, Ken Chih-Chien
Wei, Wan-Guo
Yuan, Pingwei
Dai, Peng
Trilles, Richard
Ni, Feng
Yuan, Jing
MacArthur, Ryan
Guha, Rajarshi
Johnson, Ronald L.
Su, Xin-Zhuan
Dominguez, Melissa M.
Snyder, John K.
Beeler, Aaron B.
Schaus, Scott E.
Inglese, James
Porco, John A., Jr.
TI Discovery of new antimalarial chemotypes through chemical methodology
and library development
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE chemical biology; organocatalytic; polycyclic ketal
ID PEPTIDOGLYCAN BIOSYNTHESIS INHIBITORS; PLASMODIUM-FALCIPARUM; CINCHONA
ALKALOIDS; ORIENTED SYNTHESIS; SMALL-MOLECULE; IDENTIFICATION;
MURAYMYCINS; DERIVATIVES; DIVERSITY; TARGETS
AB In an effort to expand the stereochemical and structural complexity of chemical libraries used in drug discovery, the Center for Chemical Methodology and Library Development at Boston University has established an infrastructure to translate methodologies accessing diverse chemotypes into arrayed libraries for biological evaluation. In a collaborative effort, the NIH Chemical Genomics Center determined IC(50)'s for Plasmodium falciparum viability for each of 2,070 members of the CMLD-BU compound collection using quantitative high-throughput screening across five parasite lines of distinct geographic origin. Three compound classes displaying either differential or comprehensive antimalarial activity across the lines were identified, and the nascent structure activity relationships (SAR) from this experiment used to initiate optimization of these chemotypes for further development.
C1 [Cheng, Ken Chih-Chien; MacArthur, Ryan; Guha, Rajarshi; Johnson, Ronald L.; Inglese, James] Natl Human Genome Res Inst, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
[Brown, Lauren E.; Wei, Wan-Guo; Yuan, Pingwei; Dai, Peng; Trilles, Richard; Ni, Feng; Dominguez, Melissa M.; Snyder, John K.; Beeler, Aaron B.; Schaus, Scott E.; Porco, John A., Jr.] Boston Univ, Dept Chem, Boston, MA 02215 USA.
[Brown, Lauren E.; Wei, Wan-Guo; Yuan, Pingwei; Dai, Peng; Trilles, Richard; Ni, Feng; Dominguez, Melissa M.; Snyder, John K.; Beeler, Aaron B.; Schaus, Scott E.; Porco, John A., Jr.] Boston Univ, Ctr Chem Methodol & Lib Dev CMLD BU, Boston, MA 02215 USA.
[Yuan, Jing; Su, Xin-Zhuan] Natl Inst Allergy & Infect Dis, Lab Malaria & Vector Res, Bethesda, MD 20892 USA.
RP Inglese, J (reprint author), Natl Human Genome Res Inst, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
EM jinglese@mail.nih.gov; porco@bu.edu
OI Su, Xinzhuan/0000-0003-3246-3248
FU NIGMS CMLD Initiative [P50 GM067041]; Divisions of Intramural Research
at the National Institute of Allergy and Infectious Diseases; National
Human Genome Research Institute; NIH Roadmap for Medical Research;
National Institutes of Health
FX We thank Dr. John Schwab [National Institute of General Medical Sciences
(NIGMS)] for his guidance of the CMLD Centers Program, Dr. Paul Ralifo
(BU) for assistance with NMR. Paul Shinn (NCGC) for compound management,
and Dr. Ruili Huang for informatics assistance (NCGC). We also thank Dr.
Paul Clemons (Broad Institute), Dr. Tanar Kaya (Broad Institute), and
Dr. J. Anthony Wilson (Broad Institute) for assistance with principle
moments of inertia analysis of the CMLD-BU compound collection. This
work was generously supported by NIGMS CMLD Initiative (P50 GM067041 J.
A. P., Jr.) and the Divisions of Intramural Research at the National
Institute of Allergy and Infectious Diseases and National Human Genome
Research Institute and the NIH Roadmap for Medical Research, all at the
National Institutes of Health.
NR 34
TC 22
Z9 22
U1 0
U2 11
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 APR 26
PY 2011
VL 108
IS 17
BP 6775
EP 6780
DI 10.1073/pnas.1017666108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 754WM
UT WOS:000289888500021
PM 21498685
ER
PT J
AU Miot, M
Reidy, M
Doyle, SM
Hoskins, JR
Johnston, DM
Genest, O
Vitery, MC
Masison, DC
Wickner, S
AF Miot, Marika
Reidy, Michael
Doyle, Shannon M.
Hoskins, Joel R.
Johnston, Danielle M.
Genest, Olivier
Vitery, Maria-Carmen
Masison, Daniel C.
Wickner, Sue
TI Species-specific collaboration of heat shock proteins (Hsp) 70 and 100
in thermotolerance and protein disaggregation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE Hsp40; DnaJ; M-domain; GrpE; nucleotide exchange factor
ID N-TERMINAL DOMAIN; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; PRION
PROPAGATION; CHAPERONE SYSTEM; AGGREGATED PROTEINS; CLPB; MECHANISM;
DNAK; MACHINERY
AB Yeast Hsp104 and its bacterial homolog, ClpB, are Clp/Hsp100 molecular chaperones and AAA+ ATPases. Hsp104 and ClpB collaborate with the Hsp70 and DnaK chaperone systems, respectively, to retrieve and reactivate stress-denatured proteins from aggregates. The action of Hsp104 and ClpB in promoting cell survival following heat stress is species-specific: Hsp104 cannot function in bacteria and ClpB cannot act in yeast. To determine the regions of Hsp104 and ClpB necessary for this specificity, we tested chimeras of Hsp104 and ClpB in vivo and in vitro. We show that the Hsp104 and ClpB middle domains dictate the species-specificity of Hsp104 and ClpB for cell survival at high temperature. In protein reactivation assays in vitro, chimeras containing the Hsp104 middle domain collaborate with Hsp70 and those with the ClpB middle domain function with DnaK. The region responsible for the specificity is within helix 2 and helix 3 of the middle domain. Additionally, several mutants containing amino acid substitutions in helix 2 of the ClpB middle domain are defective in protein disaggregation in collaboration with DnaK. In a bacterial two-hybrid assay, DnaK interacts with ClpB and with chimeras that have the ClpB middle domain, implying that species-specificity is due to an interaction between DnaK and the middle domain of ClpB. Our results suggest that the interaction between Hsp70/DnaK and helix 2 of the middle domain of Hsp104/ClpB determines the specificity required for protein disaggregation both in vivo and in vitro, as well as for cellular thermotolerance.
C1 [Miot, Marika; Doyle, Shannon M.; Hoskins, Joel R.; Johnston, Danielle M.; Genest, Olivier; Vitery, Maria-Carmen; Wickner, Sue] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Reidy, Michael; Masison, Daniel C.] NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
RP Wickner, S (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM WicknerS@mail.nih.gov
OI Reidy, Michael/0000-0002-9290-7595; miot,
marie-caroline/0000-0002-3697-6510
FU National Institutes of Health (NIH), National Cancer Institute, Center
for Cancer Research; National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK)
FX We thank Susan Gottesman (NCI), Len Neckers (NCI), and Jonathan Weissman
(UCSF) for strains and plasmids; A. Battesti for help with the
two-hybrid system; and Jodi Camberg and Susan Gottesman for reading of
the manuscript and discussions. This research was supported by the
Intramural Research Program of the National Institutes of Health (NIH),
National Cancer Institute, Center for Cancer Research, and National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
NR 35
TC 60
Z9 61
U1 1
U2 18
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 APR 26
PY 2011
VL 108
IS 17
BP 6915
EP 6920
DI 10.1073/pnas.1102828108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 754WM
UT WOS:000289888500047
PM 21474779
ER
PT J
AU Wei, QO
Jiang, H
Xiao, Z
Baker, A
Young, MR
Veenstra, TD
Colburn, NH
AF Wei, Qiou
Jiang, Hong
Xiao, Zhen
Baker, Alyson
Young, Matthew R.
Veenstra, Timothy D.
Colburn, Nancy H.
TI Sulfiredoxin-Peroxiredoxin IV axis promotes human lung cancer
progression through modulation of specific phosphokinase signaling
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE oncogene; signal transduction
ID CYSTEINE-SULFINIC ACID; OXIDATIVE STRESS; TARGET GENE; C-MYC; REDUCTION;
KINASE; CELLS; MICE; TRANSFORMATION; SULPHIREDOXIN
AB Oxidative stress is known to cause tumorigenesis through induction of DNA and lipid damage. It also promotes cancer progression through a largely unknown mechanism. Sulfiredoxin (Srx) is a novel oxidative stress-induced antioxidant protein whose function in tumorigenesis and cancer progression has not been well studied. We report that Srx is highly expressed in human lung cancer. Knockdown of Srx reduces anchorage-independent colony formation, cell migration, and invasion of human lung cancer cells. Srx preferentially interacts with Peroxiredoxin (Prx) IV relative to other Prxs due to its intrinsic higher binding affinity. Knockdown of Prx IV recapitulates the phenotypic changes of depleting Srx. Disruption or enhancement of the Srx-Prx IV axis leads respectively to reduction or acceleration of tumor growth and metastasis formation in vivo. Through identification and validation of the downstream mediators we unraveled the Srx-mediated signaling network that traverses AP-1-activating and other phosphokinase signaling cascades. Our work reveals that the Srx-Prx IV axis is critical for lung cancer maintenance and metastasis, suggesting that targeting the Srx-Prx IV axis may provide unique effective strategies for cancer prevention and treatment.
C1 [Wei, Qiou; Baker, Alyson; Young, Matthew R.; Colburn, Nancy H.] NCI, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA.
[Jiang, Hong] SAIC Frederick, Lab Mol Cell Biol, Clin Serv Program, Frederick, MD 21702 USA.
[Xiao, Zhen; Veenstra, Timothy D.] SAIC Frederick, Lab Prote & Analyt Technol, Adv Technol Program, Frederick, MD 21702 USA.
RP Wei, QO (reprint author), NCI, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA.
EM weiqiou@mail.nih.gov; colburna@mail.nih.gov
FU National Cancer Institute [K99/R00]; National Cancer Institute, National
Institutes of Health [HHSN261200800001E]
FX We thank Drs. D. Esposito, T. Troy, W. Gillette, and A. Stephen for
protein purification and SPR analysis; Ms. L. Dodge and Mr. D. Logsdon
for mouse experiments (Science Applications International Corporation);
Ms. K. Noer for flow cytometry analysis (National Cancer Institute); and
Dr. K. D. Tew for discussion and communication (Medical University of
South Carolina). This work was supported by funding from the National
Cancer Institute Intramural Research Program (to N.H.C.) and the
National Cancer Institute Howard Temin Pathway to Independence Award
K99/R00 (to Q.W). Q.W. is a Cancer Research Training Award fellow and a
Cancer Genetics and Signaling fellow. 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.
NR 35
TC 42
Z9 47
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 APR 26
PY 2011
VL 108
IS 17
BP 7004
EP 7009
DI 10.1073/pnas.1013012108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 754WM
UT WOS:000289888500062
PM 21487000
ER
PT J
AU Flynn, BJ
Kastenmuller, K
Wille-Reece, U
Tomaras, GD
Alam, M
Lindsay, RW
Salazar, AM
Perdiguero, B
Gomez, CE
Wagner, R
Esteban, M
Park, CG
Trumpfheller, C
Keler, T
Pantaleo, G
Steinman, RM
Seder, R
AF Flynn, Barbara J.
Kastenmueller, Kathrin
Wille-Reece, Ulrike
Tomaras, Georgia D.
Alam, Munir
Lindsay, Ross W.
Salazar, Andres M.
Perdiguero, Beatriz
Gomez, Carmen E.
Wagner, Ralf
Esteban, Mariano
Park, Chae G.
Trumpfheller, Christine
Keler, Tibor
Pantaleo, Giuseppe
Steinman, Ralph M.
Seder, Robert
TI Immunization with HIV Gag targeted to dendritic cells followed by
recombinant New York vaccinia virus induces robust T-cell immunity in
nonhuman primates
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE viral vector; Pox virus
ID POLYRIBOINOSINIC-POLYRIBOCYTIDYLIC ACID; REPLICATION-DEFECTIVE
ADENOVIRUS; PRIME-BOOST IMMUNIZATION; IN-VIVO; RHESUS MACAQUES;
RESPONSES; ANTIBODY; DNA; CD4(+); VACCINATION
AB Protein vaccines, if rendered immunogenic, would facilitate vaccine development against HIV and other pathogens. We compared in nonhuman primates (NHPs) immune responses to HIV Gag p24 within 3G9 antibody to DEC205 ("DEC-HIV Gag p24"), an uptake receptor on dendritic cells, to nontargeted protein, with or without poly ICLC, a synthetic double stranded RNA, as adjuvant. Priming s.c. with 60 mu g of both HIV Gag p24 vaccines elicited potent CD4(+) T cells secreting IL-2, IFN-gamma, and TNF-alpha, which also proliferated. The responses increased with each of three immunizations and recognized multiple Gag peptides. DEC-HIV Gag p24 showed better cross-priming for CD8(+) T cells, whereas the avidity of anti-Gag antibodies was similar to 10-fold higher with nontargeted Gag 24 protein. For both protein vaccines, poly ICLC was essential for T-and B-cell immunity. To determine whether adaptive responses could be further enhanced, animals were boosted with New York vaccinia virus (NYVAC)-HIV Gag/Pol/Nef. Gag-specific CD4(+) and CD8(+) T-cell responses increased markedly after priming with both protein vaccines and poly ICLC. These data reveal qualitative differences in antibody and T-cell responses to DEC-HIV Gag p24 and Gag p24 protein and show that prime boost with protein and adjuvant followed by NYVAC elicits potent cellular immunity.
C1 [Park, Chae G.; Trumpfheller, Christine; Steinman, Ralph M.] Rockefeller Univ, Cellular Physiol & Immunol Lab, New York, NY 10065 USA.
[Park, Chae G.; Trumpfheller, Christine; Steinman, Ralph M.] Rockefeller Univ, Chris Browne Ctr Immunol & Immune Dis, New York, NY 10065 USA.
[Flynn, Barbara J.; Kastenmueller, Kathrin; Wille-Reece, Ulrike; Lindsay, Ross W.; Seder, Robert] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Flynn, Barbara J.; Kastenmueller, Kathrin; Wille-Reece, Ulrike; Lindsay, Ross W.; Seder, Robert] NIAID, Cellular Immunol Sect, NIH, Bethesda, MD 20892 USA.
[Wille-Reece, Ulrike] Program Appropriate Technol Hlth Malaria Vaccine, Bethesda, MD 20814 USA.
[Tomaras, Georgia D.; Alam, Munir] Duke Human Vaccine Inst, Durham, NC 27710 USA.
[Lindsay, Ross W.] Int AIDS Vaccine Initiat, AIDS Vaccine Design Lab, Brooklyn, NY 11220 USA.
[Salazar, Andres M.] Oncovir, Washington, DC 20008 USA.
[Perdiguero, Beatriz; Gomez, Carmen E.; Esteban, Mariano] CSIC, Ctr Nacl Biotecnol, E-28049 Madrid, Spain.
[Wagner, Ralf] Univ Regensburg, Inst Med Microbiol & Hyg, D-93053 Regensburg, Germany.
[Keler, Tibor] Celldex Therapeut, Phillipsburg, NJ 08865 USA.
[Pantaleo, Giuseppe] CHU Vaudois, Div Immunol & Allergy, CH-1011 Lausanne, Switzerland.
[Pantaleo, Giuseppe] Univ Lausanne, Swiss Vaccine Res Inst, CH-1011 Lausanne, Switzerland.
RP Steinman, RM (reprint author), Rockefeller Univ, Cellular Physiol & Immunol Lab, New York, NY 10065 USA.
EM steinma@mail.rockefeller.edu; rseder@mail.nih.gov
RI Steinman, Ralph/F-7729-2012; Gomez, Carmen/K-1940-2014; Tomaras,
Georgia/J-5041-2016; Pantaleo, Giuseppe/K-6163-2016;
OI Gomez, Carmen/0000-0002-5414-7935; Park, Chae Gyu/0000-0003-1906-1308
FU National Institute of Allergy and Infectious Diseases [AI081677,
AI08177-01A1S1]; Bill and Melinda Gates Foundation
FX We thank Laura Vitale and Thomas O'Neill for producing 3G9-HIV Gag p24,
Judy Adams for preparation of the manuscript, and Srinivas Rao and J. P.
Todd for oversight and assistance with all the NHP immunizations and
sampling. Partial support for these studies came from the National
Institute of Allergy and Infectious Diseases, Grants AI081677 and
AI08177-01A1S1 (to R. M. S.), and the Bill and Melinda Gates Foundation
Grand Challenges in Global Health Project (R. M. S.).
NR 44
TC 78
Z9 79
U1 3
U2 13
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD APR 26
PY 2011
VL 108
IS 17
BP 7131
EP 7136
DI 10.1073/pnas.1103869108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 754WM
UT WOS:000289888500084
PM 21467219
ER
PT J
AU Stojanov, S
Lapidus, S
Chitkara, P
Feder, H
Salazar, JC
Fleisher, TA
Brown, MR
Edwards, KM
Ward, MM
Colbert, RA
Sun, HW
Wood, GM
Barham, BK
Jones, A
Aksentijevich, I
Goldbach-Mansky, R
Athreya, B
Barron, KS
Kastner, DL
AF Stojanov, Silvia
Lapidus, Sivia
Chitkara, Puja
Feder, Henry
Salazar, Juan C.
Fleisher, Thomas A.
Brown, Margaret R.
Edwards, Kathryn M.
Ward, Michael M.
Colbert, Robert A.
Sun, Hong-Wei
Wood, Geryl M.
Barham, Beverly K.
Jones, Anne
Aksentijevich, Ivona
Goldbach-Mansky, Raphaela
Athreya, Balu
Barron, Karyl S.
Kastner, Daniel L.
TI Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA)
is a disorder of innate immunity and Th1 activation responsive to IL-1
blockade
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE anakinra; autoinflammatory disease; inflammasome; therapy
ID JUVENILE IDIOPATHIC ARTHRITIS; GENE-EXPRESSION PROFILES; CERVICAL
ADENITIS; INFLAMMASOME; TONSILLECTOMY; DISEASE; ADULT; CHILD
AB The syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) is the most common periodic fever disease in children. However, the pathogenesis is unknown. Using a systems biology approach we analyzed blood samples from PFAPA patients whose genetic testing excluded hereditary periodic fevers (HPFs), and from healthy children and pediatric HPF patients. Gene expression profiling could clearly distinguish PFAPA flares from asymptomatic intervals, HPF flares, and healthy controls. During PFAPA attacks, complement (C1QB, C2, SERPING1), IL-1-related (IL-1B, IL-1RN, CASP1, IL18RAP), and IFN-induced (AIM2, IP-10/CXCL10) genes were significantly overexpressed, but T cell-associated transcripts (CD3, CD8B) were down-regulated. On the protein level, PFAPA flares were accompanied by significantly increased serum levels of chemokines for activated T lymphocytes (IP-10/CXCL10, MIG/CXCL9), G-CSF, and proinflammatory cytokines (IL-18, IL-6). PFAPA flares also manifested a relative lymphopenia. Activated CD4(+)/CD25(+) T-lymphocyte counts correlated negatively with serum concentrations of IP-10/CXCL10, whereas CD4(+)/HLA-DR(+) T lymphocyte counts correlated positively with serum concentrations of the counterregulatory IL-1 receptor antagonist. Based on the evidence for IL-1 beta activation in PFAPA flares, we treated five PFAPA patients with a recombinant IL-1 receptor antagonist. All patients showed a prompt clinical and IP-10/CXCL10 response. Our data suggest an environmentally triggered activation of complement and IL-1 beta/-18 during PFAPA flares, with induction of Th1-chemokines and subsequent retention of activated T cells in peripheral tissues. IL-1 inhibition may thus be beneficial for treatment of PFAPA attacks, with IP-10/CXCL10 serving as a potential biomarker.
C1 [Stojanov, Silvia; Lapidus, Sivia; Chitkara, Puja; Ward, Michael M.; Colbert, Robert A.; Sun, Hong-Wei; Wood, Geryl M.; Barham, Beverly K.; Jones, Anne; Aksentijevich, Ivona; Goldbach-Mansky, Raphaela; Kastner, Daniel L.] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Fleisher, Thomas A.; Brown, Margaret R.] NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA.
[Wood, Geryl M.; Barham, Beverly K.; Jones, Anne; Aksentijevich, Ivona; Kastner, Daniel L.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Barron, Karyl S.] NIAID, NIH, Bethesda, MD 20892 USA.
[Stojanov, Silvia] Univ Munich, Childrens Hosp, Dept Immunol & Infect Dis, D-80337 Munich, Germany.
[Feder, Henry; Salazar, Juan C.] Univ Connecticut, Hlth Sci Ctr, Connecticut Childrens Med Ctr, Hartford, CT 06106 USA.
[Edwards, Kathryn M.] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37232 USA.
[Athreya, Balu] Thomas Jefferson Univ, Nemours AI duPoint Hosp Children, Wilmington, DE 19803 USA.
RP Kastner, DL (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA.
EM kastnerd@mail.nih.gov
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases;
National Human Genome Research Institute; National Institute of Allergy
and Infectious Diseases; Department of Laboratory Medicine of the
Clinical Center of the National Institutes of Health
FX We thank Katherine McLaurin for excellent technical assistance, Dr.
William Mackenzie and Dr. Geraldine Neiss for recruitment of healthy
children at the Nemours A. I. duPont Hospital for Children (Wilmington,
DE), Marcia Vital for editorial assistance in preparation of the
manuscript, Dr. Elaine Remmers for critical review of the manuscript,
and all the children and their families for participation in this study
and continuous support of our research endeavors. This work was
supported by the Intramural Research Programs of the National Institute
of Arthritis and Musculoskeletal and Skin Diseases, the National Human
Genome Research Institute, the National Institute of Allergy and
Infectious Diseases, and the Department of Laboratory Medicine of the
Clinical Center of the National Institutes of Health.
NR 36
TC 85
Z9 86
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 APR 26
PY 2011
VL 108
IS 17
BP 7148
EP 7153
DI 10.1073/pnas.1103681108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 754WM
UT WOS:000289888500087
PM 21478439
ER
PT J
AU Kari, L
Goheen, MM
Randall, LB
Taylor, LD
Carlson, JH
Whitmire, WM
Virok, D
Rajaram, K
Endresz, V
McClarty, G
Nelson, DE
Caldwell, HD
AF Kari, Laszlo
Goheen, Morgan M.
Randall, Linnell B.
Taylor, Lacey D.
Carlson, John H.
Whitmire, William M.
Virok, Dezso
Rajaram, Krithika
Endresz, Valeria
McClarty, Grant
Nelson, David E.
Caldwell, Harlan D.
TI Generation of targeted Chlamydia trachomatis null mutants
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE genetics; mutation screen
ID GENE-TRANSFER; INTRACELLULAR PATHOGEN; TRYPTOPHAN SYNTHASE; VIRULENCE
FACTOR; IN-VITRO; INFECTIONS; ELECTROPORATION; RESISTANCE; MUTATIONS;
RIFALAZIL
AB Chlamydia trachomatis is an obligate intracellular bacterial pathogen that infects hundreds of millions of individuals globally, causing blinding trachoma and sexually transmitted disease. More effective chlamydial control measures are needed, but progress toward this end has been severely hampered by the lack of a tenable chlamydial genetic system. Here, we describe a reverse-genetic approach to create isogenic C. trachomatis mutants. C. trachomatis was subjected to low-level ethyl methanesulfonate mutagenesis to generate chlamydiae that contained less then one mutation per genome. Mutagenized organisms were expanded in small subpopulations that were screened for mutations by digesting denatured and reannealed PCR amplicons of the target gene with the mismatch specific endonuclease CEL I. Subpopulations with mutations were then sequenced for the target region and plaque-cloned if the desired mutation was detected. We demonstrate the utility of this approach by isolating a tryptophan synthase gene (trpB) null mutant that was otherwise isogenic to its parental clone as shown by de novo genome sequencing. The mutant was incapable of avoiding the anti-microbial effect of IFN-gamma-induced tryptophan starvation. The ability to genetically manipulate chlamydiae is a major advancement that will enhance our understanding of chlamydial pathogenesis and accelerate the development of new anti-chlamydial therapeutic control measures. Additionally, this strategy could be applied to other medically important bacterial pathogens with no or difficult genetic systems.
C1 [Kari, Laszlo; Goheen, Morgan M.; Randall, Linnell B.; Taylor, Lacey D.; Carlson, John H.; Whitmire, William M.; Caldwell, Harlan D.] NIAID, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA.
[Virok, Dezso] Univ Szeged, Inst Clin Microbiol, H-6725 Szeged, Hungary.
[Rajaram, Krithika; Nelson, David E.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
[Endresz, Valeria] Univ Szeged, Dept Med Microbiol & Immunobiol, H-6720 Szeged, Hungary.
[McClarty, Grant] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3T 2N2, Canada.
RP Kari, L (reprint author), NIAID, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA.
EM karil@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health; European Research Area-NET Pathogenomics
ChlamyTrans project
FX We thank Robert Heinzen and Paul Beare for critical review of the
manuscript, Anita Mora for assistance with graphic arts, the Genomics
Unit of the Rocky Mountain Laboratories Research Technologies Section
for the genome sequencing and analysis, and Kelly Matteson for
manuscript preparation. This work was supported by the Intramural
Research Program of the National Institute of Allergy and Infectious
Diseases, National Institutes of Health. D. V. was supported by the
European Research Area-NET Pathogenomics ChlamyTrans project.
NR 24
TC 72
Z9 73
U1 0
U2 7
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 APR 26
PY 2011
VL 108
IS 17
BP 7189
EP 7193
DI 10.1073/pnas.1102229108
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 754WM
UT WOS:000289888500094
PM 21482792
ER
PT J
AU Lavine, JS
King, AA
Bjornstad, ON
AF Lavine, Jennie S.
King, Aaron A.
Bjornstad, Ottar N.
TI Natural immune boosting in pertussis dynamics and the potential for
long-term vaccine failure
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID BORDETELLA-PERTUSSIS; UNITED-STATES; WHOOPING-COUGH; INFECTION; ADULTS;
EPIDEMIOLOGY; TRANSMISSION; ADOLESCENTS; SEROEPIDEMIOLOGY; REINFECTION
AB Incidence of whooping cough, unlike many other childhood diseases for which there is an efficacious vaccine, has been increasing over the past twenty years despite high levels of vaccine coverage. Its reemergence has been particularly noticeable among teenagers and adults. Many hypotheses have been put forward to explain these two patterns, but parsimonious reconciliation of clinical data on the limited duration of immunity with both pre- and postvaccine era age-specific incidence remains a challenge. We consider the immunologically relevant, yet epidemiologically largely neglected, possibility that a primed immune system can respond to a lower dose of antigen than a naive one. We hypothesize that during the prevaccine era teenagers' and adults' primed immunity was frequently boosted by reexposure, so maintaining herd immunity in the face of potentially eroding individual immunity. In contrast, low pathogen circulation in the current era, except during epidemic outbreaks, allows immunity to be lost before reexposure occurs. We develop and analyze an age-structured model that encapsulates this hypothesis. We find that immune boosting must be more easily triggered than primary infection to account for age-incidence data. We make age-specific and dynamical predictions through bifurcation analysis and simulation. The boosting model proposed here parsimoniously captures four key features of pertussis data from highly vaccinated countries: (i) the shift in age-specific incidence, (ii) reemergence with high vaccine coverage, (iii) the possibility for cyclic dynamics in the pre- and postvaccine eras, and (iv) the apparent shift from susceptible-infectious-recovered (SIR)-like to susceptible-infectious-recovered-susceptible (SIRS)-like phenomenology of infection and immunity to Bordetella pertussis.
C1 [Lavine, Jennie S.; Bjornstad, Ottar N.] Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
[King, Aaron A.] Univ Michigan, Dept Ecol, Ann Arbor, MI 48109 USA.
[King, Aaron A.] Univ Michigan, Dept Evolutionary Biol, Ann Arbor, MI 48109 USA.
[King, Aaron A.] Univ Michigan, Dept Math, Ann Arbor, MI 48109 USA.
[King, Aaron A.; Bjornstad, Ottar N.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Bjornstad, Ottar N.] Penn State Univ, Dept Entomol, University Pk, PA 16802 USA.
RP Lavine, JS (reprint author), Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
EM jsl236@psu.edu
RI Bjornstad, Ottar/I-4518-2012; King, Aaron/B-8092-2012
OI King, Aaron/0000-0001-6159-3207
FU Science and Technology Directorate, Department of Homeland Security;
Fogarty International Center, National Institutes of Health; Bill and
Melinda Gates Foundation
FX We thank Noelle Cocoros and the Massachusetts Department of Public
Health for providing the data. We had many valuable conversations, and
in particular would like to thank Sourya Shrestha and Helene Broutin. A.
K. and O.B. acknowledge the support of the Research and Policy for
Infectious Disease Dynamics program of the Science and Technology
Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health. O.B. additionally
acknowledges support from the Bill and Melinda Gates Foundation.
NR 52
TC 56
Z9 56
U1 2
U2 12
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 APR 26
PY 2011
VL 108
IS 17
BP 7259
EP 7264
DI 10.1073/pnas.1014394108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 754WM
UT WOS:000289888500106
PM 21422281
ER
PT J
AU Afonso, PV
Parent, CA
AF Afonso, Philippe V.
Parent, Carole A.
TI PI3K and Chemotaxis: A Priming Issue?
SO SCIENCE SIGNALING
LA English
DT Article
ID NEUTROPHIL CHEMOTAXIS; CHEMOATTRACTANT GRADIENTS; MEDIATES CHEMOTAXIS;
CELL-MIGRATION; LEADING-EDGE; 3-KINASE; ACTIVATION; ROLES;
DICTYOSTELIUM; PI3K-GAMMA
AB Although the spatiotemporal activation of phosphoinositide 3-kinases (PI3Ks) at the leading edge of chemotaxing cells represents a key marker of polarity, both Dictyostelium discoideum and neutrophils lacking measurable PI3K activity can still migrate directionally under certain conditions. Evidence from various papers suggests that the differentiation state of cells or their priming status can consolidate otherwise contradictory findings.
C1 [Afonso, Philippe V.; Parent, Carole A.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Parent, CA (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM parentc@mail.nih.gov
RI Afonso, Philippe/D-2234-2014
OI Afonso, Philippe/0000-0002-4828-3797
FU Center for Cancer Research, NCI, NIH
FX We thank M. Weiger and C. McCann for helpful comments, as well as the
Intramural Research Program of the Center for Cancer Research, NCI, NIH
for support.
NR 29
TC 13
Z9 13
U1 0
U2 3
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 APR 26
PY 2011
VL 4
IS 170
AR pe22
DI 10.1126/scisignal.2002019
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 754VC
UT WOS:000289884800003
PM 21521877
ER
PT J
AU Bostom, AG
Carpenter, MA
Kusek, JW
Levey, AS
Hunsicker, L
Pfeffer, MA
Selhub, J
Jacques, PF
Cole, E
Gravens-Mueller, L
House, AA
Kew, C
McKenney, JL
Pacheco-Silva, A
Pesavento, T
Pirsch, J
Smith, S
Solomon, S
Weir, M
AF Bostom, Andrew G.
Carpenter, Myra A.
Kusek, John W.
Levey, Andrew S.
Hunsicker, Lawrence
Pfeffer, Marc A.
Selhub, Jacob
Jacques, Paul F.
Cole, Edward
Gravens-Mueller, Lisa
House, Andrew A.
Kew, Clifton
McKenney, Joyce L.
Pacheco-Silva, Alvaro
Pesavento, Todd
Pirsch, John
Smith, Stephen
Solomon, Scott
Weir, Matthew
CA FAVORIT Study Investigators
TI Homocysteine-Lowering and Cardiovascular Disease Outcomes in Kidney
Transplant Recipients Primary Results From the Folic Acid for Vascular
Outcome Reduction in Transplantation Trial
SO CIRCULATION
LA English
DT Article
DE cardiovascular disease; risk factors; mortality; clinical trials;
kidney; kidney transplantation
ID RANDOMIZED CONTROLLED-TRIAL; STAGE RENAL-DISEASE; BETA-SYNTHASE
DEFICIENCY; B-VITAMINS; MYOCARDIAL-INFARCTION; TOTAL MORTALITY;
RISK-FACTOR; HYPERHOMOCYSTEINEMIA; EVENTS; SUPPLEMENTATION
AB Background-Kidney transplant recipients, like other patients with chronic kidney disease, experience excess risk of cardiovascular disease and elevated total homocysteine concentrations. Observational studies of patients with chronic kidney disease suggest increased homocysteine is a risk factor for cardiovascular disease. The impact of lowering total homocysteine levels in kidney transplant recipients is unknown.
Methods and Results-In a double-blind controlled trial, we randomized 4110 stable kidney transplant recipients to a multivitamin that included either a high dose (n=2056) or low dose (n=2054) of folic acid, vitamin B6, and vitamin B12 to determine whether decreasing total homocysteine concentrations reduced the rate of the primary composite arteriosclerotic cardiovascular disease outcome (myocardial infarction, stroke, cardiovascular disease death, resuscitated sudden death, coronary artery or renal artery revascularization, lower-extremity arterial disease, carotid endarterectomy or angioplasty, or abdominal aortic aneurysm repair). Mean follow-up was 4.0 years. Treatment with the high-dose multivitamin reduced homocysteine but did not reduce the rates of the primary outcome (n=547 total events; hazards ratio [95% confidence interval]=0.99 [0.84 to 1.17]), secondary outcomes of all-cause mortality (n=431 deaths; 1.04 [0.86 to 1.26]), or dialysis-dependent kidney failure (n=343 events; 1.15 [0.93 to 1.43]) compared to the low-dose multivitamin.
Conclusions-Treatment with a high-dose folic acid, B6, and B12 multivitamin in kidney transplant recipients did not reduce a composite cardiovascular disease outcome, all-cause mortality, or dialysis-dependent kidney failure despite significant reduction in homocysteine level.
C1 [Bostom, Andrew G.; McKenney, Joyce L.] Rhode Isl Hosp, Providence, RI 02903 USA.
[Carpenter, Myra A.; Gravens-Mueller, Lisa] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
[Kusek, John W.] NIDDK, Bethesda, MD USA.
[Levey, Andrew S.] Tufts Med Ctr, Boston, MA USA.
[Hunsicker, Lawrence] Univ Iowa, Iowa City, IA USA.
[Pfeffer, Marc A.; Solomon, Scott] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Selhub, Jacob; Jacques, Paul F.] Jean Mayer Human Nutr Res Ctr Aging, USDA, Boston, MA USA.
[Cole, Edward] Univ Toronto, Toronto, ON, Canada.
[House, Andrew A.] London Hlth Sci Ctr, London, ON, Canada.
[Kew, Clifton] Univ Alabama, Birmingham, AL USA.
[Pacheco-Silva, Alvaro] Univ Fed Sao Paulo, Sao Paulo, Brazil.
[Pesavento, Todd] Ohio State Univ, Columbus, OH 43210 USA.
[Pirsch, John] Univ Wisconsin, Madison, WI 53706 USA.
[Smith, Stephen] Duke Univ, Durham, NC USA.
[Weir, Matthew] Univ Maryland, Baltimore, MD 21201 USA.
RP Bostom, AG (reprint author), Rhode Isl Hosp, 110 Lockwood St,Room 242, Providence, RI 02903 USA.
EM abostom@lifespan.org
RI Pacheco-Silva, Alvaro/K-3583-2013
FU National Institute of Diabetes and Digestive and Kidney Diseases [U01
DK61700]; National Institutes of Health; Office of Dietary Supplements,
National Institutes of Health
FX This study was supported by cooperative agreement U01 DK61700 from the
National Institute of Diabetes and Digestive and Kidney Diseases, the
National Institutes of Health. Support was also provided by the Office
of Dietary Supplements, National Institutes of Health. PamLab LLC of
Covington, LA, provided the high- and low-dose multivitamins.
NR 42
TC 68
Z9 74
U1 10
U2 21
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD APR 26
PY 2011
VL 123
IS 16
BP 1763
EP 1770
DI 10.1161/CIRCULATIONAHA.110.000588
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 754DU
UT WOS:000289833500013
PM 21482964
ER
PT J
AU Cabarcas, S
Schramm, L
AF Cabarcas, Stephanie
Schramm, Laura
TI RNA polymerase III transcription in cancer: the BRF2 connection
SO MOLECULAR CANCER
LA English
DT Review
ID TATA-BINDING PROTEIN; BREAST-CANCER; RETINOBLASTOMA PROTEIN; ONCOGENIC
TRANSFORMATION; GENE-EXPRESSION; P53; CELLS; ACTIVATION; TFIIIB; TUMORS
AB RNA polymerase (pol) III transcription is responsible for the transcription of small, untranslated RNAs involved in fundamental metabolic processes such mRNA processing (U6 snRNA) and translation (tRNAs). RNA pol III transcription contributes to the regulation of the biosynthetic capacity of a cell and a direct link exists between cancer cell proliferation and deregulation of RNA pol III transcription. Accurate transcription by RNA pol III requires TFIIIB, a known target of regulation by oncogenes and tumor suppressors. There have been significant advances in our understanding of how TFIIIB-mediated transcription is deregulated in a variety of cancers. Recently, BRF2, a component of TFIIIB required for gene external RNA pol III transcription, was identified as an oncogene in squamous cell carcinomas of the lung through integrative genomic analysis. In this review, we focus on recent advances demonstrating how BRF2-TFIIIB mediated transcription is regulated by tumor suppressors and oncogenes. Additionally, we present novel data further confirming the role of BRF2 as an oncogene, extracted from the Oncomine database, a cancer microarray database containing datasets derived from patient samples, providing evidence that BRF2 has the potential to be used as a biomarker for patients at risk for metastasis. This data further supports the idea that BRF2 may serve as a potential therapeutic target in a variety of cancers.
C1 [Schramm, Laura] St Johns Univ, Dept Biol Sci, Queens, NY 11439 USA.
[Cabarcas, Stephanie] NCI, Lab Canc Prevent, Canc Stem Cell Sect, Frederick, MD 21702 USA.
RP Schramm, L (reprint author), St Johns Univ, Dept Biol Sci, Queens, NY 11439 USA.
EM schramml@stjohns.edu
FU NIH [1R15CA133842-01A1]
FX This work was supported in part by NIH grant 1R15CA133842-01A1 (LS). The
authors wish to apologize, due to space restrictions, that not all
TFIIIB studies could be mentioned. We thank Dr. Joby Jacob for his
assistance with figure preparation.
NR 61
TC 15
Z9 18
U1 0
U2 4
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 APR 25
PY 2011
VL 10
AR 47
DI 10.1186/1476-4598-10-47
PG 10
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 767OH
UT WOS:000290865400001
PM 21518452
ER
PT J
AU Shaughnessy, DT
Gangarosa, LM
Schliebe, B
Umbach, DM
Xu, ZL
MacIntosh, B
Knize, MG
Matthews, PP
Swank, AE
Sandler, RS
DeMarini, DM
Taylor, JA
AF Shaughnessy, Daniel T.
Gangarosa, Lisa M.
Schliebe, Barbara
Umbach, David M.
Xu, Zongli
MacIntosh, Beth
Knize, Mark G.
Matthews, Peggy P.
Swank, Adam E.
Sandler, Robert S.
DeMarini, David M.
Taylor, Jack A.
TI Inhibition of Fried Meat-Induced Colorectal DNA Damage and Altered
Systemic Genotoxicity in Humans by Crucifera, Chlorophyllin, and Yogurt
SO PLOS ONE
LA English
DT Article
ID HETEROCYCLIC AROMATIC-AMINES; URINARY MUTAGENICITY; BRUSSELS-SPROUTS;
CANCER-RISK; SALMONELLA MUTAGENICITY; METABOLIZING ENZYMES; FECAL
MUTAGENICITY; STRAND BREAKS; GROUND-BEEF; CONSUMPTION
AB Dietary exposures implicated as reducing or causing risk for colorectal cancer may reduce or cause DNA damage in colon tissue; however, no one has assessed this hypothesis directly in humans. Thus, we enrolled 16 healthy volunteers in a 4-week controlled feeding study where 8 subjects were randomly assigned to dietary regimens containing meat cooked at either low (100 degrees C) or high temperature (250 degrees C), each for 2 weeks in a crossover design. The other 8 subjects were randomly assigned to dietary regimens containing the high-temperature meat diet alone or in combination with 3 putative mutagen inhibitors: cruciferous vegetables, yogurt, and chlorophyllin tablets, also in a crossover design. Subjects were nonsmokers, at least 18 years old, and not currently taking prescription drugs or antibiotics. We used the Salmonella assay to analyze the meat, urine, and feces for mutagenicity, and the comet assay to analyze rectal biopsies and peripheral blood lymphocytes for DNA damage. Low-temperature meat had undetectable levels of heterocyclic amines (HCAs) and was not mutagenic, whereas high-temperature meat had high HCA levels and was highly mutagenic. The high-temperature meat diet increased the mutagenicity of hydrolyzed urine and feces compared to the low-temperature meat diet. The mutagenicity of hydrolyzed urine was increased nearly twofold by the inhibitor diet, indicating that the inhibitors enhanced conjugation. Inhibitors decreased significantly the mutagenicity of un-hydrolyzed and hydrolyzed feces. The diets did not alter the levels of DNA damage in non-target white blood cells, but the inhibitor diet decreased nearly twofold the DNA damage in target colorectal cells. To our knowledge, this is the first demonstration that dietary factors can reduce DNA damage in the target tissue of fried-meat associated carcinogenesis.
C1 [Shaughnessy, Daniel T.; Taylor, Jack A.] Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Gangarosa, Lisa M.; Schliebe, Barbara; Sandler, Robert S.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA.
[Umbach, David M.] Natl Inst Environm Hlth Sci, Biostat Branch, NIH, DHHS, Res Triangle Pk, NC USA.
[Xu, Zongli; Taylor, Jack A.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC USA.
[MacIntosh, Beth] Univ N Carolina, Clin & Translat Res Ctr, Chapel Hill, NC USA.
[Knize, Mark G.] Lawrence Livermore Natl Lab, Chem Mat & Life Sci Div, Livermore, CA USA.
[Matthews, Peggy P.; Swank, Adam E.; DeMarini, David M.] US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA.
RP Shaughnessy, DT (reprint author), Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
EM taylor@niehs.nih.gov
OI xu, zongli/0000-0002-9034-8902; taylor, jack/0000-0001-5303-6398
FU National Center of Research Resources, National Institutes of Health
[M01RR00046, UL1RR025747]; National Institute of Environmental Health
Sciences, NIH, DHHS; U.S. EPA; NIEHS
FX This project was supported in part by grants M01RR00046 and/or
UL1RR025747 from the National Center of Research Resources, National
Institutes of Health, which supports the Clinical and Translational
Research Center at the University of North Carolina at Chapel Hill. This
research was also supported in part by the Intramural Research Program
of the National Institute of Environmental Health Sciences, NIH, DHHS as
well as by the U.S. EPA. D. T. Shaughnessy acknowledges support from an
NIEHS Intramural Research Training Award. This study is registered in
clinicaltrials. gov number NCT00340743. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 48
TC 16
Z9 17
U1 0
U2 17
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 APR 25
PY 2011
VL 6
IS 4
AR e18707
DI 10.1371/journal.pone.0018707
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 756MU
UT WOS:000290016800019
PM 21541030
ER
PT J
AU El-Bassel, N
Jemmott, JB
Landis, JR
Pequegnat, W
Wingood, GM
Wyatt, GE
Bellamy, SL
AF El-Bassel, Nabila
Jemmott, John B., III
Landis, J. Richard
Pequegnat, Willo
Wingood, Gina M.
Wyatt, Gail Elizabeth
Bellamy, Scarlett L.
CA Natl Inst Mental Hlth Multisite
TI Intervention to Influence Behaviors Linked to Risk of Chronic Diseases A
Multisite Randomized Controlled Trial With African-American
HIV-Serodiscordant Heterosexual Couples
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID ANTIRETROVIRAL THERAPY; PHYSICAL-ACTIVITY; WEIGHT-LOSS; VEGETABLE
CONSUMPTION; DIABETES-MELLITUS; BLACK CHURCHES; CANCER; PREVENTION;
ADULTS; FRUIT
AB Background: The high morbidity and mortality in African Americans associated with behavior-linked chronic diseases are well documented.
Methods: We tested the efficacy of an intervention to increase multiple health-related behaviors in African Americans. In a multisite cluster-randomized controlled trial, groups of African American human immunodeficiency virus (HIV)-serodiscordant heterosexual couples in Atlanta (Georgia), Los Angeles (California), New York (New York), and Philadelphia (Pennsylvania) were allocated to an individual-focused health promotion that addressed multiple health-related behaviors or to a couple-focused HIV/sexually transmitted disease (STD) risk reduction intervention. Primary outcomes were adherence to fruit and vegetable consumption and physical activity guidelines assessed preintervention, immediately postintervention, and 6 and 12 months postintervention. Secondary outcomes included fatty food consumption, prostate and breast cancer screening, and alcohol use. Generalized estimating equations tested the efficacy of the health promotion intervention over the postintervention assessments.
Results: Health promotion intervention participants were more likely to report consuming 5 or more servings of fruits and vegetables daily (rate ratio [RR], 1.38; 95% confidence interval [CI], 1.18 to 1.62) and adhering to physical activity guidelines (1.39; 1.22 to 1.59) compared with HIV/STD intervention participants. In the health promotion intervention compared with the HIV/STD intervention, participants consumed fatty foods less frequently (mean difference, -0.18; 95% CI, -0.30 to -0.07), more men received prostate cancer screening (RR, 1.51; 95% CI, 1.21 to 1.88), and more women received a mammogram (RR, 1.26; 95% CI, 1.06 to 1.50). Alcohol use did not differ between the intervention groups.
Conclusion: This trial demonstrates the efficacy of interventions targeting multiple health-related behaviors in African American HIV-seropositive and HIV-seronegative men and women.
C1 [Pequegnat, Willo] NIMH, Ctr Mental Hlth Res AIDS, Div AIDS, NIH, Bethesda, MD 20814 USA.
[El-Bassel, Nabila] Columbia Univ, Sch Social Work, Social Intervent Grp, New York, NY USA.
[Jemmott, John B., III] Univ Penn, Annenberg Sch Commun, Philadelphia, PA 19104 USA.
[Jemmott, John B., III] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Landis, J. Richard; Bellamy, Scarlett L.] Univ Penn, Dept Biostat & Engn, Philadelphia, PA 19104 USA.
[Wingood, Gina M.] Emory Univ, Rollins Sch Publ Hlth, Dept Behav Sci & Hlth Educ, Atlanta, GA 30322 USA.
[Wyatt, Gail Elizabeth] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA.
RP Pequegnat, W (reprint author), NIMH, Ctr Mental Hlth Res AIDS, Div AIDS, NIH, 6001 Execut Blvd,Room 6219B, Bethesda, MD 20814 USA.
EM wpequegn@mail.nih.gov
RI Metzger, David/D-9499-2012
FU National Institute of Mental Health
FX This study was funded by the National Institute of Mental Health.
NR 46
TC 9
Z9 9
U1 3
U2 7
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD APR 25
PY 2011
VL 171
IS 8
BP 728
EP 736
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 754KK
UT WOS:000289853300003
PM 21518939
ER
PT J
AU Moore, HM
Kelly, AB
Jewell, SD
McShane, LM
Clark, DP
Greenspan, R
Hayes, DF
Hainaut, P
Kim, P
Mansfield, EA
Potapova, O
Riegman, P
Rubinstein, Y
Seijo, E
Somiari, S
Watson, P
Weier, HU
Zhu, C
Vaught, J
AF Moore, Helen M.
Kelly, Andrea B.
Jewell, Scott D.
McShane, Lisa M.
Clark, Douglas P.
Greenspan, Renata
Hayes, Daniel F.
Hainaut, Pierre
Kim, Paula
Mansfield, Elizabeth A.
Potapova, Olga
Riegman, Peter
Rubinstein, Yaffa
Seijo, Edward
Somiari, Stella
Watson, Peter
Weier, Heinz-Ulrich
Zhu, Claire
Vaught, Jim
TI Biospecimen Reporting for Improved Study Quality (BRISQ)
SO CANCER CYTOPATHOLOGY
LA English
DT Article
DE BRISQ; best practices; biobank; biospecimen; human; quality; research;
guidelines
ID APPROACHING CLINICAL PROTEOMICS; FUTURE FIELDS; CURRENT STATE; CANCER;
TISSUE
AB Human biospecimens are subjected to collection, processing, and storage that can significantly alter their molecular composition and consistency. These biospecimen preanalytical factors, in turn, influence experimental outcomes and the ability to reproduce scientific results. Currently, the extent and type of information specific to the biospecimen preanalytical conditions reported in scientific publications and regulatory submissions varies widely. To improve the quality of research that uses human tissues, it is crucial that information on the handling of biospecimens be reported in a thorough, accurate, and standardized manner. The Biospecimen Reporting for Improved Study Quality (BRISQ) recommendations outlined herein are intended to apply to any study in which human biospecimens are used. The purpose of reporting these details is to supply others, from researchers to regulators, with more consistent and standardized information to better evaluate, interpret, compare, and reproduce the experimental results. The BRISQ guidelines are proposed as an important and timely resource tool to strengthen communication and publications on biospecimen-related research and to help reassure patient contributors and the advocacy community that their contributions are valued and respected. Cancer (Cancer Cytopathol) 2011;119:92-101. Published 2011 by the American Cancer Society.*
C1 [Clark, Douglas P.] Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA.
[Moore, Helen M.; Vaught, Jim] Natl Canc Inst, Off Biorepositories & Biospecimen Res, Bethesda, MD USA.
[Kelly, Andrea B.] Rose Li & Associates Inc, Bethesda, MD USA.
[Jewell, Scott D.] Van Andel Res Inst, Program Biospecimen Sci, Grand Rapids, MI USA.
[McShane, Lisa M.] NCI, Div Canc Treatment & Diag, Biometr Res Branch, Bethesda, MD 20892 USA.
[Greenspan, Renata] Henry M Jackson Fdn Adv Mil Med, US Mil Canc Inst, Rockville, MD USA.
[Hayes, Daniel F.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Hainaut, Pierre] World Hlth Org, IARC, Lyon, France.
[Kim, Paula] Paula Kim Inc, TRAC, Solana Beach, CA USA.
[Mansfield, Elizabeth A.] US Dept HHS, Ctr Devices & Radiol Hlth, US FDA, Silver Spring, MD USA.
[Potapova, Olga] Cureline Inc, San Francisco, CA USA.
[Riegman, Peter] Erasmus MC Tissue Bank, Dept Pathol, Rotterdam, Netherlands.
[Rubinstein, Yaffa] NIH, Off Rare Dis Res, Bethesda, MD 20892 USA.
[Seijo, Edward] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Somiari, Stella] Windber Res Inst, Windber, PA USA.
[Watson, Peter] British Columbia Canc Agcy, Vancouver Isl Ctr, Victoria, BC, Canada.
[Weier, Heinz-Ulrich] US DOE, Div Life Sci, Lawrence Berkeley Natl Lab, Berkeley, CA USA.
[Zhu, Claire] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Clark, DP (reprint author), Johns Hopkins Univ Hosp, Dept Pathol, 600 N Wolfe St,PATH 406, Baltimore, MD 21287 USA.
EM dclark@jhmi.edu
RI Hainaut, Pierre /B-6018-2012
OI Hainaut, Pierre /0000-0002-1303-1610
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
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 No. HHSN261200800001E.
NR 11
TC 62
Z9 62
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1934-662X
EI 1934-6638
J9 CANCER CYTOPATHOL
JI Cancer Cytopathol.
PD APR 25
PY 2011
VL 119
IS 2
BP 92
EP 101
DI 10.1002/cncy.20147
PG 10
WC Oncology; Pathology
SC Oncology; Pathology
GA 751SB
UT WOS:000289636800004
PM 21433001
ER
PT J
AU Krasnova, IN
Ladenheim, B
Hodges, AB
Volkow, ND
Cadet, JL
AF Krasnova, Irina N.
Ladenheim, Bruce
Hodges, Amber B.
Volkow, Nora D.
Cadet, Jean Lud
TI Chronic Methamphetamine Administration Causes Differential Regulation of
Transcription Factors in the Rat Midbrain
SO PLOS ONE
LA English
DT Article
ID TYROSINE-HYDROXYLASE; DOPAMINE TRANSPORTER; SUBSTANTIA-NIGRA; SONIC
HEDGEHOG; INDUCED NEUROTOXICITY; NEUROCHEMICAL CONSEQUENCES; AMPHETAMINE
NEUROTOXICITY; MICROGLIAL ACTIVATION; PARKINSONS-DISEASE; STRIATAL
DOPAMINE
AB Methamphetamine (METH) is an addictive and neurotoxic psychostimulant widely abused in the USA and throughout the world. When administered in large doses, METH can cause depletion of striatal dopamine terminals, with preservation of midbrain dopaminergic neurons. Because alterations in the expression of transcription factors that regulate the development of dopaminergic neurons might be involved in protecting these neurons after toxic insults, we tested the possibility that their expression might be affected by toxic doses of METH in the adult brain. Male Sprague-Dawley rats pretreated with saline or increasing doses of METH were challenged with toxic doses of the drug and euthanized two weeks later. Animals that received toxic METH challenges showed decreases in dopamine levels and reductions in tyrosine hydroxylase protein concentration in the striatum. METH pretreatment protected against loss of striatal dopamine and tyrosine hydroxylase. In contrast, METH challenges caused decreases in dopamine transporters in both saline-and METH-pretreated animals. Interestingly, METH challenges elicited increases in dopamine transporter mRNA levels in the midbrain in the presence but not in the absence of METH pretreatment. Moreover, toxic METH doses caused decreases in the expression of the dopamine developmental factors, Shh, Lmx1b, and Nurr1, but not in the levels of Otx2 and Pitx3, in saline-pretreated rats. METH pretreatment followed by METH challenges also decreased Nurr1 but increased Otx2 and Pitx3 expression in the midbrain. These findings suggest that, in adult animals, toxic doses of METH can differentially influence the expression of transcription factors involved in the developmental regulation of dopamine neurons. The combined increases in Otx2 and Pitx3 expression after METH preconditioning might represent, in part, some of the mechanisms that served to protect against METH-induced striatal dopamine depletion observed after METH preconditioning.
C1 [Krasnova, Irina N.; Ladenheim, Bruce; Hodges, Amber B.; Cadet, Jean Lud] NIDA, Mol Neuropsychiat Res Branch, DHHS, NIH,Intramural Res Program, Bethesda, MD 20892 USA.
[Hodges, Amber B.] Morgan State Univ, Dept Psychol, Baltimore, MD 21239 USA.
[Volkow, Nora D.] NIDA, NIH, US Dept Hlth & Human Serv DHHS, Bethesda, MD 20892 USA.
RP Krasnova, IN (reprint author), NIDA, Mol Neuropsychiat Res Branch, DHHS, NIH,Intramural Res Program, Bethesda, MD 20892 USA.
EM jcadet@intra.nida.nih.gov
FU National Institute on Drug Abuse, NIH/DHHS
FX This research was supported by the Intramural Research Program of the
National Institute on Drug Abuse, NIH/DHHS. NIH had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 74
TC 14
Z9 14
U1 2
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 APR 25
PY 2011
VL 6
IS 4
AR e19179
DI 10.1371/journal.pone.0019179
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 756MU
UT WOS:000290016800035
PM 21547080
ER
PT J
AU Fogel, J
Hoover, DR
Sun, J
Mofenson, LM
Fowler, MG
Taylor, AW
Kumwenda, N
Taha, TE
Eshleman, SH
AF Fogel, Jessica
Hoover, Donald R.
Sun, Jin
Mofenson, Lynne M.
Fowler, Mary G.
Taylor, Allan W.
Kumwenda, Newton
Taha, Taha E.
Eshleman, Susan H.
TI Analysis of nevirapine resistance in HIV-infected infants who received
extended nevirapine or nevirapine/zidovudine prophylaxis
SO AIDS
LA English
DT Article
DE HIV; infants; Malawi; nevirapine; resistance
ID SINGLE-DOSE NEVIRAPINE; ANTIRETROVIRAL THERAPY; VERTICAL TRANSMISSION;
UGANDAN INFANTS; NVP RESISTANCE; SUBTYPE-A; IN-UTERO; WOMEN; HIVNET-012;
CHILDREN
AB Background: In the Post Exposure Prophylaxis of Infants (PEPI)-Malawi trial, infants received up to 14 weeks of extended nevirapine (NVP) or extended NVP with zidovudine (NVP + ZDV) to prevent postnatal HIV transmission. We examined emergence and persistence of NVP resistance in HIV-infected infants who received these regimens prior to HIV diagnosis.
Methods: Infant plasma samples collected at 14 weeks of age were tested using the ViroSeq HIV Genotyping System and a sensitive point mutation assay, LigAmp (for K103N and Y181C). Samples collected at 6 and 12 months of age were analyzed using LigAmp.
Results: At 14 weeks of age, NVP resistance was detected in samples from 82 (75.9%) of 108 HIV-infected infants. Although the frequency of NVP resistance detected by ViroSeq was lower in the extended NVP + ZDV arm than in the extended NVP arm, the difference was not statistically significant (38/55 = 69.1% vs. 44/53 = 83.0%, P = 0.12). Similar results were obtained using LigAmp. Using LigAmp, the proportion of infants who still had detectable NVP resistance at 6 and 12 months was similar among infants in the two study arms (at 6 months: 17/20 = 85.0% for extended NVP vs. 21/26 = 80.8% for extended NVP + ZDV, P = 00; at 12 months: 9/16 = 56.3% for extended NVP vs. 10/13 = 76.9% for extended NVP + ZDV, P = 0.43).
Conclusion: Infants exposed to extended NVP or extended NVP + ZDV had high rates of NVP resistance at 14 weeks of age, and resistant variants frequently persisted for 6-12 months. Frequency and persistence of NVP resistance did not differ significantly among infants who received extended NVP only vs. extended NVP + ZDV prophylaxis. (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Fogel, Jessica; Fowler, Mary G.; Eshleman, Susan H.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Hoover, Donald R.] Rutgers State Univ, Dept Stat & Biostat, Inst Hlth Healthcare Policy & Aging Res, Piscataway, NJ USA.
[Sun, Jin; Kumwenda, Newton; Taha, Taha E.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal AIDS Branch, NIH, Rockville, MD USA.
[Fowler, Mary G.; Taylor, Allan W.] Ctr Dis Control & Prevent CDC, Epidemiol Branch, Div HIV AIDS Prevent, Atlanta, GA USA.
RP Eshleman, SH (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Ross Bldg 646,720 Rutland Ave, Baltimore, MD 21205 USA.
EM seshlem@jhmi.edu
OI Mofenson, Lynne/0000-0002-2818-9808
FU National Institute of Allergy and Infectious Diseases (NIAID); Eunice
Kennedy Shriver National Institutes of Child Health and Human
Development (NICH/HD); National Institute on Drug Abuse; National
Institute of Mental Health; Office of AIDS Research, of the NIH, DHHS
[U01 AI068613]; International Maternal Pediatric and Adolescent AIDS
Clinical Trials (IMPAACT) Network [U01 AI068633]; Centers for Disease
Control and Prevention [U50/CCU022061]; [R03 HD061299]; [R01 AI087139]
FX This work was supported by R03 HD061299, R01 AI087139, the HIV
Prevention Trials Network (HPTN) sponsored by the National Institute of
Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National
Institutes of Child Health and Human Development (NICH/HD), National
Institute on Drug Abuse, National Institute of Mental Health, and Office
of AIDS Research, of the NIH, DHHS (U01 AI068613), the International
Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) Network
(U01 AI068633), and Centers for Disease Control and Prevention
Cooperative Agreement U50/CCU022061.
NR 22
TC 10
Z9 11
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD APR 24
PY 2011
VL 25
IS 7
BP 911
EP 917
DI 10.1097/QAD.0b013e328344fedc
PG 7
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 749IQ
UT WOS:000289458900004
PM 21487249
ER
PT J
AU Karim, SSA
Richardson, BA
Ramjee, G
Hoffman, IF
Chirenje, ZM
Taha, T
Kapina, M
Maslankowski, L
Coletti, A
Profy, A
Moench, TR
Piwowar-Manning, E
Masse, B
Hillier, SL
Soto-Torres, L
AF Karim, Salim S. Abdool
Richardson, Barbra A.
Ramjee, Gita
Hoffman, Irving F.
Chirenje, Zvavahera M.
Taha, Taha
Kapina, Muzala
Maslankowski, Lisa
Coletti, Anne
Profy, Albert
Moench, Thomas R.
Piwowar-Manning, Estelle
Masse, Benoit
Hillier, Sharon L.
Soto-Torres, Lydia
CA HIV Prevention Trials Network HPTN
TI Safety and effectiveness of BufferGel and 0.5% PRO2000 gel for the
prevention of HIV infection in women
SO AIDS
LA English
DT Article
DE BufferGel; HIV prevention; microbicide; PRO2000 gel; women
ID SEXUALLY-TRANSMITTED-DISEASES; RANDOMIZED CONTROLLED TRIAL; VAGINAL
MICROBICIDE; NONOXYNOL-9 GEL; DOUBLE-BLIND; IN-VITRO; PRO 2000;
TRANSMISSION; TOLERABILITY; EFFICACY
AB Objective: To determine the safety and effectiveness of BufferGel and 0.5% PRO2000 microbicide gels for the prevention of male-to-female HIV transmission.
Design: Phase II/IIb, randomized, placebo-controlled trial with three double-blinded gel arms and an open-label no gel arm.
Methods: Study participants from Malawi, South Africa, Zambia, Zimbabwe, and the USA were instructed to apply study gel up to 1 h before each sex act and safety, sexual behavior, pregnancy, gel adherence, acceptability, and HIV serostatus were assessed during follow-up.
Results: The 3101 enrolled women were followed for an average of 20.4 months with 93.6% retention and 81.1% self-reported gel adherence. Adverse event rates were similar in all study arms. HIV incidence rates in the 0.5% PRO2000 gel, BufferGel, placebo gel, and no gel arms were 2.70, 4.14, 3.91, and 4.02 per 100 women-years, respectively. HIV incidence in the 0.5% PRO2000 gel arm was lower than the placebo gel arm (hazard ratio = 0.7, P = 0.10) and the no gel arm (hazard ratio = 0.67, P = 0.06). HIV incidence rates were similar in the BufferGel and both placebo gel (hazard ratio = 1.10, P = 0.63) and no gel control arms (hazard ratio = 1.05, P = 0.78). HIV incidence was similar in the placebo gel and no gel arms (hazard ratio = 0.97, P = 0.89).
Conclusion: The 0.5% PRO2000 gel demonstrated a modest 30% reduction in HIV acquisition in women. However, these results were not statistically significant and subsequent findings from the Microbicide Development Programme (MDP) 301 trial have confirmed that 0.5% PRO2000 gel has little or no protective effect. BufferGel did not alter the risk of HIV infection. Both products were well tolerated. (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Karim, Salim S. Abdool] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
[Richardson, Barbra A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Ramjee, Gita] S African MRC, HIV Prevent Res Unit, Durban, South Africa.
[Hoffman, Irving F.] Univ N Carolina, Div Infect Dis, Chapel Hill, NC USA.
[Chirenje, Zvavahera M.] Univ Zimbabwe, Coll Hlth Sci, Dept Obstet & Gynecol, Harare, Zimbabwe.
[Taha, Taha] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Kapina, Muzala] Ctr Infect Dis Res Zambia, Lusaka, Zambia.
[Maslankowski, Lisa] Univ Penn, Philadelphia, PA 19104 USA.
[Coletti, Anne] Family Hlth Int, Durham, NC USA.
[Profy, Albert] Endo Pharmaceut Solut Inc, Preclin & Pharmaceut Sci, Lexington, MA USA.
[Moench, Thomas R.] ReProtect Inc, Baltimore, MD USA.
[Masse, Benoit] Univ Montreal, Montreal, PQ, Canada.
[Hillier, Sharon L.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Soto-Torres, Lydia] NIH, Bethesda, MD 20892 USA.
[Karim, Salim S. Abdool] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Doris Duke Med Res Inst, Ctr AIDS Program Res S Africa CAPRISA, ZA-4013 Congella, South Africa.
RP Karim, SSA (reprint author), Univ KwaZulu Natal, Nelson R Mandela Sch Med, Doris Duke Med Res Inst, Ctr AIDS Program Res S Africa CAPRISA, Private Bag X7, ZA-4013 Congella, South Africa.
EM caprisa@ukzn.ac.za
OI Masse, Benoit/0000-0002-4944-8098; Abdool Karim,
Salim/0000-0002-4986-2133
FU US National Institutes of Health (NIH) [035]; National Institute of
Allergy and Infectious Diseases (NIAID) [U01AI46749, U01AI068633,
UO1AI068615]; Eunice Kennedy Shriver National Institute of Child Health
and Human Development (NICHD); National Institute of Drug Abuse (NIDA);
National Institute of Mental Health (NIMH); NICHD; US Agency for
International Development (USAID); ReProtect; National Institutes for
Health
FX HIV Prevention Trials Network (HPTN) 035 was funded by the US National
Institutes of Health (NIH). The study was designed and implemented by
the HPTN and the Microbicide Trials Network (MTN). The HPTN (U01AI46749)
has been funded by the National Institute of Allergy and Infectious
Diseases (NIAID), the Eunice Kennedy Shriver National Institute of Child
Health and Human Development (NICHD), National Institute of Drug Abuse
(NIDA), and National Institute of Mental Health (NIMH). The MTN
(U01AI068633) has been funded by NIAID, NICHD, and NIMH. The study
products were provided free of charge by Endo Pharmaceuticals and
ReProtect Inc. The US Agency for International Development (USAID)
provided funding for manufacturing of BufferGel for this study. The
Statistical Center was supported by NIAID (UO1AI068615). We specially
acknowledge Dr Roberta Black for her unstinting support and
encouragement from conception to completion of this trial, without which
this study would not have been possible.; T.R.M. is an employee of
ReProtect that sponsored BufferGel for the study; and A. P. was an
employee of, and held an equity interest in, Endo Pharmaceuticals
Solutions (formerly Indevus Pharmaceuticals), the owner of PRO2000 gel.
L.S.-T. is an employee of the National Institutes for Health, which
funded this study. None of the other authors have any specified
relationships with any companies that might have an interest in the
submitted work in the previous 3 years; their spouses, partners, or
children have no financial relationships that may be relevant to the
submitted work; and S. S. A. K., B. A. R., G. R., I. F. H., Z.M.C., T.
T., M. K., L. M., A. C., E.P.-M., B. M., S. L. H. have no nonfinancial
interests that may be relevant to the submitted work.
NR 34
TC 109
Z9 110
U1 1
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD APR 24
PY 2011
VL 25
IS 7
BP 957
EP 966
DI 10.1097/QAD.0b013e32834541d9
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 749IQ
UT WOS:000289458900009
ER
PT J
AU Fathi, AR
Yang, CZ
Bakhtian, KD
Qi, M
Lonser, RR
Pluta, RM
AF Fathi, Ali R.
Yang, Chunzhang
Bakhtian, Kamran D.
Qi, Meng
Lonser, Russell R.
Pluta, Ryszard M.
TI Carbon dioxide influence on nitric oxide production in endothelial cells
and astrocytes: Cellular mechanisms
SO BRAIN RESEARCH
LA English
DT Article
DE Nitric oxide; Chemoregulation; Endothelial cell; Astrocyte; Cerebral
blood flow; Neurovascular unit
ID CEREBRAL-BLOOD-FLOW; SUBARACHNOID HEMORRHAGE; AUTO-REGULATION; PRIMATE
MODEL; SYNTHASE; HYPERCAPNIA; CHEMOREGULATION; VASODILATION;
DYSFUNCTION; INHIBITION
AB Cerebral vessels may regulate cerebral blood flow by responding to changes in carbon dioxide (CO(2)) through nitric oxide (NO) production. To better determine the role of NO production by human adult cerebral microvascular endothelial cells and human fetal astrocytes under different CO(2) conditions, we studied endothelial cell and astrocyte production of NO under hypo-, normo- and hypercapnic conditions. Human cerebral endothelial cell and fetal astrocyte cultures were exposed to hypocapnic (pCO(2) 21.7 +/- 6.7 mmHg), normocapnic (pCO2 40.1 +/- 0.9 mmHg) and hypercapnic (pCO(2) 56.3 +/- 8.7 mmHg) conditions. NO production was recorded continuously over 24 hours with stable pH. N-nitro-L-arginine [NLA; a nitric oxide synthase (NOS) inhibitor] and L-arginine (substrate for NO production via NOS) were used to further define the role of NOS in chemoregulation. NO levels in endothelial cells increased during hypercapnia by 36% in 8 hours and remained 25% above baseline. NO increase in astrocytes was 30% after 1 hour but returned to baseline at 8 hours. NLA blocked NO increase in endothelial cells under hypercapnia. During hypocapnia, NO levels in the endothelial cells decreased by 30% at 8 hours but were unchanged in astrocytes. L-arginine prevented NO decrease in endothelial cells under hypocapnia. NO changes in the endothelial cells correlated with changes in pCO(2) (R=0.99) and were independent of pH. This study suggests that cerebral endothelial cells and astrocytes release NO under normocapnic conditions and NO production is increased during hypercapnia and decreased during hypocapnia independent of pH. Further, this demonstrates that endothelial cells may play a pivotal role in chemoregulation by modulating NOS activity. Published by Elsevier B.V.
C1 [Fathi, Ali R.; Yang, Chunzhang; Bakhtian, Kamran D.; Qi, Meng; Lonser, Russell R.; Pluta, Ryszard M.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Fathi, Ali R.] Kantonsspital Aarau AG, Dept Neurosurg, Aarau, Switzerland.
[Qi, Meng] Nanjing Univ, Sch Med, Jinling Hosp, Dept Neurosurg, Nanjing 210008, Jiangsu Prov, Peoples R China.
RP Pluta, RM (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 3D20, Bethesda, MD 20892 USA.
EM plutar@ninds.nih.gov
RI QI, Meng/F-2802-2012
FU National Institute of Neurological Disorders and Stroke (NINDS),
National Institutes of Health (NIH); China Scholarship Council
[2008619102]; Swiss National Science Foundation [PBSKP3-123454]
FX This research was supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke (NINDS),
National Institutes of Health (NIH). We thank Dr. Eugene Major of the
Section on Molecular Virology and Genetics, Laboratory of Viral and
Molecular Pathogenesis, NINDS, NIH for generously contributing human
astrocyte cultures, and Drs. Mima Bacic and Robert J. Bock for their
assistance in preparing the human endothelial cell cultures and
measuring NO production. Dr. Meng Qi was partly supported by a
scholarship from the China Scholarship Council (2008619102). Dr. Ali R.
Fathi was supported by a grant from the Swiss National Science
Foundation (PBSKP3-123454).
NR 34
TC 12
Z9 12
U1 1
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD APR 22
PY 2011
VL 1386
BP 50
EP 57
DI 10.1016/j.brainres.2011.02.066
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 755TD
UT WOS:000289958700006
PM 21362408
ER
PT J
AU Cenik, ES
Fukunaga, R
Lu, G
Dutcher, R
Wang, YM
Hall, TMT
Zamore, PD
AF Cenik, Elif Sarinay
Fukunaga, Ryuya
Lu, Gang
Dutcher, Robert
Wang, Yeming
Hall, Traci M. Tanaka
Zamore, Phillip D.
TI Phosphate and R2D2 Restrict the Substrate Specificity of Dicer-2, an
ATP-Driven Ribonuclease
SO MOLECULAR CELL
LA English
DT Article
ID DOUBLE-STRANDED-RNA; SMALL-INTERFERING RNA; ARGONAUTE2 PAZ DOMAIN;
ENDOGENOUS SIRNAS; INTRACELLULAR PHOSPHATE; MICROPROCESSOR COMPLEX;
CAENORHABDITIS-ELEGANS; DROSHA-DGCR8 COMPLEX; PRIMARY MICRORNAS;
HELICASE DOMAIN
AB Drosophila Dicer-2 generates small interfering RNAs (siRNAs) from long double-stranded RNA (dsRNA), whereas Dicer-1 produces microRNAs (miRNAs) from pre-miRNA. What makes the two Dicers specific for their biological substrates? We find that purified Dicer-2 can efficiently cleave pre-miRNA, but that inorganic phosphate and the Dicer-2 partner protein R2D2 inhibit pre-miRNA cleavage. Dicer-2 contains C-terminal RNase III domains that mediate RNA cleavage and an N-terminal helicase motif, whose function is unclear. We show that Dicer-2 is a dsRNA-stimulated ATPase that hydrolyzes ATP to ADP; ATP hydrolysis is required for Dicer-2 to process long dsRNA, but not pre-miRNA. Wild-type Dicer-2, but not a mutant defective in ATP hydrolysis, can generate siRNAs faster than it can dissociate from a long dsRNA substrate. We propose that the Dicer-2 helicase domain uses ATP to generate many siRNAs from a single molecule of dsRNA before dissociating from its substrate.
C1 [Cenik, Elif Sarinay; Fukunaga, Ryuya; Zamore, Phillip D.] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USA.
[Cenik, Elif Sarinay; Fukunaga, Ryuya; Zamore, Phillip D.] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA.
[Lu, Gang; Dutcher, Robert; Wang, Yeming; Hall, Traci M. Tanaka] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Zamore, PD (reprint author), Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, 364 Plantat St, Worcester, MA 01605 USA.
EM phillip.zamore@umassmed.edu
RI Zamore, Phillip/A-8941-2013; Wang, Yeming/C-9082-2013;
OI Fukunaga, Ryuya/0000-0002-5814-8206
FU National Institutes of Health [GM62862, GM65236]; National Institute of
Environmental Health Sciences; JSPS; Charles A. King Trust
FX We thank Yukihide Tomari for help purifying recombinant Dicer-2, members
of the Zamore and Hall laboratories and Can Cenik for advice and
comments on the manuscript, and Sean Ryder for suggesting we test the
effect of phosphate on dicing of pre-miRNA. This work was supported in
part by grants from the National Institutes of Health to P.D.Z. (GM62862
and GM65236), the Intramural Research Program of the National Institute
of Environmental Health Sciences to T.M.T.H., and a JSPS Research
Fellowship for Research Abroad and a Charles A. King Trust Postdoctoral
Fellowship to R.F.
NR 70
TC 56
Z9 59
U1 1
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD APR 22
PY 2011
VL 42
IS 2
BP 172
EP 184
DI 10.1016/j.molcel.2011.03.002
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 754RF
UT WOS:000289873700006
PM 21419681
ER
PT J
AU Wu, H
Siegel, RM
AF Wu, Hao
Siegel, Richard M.
TI Progranulin Resolves Inflammation
SO SCIENCE
LA English
DT Editorial Material
ID COLLAGEN-INDUCED ARTHRITIS; HOST-DEFENSE; MICE
C1 [Wu, Hao] Weill Cornell Med Coll, Dept Biochem, New York, NY 10065 USA.
[Siegel, Richard M.] NIAMSD, NIH, Bethesda, MD 20814 USA.
RP Wu, H (reprint author), Weill Cornell Med Coll, Dept Biochem, New York, NY 10065 USA.
EM siegelr@mail.nih.gov
FU NIAID NIH HHS [R01 AI045937]
NR 9
TC 25
Z9 26
U1 0
U2 10
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 APR 22
PY 2011
VL 332
IS 6028
BP 427
EP 428
DI 10.1126/science.1205992
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 753NG
UT WOS:000289784900030
PM 21512023
ER
PT J
AU Peterson, AW
Pendrak, ML
Roberts, DD
AF Peterson, Alexander W.
Pendrak, Michael L.
Roberts, David D.
TI ATP Binding to Hemoglobin Response Gene 1 Protein Is Necessary for
Regulation of the Mating Type Locus in Candida albicans
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ANOMALOUS ELECTROPHORETIC BEHAVIOR; ADENYLATE KINASE;
SACCHAROMYCES-CEREVISIAE; NUCLEOTIDE-BINDING; ACIDIC PROTEIN; P-LOOP;
YEAST; CHROMATOGRAPHY; MOTIF
AB HBR1 (hemoglobin response gene 1) is an essential gene in Candida albicans that positively regulates mating type locus MTL alpha gene expression and thereby regulates cell type-specific developmental genes. Hbr1p contains a phosphate-binding loop (P-loop), a highly conserved motif characteristic of ATP-and GTP-binding proteins. Recombinant Hbr1p was isolated in an oligomeric state that specifically bound ATP with K(d) similar to 2 mu M. ATP but not ADP, AMP, GTP, or dATP specifically protected Hbr1p from proteolysis by trypsin. Site-directed mutagenesis of the highly conserved P-loop lysine (K22Q) and the less conserved glycine (G19S) decreased the binding affinity for soluble ATP and ATP immobilized through its gamma-phosphate. ATP bound somewhat more avidly than ATP gamma S to wild type and mutant Hbr1p. Although Hbr1p exhibits sequence motifs characteristic of adenylate kinases, and adenylate kinase and ATPase activities have been reported for the apparent human ortholog of Hbr1p, assays for adenylate kinase activity, autophosphorylation, and ATPase activity proved negative. Overexpression of wild type but not the mutant forms of Hbr1p restored MTl alpha 2 expression in an HBR1/hbr1 mutant, indicating that ATP binding to the P-loop is necessary for this function of Hbr1p.
C1 [Peterson, Alexander W.; Pendrak, Michael L.; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Roberts, DD (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10,Rm 2A33,10 Ctr Dr, Bethesda, MD 20892 USA.
EM droberts@helix.nih.gov
RI Roberts, David/A-9699-2008
OI Roberts, David/0000-0002-2481-2981
FU National Institutes of Health through the National Cancer Institute
Center for Cancer Research [ZIA SC 009173]
FX This work was supported, in whole or in part, by the National Institutes
of Health through the National Cancer Institute Center for Cancer
Research Intramural Research Program, ZIA SC 009173.
NR 45
TC 1
Z9 4
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 APR 22
PY 2011
VL 286
IS 16
BP 13914
EP 13924
DI 10.1074/jbc.M110.180190
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 750NW
UT WOS:000289556200014
PM 21372131
ER
PT J
AU Duvernay, MT
Wang, H
Dong, CM
Guidry, JJ
Sackett, DL
Wu, GY
AF Duvernay, Matthew T.
Wang, Hong
Dong, Chunmin
Guidry, Jesse J.
Sackett, Dan L.
Wu, Guangyu
TI alpha(2B)-Adrenergic Receptor Interaction with Tubulin Controls Its
Transport from the Endoplasmic Reticulum to the Cell Surface
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; 3RD INTRACELLULAR LOOP; ANGIOTENSIN-II
RECEPTORS; TO-GOLGI TRANSPORT; C-TERMINAL TAIL; G-BETA-GAMMA;
ALPHA(2)-ADRENERGIC RECEPTORS; ANTEROGRADE TRANSPORT; MUSCARINIC
RECEPTORS; MEMBRANE TRAFFICKING
AB It is well recognized that the C terminus (CT) plays a crucial role in modulating G protein-coupled receptor (GPCR) transport from the endoplasmic reticulum (ER) to the cell surface. However the molecular mechanisms that govern CT-dependent ER export remain elusive. To address this issue, we used alpha(2B)-adrenergic receptor (alpha(2B)-AR) as a model GPCR to search for proteins interacting with the CT. By using peptide-conjugated affinity matrix combined with proteomics and glutathione S-transferase fusion protein pull-down assays, we identified tubulin directly interacting with the alpha(2B)-AR CT. The interaction domains weremappedto the acidic CT of tubulin and the basic Arg residues in the alpha(2B)-AR CT, particularly Arg-437, Arg-441, and Arg-446. More importantly, mutation of these Arg residues to disrupt tubulin interaction markedly inhibited alpha(2B)-AR transport to the cell surface and strongly arrested the receptor in the ER. These data provide the first evidence indicating that the alpha(2B)-AR C-terminal Arg cluster mediates its association with tubulin to coordinate its ER-to-cell surface traffic and suggest a novel mechanism of GPCR export through physical contact with microtubules.
C1 [Wu, Guangyu] Georgia Hlth Sci Univ, Dept Pharmacol & Toxicol, Augusta, GA 30912 USA.
[Duvernay, Matthew T.; Wang, Hong; Dong, Chunmin; Guidry, Jesse J.; Wu, Guangyu] Louisiana State Univ, Hlth Sci Ctr, Dept Pharmacol & Expt Therapeut, New Orleans, LA 70112 USA.
[Wang, Hong] Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China.
[Sackett, Dan L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Integrat & Med Biophys, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
RP Wu, GY (reprint author), Georgia Hlth Sci Univ, Dept Pharmacol & Toxicol, Augusta, GA 30912 USA.
EM guwu@georgiahealth.edu
FU National Institutes of Health [R01GM076167, P20RR018766]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants R01GM076167 (to G. W.) and P20RR018766 Principal
Investigator: Daniel R. Kapusta, and by Intramural Research Funds of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (to D. L. S.).
NR 62
TC 19
Z9 19
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 22
PY 2011
VL 286
IS 16
BP 14080
EP 14089
DI 10.1074/jbc.M111.222323
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 750NW
UT WOS:000289556200031
PM 21357695
ER
PT J
AU Kiris, E
Ventimiglia, D
Sargin, ME
Gaylord, MR
Altinok, A
Rose, K
Manjunath, BS
Jordan, MA
Wilson, L
Feinstein, SC
AF Kiris, Erkan
Ventimiglia, Donovan
Sargin, Mehmet E.
Gaylord, Michelle R.
Altinok, Alphan
Rose, Kenneth
Manjunath, B. S.
Jordan, Mary Ann
Wilson, Leslie
Feinstein, Stuart C.
TI Combinatorial Tau Pseudophosphorylation MARKEDLY DIFFERENT REGULATORY
EFFECTS ON MICROTUBULE ASSEMBLY AND DYNAMIC INSTABILITY THAN THE SUM OF
THE INDIVIDUAL PARTS
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PROLINE-DIRECTED PHOSPHORYLATION; PAIRED HELICAL FILAMENTS;
AXONAL-TRANSPORT DEFECTS; ALZHEIMERS-DISEASE; PROTEIN-TAU;
NEUROFIBRILLARY TANGLES; NEURODEGENERATIVE DISEASES; INDIVIDUAL
MICROTUBULES; STABILIZED MICROTUBULES; SYNTHASE KINASE-3-BETA
AB Tau is a multiply phosphorylated protein that is essential for the development and maintenance of the nervous system. Errors in Tau action are associated with Alzheimer disease and related dementias. A huge literature has led to the widely held notion that aberrant Tau hyperphosphorylation is central to these disorders. Unfortunately, our mechanistic understanding of the functional effects of combinatorial Tau phosphorylation remains minimal. Here, we generated four singly pseudophosphorylated Tau proteins (at Thr(231), Ser(262), Ser(396), and Ser(404)) and four doubly pseudophosphorylated Tau proteins using the same sites. Each Tau preparation was assayed for its abilities to promote microtubule assembly and to regulate microtubule dynamic instability in vitro. All four singly pseudophosphorylated Tau proteins exhibited loss-of-function effects. In marked contrast to the expectation that doubly pseudophosphorylated Tau would be less functional than either of its corresponding singly pseudophosphorylated forms, all of the doubly pseudophosphorylated Tau proteins possessed enhanced microtubule assembly activity and were more potent at regulating dynamic instability than their compromised singly pseudophosphorylated counterparts. Thus, the effects of multiple pseudophosphorylations were not simply the sum of the effects of the constituent single pseudophosphorylations; rather, they were generally opposite to the effects of singly pseudophosphorylated Tau. Further, despite being pseudophosphorylated at different sites, the four singly pseduophosphorylated Tau proteins often functioned similarly, as did the four doubly pseudophosphorylated proteins. These data lead us to reassess the conventional view of combinatorial phosphorylation in normal and pathological Tau action. They may also be relevant to the issue of combinatorial phosphorylation as a general regulatory mechanism.
C1 [Kiris, Erkan; Ventimiglia, Donovan; Gaylord, Michelle R.; Jordan, Mary Ann; Wilson, Leslie; Feinstein, Stuart C.] Univ Calif Santa Barbara, Neurosci Res Inst, Santa Barbara, CA 93106 USA.
[Kiris, Erkan; Ventimiglia, Donovan; Gaylord, Michelle R.; Jordan, Mary Ann; Wilson, Leslie; Feinstein, Stuart C.] Univ Calif Santa Barbara, Dept Mol & Cellular & Dev Biol, Santa Barbara, CA 93106 USA.
[Kiris, Erkan; Sargin, Mehmet E.; Altinok, Alphan; Rose, Kenneth; Manjunath, B. S.; Wilson, Leslie; Feinstein, Stuart C.] Univ Calif Santa Barbara, Ctr Bioimage Informat, Santa Barbara, CA 93106 USA.
[Sargin, Mehmet E.; Altinok, Alphan; Rose, Kenneth; Manjunath, B. S.] Univ Calif Santa Barbara, Dept Elect & Comp Engn, Santa Barbara, CA 93106 USA.
[Kiris, Erkan] TRUE Res Fdn, San Antonio, TX 78217 USA.
[Kiris, Erkan] NCI, NIH, Ft Detrick, MD 21702 USA.
[Ventimiglia, Donovan] Rockefeller Univ, New York, NY 10065 USA.
[Altinok, Alphan] CALTECH, Pasadena, CA 91125 USA.
[Gaylord, Michelle R.] Univ Calif San Diego, La Jolla, CA 92093 USA.
RP Feinstein, SC (reprint author), Univ Calif Santa Barbara, Neurosci Res Inst, Bldg 571,Rm 6129, Santa Barbara, CA 93106 USA.
EM feinstei@lifesci.ucsb.edu
FU National Institutes of Health [NS-35010, NS-13560, CA-57291]; National
Science Foundation [ITR-0331697]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants NS-35010 (to S. C. F.), NS-13560 (to L. W.), and CA-57291
(to M. A. J.). This work was also supported by National Science
Foundation Grant ITR-0331697 (to B. S. M., K. R., S. C. F., and L. W.).
NR 95
TC 15
Z9 15
U1 1
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 APR 22
PY 2011
VL 286
IS 16
BP 14257
EP 14270
DI 10.1074/jbc.M111.219311
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 750NW
UT WOS:000289556200049
PM 21288907
ER
PT J
AU Gerken, TA
Jamison, O
Perrine, CL
Collette, JC
Moinova, H
Ravi, L
Markowitz, SD
Shen, W
Patel, H
Tabak, LA
AF Gerken, Thomas A.
Jamison, Oliver
Perrine, Cynthia L.
Collette, Jeremy C.
Moinova, Helen
Ravi, Lakshmeswari
Markowitz, Sanford D.
Shen, Wei
Patel, Himatkumar
Tabak, Lawrence A.
TI Emerging Paradigms for the Initiation of Mucin-type Protein
O-Glycosylation by the Polypeptide GalNAc Transferase Family of
Glycosyltransferases
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PEPTIDE ACCEPTOR PREFERENCES; ALPHA-D-GALACTOSAMINE; N-TERMINAL
RESIDUES; UDP-GALNAC; LECTIN DOMAINS; SWISS-MODEL; P-SELECTIN;
ACETYLGALACTOSAMINYLTRANSFERASE FAMILY; DROSOPHILA DEVELOPMENT; LINKED
GLYCOSYLATION
AB Mammalian mucin-type O-glycosylation is initiated by a large family of similar to 20 UDP-GalNAc: polypeptide alpha-N-acetyl-galactosaminyltransferases (ppGalNAc Ts) that transfer alpha-GalNAc from UDP-GalNAc to Ser and Thr residues of polypeptide acceptors. Characterizing the peptide substrate specificity of each isoform is critical to understanding their properties, biological roles, and significance. Presently, only the specificities of ppGalNAc T1, T2, and T10 and the fly orthologues of T1 and T2 have been systematically characterized utilizing random peptide substrates. We now extend these studies to ppGalNAc T3, T5, and T12, transferases variously associated with human disease. Our results reveal several common features; the most striking is the similar pattern of enhancements for the three residues C-terminal to the site of glycosylation for those transferases that contain a common conserved Trp. In contrast, residues N-terminal to the site of glycosylation show a wide range of isoform-specific enhancements, with elevated preferences for Pro, Val, and Tyr being the most common at the -1 position. Further analysis reveals that the ratio of positive (Arg, Lys, and His) to negative (Asp and Glu) charged residue enhancements varied among transferases, thus further modulating substrate preference in an isoform-specific manner. By utilizing the obtained transferase-specific preferences, the glycosylation patterns of the ppGalNAc Ts against a series of peptide substrates could roughly be reproduced, demonstrating the potential for predicting isoform-specific glycosylation. We conclude that each ppGalNAc T isoform may be uniquely sensitive to pep-tide sequence and overall charge, which together dictates the substrate sites that will be glycosylated.
C1 [Gerken, Thomas A.; Jamison, Oliver; Collette, Jeremy C.] Case Western Reserve Univ, WA Bernbaum Ctr Cyst Fibrosis Res, Dept Pediat, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA.
[Gerken, Thomas A.] Case Western Reserve Univ, Dept Biochem, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA.
[Gerken, Thomas A.; Perrine, Cynthia L.] Case Western Reserve Univ, Dept Chem, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA.
[Moinova, Helen; Ravi, Lakshmeswari; Markowitz, Sanford D.] Case Western Reserve Univ, Dept Med, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA.
[Shen, Wei; Patel, Himatkumar; Tabak, Lawrence A.] NIDDK, Sect Biol Chem, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Gerken, TA (reprint author), Case Western Reserve Univ, Sch Med, Dept Pediat, BRB 823,2109 Adelbert Rd, Cleveland, OH 44104 USA.
EM txg2@cwru.edu
RI shen, wei/F-7816-2012
FU National Institutes of Health from the NCI [CA78834, P30-CA43703,
CA130901]; NIDDK
FX This work was supported, in whole or in part, by National Institutes of
Health Grants CA78834 (to T. A. G.), P30-CA43703, and CA130901 (to S. D.
M.) from the NCI and NIDDK intramural program grant (to L. A. T.).
NR 76
TC 57
Z9 57
U1 0
U2 10
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD APR 22
PY 2011
VL 286
IS 16
BP 14493
EP 14507
DI 10.1074/jbc.M111.218701
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 750NW
UT WOS:000289556200070
PM 21349845
ER
PT J
AU Stewart, CA
Trinchieri, G
AF Stewart, C. Andrew
Trinchieri, Giorgio
TI At 17, In-10's Passion Need Not Inflame
SO IMMUNITY
LA English
DT Editorial Material
ID REGULATORY T-CELLS; INTERLEUKIN-10; SOCS3
AB In this issue of Immunity, Chaudhry et al. (2011) and Huber et al. (2011) report that control of Th17 cell responses during colonic inflammation requires direct signaling by IL-10 in regulatory T cells and Th17 cells.
C1 [Stewart, C. Andrew; Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Ctr Canc Res, NCI Frederick, Frederick, MD 21702 USA.
RP Trinchieri, G (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, NCI Frederick, Frederick, MD 21702 USA.
EM trinchig@mail.nih.gov
RI Stewart, Charles/G-2470-2012
NR 11
TC 2
Z9 2
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD APR 22
PY 2011
VL 34
IS 4
BP 460
EP 462
DI 10.1016/j.immuni.2011.04.004
PG 3
WC Immunology
SC Immunology
GA 761AQ
UT WOS:000290367300005
PM 21511180
ER
PT J
AU Wheeler, DC
Szymanski, KM
Black, A
Nelson, DE
AF Wheeler, David C.
Szymanski, Konrad M.
Black, Amanda
Nelson, David E.
TI Applying strategies from libertarian paternalism to decision making for
prostate specific antigen (PSA) screening
SO BMC CANCER
LA English
DT Editorial Material
ID MEDICAL-DECISIONS; INFORMED-CONSENT; CANCER; MEN; TRIAL; PHYSICIANS;
MORTALITY; DEFAULTS; CHOICE; IMPACT
AB Background: Despite the recent publication of results from two randomized clinical trials, prostate specific antigen (PSA) screening for prostate cancer remains a controversial issue. There is lack of agreement across studies that PSA screening significantly reduces prostate cancer mortality. In spite of these facts, the widespread use of PSA testing in the United States leads to overdetection and overtreatment of clinically indolent prostate cancer, and its associated harms of incontinence and impotence.
Discussion: Given the inconclusive results from clinical trials and incongruent PSA screening guidelines, the decision to screen for prostate cancer with PSA testing is an uncertain one for patients and health care providers. Screening guidelines from some health organizations recommend an informed decision making (IDM) or shared decision making (SDM) approach for deciding on PSA screening. These approaches aim to empower patients to choose among the available options by making them active participants in the decision making process. By increasing involvement of patients in the clinical decision-making process, IDM/SDM places more of the responsibility for a complex decision on the patient. Research suggests, however, that patients are not well-informed of the harms and benefits associated with prostate cancer screening and are also subject to an assortment of biases, emotion, fears, and irrational thought that interferes with making an informed decision. In response, the IDM/SDM approaches can be augmented with strategies from the philosophy of libertarian paternalism (LP) to improve decision making. LP uses the insights of behavioural economics to help people better make better choices. Some of the main strategies of LP applicable to PSA decision making are a default decision rule, framing of decision aids, and timing of the decision. In this paper, we propose that applying strategies from libertarian paternalism can help with PSA screening decision-making.
Summary: Our proposal to augment IDM and SDM approaches with libertarian paternalism strategies is intended to guide patients toward a better decision about testing while maintaining personal freedom of choice. While PSA screening remains controversial and evidence conflicting, a libertarian-paternalism influenced approach to decision making can help prevent the overdiagnosis and overtreatment of prostate cancer.
C1 [Wheeler, David C.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Szymanski, Konrad M.] McGill Univ, Ctr Hlth, Div Urol, Montreal, PQ, Canada.
[Black, Amanda] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Nelson, David E.] NCI, Canc Prevent Fellowship Program Branch, Ctr Canc Training, Bethesda, MD 20892 USA.
RP Wheeler, DC (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM dcwheels@gmail.com
NR 51
TC 8
Z9 8
U1 1
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD APR 21
PY 2011
VL 11
AR 148
DI 10.1186/1471-2407-11-148
PG 7
WC Oncology
SC Oncology
GA 772TY
UT WOS:000291260800001
PM 21510865
ER
PT J
AU Weinberg, MA
Jeang, KT
AF Weinberg, Mark A.
Jeang, Kuan-Teh
TI XMRV as a Human Pathogen?
SO CELL HOST & MICROBE
LA English
DT Editorial Material
ID CHRONIC-FATIGUE-SYNDROME; VIRUS-RELATED VIRUS; PROSTATE-CANCER;
UNITED-STATES; CONTAMINATION; RETROVIRUS; SEQUENCES; BLOOD
AB Xenotropic murine leukemia virus-related virus (XMRV) has been proposed to be associated with prostate cancer and chronic fatigue syndrome (CFS). This proposition has been controversial because many investigators have failed to replicate the reported associations. Here, we explore whether XMRV is an authentic human pathogen in the light of recent findings that indicate otherwise.
C1 [Jeang, Kuan-Teh] NIAID, Mol Virol Sect, LMM, NIH, Bethesda, MD 20892 USA.
[Weinberg, Mark A.] McGill Univ, Jewish Gen Hosp, AIDS Ctr, Montreal, PQ H3T 1E2, Canada.
RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, LMM, NIH, Bldg 4,Room 306, Bethesda, MD 20892 USA.
EM kjeang@nih.gov
RI Jeang, Kuan-Teh/A-2424-2008
NR 15
TC 0
Z9 0
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
EI 1934-6069
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD APR 21
PY 2011
VL 9
IS 4
BP 260
EP 262
DI 10.1016/j.chom.2011.04.001
PG 3
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 756HO
UT WOS:000290002500004
ER
PT J
AU Smagulova, F
Gregoretti, IV
Brick, K
Khil, P
Camerini-Otero, RD
Petukhova, GV
AF Smagulova, Fatima
Gregoretti, Ivan V.
Brick, Kevin
Khil, Pavel
Camerini-Otero, R. Daniel
Petukhova, Galina V.
TI Genome-wide analysis reveals novel molecular features of mouse
recombination hotspots
SO NATURE
LA English
DT Article
ID MEIOTIC RECOMBINATION; HOT-SPOTS; HAPLOTYPE MAP; PRDM9; GENE; EVOLUTION;
HUMANS; INSTABILITY; INITIATION
AB Meiotic recombination predominantly occurs at discrete genomic loci called recombination hotspots, but the features defining these areas are still largely unknown (reviewed in refs 1-5). To allow a comprehensive analysis of hotspot-associated DNA and chromatin characteristics, we developed a direct molecular approach for mapping meiotic DNA double-strand breaks that initiate recombination. Here we present the genome-wide distribution of recombination initiation sites in the mouse genome. Hotspot centres are mapped with approximately 200-nucleotide precision, which allows analysis of the fine structural details of the preferred recombination sites. We determine that hotspots share a centrally distributed consensus motif, possess a nucleotide skew that changes polarity at the centres of hotspots and have an intrinsic preference to be occupied by a nucleosome. Furthermore, we find that the vast majority of recombination initiation sites in mouse males are associated with testis-specific trimethylation of lysine 4 on histone H3 that is distinct from histone H3 lysine 4 trimethylation marks associated with transcription. The recombination map presented here has been derived from a homogeneous mouse population with a defined genetic background and therefore lends itself to extensive future experimental exploration. We note that the mapping technique developed here does not depend on the availability of genetic markers and hence can be easily adapted to other species with complex genomes. Our findings uncover several fundamental features of mammalian recombination hotspots and underline the power of the new recombination map for future studies of genetic recombination, genome stability and evolution.
C1 [Smagulova, Fatima; Petukhova, Galina V.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Gregoretti, Ivan V.; Brick, Kevin; Khil, Pavel; Camerini-Otero, R. Daniel] NIDDKD, NIH, Bethesda, MD 20892 USA.
RP Petukhova, GV (reprint author), Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
EM rdcamerini@mail.nih.gov; gpetukhova@usuhs.mil
RI Smagulova, Fatima/K-5459-2015
OI Khil, Pavel/0000-0002-4903-8777; Brick, Kevin/0000-0002-9596-6400;
Smagulova, Fatima/0000-0001-6883-1968
FU March of Dimes Foundation [5-FY07-667]; NIGMS, NIH [1R01GM084104-01A1];
USUHS [FS71HU, R071HU, CS71HU]; NIDDK (NIH)
FX We thank M. Lichten (NCI, NIH) and P. Hsieh (NIDDK, NIH) for comments
and discussion. We are grateful to S. Sharmeen for her help with
high-throughput sequencing. This work was supported in part by Basil
O'Connor Starter Scholar Research Award Grant No. 5-FY07-667 from the
March of Dimes Foundation (G. V. P.); NIH grant 1R01GM084104-01A1 from
NIGMS (G. V. P.); New Investigator Start-up Grants FS71HU, R071HU and
CS71HU from USUHS (G. V. P.); and the NIDDK (NIH) Intramural Research
Program (R.D.C.-O.).
NR 30
TC 131
Z9 132
U1 1
U2 38
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 APR 21
PY 2011
VL 472
IS 7343
BP 375
EP 378
DI 10.1038/nature09869
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 752VW
UT WOS:000289724600045
PM 21460839
ER
PT J
AU Seibold, MA
Wise, AL
Speer, MC
Steele, MP
Brown, KK
Loyd, JE
Fingerlin, TE
Zhang, WM
Gudmundsson, G
Groshong, SD
Evans, CM
Garantziotis, S
Adler, KB
Dickey, BF
du Bois, RM
Yang, IV
Herron, A
Kervitsky, D
Talbert, JL
Markin, C
Park, J
Crews, AL
Slifer, SH
Auerbach, S
Roy, MG
Lin, J
Hennessy, CE
Schwarz, MI
Schwartz, DA
AF Seibold, Max A.
Wise, Anastasia L.
Speer, Marcy C.
Steele, Mark P.
Brown, Kevin K.
Loyd, James E.
Fingerlin, Tasha E.
Zhang, Weiming
Gudmundsson, Gunnar
Groshong, Steve D.
Evans, Christopher M.
Garantziotis, Stavros
Adler, Kenneth B.
Dickey, Burton F.
du Bois, Roland M.
Yang, Ivana V.
Herron, Aretha
Kervitsky, Dolly
Talbert, Janet L.
Markin, Cheryl
Park, Joungjoa
Crews, Anne L.
Slifer, Susan H.
Auerbach, Scott
Roy, Michelle G.
Lin, Jia
Hennessy, Corinne E.
Schwarz, Marvin I.
Schwartz, David A.
TI A Common MUC5B Promoter Polymorphism and Pulmonary Fibrosis
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID AIRWAY EPITHELIAL-CELLS; MUCIN GENE-EXPRESSION; ASSOCIATION; LINKAGE;
DISEASE; SCORES; SIGNAL; TESTS; MAPS; SNPS
AB BACKGROUND
The mutations that have been implicated in pulmonary fibrosis account for only a small proportion of the population risk.
METHODS
Using a genomewide linkage scan, we detected linkage between idiopathic interstitial pneumonia and a 3.4-Mb region of chromosome 11p15 in 82 families. We then evaluated genetic variation in this region in gel-forming mucin genes expressed in the lung among 83 subjects with familial interstitial pneumonia, 492 subjects with idiopathic pulmonary fibrosis, and 322 controls. MUC5B expression was assessed in lung tissue.
RESULTS
Linkage and fine mapping were used to identify a region of interest on the p-terminus of chromosome 11 that included gel-forming mucin genes. The minor-allele of the single-nucleotide polymorphism (SNP) rs35705950, located 3 kb upstream of the MUC5B transcription start site, was present at a frequency of 34% among subjects with familial interstitial pneumonia, 38% among subjects with idiopathic pulmonary fibrosis, and 9% among controls (allelic association with familial interstitial pneumonia, P = 1.2x10(-15); allelic association with idiopathic pulmonary fibrosis, P = 2.5x10(-37)). The odds ratios for disease among subjects who were heterozygous and those who were homozygous for the minor allele of this SNP were 6.8 (95% confidence interval [CI], 3.9 to 12.0) and 20.8 (95% CI, 3.8 to 113.7), respectively, for familial interstitial pneumonia and 9.0 (95% CI, 6.2 to 13.1) and 21.8 (95% CI, 5.1 to 93.5), respectively, for idiopathic pulmonary fibrosis. MUC5B expression in the lung was 14.1 times as high in subjects who had idiopathic pulmonary fibrosis as in those who did not (P<0.001). The variant allele of rs35705950 was associated with up-regulation in MUC5B expression in the lung in unaffected subjects (expression was 37.4 times as high as in unaffected subjects homozygous for the wild-type allele, P<0.001). MUC5B protein was expressed in lesions of idiopathic pulmonary fibrosis.
CONCLUSIONS
A common polymorphism in the promoter of MUC5B is associated with familial interstitial pneumonia and idiopathic pulmonary fibrosis. Our findings suggest that dysregulated MUC5B expression in the lung may be involved in the pathogenesis of pulmonary fibrosis.
C1 [Fingerlin, Tasha E.; Zhang, Weiming] Univ Colorado, Sch Publ Hlth, Denver, CO 80202 USA.
[Wise, Anastasia L.; Brown, Kevin K.; Groshong, Steve D.; Schwarz, Marvin I.; Schwartz, David A.] Univ Colorado, Sch Med, Denver, CO 80202 USA.
[Speer, Marcy C.; Steele, Mark P.; Herron, Aretha] Duke Univ, Med Ctr, Durham, NC USA.
[Garantziotis, Stavros; Auerbach, Scott] NIEHS, Res Triangle Pk, NC 27709 USA.
[Adler, Kenneth B.; Park, Joungjoa; Crews, Anne L.] N Carolina State Univ, Raleigh, NC 27695 USA.
[Loyd, James E.; Markin, Cheryl] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
[Gudmundsson, Gunnar] Landspitali Univ Hosp, Reykjavik, Iceland.
[Gudmundsson, Gunnar] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Evans, Christopher M.; Dickey, Burton F.; Roy, Michelle G.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Slifer, Susan H.] Univ Miami, Miami, FL USA.
RP Schwartz, DA (reprint author), Univ Colorado, Dept Med, 12631 E 17th Ave, Aurora, CO 80045 USA.
EM david.schwartz@udenver.edu
RI Gudmundsson, Gunnar/F-1974-2013; Garantziotis, Stavros/A-6903-2009
OI Gudmundsson, Gunnar/0000-0002-7251-8322; Garantziotis,
Stavros/0000-0003-4007-375X
FU National Heart, Lung, and Blood Institute [U01-HL067467, R01-HL095393,
R01-HL097163, P01-HL092870, RC2-HL101715, R37-HL36982]; National
Institute of Environmental Health Sciences [Z01 ES101947]; National
Cancer Institute [P30-CA016672]; American Lung Association [RG-22720-N];
Cystic Fibrosis Foundation [06IO]; Chapman Foundation; InterMune
FX Supported by grants from the National Heart, Lung, and Blood Institute
(U01-HL067467, R01-HL095393, R01-HL097163, P01-HL092870, RC2-HL101715,
and R37-HL36982), the National Institutes of Health Intramural Research
Program of the National Institute of Environmental Health Sciences (Z01
ES101947), the National Cancer Institute (P30-CA016672), the American
Lung Association (RG-22720-N), and the Cystic Fibrosis Foundation (06IO)
and by the Chapman Foundation and InterMune.
NR 32
TC 250
Z9 256
U1 2
U2 20
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD APR 21
PY 2011
VL 364
IS 16
BP 1503
EP 1512
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 752VH
UT WOS:000289722700007
PM 21506741
ER
PT J
AU Feldmann, H
AF Feldmann, Heinz
TI Truly Emerging - A New Disease Caused by a Novel Virus
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID SARS
C1 [Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
[Feldmann, Heinz] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada.
RP Feldmann, H (reprint author), NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
FU Intramural NIH HHS [Z99 AI999999]
NR 11
TC 17
Z9 19
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 APR 21
PY 2011
VL 364
IS 16
BP 1561
EP 1563
DI 10.1056/NEJMe1102671
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 752VH
UT WOS:000289722700017
PM 21410394
ER
PT J
AU Boehm, M
St Hilaire, C
Gahl, WA
AF Boehm, Manfred
St Hilaire, Cynthia
Gahl, William A.
TI NT5E Mutations and Arterial Calcifications REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID ENPP1
C1 [Boehm, Manfred; St Hilaire, Cynthia] NHLBI, Bethesda, MD 20892 USA.
[Gahl, William A.] NHGRI, Bethesda, MD 20892 USA.
RP Boehm, M (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA.
EM bgahl@helix.nih.gov
RI St. Hilaire, Cynthia/I-4713-2014
NR 4
TC 0
Z9 0
U1 0
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD APR 21
PY 2011
VL 364
IS 16
BP 1579
EP 1580
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 752VH
UT WOS:000289722700026
ER
PT J
AU Hough, M
Johnson, P
Rajon, D
Jokisch, D
Lee, C
Bolch, W
AF Hough, Matthew
Johnson, Perry
Rajon, Didier
Jokisch, Derek
Lee, Choonsik
Bolch, Wesley
TI An image-based skeletal dosimetry model for the ICRP reference adult
male-internal electron sources
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID TRABECULAR BONE; ABSORBED FRACTIONS; REFERENCE NEWBORN; TRANSPORT MODEL;
PHANTOMS; MARROW; PATIENT
AB In this study, a comprehensive electron dosimetry model of the adult male skeletal tissues is presented. The model is constructed using the University of Florida adult male hybrid phantom of Lee et al (2010 Phys. Med. Biol. 55 339-63) and the EGSnrc-based Paired Image Radiation Transport code of Shah et al (2005 J. Nucl. Med. 46 344-53). Target tissues include the active bone marrow, associated with radiogenic leukemia, and total shallow marrow, associated with radiogenic bone cancer. Monoenergetic electron emissions are considered over the energy range 1 keV to 10 MeV for the following sources: bone marrow (active and inactive), trabecular bone (surfaces and volumes), and cortical bone (surfaces and volumes). Specific absorbed fractions are computed according to the MIRD schema, and are given as skeletal-averaged values in the paper with site-specific values reported in both tabular and graphical format in an electronic annex available from stacks. iop.org/PMB/56/2309/mmedia. The distribution of cortical bone and spongiosa at the macroscopic dimensions of the phantom, as well as the distribution of trabecular bone and marrow tissues at the microscopic dimensions of the phantom, is imposed through detailed analyses of whole-body ex vivo CT images (1 mm resolution) and spongiosa-specific ex vivo microCT images (30 mu m resolution), respectively, taken from a 40 year male cadaver. The method utilized in this work includes: (1) explicit accounting for changes in marrow self-dose with variations in marrow cellularity, (2) explicit accounting for electron escape from spongiosa, (3) explicit consideration of spongiosa cross-fire from cortical bone, and (4) explicit consideration of the ICRP's change in the surrogate tissue region defining the location of the osteoprogenitor cells (from a 10 mu m endosteal layer covering the trabecular and cortical surfaces to a 50 mu m shallow marrow layer covering trabecular and medullary cavity surfaces). Skeletal-averaged values of absorbed fraction in the present model are noted to be very compatible with those weighted by the skeletal tissue distributions found in the ICRP Publication 110 adult male and female voxel phantoms, but are in many cases incompatible with values used in current and widely implemented internal dosimetry software.
C1 [Hough, Matthew; Johnson, Perry; Bolch, Wesley] Univ Florida, Dept Nucl & Radiol Engn, Gainesville, FL 32610 USA.
[Rajon, Didier] Univ Florida, Dept Neurosurg, Gainesville, FL USA.
[Bolch, Wesley] Univ Florida, Dept Biomed Engn, Gainesville, FL USA.
[Jokisch, Derek] Francis Marion Univ, Dept Phys & Astron, Florence, SC USA.
[Lee, Choonsik] NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA.
RP Bolch, W (reprint author), Univ Florida, Dept Nucl & Radiol Engn, Gainesville, FL 32610 USA.
EM wbolch@ufl.edu
RI Rajon, Didier/O-9412-2014; Lee, Choonsik/C-9023-2015
OI Lee, Choonsik/0000-0003-4289-9870
FU National Cancer Institute [R01 CA116743, R01 CA96441]; US Department of
Energy [DE-FG07-06ID14773]; DOE's Office of Nuclear Engineering,
Science, and Technology
FX This research was supported in part by grants R01 CA116743 and R01
CA96441 with the National Cancer Institute, and by grant
DE-FG07-06ID14773 with the US Department of Energy. The research of MH
(first author) was supported by the US Department of Energy Health
Physics Fellowship program, sponsored by DOE's Office of Nuclear
Engineering, Science, and Technology.
NR 41
TC 24
Z9 27
U1 0
U2 4
PU IOP PUBLISHING LTD
PI BRISTOL
PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD APR 21
PY 2011
VL 56
IS 8
BP 2309
EP 2346
DI 10.1088/0031-9155/56/8/001
PG 38
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 749PL
UT WOS:000289480700002
PM 21427487
ER
PT J
AU Johnson, PB
Bahadori, AA
Eckerman, KF
Lee, C
Bolch, WE
AF Johnson, Perry B.
Bahadori, Amir A.
Eckerman, Keith F.
Lee, Choonsik
Bolch, Wesley E.
TI Response functions for computing absorbed dose to skeletal tissues from
photon irradiation-an update
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID MU-CT IMAGES; BONE-MARROW; DOSIMETRY; PROTECTION; SPONGIOSA; EXPOSURE
AB A comprehensive set of photon fluence-to-dose response functions (DRFs) is presented for two radiosensitive skeletal tissues-active and total shallow marrow-within 15 and 32 bone sites, respectively, of the ICRP reference adult male. The functions were developed using fractional skeletal masses and associated electron-absorbed fractions as reported for the UF hybrid adult male phantom, which in turn is based upon micro-CT images of trabecular spongiosa taken from a 40 year male cadaver. The new DRFs expand upon both the original set of seven functions produced in 1985, and a 2007 update calculated under the assumption of secondary electron escape from spongiosa. In this study, it is assumed that photon irradiation of the skeleton will yield charged particle equilibrium across all spongiosa regions at energies exceeding 200 keV. Kerma coefficients for active marrow, inactive marrow, trabecular bone and spongiosa at higher energies are calculated using the DRF algorithm setting the electron-absorbed fraction for self-irradiation to unity. By comparing kerma coefficients and DRF functions, dose enhancement factors and mass energy-absorption coefficient (MEAC) ratios for active marrow to spongiosa were derived. These MEAC ratios compared well with those provided by the NIST Physical Reference Data Library (mean difference of 0.8%), and the dose enhancement factors for active marrow compared favorably with values calculated in the well-known study published by King and Spiers (1985 Br. J. Radiol. 58 345-56) (mean absolute difference of 1.9 percentage points). Additionally, dose enhancement factors for active marrow were shown to correlate well with the shallow marrow volume fraction (R(2) = 0.91). Dose enhancement factors for the total shallow marrow were also calculated for 32 bone sites representing the first such derivation for this target tissue.
C1 [Johnson, Perry B.; Bahadori, Amir A.; Bolch, Wesley E.] Univ Florida, Gainesville, FL 32611 USA.
[Eckerman, Keith F.] Oak Ridge Natl Lab, Div Life Sci, Oak Ridge, TN 37831 USA.
[Lee, Choonsik] NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA.
RP Bolch, WE (reprint author), Univ Florida, Gainesville, FL 32611 USA.
EM wbolch@ufl.edu
RI Lee, Choonsik/C-9023-2015
OI Lee, Choonsik/0000-0003-4289-9870
FU National Cancer Institute [R01 CA116743, R01 CA96441]; US Department of
Energy [DE-FG07-06ID14773]
FX This research was supported in part by grants R01 CA116743 and R01
CA96441 with the National Cancer Institute, and by grant
DE-FG07-06ID14773 with the US Department of Energy.
NR 18
TC 30
Z9 33
U1 0
U2 2
PU IOP PUBLISHING LTD
PI BRISTOL
PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD APR 21
PY 2011
VL 56
IS 8
BP 2347
EP 2365
DI 10.1088/0031-9155/56/8/002
PG 19
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 749PL
UT WOS:000289480700003
PM 21427484
ER
PT J
AU Endres, CJ
Hammoud, DA
Pomper, MG
AF Endres, Christopher J.
Hammoud, Dima A.
Pomper, Martin G.
TI Reference tissue modeling with parameter coupling: application to a
study of SERT binding in HIV
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; SEROTONIN TRANSPORTER; SPATIAL CONSTRAINT;
GRAPHICAL ANALYSIS; DYNAMIC PET; HUMAN BRAIN; RECEPTOR; QUANTIFICATION;
NEURORECEPTOR; C-11-DASB
AB When applicable, it is generally preferred to evaluate positron emission tomography (PET) studies using a reference tissue-based approach as that avoids the need for invasive arterial blood sampling. However, most reference tissue methods have been shown to have a bias that is dependent on the level of tracer binding, and the variability of parameter estimates may be substantially affected by noise level. In a study of serotonin transporter (SERT) binding in HIV dementia, it was determined that applying parameter coupling to the simplified reference tissue model (SRTM) reduced the variability of parameter estimates and yielded the strongest between-group significant differences in SERT binding. The use of parameter coupling makes the application of SRTM more consistent with conventional blood input models and reduces the total number of fitted parameters, thus should yield more robust parameter estimates. Here, we provide a detailed evaluation of the application of parameter constraint and parameter coupling to [(11)C] DASB PET studies. Five quantitative methods, including three methods that constrain the reference tissue clearance (k(2)(r)) to a common value across regions were applied to the clinical and simulated data to compare measurement of the tracer binding potential (BP(ND)). Compared with standard SRTM, either coupling of k(2)(r) across regions or constraining k(2)(r) to a first-pass estimate improved the sensitivity of SRTM to measuring a significant difference in BP(ND) between patients and controls. Parameter coupling was particularly effective in reducing the variance of parameter estimates, which was less than 50% of the variance obtained with standard SRTM. A linear approach was also improved when constraining k(2)(r) to a first-pass estimate, although the SRTM-based methods yielded stronger significant differences when applied to the clinical study. This work shows that parameter coupling reduces the variance of parameter estimates and may better discriminate between-group differences in specific binding.
C1 [Endres, Christopher J.; Pomper, Martin G.] Johns Hopkins Med Inst, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21231 USA.
[Hammoud, Dima A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Pomper, Martin G.] Johns Hopkins Med Inst, Dept Psychiat, Baltimore, MD 21231 USA.
RP Endres, CJ (reprint author), Johns Hopkins Med Inst, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21231 USA.
EM endres@jhmi.edu
RI Hammoud, Dima/C-2286-2015
FU NIH [R21 MH076591]
FX The authors would like to express their appreciation to Rena Geckle for
coordinating the study, as well as the radiochemistry staff and PET
technologists at the Johns Hopkins University PET center. They
gratefully acknowledge Drs Yun Zhou and Gwenn Smith for helpful
discussions. They also acknowledge NIH R21 MH076591.
NR 20
TC 1
Z9 1
U1 0
U2 1
PU IOP PUBLISHING LTD
PI BRISTOL
PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD APR 21
PY 2011
VL 56
IS 8
BP 2499
EP 2513
DI 10.1088/0031-9155/56/8/011
PG 15
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 749PL
UT WOS:000289480700012
PM 21441649
ER
PT J
AU Hong, SK
Dawid, IB
AF Hong, Sung-Kook
Dawid, Igor B.
TI The Transcriptional Mediator Component Med12 Is Required for Hindbrain
Boundary Formation
SO PLOS ONE
LA English
DT Article
ID ZEBRAFISH HINDBRAIN; GENE-EXPRESSION; NEURAL CREST; RHOMBOMERE
BOUNDARIES; RETINOIC ACID; COMPLEX; SEGMENTATION; VERTEBRATE; MOUSE;
NOTCH
AB Background: Rhombomere boundaries form during hindbrain segmentation and are critical for maintaining segmental integrity and regulating migration in the hindbrain. Some genetic models affecting hindbrain boundary formation have been described, but involvement of components of the transcriptional mediator complex in boundary formation has not reported so far.
Principal Findings: The kto/med12 mutant zebrafish, which affects the Mediator component Med12, causes specific loss of rhombomere boundary cells even though segmentation of the hindbrain takes place at least in part. In kto mutant embryos, cells forming rhombomere boundaries were largely absent as indicated by the use of several marker genes. While no obvious increase in cell death was observed, we found a notable reduction of cell proliferation in the hindbrain of kto mutant zebrafish.
Conclusions: The kto/med12 mutation results in specific defects of boundary cell formation in the zebrafish hindbrain.
C1 [Hong, Sung-Kook; Dawid, Igor B.] Eunice Kennedy Shriver Natl Inst Child & Human De, Mol Genet Lab, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[Hong, Sung-Kook] NHGRI, Mol Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Hong, SK (reprint author), Eunice Kennedy Shriver Natl Inst Child & Human De, Mol Genet Lab, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
EM idawid@nih.gov
FU Division of Intramural Research of the National Institute of Child
Health and Human Development
FX The study was funded in its entirety by the Division of Intramural
Research of the National Institute of Child Health and Human
Development. The funder had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 46
TC 6
Z9 6
U1 0
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 APR 21
PY 2011
VL 6
IS 4
AR e19076
DI 10.1371/journal.pone.0019076
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 756ME
UT WOS:000290014500022
PM 21533047
ER
PT J
AU Corey, L
Nabel, GJ
Dieffenbach, C
Gilbert, P
Haynes, BF
Johnston, M
Kublin, J
Lane, HC
Pantaleo, G
Picker, LJ
Fauci, AS
AF Corey, Lawrence
Nabel, Gary J.
Dieffenbach, Carl
Gilbert, Peter
Haynes, Barton F.
Johnston, Margaret
Kublin, James
Lane, H. Clifford
Pantaleo, Giuseppe
Picker, Louis J.
Fauci, Anthony S.
TI HIV-1 Vaccines and Adaptive Trial Designs
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID RECOMBINANT GLYCOPROTEIN-120 VACCINE; DOUBLE-BLIND; INFECTION; EFFICACY;
THAILAND; STEP
AB Developing a vaccine against the human immunodeciency virus (HIV) poses an exceptional challenge. There are no documented cases of immune-mediated clearance of HIV from an infected individual, and no known correlates of immune protection. Although nonhuman primate models of lentivirus infection have provided valuable data about HIV pathogenesis, such models do not predict HIV vaccine efficacy in humans. The combined lack of a predictive animal model and undefined biomarkers of immune protection against HIV necessitate that vaccines to this pathogen be tested directly in clinical trials. Adaptive clinical trial designs can accelerate vaccine development by rapidly screening out poor vaccines while extending the evaluation of efficacious ones, improving the characterization of promising vaccine candidates and the identification of correlates of immune protection.
C1 [Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Corey, Lawrence; Gilbert, Peter; Kublin, James] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA.
[Corey, Lawrence] Univ Washington, Dept Med, Seattle, WA 98109 USA.
[Dieffenbach, Carl; Johnston, Margaret] NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA.
[Haynes, Barton F.] Duke Univ, Sch Med, Dept Med, Duke Human Vaccine Inst, Durham, NC 27710 USA.
[Lane, H. Clifford] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA.
[Pantaleo, Giuseppe] Univ Lausanne, CHU Vaudois, Div Immunol & Allergy, CH-1015 Lausanne, Switzerland.
[Pantaleo, Giuseppe] Swiss Vaccine Res Inst, CH-1011 Lausanne, Switzerland.
[Picker, Louis J.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Portland, OR 97205 USA.
RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
EM gnabel@nih.gov
RI Pantaleo, Giuseppe/K-6163-2016
FU NIAID NIH HHS [R37 AI054165]
NR 17
TC 17
Z9 18
U1 1
U2 6
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD APR 20
PY 2011
VL 3
IS 79
AR 79ps13
DI 10.1126/scitranslmed.3001863
PG 5
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 795LW
UT WOS:000292976700002
PM 21508308
ER
PT J
AU Kho, AN
Pacheco, JA
Peissig, PL
Rasmussen, L
Newton, KM
Weston, N
Crane, PK
Pathak, J
Chute, CG
Bielinski, SJ
Kullo, IJ
Li, RL
Manolio, TA
Chisholm, RL
Denny, JC
AF Kho, Abel N.
Pacheco, Jennifer A.
Peissig, Peggy L.
Rasmussen, Luke
Newton, Katherine M.
Weston, Noah
Crane, Paul K.
Pathak, Jyotishman
Chute, Christopher G.
Bielinski, Suzette J.
Kullo, Iftikhar J.
Li, Rongling
Manolio, Teri A.
Chisholm, Rex L.
Denny, Joshua C.
TI Electronic Medical Records for Genetic Research: Results of the eMERGE
Consortium
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID HEALTH INFORMATION-TECHNOLOGY; GENOME-WIDE ASSOCIATION; PERSONALIZED
MEDICINE; HISTORY INFORMATION; PHYSICIAN PRACTICES; DISCOVERY RESEARCH;
AMBULATORY-CARE; QUALITY; DEMENTIA; DISEASE
AB Clinical data in electronic medical records (EMRs) are a potential source of longitudinal clinical data for research. The Electronic Medical Records and Genomics Network (eMERGE) investigates whether data captured through routine clinical care using EMRs can identify disease phenotypes with sufficient positive and negative predictive values for use in genome-wide association studies (GWAS). Using data from five different sets of EMRs, we have identified five disease phenotypes with positive predictive values of 73 to 98% and negative predictive values of 98 to 100%. Most EMRs captured key information (diagnoses, medications, laboratory tests) used to define phenotypes in a structured format. We identified natural language processing as an important tool to improve case identification rates. Efforts and incentives to increase the implementation of interoperable EMRs will markedly improve the availability of clinical data for genomics research.
C1 [Kho, Abel N.; Pacheco, Jennifer A.; Chisholm, Rex L.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Kho, Abel N.] Regenstrief Inst Inc, Indianapolis, IN 46202 USA.
[Peissig, Peggy L.; Rasmussen, Luke] Marshfield Clin Res Fdn, Marshfield, WI 54449 USA.
[Newton, Katherine M.; Weston, Noah] Grp Hlth Res Inst, Seattle, WA 98101 USA.
[Newton, Katherine M.] Univ Washington, Sch Publ Hlth, Seattle, WA 98104 USA.
[Crane, Paul K.] Univ Washington, Sch Med, Seattle, WA 98104 USA.
[Pathak, Jyotishman; Chute, Christopher G.; Bielinski, Suzette J.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA.
[Kullo, Iftikhar J.] Mayo Clin, Dept Internal Med, Rochester, MN 55905 USA.
[Li, Rongling; Manolio, Teri A.] NHGRI, Off Populat Genom, Bethesda, MD 20892 USA.
[Denny, Joshua C.] Vanderbilt Univ, Dept Biomed Informat & Med, Nashville, TN 37232 USA.
RP Kho, AN (reprint author), Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
EM a-kho@northwestern.edu
RI Crane, Paul/C-8623-2014; Bielinski, Suzette/A-2238-2009;
OI Bielinski, Suzette/0000-0002-2905-5430; Pacheco,
Jennifer/0000-0001-8021-5818; Rasmussen, Luke/0000-0002-4497-8049;
Crane, Paul/0000-0003-4278-7465
FU National Human Genome Research Institute; National Institute of General
Medical Sciences [U01-HG-004610, U01-HG-004608, U01-HG-04599,
U01HG004609, U01-HG-04603]; State of Washington Life Sciences Discovery;
National Center for Research Resources, NIH [1 UL1 RR024975,
UL1RR025741]
FX The eMERGE Network was initiated and funded by the National Human Genome
Research Institute, with additional funding from the National Institute
of General Medical Sciences through grants U01-HG-004610 (Group Health
Cooperative), U01-HG-004608 (Marshfield Clinic), U01-HG-04599 (Mayo
Clinic), U01HG004609 (Northwestern University), and U01-HG-04603
(Vanderbilt University, also serving as the Coordinating Center), and
the State of Washington Life Sciences Discovery Fund award to the
Northwest Institute of Medical Genetics. The Vanderbilt BioVU and the
Synthetic Derivative were supported in part by Clinical and
Translational Research Award grant 1 UL1 RR024975 from the National
Center for Research Resources, NIH. Funding for the Northwestern
Enterprise Data Warehouse (EDW) was supported in part by Clinical and
Translational Research grant UL1RR025741 from the National Center for
Research Resources, NIH.
NR 48
TC 69
Z9 70
U1 4
U2 13
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD APR 20
PY 2011
VL 3
IS 79
AR 79re1
DI 10.1126/scitranslmed.3001807
PG 7
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 795LW
UT WOS:000292976700005
PM 21508311
ER
PT J
AU Siersbaek, R
Nielsen, R
John, S
Sung, MH
Baek, S
Loft, A
Hager, GL
Mandrup, S
AF Siersbaek, Rasmus
Nielsen, Ronni
John, Sam
Sung, Myong-Hee
Baek, Songjoon
Loft, Anne
Hager, Gordon L.
Mandrup, Susanne
TI Extensive chromatin remodelling and establishment of transcription
factor 'hotspots' during early adipogenesis
SO EMBO JOURNAL
LA English
DT Article
DE adipocyte differentiation; C/EBP beta; ChIP-seq; chromatin remodelling;
DNase I hypersensitivity
ID ACTIVATED-RECEPTOR-GAMMA; BINDING PROTEIN-BETA; ADIPOCYTE
DIFFERENTIATION; PPAR-GAMMA; C/EBP-BETA; HUMAN GENOME; ADIPOSE-TISSUE;
IN-VIVO; GLUCOCORTICOID-RECEPTOR; STIMULATES ADIPOGENESIS
AB Adipogenesis is tightly controlled by a complex network of transcription factors acting at different stages of differentiation. Peroxisome proliferator-activated receptor gamma (PPAR gamma) and CCAAT/enhancer-binding protein (C/EBP) family members are key regulators of this process. We have employed DNase I hypersensitive site analysis to investigate the genome-wide changes in chromatin structure that accompany the binding of adipogenic transcription factors. These analyses revealed a dramatic and dynamic modulation of the chromatin landscape during the first hours of adipocyte differentiation that coincides with cooperative binding of multiple early transcription factors (including glucocorticoid receptor, retinoid X receptor, Stat5a, C/EBP beta and -delta) to transcription factor 'hotspots'. Our results demonstrate that C/EBP beta marks a large number of these transcription factor 'hotspots' before induction of differentiation and chromatin remodelling and is required for their establishment. Furthermore, a subset of early remodelled C/EBP-binding sites persists throughout differentiation and is later occupied by PPAR gamma, indicating that early C/EBP family members, in addition to their well-established role in activation of PPAR gamma transcription, may act as pioneering factors for PPAR gamma binding. The EMBO Journal (2011) 30, 1459-1472. doi:10.1038/emboj.2011.65; Published online 22 March 2011 Subject Categories: chromatin & transcription
C1 [Siersbaek, Rasmus; Nielsen, Ronni; Loft, Anne; Mandrup, Susanne] Univ So Denmark, Dept Biochem & Mol Biol, DK-5230 Odense, Denmark.
[John, Sam; Sung, Myong-Hee; Baek, Songjoon; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Mandrup, S (reprint author), Univ So Denmark, Dept Biochem & Mol Biol, Campusvej 55, DK-5230 Odense, Denmark.
EM hagerg@dce41.nci.nih.gov; s.mandrup@bmb.sdu.dk
RI Loft, Anne/L-5796-2015;
OI Loft, Anne/0000-0002-5647-8295; Mandrup, Susanne/0000-0002-0961-5787
FU Danish Natural Science Research Council; Novo Nordisk Foundation; NIH,
National Cancer Institute, Center for Cancer Research
FX We thank members of the Mandrup and Hager laboratories for fruitful
discussions. This work was supported by grants from the Danish Natural
Science Research Council, the Novo Nordisk Foundation, and by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research.
NR 65
TC 146
Z9 146
U1 1
U2 17
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0261-4189
J9 EMBO J
JI Embo J.
PD APR 20
PY 2011
VL 30
IS 8
BP 1459
EP 1472
DI 10.1038/emboj.2011.65
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 760EG
UT WOS:000290306300008
PM 21427703
ER
PT J
AU Kim, YC
Kim, SY
Mellado-Gil, JM
Yadav, H
Neidermyer, W
Kamaraju, AK
Rane, SG
AF Kim, Yong-Chul
Kim, So Yoon
Mellado-Gil, Jose Manuel
Yadav, Hariom
Neidermyer, William
Kamaraju, Anil K.
Rane, Sushil G.
TI RB regulates pancreas development by stabilizing Pdx1
SO EMBO JOURNAL
LA English
DT Article
DE Cdk; pancreas; Pdx-1; RB; stability
ID RETINOBLASTOMA GENE-PRODUCT; TUMOR-SUPPRESSOR PROTEIN; BETA-CELL
FUNCTION; DIABETES-MELLITUS; BINDING PROTEIN; E2F; PRB; PHOSPHORYLATION;
MICE; DOMAIN
AB RB is a key substrate of Cdks and an important regulator of the mammalian cell cycle. RB either represses E2Fs that promote cell proliferation or enhances the activity of cell-specific factors that promote differentiation, although the mechanism that facilitates this dual interaction is unclear. Here, we demonstrate that RB associates with and stabilizes pancreatic duodenal homeobox-1 (Pdx-1) that is essential for embryonic pancreas development and adult beta-cell function. Interestingly, Pdx-1 utilizes a conserved RB-interaction motif (RIM) that is also present in E2Fs. Point mutations within the RIM reduce RB-Pdx-1 complex formation, destabilize Pdx-1 and promote its proteasomal degradation. Glucose regulates RB and Pdx1 levels, RB/Pdx-1 complex formation and Pdx-1 degradation. RB occupies the promoters of beta-cell-specific genes, and knockdown of RB results in reduced expression of Pdx-1 and its target genes. Further, RB-deficiency in vivo results in reduced pancreas size due to decreased proliferation of Pdx-1(+) pancreatic progenitors, increased apoptosis and aberrant expression of regulators of pancreatic development. These results demonstrate an unanticipated regulatory mechanism for pancreatic development and beta-cell function, which involves RB-mediated stabilization of the pancreas-specific transcription factor Pdx-1. The EMBO Journal (2011) 30, 1563-1576. doi:10.1038/emboj.2011.57; Published online 11 March 2011 Subject Categories: proteins; development
C1 [Kim, Yong-Chul; Kim, So Yoon; Mellado-Gil, Jose Manuel; Yadav, Hariom; Neidermyer, William; Kamaraju, Anil K.; Rane, Sushil G.] NIDDKD, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
RP Rane, SG (reprint author), NIDDKD, Diabet Endocrinol & Obes Branch, NIH, 10 CRC W 5-5940, Bethesda, MD 20892 USA.
EM ranes@mail.nih.gov
OI Yadav, Hariom/0000-0003-4504-1597
FU Colgate University-NIH; NIDDK, NIH
FX We thank Drs Yihong Ye, Kai Ge, Neha Rane and David Harlan for advice
and critical reading of the manuscript. We thank Drs Stephan Gaubatz,
Sabire Ozcan, William Kaelin, M Szyf, Tyler Jacks, Julien Sage and
Sibylle Mittnacht for generous gifts of reagents and technical advice.
William Neidermyer was supported in part by the Colgate University-NIH
internship program. This work was supported by NIDDK, NIH intramural
funds awarded to SGR.
NR 55
TC 18
Z9 19
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0261-4189
J9 EMBO J
JI Embo J.
PD APR 20
PY 2011
VL 30
IS 8
BP 1563
EP 1576
DI 10.1038/emboj.2011.57
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 760EG
UT WOS:000290306300016
PM 21399612
ER
PT J
AU Berezin, MY
Guo, K
Akers, W
Northdurft, RE
Culver, JP
Teng, B
Vasalatiy, O
Barbacow, K
Gandjbakhche, A
Griffiths, GL
Achilefu, S
AF Berezin, Mikhail Y.
Guo, Kevin
Akers, Walter
Northdurft, Ralph E.
Culver, Joseph P.
Teng, Bao
Vasalatiy, Olga
Barbacow, Kyle
Gandjbakhche, Amir
Griffiths, Gary L.
Achilefu, Samuel
TI Near-Infrared Fluorescence Lifetime pH-Sensitive Probes
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID STATE PROTON-TRANSFER; CYANINE DYES; ACIDIC ENVIRONMENTS; TURBID MEDIA;
IN-VIVO; SPECTROSCOPY; SYSTEMS; FLUOROPHORES; TOMOGRAPHY; INDICATORS
AB We report what we believe to be the first near-infrared pH-sensitive fluorescence lifetime molecular probe suitable for biological applications in physiological range. Specifically, we modified a known fluorophore skeleton, hexamethylindotricarbocyanine, with a tertiary amine functionality that was electronically coupled to the fluorophore, to generate a pH-sensitive probe. The pK(a) of the probe depended critically on the location of the amine. Peripheral substitution at the 5-position of the indole ring resulted in a compound with pK(a) similar to 4.9 as determined by emission spectroscopy. In contrast, substitution at the meso-position shifted the pK(a) to 5.5. The resulting compound, LS482, demonstrated steady-state and fluorescence-lifetime pH-sensitivity. This sensitivity stemmed from distinct lifetimes for protonated (similar to 1.16 ns in acidic DMSO) and deprotonated (similar to 1.4 ns in basic DMSO) components. The suitability of the fluorescent dyes for biological applications was demonstrated with a fluorescence-lifetime tomography system. The ability to interrogate cellular processes and subsequently translate the findings in living organisms further augments the potential of these lifetime-based pH probes.
C1 [Berezin, Mikhail Y.; Guo, Kevin; Akers, Walter; Northdurft, Ralph E.; Culver, Joseph P.; Achilefu, Samuel] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA.
[Achilefu, Samuel] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA.
[Teng, Bao; Vasalatiy, Olga; Barbacow, Kyle; Griffiths, Gary L.] NHLBI, Imaging Probe Dev Ctr, Washington, DC USA.
[Gandjbakhche, Amir] Eunice Shriver Natl Inst Child Hlth & Human Dev, Phys Biol Program, NIH, Washington, DC USA.
RP Achilefu, S (reprint author), Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA.
EM achilefus@mir.wustl.edu
RI Achilefu, Samuel/A-3681-2012; Berezin, Mikhail/B-4102-2009;
OI Akers, Walter/0000-0002-9697-7654; Achilefu, Samuel/0000-0002-3133-6717
FU National Institute of Biomedical Imaging and Bioengineering
[RO1EB007276]; National Institutes of Health [R01 EB008111, R01
EB001430, R01 EB008458, R01 CA 109754, R33 CA 123537, R21 CA 149814];
NIH Roadmap for Medical Research; Eunice Shriver NICHD
FX This work was supported primarily by the National Institute of
Biomedical Imaging and Bioengineering under grant No. RO1EB007276, and
in part by other funds by the National Institutes of Health under grants
No. R01 EB008111, No. R01 EB001430, No. R01 EB008458, No. R01 CA 109754,
No. R33 CA 123537, and No. R21 CA 149814 as well as the the NIH Roadmap
for Medical Research as funding source for the IPDC, and the Intramural
Research Program of Eunice Shriver NICHD.
NR 51
TC 23
Z9 23
U1 4
U2 44
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 APR 20
PY 2011
VL 100
IS 8
BP 2063
EP 2072
DI 10.1016/j.bpj.2011.02.050
PG 10
WC Biophysics
SC Biophysics
GA 754OG
UT WOS:000289864100026
PM 21504743
ER
PT J
AU Buck, CB
Lowy, DR
AF Buck, Christopher B.
Lowy, Douglas R.
TI Immune Readouts May Have Prognostic Value for the Course of Merkel Cell
Carcinoma, a Virally Associated Disease
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID POLYOMAVIRUS INFECTION; ANTIBODIES; EXPRESSION; CANCERS; TUMORS; MCV
C1 [Buck, Christopher B.; Lowy, Douglas R.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
RP Buck, CB (reprint author), NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
OI Buck, Christopher/0000-0003-3165-8094
NR 21
TC 1
Z9 1
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 APR 20
PY 2011
VL 29
IS 12
BP 1506
EP 1508
DI 10.1200/JCO.2010.34.0745
PG 3
WC Oncology
SC Oncology
GA 752SO
UT WOS:000289714600018
PM 21422431
ER
PT J
AU Nichols, HB
de Gonzalez, AB
Lacey, JV
Rosenberg, PS
Anderson, WF
AF Nichols, Hazel B.
de Gonzalez, Amy Berrington
Lacey, James V., Jr.
Rosenberg, Philip S.
Anderson, William F.
TI Declining Incidence of Contralateral Breast Cancer in the United States
From 1975 to 2006
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID EXTENDED ADJUVANT THERAPY; RISK-FACTORS; SURVIVORS; PROGNOSIS; TRENDS;
CHEMOTHERAPY; RELATIVES; TRIAL; WOMEN; CARE
AB Purpose
Contralateral breast cancer (CBC) is the most frequent new malignancy among women diagnosed with a first breast cancer. Although temporal trends for first breast cancers have been well studied, trends for CBC are not so well established.
Patients and Methods
We examined temporal trends in CBC incidence using US Surveillance, Epidemiology, and End Results database (1975 to 2006). Data were stratified by estrogen receptor (ER) status of the first breast cancer for the available time period (1990+). We estimated the annual percent change (EAPC) in CBC rates using Poisson regression models adjusted for the age at and time since first breast cancer diagnosis.
Results
Before 1985, CBC incidence rates were stable (EAPC, 0.27% per year; 95% CI, -0.4 to 0.9), after which they declined with an EAPC of -3.07% per year (95% CI, -3.5 to -2.7). From 1990 forward, the declines were restricted to CBC after an ER-positive cancer (EAPC, -3.18%; 95% CI, -4.2 to -2.2) with no clear decreases after an ER-negative cancer. Estimated current age-specific CBC rates (per 100/year) after an ER-positive first cancer were: 0.45 for first cancers diagnosed before age 30 years and 0.25 to 0.37 for age 30 years or older. Rates after an ER-negative cancer were higher: 1.26 before age 30 years, 0.85 for age 30 to 35 years, and 0.45 to 0.65 for age 40 or older.
Conclusion
Results show a favorable decrease of 3% per year for CBC incidence in the United States since 1985. This overall trend was driven by declining CBC rates after an ER-positive cancer, possibly because of the widespread usage of adjuvant hormone therapies, after the results of the Nolvadex Adjuvant Trial Organisation were published in 1983, and/or other adjuvant treatments. J Clin Oncol 29:1564-1569. (C) 2011 by American Society of Clinical Oncology
C1 Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
NCI, NIH, US Dept HHS, Bethesda, MD 20892 USA.
City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA.
RP de Gonzalez, AB (reprint author), 6120 Execut Blvd, Bethesda, MD 20892 USA.
EM berringtona@mail.nih.gov
FU National Institutes of Health, National Cancer Institute
FX Supported in part by the Intramural Research Program of the National
Institutes of Health, National Cancer Institute.
NR 30
TC 90
Z9 92
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 APR 20
PY 2011
VL 29
IS 12
BP 1564
EP 1569
DI 10.1200/JCO.2010.32.7395
PG 6
WC Oncology
SC Oncology
GA 752SO
UT WOS:000289714600027
PM 21402610
ER
PT J
AU Kitahara, CM
de Gonzalez, AB
Freedman, ND
Huxley, R
Mok, Y
Jee, SH
Samet, JM
AF Kitahara, Cari M.
de Gonzalez, Amy Berrington
Freedman, Neal D.
Huxley, Rachel
Mok, Yejin
Jee, Sun Ha
Samet, Jonathan M.
TI Total Cholesterol and Cancer Risk in a Large Prospective Study in Korea
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID TOTAL SERUM-CHOLESTEROL; BREAST-CANCER; PROSTATE-CANCER;
BETA-LIPOPROTEIN; NORWEGIAN WOMEN; STATIN USE; ASSOCIATION; COHORT;
LIPIDS; MEN
AB Purpose
To further clarify the relationship between total cholesterol and cancer, which remains unclear.
Methods
We prospectively examined the association between total cholesterol and site-specific and all-cancer incidence among 1,189,719 Korean adults enrolled in the National Health Insurance Corporation who underwent a standardized biennial medical examination in 1992 to 1995 and were observed for 14 years until cancer diagnosis or death.
Results
Over follow-up, 53,944 men and 24,475 women were diagnosed with a primary cancer. Compared with levels less than 160 mg/dL, high total cholesterol (>= 240 mg/dL) was positively associated with prostate cancer (hazard ratio [HR], 1.24; 95% CI, 1.07 to 1.44; P trend = .001) and colon cancer (HR, 1.12; 95% CI, 1.00 to 1.25; P trend = .05) in men and breast cancer in women (HR, 1.17; 95% CI, 1.03 to 1.33; P trend = .03). Higher total cholesterol was associated with a lower incidence of liver cancer (men: HR, 0.42; 95% CI, 0.38 to 0.45; P trend < .001; women: HR, 0.32; 95% CI, 0.27 to 0.39; P trend < .001), stomach cancer (men: HR, 0.87; 95% CI, 0.82 to 0.93; P trend <= .001; women: HR, 0.86; 95% CI, 0.77 to 0.97; P trend = .06), and, in men, lung cancer (HR, 0.89; 95% CI, 0.82 to 0.96; P trend < .001). Results for liver cancer were slightly attenuated after additional adjustment for liver enzyme levels and hepatitis B surface antigen status (men: HR, 0.60; P trend < .001; women: HR, 0.46; P trend = .003) and exclusion of the first 10 years of follow-up (men: HR, 0.59; P trend < .001; women: HR, 0.44; P trend < .001). Total cholesterol was inversely associated with all-cancer incidence in both men (HR, 0.84; 95% CI, 0.81 to 0.86; P trend < .001) and women (HR, 0.91; 95% CI, 0.87 to 0.95; P trend < .001), but these associations were attenuated after excluding incident liver cancers (men: HR, 0.95; P trend < .001; women: HR, 0.98; P trend = .32).
Conclusion
In this large prospective study, we found that total cholesterol was associated with the risk of several different cancers, although these relationships differed markedly by cancer site. J Clin Oncol 29:1592-1598. (C) 2011 by American Society of Clinical Oncology
C1 [Jee, Sun Ha] Yonsei Univ, Dept Epidemiol & Hlth Promot, Grad Sch Publ Hlth, Inst Hlth Promot, Seoul 120749, South Korea.
NCI, NIH, Rockville, MD USA.
Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
Univ Sydney, George Inst Int Hlth, Sydney, NSW 2006, Australia.
RP Jee, SH (reprint author), Yonsei Univ, Dept Epidemiol & Hlth Promot, Grad Sch Publ Hlth, Inst Hlth Promot, 134 Shinchondong, Seoul 120749, South Korea.
EM jsunha@yuhs.ac
RI Huxley, Rachel/J-4638-2013; Freedman, Neal/B-9741-2015; Huxley,
Rachel/C-7032-2013; Kitahara, Cari/R-8267-2016
OI Huxley, Rachel/0000-0002-2705-6616; Freedman, Neal/0000-0003-0074-1098;
Huxley, Rachel/0000-0002-2705-6616;
FU Korean Seoul City Research [10526]; Ministry for Health, Welfare and
Family Affairs, Republic of Korea [0920330]; National Cancer Institute,
National Institutes of Health
FX Supported by Grant No. 10526 from Korean Seoul City Research and Grant
No. 0920330 from the National Research and Development Program for
Cancer Control, Ministry for Health, Welfare and Family Affairs,
Republic of Korea. This study was also supported in part by the
Intramural Research Program of the National Cancer Institute, National
Institutes of Health.
NR 39
TC 74
Z9 77
U1 1
U2 13
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 APR 20
PY 2011
VL 29
IS 12
BP 1592
EP 1598
DI 10.1200/JCO.2010.31.5200
PG 7
WC Oncology
SC Oncology
GA 752SO
UT WOS:000289714600031
PM 21422422
ER
PT J
AU Dencker, D
Wortwein, G
Weikop, P
Jeon, J
Thomsen, M
Sager, TN
Mork, A
Woldbye, DPD
Wess, J
Fink-Jensen, A
AF Dencker, Ditte
Wortwein, Gitta
Weikop, Pia
Jeon, Jongrye
Thomsen, Morgane
Sager, Thomas N.
Mork, Arne
Woldbye, David P. D.
Wess, Juergen
Fink-Jensen, Anders
TI Involvement of a Subpopulation of Neuronal M-4 Muscarinic Acetylcholine
Receptors in the Antipsychotic-like Effects of the M-1/M-4 Preferring
Muscarinic Receptor Agonist Xanomeline
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID KNOCKOUT MICE; RAT; SCHIZOPHRENIA; INHIBITION; MODULATION; BINDING
AB Disturbances in central dopaminergic neurotransmission are believed to be centrally involved in the pathogenesis of schizophrenia. Central dopaminergic and cholinergic systems interact and the cholinergic muscarinic agonist xanomeline has shown antipsychotic effects in clinical studies. Preclinical studies indicate that the M-4 muscarinic cholinergic receptor subtype (mAChR) modulates the activity of the dopaminergic system and that this specific mAChR subtype is involved in mediating the antipsychotic-like effects of xanomeline. A specific neuronal subpopulation that expresses M-4 mAChRs together with D-1 dopamine receptors seems to be especially important in modulating dopamine-dependent behaviors. Using mutant mice that lack the M-4 mAChR only in D-1 dopamine receptor-expressing cells (D1-M4-KO), we investigated the role of this neuronal population in the antipsychotic-like effects of xanomeline in amphetamine-induced hyperactivity and apomorphine-induced climbing. Interestingly, the antipsychotic-like effects of xanomeline in the two models were almost completely abolished in D1-M4-KO mice, suggesting that M-4 mAChRs colocalized with D-1 dopamine receptors are centrally involved in mediating the antipsychotic-like effects of xanomeline. This is consistent with the hypothesis that activation of the M-4 mAChR represents a potential target for the future medical treatment of psychosis.
C1 [Dencker, Ditte; Wortwein, Gitta; Weikop, Pia; Woldbye, David P. D.; Fink-Jensen, Anders] Univ Copenhagen, Psychiat Ctr Copenhagen, Lab Neuropsychiat, DK-2100 Copenhagen, Denmark.
[Wortwein, Gitta] Univ Copenhagen, Dept Publ Hlth, DK-1014 Copenhagen, Denmark.
[Thomsen, Morgane] Harvard Univ, Sch Med, McLean Hosp, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USA.
[Sager, Thomas N.; Mork, Arne] H Lundbeck & Co AS, Discovery Pharmacol Res, DK-2500 Valby, Denmark.
[Woldbye, David P. D.] Univ Copenhagen, Dept Neurosci & Pharmacol, DK-2200 Copenhagen, Denmark.
[Jeon, Jongrye; Wess, Juergen] NIDDK, Mol Signaling Sect, NIH, Bethesda, MD 20892 USA.
RP Fink-Jensen, A (reprint author), Univ Copenhagen, Psychiat Ctr Copenhagen, Lab Neuropsychiat, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark.
EM a.fink-jensen@dadlnet.dk
OI Wortwein, Gitta/0000-0001-6981-7885
FU Ivan Nielsen Foundation; Lundbeck Foundation; Aase and Ejnar Danielsen
Foundation
FX This work was supported by the Ivan Nielsen Foundation, the Lundbeck
Foundation, and the Aase and Ejnar Danielsen Foundation.
NR 23
TC 22
Z9 22
U1 1
U2 9
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD APR 20
PY 2011
VL 31
IS 16
BP 5905
EP 5908
DI 10.1523/JNEUROSCI.0370-11.2011
PG 4
WC Neurosciences
SC Neurosciences & Neurology
GA 753JV
UT WOS:000289769400004
PM 21508215
ER
PT J
AU Choi, KY
Chung, S
Roche, KW
AF Choi, Kyu Yeong
Chung, Seungsoo
Roche, Katherine W.
TI Differential Binding of Calmodulin to Group I Metabotropic Glutamate
Receptors Regulates Receptor Trafficking and Signaling
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID LONG-TERM DEPRESSION; PROTEIN-COUPLED RECEPTORS; NMDA RECEPTOR; MGLUR
ACTIVATION; AMPA RECEPTORS; ALPHA-ACTININ; NR1 SUBUNIT; KINASE-C;
PHOSPHORYLATION; CALCIUM
AB Metabotropic glutamate receptors (mGluRs) are G-protein-coupled receptors that modulate excitatory neurotransmission and synaptic plasticity. The group I mGluRs (mGluR1 and mGluR5) have long intracellular C-terminal domains, which interact with many proteins. Our previous studies identified calmodulin (CaM) as a strong regulator of mGluR5 trafficking and mGluR5-induced calcium signaling. Although it has been accepted that both mGluR1 and mGluR5 interact with CaM, we now show that CaM specifically binds mGluR5 and not mGluR1. We have identified a single critical residue in mGluR5 (L896) that is required for CaM binding. In mGluR1, mutation of the corresponding residue, V909, to leucine is sufficient to confer CaM binding to mGluR1. To investigate the functional effects of CaM binding, we examined the surface expression of mGluR1 and mGluR5 in hippocampal neurons. The mutation in mGluR1 (V909L) that confers CaM binding dramatically increases mGluR1 surface expression, whereas the analogous mutation in mGluR5 that disrupts CaM binding (L896V) decreases mGluR5 surface expression. In addition, the critical residue that alters CaM binding regulates mGluR internalization. Furthermore, we find that mGluR-mediated AMPA receptor endocytosis is enhanced by CaM binding to group I mGluRs. Finally, we show that calcium responses evoked by group I mGluRs are modulated by these mutations, which regulate CaM binding. Our findings elucidate a critical mechanism that specifically affects mGluR5 trafficking and signaling, and distinguishes mGluR1 and mGluR5 regulation.
C1 [Choi, Kyu Yeong; Roche, Katherine W.] Natl Inst Neurol Disorders & Stroke, Receptor Biol Sect, NIH, Bethesda, MD 20892 USA.
[Chung, Seungsoo] Natl Inst Neurol Disorders & Stroke, Dev Synapt Plast Sect, NIH, Bethesda, MD 20892 USA.
[Chung, Seungsoo] Yonsei Univ, Coll Med, Dept Physiol, Seoul 120752, South Korea.
RP Roche, KW (reprint author), Natl Inst Neurol Disorders & Stroke, Receptor Biol Sect, NIH, 35 Convent Dr,Bldg 35,Room 2C-903, Bethesda, MD 20892 USA.
EM rochek@ninds.nih.gov
OI Roche, Katherine/0000-0001-7282-6539
FU National Institute of Neurological Disorders and Stroke (NINDS)
FX The National Institute of Neurological Disorders and Stroke (NINDS)
Intramural Research Program supported this work. We thank Dr. Carolyn
Smith (NINDS Light Imaging Facility) for assistance with confocal
microscopy, James Nagle and Debbie Kauffman (NINDS Sequencing Facility)
for DNA sequence analysis, and Dr. Elizabeth Webber for critical reading
of this manuscript.
NR 58
TC 18
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 APR 20
PY 2011
VL 31
IS 16
BP 5921
EP 5930
DI 10.1523/JNEUROSCI.6253-10.2011
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 753JV
UT WOS:000289769400006
PM 21508217
ER
PT J
AU Yao, HH
Kim, K
Duan, M
Hayashi, T
Guo, ML
Morgello, S
Prat, A
Wang, J
Su, TP
Buch, S
AF Yao, Honghong
Kim, Keejun
Duan, Ming
Hayashi, Teruo
Guo, Minglei
Morgello, Susan
Prat, Alexander
Wang, John
Su, Tsung-Ping
Buch, Shilpa
TI Cocaine Hijacks sigma 1 Receptor to Initiate Induction of Activated
Leukocyte Cell Adhesion Molecule: Implication for Increased Monocyte
Adhesion and Migration in the CNS
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; BLOOD-BRAIN-BARRIER; MICROVASCULAR
ENDOTHELIAL-CELLS; IL-1-BETA-INDUCED ICAM-1 EXPRESSION; LIPID RAFT
RECONSTITUTION; NF-KAPPA-B; TRANSENDOTHELIAL MIGRATION; TRANSMIGRATION;
INVOLVEMENT; MECHANISMS
AB Human immunodeficiency virus (HIV)-associated increase in monocyte adhesion and trafficking is exacerbated by cocaine abuse. The underlying mechanisms involve cocaine-mediated upregulation of adhesion molecules with subsequent disruption of the blood-brain barrier (BBB). Recently, a novel activated leukocyte cell adhesion molecule (ALCAM) has been implicated in leukocyte transmigration across the endothelium. We now show that upregulation of ALCAM in the brain endothelium seen in HIV(+)/cocaine drug abusers paralleled increased CD68 immunostaining compared with HIV(+)/no cocaine or uninfected controls, suggesting the important role of ALCAM in promoting leukocyte infiltration across the BBB. Furthermore, ALCAM expression was increased in cocaine-treated mice with concomitant increase in monocyte adhesion and transmigration in vivo, which was ameliorated by pretreating with the neutralizing antibody to ALCAM, lending additional support to the role of ALCAM. This new concept was further confirmed by in vitro experiments. Cocaine-mediated induction of ALCAM in human brain microvascular endothelial cells through the translocation of sigma receptor to the plasma membrane, followed by phosphorylation of PDGF-beta (platelet-derived growth factor-beta) receptor. Downstream activation of mitogen-activated protein kinases, Akt, and NF-kappa B (nuclear factor-kappa B) pathways resulted in induced expression of ALCAM. Functional implication of upregulated ALCAM was confirmed using cell adhesion and transmigration assays. Neutralizing antibody to ALCAM ameliorated this effect. Together, these findings implicate cocaine-mediated induction of ALCAM as a mediator of increased monocyte adhesion/transmigration into the CNS.
C1 [Yao, Honghong; Duan, Ming; Buch, Shilpa] Univ Nebraska Med Ctr, Dept Pharmacol & Expt Neurosci, Omaha, NE 68198 USA.
[Kim, Keejun] Univ Kansas, Med Ctr, Dept Microbiol Mol Genet & Immunol, Kansas City, KS 66160 USA.
[Hayashi, Teruo; Su, Tsung-Ping] Natl Inst Drug Abuse, Cellular Pathobiol Sect, Cellular Neurobiol Res Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Guo, Minglei; Wang, John] Univ Missouri, Kansas City Sch Med, Dept Basic Med Sci, Kansas City, MO 64108 USA.
[Morgello, Susan] Mt Sinai Hosp, Natl NeuroAIDS Tissue Consortium, New York, NY 10029 USA.
[Prat, Alexander] Univ Montreal, Neuroimmunol Res Lab, Ctr Excellence Neur, Ctr Hosp,Notre Dame Hosp, Montreal, PQ H2L 4M1, Canada.
RP Buch, S (reprint author), Univ Nebraska Med Ctr, Dept Pharmacol & Expt Neurosci, 985880 Nebraska Med Ctr,DRC 8011, Omaha, NE 68198 USA.
EM sbuch@unmc.edu
RI duan, ming/M-9892-2016
FU National Institutes of Health [MH-068212, DA020392, DA023397, DA024442,
DA030285]; Clinical Research Center of the Mount Sinai School of
Medicine [M01-RR-00071]
FX This work was supported by National Institutes of Health Grants
MH-068212, DA020392, DA023397, DA024442 (S.B.), and DA030285 (H.Y.), and
by Clinical Research Center of the Mount Sinai School of Medicine Grant
M01-RR-00071 (S.M.).
NR 35
TC 46
Z9 47
U1 0
U2 8
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 APR 20
PY 2011
VL 31
IS 16
BP 5942
EP 5955
DI 10.1523/JNEUROSCI.5618-10.2011
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 753JV
UT WOS:000289769400008
PM 21508219
ER
PT J
AU Lehmann, ML
Herkenham, M
AF Lehmann, Michael L.
Herkenham, Miles
TI Environmental Enrichment Confers Stress Resiliency to Social Defeat
through an Infralimbic Cortex-Dependent Neuroanatomical Pathway
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID MEDIAL PREFRONTAL CORTEX; TREATMENT-RESISTANT DEPRESSION; DEEP
BRAIN-STIMULATION; DELTA-FOSB; NUCLEUS-ACCUMBENS; EFFERENT PROJECTIONS;
CONDITIONED FEAR; EXTINCTION; REWARD; RAT
AB Enriched environmental (EE) housing dampens stress-induced alterations in neurobiological systems, promotes adaptability, and extinguishes submissive behavioral traits developed during social defeat stress (SD). In the present study, we hypothesized that enrichment before SD can confer stress resiliency and, furthermore, that neuronal activity in the prefrontal cortex (PFC) is requisite for this resiliency. To test these hypotheses, mice were housed in EE, standard (SE), or impoverished (IE) housing and then exposed to SD. EE conferred resilience to SD as measured in several behavioral tasks. EE-housed mice expressed elevated FosB/Delta FosB immunostaining in areas associated with emotional regulation and reward processing, i.e., infralimbic, prelimbic, and anterior cingulate cortices, amygdala, and nucleus accumbens, and this expression was mostly preserved in mice receiving EE followed by SD. In contrast, in SE-or IE-housed animals, SD increased maladaptive behaviors and greatly reduced FosB/Delta FosB staining in the forebrain. We tested the putative involvement of the PFC in mediating resilience by lesioning individual regions of the PFC either before or after EE housing and then exposing the mice to SD. We found that discrete lesions of the infralimbic but not prelimbic or cingulate cortex made before but not after EE abolished the behavioral resiliency to stress afforded by EE and attenuated FosB/Delta FosB expression in the accumbens and amygdala while increasing it in the paraventricular hypothalamic nucleus. These data suggest that pathological ventromedial PFC outputs to downstream limbic targets could predispose an individual to anxiety disorders in stressful situations, whereas enhanced ventromedial PFC outputs could convey stress resilience.
C1 [Lehmann, Michael L.; Herkenham, Miles] NIMH, Funct Neuroanat Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA.
RP Lehmann, ML (reprint author), NIMH, Funct Neuroanat Sect, Lab Cellular & Mol Regulat, NIH, Bldg 35,Room 1C911,35 Convent Dr, Bethesda, MD 20892 USA.
EM Michael.Lehmann@nih.gov
OI Lehmann, Michael/0000-0003-4476-8268; Herkenham,
Miles/0000-0003-2228-4238
FU National Institute of Mental Health/National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health/National Institutes of Health. We
thank Eric Holaday, Jay Levin, and Rebecca Brachman for technical
assistance.
NR 65
TC 75
Z9 75
U1 3
U2 15
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 APR 20
PY 2011
VL 31
IS 16
BP 6159
EP 6173
DI 10.1523/JNEUROSCI.0577-11.2011
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA 753JV
UT WOS:000289769400029
PM 21508240
ER
PT J
AU Kothapalli, NR
Norton, DD
Fugmann, SD
AF Kothapalli, Naga Rama
Norton, Darrell D.
Fugmann, Sebastian D.
TI Classical Mus musculus Ig kappa Enhancers Support Transcription but not
High Level Somatic Hypermutation from a V-Lambda Promoter in Chicken
DT40 Cells
SO PLOS ONE
LA English
DT Article
ID IMMUNOGLOBULIN GENE CONVERSION; CLASS SWITCH RECOMBINATION; CYTIDINE
DEAMINASE AID; LOCUS; DNA; DOWNSTREAM; TARGETS; DIVERSIFICATION;
ELEMENTS; REGION
AB Somatic hypermutation (SHM) of immunoglobulin genes is initiated by activation-induced cytidine deaminase (AID) in activated B cells. This process is strictly dependent on transcription. Hence, cis-acting transcriptional control elements have been proposed to target SHM to immunoglobulin loci. The Mus musculus Ig kappa locus is regulated by the intronic enhancer (iE/MAR) and the 3' enhancer (3'E), and multiple studies using transgenic and knock-out approaches in mice and cell lines have reported somewhat contradictory results about the function of these enhancers in AID-mediated sequence diversification. Here we show that the M. musculus iE/MAR and 3'E elements are active solely as transcriptional enhancer when placed in the context of the IGL locus in Gallus gallus DT40 cells, but they are very inefficient in targeting AID-mediated mutation events to this locus. This suggests that either key components of the cis-regulatory targeting elements reside outside the murine Igk transcriptional enhancer sequences, or that the targeting of AID activity to Ig loci occurs by largely species-specific mechanisms.
C1 [Kothapalli, Naga Rama; Norton, Darrell D.; Fugmann, Sebastian D.] NIA, Lab Mol Biol & Immunol, Mol Immunol Unit, NIH, Baltimore, MD 21224 USA.
RP Kothapalli, NR (reprint author), NIA, Lab Mol Biol & Immunol, Mol Immunol Unit, NIH, Baltimore, MD 21224 USA.
EM fugmanns@grc.nia.nih.gov
OI Kothapalli, Naga Rama/0000-0001-7993-8525
FU National Institute on Aging/National Institutes of Health
FX This work was entirely funded by the intramural program of the National
Institute on Aging/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 26
TC 5
Z9 5
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 APR 20
PY 2011
VL 6
IS 4
AR e18955
DI 10.1371/journal.pone.0018955
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 752UE
UT WOS:000289719400038
PM 21533098
ER
PT J
AU Richardson, K
Louie-Gao, Q
Arnett, DK
Parnell, LD
Lai, CQ
Davalos, A
Fox, CS
Demissie, S
Cupples, LA
Fernandez-Hernando, C
Ordovas, JM
AF Richardson, Kris
Louie-Gao, Qiong
Arnett, Donna K.
Parnell, Laurence D.
Lai, Chao-Qiang
Davalos, Alberto
Fox, Caroline S.
Demissie, Serkalem
Cupples, L. Adrienne
Fernandez-Hernando, Carlos
Ordovas, Jose M.
TI The PLIN4 Variant rs8887 Modulates Obesity Related Phenotypes in Humans
through Creation of a Novel miR-522 Seed Site
SO PLOS ONE
LA English
DT Article
ID FOOD FREQUENCY QUESTIONNAIRE; FACTOR-BINDING SITES; KAPPA-B ACTIVATION;
BODY-MASS INDEX; PERILIPIN GENE; ADIPOSE-TISSUE; FATTY-ACIDS; TNF-ALPHA;
EICOSAPENTAENOIC ACID; ADIPOCYTE LIPOLYSIS
AB PLIN4 is a member of the PAT family of lipid storage droplet (LSD) proteins. Associations between seven single nucleotide polymorphisms (SNPs) at human PLIN4 with obesity related phenotypes were investigated using meta-analysis followed by a determination if these phenotypes are modulated by interactions between PLIN4 SNPs and dietary PUFA. Samples consisted of subjects from two populations of European ancestry. We demonstrated association of rs8887 with anthropometrics. Meta-analysis demonstrated significant interactions between the rs8887 minor allele with PUFA n3 modulating anthropometrics. rs884164 showed interaction with both n3 and n6 PUFA modulating anthropometric and lipid phenotypes. In silico analysis of the PLIN4 3'UTR sequence surrounding the rs8887 minor A allele predicted a seed site for the human microRNA-522 (miR-522), suggesting a functional mechanism. Our data showed that a PLIN4 3'UTR luciferase reporter carrying the A allele of rs8887 was reduced in response to miR-522 mimics compared to the G allele. These results suggest variation at the PLIN4 locus, and its interaction with PUFA as a modulator of obesity related phenotypes, acts in part through creation of a miR-522 regulatory site.
C1 [Richardson, Kris; Parnell, Laurence D.; Lai, Chao-Qiang; Ordovas, Jose M.] Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, Nutr & Genom Lab, Boston, MA 02111 USA.
[Louie-Gao, Qiong; Demissie, Serkalem; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Arnett, Donna K.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.
[Arnett, Donna K.] Univ Alabama Birmingham, Clin Nutr Res Ctr, Birmingham, AL USA.
[Davalos, Alberto; Fernandez-Hernando, Carlos] NYU, Sch Med, Dept Med, Leon H Charney Div Cardiol, New York, NY USA.
[Davalos, Alberto; Fernandez-Hernando, Carlos] NYU, Sch Med, Dept Cell Biol, Leon H Charney Div Cardiol, New York, NY 10016 USA.
[Davalos, Alberto; Fernandez-Hernando, Carlos] NYU, Sch Med, Vasc Biol & Dis Program, Marc & Ruti Bell Program, New York, NY 10016 USA.
[Fox, Caroline S.; Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Fox, Caroline S.] NHLBI, Ctr Populat Studies, Framingham, MA USA.
[Davalos, Alberto] Inst Madrileno Estudios Avanzados IMDEA Alimentac, Madrid, Spain.
[Ordovas, Jose M.] CNIC, Dept Cardiovasc Epidemiol & Populat Genet, Madrid, Spain.
RP Richardson, K (reprint author), Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer US Dept Agr, Nutr & Genom Lab, Boston, MA 02111 USA.
EM Kris.richardson@tufts.edu
OI Davalos, Alberto/0000-0001-5709-6443; Cupples, L.
Adrienne/0000-0003-0273-7965; Ordovas, Jose/0000-0002-7581-5680
FU National Heart, Lung, and Blood Institute [HL-54776, U01 HL72524];
National Institute of Diabetes and Digestive and Kidney Diseases
[DK075030]; US Department of Agriculture Research [53-K06-5-10,
58-1950-9-001]
FX This work was supported by National Heart, Lung, and Blood Institute
grants HL-54776 and U01 HL72524; National Institute of Diabetes and
Digestive and Kidney Diseases, Grant Number DK075030; and by contracts
53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture
Research. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 54
TC 24
Z9 24
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 APR 20
PY 2011
VL 6
IS 4
AR e17944
DI 10.1371/journal.pone.0017944
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 752UE
UT WOS:000289719400004
PM 21533135
ER
PT J
AU Rockx, B
Feldmann, F
Brining, D
Gardner, D
LaCasse, R
Kercher, L
Long, D
Rosenke, R
Virtaneva, K
Sturdevant, DE
Porcella, SF
Mattoon, J
Parnell, M
Baric, RS
Feldmann, H
AF Rockx, Barry
Feldmann, Friederike
Brining, Douglas
Gardner, Don
LaCasse, Rachel
Kercher, Lisa
Long, Dan
Rosenke, Rebecca
Virtaneva, Kimmo
Sturdevant, Daniel E.
Porcella, Stephen F.
Mattoon, John
Parnell, Michael
Baric, Ralph S.
Feldmann, Heinz
TI Comparative Pathogenesis of Three Human and Zoonotic SARS-CoV Strains in
Cynomolgus Macaques
SO PLOS ONE
LA English
DT Article
ID ACUTE RESPIRATORY SYNDROME; SYNDROME CORONAVIRUS INFECTION; HUMAN
MONOCLONAL-ANTIBODY; CYTOKINE/CHEMOKINE PROFILES; ANIMAL-MODEL;
TRANSMISSION; RECEPTOR; DISEASE; ACE2; EXPRESSION
AB The severe acute respiratory syndrome (SARS) epidemic was characterized by increased pathogenicity in the elderly due to an early exacerbated innate host response. SARS-CoV is a zoonotic pathogen that entered the human population through an intermediate host like the palm civet. To prevent future introductions of zoonotic SARS-CoV strains and subsequent transmission into the human population, heterologous disease models are needed to test the efficacy of vaccines and therapeutics against both late human and zoonotic isolates. Here we show that both human and zoonotic SARS-CoV strains can infect cynomolgus macaques and resulted in radiological as well as histopathological changes similar to those seen in mild human cases. Viral replication was higher in animals infected with a late human phase isolate compared to a zoonotic isolate. While there were significant differences in the number of host genes differentially regulated during the host responses between the three SARS-CoV strains, the top pathways and functions were similar and only apparent early during infection with the majority of genes associated with interferon signaling pathways. This study characterizes critical disease models in the evaluation and licensure of therapeutic strategies against SARS-CoV for human use.
C1 [Rockx, Barry; Feldmann, Friederike; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
[Brining, Douglas; Gardner, Don; LaCasse, Rachel; Kercher, Lisa; Long, Dan; Rosenke, Rebecca; Parnell, Michael] NIAID, Rocky Mt Vet Branch, Div Intramural Res, NIH, Hamilton, MT USA.
[Virtaneva, Kimmo; Sturdevant, Daniel E.; Porcella, Stephen F.] NIAID, Genom Unit, Res Technol Sect, Div Intramural Res,NIH, Hamilton, MT USA.
[Mattoon, John] Washington State Univ, Dept Vet Clin Sci, Pullman, WA 99164 USA.
[Baric, Ralph S.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Rockx, Barry] Univ Texas Med Branch, Dept Pathol, Galveston, TX USA.
[Rockx, Barry] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX USA.
RP Rockx, B (reprint author), NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
EM barry.rockx@utmb.edu
OI Tripp, Ralph/0000-0002-2924-9956
FU NIH NIAID [U54 AI081680, AI075297]; Division of Intramural Research
(DIR), NIAID, NIH
FX The study was financially supported by NIH NIAID grants U54 AI081680 and
AI075297 to R. B. and the Division of Intramural Research (DIR), NIAID,
NIH. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 44
TC 9
Z9 9
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 APR 20
PY 2011
VL 6
IS 4
AR e18558
DI 10.1371/journal.pone.0018558
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 752UE
UT WOS:000289719400013
PM 21533129
ER
PT J
AU Wendler, D
AF Wendler, David
TI How to Enroll Participants in Research Ethically
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID CONSENT
C1 NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Wendler, D (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM dwendler@nih.gov
NR 6
TC 7
Z9 7
U1 0
U2 0
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 APR 20
PY 2011
VL 305
IS 15
BP 1587
EP 1588
DI 10.1001/jama.2011.421
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 752HU
UT WOS:000289683000029
PM 21505137
ER
PT J
AU Song, MH
Liu, Y
Anderson, DE
Jahng, WJ
O'Connell, KF
AF Song, Mi Hye
Liu, Yan
Anderson, D. Eric
Jahng, Wan Jin
O'Connell, Kevin F.
TI Protein Phosphatase 2A-SUR-6/B55 Regulates Centriole Duplication in C.
elegans by Controlling the Levels of Centriole Assembly Factors
SO DEVELOPMENTAL CELL
LA English
DT Article
ID CENTROSOME DUPLICATION; HUMAN-CELLS; CAENORHABDITIS-ELEGANS; ZYG-1;
SAS-4; PHOSPHORYLATION; INSTABILITY; MATURATION; REQUIRE; SIZE
AB Centrioles play a crucial role in mitotic spindle assembly and duplicate precisely once per cell cycle. In worms, flies, and humans, centriole assembly is dependent upon a key regulatory kinase (ZYG-1/Sak/Plk4) and its downstream effectors SAS-5 and SAS-6. Here we report a role for protein phosphatase 2A (PP2A) in centriole duplication. We find that the PP2A catalytic subunit LET-92, the scaffolding subunit PAA-1, and the 655 regulatory subunit SUR-6 function together to positively regulate centriole assembly. In PP2A-SUR-6-depleted embryos, the levels of ZYG-1 and SAS-5 are reduced and the ZYG-1- and SAS-5-dependent recruitment of SAS-6 to the nascent centriole fails. We show that PP2A physically associates with SAS-5 in vivo and that inhibiting proteolysis can rescue SAS-5 levels and the centriole duplication defect of PP2A-depleted embryos. Together, our findings indicate that PP2A-SUR-6 promotes centriole assembly by protecting ZYG-1 and SAS-5 from degradation.
C1 [Song, Mi Hye; Liu, Yan; O'Connell, Kevin F.] NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
[Anderson, D. Eric] NIDDKD, Prote & Mass Spectrometry Facil, NIH, Bethesda, MD 20892 USA.
[Song, Mi Hye; Jahng, Wan Jin] Michigan Technol Univ, Dept Biol Sci, Houghton, MI 49931 USA.
RP Song, MH (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
EM mhsong@mtu.edu; kevino@mail.nih.gov
OI Song, Mi Hye/0000-0001-8326-6602
FU National Institutes Health; National Institute of Diabetes and Digestive
and Kidney Diseases
FX We thank members of the O'Connell and Song laboratories, David Weisblat,
Alexander Dammerman, Tony Hyman, Markus Decker, Karen Oegema, Martin
Srayko, and Orna Cohen-Fix for sharing strains and reagents and/or
providing advice. Some strains were provided by The Caenorhabditis
Genetics Center and The National Bioresource Project, Japan. This work
was supported by the Intramural Research Program of the National
Institutes Health and by the National Institute of Diabetes and
Digestive and Kidney Diseases.
NR 31
TC 28
Z9 43
U1 1
U2 4
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 APR 19
PY 2011
VL 20
IS 4
BP 563
EP 571
DI 10.1016/j.devcel.2011.03.007
PG 9
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 755JC
UT WOS:000289924700017
PM 21497766
ER
PT J
AU Yang, SS
Tu, ZJ
Cheung, F
Xu, WW
Lamb, JFS
Jung, HJG
Vance, CP
Gronwald, JW
AF Yang, S. Samuel
Tu, Zheng Jin
Cheung, Foo
Xu, Wayne Wenzhong
Lamb, JoAnn F. S.
Jung, Hans-Joachim G.
Vance, Carroll P.
Gronwald, John W.
TI Using RNA-Seq for gene identification, polymorphism detection and
transcript profiling in two alfalfa genotypes with divergent cell wall
composition in stems
SO BMC GENOMICS
LA English
DT Article
ID MEDICAGO-SATIVA L.; MASKING BIASED PROBES; SUCROSE TRANSPORTER;
CELLULOSE SYNTHESIS; DOWN-REGULATION; SNP DISCOVERY; PHOSPHATE
DEFICIENCY; OPTIMIZING ANALYSIS; EXPRESSION ANALYSIS; TRANSGENIC ALFALFA
AB Background: Alfalfa, [Medicago sativa (L.) sativa], a widely-grown perennial forage has potential for development as a cellulosic ethanol feedstock. However, the genomics of alfalfa, a non-model species, is still in its infancy. The recent advent of RNA-Seq, a massively parallel sequencing method for transcriptome analysis, provides an opportunity to expand the identification of alfalfa genes and polymorphisms, and conduct in-depth transcript profiling.
Results: Cell walls in stems of alfalfa genotype 708 have higher cellulose and lower lignin concentrations compared to cell walls in stems of genotype 773. Using the Illumina GA-II platform, a total of 198,861,304 expression sequence tags (ESTs, 76 bp in length) were generated from cDNA libraries derived from elongating stem (ES) and post-elongation stem (PES) internodes of 708 and 773. In addition, 341,984 ESTs were generated from ES and PES internodes of genotype 773 using the GS FLX Titanium platform. The first alfalfa (Medicago sativa) gene index (MSGI 1.0) was assembled using the Sanger ESTs available from GenBank, the GS FLX Titanium EST sequences, and the de novo assembled Illumina sequences. MSGI 1.0 contains 124,025 unique sequences including 22,729 tentative consensus sequences (TCs), 22,315 singletons and 78,981 pseudo-singletons. We identified a total of 1,294 simple sequence repeats (SSR) among the sequences in MSGI 1.0. In addition, a total of 10,826 single nucleotide polymorphisms (SNPs) were predicted between the two genotypes. Out of 55 SNPs randomly selected for experimental validation, 47 (85%) were polymorphic between the two genotypes. We also identified numerous allelic variations within each genotype. Digital gene expression analysis identified numerous candidate genes that may play a role in stem development as well as candidate genes that may contribute to the differences in cell wall composition in stems of the two genotypes.
Conclusions: Our results demonstrate that RNA-Seq can be successfully used for gene identification, polymorphism detection and transcript profiling in alfalfa, a non-model, allogamous, autotetraploid species. The alfalfa gene index assembled in this study, and the SNPs, SSRs and candidate genes identified can be used to improve alfalfa as a forage crop and cellulosic feedstock.
C1 [Yang, S. Samuel; Lamb, JoAnn F. S.; Jung, Hans-Joachim G.; Vance, Carroll P.; Gronwald, John W.] USDA ARS, Plant Sci Res Unit, St Paul, MN 55108 USA.
[Tu, Zheng Jin; Xu, Wayne Wenzhong] Univ Minnesota, Supercomp Inst Adv Computat Res, Minneapolis, MN 55455 USA.
[Cheung, Foo] J Craig Venter Inst, Rockville, MD 20892 USA.
[Lamb, JoAnn F. S.; Jung, Hans-Joachim G.; Vance, Carroll P.; Gronwald, John W.] Univ Minnesota, Dept Agron & Plant Genet, St Paul, MN 55108 USA.
[Cheung, Foo] NIH, Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD 20892 USA.
RP Yang, SS (reprint author), USDA ARS, Plant Sci Res Unit, St Paul, MN 55108 USA.
EM sam.yang@ars.usda.gov; carroll.vance@ars.usda.gov;
john.gronwald@ars.usda.gov
FU USDA-ARS CRIS [3640-12210-001-00D]
FX This work was carried out in part using computing resources at the
University of Minnesota Supercomputing Institute for Advance
Computational Research. Funding for this research was provided by
USDA-ARS CRIS Project 3640-12210-001-00D. Mention of trade names or
commercial products in this publication is solely for the purpose of
providing specific information and does not imply recommendation or
endorsement by the U. S. Department of Agriculture. We thank Dr. David
Garvin, Dr. Jamie O'Rourke, and Dr. Deborah Samac for critical review of
the manuscript.
NR 107
TC 72
Z9 74
U1 5
U2 52
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD APR 19
PY 2011
VL 12
AR 199
DI 10.1186/1471-2164-12-199
PG 19
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 775ST
UT WOS:000291484400001
PM 21504589
ER
PT J
AU England, K
Crew, R
Slayden, RA
AF England, Kathleen
Crew, Rebecca
Slayden, Richard A.
TI Mycobacterium tuberculosis septum site determining protein, Ssd encoded
by rv3660c, promotes filamentation and elicits an alternative metabolic
and dormancy stress response
SO BMC MICROBIOLOGY
LA English
DT Article
DE Mycobacterium tuberculosis dormancy; Dos regulon; septum site
determining protein; cell division
ID CELL-DIVISION; DRUG DISCOVERY; SIGMA-FACTORS; DOSR REGULON; Z-RING;
GENE; VIRULENCE; FTSZ; INHIBITION; POLYMERIZATION
AB Background: Proteins that are involved in regulation of cell division and cell cycle progression remain undefined in Mycobacterium tuberculosis. In addition, there is a growing appreciation that regulation of cell replication at the point of division is important in establishing a non-replicating persistent state. Accordingly, the objective of this study was to use a systematic approach consisting of consensus-modeling bioinformatics, ultrastructural analysis, and transcriptional mapping to identify septum regulatory proteins that participate in adaptive metabolic responses in M. tuberculosis.
Results: Septum site determining protein (Ssd), encoded by rv3660c was discovered to be an ortholog of septum site regulating proteins in actinobacteria by bioinformatics analysis. Increased expression of ssd in M. smegmatis and M. tuberculosis inhibited septum formation resulting in elongated cells devoid of septa. Transcriptional mapping in M. tuberculosis showed that increased ssd expression elicited a unique response including the dormancy regulon and alternative sigma factors that are thought to play a role in adaptive metabolism. Disruption of rv3660c by transposon insertion negated the unique transcriptional response and led to a reduced bacterial length.
Conclusions: This study establishes the first connection between a septum regulatory protein and induction of alternative metabolism consisting of alternative sigma factors and the dormancy regulon that is associated with establishing a non-replicating persistent intracellular lifestyle. The identification of a regulatory component involved in cell cycle regulation linked to the dormancy response, whether directly or indirectly, provides a foundation for additional studies and furthers our understanding of the complex mechanisms involved in establishing a non-replicating state and resumption of growth.
C1 [England, Kathleen; Crew, Rebecca; Slayden, Richard A.] Colorado State Univ, Mycobacteria Res Labs, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA.
[England, Kathleen] NIAID, TB Res Sect, NIH, Bethesda, MD 20892 USA.
RP Slayden, RA (reprint author), Colorado State Univ, Mycobacteria Res Labs, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA.
EM richard.slayden@colostate.edu
RI Slayden, Richard/O-8626-2016
OI Slayden, Richard/0000-0001-6857-7277
FU [RO1 AI055298]
FX We gratefully acknowledge Dr. Melissa Ramirez, Dr. Dennis L. Knudson,
and Ms. Kerry Brookman for technical and editorial assistance, and Mr.
Michael Sherman for assistance with electron microscopy. This work was
support by RO1 AI055298 (RAS). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 37
TC 12
Z9 12
U1 0
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2180
J9 BMC MICROBIOL
JI BMC Microbiol.
PD APR 19
PY 2011
VL 11
AR 79
DI 10.1186/1471-2180-11-79
PG 12
WC Microbiology
SC Microbiology
GA 764FN
UT WOS:000290614600001
PM 21504606
ER
PT J
AU Eller, MA
Blom, KG
Gonzalez, VD
Eller, LA
Naluyima, P
Laeyendecker, O
Quinn, TC
Kiwanuka, N
Serwadda, D
Sewankambo, NK
Tasseneetrithep, B
Wawer, MJ
Gray, RH
Marovich, MA
Michael, NL
de Souza, MS
Wabwire-Mangen, F
Robb, ML
Currier, JR
Sandberg, JK
AF Eller, Michael A.
Blom, Kim G.
Gonzalez, Veronica D.
Eller, Leigh Anne
Naluyima, Prossy
Laeyendecker, Oliver
Quinn, Thomas C.
Kiwanuka, Noah
Serwadda, David
Sewankambo, Nelson K.
Tasseneetrithep, Boonrat
Wawer, Maria J.
Gray, Ronald H.
Marovich, Mary A.
Michael, Nelson L.
de Souza, Mark S.
Wabwire-Mangen, Fred
Robb, Merlin L.
Currier, Jeffrey R.
Sandberg, Johan K.
TI Innate and Adaptive Immune Responses Both Contribute to Pathological CD4
T Cell Activation in HIV-1 Infected Ugandans
SO PLOS ONE
LA English
DT Article
ID HIV-INFECTED INDIVIDUALS; AFRICAN-GREEN MONKEYS; MICROBIAL
TRANSLOCATION; VIRAL LOAD; DISEASE PROGRESSION; PERIPHERAL-BLOOD;
LYMPHOCYTE-ACTIVATION; VIRUS-INFECTIONS; PD-1 EXPRESSION; RAKAI DISTRICT
AB HIV-1 disease progression is associated with persistent immune activation. However, the nature of this association is incompletely understood. Here, we investigated immune activation in the CD4 T cell compartment of chronically HIV-1 infected individuals from Rakai, Uganda. Levels of CD4 T cell activation, assessed as co-expression of PD-1, CD38 and HLA-DR, correlated directly to viral load and inversely to CD4 count. Deeper characterization of these cells indicated an effector memory phenotype with relatively frequent expression of Ki67 despite their PD-1 expression, and levels of these cells were inversely associated with FoxP3+ regulatory T cells. We therefore use the term deregulated effector memory (DEM) cells to describe them. CD4 T cells with a DEM phenotype could be generated by antigen stimulation of recall responses in vitro. Responses against HIV-1 and CMV antigens were enriched among the DEM CD4 T cells in patients, and the diverse V beta repertoire of DEM CD4 T cells suggested they include diverse antigen-specificities. Furthermore, the levels of DEM CD4 T cells correlated directly to soluble CD14 (sCD14) and IL-6, markers of innate immune activation, in plasma. The size of the activated DEM CD4 T cell subset was predictive of the rate of disease progression, whereas IL-6 was only weakly predictive and sCD14 was not predictive. Taken together, these results are consistent with a model where systemic innate immune activation and chronic antigen stimulation of adaptive T cell responses both play important roles in driving pathological CD4 T cell immune activation in HIV-1 disease.
C1 [Eller, Michael A.; Eller, Leigh Anne; Naluyima, Prossy; Wabwire-Mangen, Fred] Makerere Univ, Walter Reed Project, Kampala, Uganda.
[Eller, Michael A.; Eller, Leigh Anne; Tasseneetrithep, Boonrat; Marovich, Mary A.; Michael, Nelson L.; de Souza, Mark S.; Robb, Merlin L.; Currier, Jeffrey R.] US Mil HIV Res Program, Rockville, MD USA.
[Eller, Michael A.; Blom, Kim G.; Gonzalez, Veronica D.; Sandberg, Johan K.] Karolinska Inst, Ctr Infect Med, Dept Med, Karolinska Univ Hosp Huddinge, Stockholm, Sweden.
[Laeyendecker, Oliver; Quinn, Thomas C.] NIAID, NIH, Bethesda, MD 20892 USA.
[Laeyendecker, Oliver; Quinn, Thomas C.] Johns Hopkins Sch Med, Baltimore, MD USA.
[Kiwanuka, Noah; Serwadda, David; Wabwire-Mangen, Fred] Makerere Univ, Sch Publ Hlth, Coll Hlth Sci, Kampala, Uganda.
[Kiwanuka, Noah; Serwadda, David; Sewankambo, Nelson K.; Wawer, Maria J.; Gray, Ronald H.] Uganda Virus Res Inst, Rakai Hlth Sci Program, Entebbe, Uganda.
[Sewankambo, Nelson K.] Makerere Univ, Fac Med, Coll Hlth Sci, Kampala, Uganda.
[Tasseneetrithep, Boonrat] Mahidol Univ, Fac Med, Siriraj Hosp, Bangkok 10700, Thailand.
[Wawer, Maria J.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
[Gray, Ronald H.] Johns Hopkins Ctr Global Hlth, Baltimore, MD USA.
[de Souza, Mark S.] Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand.
RP Eller, MA (reprint author), Makerere Univ, Walter Reed Project, Kampala, Uganda.
EM johan.sandberg@ki.se
RI Laeyendecker, Oliver/B-9331-2009;
OI Sewankambo, Nelson/0000-0001-9362-053X; Laeyendecker,
Oliver/0000-0002-6429-4760; Sandberg, Johan/0000-0002-6275-0750
FU National Institute of Allergy and Infectious Diseases (NIAID) [R01
A134826, R01 A134265]; National Institute of Child and Health
Development [5P30HD06826]; Fogarty Foundation [5D43TW00010]; NIH [R01
A134826]
FX Primary support was provided by a cooperative agreement
(W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the
Advancement of Military Medicine, Inc., and the U. S. Department of
Defense. Data collection was supported, in part, by grants R01 A134826
and R01 A134265 from the National Institute of Allergy and Infectious
Diseases (NIAID); grant 5P30HD06826 from the National Institute of Child
and Health Development; grant 5D43TW00010 from the Fogarty Foundation
and NIH grant R01 A134826. Additional support was provided by the
Swedish Research Council, the Swedish Cancer Foundation, the Stockholm
County Council, Karolinska Institutet, and the Division of Intramural
Research, NIAID, NIH. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 49
TC 25
Z9 25
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 APR 19
PY 2011
VL 6
IS 4
AR e18779
DI 10.1371/journal.pone.0018779
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 752EC
UT WOS:000289671100021
PM 21526194
ER
PT J
AU Namiki, T
Tanemura, A
Valencia, JC
Coelho, SG
Passeron, T
Kawaguchi, M
Vieira, WD
Ishikawa, M
Nishijima, W
Izumo, T
Kaneko, Y
Katayama, I
Yamaguchi, Y
Yin, LL
Polley, EC
Liu, HF
Kawakami, Y
Eishi, Y
Takahashi, E
Yokozeki, H
Hearing, VJ
AF Namiki, Takeshi
Tanemura, Atsushi
Valencia, Julio C.
Coelho, Sergio G.
Passeron, Thierry
Kawaguchi, Masakazu
Vieira, Wilfred D.
Ishikawa, Masashi
Nishijima, Wataru
Izumo, Toshiyuki
Kaneko, Yasuhiko
Katayama, Ichiro
Yamaguchi, Yuji
Yin, Lanlan
Polley, Eric C.
Liu, Hongfang
Kawakami, Yutaka
Eishi, Yoshinobu
Takahashi, Eishi
Yokozeki, Hiroo
Hearing, Vincent J.
TI AMP kinase-related kinase NUAK2 affects tumor growth, migration, and
clinical outcome of human melanoma
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE sucrose nonfermenting-like kinase; chromosome 1q
ID GENE-EXPRESSION; MALIGNANT-MELANOMA; SOLID TUMORS; ROC CURVES;
IDENTIFICATION; 1Q; GAINS; TUMORIGENESIS; CANCER; PROLIFERATION
AB The identification of genes that participate in melanomagenesis should suggest strategies for developing therapeutic modalities. We used a public array comparative genomic hybridization (CGH) database and real-time quantitative PCR (qPCR) analyses to identify the AMP kinase (AMPK)-related kinase NUAK2 as a candidate gene for melanomagenesis, and we analyzed its functions in melanoma cells. Our analyses had identified a locus at 1q32 where genomic gain is strongly associated with tumor thickness, and we used real-time qPCR analyses and regression analyses to identify NUAK2 as a candidate gene at that locus. Associations of relapse-free survival and overall survival of 92 primary melanoma patients with NUAK2 expression measured using immunohistochemistry were investigated using Kaplan-Meier curves, log rank tests, and Cox regression models. Knockdown of NUAK2 induces senescence and reduces S-phase, decreases migration, and down-regulates expression of mammalian target of rapamycin (mTOR). In vivo analysis demonstrated that knockdown of NUAK2 suppresses melanoma tumor growth in mice. Survival analysis showed that the risk of relapse is greater in acral melanoma patients with high levels of NUAK2 expression than in acral melanoma patients with low levels of NUAK2 expression (hazard ratio = 3.88; 95% confidence interval = 1.44-10.50; P = 0.0075). These data demonstrate that NUAK2 expression is significantly associated with the oncogenic features of melanoma cells and with the survival of acral melanoma patients. NUAK2 may provide a drug target to suppress melanoma progression. This study further supports the importance of NUAK2 in cancer development and tumor progression, while AMPK has antioncogenic properties.
C1 [Namiki, Takeshi; Valencia, Julio C.; Coelho, Sergio G.; Passeron, Thierry; Kawaguchi, Masakazu; Vieira, Wilfred D.; Yamaguchi, Yuji; Yin, Lanlan; Hearing, Vincent J.] USN Hosp, NCI, Cell Biol Lab, Bethesda, MD 20814 USA.
[Polley, Eric C.] USN Hosp, NCI, Biometr Res Branch, Bethesda, MD 20814 USA.
[Liu, Hongfang] USN Hosp, NCI, Mol Pharmacol Lab, Bethesda, MD 20814 USA.
[Tanemura, Atsushi; Katayama, Ichiro] Osaka Univ, Grad Sch Med, Dept Dermatol, Suita, Osaka 5650871, Japan.
[Ishikawa, Masashi] Saitama Canc Ctr, Dept Dermatol, Kita Adachi, Saitama 3620806, Japan.
[Nishijima, Wataru] Saitama Canc Ctr, Dept Head & Neck Surg, Kita Adachi, Saitama 3620806, Japan.
[Izumo, Toshiyuki] Saitama Canc Ctr, Dept Pathol, Kita Adachi, Saitama 3620806, Japan.
[Kaneko, Yasuhiko] Saitama Canc Ctr, Res Inst Clin Oncol, Kita Adachi, Saitama 3620806, Japan.
[Yamaguchi, Yuji] Nagoya City Univ, Grad Sch Med, Dept Dermatol, Mizuho Ku, Nagoya, Aichi 4678601, Japan.
[Kawakami, Yutaka] Keio Univ, Sch Med, Inst Adv Med Res, Div Cellular Signaling, Tokyo 1608582, Japan.
[Eishi, Yoshinobu] Tokyo Med & Dent Univ, Grad Sch, Dept Pathol, Fac Med,Bunkyo Ku, Tokyo 1130034, Japan.
[Takahashi, Eishi; Yokozeki, Hiroo] Tokyo Med & Dent Univ, Grad Sch, Dept Dermatol, Fac Med,Bunkyo Ku, Tokyo 1130034, Japan.
RP Hearing, VJ (reprint author), USN Hosp, NCI, Cell Biol Lab, Bethesda, MD 20814 USA.
EM hearingv@nih.gov
RI Kawakami, Yutaka /E-7429-2013;
OI Kawakami, Yutaka /0000-0003-4836-2855; Passeron,
Thierry/0000-0002-0797-6570
FU National Cancer Institute at the National Institutes of Health
FX We thank Drs. K. Miura (pathologist), T. Yamanaka (dermatologist), and
K. Nishida, K. Sakamaki, A. Tamura, N. Ando, and C. Miyagishi (Pathology
Staff Members) for their assistance. We also thank D. R. Lowy for
valuable comments and suggestions about the study and Drs. Stuart Yuspa
and Luowei Li for help with the wound-healing assay. We are grateful to
Dr. Richard Simon for his advice and suggestions for improving and
clarifying the manuscript. This work was supported in part by the
Intramural Research Program of the National Cancer Institute at the
National Institutes of Health.
NR 37
TC 20
Z9 20
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 APR 19
PY 2011
VL 108
IS 16
BP 6597
EP 6602
DI 10.1073/pnas.1007694108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 752GV
UT WOS:000289680400054
PM 21460252
ER
PT J
AU Zhou, ZF
Yuan, QP
Mash, DC
Goldman, D
AF Zhou, Zhifeng
Yuan, Qiaoping
Mash, Deborah C.
Goldman, David
TI Substance-specific and shared transcription and epigenetic changes in
the human hippocampus chronically exposed to cocaine and alcohol
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE drug addiction; histone methylation
ID NUCLEUS-ACCUMBENS; MESSENGER-RNA; HUMAN GENOME; EXPRESSION; RECEPTOR;
BRAIN; METABOLISM; PATTERNS; GENE; METHYLATIONS
AB The hippocampus is a key brain region involved in both short- and long-term memory processes and may play critical roles in drug-associated learning and addiction. Using whole genome sequencing of mRNA transcripts (RNA-Seq) and immunoprecipitation-enriched genomic DNA (ChIP-Seq) coupled with histone H3 lysine 4 trimethylation (H3K4me3), we found extensive hippocampal gene expression changes common to both cocaine-addicted and alcoholic individuals that may reflect neuronal adaptations common to both addictions. However, we also observed functional changes that were related only to long-term cocaine exposure, particularly the inhibition of mitochondrial inner membrane functions related to oxidative phosphorylation and energy metabolism, which has also been observed previously in neurodegenerative diseases. Cocaine- and alcohol-related histone H3K4me3 changes highly overlapped, but greater effects were detected under cocaine exposure. There was no direct correlation, however, between either cocaine- or alcohol- related histone H3k4me3 and gene expression changes at an individual gene level, indicating that transcriptional regulation as well as drug-related gene expression changes are outcomes of a complex gene-regulatory process that includes multifaceted histone modifications.
C1 [Zhou, Zhifeng; Yuan, Qiaoping; Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20849 USA.
[Mash, Deborah C.] Univ Miami, Sch Med, Dept Neurol, Miami, FL 33146 USA.
RP Goldman, D (reprint author), NIAAA, Neurogenet Lab, NIH, Rockville, MD 20849 USA.
EM davidgoldman@mail.nih.gov
RI Goldman, David/F-9772-2010
OI Goldman, David/0000-0002-1724-5405
FU Public Health Service [DA06227-18]
FX We thank M.-A. Enoch for critical reading of the manuscript, and E.
Moore for technical support. The acquisition of brain specimens was
supported by Public Health Service Grant DA06227-18.
NR 27
TC 63
Z9 65
U1 3
U2 25
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 APR 19
PY 2011
VL 108
IS 16
BP 6626
EP 6631
DI 10.1073/pnas.1018514108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 752GV
UT WOS:000289680400059
PM 21464311
ER
PT J
AU Park, JW
Piszczek, G
Rhee, SG
Chock, PB
AF Park, Ji Won
Piszczek, Grzegorz
Rhee, Sue Goo
Chock, P. Boon
TI Glutathionylation of Peroxiredoxin I Induces Decamer to Dimers
Dissociation with Concomitant Loss of Chaperone Activity
SO BIOCHEMISTRY
LA English
DT Article
ID PROTEIN S-GLUTATHIONYLATION; 2-CYS PEROXIREDOXIN; MAMMALIAN
PEROXIREDOXIN; SEDIMENTATION-VELOCITY; TYROSINE-PHOSPHATASE;
SIGNAL-TRANSDUCTION; REDUCE PEROXIDES; PHOSPHORYLATION; CELLS; H2O2
AB Reversible protein glutathionylation, a redox-sensitive regulatory mechanism, plays a key role in cellular regulation and cell signaling. Peroxiredoxins (Prxs), a family of peroxidases that is involved in removing H2O2 and organic hydroperoxides, are known to undergo a functional change from peroxidase to molecular chaperone upon overoxidation of its catalytic cysteine. The functional change is caused by a structural change from low molecular weight oligomers to high molecular weight complexes that possess molecular chaperone activity. We reported earlier that Prx I can be glutathionylated at three of its cysteine residues, Cys52, -83, and -173 [Park et al. et al. (2009) J. Biol. Chem., 284, 23364]. In this study, using analytical ultracentrifugation analysis, we reveal that glutathionylation of Prx WT, or its C52S/C173S double mutant shifted its oligomeric status from decamers to a population consisting mainly of dimers. Cys83 is localized at the putative dimer-dimer interface, implying that the redox status of Cys83 may play an important role in stabilizing the oligomeric state of Prx I. Studies with the Prx I (C83S) mutant show that while Cys83 is not essential for the formation of high molecular weight complexes, it affects the dimer-decamer equilibrium. Glutathionylation of the C83S mutant leads to accumulation of dimers and monomers. In addition, glutathionylation of Prx I, both the WT and C52S/C173S mutants, greatly reduces their molecular chaperone activity in protecting citrate synthase from thermally induced aggregation. Together, these results reveal that glutathionylation of Prx I promotes changes in its quaternary structure from decamers to smaller oligomers and concomitantly inactivates its molecular chaperone function.
C1 [Park, Ji Won; Rhee, Sue Goo] Ewha Womans Univ, Div Life & Pharmaceut Sci, Seoul 120750, South Korea.
[Park, Ji Won; Piszczek, Grzegorz; Chock, P. Boon] NHLBI, Biochem Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
RP Rhee, SG (reprint author), Ewha Womans Univ, Div Life & Pharmaceut Sci, Seoul 120750, South Korea.
EM rheesg@ewha.ac.kr; chockp@mail.nih.gov
FU NIH, NHLBI; Brain Korea 21 grant; Korea Science and Engineering
Foundation
FX This research was supported by the Intramural Research Program of the
NIH, NHLBI. This study was also supported in part by a Brain Korea 21
grant (to J.W.P.) and by BioR and D Program grants from the Korea
Science and Engineering Foundation (to S.G.R.).
NR 36
TC 39
Z9 39
U1 0
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD APR 19
PY 2011
VL 50
IS 15
BP 3204
EP 3210
DI 10.1021/bi101373h
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 747KW
UT WOS:000289319700016
PM 21401077
ER
PT J
AU Guo, X
Chen, QR
Song, YK
Wei, JS
Khan, J
AF Guo, Xiang
Chen, Qing-Rong
Song, Young K.
Wei, Jun S.
Khan, Javed
TI Exon array analysis reveals neuroblastoma tumors have distinct
alternative splicing patterns according to stage and MYCN amplification
status
SO BMC MEDICAL GENOMICS
LA English
DT Article
ID PYRUVATE-KINASE; EXPRESSION ARRAYS; PROSTATE-CANCER; GLOBAL ANALYSIS;
GROWTH; IDENTIFICATION; M2; MICROARRAYS; PROGRESSION; METABOLISM
AB Background: Neuroblastoma (NB) tumors are well known for their pronounced clinical and molecular heterogeneity. The global gene expression and DNA copy number alterations have been shown to have profound differences in tumors of low or high stage and those with or without MYCN amplification. RNA splicing is an important regulatory mechanism of gene expression, and differential RNA splicing may be associated with the clinical behavior of a tumor.
Methods: In this study, we used exon array profiling to investigate global alternative splicing pattern of 47 neuroblastoma samples in stage 1 and stage 4 with normal or amplified MYCN copy number (stage 1-, 4- and 4+). The ratio of exon-level expression to gene-level expression was used to detect alternative splicing events, while the gene-level expression was applied to characterize whole gene expression change.
Results: Principal component analysis (PCA) demonstrated distinct splicing pattern in three groups of samples. Pairwise comparison identified genes with splicing changes and/or whole gene expression changes in high stage tumors. In stage 4- compared with stage 1- tumors, alternatively spliced candidate genes had little overlap with genes showing whole gene expression changes, and most of them were involved in different biological processes. In contrast, a larger number of genes exhibited either exon-level splicing, gene-level expression or both changes in stage 4+ versus stage 1- tumors. Those biological processes involved in stage 4- tumors were disrupted to a greater extent by both splicing and transcription regulations in stage 4+ tumors.
Conclusions: Our results demonstrated a significant role of alternative splicing in high stage neuroblastoma, and suggested a MYCN-associated splicing regulation pathway in stage 4+ tumors. The identification of differentially spliced genes and pathways in neuroblastoma tumors of different stages and molecular subtypes may be important to the understanding of cancer biology and the discovery of diagnostic markers or therapeutic targets in neuroblastoma.
C1 [Guo, Xiang; Chen, Qing-Rong; Song, Young K.; Wei, Jun S.; Khan, Javed] NCI, Oncogen Sect, Pediat Oncol Branch, NIH, Gaithersburg, MD 20877 USA.
[Guo, Xiang] NCI, Adv Biomed Comp Ctr, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Khan, J (reprint author), NCI, Oncogen Sect, Pediat Oncol Branch, NIH, Gaithersburg, MD 20877 USA.
EM khanjav@mail.nih.gov
RI Khan, Javed/P-9157-2014
OI Khan, Javed/0000-0002-5858-0488
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research. We thank
Drs. John Maris, Wendy London of the Children's Oncology Group (COG),
Steven Qualman of the Cooperative Human Tissue Network (CHTN), Daniel
Catchpoole at the Children's Hospital at Westmead, Australia, Frank
Westermann, Manfred Schwab of German Cancer Research Center and Frank
Berthold, University of Cologne, Germany for the tumor samples and
patient demographic information. We thank Xinyu Wen and Jianbin He for
their technical assistance in exon array database development. We also
thank Drs. Shahab Asgharzadeh and Robert Seeger for the helpful
discussions.
NR 42
TC 14
Z9 14
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1755-8794
J9 BMC MED GENOMICS
JI BMC Med. Genomics
PD APR 18
PY 2011
VL 4
AR 35
DI 10.1186/1755-8794-4-35
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 766SA
UT WOS:000290805600001
PM 21501490
ER
PT J
AU Salmon, DJ
de Holding, CLT
Thomas, L
Peterson, KV
Goodman, GP
Saayedra, JE
Srinivasan, A
Davies, KM
Keefer, LK
Miranda, KM
AF Salmon, Debra J.
de Holding, Claudia L. Torres
Thomas, Lynta
Peterson, Kyle V.
Goodman, Gens P.
Saayedra, Joseph E.
Srinivasan, Aloka
Davies, Keith M.
Keefer, Larry K.
Miranda, Katrina M.
TI HNO and NO Release from a Primary Amine-Based Diazeniumdiolate As a
Function of pH
SO INORGANIC CHEMISTRY
LA English
DT Article
ID NITRIC-OXIDE NO; AQUEOUS-SOLUTION; NITROXYL HNO; ANGELIS SALT; DEPENDENT
DECOMPOSITION; CARDIOVASCULAR-SYSTEM; IN-VIVO; CHEMISTRY; MECHANISM;
KINETICS
AB The growing evidence that nitroxyl (HNO) has a rich pharmacological potential that differs from that of nitric oxide (NO) has intensified interest in HNO donors. Recently, Recently, the diazeniumdiolate (NONOate) based on isopropylamine (IPA/NO; Na[(CH3)(2)CHNH(N(O)NO)]) was demonstrated to function under physiological conditions as an organic analogue to the commonly used HNO donor Angeli's salt (Na2N2O3). The decomposition mechanism of Angeli's salt is dependent on pH, with transition from an HNO to an NO donor occurring abruptly near pH 3. Here, pH is shown to also affect product formation from IPA/NO. Chemical analysis of HNO and NO production led to refinement of an earlier, quantum mechanically based prediction of the pH-dependent decomposition mechanisms of primary amine NONOates such as IPA/NO. Under basic conditions, the amine proton of IPA/NO is able to initiate decomposition to HNO by tautomerization to the nitroso nitrogen (N-2). At lower pH, protonation activates a competing pathway to NO production. At pH 8, the donor properties of IPA/NO and Angeli's salt are demonstrated to be comparable, suggesting that at or above this pH, IPA/NO is primarily an HNO donor. Below pH 5, NO is the major product, while IPA/NO functions as a dual donor of HNO and NO at intermediate pH. This pH-dependent variability in product formation may prove useful in examination of the chemistry of NO and HNO. Furthermore, primary amine NONOates may serve as a tunable class of nitrogen oxide donor.
C1 [Salmon, Debra J.; de Holding, Claudia L. Torres; Thomas, Lynta; Peterson, Kyle V.; Goodman, Gens P.; Miranda, Katrina M.] Univ Arizona, Dept Chem & Biochem, Tucson, AZ 85721 USA.
[Saayedra, Joseph E.] NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA.
[Srinivasan, Aloka; Keefer, Larry K.] NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA.
[Davies, Keith M.] George Mason Univ, Dept Chem, Fairfax, VA 22030 USA.
RP Miranda, KM (reprint author), Univ Arizona, Dept Chem & Biochem, Tucson, AZ 85721 USA.
EM kmiranda@email.arizona.edu
RI Miranda, Katrina/B-7823-2009; Keefer, Larry/N-3247-2014
OI Keefer, Larry/0000-0001-7489-9555
FU National Institutes of Health [R01-GM076247, 1F31AA018069-01A1];
National Cancer Institute [HHSN261200800001E]; NIH, National Cancer
Institute, Center for Cancer Research
FX This work was supported by the National Institutes of Health
(R01-GM076247 to K.M.M.; 1F31AA018069-01A1 to D.J.S.), by the National
Cancer Institute under contract HHSN261200800001E, and by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research. We thank Gail Willette (UA) for technical assistance.
NR 50
TC 33
Z9 33
U1 0
U2 18
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0020-1669
J9 INORG CHEM
JI Inorg. Chem.
PD APR 18
PY 2011
VL 50
IS 8
BP 3262
EP 3270
DI 10.1021/ic101736e
PG 9
WC Chemistry, Inorganic & Nuclear
SC Chemistry
GA 762FA
UT WOS:000290457700015
PM 21405089
ER
PT J
AU Crea, F
Hurt, EM
Mathews, LA
Cabarcas, SM
Sun, L
Marquez, VE
Danesi, R
Farrar, WL
AF Crea, Francesco
Hurt, Elaine M.
Mathews, Lesley A.
Cabarcas, Stephanie M.
Sun, Lei
Marquez, Victor E.
Danesi, Romano
Farrar, William L.
TI Pharmacologic disruption of Polycomb Repressive Complex 2 inhibits
tumorigenicity and tumor progression in prostate cancer
SO MOLECULAR CANCER
LA English
DT Article
ID EPITHELIAL-MESENCHYMAL TRANSITION; GROUP PROTEIN EZH2; STEM-CELLS;
E-CADHERIN; METASTASIS; GROWTH; ROLES; DNA
AB Background: Polycomb repressive complex 2 (PRC2) mediates gene silencing through histone H3K27 methylation. PRC2 components are over-expressed in metastatic prostate cancer (PC), and are required for cancer stem cell (CSC) self-renewal. 3-Dezaneplanocin-A (DZNeP) is an inhibitor of PRC2 with broad anticancer activity.
Method: we investigated the effects of DZNeP on cell proliferation, tumorigenicity and invasive potential of PC cell lines (LNCaP and DU145).
Results: Exploring GEO and Oncomine databases, we found that specific PRC2 genes (EED, EZH2, SUZ12) predict poor prognosis in PC. Non-toxic DZNeP concentrations completely eradicated LNCaP and DU145 prostatosphere formation, and significantly reduced the expression of CSC markers. At comparable doses, other epigenetic drugs were not able to eradicate CSCs. DZNeP was also able to reduce PC cell invasion. Cells pre-treated with DZNeP were significantly less tumorigenic (LNCaP) and formed smaller tumors (DU145) in immunocompromised mice.
Conclusion: DZNeP is effective both in vitro and in vivo against PC cells. DZNeP antitumor activity is in part mediated by inhibition of CSC tumorigenic potential.
C1 [Crea, Francesco; Mathews, Lesley A.; Cabarcas, Stephanie M.; Sun, Lei; Farrar, William L.] NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21701 USA.
[Hurt, Elaine M.] Medimmune Inc, Gaithersburg, MD 20878 USA.
[Marquez, Victor E.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21701 USA.
[Danesi, Romano] Pisa Med Sch, Div Pharmacol, Dept Internal Med, Pisa, Italy.
RP Farrar, WL (reprint author), NCI, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21701 USA.
EM farrarw@mail.nih.gov
RI Sun, Lei/N-8847-2014; Crea, Francesco /I-8383-2015; Sun,
Lei/J-9943-2015;
OI Crea, Francesco/0000-0002-4903-2973
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001F]; NIH, National Cancer Institute, Center for Cancer
Research
FX This publication has been funded in part with Federal funds from the
National Cancer Institute, National Institutes of Health, under contract
No HHSN261200800001F. 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 US Government
NR 40
TC 81
Z9 85
U1 1
U2 11
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 APR 18
PY 2011
VL 10
AR 40
DI 10.1186/1476-4598-10-40
PG 10
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 767OF
UT WOS:000290865200001
PM 21501485
ER
PT J
AU Castiello, L
Stroncek, DF
Finn, MW
Wang, E
Marincola, FM
Clayberger, C
Krensky, AM
Sabatino, M
AF Castiello, Luciano
Stroncek, David F.
Finn, Michael W.
Wang, Ena
Marincola, Francesco M.
Clayberger, Carol
Krensky, Alan M.
Sabatino, Marianna
TI 15 kDa Granulysin versus GM-CSF for monocytes differentiation: analogies
and differences at the transcriptome level
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
ID COLONY-STIMULATING FACTOR; HUMAN DENDRITIC CELLS; T-CELLS; EXPRESSION;
RECEPTORS; SURVIVAL; ANTIGEN; GAMMA; ACTIVATION; MICROARRAY
AB Background: Granulysin is an antimicrobial and proinflammatory protein with several isoforms. While the 9 kDa isoform is a well described cytolytic molecule with pro-inflammatory activity, the functions of the 15 kDa isoform is less well understood. Recently it was shown that 15 kDa Granulysin can act as an alarmin that is able to activate monocytes and immature dendritic cells. Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) is a growth factor widely used in immunotherapy both for in vivo and ex vivo applications, especially for its proliferative effects.
Methods: We analyzed gene expression profiles of monocytes cultured with 15 kDa Granulysin or GM-CSF for 4, 12, 24 and 48 hours to unravel both similarities and differences between the effects of these stimulators.
Results: The analysis revealed a common signature induced by both factors at each time point, but over time, a more specific signature for each factor became evident. At all time points, 15 kDa Granulysin induced immune response, chemotaxis and cell adhesion genes. In addition, only 15 kDa Granulsyin induced the activation of pathways related to fundamental dendritic cell functions, such as co-stimulation of T-cell activation and Th1 development. GM-CSF specifically down-regulated genes related to cell cycle arrest and the immune response. More specifically, cytokine production, lymphocyte mediated immunity and humoral immune response were down-regulated at late time points.
Conclusion: This study provides important insights on the effects of a novel agent, 15 kDa granulysin, that holds promise for therapeutic applications aimed at the activation of the immune response.
C1 [Castiello, Luciano; Stroncek, David F.; Sabatino, Marianna] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Finn, Michael W.; Clayberger, Carol; Krensky, Alan M.] NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Wang, Ena; Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Wang, Ena; Marincola, Francesco M.] NIH, CHI, Bethesda, MD 20892 USA.
RP Stroncek, DF (reprint author), NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM DStroncek@cc.nih.gov
RI Castiello, Luciano/K-8616-2016
OI Castiello, Luciano/0000-0001-7146-3158
FU National Institutes of Health Clinical Center; National Cancer Institute
FX This work is supported by the Intramural Programs of the National
Institutes of Health Clinical Center and National Cancer Institute.
NR 55
TC 4
Z9 4
U1 0
U2 1
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 APR 18
PY 2011
VL 9
AR 41
DI 10.1186/1479-5876-9-41
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 762AJ
UT WOS:000290444300001
PM 21501511
ER
PT J
AU Zhang, SC
Yajima, H
Huynh, H
Zheng, JK
Callen, E
Chen, HT
Wong, N
Bunting, S
Lin, YF
Li, MX
Lee, KJ
Story, M
Gapud, E
Sleckman, BP
Nussenzweig, A
Zhang, CC
Chen, DJ
Chen, BPC
AF Zhang, Shichuan
Yajima, Hirohiko
Huynh, HoangDinh
Zheng, Junke
Callen, Elsa
Chen, Hua-Tang
Wong, Nancy
Bunting, Samuel
Lin, Yu-Fen
Li, Mengxia
Lee, Kyung-Jone
Story, Michael
Gapud, Eric
Sleckman, Barry P.
Nussenzweig, Andre
Zhang, Cheng Cheng
Chen, David J.
Chen, Benjamin P. C.
TI Congenital bone marrow failure in DNA-PKcs mutant mice associated with
deficiencies in DNA repair
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID DEPENDENT PROTEIN-KINASE; HEMATOPOIETIC STEM-CELLS; DOUBLE-STRAND
BREAKS; FANCONI ANEMIA/BRCA PATHWAY; CROSS-LINK REPAIR; CATALYTIC
SUBUNIT; HOMOLOGOUS RECOMBINATION; V(D)J RECOMBINATION; PHOSPHORYLATION
SITES; MAMMALIAN-CELLS
AB The nonhomologous end-joining (NHEJ) pathway is essential for radioresistance and lymphocyte-specific V(D)J (variable [diversity] joining) recombination. Defects in NHEJ also impair hematopoietic stem cell (HSC) activity with age but do not affect the initial establishment of HSC reserves. In this paper, we report that, in contrast to deoxyribonucleic acid (DNA)-dependent protein kinase catalytic subunit (DNA-PKcs)-null mice, knockin mice with the DNA-PKcs(3A/3A) allele, which codes for three alanine substitutions at the mouse Thr2605 phosphorylation cluster, die prematurely because of congenital bone marrow failure. Impaired proliferation of DNA-PKcs(3A/3A) HSCs is caused by excessive DNA damage and p53-dependent apoptosis. In addition, increased apoptosis in the intestinal crypt and epidermal hyperpigmentation indicate the presence of elevated genotoxic stress and p53 activation. Analysis of embryonic fibroblasts further reveals that DNA-PKcs(3A/3A) cells are hypersensitive to DNA cross-linking agents and are defective in both homologous recombination and the Fanconi anemia DNA damage response pathways. We conclude that phosphorylation of DNA-PKcs is essential for the normal activation of multiple DNA repair pathways, which in turn is critical for the maintenance of diverse populations of tissue stem cells in mice.
C1 [Zhang, Shichuan; Yajima, Hirohiko; Lin, Yu-Fen; Li, Mengxia; Lee, Kyung-Jone; Story, Michael; Chen, David J.; Chen, Benjamin P. C.] Univ Texas SW Med Ctr Dallas, Div Mol Radiat Biol, Dept Radiat Oncol, Dallas, TX 75390 USA.
[Huynh, HoangDinh; Zheng, Junke; Zhang, Cheng Cheng] Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75390 USA.
[Callen, Elsa; Chen, Hua-Tang; Wong, Nancy; Bunting, Samuel; Nussenzweig, Andre] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Gapud, Eric; Sleckman, Barry P.] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63110 USA.
RP Chen, BPC (reprint author), Univ Texas SW Med Ctr Dallas, Div Mol Radiat Biol, Dept Radiat Oncol, Dallas, TX 75390 USA.
EM benjamin.chen@utsouthwestern.edu
RI Lin, Yu-Fen/A-2570-2016
FU National Aeronautics and Space Administration [NNX07AP84G]; National
Institutes of Health [CA50519, CA120099]; Michael. L. Rosenberg Endowed
Scholar Fund; American Cancer Society; American Society of Hematology;
Robert A. Welch Foundation; March of Dimes Foundation
FX B. P. C. Chen is supported by National Aeronautics and Space
Administration grant NNX07AP84G, D.J. Chen is supported by National
Institutes of Health grant CA50519, and C. C. Zhang is supported by
National Institutes of Health grant CA120099, the Michael. L. Rosenberg
Endowed Scholar Fund, the American Cancer Society, the American Society
of Hematology Junior Faculty Award, the Robert A. Welch Foundation, and
the Basil O'Connor Starter Scholar Award from the March of Dimes
Foundation.
NR 56
TC 56
Z9 57
U1 0
U2 0
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD APR 18
PY 2011
VL 193
IS 2
BP 295
EP 305
DI 10.1083/jcb.201009074
PG 11
WC Cell Biology
SC Cell Biology
GA 752ES
UT WOS:000289673000007
PM 21482716
ER
PT J
AU Brown, LM
Hansen, CT
Huberty, AF
Castonguay, TW
AF Brown, Lynda M.
Hansen, Carl T.
Huberty, Andrea F.
Castonguay, T. W.
TI Traits of the metabolic syndrome alter corpulent obesity in LAN, SHR and
DSS rats: Behavioral and metabolic interactions with adrenalectomy
SO PHYSIOLOGY & BEHAVIOR
LA English
DT Article
DE Obesity; Hypothalamic-pituitary-adrenal axis; Corticosterone; Strain
differences; Leptin; Neuropeptide Y
ID MONA-LISA HYPOTHESIS; SALT-RESISTANT RATS; BODY-WEIGHT; DIETARY OBESITY;
FOOD-INTAKE; DB/DB MICE; LA/N-CP; STRAIN; LEPTIN; RESPONSES
AB Obesity results from a complex interaction of genes with environmental factors. Our experimental design compared obesity in three rat strains with the corpulent (cp) mutation. The three strains included Lister and Albany NIH (LAN) rats, Spontaneously Hypertensive Rats (SHR) and Dahl Salt Sensitive (DSS) rats that were congenically bred. The strains were selected because of different reported metabolic complications generally clustered with obesity, and defined as the metabolic syndrome. Body weight, food intake, carcass composition, plasma hormones and hypothalamic expression of Y5 receptors were assessed in obese (cp) and lean (wt) rats after adrenalectomy (ADX) or sham surgeries. Plasma corticosterone in sham-operated wtDSS and cpDSS were significantly higher (approx. 165 ng/ml) than that in cpLAN and cpSHR (similar to 77 and 68 ng/ml respectively). All cp groups had a higher % carcass fat than wt groups. The % carcass fat was greater in cpDSS > cpLAN > cpSHR but plasma leptin was greatest in cpLAN > cpSHR > cpDSS. Hypothalamic expression of the Y5R after ADX resulted in a phenotype x surgery interaction since Y5R expression was slightly increased in cp rats and slightly decreased in wt rats. The strain with greatest number of metabolic syndrome traits, SHR, was not the fattest of the strains and had little response to ADX. The strains with fewer metabolic syndrome traits LAN and DSS had more extreme obesities which were attenuated after ADX. The results of the current experiment provide evidence that the corpulent mutation is not fully characterized in one strain. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Brown, Lynda M.] Univ N Carolina, Dept Nutr, Greensboro, NC 27402 USA.
[Hansen, Carl T.] NIH, Div Vet Resources, Bethesda, MD 20892 USA.
[Huberty, Andrea F.] Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA.
[Castonguay, T. W.] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA.
RP Brown, LM (reprint author), Univ N Carolina, Dept Nutr, POB 26170, Greensboro, NC 27402 USA.
EM lmbrown6@uncg.edu
OI Castonguay, Thomas/0000-0003-1176-5095
NR 48
TC 1
Z9 1
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0031-9384
J9 PHYSIOL BEHAV
JI Physiol. Behav.
PD APR 18
PY 2011
VL 103
IS 1
SI SI
BP 98
EP 103
DI 10.1016/j.physbeh.2010.12.020
PG 6
WC Psychology, Biological; Behavioral Sciences
SC Psychology; Behavioral Sciences
GA 749VR
UT WOS:000289499800016
PM 21199663
ER
PT J
AU Bevans, MF
Mitchell, SA
Barrett, AJ
Bishop, M
Childs, R
Fowler, D
Krumlauf, M
Prince, P
Shelburne, N
Wehrlen, L
AF Bevans, Margaret F.
Mitchell, Sandra A.
Barrett, A. John
Bishop, Michael
Childs, Richard
Fowler, Daniel
Krumlauf, Michael
Prince, Patricia
Shelburne, Nonniekaye
Wehrlen, Leslie
TI Function, Adjustment, Quality of Life and Symptoms (FAQS) in Allogeneic
Hematopoietic Stem Cell Transplantation (HSCT) Survivors: A Study
Protocol
SO HEALTH AND QUALITY OF LIFE OUTCOMES
LA English
DT Article
ID BONE-MARROW-TRANSPLANTATION; LONG-TERM SURVIVORS; CHRONIC
MYELOID-LEUKEMIA; BENIGN PROSTATIC HYPERPLASIA; ACUTE MYELOGENOUS
LEUKEMIA; CUBAN-AMERICAN POPULATION; VERSUS-HOST-DISEASE; SF-36 HEALTH
SURVEY; ADULT SURVIVORS; SPANISH VERSION
AB Background: The population of survivors following allogeneic HSCT continues to increase, and yet their experiences of recovery and long-term survivorship have not been fully characterized. This paper presents a study protocol examining over time the functional status, psychosocial adjustment, health-related quality of life, and symptom experience of survivors who have undergone allogeneic transplantation. The aims of the study are to: 1) explore the patterns of change in these health outcomes during the survivorship phase; 2) characterize subgroups of survivors experiencing adverse outcomes; and 3) examine relationships among outcomes and demographic and clinical factors (such as age, graft-versus-host disease (GVHD), and disease relapse).
Methods: In this longitudinal observational study, adults who survive a minimum of 3 years from date of allogeneic transplantation complete a series of questionnaires annually. Demographic and clinical data are collected along with a series of patient-reported outcome measures, specifically: 1) Medical Outcomes Study SF-36; 2) Functional Assessment of Chronic Illness Therapy (FACIT) - General, 3) FACIT-Fatigue; 4) FACIT-Spiritual; 5) Psychosocial Adjustment to Illness Scale; 6) Rotterdam Symptom Checklist-Revised; and 7) Pittsburgh Sleep Quality Index.
Conclusions: This study will provide multidimensional patient-reported outcomes data to expand the understanding of the survivorship experience across the trajectory of allogeneic transplantation recovery. There are a number of inherent challenges in recruiting and retaining a diverse and representative sample of long-term transplant survivors. Study results will contribute to an understanding of outcomes experienced by transplant survivors, including those with chronic GVHD, malignant disease relapse, and other late effects following allogeneic transplantation.
C1 [Bevans, Margaret F.; Krumlauf, Michael; Prince, Patricia; Wehrlen, Leslie] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Mitchell, Sandra A.; Bishop, Michael; Fowler, Daniel; Shelburne, Nonniekaye] NCI, NIH, Bethesda, MD 20892 USA.
[Barrett, A. John; Childs, Richard] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Bevans, MF (reprint author), NIH, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM mbevans@cc.nih.gov
FU NIH Clinical Center
FX Funding for this study was provided by the NIH Clinical Center
Intramural Research Program.
NR 90
TC 9
Z9 9
U1 3
U2 6
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 APR 17
PY 2011
VL 9
AR 24
DI 10.1186/1477-7525-9-24
PG 9
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 768EL
UT WOS:000290914200001
PM 21496339
ER
PT J
AU Kotin, RM
AF Kotin, Robert M.
TI Large-scale recombinant adeno-associated virus production
SO HUMAN MOLECULAR GENETICS
LA English
DT Review
ID ADENO-ASSOCIATED VIRUS; ION-EXCHANGE CHROMATOGRAPHY; BACULOVIRUS
EXPRESSION SYSTEM; VIRAL VECTOR PRODUCTION; SERUM-FREE PRODUCTION;
DNA-BINDING PROTEIN; HIGH-TITER; INSECT CELLS; INFECTED-CELLS; COLUMN
CHROMATOGRAPHY
AB Since recombinant adeno-associated virus (rAAV) was first described as a potential mammalian cell transducing system, frequent reports purportedly solving the problems of scalable production have appeared. Yet few of these processes have enabled the development of robust and economical rAAV production. Two production platforms have emerged that have gained broad support for producing both research and clinical grade vectors. These processes differ fundamentally in several aspects. One approach is based on adherent mammalian cells and uses optimized chemical transient transfection for introducing the essential genetic components into the cells. The other approach utilizes suspension cultures of invertebrate cells. Baculovirus expression vectors are used for introducing the AAV genes into the cells. In addition, the baculovirus provides the helper functions necessary for efficient AAV DNA replication. The use of suspension cell culture provides an intrinsically more scalable platform system than using adherent cells. The upstream processes for suspension cultures are amenable for automation and are easily monitored and regulated to maintain optimum conditions that produce consistent yields of rAAV. Issues relating to developing new and improving existing rAAV production methods are discussed.
C1 NHLBI, Lab Mol Virol & Gene Therapy, Ctr Dev Biol & Genet, NIH, Bethesda, MD 20892 USA.
RP Kotin, RM (reprint author), NHLBI, Lab Mol Virol & Gene Therapy, Ctr Dev Biol & Genet, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM kotinr@nhlbi.nih.gov
FU National Institutes of Health, National Heart, Lung, and Blood
Institute, Division of Intramural Research [1ZIAHL002237-16];
International Collaborative Effort (ICE) for Duchenne Muscular
Dystrophy; Association Monogasque contra les Myopathies; NIH
FX This work was supported by the National Institutes of Health, National
Heart, Lung, and Blood Institute, Division of Intramural Research
(1ZIAHL002237-16). Additional funding was provided by the International
Collaborative Effort (ICE) for Duchenne Muscular Dystrophy comprised of
the French Duchenne Parent Project and the Association Monogasque contra
les Myopathies.; Conflict of Interest statement. Portions of the
technology described in this report are covered by United States and
European patents assigned to the Secretary of the Department of Health
and Human Services. A fraction of the licensing fees and royalty
payments made to the NIH are distributed to the inventors in accordance
with US Government and NIH policy.
NR 56
TC 38
Z9 38
U1 0
U2 7
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 APR 15
PY 2011
VL 20
SI 1
BP R2
EP R6
DI 10.1093/hmg/ddr141
PG 5
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 763VG
UT WOS:000290587200002
PM 21531790
ER
PT J
AU Ramsden, CE
Mann, JD
Faurot, KR
Lynch, C
Imam, ST
MacIntosh, BA
Hibbeln, JR
Loewke, J
Smith, S
Coble, R
Suchindran, C
Gaylord, SA
AF Ramsden, Christopher E.
Mann, J. Douglas
Faurot, Keturah R.
Lynch, Chanee
Imam, Syed Taha
MacIntosh, Beth A.
Hibbeln, Joseph R.
Loewke, James
Smith, Sunyata
Coble, Rebecca
Suchindran, Chirayath
Gaylord, Susan A.
TI Low omega-6 vs. low omega-6 plus high omega-3 dietary intervention for
Chronic Daily Headache: Protocol for a randomized clinical trial
SO TRIALS
LA English
DT Article
ID FATTY-ACID-COMPOSITION; ADIPOSE-TISSUE COMPOSITION; HUMAN DEPOT FAT;
ARACHIDONIC-ACID; IN-VIVO; MIGRAINE DISABILITY; PSYCHOMETRIC PROPERTIES;
PATIENT EXPECTATIONS; POPULATION-SAMPLE; NMDA RECEPTORS
AB Background: Targeted analgesic dietary interventions are a promising strategy for alleviating pain and improving quality of life in patients with persistent pain syndromes, such as chronic daily headache (CDH). High intakes of the omega-6 (n-6) polyunsaturated fatty acids (PUFAs), linoleic acid (LA) and arachidonic acid (AA) may promote physical pain by increasing the abundance, and subsequent metabolism, of LA and AA in immune and nervous system tissues. Here we describe methodology for an ongoing randomized clinical trial comparing the metabolic and clinical effects of a low n-6, average n-3 PUFA diet, to the effects of a low n-6 plus high n-3 PUFA diet, in patients with CDH. Our primary aim is to determine if: A) both diets reduce n-6 PUFAs in plasma and erythrocyte lipid pools, compared to baseline; and B) the low n-6 plus high n-3 diet produces a greater decline in n-6 PUFAs, compared to the low n-6 diet alone. Secondary clinical outcomes include headache-specific quality-of-life, and headache frequency and intensity.
Methods: Adults meeting the International Classification of Headache Disorders criteria for CDH are included. After a 6-week baseline phase, participants are randomized to a low n-6 diet, or a low n-6 plus high n-3 diet, for 12 weeks. Foods meeting nutrient intake targets are provided for 2 meals and 2 snacks per day. A research dietitian provides intensive dietary counseling at 2-week intervals. Web-based intervention materials complement dietitian advice. Blood and clinical outcome data are collected every 4 weeks.
Results: Subject recruitment and retention has been excellent; 35 of 40 randomized participants completed the 12-week intervention. Preliminary blinded analysis of composite data from the first 20 participants found significant reductions in erythrocyte n-6 LA, AA and % n-6 in HUFA, and increases in n-3 EPA, DHA and the omega-3 index, indicating adherence.
C1 [Ramsden, Christopher E.; Hibbeln, Joseph R.; Loewke, James] NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA.
[Mann, J. Douglas] Univ N Carolina, Sch Med, Dept Neurol, Chapel Hill, NC 27599 USA.
[Ramsden, Christopher E.; Faurot, Keturah R.; Lynch, Chanee; Imam, Syed Taha; Smith, Sunyata; Coble, Rebecca; Gaylord, Susan A.] Univ N Carolina, Sch Med, Program Integrat Med, Dept Phys Med & Rehabil, Chapel Hill, NC USA.
[MacIntosh, Beth A.] Univ N Carolina, N Carolina Translat & Clin Sci Inst, Chapel Hill, NC USA.
[Suchindran, Chirayath] Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA.
RP Ramsden, CE (reprint author), NIAAA, Sect Nutr Neurosci, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA.
EM chris.ramsden@nih.gov
FU Mayday Fund; UNC (NCCAM, NIH) [T32-AT003378]; North Carolina Clinical
and Translational Sciences Institute (NCRR, NIH) [UL1RR025747]; UNC
Nutrition Obesity Research Center (NIDDK, NIH) [DK056350]; National
Headache Foundation; National Institute on Alcohol Abuse and Alcoholism,
NIH
FX The authors gratefully acknowledge funding support for this trial from
the Mayday Fund (primary source); the UNC Research Fellowship in
Complementary and Alternative Medicine (grant T32-AT003378, NCCAM, NIH);
the North Carolina Clinical and Translational Sciences Institute (grant
UL1RR025747, NCRR, NIH); the UNC Nutrition Obesity Research Center, CHAI
Core (grant DK056350, NIDDK, NIH); the National Headache Foundation
(pilot grant for inflammatory gene expression); and the National
Institute on Alcohol Abuse and Alcoholism, NIH. Its contents are solely
the responsibility of the authors and do not necessarily represent the
official views of the Mayday Fund, National Headache Foundation, or the
National Institutes of Health.
NR 59
TC 20
Z9 20
U1 0
U2 13
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6215
J9 TRIALS
JI Trials
PD APR 15
PY 2011
VL 12
AR 97
DI 10.1186/1745-6215-12-97
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 765TN
UT WOS:000290731600001
PM 21496264
ER
PT J
AU Kim, HY
Moon, HS
Cao, DH
Lee, J
Kevala, K
Jun, SB
Lovinger, DM
Akbar, M
Huang, BX
AF Kim, Hee-Yong
Moon, Hyun-Seuk
Cao, Dehua
Lee, Jeongrim
Kevala, Karl
Jun, Sang Beom
Lovinger, David M.
Akbar, Mohammed
Huang, Bill X.
TI N-Docosahexaenoylethanolamide promotes development of hippocampal
neurons
SO BIOCHEMICAL JOURNAL
LA English
DT Article
DE docosahexaenoic acid (DHA); N-docosahexaenoylethanolamide (DEA);
hippocampus; neurite growth; neuron; synaptogenesis
ID POLYUNSATURATED FATTY-ACIDS; DOCOSAHEXAENOIC ACID; ENDOCANNABINOID
ANANDAMIDE; CANNABINOID RECEPTOR; RAT-BRAIN; IDENTIFICATION;
NEUROGENESIS; PERFORMANCE; PREGNANCY; PATHWAY
AB DHA (docosahexaenoic acid, C(22:6,n-3)) has been shown to promote neurite growth and synaptogenesis in embryonic hippocampal neurons, supporting the importance of DHA known for hippocampus-related learning and memory function. In the present study, we demonstrate that DHA metabolism to DEA (N-docosahexaenoylethanolamide) is a significant mechanism for hippocampal neuronal development, contributing to synaptic function. We found that a fatty acid amide hydrolase inhibitor URB597 potentiates DHA-induced neurite growth, synaptogenesis and synaptic protein expression. Active metabolism of DHA to DEA was observed in embryonic day 18 hippocampal neuronal cultures, which was increased further by URB597. Synthetic DEA promoted hippocampal neurite growth and synaptogenesis at substantially lower concentrations in comparison with DHA. DEA-treated neurons increased the expression of synapsins and glutamate receptor subunits and exhibited enhanced glutamatergic synaptic activity, as was the case for DHA. The DEA level in mouse fetal hippocampi was altered according to the maternal dietary supply of n-3 fatty acids, suggesting that DEA formation is a relevant in vivo process responding to the DHA status. In conclusion, DHA metabolism to DEA is a significant biochemical mechanism for neurite growth, synaptogenesis and synaptic protein expression, leading to enhanced glutamatergic synaptic function. The novel DEA-dependent mechanism offers a new molecular insight into hippocampal neurodevelopment and function.
C1 [Kim, Hee-Yong; Moon, Hyun-Seuk; Cao, Dehua; Lee, Jeongrim; Kevala, Karl; Akbar, Mohammed; Huang, Bill X.] NIAAA, Lab Mol Signaling, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA.
[Jun, Sang Beom] Ewha Womans Univ, Dept Elect Engn, Seoul, South Korea.
[Lovinger, David M.] NIAAA, Lab Integrat Neurosci, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA.
RP Kim, HY (reprint author), NIAAA, Lab Mol Signaling, Div Intramural Clin & Biol Res, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA.
EM hykim@nih.gov
RI Moon, Hyun-Seuk/G-8576-2015
OI Moon, Hyun-Seuk/0000-0002-5216-2090
FU National Institute of Alcohol Abuse and Alcoholism, National Institutes
of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Alcohol Abuse and Alcoholism, National Institutes
of Health.
NR 35
TC 41
Z9 42
U1 1
U2 6
PU PORTLAND PRESS LTD
PI LONDON
PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND
SN 0264-6021
J9 BIOCHEM J
JI Biochem. J.
PD APR 15
PY 2011
VL 435
BP 327
EP 336
DI 10.1042/BJ20102118
PN 2
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 754TI
UT WOS:000289879700003
PM 21281269
ER
PT J
AU Sonder, SU
Saret, S
Tang, W
Sturdevant, DE
Porcella, SF
Siebenlist, U
AF Sonder, Soren Ulrik
Saret, Sun
Tang, Wanhu
Sturdevant, Dan E.
Porcella, Stephen F.
Siebenlist, Ulrich
TI IL-17-induced NF-kappa B Activation via CIKS/Act1 PHYSIOLOGIC
SIGNIFICANCE AND SIGNALING MECHANISMS
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID MESSENGER-RNA STABILIZATION; ADAPTER PROTEIN CIKS/ACT1;
EPITHELIAL-CELLS; GENE-EXPRESSION; NUCLEAR-PROTEIN; TNF-ALPHA; IL-17;
RECEPTOR; ACT1; INTERLEUKIN-17
AB Interleukin-17 (IL-17) is essential in host defense against extracellular bacteria and fungi, especially at mucosal sites, but it also contributes significantly to inflammatory and autoimmune disease pathologies. Binding of IL-17 to its receptor leads to recruitment of adaptor protein CIKS/Act1 via heterotypic association of their respective SEFIR domains and activation of transcription factor NF-kappa B; it is not known whether CIKS and/or NE-kappa B are required for all gene induction events. Here we report that CIKS is essential for all IL-17-induced immediate-early genes in primary mouse embryo fibroblasts, whereas NF-kappa B is profoundly involved. We also identify a novel subdomain in the N terminus of CIKS that is essential for IL-17-mediated NF-kappa B activation. This domain is both necessary and sufficient for interaction between CIKS and TRAF6, an adaptor required for NF-kappa B activation. The ability of decoy peptides to block this interaction may provide a new therapeutic strategy for intervention in IL-17-driven autoimmune and inflammatory diseases.
C1 [Sonder, Soren Ulrik; Saret, Sun; Tang, Wanhu; Siebenlist, Ulrich] NIA1D, Immunoregulat Lab, NIH, Rockville, MD 20852 USA.
[Sturdevant, Dan E.; Porcella, Stephen F.] NIAID, Genom Unit, Res Technol Sect, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
RP Siebenlist, U (reprint author), Bldg 10,Rm 11B15A, Bethesda, MD 20892 USA.
EM usiebenlist@niaid.nih.gov
FU National Institutes of Health NIAID
FX This work was supported, in whole or in part, by the National Institutes
of Health intramural research program of NIAID.
NR 49
TC 50
Z9 51
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 APR 15
PY 2011
VL 286
IS 15
BP 12881
EP 12890
DI 10.1074/jbc.M110.199547
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 746XH
UT WOS:000289282200008
PM 21335551
ER
PT J
AU Hondares, E
Iglesias, R
Giralt, A
Gonzalez, FJ
Giralt, M
Mampel, T
Villarroya, F
AF Hondares, Elayne
Iglesias, Roser
Giralt, Albert
Gonzalez, Frank J.
Giralt, Marta
Mampel, Teresa
Villarroya, Francesc
TI Thermogenic Activation Induces FGF21 Expression and Release in Brown
Adipose Tissue
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID INCREASES ENERGY-EXPENDITURE; INSULIN SENSITIVITY; PPAR-ALPHA; METABOLIC
REGULATOR; GLUCOSE-METABOLISM; LIPID-METABOLISM; GENE-EXPRESSION;
BLOOD-FLOW; MICE; FIBROBLAST-GROWTH-FACTOR-21
AB FGF21 is a novel metabolic regulator involved in the control of glucose homeostasis, insulin sensitivity, and ketogenesis. The liver has been considered the main site of production and release of FGF21 into the blood. Here, we show that, after thermogenic activation, brown adipose tissue becomes a source of systemic FGF21. This is due to a powerful cAMP-mediated pathway of regulation of FGF21 gene transcription. Norepinephrine, acting via beta-adrenergic, cAMP-mediated, mechanisms and subsequent activation of protein kinase A and p38 MAPK, induces FGF21 gene transcription and also FGT21 release in brown adipocytes. ATF2 binding to the FGF21 gene promoter mediates cAMP-dependent induction of FGF21 gene transcription. FGF21 release by brown fat in vivo was assessed directly by analyzing arteriovenous differences in FGF21 concentration across interscapular brown fat, in combination with blood flow to brown adipose tissue and assessment of FGF21 half-life. This analysis demonstrates that exposure of rats to cold induced a marked release of FGF21 by brown fin in vivo, in association with a reduction in systemic FGF21 half-life. The present findings lead to the recognition of a novel pathway of regulation the FGF21 gene and an endocrine role of brown fat, as a source of FGF21 that may be especially relevant in conditions of activation of thermogenic activity.
C1 [Hondares, Elayne] Univ Barcelona, Dept Biochem & Mol Biol, Fac Biol, E-08028 Barcelona, Catalonia, Spain.
[Hondares, Elayne; Iglesias, Roser; Giralt, Albert; Giralt, Marta; Mampel, Teresa; Villarroya, Francesc] Univ Barcelona, Inst Biomed, E-08028 Barcelona, Catalonia, Spain.
[Hondares, Elayne; Iglesias, Roser; Giralt, Albert; Giralt, Marta; Mampel, Teresa; Villarroya, Francesc] CIBER Fisiopatol Obesidad & Nutr, Barcelona 08028, Catalonia, Spain.
[Gonzalez, Frank J.] NCI, Met Lab, NIH, Bethesda, MD 20892 USA.
RP Hondares, E (reprint author), Univ Barcelona, Dept Biochem & Mol Biol, Fac Biol, Avda Diagonal 645, E-08028 Barcelona, Catalonia, Spain.
EM hondareselayne@ub.edu
RI Giralt, Marta/A-4756-2013; Villarroya, Francesc/K-4357-2014;
OI Giralt, Marta/0000-0001-7968-4190; Villarroya,
Francesc/0000-0003-1266-9142
FU Ministerio de Ciencia e Innovacion [SAF2008-01896]; Institut de Salud
Carlos III [PI081715]; Generalitat de Catalunya (Spain) [2009SGR284]
FX This work was supported by grants from Ministerio de Ciencia e
Innovacion (SAF2008-01896), the Institut de Salud Carlos III (PI081715),
and the Generalitat de Catalunya (Spain) (2009SGR284).
NR 33
TC 162
Z9 164
U1 3
U2 21
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 APR 15
PY 2011
VL 286
IS 15
BP 12983
EP 12990
DI 10.1074/jbc.M110.215889
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 746XH
UT WOS:000289282200018
PM 21317437
ER
PT J
AU Kim, CS
Epand, RF
Leikina, E
Epand, RM
Chernomordik, LV
AF Kim, Chang Sup
Epand, Raquel F.
Leikina, Eugenia
Epand, Richard M.
Chernomordik, Leonid V.
TI The Final Conformation of the Complete Ectodomain of the HA2 Subunit of
Influenza Hemagglutinin Can by Itself Drive Low pH-dependent Fusion
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID VIRUS MEMBRANE-FUSION; HEMIFUSION INTERMEDIATE; TRANSMEMBRANE DOMAIN;
PORE FORMATION; COILED-COIL; PROTEINS; MECHANISM; PEPTIDE; STABILITY;
STATE
AB One of the best characterized fusion proteins, the influenza virus hemagglutinin (HA), mediates fusion between the viral envelope and the endosomal membrane during viral entry into the cell. In the initial conformation of HA, its fusogenic subunit, the transmembrane protein HA2, is locked in a metastable conformation by the receptor-binding HA1 subunit of HA. Acidification in the endosome triggers HA2 refolding toward the final lowest energy conformation. Is the fusion process driven by this final conformation or, as often suggested, by the energy released by protein restructuring? Here we explored structural properties as well as the fusogenic activity of the full sized trimeric HA2(1-185) (here called HA2*) that presents the final conformation of the HA2 ectodomain. We found HA2* to mediate fusion between lipid bilayers and between biological membranes in a low pH-dependent manner. Two mutations known to inhibit HA-mediated fusion strongly inhibited the fusogenic activity of HA2*. At surface densities similar to those of HA in the influenza virus particle, HA2* formed small fusion pores but did not expand them. Our results confirm that the HA1 subunit responsible for receptor binding as well as the transmembrane and cytosolic domains of HA2 is not required for fusion pore opening and substantiate the hypothesis that the final form of HA2 is more important for fusion than the conformational change that generates this form.
C1 [Kim, Chang Sup] Hanbat Natl Univ, Div Appl Chem & Biotechnol, Dept Biotechnol, Taejon 305719, South Korea.
[Epand, Raquel F.; Epand, Richard M.] McMaster Univ, Dept Biochem, Hamilton, ON L8N 3Z5, Canada.
[Leikina, Eugenia; Chernomordik, Leonid V.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Membrane Biol, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
RP Kim, CS (reprint author), Hanbat Natl Univ, Div Appl Chem & Biotechnol, Dept Biotechnol, Taejon 305719, South Korea.
EM changskim@hanbat.ac.kr; epand@mcmaster.ca; chernoml@mail.nih.gov
FU Ministry of Education, Science and Technology [NRF-2007-313-D00237];
Canadian Institutes of Health Research [MOP 86608]
FX This work was supported, in whole or in part, by the National Institutes
of Health Intramural Research Program of the Eunice Kennedy Shriver
NICHD and by an intramural biodefense research grant from the NIAID
(both to L. V. C.). This work was also supported by the Basic Science
Research Program through the National Research Foundation of Korea (NRF)
funded by the Ministry of Education, Science and Technology (Grant
NRF-2007-313-D00237) (to C. S. K.) and in part by Canadian Institutes of
Health Research Grant MOP 86608 (to R. M. E.).
NR 70
TC 15
Z9 16
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 APR 15
PY 2011
VL 286
IS 15
BP 13226
EP 13234
DI 10.1074/jbc.M110.181297
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 746XH
UT WOS:000289282200043
PM 21292763
ER
PT J
AU Chen, Y
Yue, S
Xie, L
Pu, XH
Jin, T
Cheng, SY
AF Chen, Yan
Yue, Shen
Xie, Lu
Pu, Xiao-hong
Jin, Tian
Cheng, Steven Y.
TI Dual Phosphorylation of Suppressor of Fused (Sufu) by PKA and GSK3 beta
Regulates Its Stability and Localization in the Primary Cilium
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HEDGEHOG SIGNAL-TRANSDUCTION; INTRAFLAGELLAR TRANSPORT; GLI; PROTEINS;
MOUSE; TRANSCRIPTION; ASSOCIATION; DROSOPHILA; PARADIGMS; MECHANISM
AB Suppressor of fused (Sufu) is an essential negative regulator of the sonic hedgehog (Shh) pathway, but little is known about how Sufu itself is normally regulated. Here, we report that Sufu is phosphorylated at Ser-342 and Ser-346 by GSK3 beta and cAMP-dependent protein kinase A (PKA), respectively, and phosphorylation at this dual site stabilizes Sufu against Shh signaling-induced degradation. We further show that localization of Sufu in the primary cilium is induced by Shh signaling and is required for the turnover of both phosphorylated and total Sufu. Perturbing Sufu phosphorylation with PKA inhibitors or replacing Ser-346 with alanine reduced the stay and replacing Ser-342 and Ser-346 with aspartic acid prolonged the stay of Sufu in the cilia. Finally, ciliary localization of Gli2/3 also required Smo and was similarly influenced by perturbations of PKA activity or mutations at the dual Sufu phosphorylation site. Thus, Shh likely induced trafficking of phospho-Sufu into the primary cilium in a complex with Gli2/3, and dephosphorylation triggered a retrograde export, allowing Sufu to be degraded by the ubiquitin-proteasome system.
C1 [Chen, Yan; Yue, Shen; Xie, Lu; Pu, Xiao-hong; Cheng, Steven Y.] Nanjing Med Univ, Dept Dev Genet, Ctr Canc Res, Nanjing 210029, Jiangsu, Peoples R China.
[Chen, Yan; Yue, Shen; Xie, Lu; Pu, Xiao-hong; Cheng, Steven Y.] Nanjing Med Univ, Ctr Regenerat Med, Nanjing 210029, Jiangsu, Peoples R China.
[Jin, Tian] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Cheng, SY (reprint author), Nanjing Med Univ, Dept Dev Genet, Ctr Canc Res, 140 Hanzhong Rd, Nanjing 210029, Jiangsu, Peoples R China.
EM sycheng@njmu.edu.cn
FU Chinese National Science Foundation [30771079]; Chinese Ministry of
Science and Technology [2009CB918403]; University Research Grant
[08NMUM010]; National Institutes of Health NIAID
FX This work was supported by Chinese National Science Foundation Grant
30771079 (to S. Y. C.), 973 State Key Research Project of Chinese
Ministry of Science and Technology Grant 2009CB918403 (to S. Y. C.), and
University Research Grant 08NMUM010 (to S. Y.). This work was also
supported in part by National Institutes of Health NIAID intramural fund
(to T. J.).
NR 42
TC 32
Z9 38
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 APR 15
PY 2011
VL 286
IS 15
BP 13502
EP 13511
DI 10.1074/jbc.M110.217604
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 746XH
UT WOS:000289282200070
PM 21317289
ER
PT J
AU Cirio, MC
Hui, Z
Haldin, CE
Cosentino, CC
Stuckenholz, C
Chen, XF
Hong, SK
Dawid, IB
Hukriede, NA
AF Cirio, M. Cecilia
Hui, Zhao
Haldin, Caroline E.
Cosentino, Chiara Cianciolo
Stuckenholz, Carsten
Chen, Xiongfong
Hong, Sung-Kook
Dawid, Igor B.
Hukriede, Neil A.
TI Lhx1 Is Required for Specification of the Renal Progenitor Cell Field
SO PLOS ONE
LA English
DT Article
ID CIS-ACTING ELEMENTS; IN-VITRO INDUCTION; HOMEOBOX GENE LIM1;
XENOPUS-LAEVIS; KIDNEY DEVELOPMENT; RETINOIC ACID; INTERMEDIATE
MESODERM; PRONEPHRIC KIDNEY; ZEBRAFISH PRONEPHROS; TRANSCRIPTION FACTOR
AB In the vertebrate embryo, the kidney is derived from the intermediate mesoderm. The LIM-class homeobox transcription factor lhx1 is expressed early in the intermediate mesoderm and is one of the first genes to be expressed in the nephric mesenchyme. In this study, we investigated the role of Lhx1 in specification of the kidney field by either overexpressing or depleting lhx1 in Xenopus embryos or depleting lhx1 in an explant culture system. By overexpressing a constitutively-active form of Lhx1, we established its capacity to expand the kidney field during the specification stage of kidney organogenesis. In addition, the ability of Lhx1 to expand the kidney field diminishes as kidney organogenesis transitions to the morphogenesis stage. In a complimentary set of experiments, we determined that embryos depleted of lhx1, show an almost complete loss of the kidney field. Using an explant culture system to induce kidney tissue, we confirmed that expression of genes from both proximal and distal kidney structures is affected by the absence of lhx1. Taken together our results demonstrate an essential role for Lhx1 in driving specification of the entire kidney field from the intermediate mesoderm.
C1 [Cirio, M. Cecilia; Haldin, Caroline E.; Cosentino, Chiara Cianciolo; Hukriede, Neil A.] Univ Pittsburgh, Dept Dev Biol, Pittsburgh, PA USA.
[Hui, Zhao] Chinese Univ Hong Kong, Sch Biomed Sci, Ma Liu Shui, Hong Kong, Peoples R China.
[Stuckenholz, Carsten] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Chen, Xiongfong] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Unit Biol Computat, Bethesda, MD USA.
[Hong, Sung-Kook; Dawid, Igor B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Mol Genet Lab, Bethesda, MD USA.
[Hukriede, Neil A.] Univ Pittsburgh, Drug Discovery Inst, Pittsburgh, PA USA.
RP Cirio, MC (reprint author), Univ Pittsburgh, Dept Dev Biol, Pittsburgh, PA USA.
EM hukriede@pitt.edu
RI Zhao, Hui/B-8429-2016
FU National Institutes of Health [R01DK069403]; National Institute of Child
Health and Human Development
FX This work was supported by National Institutes of Health grant
R01DK069403 (NAH) and by the intramural research program of the National
Institute of Child Health and Human Development (IBD). The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 70
TC 9
Z9 11
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 15
PY 2011
VL 6
IS 4
AR e18858
DI 10.1371/journal.pone.0018858
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 750WK
UT WOS:000289578600036
PM 21526205
ER
PT J
AU Malachowa, N
Whitney, AR
Kobayashi, SD
Sturdevant, DE
Kennedy, AD
Braughton, KR
Shabb, DW
Diep, BA
Chambers, HF
Otto, M
DeLeo, FR
AF Malachowa, Natalia
Whitney, Adeline R.
Kobayashi, Scott D.
Sturdevant, Daniel E.
Kennedy, Adam D.
Braughton, Kevin R.
Shabb, Duncan W.
Diep, Binh An
Chambers, Henry F.
Otto, Michael
DeLeo, Frank R.
TI Global Changes in Staphylococcus aureus Gene Expression in Human Blood
SO PLOS ONE
LA English
DT Article
ID PANTON-VALENTINE LEUKOCIDIN; GAMMA-HEMOLYSIN; VIRULENCE DETERMINANT;
STREAM INFECTIONS; IRON; IDENTIFICATION; USA300; MODEL; PHAGOCYTOSIS;
SIDEROPHORE
AB Staphylococcus aureus is a leading cause of bloodstream infections worldwide. In the United States, many of these infections are caused by a strain known as USA300. Although progress has been made, our understanding of the S. aureus molecules that promote survival in human blood and ultimately facilitate metastases is incomplete. To that end, we analyzed the USA300 transcriptome during culture in human blood, human serum, and trypticase soy broth (TSB), a standard laboratory culture media. Notably, genes encoding several cytolytic toxins were up-regulated in human blood over time, and hlgA, hlgB, and hlgC (encoding gamma-hemolysin subunits HlgA, HlgB, and HlgC) were among the most highly up-regulated genes at all time points. Compared to culture supernatants from a wild-type USA300 strain (LAC), those derived from an isogenic hlgABC-deletion strain (LAC Delta hlgABC) had significantly reduced capacity to form pores in human neutrophils and ultimately cause neutrophil lysis. Moreover, LAC Delta hlgABC had modestly reduced ability to cause mortality in a mouse bacteremia model. On the other hand, wild-type and LAC Delta hlgABC strains caused virtually identical abscesses in a mouse skin infection model, and bacterial survival and neutrophil lysis after phagocytosis in vitro was similar between these strains. Comparison of the cytolytic capacity of culture supernatants from wild-type and isogenic deletion strains lacking hlgABC, lukS/F-PV (encoding PVL), and/or lukDE revealed functional redundancy among two-component leukotoxins in vitro. These findings, along with a requirement of specific growth conditions for leukotoxin expression, may explain the apparent limited contribution of any single two-component leukotoxin to USA300 immune evasion and virulence.
C1 [Malachowa, Natalia; Whitney, Adeline R.; Kobayashi, Scott D.; Kennedy, Adam D.; Braughton, Kevin R.; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Sturdevant, Daniel E.; Shabb, Duncan W.] NIAID, Genom Unit, Res Technol Sect, Rocky Mt Labs,NIH, Hamilton, MT USA.
[Diep, Binh An; Chambers, Henry F.] Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA USA.
[Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA.
RP Malachowa, N (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA.
EM fdeleo@niaid.nih.gov
OI DeLeo, Frank/0000-0003-3150-2516; Otto, Michael/0000-0002-2222-4115
FU National Institute of Allergy and Infectious Diseases; National
Institutes of Health (NIH); U.S. Public Health Service from National
Institute of Allergy and Infectious Diseases, NIH [R01 AI070289, R01
AI087674]
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health (NIH) and U.S. Public Health Service grants, R01
AI070289 (HFC) and R01 AI087674 (BAD), from the National Institute of
Allergy and Infectious Diseases, NIH. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 46
TC 90
Z9 91
U1 0
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 15
PY 2011
VL 6
IS 4
AR e18617
DI 10.1371/journal.pone.0018617
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 750WK
UT WOS:000289578600018
PM 21525981
ER
PT J
AU Shimbo, D
Muntner, P
Mann, D
Barr, RG
Tang, WH
Post, W
Lima, J
Burke, G
Bluemke, D
Shea, S
AF Shimbo, Daichi
Muntner, Paul
Mann, Devin
Barr, R. Graham
Tang, Weihong
Post, Wendy
Lima, Joao
Burke, Gregory
Bluemke, David
Shea, Steven
TI Association of Left Ventricular Hypertrophy With Incident Hypertension:
The Multi-Ethnic Study of Atherosclerosis
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE hypertension; hypertrophy; left ventricular; magnetic resonance imaging;
risk factors
ID CARDIOVASCULAR MAGNETIC-RESONANCE; BLOOD-PRESSURE;
ARTERIAL-HYPERTENSION; MASS; HEART; RISK; GEOMETRY; IMPACT; PATTERNS;
VOLUME
AB Increased left ventricular (LV) mass and changes in LV geometry may precede hypertension onset. The authors examined the associations of LV mass and geometry, assessed by cardiac magnetic resonance imaging, with hypertension incidence in 2,567 normotensive participants enrolled in 2000-2002 in the Multi-Ethnic Study of Atherosclerosis, an ethnically diverse, population-based, US study. Over a median follow-up of 4.8 years, 745 (29%) participants developed hypertension. In a fully adjusted model including baseline blood pressure, the relative risks of incident hypertension from the lowest to highest LV mass quartile were 1.00 (referent), 1.13 (95% confidence interval (CI): 0.89, 1.43), 1.28 (95% CI: 1.00, 1.63), and 1.78 (95% CI: 1.38, 2.30) (P < 0.001 for linear trend). Higher levels of LV concentric geometry, defined by higher LV mass to end-diastolic volume quartiles, were associated with higher risk of incident hypertension in a fully adjusted model (P = 0.044 for linear trend). In a final model containing both quartiles of LV mass and LV mass/volume along with all covariates including baseline blood pressure, higher LV mass quartiles were associated with incident hypertension (P < 0.001 for linear trend), whereas higher LV mass/volume quartiles were not (P = 0.643 for linear trend). In this multiethnic cohort, alterations in LV mass preceded hypertension onset among normotensive individuals.
C1 [Shimbo, Daichi; Barr, R. Graham; Shea, Steven] Columbia Univ, Dept Med, Med Ctr, New York, NY 10031 USA.
[Muntner, Paul] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA.
[Mann, Devin] Mt Sinai Sch Med, Dept Med, New York, NY USA.
[Tang, Weihong] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Post, Wendy; Lima, Joao] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Lima, Joao] Johns Hopkins Univ, Sch Med, Dept Radiol & Radiol Sci, Baltimore, MD USA.
[Burke, Gregory] Wake Forest Univ, Bowman Gray Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA.
[Bluemke, David] NIH, Bethesda, MD 20892 USA.
[Barr, R. Graham; Shea, Steven] Columbia Univ, Dept Epidemiol, Med Ctr, New York, NY 10031 USA.
RP Shimbo, D (reprint author), Columbia Univ, Dept Med, Med Ctr, 622 W 168th St,PH 9-949, New York, NY 10031 USA.
EM ds2231@columbia.edu
OI Bluemke, David/0000-0002-8323-8086; Mann, Devin/0000-0002-2099-0852
FU National Heart, Lung, and Blood Institute, Bethesda, Maryland
[N01-HC-95159, N01-HC-95169]
FX This work was supported by contracts N01-HC-95159 through N01-HC-95169
from the National Heart, Lung, and Blood Institute, Bethesda, Maryland.
NR 30
TC 11
Z9 11
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD APR 15
PY 2011
VL 173
IS 8
BP 898
EP 905
DI 10.1093/aje/kwq509
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 747DY
UT WOS:000289301700008
PM 21422061
ER
PT J
AU Hu, XL
Yang, DF
Zimmerman, M
Liu, FY
Yang, JN
Kannan, S
Burchert, A
Szulc, Z
Bielawska, A
Ozato, K
Bhalla, K
Liu, KB
AF Hu, Xiaolin
Yang, Dafeng
Zimmerman, Mary
Liu, Feiyan
Yang, Jine
Kannan, Swati
Burchert, Andreas
Szulc, Zdzislaw
Bielawska, Alicja
Ozato, Keiko
Bhalla, Kapil
Liu, Kebin
TI IRF8 Regulates Acid Ceramidase Expression to Mediate Apoptosis and
Suppresses Myelogeneous Leukemia
SO CANCER RESEARCH
LA English
DT Article
ID SEQUENCE-BINDING-PROTEIN; MYELOID CELLS; ICSBP DEFICIENCY;
TUMOR-REGRESSION; BIOACTIVE SPHINGOLIPIDS; GENE-TRANSCRIPTION;
PROGENITOR CELLS; DNA METHYLATION; IN-VIVO; FACTOR-8
AB IFN regulatory factor 8 (IRF8) is a key transcription factor for myeloid cell differentiation and its expression is frequently lost in hematopoietic cells of human myeloid leukemia patients. IRF8-deficient mice exhibit uncontrolled clonal expansion of undifferentiated myeloid cells that can progress to a fatal blast crisis, thereby resembling human chronic myelogeneous leukemia (CML). Therefore, IRF8 is a myeloid leukemia suppressor. Whereas the understanding of IRF8 function in CML has recently improved, the molecular mechanisms underlying IRF8 function in CML are still largely unknown. In this study, we identified acid ceramidase (A-CDase) as a general transcription target of IRF8. We demonstrated that IRF8 expression is regulated by IRF8 promoter DNA methylation in myeloid leukemia cells. Restoration of IRF8 expression repressed A-CDase expression, resulting in C16 ceramide accumulation and increased sensitivity of CML cells to FasL-induced apoptosis. In myeloid cells derived from IRF8-deficient mice, A-CDase protein level was dramatically increased. Furthermore, we demonstrated that IRF8 directly binds to the A-CDase promoter. At the functional level, inhibition of A-CDase activity, silencing A-CDase expression, or application of exogenous C16 ceramide sensitized CML cells to FasL-induced apoptosis, whereas overexpression of A-CDase decreased CML cells' sensitivity to FasL-induced apoptosis. Consequently, restoration of IRF8 expression suppressed CML development in vivo at least partially through a Fas-dependent mechanism. In summary, our findings determine the mechanism of IRF8 downregulation in CML cells and they determine a primary pathway of resistance to Fas-mediated apoptosis and disease progression. Cancer Res; 71(8); 2882-91. (C)2011 AACR.
C1 [Hu, Xiaolin; Yang, Dafeng; Zimmerman, Mary; Liu, Feiyan; Yang, Jine; Kannan, Swati; Liu, Kebin] Georgia Hlth Sci Univ, Dept Biochem & Mol Biol, Augusta, GA 30912 USA.
[Bhalla, Kapil; Liu, Kebin] Georgia Hlth Sci Univ, Ctr Canc, Augusta, GA 30912 USA.
[Burchert, Andreas] Univ Klinikum Marburg, Klin Hamatol Onkol & Immunol, Marburg, Germany.
[Szulc, Zdzislaw; Bielawska, Alicja] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA.
[Ozato, Keiko] NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA.
RP Liu, KB (reprint author), Georgia Hlth Sci Univ, Dept Biochem & Mol Biol, 1459 Laney Walker Blvd, Augusta, GA 30912 USA.
EM Kliu@georgiahealth.edu
OI Liu, Kebin/0000-0003-1965-7240
FU NIH [CA133085]; American Cancer Society [RSG-09-209-01-TBG]
FX This work was supported by the NIH (CA133085 to K. Liu) and the American
Cancer Society (RSG-09-209-01-TBG to K. Liu).
NR 50
TC 35
Z9 35
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
IS 8
BP 2882
EP 2891
DI 10.1158/0008-5472.CAN-10-2493
PG 10
WC Oncology
SC Oncology
GA 749YL
UT WOS:000289507800009
PM 21487040
ER
PT J
AU Yang, XY
Popescu, NC
Zimonjic, DB
AF Yang, Xuyu
Popescu, Nicholas C.
Zimonjic, Drazen B.
TI DLC1 Interaction with S100A10 Mediates Inhibition of In Vitro Cell
Invasion and Tumorigenicity of Lung Cancer Cells through a
RhoGAP-Independent Mechanism
SO CANCER RESEARCH
LA English
DT Article
ID GTPASE-ACTIVATING PROTEIN; HUMAN HEPATOCELLULAR-CARCINOMA; FOCAL
ADHESION-LOCALIZATION; END-PRODUCTS RAGE; TUMOR-SUPPRESSOR; RHOA GTPASE;
ANNEXIN-II; PROLIFERATION; EXPRESSION; GROWTH
AB The DLC1 gene encodes a Rho GTPase-activating protein (RhoGAP) that functions as a tumor suppressor in several common human cancers. The multidomain structure of DLC1 enables interaction with a number of other proteins. Here we report that the proinflammatory protein S100A10 (also known as p11), a key cell surface receptor for plasminogen which regulates pericellular proteolysis and tumor cell invasion, is a new binding partner of DLC1 in human cells. We determined that the 2 proteins colocalize in the cell cytoplasm and that their binding is mediated by central sequences in the central domain of DLC1 and the C-terminus of S100A10. Because the same S100A10 sequence also mediates binding to Annexin 2, we found that DLC1 competed with Annexin 2 for interaction with S100A10. DLC1 binding to S100A10 did not affect DLC1's RhoGAP activity, but it decreased the steady-state level of S100A10 expression in a dose-dependent manner by displacing it from Annexin 2 and making it accessible to ubiquitin-dependent degradation. This process attenuated plasminogen activation and resulted in inhibition of in vitro cell migration, invasion, colony formation, and anchorage-independent growth of aggressive lung cancer cells. These results suggest that a novel GAP-independent mechanism contributes to the tumor suppressive activity of DLC1, and highlight the importance and complexity of protein-protein interactions involving DLC1 in certain cancers. Cancer Res; 71(8); 2916-25. (C)2011 AACR.
C1 [Yang, Xuyu; Popescu, Nicholas C.; Zimonjic, Drazen B.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Popescu, NC (reprint author), 37 Convent Dr,MSC 4262, Bethesda, MD 20892 USA.
EM popescun@mail.nih.gov
RI yang, xuyu/D-1414-2012
FU National Cancer Institute, NIH
FX This research was supported by the Intramural Research Program of the
National Cancer Institute, NIH.
NR 32
TC 26
Z9 31
U1 1
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
IS 8
BP 2916
EP 2925
DI 10.1158/0008-5472.CAN-10-2158
PG 10
WC Oncology
SC Oncology
GA 749YL
UT WOS:000289507800012
PM 21372205
ER
PT J
AU Qin, HD
Shugart, YY
Bei, JX
Pan, QH
Chen, LN
Feng, QS
Chen, LZ
Huang, W
Liu, JJ
Jorgensen, TJ
Zeng, YX
Jia, WH
AF Qin, Hai-De
Shugart, Yin Yao
Bei, Jin-Xin
Pan, Qing-Hua
Chen, Lina
Feng, Qi-Sheng
Chen, Li-Zhen
Huang, Wei
Liu, Jian Jun
Jorgensen, Timothy J.
Zeng, Yi-Xin
Jia, Wei-Hua
TI Comprehensive Pathway-Based Association Study of DNA Repair Gene
Variants and the Risk of Nasopharyngeal Carcinoma
SO CANCER RESEARCH
LA English
DT Article
ID EPSTEIN-BARR-VIRUS; GENOME-WIDE ASSOCIATION; CANCER-RISK; SUSCEPTIBILITY
LOCUS; POLYMORPHISMS; LINKAGE; RAD51; INSTABILITY; DAMAGE; HAPLOTYPES
AB DNA repair plays a central role in protecting against environmental carcinogenesis, and genetic variants of DNA repair genes have been reported to be associated with several human malignancies. To assess whether DNA gene variants were associated with nasopharyngeal carcinoma (NPC) risk, a candidate gene association study was conducted among the Cantonese population within the Guangdong Province, China, the ethnic group with the highest risk for NPC. A 2-stage study design was utilized. In the discovery stage, 676 tagging SNPs covering 88 DNA repair genes were genotyped in a matched case-control study (cases/controls = 755/755). Eleven SNPs with P-trend < 0.01 were identified. Seven of these SNPs were located within 3 genes, RAD51L1, BRCA2, and TP53BP1. In the validation stage, these 11 SNPs were genotyped in a separate Cantonese population (cases/controls 1,568/1,297). Two of the SNPs (rs927220 and rs11158728), both in RAD51L1, remained strongly associated with NPC. The SNP rs927220 had a significant P-combined of 5.55 x 10(-5), with OR = 1.20 (95% CI = 1.10-1.30), Bonferroni corrected P = 0.0381. The other SNP (rs11158728), which is in strong linkage disequilibrium with rs927220 (r(2) = 0.7), had a significant P-combined of 2.0 x 10(-4), Bonferroni corrected P = 0.1372. Gene-environment interaction analysis suggested that the exposures of salted fish consumption and cigarette smoking had potential interactions with DNA repair gene variations, but need to be further investigated. Our findings support the notion that DNA repair genes, in particular RAD51L1, play a role in NPC etiology and development. Cancer Res; 71(8); 3000-8. (C)2011 AACR.
C1 [Qin, Hai-De; Bei, Jin-Xin; Pan, Qing-Hua; Feng, Qi-Sheng; Chen, Li-Zhen; Zeng, Yi-Xin; Jia, Wei-Hua] Sun Yat Sen Univ, State Key Lab Oncol S China, Dept Expt Res, Ctr Canc, Guangzhou 510060, Guangdong, Peoples R China.
[Shugart, Yin Yao] NIMH, Unit Stat Genom, Div Intramural Div Program, NIH, Bethesda, MD 20892 USA.
[Chen, Lina] Univ Bristol, Dept Social Med, Bristol, Avon, England.
[Huang, Wei] Chinese Natl Human Genome Ctr, Dept Genet, Shanghai MOST Key Lab Hlth & Dis Genom, Shanghai, Peoples R China.
[Liu, Jian Jun] Genome Inst Singapore, Singapore, Singapore.
[Jorgensen, Timothy J.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Jess & Mildred Fisher Ctr Familial Canc Res, Washington, DC USA.
RP Jia, WH (reprint author), Sun Yat Sen Univ, State Key Lab Oncol S China, Dept Expt Res, Ctr Canc, Guangzhou 510060, Guangdong, Peoples R China.
EM jiaweih@mail.sysu.edu.cn
FU National Natural Science Foundation of China [30671798, 30471487,
u0732005]; National Science and Technology Support Program of China
[2006BAI02A11]; National Major Basic Research Program of China (863)
[2006AA02A404]; National Institute of Health, USA [RO3CA113240-01]
FX This work was supported by the National Natural Science Foundation of
China (30671798, 30471487, u0732005), the National Science and
Technology Support Program of China (2006BAI02A11), the National Major
Basic Research Program of China (863: 2006AA02A404) and the National
Institute of Health (RO3CA113240-01), USA.
NR 46
TC 22
Z9 25
U1 0
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
IS 8
BP 3000
EP 3008
DI 10.1158/0008-5472.CAN-10-0469
PG 9
WC Oncology
SC Oncology
GA 749YL
UT WOS:000289507800020
PM 21368091
ER
PT J
AU Shi, Z
Tiwari, AK
Shukla, S
Robey, RW
Singh, S
Kim, IW
Bates, SE
Peng, XX
Abraham, I
Ambudkar, SV
Talele, TT
Fu, LW
Chen, ZS
AF Shi, Zhi
Tiwari, Amit K.
Shukla, Suneet
Robey, Robert W.
Singh, Satyakam
Kim, In-Wha
Bates, Susan E.
Peng, Xingxiang
Abraham, Ioana
Ambudkar, Suresh V.
Talele, Tanaji T.
Fu, Li-Wu
Chen, Zhe-Sheng
TI Sildenafil Reverses ABCB1-and ABCG2-Mediated Chemotherapeutic Drug
Resistance
SO CANCER RESEARCH
LA English
DT Article
ID SUBFAMILY-B MEMBER-1; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; ACQUIRED
MUTATIONS; CYCLOSPORINE-A; CANCER-CELLS; PROTEIN MRP; BINDING; ABCG2;
TRANSPORTER
AB Sildenafil is a potent and selective inhibitor of the type 5 cGMP (cyclic guanosine 3',5'-monophosphate)-specific phosphodiesterase that is used clinically to treat erectile dysfunction and pulmonary arterial hypertension. Here, we report that sildenafil has differential effects on cell surface ABC transporters such as ABCB1, ABCC1, and ABCG2 that modulate intracompartmental and intracellular concentrations of chemotherapeutic drugs. In ABCB1-overexpressing cells, nontoxic doses of sildenafil inhibited resistance and increased the effective intracellular concentration of ABCB1 substrate drugs such as paclitaxel. Similarly, in ABCG2-overexpressing cells, sildenafil inhibited resistance to ABCG2 substrate anticancer drugs, for example, increasing the effective intracellular concentration of mitoxantrone or the fluorescent compound BODIPY-prazosin. Sildenafil also moderately inhibited the transport of E(2)17 beta G and methotrexate by the ABCG2 transporter. Mechanistic investigations revealed that sildenafil stimulated ABCB1 ATPase activity and inhibited photolabeling of ABCB1 with [I-125]-iodoarylazidoprazosin (IAAP), whereas it only slightly stimulated ABCG2 ATPase activity and inhibited photolabeling of ABCG2 with [I-125]-IAAP. In contrast, sildenafil did not alter the sensitivity of parental, ABCB1-, or ABCG2-overexpressing cells to non-ABCB1 and non-ABCG2 substrate drugs, nor did sildenafil affect the function of another ABC drug transporter, ABCC1. Homology modeling predicted the binding conformation of sildenafil within the large cavity of the transmembrane region of ABCB1. Overall, we found that sildenafil inhibits the transporter function of ABCB1 and ABCG2, with a stronger effect on ABCB1. Our findings suggest a possible strategy to enhance the distribution and potentially the activity of anticancer drugs by jointly using a clinically approved drug with known side effects and drug-drug interactions. Cancer Res; 71(8); 3029-41. (C)2011 AACR.
C1 [Shi, Zhi; Tiwari, Amit K.; Singh, Satyakam; Peng, Xingxiang; Abraham, Ioana; Talele, Tanaji T.; Chen, Zhe-Sheng] St Johns Univ, Dept Pharmaceut Sci, Coll Pharm & Allied Hlth Profess, New York, NY USA.
[Shi, Zhi; Fu, Li-Wu] Sun Yat Sen Univ, State Key Lab Oncol S China, Ctr Canc, Guangzhou 510275, Guangdong, Peoples R China.
[Shukla, Suneet; Kim, In-Wha; Ambudkar, Suresh V.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Robey, Robert W.; Bates, Susan E.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Chen, ZS (reprint author), St Johns Univ, Dept Pharmaceut Sci, Jamaica, NY 11439 USA.
EM Fulw@mail.sysu.edu.cn; Chenz@stjohns.edu
RI Tiwari, Amit/A-3667-2012; shukla, suneet/B-4626-2012;
OI Tiwari, Amit/0000-0002-7427-7155; Singh, Satyakam/0000-0001-9115-3296
FU NIH [1R15CA143701]; St. John's University [579-1110-7002]; Chinese
National Natural Science Foundation [81061160507]; Intramural Research
Program; NCI; Center for Cancer Research; St. John's University from Sun
Yat-Sen University
FX This work was supported by funds from NIH (No. 1R15CA143701 to Z.S.
Chen), St. John's University Research Seed Grant (No. 579-1110-7002 to
Z.S. Chen), and the Chinese National Natural Science Foundation (No.
81061160507 to L. W. Fu). I. W. Kim, S. Shukla, R. W. Robey, S. E.
Bates, and S. V. Ambudkar were supported by the Intramural Research
Program, NIH, NCI, Center for Cancer Research. Z. Shi is a recipient of
Kaisi fellowship for overseas study at St. John's University from Sun
Yat-Sen University.
NR 38
TC 72
Z9 75
U1 2
U2 14
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
IS 8
BP 3029
EP 3041
DI 10.1158/0008-5472.CAN-10-3820
PG 13
WC Oncology
SC Oncology
GA 749YL
UT WOS:000289507800023
PM 21402712
ER
PT J
AU Alsarraj, J
Walker, RC
Webster, JD
Geiger, TR
Crawford, NPS
Simpson, RM
Ozato, K
Hunter, KW
AF Alsarraj, Jude
Walker, Renard C.
Webster, Joshua D.
Geiger, Thomas R.
Crawford, Nigel P. S.
Simpson, R. Mark
Ozato, Keiko
Hunter, Kent W.
TI Deletion of the Proline-Rich Region of the Murine Metastasis
Susceptibility Gene Brd4 Promotes Epithelial-to-Mesenchymal Transition-
and Stem Cell-Like Conversion
SO CANCER RESEARCH
LA English
DT Article
ID BROMODOMAIN PROTEIN BRD4; BREAST-CANCER SURVIVAL; IN-VITRO PROPAGATION;
TUMOR PROGRESSION; AGGRESSIVE CARCINOMA; POOR-PROGNOSIS; P-TEFB;
DIFFERENTIATION; TRANSCRIPTION; EXPRESSION
AB The bromodomain-containing chromatin-modifying factor BRD4 is an inherited susceptibility gene for breast cancer progression and metastasis, but its functionality in these settings has yet to be explored. Here we show that deletion of either of the BRD4 bromodomains had modest effects on the metastatic suppression ability of BRD4. In contrast, expression of the natural short isoform of BRD4 that truncates the protein after the SEED domain restored progression and metastatic capacity. Unexpectedly, deletion of the proline-rich region induced mesenchymal-like conversion and acquisition of cancer stem cell-like properties, which are mediated by the carboxy-terminal P-TEFb binding domain. Deletion of this proline-rich region also induced a gene expression signature that predicted poor outcome in human breast cancer data sets and that overlapped G3 grade human breast tumors. Thus our findings suggest that BRD4 may be altering the predisposition of tumors to undergo conversion to a more de-differentiated or primitive state during metastatic progression. Cancer Res; 71(8); 3121-31. (C) 2011 AACR.
C1 [Alsarraj, Jude; Walker, Renard C.; Webster, Joshua D.; Geiger, Thomas R.; Crawford, Nigel P. S.; Simpson, R. Mark; Hunter, Kent W.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
[Ozato, Keiko] NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA.
RP Hunter, KW (reprint author), 37 Convent Dr,Room 5046, Bethesda, MD 20892 USA.
EM hunterk@mail.nih.gov
FU Intramural NIH HHS [Z01 CP010146-09, Z99 CA999999, ZIA BC011255-01, Z01
CP010146-08, ZIA CP010146-08]
NR 37
TC 27
Z9 27
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
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
IS 8
BP 3121
EP 3131
DI 10.1158/0008-5472.CAN-10-4417
PG 11
WC Oncology
SC Oncology
GA 749YL
UT WOS:000289507800031
PM 21389092
ER
PT J
AU Williams, RS
Kunkel, TA
AF Williams, R. Scott
Kunkel, Thomas A.
TI FEN Nucleases: Bind, Bend, Fray, Cut
SO CELL
LA English
DT Editorial Material
ID REPAIR; MECHANISM
C1 [Williams, R. Scott; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Williams, RS (reprint author), NIEHS, Struct Biol Lab, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM williamsrs@niehs.nih.gov; kunkel@niehs.nih.gov
RI Williams, Robert/A-6059-2015
FU Intramural NIH HHS [ZIA ES102765-01]
NR 10
TC 8
Z9 8
U1 0
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD APR 15
PY 2011
VL 145
IS 2
BP 171
EP 172
DI 10.1016/j.cell.2011.03.039
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 750MA
UT WOS:000289549900005
PM 21496637
ER
PT J
AU Zhang, JM
Wang, Y
Chi, ZK
Keuss, MJ
Pai, YME
Kang, HC
Shin, JH
Bugayenko, A
Wang, H
Xiong, YL
Pletnikov, MV
Mattson, MP
Dawson, TM
Dawson, VL
AF Zhang, Jianmin
Wang, Yue
Chi, Zhikai
Keuss, Matthew J.
Pai, Ying-Min Emily
Kang, Ho Chul
Shin, Joo-Ho
Bugayenko, Artem
Wang, Hong
Xiong, Yulan
Pletnikov, Mikhail V.
Mattson, Mark P.
Dawson, Ted M.
Dawson, Valina L.
TI The AAA(+) ATPase Thorase Regulates AMPA Receptor-Dependent Synaptic
Plasticity and Behavior
SO CELL
LA English
DT Article
ID TRANSGENIC MICE; GLUR2; SYNAPSES; MEMORY; NMDA; TRAFFICKING; SUBUNIT;
COMPLEX; BINDING; PROTEIN
AB The synaptic insertion or removal of AMPA receptors (AMPAR) plays critical roles in the regulation of synaptic activity reflected in the expression of long-term potentiation (LTP) and long-term depression (LTD). The cellular events underlying this important process in learning and memory are still being revealed. Here we describe and characterize the AAA(+) ATPase Thorase, which regulates the expression of surface AMPAR. In an ATPase-dependent manner Thorase mediates the internalization of AMPAR by disassembling the AMPAR-GRIP1 complex. Following genetic deletion of Thorase, the internalization of AMPAR is substantially reduced, leading to increased amplitudes of miniature excitatory postsynaptic currents, enhancement of LTP, and elimination of LTD. These molecular events are expressed as deficits in learning and memory in Thorase null mice. This study identifies an AAA(+) ATPase that plays a critical role in regulating the surface expression of AMPAR and thereby regulates synaptic plasticity and learning and memory.
C1 [Zhang, Jianmin; Keuss, Matthew J.; Pai, Ying-Min Emily; Kang, Ho Chul; Shin, Joo-Ho; Bugayenko, Artem; Xiong, Yulan; Dawson, Ted M.; Dawson, Valina L.] Johns Hopkins Univ, Sch Med, Neuroregenerat & Stem Cell Programs, Inst Cell Engn, Baltimore, MD 21205 USA.
[Zhang, Jianmin; Chi, Zhikai; Pai, Ying-Min Emily; Kang, Ho Chul; Shin, Joo-Ho; Bugayenko, Artem; Xiong, Yulan; Pletnikov, Mikhail V.; Dawson, Ted M.; Dawson, Valina L.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Chi, Zhikai; Wang, Hong; Mattson, Mark P.; Dawson, Ted M.; Dawson, Valina L.] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA.
[Dawson, Valina L.] Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA.
[Pletnikov, Mikhail V.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Keuss, Matthew J.] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21205 USA.
[Wang, Yue; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
RP Dawson, TM (reprint author), Johns Hopkins Univ, Sch Med, Neuroregenerat & Stem Cell Programs, Inst Cell Engn, Baltimore, MD 21205 USA.
EM tdawson@jhmi.edu; vdawson@jhmi.edu
RI Mattson, Mark/F-6038-2012;
OI Dawson, Valina/0000-0002-2915-3970
FU National Institute on Aging, USPHS [AG029368, DA00266]; Simon's
Foundation Autism Research Initiative; McKnight Endowment for the
Neuroscience; American Heart Association [0725470U]
FX We apologize that, due to space limitations, we were not able to cite
all the primary papers on AMPAR trafficking, LTD, and LTP. We thank all
of our colleagues who generously contributed reagents as noted in the
Supplemental Information and Dr. Richard Huganir for the generous gift
of monoclonal anti-GluR1 N-terminal antibody. Research was supported by
the Intramural Research Program of the National Institute on Aging,
USPHS grants AG029368 and DA00266, the Simon's Foundation Autism
Research Initiative, McKnight Endowment for the Neuroscience, and an
American Heart Association Postdoctoral Fellowship to J.Z. (0725470U).
We thank the Comparative Medicine Section of NIA for technical support.
T.M.D. is the Leonard and Madlyn Abramson Professor in Neurodegenerative
Diseases.
NR 32
TC 24
Z9 31
U1 4
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD APR 15
PY 2011
VL 145
IS 2
BP 284
EP 299
DI 10.1016/j.cell.2011.03.016
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 750MA
UT WOS:000289549900016
PM 21496646
ER
PT J
AU Finkel, T
AF Finkel, Toren
TI Telomeres and Mitochondrial Function
SO CIRCULATION RESEARCH
LA English
DT Editorial Material
ID P53
C1 NIH, Ctr Mol Med, Bethesda, MD 20892 USA.
RP Finkel, T (reprint author), NIH, Ctr Mol Med, Bldg 10,CRC 5-3330, Bethesda, MD 20892 USA.
EM finkelt@nih.gov
FU Intramural NIH HHS [ZIA HL006037-03]
NR 8
TC 5
Z9 5
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7330
EI 1524-4571
J9 CIRC RES
JI Circ.Res.
PD APR 15
PY 2011
VL 108
IS 8
BP 903
EP 904
DI 10.1161/RES.0b013e31821bc2d8
PG 2
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 749ZF
UT WOS:000289510800003
PM 21493920
ER
PT J
AU Kang, W
Tong, JHM
Chan, AWH
Lee, TL
Lung, RWM
Leung, PPS
So, KKY
Wu, KC
Fan, DM
Yu, J
Sung, JJY
To, KF
AF Kang, Wei
Tong, Joanna H. M.
Chan, Anthony W. H.
Lee, Tin-Lap
Lung, Raymond W. M.
Leung, Patrick P. S.
So, Ken K. Y.
Wu, Kaichun
Fan, Daiming
Yu, Jun
Sung, Joseph J. Y.
To, Ka-Fai
TI Yes-Associated Protein 1 Exhibits Oncogenic Property in Gastric Cancer
and Its Nuclear Accumulation Associates with Poor Prognosis
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID MESSENGER-RNA EXPRESSION; CELL CONTACT INHIBITION; TUMOR-SUPPRESSOR;
GROWTH-CONTROL; HIPPO PATHWAY; WW DOMAIN; YAP; GENE; IDENTIFICATION;
CARCINOMA
AB Purpose: Yes-associated protein 1 (YAP1) is a multifunctional protein that can interact with different transcription factors to activate gene expression. The role of YAP1 in tumorigenesis is unclear. We aimed to investigate the functional role of YAP1 in tumorigenesis of gastric cancer.
Experimental Design: YAP1 expresson in gastric adenocarcinoma was evaluated. The biological function was determined by proliferation assay, colony formation, cell invasion, and flow cytometric analysis through knocking down or ectopic expressing YAP1 in gastric cancer cell lines coupled with in vivo study. The possible downstream effectors of YAP1 were investigated by expression microarray.
Results: YAP1 protein expression was upregulated in gastric cancer. Nuclear accumulation of YAP1 was associated with poor disease-specific survival (P = 0.021), especially in patients with early-stage diseases (P < 0.001). Knockdown YAP1 resulted in a significant reduction in proliferation, anchorage-dependent colony formation, cell invasion, and cell motility. Ectopic YAP1 expression promoted anchorage-independent colony formation, induced a more invasive phenotype, and accelerated cell growth both in vitro and in vivo. Microarray analysis highlighted the alteration of MAPK (mitogen-activated protein kinase) pathway by YAP1. We confirmed a constitutive activation of RAF/MEK/ERK (extracellular signal-regulated kinase) in YAP1-expressing MKN45 cells and further showed that YAP1 enhanced serum/epidermal growth factor-induced c-Fos expression in gastric cancer cells.
Conclusions: Our findings supported that YAP1 exhibits oncogenic property in gastric cancer. We provided the first evidence that YAP1 exerted the oncogenic function by enhancing the capacity to activate the early-response gene pathway. YAP1 could be a prognostic biomarker and potential therapeutic target for gastric cancer. Clin Cancer Res; 17(8); 2130-9. (C) 2011 AACR.
C1 [Kang, Wei; Tong, Joanna H. M.; Chan, Anthony W. H.; Lung, Raymond W. M.; Leung, Patrick P. S.; So, Ken K. Y.; To, Ka-Fai] Sir YK Pao Ctr Canc, State Key Lab Oncol S China, Dept Anat & Cellular Pathol, Hong Kong, Hong Kong, Peoples R China.
[Kang, Wei; Tong, Joanna H. M.; Lung, Raymond W. M.; Leung, Patrick P. S.; So, Ken K. Y.; Yu, Jun; Sung, Joseph J. Y.; To, Ka-Fai] Chinese Univ Hong Kong, Inst Digest Dis, Hong Kong, Hong Kong, Peoples R China.
[Kang, Wei; Tong, Joanna H. M.; Lung, Raymond W. M.; Leung, Patrick P. S.; So, Ken K. Y.; Yu, Jun; Sung, Joseph J. Y.; To, Ka-Fai] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China.
[Yu, Jun; Sung, Joseph J. Y.] Chinese Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China.
[Wu, Kaichun; Fan, Daiming] Fourth Mil Med Univ, Xijing Hosp, State Key Lab Canc Biol, Xian 710032, Peoples R China.
[Wu, Kaichun; Fan, Daiming] Fourth Mil Med Univ, Xijing Hosp, Inst Digest Dis, Xian 710032, Peoples R China.
[Lee, Tin-Lap] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP To, KF (reprint author), Chinese Univ Hong Kong, Prince Wales Hosp, Inst Digest Dis, Dept Anat & Cellular Pathol, Shatin, Hong Kong, Peoples R China.
EM kfto@cuhk.edu.hk
RI Lee, Tin-Lap/A-7853-2009; Kang, Wei/C-5451-2016; Raymond ,
Lung/G-3200-2011; Tong, Joanna/J-9327-2013; Lung, Raymond/D-1274-2014;
Yu, Jun /D-8569-2015;
OI Lee, Tin-Lap/0000-0002-6654-0988; Raymond , Lung/0000-0002-0813-7429;
Chan, Anthony/0000-0002-1771-163X
FU National Basic Research Program of China (973 Program) [2010CB529305]
FX The project was supported by a research grant of National Basic Research
Program of China (973 Program, 2010CB529305).
NR 32
TC 69
Z9 71
U1 1
U2 12
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 APR 15
PY 2011
VL 17
IS 8
BP 2130
EP 2139
DI 10.1158/1078-0432.CCR-10-2467
PG 10
WC Oncology
SC Oncology
GA 750NP
UT WOS:000289555500008
PM 21346147
ER
PT J
AU Breinig, M
Mayer, P
Harjung, A
Goeppert, B
Malz, M
Penzel, R
Neumann, O
Hartmann, A
Dienemann, H
Giaccone, G
Schirmacher, P
Kern, MA
Chiosis, G
Rieker, RJ
AF Breinig, Marco
Mayer, Philipp
Harjung, Andreas
Goeppert, Benjamin
Malz, Mona
Penzel, Roland
Neumann, Olaf
Hartmann, Arndt
Dienemann, Hendrik
Giaccone, Giuseppe
Schirmacher, Peter
Kern, Michael Andre
Chiosis, Gabriela
Rieker, Ralf Joachim
TI Heat Shock Protein 90-Sheltered Overexpression of Insulin-Like Growth
Factor 1 Receptor Contributes to Malignancy of Thymic Epithelial Tumors
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID HSP90 MOLECULAR CHAPERONE; FACTOR-I RECEPTOR; CELL LUNG-CANCER;
HEAT-SHOCK-PROTEIN-90 INHIBITOR; ONCOGENE ADDICTION; GLIOBLASTOMA CELLS;
ANTITUMOR-ACTIVITY; MUTATIONAL STATUS; TRANSGENIC MICE; CARCINOMA
AB Purpose: The underlying molecular mechanisms of thymic epithelial malignancies (TEMs) are poorly understood. Consequently, there is a lack of efficacious targeted therapies and patient prognosis remains dismal, particularly for advanced TEMs. We sought to investigate protumorigenic mechanism relevant to this understudied cancer.
Experimental Design: Recently established cell lines derived from thymic epithelial tumors were used as a model system. The antitumor activity of specific heat shock protein 90 (Hsp90) inhibitors was investigated by an analysis of cell viability, cell cycle, and apoptosis using MTT-assays and flow cytometry. Western blotting was used to investigate the altered expression of Hsp90 clients. Pharmacological inhibitors against select Hsp90 clients, as well as RNAi, were employed to test the relevance of each client independently. Tissue microarray analysis was performed to match the in vitro findings with observations obtained from patient-derived samples.
Results: Hsp90 inhibition significantly reduces cell viability of thymic carcinoma cells, induces cell cycle arrest and apoptosis, and blocks invasiveness. Hsp90 inhibition triggers the degradation of multiple oncogenic clients, for example insulin-like growth factor 1 receptor (IGF-1R), CDK4, and the inactivation of PI3K/Akt and RAF/Erk signaling. Mechanistically, the IGF/IGF-1R-signaling axis contributes to the establishment of the antiapoptotic phenotype of thymic cancer cells. Finally, IGF-1R is overexpressed in advanced TEMs.
Conclusions: We have unraveled a novel protumorigenic mechanism in TEMs, namely Hsp90-capacitated overexpression of IGF-1R, which confers apoptosis evasion in malignant thymic epithelial cells. Our data indicate that Hsp90 inhibition, which simultaneously blocks multiple cancer hallmarks, represents a therapeutic strategy in TEMs that may merit evaluation in clinical trials. Clin Cancer Res; 17(8); 2237-49. (C) 2011 AACR.
C1 [Breinig, Marco] Univ Heidelberg Hosp, Inst Pathol, Dept Gen Pathol, D-69120 Heidelberg, Germany.
[Hartmann, Arndt; Rieker, Ralf Joachim] Univ Hosp Erlangen, Dept Pathol, Erlangen, Germany.
[Dienemann, Hendrik] Thoraxklin Univ Klinikum Heidelberg, Dept Thorac Surg, Heidelberg, Germany.
[Giaccone, Giuseppe] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
[Chiosis, Gabriela] Mem Sloan Kettering Canc Ctr, Dept Med, Program Mol Pharmacol & Chem, New York, NY 10021 USA.
RP Breinig, M (reprint author), Univ Heidelberg Hosp, Inst Pathol, Dept Gen Pathol, D-69120 Heidelberg, Germany.
EM marco.breinig@med.uni-heidelberg.de
RI Giaccone, Giuseppe/E-8297-2017
OI Giaccone, Giuseppe/0000-0002-5023-7562
FU Mr. William H. and Mrs. Alice Goodwin and the Commonwealth Foundation
for Cancer Research; Experimental Therapeutics Center of Memorial
Sloan-Kettering Cancer Center; Deutsche Krebshilfe [Ke107685];
Forschungsschwerpunktprogramm des Landes Baden Wurttemberg [Kapitel.
1423;Tit.Gr 74]
FX This work was supported by "Mr. William H. and Mrs. Alice Goodwin and
the Commonwealth Foundation for Cancer Research" and "The Experimental
Therapeutics Center of Memorial Sloan-Kettering Cancer Center" to G.
Chiosis, by grants from the Deutsche Krebshilfe to M.A. Kern and P.
Schirmacher (Ke107685), and by grants from the
"Forschungsschwerpunktprogramm des Landes Baden Wurttemberg" (Kapitel.
1423;Tit.Gr 74).
NR 49
TC 15
Z9 16
U1 0
U2 1
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 APR 15
PY 2011
VL 17
IS 8
BP 2237
EP 2249
DI 10.1158/1078-0432.CCR-10-1689
PG 13
WC Oncology
SC Oncology
GA 750NP
UT WOS:000289555500018
PM 21372220
ER
PT J
AU Schecter, A
Malik, N
Haffner, D
Smith, S
Harris, TR
Paepke, O
Birnbaum, L
AF Schecter, Arnold
Malik, Noor
Haffner, Darrah
Smith, Sarah
Harris, T. Robert
Paepke, Olaf
Birnbaum, Linda
TI Reply to Comments on "Bisphenol A (BPA) in U.S. Food"
SO ENVIRONMENTAL SCIENCE & TECHNOLOGY
LA English
DT Letter
C1 [Schecter, Arnold; Malik, Noor; Haffner, Darrah; Smith, Sarah; Harris, T. Robert] Univ Texas Sch Publ Hlth, Dallas, TX 75390 USA.
[Paepke, Olaf] Eurofins GfA GmbH Lab, Hamburg, Germany.
[Birnbaum, Linda] NCI, Bethesda, MD 20892 USA.
[Birnbaum, Linda] NIH, Res Triangle Pk, NC USA.
RP Schecter, A (reprint author), Univ Texas Sch Publ Hlth, Dallas, TX 75390 USA.
NR 6
TC 0
Z9 0
U1 1
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0013-936X
J9 ENVIRON SCI TECHNOL
JI Environ. Sci. Technol.
PD APR 15
PY 2011
VL 45
IS 8
BP 3814
EP 3815
DI 10.1021/es200613m
PG 2
WC Engineering, Environmental; Environmental Sciences
SC Engineering; Environmental Sciences & Ecology
GA 747SZ
UT WOS:000289341300088
ER
PT J
AU Anantharaman, V
Abhiman, S
de Souza, RF
Aravind, L
AF Anantharaman, Vivek
Abhiman, Saraswathi
de Souza, Robson F.
Aravind, L.
TI Comparative genomics uncovers novel structural and functional features
of the heterotrimeric GTPase signaling system
SO GENE
LA English
DT Article
DE Protein sequence analysis; GPCR; RGS; G-proteins; START domain; PAS
domain; CHASE domain; 7TM
ID PROTEIN-COUPLED RECEPTORS; PLASMA-MEMBRANE; ALPHA-SUBUNITS; RGS
PROTEINS; TRANSMEMBRANE RECEPTORS; STRUCTURE PREDICTION; ACTIVATING
PROTEINS; KINASE ACTIVATION; CRYSTAL-STRUCTURE; BINDING DOMAIN
AB Though the heterotrimeric G-proteins signaling system is one of the best studied in eukaryotes, its provenance and its prevalence outside of model eukaryotes remains poorly understood. We utilized the wealth of sequence data from recently sequenced eukaryotic genomes to uncover robust G-protein signaling systems in several poorly studied eukaryotic lineages such as the parabasalids, heteroloboseans and stramenopiles. This indicated that the G alpha subunit is likely to have separated from the ARF-like GTPases prior to the last eukaryotic common ancestor. We systematically identified the structure and sequence features associated with this divergence and found that most of the neomorphic positions in Ga form a ring of residues centered on the nucleotide binding site, several of which are likely to be critical for interactions with the RCS domain for its GAP function. We also present evidence that in some of the potentially early branching eukaryotic lineages, like Trichontonas, G alpha is likely to function independently of the G beta gamma subunits. We were able to identify previously unknown G gamma subunits in Naegleria, suggesting that the trimeric version was already present by the time of the divergence of the heteroloboseans from the remaining eukaryotes. Evolution of G alpha subunits is dominated by several independent lineage-specific expansions (LSEs). In most of these cases there are concomitant, independent LSEs of RGS proteins along with an extraordinary diversification of their domain architectures. The diversity of RGS domains from Naegleria in particular, which has the largest complement of G alpha and RGS proteins for any eukaryote, provides new insights into RGS function and evolution. We uncovered a new class of soluble ligand receptors of bacterial origin with RGS domains and an extraordinary diversity of membrane-linked, redox-associated, adhesion-dependent and small molecule-induced G-protein signaling networks that evolved in early-branching eukaryotes, independently of parallel systems in animals. Furthermore, this newly characterized diversity of RCS domains helps in defining their ancestral conserved interfaces with G alpha and also those interfaces that are prone to extensive lineage-specific diversification and are thereby responsible for selectivity in G alpha-RCS interactions. Several mushrooms show LSEs of G alpha s but not of RGS proteins pointing to the probable differentiation of Gas in conjunction with mating-type diversity. When combined with the characterization of the 7TM receptors (GPCRs), it becomes apparent that, through much of eukaryotic evolution, cells contained both 7TM receptors that acted as GEFs and those as GAPs (with C-terminal RCS domains) for G alpha s. Only in some lineages like animals and stramenopiles the 7TM receptors were restricted to GEF only roles, probably due to selection imposed by the rate-constants of the G alpha s that underwent lineage-specific expansion in them. In the alveolate lineage the 7TM receptors occur independently of heterotrimeric G-proteins, suggesting the prevalence of G-protein-independent signaling in these organisms. Published by Elsevier B.V.
C1 [Anantharaman, Vivek; 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
OI Anantharaman, Vivek/0000-0001-8395-0009
FU National Library of Medicine, NIH
FX The work by the authors was supported by the intramural funds of the
National Library of Medicine, NIH. We would like to thank Lakshminarayan
M. Iyer for his role in an early stage of this early work and for
reading the final manuscript.
NR 115
TC 21
Z9 22
U1 3
U2 16
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-1119
J9 GENE
JI Gene
PD APR 15
PY 2011
VL 475
IS 2
BP 63
EP 78
DI 10.1016/j.gene.2010.12.001
PG 16
WC Genetics & Heredity
SC Genetics & Heredity
GA 748OX
UT WOS:000289401000002
PM 21182906
ER
PT J
AU Juan, AH
Derfoul, A
Feng, XS
Ryall, JG
Dell'Orso, S
Pasut, A
Zare, H
Simone, JM
Rudnicki, MA
Sartorelli, V
AF Juan, Aster H.
Derfoul, Assia
Feng, Xuesong
Ryall, James G.
Dell'Orso, Stefania
Pasut, Alessandra
Zare, Hossein
Simone, James M.
Rudnicki, Michael A.
Sartorelli, Vittorio
TI Polycomb EZH2 controls self-renewal and safeguards the transcriptional
identity of skeletal muscle stem cells
SO GENES & DEVELOPMENT
LA English
DT Article
DE Polycomb; Ezh2; satellite cells; muscle growth; muscle regeneration
ID SATELLITE CELLS; DEVELOPMENTAL REGULATORS; GENE-EXPRESSION; PROTEIN
EZH2; DIFFERENTIATION; REGENERATION; PAX7; PROGENITORS;
METHYLTRANSFERASE; HETEROGENEITY
AB Satellite cells (SCs) sustain muscle growth and empower adult skeletal muscle with vigorous regenerative abilities. Here, we report that EZH2, the enzymatic subunit of the Polycomb-repressive complex 2 (PRC2), is expressed in both Pax7(+)/Myf5(-) stem cells and Pax7(+)/Myf5(+) committed myogenic precursors and is required for homeostasis of the adult SC pool. Mice with conditional ablation of Ezh2 in SCs have fewer muscle postnatal Pax7(+) cells and reduced muscle mass and fail to appropriately regenerate. These defects are associated with impaired SC proliferation and derepression of genes expressed in nonmuscle cell lineages. Thus, EZH2 controls self-renewal and proliferation, and maintains an appropriate transcriptional program in SCs.
C1 [Juan, Aster H.; Derfoul, Assia; Feng, Xuesong; Ryall, James G.; Dell'Orso, Stefania; Zare, Hossein; Sartorelli, Vittorio] Natl Inst Arthrit Musculoskeletal & Skin Dis NIAM, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA.
[Pasut, Alessandra; Rudnicki, Michael A.] Ottawa Hosp Res Inst, Sprott Ctr Stem Cell Res, Regenerat Med Program, Ottawa, ON K1H 8L6, Canada.
[Simone, James M.] NIAMS, Flow Cytometry Sect, NIH, Bethesda, MD 20892 USA.
RP Sartorelli, V (reprint author), Natl Inst Arthrit Musculoskeletal & Skin Dis NIAM, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA.
EM sartorev@mail.nih.gov
OI Ryall, James/0000-0003-4702-1143
FU NH and MRC (Australia); National Institute of Arthritis,
Musculoskeletal, and Skin Diseases of the National Institutes of Health
FX We thank Mario Capecchi, David Goldhamer, and Alexander Tarakhovsky for
sharing the Pax7-Cre, MyoD-Cre, and Ezh2fl/fl animals,
respectively. Fabio Rossi provided advice with the FACS experiments,
Jeffrey Lay helped with cell sorting, and Gustavo Gutierrez-Cruz
assisted with animal genotyping. Members of the NIAMS Laboratory Animal
Care and Use Section and NIAMS Light Imaging Section are kindly
acknowledged. J.G.R. was supported by an Overseas Biomedical Research
Fellowship from the NH and MRC (Australia). This work was supported in
part by the Intramural Research Program of the National Institute of
Arthritis, Musculoskeletal, and Skin Diseases of the National Institutes
of Health.
NR 35
TC 98
Z9 99
U1 1
U2 6
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
EI 1549-5477
J9 GENE DEV
JI Genes Dev.
PD APR 15
PY 2011
VL 25
IS 8
BP 789
EP 794
DI 10.1101/gad.2027911
PG 6
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 750PD
UT WOS:000289559600002
PM 21498568
ER
PT J
AU Huang, YF
Chen, LA
Zhou, Y
Liu, H
Yang, JQ
Liu, ZG
Wang, C
AF Huang, Yuefeng
Chen, Liang
Zhou, Yi
Liu, Heng
Yang, Jueqing
Liu, Zhenggang
Wang, Chen
TI UXT-V1 protects cells against TNF-induced apoptosis through modulating
complex II formation
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID NF-KAPPA-B; ALPHA-INDUCED APOPTOSIS; C-FLIP; CASPASE-8 ACTIVATION;
STRUCTURAL BASIS; KINASE RIP; DEATH; INHIBITION; INDUCTION; PATHWAYS
AB Proteins that directly regulate tumor necrosis factor (TNF) signaling have critical roles in determining cell death and survival. Previously we characterized ubiquitously expressed transcript (UXT)-V2 as a novel transcriptional cofactor to regulate nuclear factor-kappa B in the nucleus. Here we report that another splicing isoform of UXT, UXT-V1, localizes in cytoplasm and regulates TNF-induced apoptosis. UXT-V1 knockdown cells are hypersensitive to TNF-induced apoptosis. We demonstrated that UXT-V1 is a new component of TNF receptor signaling complex. We found that UXT-V1 binds to TNF receptor-associated factor 2 and prevents TNF receptor-associated death domain protein from recruiting Fas-associated protein with death domain. More importantly, UXT-V1 is a short-half-life protein, the degradation of which facilitates the formation of the apoptotic receptor complex II in response to TNF treatment. This study demonstrates that UXT-V1 is a novel regulator of TNF-induced apoptosis and sheds new light on the underlying molecular mechanism of this process.
C1 [Huang, Yuefeng; Chen, Liang; Zhou, Yi; Liu, Heng; Yang, Jueqing; Wang, Chen] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, Shanghai 200031, Peoples R China.
[Liu, Zhenggang] NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Wang, C (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, Shanghai 200031, Peoples R China.
EM zgliu@box-z.nih.gov; cwang01@sibs.ac.cn
FU Ministry of Science and Technology of Shanghai [09XD1404800]; National
Natural Science Foundation of China [31030021]; Ministry of Science and
Technology of China [2010CB529703, 2011CB910904, 2007CB914504]; Chinese
Academy of Sciences [KSCX1-YW-R-06]
FX We thank Wilhelm Krek (ETH Zurich), Lin Li (Shanghai Institutes for
Biological Sciences [SIBS]), and Zhengjun Chen (SIBS) for reagents.
Zhenggang Liu and Chen Wang are members of the Center for Signal
Transduction, Chinese Academy of Sciences. This work was supported by
grants from Ministry of Science and Technology of Shanghai
(09XD1404800); the National Natural Science Foundation of China
(31030021); the Ministry of Science and Technology of China
(2010CB529703, 2011CB910904, 2007CB914504); and the Chinese Academy of
Sciences (KSCX1-YW-R-06).
NR 33
TC 9
Z9 9
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
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD APR 15
PY 2011
VL 22
IS 8
BP 1389
EP 1397
DI 10.1091/mbc.E10-10-0827
PG 9
WC Cell Biology
SC Cell Biology
GA 750OU
UT WOS:000289558600023
PM 21307340
ER
PT J
AU Xu, F
Wu, HX
Katritch, V
Han, GW
Jacobson, KA
Gao, ZG
Cherezov, V
Stevens, RC
AF Xu, Fei
Wu, Huixian
Katritch, Vsevolod
Han, Gye Won
Jacobson, Kenneth A.
Gao, Zhan-Guo
Cherezov, Vadim
Stevens, Raymond C.
TI Structure of an Agonist-Bound Human A(2A) Adenosine Receptor
SO SCIENCE
LA English
DT Article
ID PROTEIN-COUPLED-RECEPTOR; CRYSTAL-STRUCTURE; CONFORMATIONAL-CHANGES;
ALLOSTERIC MODULATION; SUBTYPE-SELECTIVITY; LIGAND RECOGNITION;
BINDING-SITE; ANTAGONIST; RESIDUES; COMPLEX
AB Activation of G protein-coupled receptors upon agonist binding is a critical step in the signaling cascade for this family of cell surface proteins. We report the crystal structure of the A(2A) adenosine receptor (A(2A)AR) bound to an agonist UK-432097 at 2.7 angstrom resolution. Relative to inactive, antagonist-bound A(2A)AR, the agonist-bound structure displays an outward tilt and rotation of the cytoplasmic half of helix VI, a movement of helix V, and an axial shift of helix III, resembling the changes associated with the active-state opsin structure. Additionally, a seesaw movement of helix VII and a shift of extracellular loop 3 are likely specific to A(2A)AR and its ligand. The results define the molecule UK-432097 as a "conformationally selective agonist" capable of receptor stabilization in a specific active-state configuration.
C1 [Xu, Fei; Wu, Huixian; Han, Gye Won; Cherezov, Vadim; Stevens, Raymond C.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
[Katritch, Vsevolod] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.
[Katritch, Vsevolod] Univ Calif San Diego, San Diego Supercomp Ctr, La Jolla, CA 92093 USA.
[Jacobson, Kenneth A.; Gao, Zhan-Guo] NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA.
RP Stevens, RC (reprint author), Scripps Res Inst, Dept Mol Biol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM stevens@scripps.edu
RI Jacobson, Kenneth/A-1530-2009; Cherezov, Vadim/L-9812-2013; Wu,
Huixian/N-6353-2014; Katritch, Vsevolod/Q-8357-2016;
OI Jacobson, Kenneth/0000-0001-8104-1493; Cherezov,
Vadim/0000-0002-5265-3914; Wu, Huixian/0000-0003-1357-9747; Katritch,
Vsevolod/0000-0003-3883-4505
FU National Institute of Diabetes and Digestive and Kidney Diseases; NIH
Roadmap Initiative [P50 GM073197]; NIH [GM075915]; NSF [IIS0308078];
Science Foundation Ireland [02-IN1-B266]; National Cancer Institute
[Y1-CO-1020]; National Institute of General Medical Sciences
[Y1-GM-1104]; [U54 GM094618]
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases (K.A.J.
and Z.-G.G.), PSI: Biology grant U54 GM094618 for structure production,
and NIH Roadmap Initiative grant P50 GM073197 for technology
development. R. C. S. thanks N. Dekker at AstraZeneca for suggesting the
UK-432097 compound for biochemical and structural studies. We thank J.
Velasquez for help on molecular biology; C. Cornillez-Ty, T. Trinh, and
K. Allin for help on baculovirus expression; E. Chien and W. Liu for
advice on protein purification and LCP crystallization; I. Wilson, M.
Hanson, and A. IJzerman for careful review and scientific feedback on
the manuscript; K. Kadyshevskaya for assistance with figure preparation;
A. Walker for assistance with manuscript preparation; L. Heitman for
A2AAR compounds used in thermal stability studies; Y. Zheng
and M. Caffrey for use of an in meso robot (built with support from NIH
grant GM075915, NSF grant IIS0308078, and Science Foundation Ireland
grant 02-IN1-B266); and J. Smith, R. Fischetti, and N. Sanishvili for
assistance in development and use of the minibeam and beamtime at
GM/CA-CAT beamline 23-ID at the Advanced Photon Source, which is
supported by National Cancer Institute grant Y1-CO-1020 and National
Institute of General Medical Sciences grant Y1-GM-1104. R. C. S. is a
founder and member of the board of directors of Receptos, a GPCR
structure-based drug discovery company. Atomic coordinates and structure
factors have been deposited in the Protein Data Bank with identification
code 3QAK.
NR 36
TC 433
Z9 439
U1 7
U2 62
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD APR 15
PY 2011
VL 332
IS 6027
BP 322
EP 327
DI 10.1126/science.1202793
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 750AT
UT WOS:000289516600036
PM 21393508
ER
PT J
AU Holm, TM
Habashi, JP
Doyle, JJ
Bedja, D
Chen, YC
van Erp, C
Lindsay, ME
Kim, D
Schoenhoff, F
Cohn, RD
Loeys, BL
Thomas, CJ
Patnaik, S
Marugan, JJ
Judge, DP
Dietz, HC
AF Holm, Tammy M.
Habashi, Jennifer P.
Doyle, Jefferson J.
Bedja, Djahida
Chen, YiChun
van Erp, Christel
Lindsay, Mark E.
Kim, David
Schoenhoff, Florian
Cohn, Ronald D.
Loeys, Bart L.
Thomas, Craig J.
Patnaik, Samarjit
Marugan, Juan J.
Judge, Daniel P.
Dietz, Harry C.
TI Noncanonical TGF beta Signaling Contributes to Aortic Aneurysm
Progression in Marfan Syndrome Mice
SO SCIENCE
LA English
DT Article
ID N-TERMINAL KINASE; MOUSE MODEL; NOONANS-SYNDROME; ACTIVATION; RECEPTOR;
CELLS; PATHOGENESIS; INHIBITOR; MUTATIONS; VALSALVA
AB Transforming growth factor-beta (TGF beta) signaling drives aneurysm progression in multiple disorders, including Marfan syndrome (MFS), and therapies that inhibit this signaling cascade are in clinical trials. TGF beta can stimulate multiple intracellular signaling pathways, but it is unclear which of these pathways drives aortic disease and, when inhibited, which result in disease amelioration. Here we show that extracellular signal-regulated kinase (ERK) 1 and 2 and Smad2 are activated in a mouse model of MFS, and both are inhibited by therapies directed against TGF beta. Whereas selective inhibition of ERK1/2 activation ameliorated aortic growth, Smad4 deficiency exacerbated aortic disease and caused premature death in MFS mice. Smad4-deficient MFS mice uniquely showed activation of Jun N-terminal kinase-1 (JNK1), and a JNK antagonist ameliorated aortic growth in MFS mice that lacked or retained full Smad4 expression. Thus, noncanonical (Smad-independent) TGF beta signaling is a prominent driver of aortic disease in MFS mice, and inhibition of the ERK1/2 or JNK1 pathways is a potential therapeutic strategy for the disease.
C1 [Holm, Tammy M.; Habashi, Jennifer P.; Doyle, Jefferson J.; Chen, YiChun; van Erp, Christel; Lindsay, Mark E.; Kim, David; Schoenhoff, Florian; Cohn, Ronald D.; Dietz, Harry C.] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA.
[Holm, Tammy M.; Habashi, Jennifer P.; Doyle, Jefferson J.; Chen, YiChun; van Erp, Christel; Lindsay, Mark E.; Kim, David; Schoenhoff, Florian; Cohn, Ronald D.; Dietz, Harry C.] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD 21205 USA.
[Habashi, Jennifer P.; Lindsay, Mark E.; Cohn, Ronald D.; Dietz, Harry C.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Pediat Cardiol, Baltimore, MD 21205 USA.
[Bedja, Djahida] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD 21205 USA.
[Loeys, Bart L.] Univ Ghent, Ctr Med Genet, B-9000 Ghent, Belgium.
[Thomas, Craig J.; Patnaik, Samarjit; Marugan, Juan J.] NIH, Chem Genom Ctr, Rockville, MD 20850 USA.
[Judge, Daniel P.; Dietz, Harry C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
RP Dietz, HC (reprint author), Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA.
EM hdietz@jhmi.edu
RI Doyle, Jefferson/C-3156-2013; Chen, Yi-Chun/H-4468-2013
FU National Institutes of Health; Howard Hughes Medical Institute; National
Marfan Foundation; Cellular and Molecular Medicine Training Program;
National Human Genome Research Institute; Smilow Center for Marfan
Syndrome Research
FX Supported by the National Institutes of Health (H. C. D. and D.P.J),
Howard Hughes Medical Institute (H. C. D.), National Marfan Foundation
(H. C. D., J.P.H., and J.J.D.), Cellular and Molecular Medicine Training
Program (J.J.D.), National Human Genome Research Institute Intramural
Research Program and the NIH Therapeutics for Rare and Neglected
Diseases Program (C.J.T., S. P., and J.J.M.), and the Smilow Center for
Marfan Syndrome Research (H. C. D.). We thank Dr. C. Deng for the
Smad4-targeted mice. Johns Hopkins University and the authors (H. C. D.,
J.P.H., D.P.J., and R. C.) have filed a patent relating to the use of
TGF beta antagonists, including angiotensin II type 1 receptor blockers,
for the treatment of Marfan syndrome.
NR 26
TC 182
Z9 187
U1 0
U2 28
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD APR 15
PY 2011
VL 332
IS 6027
BP 358
EP 361
DI 10.1126/science.1192149
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 750AT
UT WOS:000289516600047
PM 21493862
ER
PT J
AU Tang, J
Maddali, K
Dreis, CD
Sham, YY
Vince, R
Pommier, Y
Wang, ZQ
AF Tang, Jing
Maddali, Kasthuraiah
Dreis, Christine D.
Sham, Yuk Y.
Vince, Robert
Pommier, Yves
Wang, Zhengqiang
TI 6-Benzoyl-3-hydroxypyrimidine-2,4-diones as dual inhibitors of HIV
reverse transcriptase and integrase
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE HIV; 6-Benzoyl-3-hydroxypyrimidine-2,4-diones; Dual inhibitors; Reverse
transcriptase; Integrase
ID NONNUCLEOSIDE INHIBITORS; ANTIRETROVIRAL THERAPY; PHARMACOPHORE MODEL;
ANTI-HIV-1 ACTIVITY; DESIGN; PYRIMIDINEDIONES; STRATEGIES; ADHERENCE;
ANALOGS; UPDATE
AB N-3-Hydroxylation of pyrimidine-2,4-diones was recently found to yield inhibitors of both HIV-1 reverse transcriptase (RT) and integrase (IN). An extended series of analogues featuring a benzoyl group at the C-6 position of the pyrimidine ring was synthesized. Through biochemical studies it was found that these new analogues are dually active against both RT and IN in low micromolar range. Antiviral assays confirmed that these new inhibitors are active against HIV-1 in cell culture at nanomolar to low micromolar range, further validating 3-hydroxypyrimidine-2,4-diones as a viable scaffold for antiviral development. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Tang, Jing; Dreis, Christine D.; Sham, Yuk Y.; Vince, Robert; Wang, Zhengqiang] Univ Minnesota, Acad Hlth Ctr, Ctr Drug Design, Minneapolis, MN 55455 USA.
[Maddali, Kasthuraiah; Pommier, Yves] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA.
RP Wang, ZQ (reprint author), Univ Minnesota, Acad Hlth Ctr, Ctr Drug Design, 516 Delaware St SE, Minneapolis, MN 55455 USA.
EM wangx472@umn.edu
FU Center for Drug Design at the University of Minnesota; Center for Cancer
Research, National Cancer Institute, NIH; NIH-IATAP
FX This research was supported by the Center for Drug Design at the
University of Minnesota, by the Center for Cancer Research, National
Cancer Institute, NIH, and by an NIH-IATAP grant to Y. P. and K. M. We
thank Roger Ptak at Southern Research Institute for antiviral assays and
the Minnesota Supercomputing Institute for modeling resources.
NR 29
TC 17
Z9 19
U1 0
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD APR 15
PY 2011
VL 21
IS 8
BP 2400
EP 2402
DI 10.1016/j.bmcl.2011.02.069
PG 3
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 744DP
UT WOS:000289074700047
PM 21392991
ER
PT J
AU Gutierrez-Lugo, MT
Bewley, CA
AF Gutierrez-Lugo, Maria-Teresa
Bewley, Carole A.
TI Susceptibility and mode of binding of the Mycobacterium tuberculosis
cysteinyl transferase mycothiol ligase to tRNA synthetase inhibitors
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Mycothiol; Mycobacteria; STD NMR; Antituberculars; Aminoacyl adenosine
ID SMEGMATIS; MSHC; GROWTH; ENZYME
AB The cysteinyl transferase mycothiol ligase, or MshC, catalyzes the fourth step in the biosynthesis of the small molecular weight thiol mycothiol. MshC is essential for growth of Mycobacterium tuberculosis. Two groups of known aminoacyl tRNA synthetase inhibitors were evaluated for inhibition of M. tuberculosis MshC including aminoacyl adenosine analogs and natural products. Using enzyme assays, isothermal titration calorimetry and NMR, we show that MshC is selectively inhibited by cysteinyl sulfamoyl adenosine, and that discrimination occurs at the amino acid moiety. Published by Elsevier Ltd.
C1 [Gutierrez-Lugo, Maria-Teresa; Bewley, Carole A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Bewley, CA (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
EM caroleb@mail.nih.gov
FU NIH (NIDDK); Office of the Director, NIH
FX This work was supported by the NIH Intramural Research Program (NIDDK)
and the Intramural AIDS Targeted Antiviral Program, Office of the
Director, NIH (C.A.B.).
NR 18
TC 9
Z9 10
U1 0
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD APR 15
PY 2011
VL 21
IS 8
BP 2480
EP 2483
DI 10.1016/j.bmcl.2011.02.042
PG 4
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 744DP
UT WOS:000289074700064
PM 21392992
ER
PT J
AU Patterson, EE
Holloway, AK
Weng, J
Fojo, T
Kebebew, E
AF Patterson, Erin E.
Holloway, Alisha K.
Weng, Julie
Fojo, Tito
Kebebew, Electron
TI MicroRNA Profiling of Adrenocortical Tumors Reveals miR-483 as a Marker
of Malignancy
SO CANCER
LA English
DT Article
DE adrenocortical carcinoma; adrenal; microRNA; diagnostic marker
ID CDNA MICROARRAY DATA; GROWTH-FACTOR-II; GENE-EXPRESSION; CARCINOMA;
CANCER; NORMALIZATION; CLASSIFICATION; BIOMARKERS; SIGNATURE; SURVIVAL
AB BACKGROUND: The authors are interested in identifying molecular markers that can aid in the diagnosis of adrenocortical carcinoma (ACC). The aim of this study was to identify microRNAs (miRNAs or miRs) that are differentially expressed in malignant adrenocortical tumors as compared with benign tumors and assess their potential as diagnostic predictors. METHODS: Differentially expressed miRNAs were identified using microarray profiling of adrenocortical tumors and validated by quantitative real-time RT-PCR. RESULTS: Microarray profiling in benign and primary malignant adrenocortical tumors revealed several significant differences between these histological groups. By using directed quantitative RT-PCR analysis on a subset of these differentially expressed miRNAs, the authors determined that miRs -100, -125b, and -195 were significantly down-regulated, whereas miR-483-5p was significantly up-regulated in malignant as compared with benign tumors. Furthermore, the current study shows that miR-483-5p expression can accurately categorize tumors as benign or malignant. CONCLUSIONS: The authors identified 4 miRNAs that are dysregulated in adrenocortical carcinoma. The high expression of one of these, miR-483-5p, appears to be a defining characteristic of adrenocortical malignancies, and can thus be used to accurately distinguish between benign and malignant adrenocortical tumors. Cancer 2011;117:1630-9. (C) 2010 American Cancer Society.
C1 [Patterson, Erin E.; Kebebew, Electron] NCI, Endocrine Oncol Sect, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Holloway, Alisha K.] Gladstone Inst San Francisco, San Francisco, CA USA.
[Weng, Julie; Fojo, Tito] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA.
[Fojo, Tito] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Kebebew, E (reprint author), NCI, Endocrine Oncol Sect, Surg Branch, NIH, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
RI Holloway, Alisha/H-9574-2013
OI Holloway, Alisha/0000-0001-9810-389X
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
NR 39
TC 83
Z9 86
U1 2
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD APR 15
PY 2011
VL 117
IS 8
BP 1630
EP 1639
DI 10.1002/cncr.25724
PG 10
WC Oncology
SC Oncology
GA 746AM
UT WOS:000289213300011
PM 21472710
ER
PT J
AU Sui, J
Sheehan, J
Hwang, WC
Bankston, LA
Burchett, SK
Huang, CY
Liddington, RC
Beigel, JH
Marasco, WA
AF Sui, Jianhua
Sheehan, Jared
Hwang, William C.
Bankston, Laurie A.
Burchett, Sandra K.
Huang, Chiung-Yu
Liddington, Robert C.
Beigel, John H.
Marasco, Wayne A.
TI Wide Prevalence of Heterosubtypic Broadly Neutralizing Human
Anti-Influenza A Antibodies
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID INFLUENZA-A VIRUS; UNIVERSAL ANTIBODIES; AVIAN INFLUENZA; FUSION
PEPTIDE; HEMAGGLUTININ; INFECTION; SUBTYPES; VACCINE; PROTECTION;
INDUCTION
AB Background. Lack of life-long immunity against influenza viruses represents a major global health care problem with profound medical and economic consequences. A greater understanding of the broad-spectrum "heterosubtypic'' neutralizing human antibody (BnAb) response to influenza should bring us closer toward a universal influenza vaccine.
Methods. Serum samples obtained from 77 volunteers in an H5N1 vaccine study were analyzed for cross-reactive antibodies (Abs) against both subtype hemagglutinins (HAs) and a highly conserved pocket on the HA stem of Group 1 viruses. Cross-reactive Abs in commercial intravenous immunoglobulin were affinity purified using H5-coupled beads followed by step-wise monoclonal antibody competition or acid elution. Enzyme-linked immunosorbent assays were used to quantify cross-binding, and neutralization activity was determined with HA-pseudotyped viruses.
Results. Prevaccination serum samples have detectable levels of heterosubtypic HA binding activity to both Group 1 and 2 influenza A viruses, including subtypes H5 and H7, respectively, to which study subjects had not been vaccinated. Two different populations of Broadly neutralizing Abs (BnAbs) were purified from intravenous immunoglobulin by H5 beads: similar to 0.01% of total immunoglobulin G can bind to HAs from both Group 1 and 2 and neutralize H1N1 and H5N1 viruses; similar to 0.001% is F10-like Abs directed against the HA stem pocket on Group 1 viruses.
Conclusion. These data-to our knowledge, for the first time-quantitatively show the presence, albeit at low levels, of two populations of heterosubtypic BnAbs against influenza A in human serum. These observations warrant further investigation to determine their origin, host polymorphism(s) that may affect their expression levels and how to boost these BnAb responses by vaccination to reach sustainable protective levels.
C1 [Sui, Jianhua; Sheehan, Jared; Marasco, Wayne A.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Sui, Jianhua; Marasco, Wayne A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Burchett, Sandra K.] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Hwang, William C.; Bankston, Laurie A.; Burchett, Sandra K.; Liddington, Robert C.] Sanford Burnham Med Res Inst, Infect & Inflammatory Dis Ctr, La Jolla, CA USA.
[Huang, Chiung-Yu] NIAID, NIH, Bethesda, MD 20892 USA.
[Beigel, John H.] SAIC Frederick Inc, NIAID, NCI, Lab Immunoregulat,Div Intramural Res, Frederick, MD USA.
RP Marasco, WA (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA.
EM wayne_marasco@dfci.harvard.edu
OI SUI, JIANHUA/0000-0002-1272-9662
FU National Institute of Allergy and Infectious Diseases, National
Institute of Health [U01-AI074518]; National Cancer Institute, National
Institute of Health [HHSN261200800001E]; National Institutes of Health
(NIH)
FX This project has been funded in whole or in part with federal funds from
the National Institute of Allergy and Infectious Diseases, National
Institute of Health (U01-AI074518); and the National Cancer Institute,
National Institute of Health (HHSN261200800001E). The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the US
Government.; J. Sui and W.A.M. have received a share of patent royalties
paid to their institution from Genentech/Roche for the licensed patent
that covers antibodies such as the F10 that was used in the study. R.L.
and L.B. have received grant support, travel/meeting expenses, and
institutional support for writing assistance, medicines, equipment, or
administrative support from the National Institutes of Health (NIH).
W.C.H. and J. Sheehan have received support from the NIH through their
institutions. All other authors: no conflicts.
NR 24
TC 56
Z9 57
U1 1
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD APR 15
PY 2011
VL 52
IS 8
BP 1003
EP 1009
DI 10.1093/cid/cir121
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 747DI
UT WOS:000289300100008
PM 21460314
ER
PT J
AU Fogel, J
Li, Q
Taha, TE
Hoover, DR
Kumwenda, NI
Mofenson, LM
Kumwenda, JJ
Fowler, MG
Thigpen, MC
Eshleman, SH
AF Fogel, Jessica
Li, Qing
Taha, Taha E.
Hoover, Donald R.
Kumwenda, Newton I.
Mofenson, Lynne M.
Kumwenda, Johnstone J.
Fowler, Mary Glenn
Thigpen, Michael C.
Eshleman, Susan H.
TI Initiation of Antiretroviral Treatment in Women After Delivery Can
Induce Multiclass Drug Resistance in Breastfeeding HIV-Infected Infants
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID TO-CHILD TRANSMISSION; DAR-ES-SALAAM; EXTENDED ZIDOVUDINE; IN-UTERO;
NEVIRAPINE; PROPHYLAXIS; PREVENTION; TANZANIA; BOTSWANA; THERAPY
AB Background. The World Health Organization currently recommends initiation of highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV)-infected lactating women with CD4+ cell counts <350 cells/mu L or stage 3 or 4 disease. We analyzed antiretroviral drug resistance in HIV-infected infants in the Post Exposure Prophylaxis of Infants trial whose mothers initiated HAART postpartum (with a regimen of nevirapine [NVP], stavudine, and lamivudine). Infants in the trial received single-dose NVP and a week of zidovudine (ZDV) at birth; some infants also received extended daily NVP prophylaxis, with or without extended ZDV prophylaxis.
Methods. We analyzed drug resistance in plasma samples collected from all HIV-infected infants whose mothers started HAART in the first postpartum year. Resistance testing was performed using the first plasma sample collected within 6 months after maternal HAART initiation. Categorical variables were compared by exact or trend tests; continuous variables were compared using rank-sum tests.
Results. Multiclass resistance (MCR) was detected in HIV from 11 (29.7%) of 37 infants. Infants were more likely to develop MCR infection if their mothers initiated HAART earlier in the postpartum period (by 14 weeks vs after 14 weeks and up to 6 months vs after 6 months, P = .0009), or if the mother was exclusively breastfeeding at the time of HAART initiation (exclusive breastfeeding vs mixed feeding vs no breastfeeding, P = .003).
Conclusions. postpartum maternal HAART initiation was associated with acquisition of MCR in HIV-infected breastfeeding infants. The risk was higher among infants whose mothers initiated HAART closer to the time of delivery or were still exclusively breastfeeding when they first reported HAART use.
C1 [Fogel, Jessica; Fowler, Mary Glenn; Eshleman, Susan H.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Taha, Taha E.; Kumwenda, Newton I.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA.
[Li, Qing] NHGRI, NIH, Inherited Dis Res Branch, Baltimore, MD USA.
[Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Pediat Adolescent & Maternal AIDS Branch, Rockville, MD USA.
[Hoover, Donald R.] Rutgers State Univ, Dept Stat & Biostat, Piscataway, NJ USA.
[Hoover, Donald R.] Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, Piscataway, NJ USA.
[Fowler, Mary Glenn; Thigpen, Michael C.] Ctr Dis Control & Prevent, Epidemiol Branch, Div HIV AIDS Prevent, Atlanta, GA USA.
[Kumwenda, Johnstone J.] Univ Malawi, Dept Med, Blantyre, Malawi.
RP Eshleman, SH (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Ross Bldg 646,720 Rutland Ave, Baltimore, MD 21205 USA.
EM seshlem@jhmi.edu
OI Mofenson, Lynne/0000-0002-2818-9808
FU National Institute of Allergy and Infectious Diseases (NIAID/NIH) [R01
HD050180]; Eunice Kennedy Shriver National Institutes of Child Health
and Human Development of the National Institutes of Health (NICHD/NIH)
[R03 HD061299]; Centers for Disease Control and Prevention
[U50/CCU022061]; International Maternal Pediatric and Adolescent AIDS
Clinical Trials (IMPAACT) Network [U01 AI068633]; NIAID; National
Institute on Drug Abuse; National Institute of Mental Health; Office of
AIDS Research of the NIH, DHHS [U01 AI068613]; National Human Genome
Research Institute, NIH
FX The National Institute of Allergy and Infectious Diseases (NIAID/NIH)
(R01 HD050180), the Eunice Kennedy Shriver National Institutes of Child
Health and Human Development of the National Institutes of Health
(NICHD/NIH) (R03 HD061299), the Centers for Disease Control and
Prevention (Cooperative Agreement U50/CCU022061), the International
Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) Network
(U01 AI068633), the HIV Prevention Trials Network (HPTN) sponsored by
NIAID, the National Institute on Drug Abuse, the National Institute of
Mental Health, and the Office of AIDS Research of the NIH, DHHS (U01
AI068613), and the Intramural Research Program of the National Human
Genome Research Institute, NIH.
NR 26
TC 26
Z9 26
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD APR 15
PY 2011
VL 52
IS 8
BP 1069
EP 1076
DI 10.1093/cid/cir008
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 747DI
UT WOS:000289300100021
PM 21460326
ER
PT J
AU Gordon, SN
Cecchinato, V
Andresen, V
Heraud, JM
Hryniewicz, A
Parks, RW
Venzon, D
Chung, HK
Karpova, T
McNally, J
Silvera, P
Reimann, KA
Matsui, H
Kanehara, T
Shinmura, Y
Yokote, H
Franchini, G
AF Gordon, Shari N.
Cecchinato, Valentina
Andresen, Vibeke
Heraud, Jean-Michel
Hryniewicz, Anna
Parks, Robyn Washington
Venzon, David
Chung, Hye-kyung
Karpova, Tatiana
McNally, James
Silvera, Peter
Reimann, Keith A.
Matsui, Hajime
Kanehara, Tomomi
Shinmura, Yasuhiko
Yokote, Hiroyuki
Franchini, Genoveffa
TI Smallpox Vaccine Safety Is Dependent on T Cells and Not B Cells
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID VIRUS SIVMAC251 INFECTION; ATOPIC-DERMATITIS; ADVERSE EVENTS;
UNITED-STATES; PROGRESSIVE VACCINIA; CYNOMOLGUS MONKEYS; ECZEMA
VACCINATUM; PROTECTS MONKEYS; NAIVE ADULTS; COMPLICATIONS
AB The licensed smallpox vaccine, ACAM2000, is a cell culture derivative of Dryvax. Both ACAM2000 and Dryvax are administered by skin scarification and can cause progressive vaccinia, with skin lesions that disseminate to distal sites. We have investigated the immunologic basis of the containment of vaccinia in the skin with the goal to identify safer vaccines for smallpox. Macaques were depleted systemically of T or B cells and vaccinated with either Dryvax or an attenuated vaccinia vaccine, LC16m8. B cell depletion did not affect the size of skin lesions induced by either vaccine. However, while depletion of both CD4(+) and CD8(+) T cells had no adverse effects on LC16m8-vaccinated animals, it caused progressive vaccinia in macaques immunized with Dryvax. As both Dryvax and LC16m8 vaccines protect healthy macaques from a lethal monkeypox intravenous challenge, our data identify LC16m8 as a safer and effective alternative to ACAM2000 and Dryvax vaccines for immunocompromised individuals.
C1 [Gordon, Shari N.; Cecchinato, Valentina; Andresen, Vibeke; Hryniewicz, Anna; Parks, Robyn Washington; Franchini, Genoveffa] Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA.
[Venzon, David] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
[Karpova, Tatiana] Lab Receptor Biol Gene Express & Metab, Fluorescence Imaging Facil, Bethesda, MD USA.
[McNally, James; Silvera, Peter] So Res Inst, Frederick, MD USA.
[Chung, Hye-kyung] Adv Bioscience Labs, Kensington, MD USA.
[Reimann, Keith A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis,Dept Med, Boston, MA 02215 USA.
[Heraud, Jean-Michel] Inst Pasteur Madagascar, World Hlth Org Natl Influenza Lab, Antananarivo, Madagascar.
[Matsui, Hajime; Kanehara, Tomomi; Shinmura, Yasuhiko; Yokote, Hiroyuki] Chemoserotherapeut Res Inst KAKETSUKEN, Kumamoto, Japan.
RP Franchini, G (reprint author), Anim Models & Retroviral Vaccines Sect, 9000 Rockville Pike NCI,41-D804, Bethesda, MD 20892 USA.
EM franchig@mail.nih.gov
RI HERAUD, Jean-Michel/O-1464-2013
OI HERAUD, Jean-Michel/0000-0003-1107-0859
FU National Institute of Health; Chemo-Sero-Therapeutic Research Institute
FX This research was partially funded by the intramural budget of Dr.
Franchini at the National Institute of Health and through a
Collaborative Research and Development Agreement by the
Chemo-Sero-Therapeutic Research Institute.
NR 46
TC 25
Z9 25
U1 0
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD APR 15
PY 2011
VL 203
IS 8
BP 1043
EP 1053
DI 10.1093/infdis/jiq162
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 745MC
UT WOS:000289168500003
PM 21450994
ER
PT J
AU Faust, H
Pastrana, DV
Buck, CB
Dillner, J
Ekstrom, J
AF Faust, Helena
Pastrana, Diana V.
Buck, Christopher B.
Dillner, Joakim
Ekstrom, Johanna
TI Antibodies to Merkel Cell Polyomavirus Correlate to Presence of Viral
DNA in the Skin
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID CARCINOMA; TUMORS
AB To validate whether Merkel cell polyomavirus (MCV) serology correlates with MCV infection, we compared real-time polymerase chain reaction results for MCV DNA on fresh-frozen biopsy specimens from various skin lesions and healthy skin from 434 patients to MCV serology results using viruslike particles (VLPs) and MCV neutralization assays. Sixty- five percent of participants were MCV seropositive and 18% were MCV DNA positive. The presence of antibodies was correlated with the presence of virus DNA (odds ratio, 27.85 [95% confidence interval, 6.6-166.5]), with 97% of patients who tested positive for MCV DNA being MCV seropositive. VLP antibody levels correlated to neutralization titers (r = 5.72), and high antibody levels correlated to high MCV load (P<.01).
C1 [Dillner, Joakim] Lund Univ, Malmo Univ Hosp, Dept Med Microbiol, UMAS, SE-20502 Malmo, Sweden.
[Dillner, Joakim] Karolinska Inst, Dept Lab Med Med Epidemiol & Biostat, Stockholm, Sweden.
[Pastrana, Diana V.; Buck, Christopher B.] NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA.
RP Dillner, J (reprint author), Lund Univ, Malmo Univ Hosp, Dept Med Microbiol, UMAS, Entrance 78, SE-20502 Malmo, Sweden.
EM joakim.dillner@med.lu.se
OI Buck, Christopher/0000-0003-3165-8094
FU Swedish Cancer Society [2098]; Swedish Research Council [K
2001-57x-21044-01-3]; Clinical Research Committee of the Skane County
Council [M2007/1656]
FX This work was supported by the Swedish Cancer Society (grant no. 2098);
the Swedish Research Council K 2001-57x-21044-01-3; and the Clinical
Research Committee of the Skane County Council M2007/1656.
NR 15
TC 22
Z9 22
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 APR 15
PY 2011
VL 203
IS 8
BP 1096
EP 1100
DI 10.1093/infdis/jiq173
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 745MC
UT WOS:000289168500009
PM 21450999
ER
PT J
AU Morrison, SG
Farris, CM
Sturdevant, GL
Whitmire, WM
Morrison, RP
AF Morrison, Sandra G.
Farris, Christina M.
Sturdevant, Gail L.
Whitmire, William M.
Morrison, Richard P.
TI Murine Chlamydia trachomatis Genital Infection Is Unaltered by Depletion
of CD4(+) T cells and Diminished Adaptive Immunity
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID TRACT INFECTION; MICE; REINFECTION; ANTIBODY; ENTEROTOXIN; RESOLUTION;
MUTATIONS; RESPONSES; STRAINS; DISEASE
AB Chlamydia muridarum and Chlamydia trachomatis mouse models of genital infection have been used to study chlamydial immunity and vaccine development. To assess the protective role of CD4(+) T cells in resolving C. trachomatis and C. muridarum genital tract infections, we used the female mouse model and evaluated infection in the presence and absence of CD4(+) T cells. In contrast to C. muridarum infection, C. trachomatis infection was unaltered in the absence of CD4(+) T cells. Mice infected with C. trachomatis developed protective immunity to re-challenge, but unlike C. muridarum infection, optimum resistance required multiple infectious challenges, despite the generation of adaptive serum and local chlamydial specific immune responses. Thus, understanding the chlamydial pathogenic and host immunologic factors that result in a diminished protective role for CD4(+) T cells in C. trachomatis murine infection might lead to new insights important to human immunity and vaccine development.
C1 [Morrison, Sandra G.; Farris, Christina M.; Morrison, Richard P.] Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA.
[Farris, Christina M.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA.
[Sturdevant, Gail L.; Whitmire, William M.] NIAID, Intracellular Parasites Lab, NIH, Hamilton, MT USA.
RP Morrison, RP (reprint author), Univ Arkansas Med Sci, Dept Microbiol & Immunol, 4301 W Markham St,Slot 511, Little Rock, AR 72205 USA.
EM rpmorrison@uams.edu
FU National Institutes of Health [AI-038991]; Arkansas Bioscience Institute
FX The National Institutes of Health grant AI-038991 and the Arkansas
Bioscience Institute.
NR 41
TC 18
Z9 18
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 APR 15
PY 2011
VL 203
IS 8
BP 1120
EP 1128
DI 10.1093/infdis/jiq176
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 745MC
UT WOS:000289168500012
PM 21321103
ER
PT J
AU Spearman, P
Lally, MA
Elizaga, M
Montefiori, D
Tomaras, GD
McElrath, MJ
Hural, J
De Rosa, SC
Sato, A
Huang, YD
Frey, SE
Sato, P
Donnelly, J
Barnett, S
Corey, LJ
AF Spearman, Paul
Lally, Michelle A.
Elizaga, Marnie
Montefiori, David
Tomaras, Georgia D.
McElrath, M. Juliana
Hural, John
De Rosa, Stephen C.
Sato, Alicia
Huang, Yunda
Frey, Sharon E.
Sato, Paul
Donnelly, John
Barnett, Susan
Corey, Lawrence J.
CA HIV Vaccine Trials Network NIAID
TI A Trimeric, V2-Deleted HIV-1 Envelope Glycoprotein Vaccine Elicits
Potent Neutralizing Antibodies but Limited Breadth of Neutralization in
Human Volunteers
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; SUBTYPE-B; CATIONIC
MICROPARTICLES; PARTIAL DELETION; RHESUS MACAQUES; TYPE-1 ISOLATE; DNA
VACCINES; DOUBLE-BLIND; INFECTION
AB Methods. This phase 1 clinical trial employed a DNA prime and subunit envelope protein boost in an attempt to generate cellular and humoral immune responses that might be desirable in a protective HIV vaccine. Priming was performed via intramuscular injection with gag and env DNA adsorbed to polylactide coglycolide microspheres, followed by boosting with a recombinant trimeric envelope (Env) glycoprotein delivered in MF59 adjuvant.
Results. The DNA prime and protein boost were generally safe and well-tolerated. Env-specific CD4(+) cellular responses were generated that were predominantly detected after Env protein boosting. Neutralizing antibody responses against the homologous SF162 viral isolate were remarkably strong and were present in the majority of vaccine recipients, including a strong response against CD4-induced epitopes on gp120. Despite the promising potency of this vaccine approach, neutralization breadth against heterologous tier 2 strains of HIV-1 was minimal.
Conclusions. Potent neutralization against neutralization-sensitive strains of HIV is achievable in humans through a DNA prime, recombinant oligomeric Env protein boost regimen. Eliciting substantial breadth of neutralization remains an elusive goal.
Clinical Trials Registration. NCT00073216.
C1 [Spearman, Paul] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA.
[Spearman, Paul] Childrens Healthcare Atlanta, Atlanta, GA 30322 USA.
[Lally, Michelle A.] Miriam Hosp, Dept Med, Providence, RI 02906 USA.
[Lally, Michelle A.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA.
[Elizaga, Marnie; McElrath, M. Juliana; Hural, John; De Rosa, Stephen C.; Sato, Alicia; Huang, Yunda; Corey, Lawrence J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Montefiori, David; Tomaras, Georgia D.] Duke Univ, Sch Med, Dept Surg, Durham, NC USA.
[Frey, Sharon E.] St Louis Univ, Sch Med, Dept Internal Med, St Louis, MO 63103 USA.
[Sato, Paul] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
[Donnelly, John; Barnett, Susan] Novartis Vaccines & Diagnost, Cambridge, MA USA.
RP Spearman, P (reprint author), Emory Univ, Sch Med, Dept Pediat, 2015 Uppergate Dr, Atlanta, GA 30322 USA.
EM paul.spearman@emory.edu
RI Lally, Michelle/I-4865-2016; Tomaras, Georgia/J-5041-2016
OI Lally, Michelle/0000-0003-0716-4668;
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health [U01 AI068614, NO1-AI05396]
FX National Institute of Allergy and Infectious Diseases, National
Institutes of Health (U01 AI068614 and NO1-AI05396). The Emory Center
for AIDS Research (P30 AI050409) provided some support for the
preparation of this manuscript.
NR 35
TC 45
Z9 45
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD APR 15
PY 2011
VL 203
IS 8
BP 1165
EP 1173
DI 10.1093/infdis/jiq175
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 745MC
UT WOS:000289168500017
PM 21451004
ER
PT J
AU Handwerker, DA
Bandettini, PA
AF Handwerker, Daniel A.
Bandettini, Peter A.
TI Hemodynamic signals not predicted? Not so: A comment on Sirotin and Das
(2009)
SO NEUROIMAGE
LA English
DT Editorial Material
AB In their 2009 Nature article: "Anticipatory haemodynamic signals in sensory cortex not predicted by local neuronal activity," Yevginiy Sirotin and Aniruddha Das suggest that hemodynamic signals, the basis of functional MRI (fMRI), can arise without any measurable neuronal activity. They report that hemodynamic signals in visual cortex were associated with and time-locked to the anticipation of a visual stimulus, and importantly, without any associated neuronal activity as measured with direct electrophysiological recordings. In this commentary, we demonstrate, using an assessment of their own data, that their claims are not strongly supported. In fact, we found that specific LFP frequency ranges predicted with a high degree of accuracy, the "dark" or "anticipatory" hemodynamic response. For other frequency ranges, we found differences in phase but not magnitude of the measured and predicted hemodynamic response. Importantly, when comparing simply the magnitude as well as the time series standard deviation of the electrophysiological recordings with those of the measured hemodynamic responses, we found a direct correspondence of the dark/stimulated magnitude and standard deviation between the electrophysiological recordings and the hemodynamic responses. All of these analyses strongly imply that anticipatory hemodynamic responses are, in fact, accurately predicted in phase and magnitude by several LFP frequency bands, and are predicted in standard deviation and magnitude by the standard deviation and magnitude of even a wider range of LFP frequencies. We argue that rather than casting doubt on fMRI signal changes, these studies open up an interesting window into exploring more subtle neurovascular relationships. Published by Elsevier Inc.
C1 [Handwerker, Daniel A.; Bandettini, Peter A.] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Bandettini, Peter A.] NIMH, Funct MRI Facil, NIH, Bethesda, MD 20892 USA.
RP Bandettini, PA (reprint author), Bldg 10,Room 1D80,10 Ctr Dr,MSC 1148, Bethesda, MD 20892 USA.
EM Bandettini@nih.gov
FU Intramural NIH HHS [Z99 MH999999]
NR 3
TC 12
Z9 12
U1 1
U2 2
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 APR 15
PY 2011
VL 55
IS 4
BP 1409
EP 1412
DI 10.1016/j.neuroimage.2010.04.037
PG 4
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 741DO
UT WOS:000288843500001
PM 20406693
ER
PT J
AU Handwerker, DA
Bandettini, PA
AF Handwerker, Daniel A.
Bandettini, Peter A.
TI Simple explanations before complex theories: Alternative interpretations
of Sirotin and Das' observations
SO NEUROIMAGE
LA English
DT Editorial Material
AB We make a few additional points regarding our discussion with Sirotin and Das' 2009 Nature paper and their 2011 NeuroImage response to our commentary. While we find their data interesting in itself, we remain concerned with how the data are interpreted by the authors. We discuss two categories of methodological issues that limit the conclusions one can draw from their results. (1) The measures of fit quality between the optical and electrical data: kernel shape variation, variance of predicted/measured signals, and R(2), interact with each other and are confounded by the fact that one condition has a lower signal magnitude and therefore, lower signal-to-noise-ratio (SNR). (2) Hemodynamic responses to distinct events will be incorrectly or inefficiently estimated if the hemodynamic responses overlap across periodic trials that are not jittered and have an inter-trial interval less than 15 s. Most importantly, the overlapping responses across trials might cause transient effects that look similar to the anticipatory effects presented by Sirotin and Das. While their study demonstrates a potentially useful way to probe neurovascular coupling, we believe the current results have little practical relevance for interpreting hemodynamic measures of neural activity such as those used in fMRI. We conclude by making several suggestions for future analyses, which might help elucidate the mechanisms behind these observations and lead to a better understanding of how these observations relate to hemodynamic based measures of neural activation. Published by Elsevier Inc.
C1 [Handwerker, Daniel A.; Bandettini, Peter A.] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD USA.
[Bandettini, Peter A.] NIMH, Funct MRI Facil, NIH, Bethesda, MD USA.
RP Bandettini, PA (reprint author), Bldg 10,Room 1D80,10 Ctr Dr,MSC 1148, Bethesda, MD 20892 USA.
EM Bandettini@nih.gov
FU Intramural NIH HHS [Z99 MH999999]
NR 4
TC 7
Z9 7
U1 0
U2 0
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 APR 15
PY 2011
VL 55
IS 4
BP 1419
EP 1422
DI 10.1016/j.neuroimage.2011.01.029
PG 4
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 741DO
UT WOS:000288843500003
PM 21256227
ER
PT J
AU Slobounov, SM
Gay, M
Zhang, K
Johnson, B
Pennell, D
Sebastianelli, W
Horovitz, S
Hallett, M
AF Slobounov, S. M.
Gay, M.
Zhang, K.
Johnson, B.
Pennell, D.
Sebastianelli, W.
Horovitz, S.
Hallett, M.
TI Alteration of brain functional network at rest and in response to YMCA
physical stress test in concussed athletes: RsFMRI study
SO NEUROIMAGE
LA English
DT Article
DE Mild traumatic brain injury (mTBI); Resting state fMRI (rsFMRI); YMCA
physical stress test
ID DIFFUSE AXONAL INJURY; ALZHEIMERS-DISEASE; CORPUS-CALLOSUM; MILD;
CONNECTIVITY; ABNORMALITIES; MRI; FMRI; SYMPTOMS; SCALE
AB There is still controversy in the literature whether a single episode of mild traumatic brain injury (mTBI) results in short- and/or long-term functional and structural deficits in the concussed brain. With the inability of traditional brain imaging techniques to properly assess the severity of brain damage induced by a concussive blow, there is hope that more advanced applications such as resting state functional magnetic resonance imaging (rsFMRI) will be more specific in accurately diagnosing mTBI. In this rsFMRI study, we examined 17 subjects 10 +/- 2 days post-sports-related mTBI and 17 age-matched normal volunteers (NVs) to investigate the possibility that the integrity of the resting state brain network is disrupted following a single concussive blow. We hypothesized that advanced brain imaging techniques may reveal subtle alterations of functional brain connections in asymptomatic mTBI subjects. There are several findings of interest. All mTBI subjects were asymptomatic based upon clinical evaluation and neuropsychological (NP) assessments prior to the MRI session. The mTBI subjects revealed a disrupted functional network both at rest and in response to the YMCA physical stress test. Specifically, interhemispheric connectivity was significantly reduced in the primary visual cortex, hippocampal and dorsolateral prefrontal cortex networks (p < 0.05). The YMCA physical stress induced nonspecific and similar changes in brain network connectivity patterns in both the mTBI and NV groups. These major findings are discussed in relation to underlying mechanisms, clinical assessment of mTBI, and current debate regarding functional brain connectivity in a clinical population. Overall, our major findings clearly indicate that functional brain alterations in the acute phase of injury are overlooked when conventional clinical and neuropsychological examinations are used. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Slobounov, S. M.; Gay, M.; Zhang, K.; Johnson, B.] Penn State Univ, Dept Kinesiol, University Pk, PA 16802 USA.
[Slobounov, S. M.; Horovitz, S.; Hallett, M.] NINDS, NIH, Bethesda, MD USA.
[Pennell, D.] Penn State Univ, Chandlee Lab, Social Life & Engn Sci Imaging Ctr, University Pk, PA 16802 USA.
[Slobounov, S. M.; Gay, M.; Sebastianelli, W.] Penn State Univ, Dept Orthopaed & Med Rehabil, HMC, University Pk, PA 16802 USA.
RP Slobounov, SM (reprint author), Penn State Univ, Dept Kinesiol, 19 Recreat Bldg, University Pk, PA 16802 USA.
EM sms18@psu.edu
RI Li, Yiou/G-4991-2010
FU NIH [RO1 NS056227-01A2]
FX This study was supported by NIH Grant RO1 NS056227-01A2 "Identification
of Athletes at Risk for Traumatic Brain Injury" awarded to Dr.
Slobounov, PI.
NR 58
TC 65
Z9 68
U1 1
U2 14
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 APR 15
PY 2011
VL 55
IS 4
BP 1716
EP 1727
DI 10.1016/j.neuroimage.2011.01.024
PG 12
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 741DO
UT WOS:000288843500033
PM 21255654
ER
PT J
AU Athar, M
Walsh, SB
Kopelovich, L
Elmets, CA
AF Athar, Mohammad
Walsh, Stephanie B.
Kopelovich, Levy
Elmets, Craig A.
TI Pathogenesis of nonmelanoma skin cancers in organ transplant recipients
SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
LA English
DT Review
DE Immunosuppression; Skin cancer; Organ transplant recepients;
Pathogenesis; Prevention
ID ULTRAVIOLET-RADIATION; CYCLOSPORINE-A; IMMUNOSUPPRESSIVE THERAPY;
ORNITHINE-DECARBOXYLASE; MEDICAL PROGRESS; CELL CARCINOMA; INDUCED
TUMORS; HAIRLESS MICE; CHEMOPREVENTION; CARCINOGENESIS
AB Nonmelanoma skin cancer (NMSC) is the most common human cancer, with an incidence of more than 1.2 million per year in the USA. The risk for the development of NMSCs increases by approximately 10-250 fold in chronically immune suppressed organ transplant recipients (OTRs). Solar UVB is the most common etiologic factor in the development of this neoplasm, both in immune competent and immune suppressed populations. This review provides a description of NMSC in OTRs. It also provides an account of the various immunologic and non-immune-dependent mechanisms involved in the pathogenesis and progression of NMSCs in OTRs. Finally, this review addresses possible strategies for the prevention of this cancer, particularly focusing on the aspects that may be incorporated to prevent negative effects of chemopreventive chemicals on graft survival. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Athar, Mohammad; Walsh, Stephanie B.; Elmets, Craig A.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA.
[Athar, Mohammad; Walsh, Stephanie B.; Elmets, Craig A.] Univ Alabama, Skin Dis Res Ctr, Birmingham, AL 35294 USA.
[Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Elmets, Craig A.] Birmingham VA Med Ctr, Birmingham, AL USA.
RP Athar, M (reprint author), Univ Alabama, Dept Dermatol, Volker Hall,Room 509,1530 3rd Ave S, Birmingham, AL 35294 USA.
EM mathar@uab.edu
FU NIH [R01 ES015323, N01-CN-43300, P30 AR050948, R21 ES017494, T32
AR053458]
FX This work was supported in part by NIH grants R01 ES015323 (to MA),
N01-CN-43300 (to MA), P30 AR050948, R21 ES017494 (to MA), and T32
AR053458 (SBW).
NR 53
TC 18
Z9 18
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-9861
J9 ARCH BIOCHEM BIOPHYS
JI Arch. Biochem. Biophys.
PD APR 15
PY 2011
VL 508
IS 2
SI SI
BP 159
EP 163
DI 10.1016/j.abb.2011.01.004
PG 5
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 740DO
UT WOS:000288772000006
PM 21232524
ER
PT J
AU Li, F
Patterson, AD
Hofer, CC
Krausz, KW
Gonzalez, FJ
Idle, JR
AF Li, Fei
Patterson, Andrew D.
Hoefer, Constance C.
Krausz, Kristopher W.
Gonzalez, Frank J.
Idle, Jeffrey R.
TI A comprehensive understanding of thioTEPA metabolism in the mouse using
UPLC-ESI-QTOFMS-based metabolomics
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE ThioTEPA; Metabolomics; Ultraperformance liquid chromatography;
Time-of-flight mass spectrometry; Tandem mass spectrometry
ID PANCREATIC ENCEPHALOPATHY; IFOSFAMIDE ENCEPHALOPATHY; THIODIGLYCOLIC
ACID; THIAMINE-DEFICIENCY; URINARY-EXCRETION; MASS-SPECTROMETRY;
AQUEOUS-SOLUTIONS; BREAST-CANCER; PHASE-I;
N,N',N''-TRIETHYLENETHIOPHOSPHORAMIDE
AB ThioTEPA, an alkylating agent with anti-tumor activity, has been used as an effective anticancer drug since the 1950s. However, a complete understanding of how its alkylating activity relates to clinical efficacy has not been achieved, the total urinary excretion of thioTEPA and its metabolites is not resolved, and the mechanism of formation of the potentially toxic metabolites S-carboxymethylcysteine (SCMC) and thiodiglycolic acid (TDGA) remains unclear. In this study, the metabolism of thioTEPA in a mouse model was comprehensively investigated using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) based-metabolomics. The nine metabolites identified in mouse urine suggest that thioTEPA underwent ring-opening, N-dechloroethylation, and conjugation reactions in vivo. SCMC and TDGA, two downstream thioTEPA metabolites, were produced from thioTEPA from two novel metabolites 1,2,3-trichloroTEPA (VII) and dechloroethyltrichloroTEPA (VIII). SCMC and TDGA excretion were increased about 4-fold and 2-fold, respectively, in urine following the thioTEPA treatment. The main mouse metabolites of thioTEPA in vivo were TEPA (II), monochloroTEPA (III) and thioTEPA-mercapturate (IV). In addition, five thioTEPA metabolites were detected in serum and all shared similar disposition. Although thioTEPA has a unique chemical structure which is not maintained in the majority of its metabolites, metabolomic analysis of its biotransformation greatly contributed to the investigation of thioTEPA metabolism in vivo, and provides useful information to understand comprehensively the pharmacological activity and potential toxicity of thioTEPA in the clinic. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Idle, Jeffrey R.] Univ Bern, Inst Clin Pharmacol, CH-3010 Bern, Switzerland.
[Li, Fei; Patterson, Andrew D.; Krausz, Kristopher W.; Gonzalez, Frank J.; Idle, Jeffrey R.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20852 USA.
[Hoefer, Constance C.] DMPKORE, D-85057 Ingolstadt, Germany.
RP Idle, JR (reprint author), Univ Bern, Inst Clin Pharmacol, Murtenstr 35, CH-3010 Bern, Switzerland.
EM lif3@mail.nih.gov; andrewpatterson@mail.nih.gov; c.hoefer@dmpkore.com;
krauszk@intra.nci.nih.gov; fjgonz@helix.nih.gov; jeff.idle@ikp.unibe.ch
RI Patterson, Andrew/G-3852-2012; Li, Fei/F-6849-2013;
OI Patterson, Andrew/0000-0003-2073-0070; Idle, Jeff/0000-0002-6143-1520
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
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.
NR 45
TC 18
Z9 19
U1 0
U2 15
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD APR 15
PY 2011
VL 81
IS 8
BP 1043
EP 1053
DI 10.1016/j.bcp.2011.01.024
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 743RM
UT WOS:000289036400009
PM 21300029
ER
PT J
AU Feder, A
Skipper, J
Blair, JR
Buchholz, K
Mathew, SJ
Schwarz, M
Doucette, JT
Alonso, A
Collins, KA
Neumeister, A
Charney, DS
AF Feder, Adriana
Skipper, Jamie
Blair, James R.
Buchholz, Katherine
Mathew, Sanjay J.
Schwarz, Markus
Doucette, John T.
Alonso, Angelique
Collins, Katherine A.
Neumeister, Alexander
Charney, Dennis S.
TI Tryptophan Depletion and Emotional Processing in Healthy Volunteers at
High Risk for Depression
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Affective go/no-go; emotional processing; family history; high risk;
major depression; tryptophan depletion
ID 1ST-DEGREE RELATIVES; UNMEDICATED PATIENTS; MONOAMINE DEPLETION; STROOP
TASK; MOOD; PERFORMANCE; SEROTONIN; RESPONSES; DISORDER; BIAS
AB Background: Studies in depressed patients have demonstrated the presence of emotional bias toward negative stimuli, as well as dysregulated brain serotonin function. The present study compared the effects of acute tryptophan depletion (ATD) on both an emotional processing and a planning task in never-depressed healthy volunteers at high and low familial risk for depression.
Methods: Young adults with no personal psychiatric history were stratified into two groups based on family history (n = 25). Participants were enrolled in a randomized, double-blind, placebo-controlled crossover ATD study and completed the affective go/no-go and Tower of London tasks once during each condition.
Results: There was a significant treatment by valence by group interaction on the affective go/no-go, driven primarily by a greater frequency of inappropriate responses to sad than to happy distracters in the high-risk group during ATD. No group differences were observed on the Tower of London.
Conclusions: Asymptomatic individuals at high familial risk for depression showed abnormalities in emotional processing while undergoing experimentally induced tryptophan depletion. These findings support emotional processing disturbances as potential trait-level abnormalities associated with the risk of mood disorder.
C1 [Feder, Adriana; Skipper, Jamie; Buchholz, Katherine; Mathew, Sanjay J.; Alonso, Angelique; Collins, Katherine A.; Neumeister, Alexander; Charney, Dennis S.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA.
[Doucette, John T.] Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY 10029 USA.
[Charney, Dennis S.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA.
[Charney, Dennis S.] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA.
[Blair, James R.] NIMH, NIH, Bethesda, MD 20892 USA.
[Mathew, Sanjay J.] Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA.
[Schwarz, Markus] Univ Munich, Univ Psychiat Hosp, Munich, Germany.
RP Feder, A (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA.
EM adriana.feder@mssm.edu
FU National Center for Research Resources, a component of the National
Institutes of Health [MO1-RR00071]; GlaxoSmithKline; Alexza
Pharmaceuticals; Novartis; National Alliance for Research on
Schizophrenia and Depression; Roche; AstraZeneca; Evotec Jazz
Pharmaceuticals; Merck; Pfizer; Pfizer, Inc.; Eli Lilly; UCB Pharma,
Inc.; Ortho-McNeil Janssen Scientific Affairs, LLC.
FX This work was performed at the Mood and Anxiety Disorders Program,
Department of Psychiatry, Mount Sinai School of Medicine, New York, New
York, and was funded by Grant Number MO1-RR00071 from the National
Center for Research Resources, a component of the National Institutes of
Health.; Dr. Feder has received grant/research support from
GlaxoSmithKline. Dr. Mathew has received grant/research support from
Alexza Pharmaceuticals, GlaxoSmithKline, Novartis, National Alliance for
Research on Schizophrenia and Depression, and Roche and has received
consulting or lecture fees from AstraZeneca, Evotec Jazz
Pharmaceuticals, Merck, and Pfizer. Dr. Neumeister has received
grant/research support from Pfizer, Inc.; Eli Lilly; UCB Pharma, Inc.;
and Ortho-McNeil Janssen Scientific Affairs, LLC. In addition, Drs.
Charney and Mathew have been named as inventors on a use-patent of
ketamine for the treatment of depression. Dr. Charney reported no other
biomedical financial interests or potential conflicts of interest. Ms.
Skipper, Dr. Blair, Ms. Buchholz, Dr. Schwarz, Dr. Doucette, Ms. Alonso,
and Ms. Collins reported no biomedical financial interests or potential
conflicts of interest.
NR 21
TC 20
Z9 21
U1 1
U2 8
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 APR 15
PY 2011
VL 69
IS 8
BP 804
EP 807
DI 10.1016/j.biopsych.2010.12.033
PG 4
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 741GS
UT WOS:000288852800019
PM 21377656
ER
PT J
AU Abaan, OD
Francis, P
Pineda, M
Walker, R
Bilke, S
Davis, SR
Meltzer, PS
AF Abaan, Ogan D.
Francis, Princy
Pineda, Marbin
Walker, Robert
Bilke, Sven
Davis, Sean R.
Meltzer, Paul S.
TI Identification of novel cancer DNA sequence variants in human sarcomas
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Abaan, Ogan D.; Francis, Princy; Pineda, Marbin; Walker, Robert; Bilke, Sven; Davis, Sean R.; Meltzer, Paul S.] NCI, CCR, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 3934
DI 10.1158/1538-7445.AM2011-3934
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701403257
ER
PT J
AU Adams-Campbell, LL
Makambi, KH
Collins, TA
Bright-Gbebry, M
Rosenberg, L
Palmer, JR
AF Adams-Campbell, Lucile L.
Makambi, Kepher H.
Collins, Tanya Agurs
Bright-Gbebry, Mireille
Rosenberg, Lynn
Palmer, Julie R.
TI Dietary patterns and the risk of colorectal adenomas: The Black Women's
Health Study
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Adams-Campbell, Lucile L.; Makambi, Kepher H.; Bright-Gbebry, Mireille] Georgetown Lombardi Comp Canc Ctr, Washington, DC USA.
[Collins, Tanya Agurs] NCI, Bethesda, MD 20892 USA.
[Rosenberg, Lynn; Palmer, Julie R.] Boston Univ, Sch Med, Slone Epidemiol Ctr, Brookine, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 1925
DI 10.1158/1538-7445.AM2011-1925
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701406004
ER
PT J
AU Akalu, A
Liebes, L
Xu, RL
Schneider, R
Takebe, N
Cohen, D
AF Akalu, Abebe
Liebes, Leonard
Xu, Rulang
Schneider, Robert
Takebe, Naoko
Cohen, Deirdre
TI Quantitative expression of the hedgehog (Hh) signaling pathway in
gastric carcinoma: A novel protocol to process RNA from
paraffin-embedded tissue
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Akalu, Abebe; Liebes, Leonard; Xu, Rulang; Schneider, Robert; Cohen, Deirdre] NYU, Med Ctr, New York, NY 10016 USA.
[Takebe, Naoko] NCI, NIH, Betheda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 2230
DI 10.1158/1538-7445.AM2011-2230
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701405182
ER
PT J
AU Alley, MC
Hollingshead, MG
Borgel, SD
Plater, K
Burkett, MW
Anver, MR
Yen, BR
Hite, KM
Scudiero, DA
Monks, A
Mertins, SD
Shoemaker, RH
Niederhuber, JE
AF Alley, Michael C.
Hollingshead, Melinda G.
Borgel, Suzanne D.
Plater, Kevin
Burkett, Mark W.
Anver, Miriam R.
Yen, Brandon R.
Hite, Karen M.
Scudiero, Dominic A.
Monks, Anne
Mertins, Susan D.
Shoemaker, Robert H.
Niederhuber, John E.
TI Human colon cancer cell lines contain subsets of cells with the capacity
to initiate highly prolific clonal growth in soft agar culture and to
form transplantable tumor xenografts in vivo
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Alley, Michael C.; Hollingshead, Melinda G.; Yen, Brandon R.; Mertins, Susan D.; Shoemaker, Robert H.] NCI, Frederick, MD 21701 USA.
[Borgel, Suzanne D.; Plater, Kevin; Burkett, Mark W.; Anver, Miriam R.; Hite, Karen M.; Scudiero, Dominic A.; Monks, Anne] SAIC Frederick, Frederick, MD USA.
[Niederhuber, John E.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 5202
DI 10.1158/1538-7445.AM2011-5202
PG 1
WC Oncology
SC Oncology
GA V43SO
UT WOS:000209701300376
ER
PT J
AU Altwerger, GH
Han, JJ
Kohn, EC
Yu, MS
AF Altwerger, Gary H.
Han, Jasmine J.
Kohn, Elise C.
Yu, Minshu
TI SLPI enhances the expression of PLSCR1 in the HEY-A8 ovarian cancer cell
line
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Altwerger, Gary H.; Han, Jasmine J.; Kohn, Elise C.; Yu, Minshu] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 1508
DI 10.1158/1538-7445.AM2011-1508
PG 1
WC Oncology
SC Oncology
GA V43SO
UT WOS:000209701300277
ER
PT J
AU Ames, MM
Reid, JM
Buhrow, SA
Kuffel, MJ
Walden, CA
Covey, JM
Behrsing, HP
Millin, MD
AF Ames, Matthew M.
Reid, Joel M.
Buhrow, Sarah A.
Kuffel, Mary J.
Walden, Chad A.
Covey, Joseph M.
Behrsing, Holger P.
Millin, Myrtle Davis
TI Characterization of the metabolite profile for batracylin and
N-acetylbatracylin in rat and human models of invitro and in vivo
metabolism: Elucidation of pathways that might contribute to batracylin
toxicity
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Ames, Matthew M.; Reid, Joel M.; Buhrow, Sarah A.; Kuffel, Mary J.; Walden, Chad A.] Mayo Clin, Rochester, MN USA.
[Covey, Joseph M.; Millin, Myrtle Davis] NCI, Rockville, MD USA.
[Behrsing, Holger P.] NCI, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 1303
DI 10.1158/1538-7445.AM2011-1303
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701405296
ER
PT J
AU Anderson, KE
Mongin, SJ
Sinha, R
Stolzenberg-Solomon, R
Gross, MD
Ziegler, RG
Mabie, JE
Risch, A
Kazin, SS
Church, TR
AF Anderson, Kristin E.
Mongin, Steven J.
Sinha, Rashmi
Stolzenberg-Solomon, Rachael
Gross, Myron D.
Ziegler, Regina G.
Mabie, Jerome E.
Risch, Adam
Kazin, Sally S.
Church, Timothy R.
TI Pancreatic cancer risk update: Associations with meat-derived carcinogen
intake in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening
Trial (PLCO) cohort
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Anderson, Kristin E.; Mongin, Steven J.; Gross, Myron D.; Church, Timothy R.] Univ Minnesota, Minneapolis, MN USA.
[Sinha, Rashmi; Stolzenberg-Solomon, Rachael; Ziegler, Regina G.] NCI, Rockville, MD USA.
[Mabie, Jerome E.; Risch, Adam; Kazin, Sally S.] Informat Management Serv Inc, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 1907
DI 10.1158/1538-7445.AM2011-1907
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701406091
ER
PT J
AU Anderson, WF
Katki, H
Rosenberg, PS
AF Anderson, William F.
Katki, Hormuzd
Rosenberg, Philip S.
TI Reappraisal of breast cancer incidence in the United States
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Anderson, William F.; Katki, Hormuzd; Rosenberg, Philip S.] NCI, NIH, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA LB-445
DI 10.1158/1538-7445.AM2011-LB-445
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701406039
ER
PT J
AU Angelos, MG
Kohn, EC
McCollum, AK
AF Angelos, Mathew G.
Kohn, Elise C.
McCollum, Andrea K.
TI Novel cell cycle regulation through the WW-domain of the co-chaperone
BAG3
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Angelos, Mathew G.; Kohn, Elise C.; McCollum, Andrea K.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA LB-190
DI 10.1158/1538-7445.AM2011-LB-190
PG 2
WC Oncology
SC Oncology
GA V43SO
UT WOS:000209701305425
ER
PT J
AU Annunziata, CM
Hsu, S
Hernandez, L
Kohn, E
Davidson, B
AF Annunziata, Christina M.
Hsu, Sarah
Hernandez, Lidia
Kohn, Elise
Davidson, Ben
TI IKK-epsilon contributes to the malignant progression of ovarian cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Annunziata, Christina M.; Hsu, Sarah; Hernandez, Lidia; Kohn, Elise] NCI, Bethesda, MD 20892 USA.
[Davidson, Ben] Oslo Univ Hosp, Oslo, Norway.
RI Annunziata, Christina/L-3219-2016
OI Annunziata, Christina/0000-0003-2033-6532
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 1479
DI 10.1158/1538-7445.AM2011-1479
PG 1
WC Oncology
SC Oncology
GA V43SO
UT WOS:000209701301459
ER
PT J
AU Anthony, K
Skinner, MA
Buchoff, JR
McCarthy, N
Schaefer, CF
Buetow, KH
AF Anthony, Kira
Skinner, Mhairi A.
Buchoff, Jeffrey R.
McCarthy, Nicola
Schaefer, Carl F.
Buetow, Kenneth H.
TI The NCI-Nature Pathway Interaction Database: A comprehensive resource
for cell signaling information
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Anthony, Kira] Nat Publishing Grp, Cambridge, MA USA.
[Skinner, Mhairi A.] Univ Guelph, Guelph, ON N1G 2W1, Canada.
[Buchoff, Jeffrey R.] SRA Int Inc, Fairfax, VA USA.
[McCarthy, Nicola] Nat Publishing Grp, London, England.
[Schaefer, Carl F.; Buetow, Kenneth H.] NCI, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 2885
DI 10.1158/1538-7445.AM2011-2885
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701403106
ER
PT J
AU Antony, S
Wu, YZ
Liu, H
Jiang, GJ
Juhasz, A
Lu, JM
Roy, KK
Doroshow, JH
AF Antony, Smitha
Wu, Yongzhong
Liu, Han
Jiang, Guojian
Juhasz, Agnes
Lu, Jiamo
Roy, Krishnendu K.
Doroshow, James H.
TI Regulation of Hif-1 alpha expression by NADPH oxidase 5 (Nox5) in human
cancer cell lines
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Antony, Smitha; Wu, Yongzhong; Liu, Han; Jiang, Guojian; Juhasz, Agnes; Lu, Jiamo; Roy, Krishnendu K.; Doroshow, James H.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 4205
DI 10.1158/1538-7445.AM2011-4205
PG 2
WC Oncology
SC Oncology
GA V43SO
UT WOS:000209701305131
ER
PT J
AU Aragon, R
Dickherber, A
Litwack, D
Vaught, J
Compton, C
AF Aragon, Richard
Dickherber, Anthony
Litwack, David
Vaught, Jimmie
Compton, Carolyn
TI The NCI-NIST-FDA effort to develop fitness-for-purpose biospecimen
assessment standards: Development of quality assessment metrics and
standards for optimal biospecimen utilization
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Aragon, Richard; Dickherber, Anthony; Litwack, David; Vaught, Jimmie; Compton, Carolyn] NCI, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 5078
DI 10.1158/1538-7445.AM2011-5078
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701405057
ER
PT J
AU Arnaldez, FI
Yeung, CL
Helman, LJ
AF Arnaldez, Fernanda I.
Yeung, Choh L.
Helman, Lee J.
TI In vivo and in vitro alveolar rhabdomyosarcoma cell growth is affected
by TNK2 expression
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Arnaldez, Fernanda I.; Yeung, Choh L.; Helman, Lee J.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 5348
DI 10.1158/1538-7445.AM2011-5348
PG 1
WC Oncology
SC Oncology
GA V43SO
UT WOS:000209701301410
ER
PT J
AU Arons, E
Suntum, T
Roth, L
Sapolsky, J
Kreitman, RJ
AF Arons, Evgeny
Suntum, Tara
Roth, Laura
Sapolsky, Jeffrey
Kreitman, Robert J.
TI Analysis of somatic hypermutations in IGHV genes from Hairy Cell
Leukemia Immunoglobulin Heavy Chain rearrangements
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Arons, Evgeny; Suntum, Tara; Roth, Laura; Sapolsky, Jeffrey; Kreitman, Robert J.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 348
DI 10.1158/1538-7445.AM2011-348
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701405132
ER
PT J
AU Banegas, MP
Gail, MH
LaCroix, A
Thompson, B
Martinez, ME
Wactawski-Wende, J
John, EM
Hubbell, FA
Yasmeen, S
Katki, HA
AF Banegas, Matthew P.
Gail, Mitchell H.
LaCroix, Andrea
Thompson, Beti
Martinez, M. Elena
Wactawski-Wende, Jean
John, Esther M.
Hubbell, F. Allan
Yasmeen, Shagufta
Katki, Hormuzd A.
TI Evaluation and comparison of breast cancer risk prediction models for
Hispanic and non-Hispanic white women in the Women's Health Initiative
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Banegas, Matthew P.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Banegas, Matthew P.; LaCroix, Andrea; Thompson, Beti] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Gail, Mitchell H.; Katki, Hormuzd A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Martinez, M. Elena] Univ Arizona, Coll Publ Hlth, Tucson, AZ USA.
[Martinez, M. Elena] Univ Arizona, Arizona Canc Ctr, Canc Prevent & Control Program, Tucson, AZ USA.
[Wactawski-Wende, Jean] Univ Buffalo, Dept Social & Prevent Med, Buffalo, NY USA.
[John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA.
[Hubbell, F. Allan] Univ Calif Irvine, Sch Med, Irvine, CA 92717 USA.
[Yasmeen, Shagufta] Univ Calif Davis, Sch Med, Sacramento, CA 95817 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 3717
DI 10.1158/1538-7445.AM2011-3717
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701406083
ER
PT J
AU Bang, D
Wilson, W
Yeh, JJ
Baldwin, AS
AF Bang, Deepali
Wilson, Willie
Yeh, Jen Jen
Baldwin, Albert S.
TI Glycogen synthase kinase-3 alpha regulates cell proliferation in
pancreatic cancer cells by regulating constitutive TAK1 and NF-kappa B
signaling
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Bang, Deepali; Yeh, Jen Jen; Baldwin, Albert S.] Univ N Carolina, Chapel Hill, NC USA.
[Wilson, Willie] NCI, NIH, Natl Naval Med Ctr, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 2892
DI 10.1158/1538-7445.AM2011-2892
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701403184
ER
PT J
AU Barsegian, A
Chattopadhyay, M
Kodela, R
Boring, D
Crowell, JA
Kashfi, K
AF Barsegian, Arpine
Chattopadhyay, Mitali
Kodela, Ravinder
Boring, Daniel
Crowell, James A.
Kashfi, Khosrow
TI Hydrogen sulfide-releasing aspirin suppresses NF-kappa B signaling in
estrogen receptor negative breast cancer cells in vitro and in vivo
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Barsegian, Arpine; Chattopadhyay, Mitali; Kodela, Ravinder; Kashfi, Khosrow] CUNY, Sch Med, New York, NY 10031 USA.
[Boring, Daniel; Crowell, James A.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 1349
DI 10.1158/1538-7445.AM2011-1349
PG 2
WC Oncology
SC Oncology
GA V43SO
UT WOS:000209701304263
ER
PT J
AU Basseville, A
Tamaki, A
Ierano, C
Ward, Y
Robey, RW
Hegde, R
Bates, SE
AF Basseville, Agnes
Tamaki, Akina
Ierano, Caterina
Ward, Yvona
Robey, Robert W.
Hegde, Ramanujan
Bates, Susan E.
TI Histone deacetylase inhibitors mediate pharmacological rescue of the
ABCG2 Q141K variant: Potential for therapeutics in cancer and gout
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Basseville, Agnes; Tamaki, Akina; Ierano, Caterina; Ward, Yvona; Robey, Robert W.; Bates, Susan E.] NCI, NIH, Bethesda, MD 20892 USA.
[Hegde, Ramanujan] NICHD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 2610
DI 10.1158/1538-7445.AM2011-2610
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701401093
ER
PT J
AU Bassig, BA
Zhang, LP
Tang, XJ
Vermeulen, R
Shen, M
Smith, MT
Qiu, CY
Ge, YC
Ji, ZY
Reiss, B
Liu, SW
Guo, WH
Purdue, M
Hui, W
Li, LY
Rothman, N
Huang, HL
Lan, Q
AF Bassig, Bryan A.
Zhang, Luoping
Tang, Xiaojiang
Vermeulen, Roel
Shen, Min
Smith, Martyn T.
Qiu, Chuangyi
Ge, Yichen
Ji, Zhiying
Reiss, Boris
Liu, Songwang
Guo, Weihong
Purdue, Mark
Hui, Wei
Li, Laiyu
Rothman, Nathaniel
Huang, Hanlin
Lan, Qing
TI Occupational exposure to trichloroethylene and plasma concentrations of
IL6, IL10, and TNF alpha
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Bassig, Bryan A.; Shen, Min; Purdue, Mark; Hui, Wei; Rothman, Nathaniel; Lan, Qing] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Zhang, Luoping; Smith, Martyn T.; Ji, Zhiying; Guo, Weihong] Univ Calif Berkeley, Berkeley, CA 94720 USA.
[Tang, Xiaojiang; Qiu, Chuangyi; Ge, Yichen; Li, Laiyu; Huang, Hanlin] Guangdong Poisoning Control Ctr, Guangzhou, Guangdong, Peoples R China.
[Vermeulen, Roel; Reiss, Boris] Univ Utrecht, Univ Med Ctr, Utrecht, Netherlands.
[Liu, Songwang] Qiaotou Hosp, Dongguan, Guangdong, Peoples R China.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 4646
DI 10.1158/1538-7445.AM2011-4646
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701406064
ER
PT J
AU Bhan, S
Shao, CB
Wang, HB
Glazer, C
Lobanenkov, V
Ha, P
Califano, J
AF Bhan, Sheetal
Shao, Chunbo
Wang, Hao
Glazer, Chad
Lobanenkov, Victor
Ha, Patrick
Califano, Joseph
TI BORIS and MageA expression correlate positively in melanoma
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Bhan, Sheetal; Shao, Chunbo; Wang, Hao; Glazer, Chad; Ha, Patrick; Califano, Joseph] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
[Lobanenkov, Victor] NIH, Inst Allergy & Infect Dis, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 5001
DI 10.1158/1538-7445.AM2011-5001
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701402094
ER
PT J
AU Bian, Y
Hall, B
Sun, ZJ
Molinolo, A
Chen, WJ
Van Waes, C
Kulkarni, A
AF Bian, Yansong
Hall, Bradford
Sun, Zhi-Jun
Molinolo, Alfredo
Chen, Wanjun
Van Waes, Carter
Kulkarni, Ashok
TI Loss of TGF-beta receptor I and PTEN promotes HNSCC
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Bian, Yansong; Van Waes, Carter] NIDCD, NIH, Bethesda, MD USA.
[Hall, Bradford; Sun, Zhi-Jun; Molinolo, Alfredo; Chen, Wanjun; Kulkarni, Ashok] NIDCR, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 4324
DI 10.1158/1538-7445.AM2011-4324
PG 1
WC Oncology
SC Oncology
GA V43SO
UT WOS:000209701301333
ER
PT J
AU Bible, KC
Peethambaram, PP
Oberg, AL
Maples, WJ
Groteluschen, DL
Boente, M
Burton, JK
Gomez-Dahl, LC
Tibodeau, JD
Isham, CR
Kukla, AK
Voll, KJ
Colevas, AD
Wright, J
Doyle, LA
Erlichman, C
AF Bible, Keith Christopher
Peethambaram, Prema P.
Oberg, Ann L.
Maples, William J.
Groteluschen, David L.
Boente, Matthew
Burton, Jill K.
Gomez-Dahl, Leigh C.
Tibodeau, Jennifer D.
Isham, Crescent R.
Kukla, Andrea K.
Voll, Kalli J.
Colevas, Alexander D.
Wright, John
Doyle, L. Austin
Erlichman, Charles
CA Mayo Phase Consortium
TI Evidence of clinical efficacy of the combination of flavopiridol
(Alvocidib) and cisplatin in platin-resistant ovarian and primary
peritoneal carcinoma: Phase 2 trial MCO261
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Bible, Keith Christopher; Peethambaram, Prema P.; Oberg, Ann L.; Burton, Jill K.; Gomez-Dahl, Leigh C.; Tibodeau, Jennifer D.; Isham, Crescent R.; Kukla, Andrea K.; Voll, Kalli J.; Erlichman, Charles] Mayo Clin, Coll Med, Rochester, MN USA.
[Maples, William J.; Mayo Phase Consortium] Mayo Clin, Coll Med, Jacksonville, FL USA.
[Groteluschen, David L.] St Vincent Hosp, Green Bay Oncol, Green Bay, WI USA.
[Boente, Matthew] Metro MN CCOP, St Louis Pk, MN USA.
[Colevas, Alexander D.; Wright, John; Doyle, L. Austin] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 4712
DI 10.1158/1538-7445.AM2011-4712
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701404364
ER
PT J
AU Biswas, K
Das, R
Alter, BP
Kuznetsoy, S
North, SL
Stauffer, S
Burkett, S
Brody, LC
Meyer, S
Byrd, AR
Sharan, SK
AF Biswas, Kajal
Das, Ranabir
Alter, Blanche P.
Kuznetsoy, Sergey
North, Susan L.
Stauffer, Stacey
Burkett, Sandra
Brody, Lawrence C.
Meyer, Stefan
Byrd, Andrew R.
Sharan, Shyam K.
TI A comprehensive study to functionally classify the BRCA2 missense
mutations found in Fanconi anemia patients
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Biswas, Kajal; Das, Ranabir; Kuznetsoy, Sergey; North, Susan L.; Stauffer, Stacey; Burkett, Sandra; Byrd, Andrew R.; Sharan, Shyam K.] NCI, Frederick, MD 21701 USA.
[Alter, Blanche P.] NCI, Rockville, MD USA.
[Brody, Lawrence C.] NHGRI, Bethesda, MD 20892 USA.
[Meyer, Stefan] Univ Manchester, Manchester, Lancs, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 228
DI 10.1158/1538-7445.AM2011-228
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701402379
ER
PT J
AU Blevins, M
An, JH
Jones, S
Swaroop, M
Ferrer, M
Ford, H
Zhao, R
AF Blevins, Melanie
An, Jianghong
Jones, Steven
Swaroop, Manju
Ferrer, Marc
Ford, Heide
Zhao, Rui
TI Identification of potential anti-tumor therapeutics targeting the Six1
transcriptional complex
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Blevins, Melanie; Ford, Heide; Zhao, Rui] Univ Colorado Anschutz Med Campus, Aurora, CO USA.
[An, Jianghong; Jones, Steven] British Columbia Canc Agcy, Genome Sci Ctr, Vancouver, BC V5Z 4E6, Canada.
[Swaroop, Manju; Ferrer, Marc] NIH, Chem Genom Ctr, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 1373
DI 10.1158/1538-7445.AM2011-1373
PG 2
WC Oncology
SC Oncology
GA V43SO
UT WOS:000209701304219
ER
PT J
AU Bode, AM
Li, JX
Cho, YY
Ericson, ME
Lubet, RA
Grubbs, CJ
AF Bode, Ann M.
Li, Jixia
Cho, Yong-Yeon
Ericson, Marna E.
Lubet, Ronald A.
Grubbs, Clinton J.
TI CREB (Ser133) phosphorylation is abnormally increased in tumors showing
resistance to Iressa treatment
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Bode, Ann M.; Li, Jixia; Cho, Yong-Yeon] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA.
[Ericson, Marna E.] Univ Minnesota, Minneapolis, MN USA.
[Lubet, Ronald A.] NCI, Bethesda, MD 20892 USA.
[Grubbs, Clinton J.] Univ Alabama Birmingham, Birmingham, AL USA.
RI ericson, marna/C-9591-2017
OI ericson, marna/0000-0003-1862-4957
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 1039
DI 10.1158/1538-7445.AM2011-1039
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701400084
ER
PT J
AU Brooks, AD
Thompson, CR
Pompei, RJ
Booth, N
Gustafson, KR
Henrich, CJ
McMahon, JB
Sayers, TJ
AF Brooks, Alan D.
Thompson, Candace R.
Pompei, Richard J.
Booth, Nancy
Gustafson, Kirk R.
Henrich, Curtis J.
McMahon, James B.
Sayers, Thomas J.
TI Differing molecular mechanisms involved in the sensitization of human
renal cancer cells to TRAIL-induced apoptosis
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Brooks, Alan D.; Henrich, Curtis J.; Sayers, Thomas J.] NCI Frederick, SAIC Frederick, Frederick, MD USA.
[Thompson, Candace R.; Pompei, Richard J.; Booth, Nancy; Gustafson, Kirk R.; McMahon, James B.] NCI Frederick, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 4102
DI 10.1158/1538-7445.AM2011-4102
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701402074
ER
PT J
AU Brooks, BR
Yin, H
Chow, D
Sereduk, C
Koeman, J
Qian, CN
MacKeigan, JP
Jung, S
Kim, S
Xu, M
Weeraratna, A
Brown, KM
Trent, J
AF Brooks, Bradford R.
Yin, Holly
Chow, Donald
Sereduk, Chris
Koeman, Julie
Qian, Chaonan
MacKeigan, Jeffrey P.
Jung, Sungwon
Kim, Seungchan
Xu, Mai
Weeraratna, Ashani
Brown, Kevin M.
Trent, Jeffrey
TI Association of PTEN and p16 mutational status with MITF expression may
provide a novel context for a phenotype switch in melanoma
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Brooks, Bradford R.; Koeman, Julie; Qian, Chaonan; MacKeigan, Jeffrey P.; Trent, Jeffrey] Van Andel Res Inst, Grand Rapids, MI USA.
[Yin, Holly; Chow, Donald; Sereduk, Chris; Jung, Sungwon; Kim, Seungchan; Brown, Kevin M.] Translat Genom Res Inst, Phoenix, AZ USA.
[Xu, Mai; Weeraratna, Ashani] NIA, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 4984
DI 10.1158/1538-7445.AM2011-4984
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701404203
ER
PT J
AU Broussar, EK
Pritchard, DK
Lubet, RA
Disis, ML
AF Broussar, Elizabeth K.
Pritchard, David K.
Lubet, Ronald A.
Disis, Mary L.
TI Identification of potential immunologic targets found in mice and man
that are expressed in colon adenomas and colorectal cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Broussar, Elizabeth K.; Pritchard, David K.; Disis, Mary L.] Univ Washington, Seattle, WA 98195 USA.
[Lubet, Ronald A.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 2681
DI 10.1158/1538-7445.AM2011-2681
PG 1
WC Oncology
SC Oncology
GA V43SO
UT WOS:000209701301269
ER
PT J
AU Bulut, G
Hong, SH
Chen, KV
Rahim, S
Kosturko, GW
Beauchamp, EM
Glasgow, E
Toretsky, JA
Khanna, C
Uren, A
AF Bulut, Gulay
Hong, Sung-Hyeok
Chen, Kevin
Rahim, Said
Kosturko, George W.
Beauchamp, Elspeth M.
Glasgow, Eric
Toretsky, Jeffrey A.
Khanna, Chand
Uren, Aykut
TI Development of small molecules to target ezrin as anti-metastatic agents
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Bulut, Gulay; Chen, Kevin; Rahim, Said; Kosturko, George W.; Beauchamp, Elspeth M.; Glasgow, Eric; Toretsky, Jeffrey A.; Uren, Aykut] Georgetown Lombardi Comp Canc Ctr, Washington, DC USA.
[Hong, Sung-Hyeok; Khanna, Chand] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 4505
DI 10.1158/1538-7445.AM2011-4505
PG 1
WC Oncology
SC Oncology
GA V43SO
UT WOS:000209701300128
ER
PT J
AU Cai, QY
Beeghly-Fadiel, A
Shrubsole, MJ
Shu, XO
Yang, G
Ji, BT
Li, HL
Chow, WH
Gao, YT
Zheng, W
AF Cai, Qiuyin
Beeghly-Fadiel, Alicia
Shrubsole, Martha J.
Shu, Xiao-Ou
Yang, Gong
Ji, Bu-Tian
Li, Honglan
Chow, Wong-Ho
Gao, Yu-Tang
Zheng, Wei
TI Dietary intake of riboflavin and risk of lung cancer among non-smokers:
A prospective cohort study among Chinese women
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Cai, Qiuyin; Beeghly-Fadiel, Alicia; Shrubsole, Martha J.; Shu, Xiao-Ou; Yang, Gong; Zheng, Wei] Vanderbilt Univ, Sch Med, Div Epidemiol, Nashville, TN 37212 USA.
[Cai, Qiuyin; Beeghly-Fadiel, Alicia; Shrubsole, Martha J.; Shu, Xiao-Ou; Yang, Gong; Zheng, Wei] Vanderbilt Univ, Sch Med, Dept Med, Vanderbilt Epidemiol Ctr, Nashville, TN 37212 USA.
[Cai, Qiuyin; Beeghly-Fadiel, Alicia; Shrubsole, Martha J.; Shu, Xiao-Ou; Yang, Gong; Zheng, Wei] Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Ji, Bu-Tian; Chow, Wong-Ho] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Li, Honglan; Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 1911
DI 10.1158/1538-7445.AM2011-1911
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701406095
ER
PT J
AU Camargo, MC
Anderson, WF
King, JB
Correa, P
Thomas, CC
Rosenberg, PS
Eheman, CR
Rabkin, CS
AF Camargo, M. Constanza
Anderson, William F.
King, Jessica B.
Correa, Pelayo
Thomas, Cheryl C.
Rosenberg, Philip S.
Eheman, Christie R.
Rabkin, Charles S.
TI Divergent trends for gastric cancer incidence by anatomic subsite in US
adults
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Camargo, M. Constanza; Anderson, William F.; Rosenberg, Philip S.; Rabkin, Charles S.] NCI, Rockville, MD USA.
[King, Jessica B.; Thomas, Cheryl C.; Eheman, Christie R.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Correa, Pelayo] Vanderbilt Univ, Nashville, TN 37235 USA.
RI Camargo, M. Constanza/R-9891-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 1916
DI 10.1158/1538-7445.AM2011-1916
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701405484
ER
PT J
AU Cao, L
Yu, YK
Bilke, S
Walker, RL
Azorsa, DO
Helman, LJ
Meltzer, PS
AF Cao, Liang
Yu, Yunkai
Bilke, Sven
Walker, Robert L.
Azorsa, David O.
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 Meeting Abstract
C1 [Cao, Liang; Yu, Yunkai; Bilke, Sven; Walker, Robert L.; Helman, Lee J.; Meltzer, Paul S.] NCI, Bethesda, MD 20892 USA.
[Azorsa, David O.] TGen, Scottsdale, AZ USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 5344
DI 10.1158/1538-7445.AM2011-5344
PG 1
WC Oncology
SC Oncology
GA V43SO
UT WOS:000209701301406
ER
PT J
AU Carol, H
Lock, RB
Maris, JM
Keir, ST
Gorlick, R
Kolb, EA
Kang, MH
Reynolds, CP
Morton, CL
Smith, PG
Thomas, M
McDonald, A
Houghton, PJ
Smith, MA
AF Carol, Hernan
Lock, Richard B.
Maris, John M.
Keir, Stephen T.
Gorlick, Richard
Kolb, E. Anders
Kang, Min H.
Reynolds, C. Patrick
Morton, Christopher L.
Smith, Peter G.
Thomas, Michael
McDonald, Alice
Houghton, Peter J.
Smith, Malcolm A.
TI Pediatric Preclinical Testing Program (PPTP) evaluation of the
NEDD8-activating enzyme (NAE) inhibitor MLN4924
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Carol, Hernan; Lock, Richard B.] Childrens Canc Inst Australia, Randwick, NSW, Australia.
[Maris, John M.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA.
[Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
[Kolb, E. Anders] AI duPont Hosp, Wilmington, DE USA.
[Kang, Min H.; Reynolds, C. Patrick] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79409 USA.
[Morton, Christopher L.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Smith, Peter G.; Thomas, Michael; McDonald, Alice] Millennium Pharmaceut Inc, Cambridge, MA USA.
[Houghton, Peter J.] Nationwide Childrens Hosp, Columbus, OH USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 740
DI 10.1158/1538-7445.AM2011-740
PG 2
WC Oncology
SC Oncology
GA V43SO
UT WOS:000209701300062
ER
PT J
AU Caron, WP
Clewell, H
Dedrick, R
Ramanathan, RK
Yu, N
Schellens, JH
Beijnen, JH
Zamboni, WC
AF Caron, Whitney P.
Clewell, Harvey
Dedrick, Robert
Ramanathan, Ramesh K.
Yu, Ning
Schellens, Jan H.
Beijnen, Jos H.
Zamboni, William C.
TI Allometric scaling of the pharmacokinetics of pegylated liposomal
anticancer drugs
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Caron, Whitney P.; Zamboni, William C.] Univ N Carolina, Chapel Hill, NC USA.
[Clewell, Harvey] Hamner Inst, Res Triangle Pk, NC USA.
[Dedrick, Robert] NIH, Bethesda, MD 20892 USA.
[Ramanathan, Ramesh K.] Univ Pittsburgh, Pittsburgh, PA USA.
[Yu, Ning] ALZA Corp, Mountain View, CA USA.
[Schellens, Jan H.; Beijnen, Jos H.] Netherlands Canc Inst, Amsterdam, Netherlands.
NR 0
TC 0
Z9 0
U1 10
U2 10
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 373
DI 10.1158/1538-7445.AM2011-373
PG 2
WC Oncology
SC Oncology
GA V43SO
UT WOS:000209701305053
ER
PT J
AU Carothers, AM
Rizvi, H
Lubet, R
Bertagnolli, M
AF Carothers, Adelaide M.
Rizvi, Hira
Lubet, Ronald
Bertagnolli, Monica
TI Absent E2 liganded AhR inhibits tumor inhibition by ER alpha in Min mice
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Carothers, Adelaide M.; Rizvi, Hira; Bertagnolli, Monica] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Lubet, Ronald] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 2292
DI 10.1158/1538-7445.AM2011-2292
PG 2
WC Oncology
SC Oncology
GA V43SO
UT WOS:000209701303010
ER
PT J
AU Casagrande, G
Yu, MS
Rodriguez-Canales, J
Kohn, EC
Virador, VM
AF Casagrande, Giovanna
Yu, Minshu
Rodriguez-Canales, Jaime
Kohn, Elise C.
Virador, Victoria M.
TI Targeted expression of BAG3 to the murine mammary gland (MMTV-hBAG3)
reveals a role in mammary tumorigenesis
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Casagrande, Giovanna; Yu, Minshu; Rodriguez-Canales, Jaime; Kohn, Elise C.; Virador, Victoria M.] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 2388
DI 10.1158/1538-7445.AM2011-2388
PG 1
WC Oncology
SC Oncology
GA V43SO
UT WOS:000209701300429
ER
PT J
AU Cerna, D
Li, HY
Flaherty, S
Carter, D
Coleman, CN
Yoo, S
AF Cerna, David
Li, Hongyun
Flaherty, Siobhan
Carter, Donna
Coleman, C. Norman
Yoo, Stephen
TI Radiosensitization of solid tumor cell lines by an MDM2 inhibitor
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Cerna, David; Li, Hongyun; Flaherty, Siobhan; Carter, Donna] SAIC Frederick, Frederick, MD USA.
[Coleman, C. Norman; Yoo, Stephen] NCI, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 2668
DI 10.1158/1538-7445.AM2011-2668
PG 1
WC Oncology
SC Oncology
GA V43SO
UT WOS:000209701300303
ER
PT J
AU Chakraborty, AR
Robey, RW
Collie, N
Gillet, JP
Piekarz, RL
Gottesman, MM
Bates, SE
AF Chakraborty, Arup R.
Robey, Robert W.
Collie, Nathan
Gillet, Jean-Pierre
Piekarz, Richard L.
Gottesman, Michael M.
Bates, Susan E.
TI Elevated expression of phosphorylated mitogen activated protein kinase
kinase (MEK) as a mechanism of resistance to the histone deacetylase
inhibitor romidepsin in HUT 78 cutaneous T-cell lymphoma cells
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Chakraborty, Arup R.; Collie, Nathan] Texas Tech Univ, Lubbock, TX 79409 USA.
[Robey, Robert W.; Gillet, Jean-Pierre; Piekarz, Richard L.; Gottesman, Michael M.; Bates, Susan E.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 2624
DI 10.1158/1538-7445.AM2011-2624
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701401108
ER
PT J
AU Chang, WCL
Ferrara, CM
Cooper, HS
Mosier, SL
Kaunga, E
Grubbs, CJ
Lubet, RA
Clapper, ML
AF Chang, Wen-Chi L.
Ferrara, Christina M.
Cooper, Harry S.
Mosier, Stacy L.
Kaunga, Esther
Grubbs, Clinton J.
Lubet, Ronald A.
Clapper, Margie Lee
TI Effect of naproxen and NO-naproxen on intestinal neoplasia in the Apc
plus /Min-FCCC mouse model
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Chang, Wen-Chi L.; Ferrara, Christina M.; Cooper, Harry S.; Mosier, Stacy L.; Kaunga, Esther; Clapper, Margie Lee] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Grubbs, Clinton J.] Univ Alabama Birmingham, Birmingham, AL USA.
[Lubet, Ronald A.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA LB-457
DI 10.1158/1538-7445.AM2011-LB-457
PG 2
WC Oncology
SC Oncology
GA V43SO
UT WOS:000209701302377
ER
PT J
AU Chang, YS
Meza, LM
Onozawa, M
Gills, JJ
Aplan, PD
Dennis, PA
AF Chang, Yoon Soo
Meza, Leah M.
Onozawa, Masahiro
Gills, Joell J.
Aplan, Peter D.
Dennis, Phillip A.
TI Inhibition of Notch and mTOR by nelfinavir as a novel approach for T
cell acute lymphoblastic leukemia (T-ALL)
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Chang, Yoon Soo; Meza, Leah M.; Gills, Joell J.; Dennis, Phillip A.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
[Onozawa, Masahiro; Aplan, Peter D.] NCI, Genet Branch, Bethesda, MD 20892 USA.
RI Aplan, Peter/K-9064-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 2603
DI 10.1158/1538-7445.AM2011-2603
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701400423
ER
PT J
AU Chanock, SJ
AF Chanock, Stephen J.
TI The heritable component of cancer: Insights from genome-wide association
studies and beyond
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Chanock, Stephen J.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA PL01-02
DI 10.1158/1538-7445.AM2011-PL01-02
PG 2
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701404339
ER
PT J
AU Chen, KX
Cheng, HY
Zhang, LM
Cogdeil, DE
Zheng, H
Schetter, AJ
Nykter, M
Harris, CC
Hamilton, SR
Zhang, W
AF Chen, Kexin
Cheng, Hanyin
Zhang, Lina
Cogdeil, David E.
Zheng, Hong
Schetter, Aaron J.
Nykter, Matti
Harris, Curtis C.
Hamilton, Stanley R.
Zhang, Wei
TI Circulating plasma MiR-141 is a novel biomarker for metastatic colon
cancer and predicts poor prognosis
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Chen, Kexin; Zhang, Lina; Zheng, Hong] Tianjin Med Univ, Canc Inst & Hosp, Tianjin, Peoples R China.
[Cheng, Hanyin; Cogdeil, David E.; Hamilton, Stanley R.; Zhang, Wei] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Schetter, Aaron J.; Harris, Curtis C.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Nykter, Matti] Tampere Univ Technol, FIN-33101 Tampere, Finland.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 1145
DI 10.1158/1538-7445.AM2011-1145
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701404104
ER
PT J
AU Chen, M
Nawab, A
Hoffmann, V
Zajac-Kaye, M
AF Chen, Min
Nawab, Akbar
Hoffmann, Vickie
Zajac-Kaye, Maria
TI Transgenic expression of human Thymidylate Synthase cooperates with an
Ink4a/Arf mutation to enhance tumor progression
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Chen, Min; Nawab, Akbar; Zajac-Kaye, Maria] Univ Florida, Gainesville, FL USA.
[Hoffmann, Vickie] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 4315
DI 10.1158/1538-7445.AM2011-4315
PG 1
WC Oncology
SC Oncology
GA V43SO
UT WOS:000209701301324
ER
PT J
AU Chen, XY
Quan, QM
Xie, J
AF Chen, Xiaoyuan
Quan, Qimeng
Xie, Jin
TI HSA coated iron oxide nanoparticle as a drug delivery vehicle for cancer
therapy
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Chen, Xiaoyuan; Quan, Qimeng; Xie, Jin] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 4437
DI 10.1158/1538-7445.AM2011-4437
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701401292
ER
PT J
AU Chung, CC
Yeager, M
Boland, J
Greene, M
Chanock, S
Kratz, C
AF Chung, Charles C.
Yeager, Meredith
Boland, Joseph
Greene, Mark
Chanock, Stephen
Kratz, Christian
TI Resequence-analysis of 166kb KITLG region in eamilial testicular germ
cell tumors
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Chung, Charles C.; Yeager, Meredith; Boland, Joseph; Greene, Mark; Chanock, Stephen; Kratz, Christian] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 28
DI 10.1158/1538-7445.AM2011-28
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701400185
ER
PT J
AU Ciampa, JG
Holmes, C
Chatterjee, N
AF Ciampa, Julia G.
Holmes, Chris
Chatterjee, Nilanjan
TI Application of a novel multi-locus test for genetic association
incorporating gene-gene interaction suggests functionality for multiple
susceptibility loci for prostate cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Ciampa, Julia G.; Chatterjee, Nilanjan] NCI, Rockville, MD USA.
[Holmes, Chris] Univ Oxford, Oxford, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 2747
DI 10.1158/1538-7445.AM2011-2747
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701406116
ER
PT J
AU Correale, P
Rotundo, MT
Botta, C
Apollinari, S
Remondo, C
Tsang, KY
Ciliberto, D
Tassone, P
Ridolfi, R
Tagliaferri, P
AF Correale, Pierpaolo
Rotundo, Maria Teresa
Botta, Cirino
Apollinari, Serena
Remondo, Cinzia
Tsang, Kwong Yok
Ciliberto, Domenico
Tassone, Pierfrancesco
Ridolfi, Ruggero
Tagliaferri, Pierosandro
TI Chemo-immunotherapy with gemcitabine plus FOLFOX followed by
granulocyte-macrophage colony stimulating factor and low dose
aldesleukine (GOLFIG regimen) is a highly active frontline treatment for
advanced colorectal carcinoma: Results from the GOLFIG/2 phase III trial
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Correale, Pierpaolo; Botta, Cirino; Apollinari, Serena; Remondo, Cinzia] Sect Med Oncol, Lab Translat Immune Oncol, Siena, Italy.
[Rotundo, Maria Teresa; Ciliberto, Domenico; Tassone, Pierfrancesco; Tagliaferri, Pierosandro] Med Oncol Unit, Catanzaro, Italy.
[Tsang, Kwong Yok] NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA.
[Ridolfi, Ruggero] IRST, Forli, Italy.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 5511
DI 10.1158/1538-7445.AM2011-5511
PG 2
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701405086
ER
PT J
AU Correale, P
Rotundo, MT
Botta, C
Apollinari, S
Remondo, C
Tsang, KY
Ciliberto, D
Tassone, P
Ridolfi, R
Tagliaferri, P
AF Correale, Pierpaolo
Rotundo, Maria Teresa
Botta, Cirino
Apollinari, Serena
Remondo, Cinzia
Tsang, Kwong Yok
Ciliberto, Domenico
Tassone, Pierfrancesco
Ridolfi, Ruggero
Tagliaferri, Pierosandro
TI Chemo-immunotherapy with gemcitabine plus FOLFOX followed by
granulocyte-macrophage colony stimulating factor and low dose
aldesleukine (GOLFIG regimen) is a highly active frontline treatment for
advanced colorectal carcinoma: Results from the GOLFIG/2 phase III trial
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Correale, Pierpaolo; Botta, Cirino; Apollinari, Serena; Remondo, Cinzia] Sect Med Oncol, Lab Translat Immune Oncol, Siena, Italy.
[Rotundo, Maria Teresa] Campus Salvatore Venuta, Med Oncol Unit, Catanzaro, Italy.
[Tsang, Kwong Yok] NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA.
[Ciliberto, Domenico; Tassone, Pierfrancesco; Tagliaferri, Pierosandro] Med Oncol Unit, Catanzaro, Italy.
[Ridolfi, Ruggero] IRST, Forli, Italy.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 5511
DI 10.1158/1538-7445.AM2011-5511
PG 2
WC Oncology
SC Oncology
GA V43SO
UT WOS:000209701301025
ER
PT J
AU Das, N
Baumgartner, KB
Kerber, RA
Rai, SN
Ulrich, CM
Neuhouser, ML
Bernstein, L
Mc Tiernan, A
Ballard-Barbash, R
Baumgartner, RN
AF Das, Nandita
Baumgartner, Kathy B.
Kerber, Richard A.
Rai, Shesh N.
Ulrich, Cornelia M.
Neuhouser, Marian L.
Bernstein, Leslie
Mc Tiernan, Anne
Ballard-Barbash, Rachel
Baumgartner, Richard N.
TI Associations between genetic variability in folate metabolism and breast
cancer survival
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Das, Nandita; Baumgartner, Kathy B.; Kerber, Richard A.; Rai, Shesh N.; Baumgartner, Richard N.] Univ Louisville, Louisville, KY 40292 USA.
[Ulrich, Cornelia M.] Natl Ctr Tumor Dis NCT, Heidelberg, Germany.
[Neuhouser, Marian L.; Mc Tiernan, Anne] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
[Ballard-Barbash, Rachel] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 2750
DI 10.1158/1538-7445.AM2011-2750
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701406099
ER
PT J
AU Das, S
Xiao, Z
Bosley, AD
Chan, KC
Issaq, HJ
Veenstra, TD
Andresson, T
Green, JE
AF Das, Sudipto
Xiao, Zhen
Bosley, Allen D.
Chan, King C.
Issaq, Haleem J.
Veenstra, Timothy D.
Andresson, Thorkell
Green, Jeffery E.
TI Protein complexes in cancer: A novel strategy to identify protein
complexes through reduction of false discovery rate
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Das, Sudipto; Xiao, Zhen; Bosley, Allen D.; Chan, King C.; Issaq, Haleem J.; Veenstra, Timothy D.; Andresson, Thorkell] SAIC Frederick Inc, Frederick, MD USA.
[Green, Jeffery E.] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 4873
DI 10.1158/1538-7445.AM2011-4873
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701403453
ER
PT J
AU Daugherty, SE
Moore, S
Pfeiffer, R
Park, Y
Rajaraman, P
AF Daugherty, Sarah E.
Moore, Steve
Pfeiffer, Ruth
Park, Yikyung
Rajaraman, Preetha
TI Non-steroidal anti-inflammatory drugs and brain cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Daugherty, Sarah E.; Moore, Steve; Pfeiffer, Ruth; Park, Yikyung; Rajaraman, Preetha] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA LB-447
DI 10.1158/11538-7445.AM2011-LB-447
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701406041
ER
PT J
AU Dave, H
Baskar, S
Khan, J
Wayne, A
Rader, C
AF Dave, Hema
Baskar, Sivasubramanian
Khan, Javed
Wayne, Alan
Rader, Christoph
TI ROR1: A novel target for pre-B acute lymphoblastic leukemia and
neuroblastoma
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Dave, Hema; Baskar, Sivasubramanian; Khan, Javed; Wayne, Alan; Rader, Christoph] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 2578
DI 10.1158/1538-7445.AM2011-2578
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701400397
ER
PT J
AU Day, CP
Esposito, D
Mahesh, CR
Merlino, G
AF Day, Chi-Ping
Esposito, Dominic
Mahesh, Cynthia R.
Merlino, Glenn
TI Notch pathway mediates post-treatment repopulation of lung squamous cell
carcinoma cells
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Day, Chi-Ping; Mahesh, Cynthia R.; Merlino, Glenn] NIH, Bethesda, MD 20892 USA.
[Esposito, Dominic] NCI, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 1640
DI 10.1158/1538-7445.AM2011-1640
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701401052
ER
PT J
AU de Bruin, EC
Cowell, CF
Howell, M
Varmus, HE
Politi, K
Downward, J
AF de Bruin, Elza C.
Cowell, Catherine F.
Howell, Michael
Varmus, Harold E.
Politi, Katerina
Downward, Julian
TI Identification of novel mechanisms of resistance to EGFR tyrosine kinase
inhibitors in non-small cell lung cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [de Bruin, Elza C.; Cowell, Catherine F.; Howell, Michael; Downward, Julian] Canc Res UK London Res Inst, London WC2A 3PX, England.
[Varmus, Harold E.] NHGRI, Bethesda, MD 20892 USA.
[Politi, Katerina] Yale Univ, New Haven, CT USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA LB-398
DI 10.1158/1538-7445.AM2011-LB-398
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701400322
ER
PT J
AU de Kluyver, RL
Brooks, AT
Sayers, TJ
AF de Kluyver, Rachel L.
Brooks, Alan T.
Sayers, Thomas J.
TI Nanog-expressing breast cancer tumor initiating cells (TICs) are highly
metastatic and are resistant to the effects of proteasome inhibition
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [de Kluyver, Rachel L.] NCI, Frederick, MD 21701 USA.
[Brooks, Alan T.; Sayers, Thomas J.] SAIC, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 3349
DI 10.1158/1538-7445.AM2011-3349
PG 2
WC Oncology
SC Oncology
GA V43SO
UT WOS:000209701304099
ER
PT J
AU De Luca, P
Moiola, C
Zalazar, F
Gueron, G
Cotignola, J
Vazquez, E
Gardner, K
De Siervi, A
AF De Luca, Paola
Moiola, Cristian
Zalazar, Florencia
Gueron, Geraldine
Cotignola, Javier
Vazquez, Elba
Gardner, Kevin
De Siervi, Adriana
TI Critical BRCA1 role as a transcriptional regulator in prostate cancer
DNA damage response
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [De Luca, Paola; Moiola, Cristian; Zalazar, Florencia; Gueron, Geraldine; Cotignola, Javier; Vazquez, Elba; De Siervi, Adriana] Univ Buenos Aires, Buenos Aires, DF, Argentina.
[Gardner, Kevin] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 2160
DI 10.1158/1538-7445.AM2011-2160
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701402169
ER
PT J
AU De Mukhopadhyay, K
Bandyopadhyay, A
Elkahloun, AG
Cornell, JE
Yang, JH
Sun, LZ
AF De Mukhopadhyay, Keya
Bandyopadhyay, Abhik
Elkahloun, Abdel G.
Cornell, John E.
Yang, Junhua
Sun, LuZhe
TI Unraveling the molecular signature that drives breast cancer-induced
brain metastasis in a mouse xenograft model
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [De Mukhopadhyay, Keya; Bandyopadhyay, Abhik; Cornell, John E.; Yang, Junhua; Sun, LuZhe] UT Hlth Sci Ctr, San Antonio, TX USA.
[Elkahloun, Abdel G.] NHGRI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 5168
DI 10.1158/1538-7445.AM2011-5168
PG 2
WC Oncology
SC Oncology
GA V43SO
UT WOS:000209701304026
ER
PT J
AU DeCicco-Skinner, KL
Nolan, S
Dempsey, T
Trovato, E
Weist, J
AF DeCicco-Skinner, Kathleen L.
Nolan, Sabrina
Dempsey, Taylor
Trovato, Erika
Weist, Jonathan
TI Tumor progression locus 2 (Tpl2) knockout mice have a dysregulation in
COX-2 signaling in two-stage skin carcinogenesis
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [DeCicco-Skinner, Kathleen L.; Nolan, Sabrina; Dempsey, Taylor; Trovato, Erika] Amer Univ, Washington, DC 20016 USA.
[Weist, Jonathan] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 2109
DI 10.1158/1538-7445.AM2011-2109
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701402003
ER
PT J
AU Degheidy, HA
Venzon, D
Farooqui, M
Abbasi, F
Arthur, D
Wiestner, A
Stetler-Stevenson, M
Gerald, M
AF Degheidy, Heba A.
Venzon, David
Farooqui, Mohammed
Abbasi, Fatima
Arthur, Diane
Wiestner, Adrian
Stetler-Stevenson, Maryalice
Gerald, Marti
TI Improved ZAP-70 assay using two clones: Multiple methods of analysis,
and a scoring system
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Degheidy, Heba A.; Abbasi, Fatima; Gerald, Marti] US FDA, CBER, Bethesda, MD 20014 USA.
[Venzon, David] NCI, Biostatistc & Data Management, Bethesda, MD 20892 USA.
[Farooqui, Mohammed; Wiestner, Adrian] NHLBI, NIH, Bethesda, MD 20892 USA.
[Arthur, Diane; Stetler-Stevenson, Maryalice] NCI, Pathol Lab, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 5080
DI 10.1158/1538-7445.AM2011-5080
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701405060
ER
PT J
AU Deng, CX
Kim, HS
Vassilopoulos, A
Wang, RH
Lahusen, T
Xiao, Z
Xu, XL
Li, CL
Veenstra, TD
Ji, JF
Wang, XW
Park, SH
Gius, D
AF Deng, Chuxia
Kim, Hyun-Seok
Vassilopoulos, Athanassios
Wang, Rui-Hong
Lahusen, Tyler
Xiao, Zhen
Xu, Xiaoling
Li, Cuiling
Veenstra, Timothy D.
Ji, Junfang
Wang, Xin-Wei
Park, Seong-Hoon
Gius, David
TI Knockout mouse models for sirtuins: Genome integrity, metabolism, and
cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Deng, Chuxia; Kim, Hyun-Seok; Vassilopoulos, Athanassios; Wang, Rui-Hong; Lahusen, Tyler; Xu, Xiaoling; Li, Cuiling] NIDDK, NIH, Bethesda, MD 20892 USA.
[Xiao, Zhen; Veenstra, Timothy D.; Ji, Junfang; Wang, Xin-Wei] NCI, NIH, Frederick, MD 21701 USA.
[Park, Seong-Hoon; Gius, David] Vanderbilt Univ, Med Ctr, Dept Radiat Oncol & Pediat, Nashville, TN USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA SY11-01
DI 10.1158/1538-7445.AM2011-SY11-01
PG 2
WC Oncology
SC Oncology
GA V43SO
UT WOS:000209701302352
ER
PT J
AU Di, LJ
Fernandez, A
Gardner, K
AF Di, Lijun
Fernandez, Alfonso
Gardner, Kevin
TI Transcriptional control of the BRCA1 expression by a metabolic switch
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Di, Lijun; Fernandez, Alfonso; Gardner, Kevin] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA 226
DI 10.1158/1538-7445.AM2011-226
PG 1
WC Oncology
SC Oncology
GA V43SP
UT WOS:000209701402378
ER
PT J
AU Disis, M
Gad, E
Herendeen, D
Cecil, D
Park, KH
O'Meara, MM
Lai, VP
Lubet, RA
AF Disis, Mary
Gad, Ekram
Herendeen, Daniel
Cecil, Denise
Park, Kyong Hwa
O'Meara, Megan M.
Lai, Vy P.
Lubet, Ronald A.
TI Vaccines for the prevention of cancer
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Disis, Mary; Gad, Ekram; Herendeen, Daniel; Cecil, Denise; Park, Kyong Hwa; O'Meara, Megan M.; Lai, Vy P.] Univ Washington, Seattle, WA 98195 USA.
[Lubet, Ronald A.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2011
VL 71
SU 8
MA SY24-03
DI 10.1158/1538-7445.AM2011-SY24-03
PG 2
WC Oncology
SC Oncology
GA V43SO
UT WOS:000209701300263
ER
EF